title: I Am Groot

text: Work on the series' photorealistic animation style began by August 2021. Winderbaum explained that Marvel Studios wanted "I Am Groot" to feel "directly rooted in the language of the films", which is why they chose visual effects company Luma Pictures to animate the series since they previously designed and worked on Baby Groot for "Vol. 2". Winderbaum highlighted how Lepore's experience working with stop motion animation translated to her directing computer-generated animation. When talking to Lepore, Gunn compared Baby Groot's poses and facial expressions to emojis due the character's face just having eyes and a mouth.


title: I Am Groot

text: Initial conceptions of the episodes in the storyboard and animatic stages resulted in the shorts being about five minutes. Lepore was aiming for each short to be approximately three minutes in length, and made refinements and "edited very carefully" to get them to that runtime.


title: I Am Groot

text: Daniele Luppi served as the composer for the first five shorts of "I Am Groot". Lepore chose Luppi to score the series given his past work with an electronic sound, which helped translate to the "strange" sound she was looking for. She added that his score "sounds like it came out of a spaghetti western with the same kind of patina on it from that era". Luppi used old microphones, keyboards, and other analog instruments to give his score an "authentic, more organic sound". A single featuring the songs "Groot Bossa Nova" and "Groot Tuttifrutti" from the shorts was released digitally by Marvel Music and Hollywood Records on August 4, 2022.


title: I Am Groot

text: Lepore wanted to feature music from the 1960s and 1970s, and looked at music from around the world instead of just the United States, to differ it from the music featured in the "Guardians of the Galaxy" films. Licensed songs in the series include "In the Hall of the Mountain Queen" by Raymond Scott in "Groot's First Steps", which Lepore noted instantly gives the short a "really weird flavor, this spacey, early electro feel", "Ran Kan Kan" by Tito Puente in "Groot's Pursuit", and "You Can Get It If You Really Want" by Jimmy Cliff in "Magnum Opus".


title: I Am Groot

text: Brief footage from the series was shown during Disney's annual meeting of shareholders in March 2022 within a content highlight reel. The first poster for the series, announcing its release date, was revealed on June 5, which made the series "immediately [begin] trending online". According to "Variety" Trending TV chart, it amassed 231,000 user engagements, which measure the combination of tweets, retweets, likes, and hashtags, the second most for the week of May 30 to June 5, behind the Netflix series "Stranger Things". Marvel Studios partnered with Wonderful Pistachios and Framestore for a "Groot Gets Crackin'" marketing campaign, featuring Groot across television advertisements, digital and social media posts, and limited-edition packaging for their pistachios, as well as in-store displays until August 31. A 15-second television spot was released on June 6, as part of the campaign. Tickets to attend Marvel's Avengers S.T.A.T.I.O.N. in Las Vegas were also set to be given out randomly to customers who bought their pistachios as part of the campaign.


title: I Am Groot

text: The short "Magnum Opus" debuted at the El Capitan Theatre, appearing before select screenings of the MCU film "" (2022), from July 18 to 24. The short "Groot Takes a Bath" was shown during Marvel Studios' animation panel at San Diego Comic-Con on July 22, where Lepore discussed the series and a trailer for all of the shorts was also released. Posters for each short were released ahead of their premiere.


title: I Am Groot

text: "I Am Groot" was the third highest streaming series for viewers in the United States for the week ending August 14, 2022, according to Whip Media's TV Time.


title: I Am Groot

text: The review aggregator website Rotten Tomatoes reported an 87% approval rating, with an average score of 7.70/10, based on 15 reviews. The website's critics consensus reads: "He is Groot, and that novelty alone ought to give MCU fans a rooting interest in this slight but fun series of hijinks."


title: I Am Groot

text: Matt Fowler of "IGN" gave "I Am Groot" 7 out of 10, finding the shorts "adorable as an animated offshoot of the MCU but also contain a quirky dark humor thanks to [Baby] Groot's own temper and penchant for getting punchy." Fowler noted how Groot's prickliness was "a saving grace... as these types of shorts rarely showcase a brat." Andrew Webster of "The Verge" considered the series as one of the greatest animated shorts on Disney+, feeling the shorts were "fun and goofy". Webster also found that the short runtime "works well here — the gimmick doesn't last long enough to overstay its welcome." "Variety"s Wilson Chapman said "I Am Groot" was "charming, briskly paced and — in a rarity for a Marvel streaming TV show — completely self-contained, with no cameos or set-ups for another show to speak-of". Brett White from "Decider" likened the series to "Looney Tunes" with "mayhem in the best way possible" and called "I Am Groot" "a damn from beginning to end", saying, "Each short zips along at a perfect pace, deploying sight gags that hit their mark every time." White was frustrated, however, with each short being their own entry on Disney+ rather than collected under one title. Nick Schager at "The Daily Beast" was positive on the shorts, saying their "brevity prevents it from growing stale, and yet given that each chapter runs only four minutes, a little extra time might have let it playfully elaborate upon its conceits". He also enjoyed the animation, saying "I Am Groot" "boasts a handsome vibrancy and level of detail".


title: Karen O

text: Karen Lee Orzolek (born November 22, 1978) is a South Korean-born American singer, musician, and songwriter. She is the lead vocalist for the indie rock band Yeah Yeah Yeahs.


title: Karen O

text: She was born in Seoul, South Korea, the daughter of a Korean mother and a Polish father. The family eventually moved to Englewood, New Jersey, where she grew up and graduated from The Elisabeth Morrow School and Dwight-Englewood School. About her childhood, she stated that "it's almost embarrassing how well-behaved I was, which is probably why I do things like spit water on myself on stage as an adult". She attended Oberlin College before transferring to New York University's Tisch School of the Arts.


title: Karen O

text: O is known as the lead vocalist for the band Yeah Yeah Yeahs. She has also been noted for her sense of fashion, wearing ostentatious outfits made by her friend, fashion designer Christian Joy. In the early days of the band, she became well-known for her outrageous antics during live shows. Their first ever gig was opening for the White Stripes in 2000.


title: Karen O

text: During a tour for the 2003 Livid Festival in Australia, at a sideshow at The Metro in Sydney, O accidentally danced off the stage and was reluctantly taken to a hospital. A few days later, at the Sydney leg of the Livid Festival, she appeared in a wheelchair pushed onstage by Angus Andrew.


title: Karen O

text: In 2007, O was placed at number three on Spinner's "Women Who Rock Right Now" list. The following year, she debuted a side project called Native Korean Rock with fellow New York City musicians, with two intimate performances at Union Pool in Brooklyn on July 21.


title: Karen O

text: In 2009, she contributed backing vocals, screaming animal sounds, and noises to the songs "Gemini Syringes", "I Can Be A Frog", and "Watching the Planets" on The Flaming Lips album "Embryonic". In 2011, she contributed vocals on the song "Pinky's Dream" on the David Lynch debut album "Crazy Clown Time". In 2012, she collaborated with experimental rock group Swans on the song "Song for a Warrior" on their album "The Seer". She also lends vocals to the song "GO!" on Santigold's 2012 album "Master of My Make-Believe".


title: Karen O

text: On the collaboration project with N.A.S.A. on "The Spirit of Apollo", she appears on the track "Strange Enough", together with Ol' Dirty Bastard and Fatlip. O's vocal approach has been described as "ethereal", and has been described as "yelping" at times. She described her approach:


title: Karen O

text: O has also collaborated with James Iha on his second solo LP "Look to the Sky" in 2012. In 2014, Target used a version of the song "A Marshmallow World" sung by O. In 2015 she did a remake of Animotion's Obsession, written by legendary songwriter, Holly Knight for a new STARZ show, Flesh and Bone. On May 5, 2015, a song by Karen O in tribute to Nellie Bly was used as part of a Google doodle commemorating Bly's 151st birthday. The same year, Microsoft approached O to pen a theme song for Square Enix's game "Rise of the Tomb Raider", which resulted in the song "I Shall Rise".


title: Karen O

text: O was featured in the track "Cut Me Up" by Har Mar Superstar for the soundtrack to the 2005 horror film "House of Wax". For the movie "Jackass 2", O collaborated with electronic artist Peaches and Johnny Knoxville to record a track entitled "Backass"; for "Jackass 3D", she covered the Roger Alan Wade's "If You're Gonna Be Dumb" under the alternative title of "If You're Gonna Be Dumb, You Gotta Be Tough". In 2007, she also contributed vocals to a version of Bob Dylan's "Highway 61 Revisited" for the "I'm Not There" film soundtrack. At the end of episode 409, "Brothers Cinco", of the "Tim and Eric Awesome Show, Great Job!" she performed a short song. She also has a song titled "Strange Love" on the album "Frankenweenie Unleashed!"


title: Karen O

text: O collaborated with Trent Reznor and Atticus Ross on a cover version of Led Zeppelin's "Immigrant Song" for the soundtrack to the 2011 film "The Girl with the Dragon Tattoo", for which Reznor and Ross composed the score. In December 2011, it was announced that the song would open the soundtrack album, be released as the opening single, and be available free to all who pre-ordered before the official release date of December 9.


title: Karen O

text: O and Spike Jonze collaborated on a 2005 Adidas commercial, "Hello Tomorrow", after Jonze had directed the video for the Yeah Yeah Yeahs' 2004 single "Y Control". O composed all songs on of Jonze's film "Where the Wild Things Are" (with the exception of a cover of the Daniel Johnston song "Worried Shoes") in collaboration with Carter Burwell. She is listed on the soundtrack as "Karen O and the Kids". The song "All Is Love", written by O and Nick Zinner and included in this soundtrack, was nominated for the Grammy Award for Best Song Written for a Motion Picture, Television or Other Visual Media, a songwriter's award, at the 2010 Grammy Awards.


title: Karen O

text: O also contributed "The Moon Song" to Jonze's 2013 film "Her". O and Jonze were nominated in 2014 for an Academy Award for Best Original Song for "The Moon Song".


title: Karen O

text: In 2004, O, using the moniker Marshmellow, directed the music video for "We Fenced Other Gardens with the Bones of Our Own" by Liars, fronted by her then-boyfriend Angus Andrew. The following year, she directed the "Blessed Evening" video for Foetus with her then-boyfriend Spike Jonze working as cinematographer. In 2006, she directed the Yeah Yeah Yeahs video for "Cheated Hearts".


title: Karen O

text: Under the moniker Kids with Canes, O and her now-husband Barnaby Clay directed the music video for the Tiny Masters of Today song "Hologram World", released in 2008. O also contributed vocals to the song and served as choreographer of the video, in which she appears with Yeah Yeah Yeahs bandmates Nick Zinner and Brian Chase, as well as Mike D from the Beastie Boys, Gibby Haynes from the Butthole Surfers, Russell Simins from the Blues Explosion, and Sam James from The Mooney Suzuki.


title: Karen O

text: On December 10, 2006, a home-recorded album titled "KO at Home" was leaked via an invite-only BitTorrent tracking site. The album, originally a personal gift to Dave Sitek of TV on the Radio, was discovered inside a suitcase that Sitek had left behind in a New York City apartment. The disc's 14 tracks and scan of the cover (a photograph of O with a poem written by Oscar Wilde on the back side of the photo) quickly spread. News sites broke the story of the leak when Sitek lashed out at the fan who leaked the demos. Eventually, Sitek followed up his comments with an apology letter. In response to the leak, O said that "shit happens", and although she was "a little grossed out", she offered commentary on which of the songs she liked the most.


title: Karen O

text: O's debut solo album, "Crush Songs", was released on September 9, 2014. It was released on Cult Records via Kobalt Label Services. On February 17, 2015, O released a live album titled "Live from Crush Palace", recorded during three shows at Hollywood Forever Cemetery's Masonic Lodge in Los Angeles in September 2014. The album features live renditions of songs from "Crush Songs", as well as "Hideaway" from "Where the Wild Things Are" and "The Moon Song" from "Her". On January 11, 2018, O released the song "Yo! My Saint", featuring guest vocals from Michael Kiwanuka, in support of Kenzo's Spring Summer 2018 collection.


title: Karen O

text: Lux Prima is the collaborative album from Karen O and musician-producer Danger Mouse, released March 15, 2019. The two originally met to discuss collaboration in 2007 as mutual admirers, but did not collaborate until 2016 due to scheduling and availability, resulting in the album "Lux Prima" three years later.


title: Karen O

text: "An Encounter with Lux Prima" was an immersive art piece and communal listening experience soundtracked by Karen O and Danger Mouse's collaborative album "Lux Prima". The installation premiered at Los Angeles' Marciano Art Foundation in April 2019, where it played to sold-out audiences. The piece saw the duo collaborate with a number of artists, including creative director Barnaby Clay, sound designer Ren Klyce, lighting designer Tobias Rylander and visual artist Davy Evans, in collaboration with George Lucas' Skywalker Sound and Meyer Sound on audio design and build, as well as MSG's Obscura Digital on projection mapping.


title: Karen O

text: O has dated Spike Jonze and Liars lead singer Angus Andrew, the latter of whom was the subject of the Yeah Yeah Yeahs' song "Maps". In December 2011, she married director Barnaby Clay. Their son Django was born in August 2015.


title: Karen O

text: O was nominated for the Academy Award for Best Original Song for co-writing "The Moon Song" with Spike Jonze for the film "Her".


title: Jeezy

text: Jay Wayne Jenkins (born September 28, 1977), known by his stage name Jeezy (or Young Jeezy), is an American rapper. Signing to Def Jam Recordings in 2004, his major label debut, "", was released the following year and debuted at #2 on the "Billboard" 200, selling 172,000 copies in its first week and was later receiving platinum certification by the Recording Industry Association of America (RIAA). Jeezy is credited, along with fellow Atlanta-based rappers T.I. and Gucci Mane, for helping to pioneer and popularize trap music with a mainstream audience.


title: Jeezy

text: Jeezy began his music career in 2001 as Lil J with the release of "Thuggin' Under the Influence (T.U.I.)". In total, Jeezy has released ten studio albums, as well as numerous successful singles, including the top five hit "Soul Survivor" (featuring Akon), as well as the top 40 hits "I Luv It", "Go Getta" (featuring R. Kelly), and "Put On" (featuring Kanye West). In addition, Jeezy has also been featured on numerous hip hop and R&B hit singles, including "Say I" by Christina Milian, "I'm So Paid" by Akon, "Hard" by Rihanna and "Love in This Club" by Usher, with the latter reaching number one on the US "Billboard" Hot 100 in 2008.


title: Jeezy

text: Outside of his solo career, Jeezy is also the "de facto" leader of the Southern hip-hop group United Streets Dopeboyz of America (U.S.D.A) and a former member of the Bad Boy Records' rap group Boyz n da Hood.


title: Jeezy

text: Jay Wayne Jenkins was born on September 28, 1977, in Columbia, South Carolina. When he was a toddler, Jenkins relocated to Atlanta, Georgia, where he lived with different family members, as a result of his parents separating. In an interview with "XXL" magazine, he described his childhood as "empty". At a point in time he lived in Hawkinsville, Georgia, at 600 N Lumpkin. He had lived in Macon, Georgia at an older age, where he befriended many Crip gang members and even affiliated himself with the Crips and started his affiliation with Kinky B who helped his career along with many others.


title: Jeezy

text: In 1994, Jeezy spent nine months in YCA (Youth Challenge Academy), a boot camp in Fort Stewart, Georgia, for narcotics possession. Four years later, in 1998, Jeezy launched the label imprint CTE World, then known as Corporate Thugz Entertainment.


title: Jeezy

text: In 2001, under the name Lil J, Young Jeezy released his first independent album, "Thuggin' Under the Influence (T.U.I.)". The album included features from artists Freddy J., Kinky B, Fidank, and Lil Jon, who also produced some of the songs. In 2003, Jeezy independently released "Come Shop wit Me", a two-CD set featuring new tracks along with some songs previously released on "T.U.I""." In 2004, Jeezy signed with Bad Boy Records and joined the group Boyz n da Hood, whose self-titled album was released in June 2005 and peaked at #5 on the "Billboard" 200 album chart.


title: Jeezy

text: In May 2004, Jazze Pha's manager, Henry 'Noonie' Lee, showed Jeezy's demo to his friend Shakir Stewart, then Vice President Artist and Repertoire (VP A&R) at Def Jam. Stewart "fell in love with it [the demo] the first time [he] heard it" and took it to L.A. Reid. Reid recognized Jeezy's talent and gave Stewart the green light to sign him. However, due to Jeezy's rising popularity, other record labels began pursuing him simultaneously to sign with them, most notably, Warner and Interscope. Ultimately, Jeezy decided he wanted to be in business with Stewart and Reid and signed with Def Jam Records as a result.


title: Jeezy

text: Jeezy released his major label debut, "", on July 26, 2005. The album debuted at #2 on the Billboard 200, selling 172,000 copies in its first week and was later certified Platinum by the RIAA. The debut single off his debut album, "And Then What" featured Mannie Fresh and reached #67 on the "Billboard" Hot 100. The second single off the album, "Soul Survivor" featuring Akon, reached #4 on the Billboard Hot 100 and would become Jeezy's highest-charting single of his career. The third single, "My Hood", reached #77 on the Billboard Hot 100. In an interview with HitQuarters, A&R Shakir Stewart said that Jeezy had recorded over 60 songs for the album.


title: Jeezy

text: In interviews and on several records, Jeezy has affirmed his resistance to commercialism in his music. According to Jeezy, maintaining his street credibility, is of the utmost concern to him as an artist. In 2005, Jeezy was featured in several popular hip hop songs including Gucci Mane's "Icy" and Boyz n da Hood's "Dem Boyz". He would later leave the group after successfully establishing himself as a solo artist.


title: Jeezy

text: In 2006, Jeezy was featured in Christina Milian's single "Say I". Later that year, on December 12, he released his second major label album, "The Inspiration". It topped the Billboard 200 with first-week sales of 352,000 copies and would go on to be certified Platinum by the RIAA. The album's first single, "I Luv It", peaked at #14 on the Billboard Hot 100 and the second single, "Go Getta" featuring R. Kelly, peaked at #18.


title: Jeezy

text: Jeezy also extended himself into gaming, portraying himself in the 3D hip-hop fighting game "," released in March 2007. Also in 2007, Jeezy's group U.S.D.A (alongside Blood Raw and Slick Pulla) released their debut album, "Cold Summer". The album debuted at number 4 on the "Billboard" 200, selling 95,000 copies in its first week.


title: Jeezy

text: On December 17, 2007, Jeezy and CTE started their week-long toy drive and charity event series called the Toyz N Da Hood Drive. The series presented 1,000 toys for 1,000 kids at various locations in Macon and Atlanta. The CTE Christmas Kickoff portion of the event ran from 10 pm to 5 am at Club Miami. The toy giveaway took place in the Unionville neighborhood of Macon and at the Old Fourth Ward Community in Atlanta.


title: Jeezy

text: On September 2, 2008, Jeezy released "The Recession", his third studio album and, what would be, his second consecutive number one album. It topped the Billboard 200, selling 260,000 copies in its first week and was later certified gold by the RIAA. The album's lead single, "Put On", featured Kanye West and reached #12 on the Billboard Hot 100. T"he Recession" also earned Jeezy a Grammy Award nomination for Best Rap performance by a duo. Other singles off the album included "Vacation", "Crazy World", "My President" featuring Nas, and "Who Dat" featuring Shawty Redd. Separately, Jeezy made appearances on Usher's "Love in This Club" and Akon's "I'm So Paid", which was also with Lil Wayne. "Love in This Club" peaked at #1 on the "Billboard" Hot 100. Later, Jeezy performed on Ciara's single "Never Ever", from her album "Fantasy Ride".


title: Jeezy

text: In the summer of 2008, Jeezy was at the center of a controversy over his choice for president. While he had previously endorsed Barack Obama, during an interview with "Vibe", Jeezy spoke about meeting and supporting John McCain. The statement caused a stir, and Jeezy quickly clarified his stance via a viral video. In the four-minute explanation, Jeezy made it clear that Obama was his main choice. "I represent the Democratic party. ... I've never been nor do I ever plan to be a John McCain supporter", the rapper said. "I support Barack Obama." Jeezy and Jay-Z performed in a concert to celebrate the inauguration of President Obama on January 18, 2009. On "The O'Reilly Factor", commentator Bill O'Reilly criticized their performance as a "rant that offended people", but Jeezy responded: "I got white friends. It's nothing like that. I'm a taxpayer, I got a right to voice my opinion at any point in time. I don't think he really understands my struggle."


title: Jeezy

text: It was announced in November 2009 that Jeezy started working on "Thug Motivation 103". In March 2010, it was reported that Young Jeezy dropped "Young" from his stage name. Later, Young Jeezy denied the name change and claimed it was just a rumor: However, on the cover for his single "Lose My Mind", his name is printed as "Jeezy". "Lose My Mind" peaked at #35 on the Billboard Hot 100.


title: Jeezy

text: On March 4, 2010, Jeezy released "Illin", featuring Pusha T of the rap duo Clipse. On the track, Pusha T raps, "No amount of record sales could derail this ...Stuffing dead prezzies in the wall like that Yale bitch..." This line was controversial as many felt the line was in bad taste since it references Yale student Annie Le, who was murdered in 2009. Many felt Young Jeezy and Pusha were making light of Le's tragic death.


title: Jeezy

text: Nearly two years after first announcing work on "Thug Motivation 103", on May 17, 2011, Jeezy released the first single off the album, "Ballin", which features Lil Wayne and peaked at #57 on the "Billboard" Hot 100. Two months later, on July 22, the second intended single off the album was released, a track called "Shake Life," although it was later scrapped. On July 26, 2011, Jeezy announced a September 20, 2011 release date for "Thug Motivation 103". However the album was pushed back yet again, this time to December 20, 2011. On September 29, 2011, Jeezy released the third single off "Thug Motivation 103", named "F.A.M.E." (Fake Ass Motherfuckers Envy), featuring T.I. The song was T.I.'s first appearance on a song since his release from prison. On December 20, 2011, "Thug Motivation 103" was finally released. The album debuted at #3 on the Billboard 200, selling 233,000 copies in its first week, becoming certified Gold by the RIAA. "I Do" featuring André 3000 and Jay-Z was the album's fourth single; it peaked at #61 on the Billboard Hot 100. "Leave You Alone" featuring Ne-Yo was the album's fifth single and reached #51 on the Billboard Hot 100. In 2012, Young Jeezy's "I Do" received a Grammy nomination for Best Rap Performance.


title: Jeezy

text: In October 2012, Jeezy released a new single called "Get Right" on ITunes and sent it to radio. Shortly after the single's release, Jeezy confirmed he had plans to release a new mixtape by the end of 2012 as well as a new album in 2013. On December 12, 2012, Jeezy released "It's Tha World", the aforementioned mixtape, hosted by DJ Drama. The mixtape features 2 Chainz, Trey Songz, Lil Boosie, Birdman, YG and E-40. Production came from Jahlil Beats, The Renegades, DJ Mustard, Warren G, Mike WiLL Made It, Cardo and Black Metaphor.


title: Jeezy

text: On August 13, 2013, Young Jeezy released a compilation mixtape titled "Boss Yo Life Up Gang" with CTE World artists, Doughboyz Cashout and YG . The mixtape has two singles, "My Nigga" by YG and "Mob Life" by Doughboyz Cashout, both of which Young Jeezy was featured on. On September 17, 2013, Jeezy premiered the first single "In My Head" produced by Childish Major, from his CTE collaboration mixtape "Its Tha World 2". The following day he announced plans to release his next album, saying it will more deeply detail his street origins. He revealed that Future, Usher, Ludacris, and Don Cannon would be involved in the album.


title: Jeezy

text: On May 30, 2014, Jeezy released the first single "Me Ok" from his upcoming fifth studio album "". On July 1, 2014, he released the second single, "Seen It All", featuring Jay-Z. On August 31, 2015, Jeezy announced that he would release a new project entitled "Church in These Streets". Four singles were released and the project as a whole came on November 13, 2015. It debuted at #4 on the Billboard 200.


title: Jeezy

text: On October 28, 2016, Jeezy released his new album "Trap or Die 3", which became available for pre-order on iTunes earlier that month. It debuted at number one on the "Billboard" 200, becoming Jeezy's third album to top the chart.


title: Jeezy

text: On December 15, 2017, Jeezy released his eighth studio album "Pressure" (originally titled Snow Season).


title: Jeezy

text: On August 23, 2019, Jeezy released his ninth album, "". It was planned to be his final album, as he wanted to venture into acting at the time.


title: Jeezy

text: On November 20, 2020, Jeezy released his tenth studio album, "The Recession 2". As with the original, "The Recession", which was released 12 years prior, it is a reflection of the "current times", as Jeezy explained: "It just really inspired me to touch on some of that, but at the same time, motivate my people and give them something to help them through these times and to celebrate, because the shift is happening". The 15-track album features guest appearances from Rick Ross, Ne-Yo, Yo Gotti, E-40, and Demi Lovato, among others. The night before the album's release, Jeezy went live for a "Verzuz" against Gucci Mane. In addition to the album, he announced a limited series podcast called The (Re)Session Podcast.


title: Jeezy

text: After Hurricane Katrina, Jeezy opened his house to victims, offering those who had been displaced from their homes a place to call home. He has children from previous relationships.


title: Jeezy

text: On March 11, 2005, Jeezy was arrested after an alleged shooting with some of his friends in Miami Beach, Florida. He was charged with two counts of carrying a concealed weapon without a permit; however, prosecutors dropped his charges two months later due to lack of evidence.


title: Jeezy

text: On April 16, 2013, Brian Smith filed a copyright infringement complaint seeking an injunction, damages, and attorney fees against Jay W. Jenkins d/b/a Young Jeezy Music and others in the United States District Court for the Northern District of Georgia, concerning the work "Jizzle" which was released in July 2010.


title: Jeezy

text: On August 27, 2013, Leroy Hutson aka Lee Hutson Sr., former lead singer of 1970s R&B group The Impressions, filed a complaint against Young Jeezy and others alleging that Young Jeezy's song "Time" inappropriately incorporated the instrumental portion of "Getting it On", which was registered with the United States Copyright Office in 1973.


title: Jeezy

text: On January 4, 2014, Jeezy was arrested for battery, false imprisonment, and terrorist threats, after an alleged fight with his son in September 2012.


title: Jeezy

text: On August 24, 2014, Jeezy was arrested before performing at the Irvine, California, stop on the Under The Influence Tour in connection with the deadly shooting two days prior in the backstage area, on another stop of the tour in Mountain View, California. When the police raided Jeezy's tour bus, they found an AK-47 military-style assault rifle and guns on several members of his entourage. In total six people, including Jeezy were arrested, because "no one admitted to owning the assault rifle." His bail was set at one million dollars. On August 26, Jeezy, as well as the five other men he was arrested with, entered not guilty pleas to possession of an illegal assault rifle. Two days later, Jeezy and his associates bonded out. Officers were reportedly told repeatedly that the registered owner of the AK-47 was the tour security chief, who was hospitalized at the time.


title: Prostate cancer

text: Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. It is located in the hypogastric region of the abdomen. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior. Only those who have male reproductive organs are able to get prostate cancer. Most prostate cancers are slow growing. Cancerous cells may spread to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty urinating, blood in the urine, or pain in the pelvis or back. Benign prostatic hyperplasia may produce similar symptoms. Other late symptoms include fatigue, due to low levels of red blood cells.


title: Prostate cancer

text: Factors that increase the risk of prostate cancer include older age, family history and race. About 99% of cases occur after age 50. A first-degree relative with the disease increases the risk two- to three-fold. Other factors include a diet high in processed meat and red meat, while the risk from a high intake of milk products is inconclusive. An association with gonorrhea has been found, although no reason for this relationship has been identified. An increased risk is associated with the "BRCA "mutations. Diagnosis is by biopsy. Medical imaging may be done to assess whether metastasis is present.


title: Prostate cancer

text: Prostate cancer screening, including prostate-specific antigen (PSA) testing, increases cancer detection but whether it improves outcomes is controversial. Informed decision making is recommended for those 55 to 69 years old. Testing, if carried out, is more appropriate for those with a longer life expectancy. Although 5α-reductase inhibitors appear to decrease low-grade cancer risk, they do not affect high-grade cancer risk, and are not recommended for prevention. Vitamin or mineral supplementation does not appear to affect risk.


title: Prostate cancer

text: Many cases are managed with active surveillance or watchful waiting. Other treatments may include a combination of surgery, radiation therapy, hormone therapy, or chemotherapy. Tumors limited to the prostate may be curable. Pain medications, bisphosphonates, and targeted therapy, among others, may be useful. Outcomes depend on age, health status and how aggressive and extensive the cancer is. Most men with prostate cancer do not die from it. The United States five-year survival rate is 98%.


title: Prostate cancer

text: Globally, it is the second-most common cancer. It is the fifth-leading cause of cancer-related death in men. In 2018, it was diagnosed in 1.2 million and caused 359,000 deaths. It was the most common cancer in males in 84 countries, occurring more commonly in the developed world. Rates have been increasing in the developing world. Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing. One study reported prostate cancer in 30% to 70% of Russian and Japanese men over age 60 who had died of unrelated causes.


title: Prostate cancer

text: Early prostate cancer usually has no clear symptoms. When they do appear, they are often similar to those of benign prostatic hyperplasia. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria (blood in the urine), dysuria (painful urination) as well as fatigue due to anemia, and bone pain. One study found that about a third of diagnosed patients had one or more such symptoms.


title: Prostate cancer

text: Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.


title: Prostate cancer

text: Metastatic prostate cancer can cause additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the part of the bone nearer to the prostate. Prostate cancer in the spine can compress the spinal cord, causing tingling, leg weakness, and urinary and fecal incontinence.


title: Prostate cancer

text: The primary risk factors are obesity, age, and family history. Obese men have been found to have a 34% greater death rate from prostate cancer than those with normal weight. Prostate cancer is uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes found prostate cancer in 30% of men in their 50s, and in 80% of men in their 70s.


title: Prostate cancer

text: Men with high blood pressure are more likely to develop prostate cancer. A small increase in risk is associated with lack of exercise. Elevated blood testosterone levels may increase risk.


title: Prostate cancer

text: Genetics may affect risk, as suggested by associations with race, family, and specific gene variants. Men who have a first-degree relative (father or brother) with prostate cancer have twice the risk of developing prostate cancer, and those with two first-degree relatives affected have a five-fold greater risk compared with men with no family history. This risk appears to be greater for men with an affected brother than for those with an affected father. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men. In contrast, the incidence and mortality rates for Hispanic men are one-third lower than for non-Hispanic whites. Twin studies in Scandinavia suggest that 58% of prostate cancer risk can be explained by inherited factors.


title: Prostate cancer

text: Many genes are involved in inherited risk for prostate cancer. The first gene linked to inherited prostate cancer in families was hereditary prostate cancer gene 1 ("HPC1"). Mutations within the HOXB13 gene can also carry strong risk for prostate cancer. Inherited genetic variation of the chromosome 8q24 locus, one that is prominently observed through genome-wide association study (GWAS) of both familial and sporadic prostate cancer, can carry near-Mendelian (up to 20-fold) risk for prostate cancer. This region encompasses regulatory elements, non-coding genes, and the stem cell related POU5F1B gene. Roughly 4% of families in which multiple men are affected by prostate cancer carry mutations in HOXB13, and another 4% carry mutations at 8q24. Mutations in "BRCA1" and "BRCA2" (important risk factors for ovarian cancer and breast cancer in women) have also been implicated.


title: Prostate cancer

text: Two large GWAS discovered common low-risk single-nucleotide polymorphisms (SNPs) that are associated with prostate cancer in 2008. These studies identified several relevant SNPs. For example, individuals with TT allele pair at SNP rs10993994 were reported to be at 1.6 times higher risk than those with the CC allele pair. This SNP explains part of the increased risk faced by African-Americans. The C allele is much more prevalent in the latter; this SNP is located in the promoter region of the "MSMB" gene, thus affects the amount of MSMB protein synthesized and secreted by epithelial cells of the prostate.


title: Prostate cancer

text: While fewer studies have been conducted assessing the risk of being diagnosed with aggressive prostate cancer, a GWAS of 12,518 prostate cancer cases identified two loci associated with high Gleason sum score, SNP rs78943174 nearest to the gene "NAALADL2" and SNP rs35148638 nearest to "RASA1".


title: Prostate cancer

text: A number of somatic mutations (acquired rather than inherited) have also been defined in prostate tumors that drive their growth. TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth. These fusions can arise via complex rearrangement chains called chromoplexy.


title: Prostate cancer

text: Plant-based diets are associated with a lower risk for prostate cancer. Switching to a plant-based diet shows favorable results for cancer outcomes in men with prostate cancer. Especially vegan diets consistently show favorable associations with prostate cancer risk and outcomes.


title: Prostate cancer

text: Consuming fruits and vegetables has been found to be of little preventive benefit. Some studies report that higher meat consumption was associated with higher risk.


title: Prostate cancer

text: The consumption of milk may be related to prostate cancer. A 2020 systematic review found the results on milk consumption and prostate cancer inconclusive but stated that individuals with higher risk may reduce or eliminate milk. A 2019 overview stated that the evidence that linked milk to higher rates of prostate cancer was inconsistent and inconclusive. A 2021 study from Japan looking at 26,464 men found that milk consumption increased the risk of prostate cancer by 37%.


title: Prostate cancer

text: Lower blood levels of vitamin D may increase risks. One study found no effect of folic acid supplements on risk.


title: Prostate cancer

text: Some links have been established between prostate cancer and medications, medical procedures, and medical conditions. Statins may also decrease risk.


title: Prostate cancer

text: Prostatitis (infection or inflammation) may increase risk. In particular, infection with the sexually transmitted infections "Chlamydia", gonorrhea, or syphilis seems to increase risk.


title: Prostate cancer

text: Papilloma virus has been proposed to have a potential role, but as of 2015, the evidence was inconclusive; as of 2018, the increased risk was debated.


title: Prostate cancer

text: US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.


title: Prostate cancer

text: Although some evidence from prospective cohort studies indicates that frequent ejaculation may reduce prostate cancer risk, no randomized controlled trials reported this benefit. An association between vasectomy and prostate cancer was found, but causality has not been established.


title: Prostate cancer

text: The prostate is part of the male reproductive system that helps make and store seminal fluid. In adult men, a typical prostate is about 3 cm long and weighs about 20 g. It is located in the pelvis, under the urinary bladder and in front of the rectum. The prostate surrounds part of the urethra, the tube that carries urine from the bladder during urination and semen during ejaculation. The prostate contains many small glands, which make about 20% of the fluid constituting semen.


title: Prostate cancer

text: Superiorly, the prostate base is contiguous with the bladder outlet. Inferiorly, the prostate's apex heads in the direction of the urogenital diaphragm, which is pointed anterio-inferiorly. The prostate can be divided into four anatomic spaces: peripheral, central, transitional, and anterior fibromuscular stroma. The peripheral space contains the posterior and lateral portions of the prostate, as well as the inferior portions of the prostate. The central space contains the superior portion of the prostate including the most proximal aspects of the urethra and bladder neck. The transitional space is located just anterior to the central space and includes urethra distal to the central gland urethra. The neurovascular bundles course along the posterolateral prostate surface and penetrate the prostatic capsule there as well.


title: Prostate cancer

text: Most of the glandular tissue is found in the peripheral and central zones (peripheral zone: 70-80% of glandular tissue; central zone: 20% of glandular tissue). Some is found in the transitional space (5% of glandular tissue). Thus, most cancers that develop from glandular tissue are found in the peripheral and central spaces, while about 5% is found in the transitional space. None is found in the anterior fibromuscular stroma since no glands are in that anatomic space.


title: Prostate cancer

text: The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes;dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.


title: Prostate cancer

text: Because of the prostate's location, prostate diseases often affect urination, ejaculation, and rarely defecation. In prostate cancer, the cells of these glands mutate into cancer cells.


title: Prostate cancer

text: Most prostate cancers are classified as adenocarcinomas, or glandular cancers, that begin when semen-secreting gland cells mutate into cancer cells. The region of the prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain within otherwise normal prostate glands, a condition known as carcinoma "in situ" or prostatic intraepithelial neoplasia (PIN). Although no proof establishes that PIN is a cancer precursor, it is closely associated with cancer. Over time, these cells multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.


title: Prostate cancer

text: Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or tumor cells may develop the ability to travel in the bloodstream and lymphatic system.


title: Prostate cancer

text: Prostate cancer is considered a malignant tumor because it can invade other areas of the body. This invasion is called metastasis. Prostate cancer most commonly metastasizes to the bones and lymph nodes, and may invade the rectum, bladder, and lower ureters after local progression. The route of metastasis to bone is thought to be venous, as the prostatic venous plexus draining the prostate connects with the vertebral veins.


title: Prostate cancer

text: The prostate is a zinc-accumulating, citrate-producing organ. Transport protein ZIP1 is responsible for the transport of zinc into prostate cells. One of zinc's important roles is to change the cell's metabolism to produce citrate, an important semen component. The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells require enormous amounts of energy (ATP) to accomplish this task. Prostate cancer cells are generally devoid of zinc. Prostate cancer cells save energy by not making citrate, and use the conserved energy to grow, reproduce and spread.


title: Prostate cancer

text: The absence of zinc is thought to occur via silencing the gene that produces ZIP1. It is called a tumor suppressor gene product for the gene "SLC39A1". The cause of the epigenetic silencing is unknown. Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-κB pathways, is antiproliferative, and induces apoptosis in abnormal cells. Unfortunately, oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without ZIP1.


title: Prostate cancer

text: Loss of cancer suppressor genes, early in prostatic carcinogenesis, have been localized to chromosomes" 8p", "10q", "13q", and "16q". P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are a late event in the pathology. Other tumor suppressor genes that are thought to play a role include "PTEN" and "KAI1". "Up to 70 percent of men with prostate cancer have lost one copy of the "PTEN" gene at the time of diagnosis". Relative frequency of loss of E-cadherin and CD44 has also been observed. Loss of the retinoblastoma (RB) protein induces androgen receptor deregulation in castration-resistant prostate cancer by deregulating 'E2F1 expression"."


title: Prostate cancer

text: The factors that drive disease progression and clinical prognosis remain only partly understood but a variety of molecular determinants has been identified that appear to be involved. The most important of these might be the tyrosine phosphatase ACP1 of which the expression might outperform the Gleason grading system for predicting disease course. Other molecules identified include the transcription factor RUNX2 which may prevent cancer cells from undergoing apoptosis, the PI3k/Akt signaling cascade in conjunction with the transforming growth factor beta/SMAD signaling cascade that also protect against apoptosis. Pim-1 is upregulated in prostate cancer. X-linked inhibitor of apoptosis (XIAP) is hypothesized to promote cancer cell survival and growth, the Macrophage inhibitory cytokine-1 (MIC-1) that stimulates the focal adhesion kinase (FAK) signaling pathway. Nevertheless, it is fair to say that the molecular factors that determine why some patients have quiescent disease while otherdisplay prognosis remain largely obscure.


title: Prostate cancer

text: The androgen receptor helps cancer cells to survive. Prostate-specific membrane antigen (PSMA) stimulates cancer development by increasing folate levels, helping the cancer cells to survive and grow; it increases available folates for use by hydrolyzing glutamated folates.


title: Prostate cancer

text: Several other tests can be used to gather information about the prostate and the urinary tract. Digital rectal examination may allow a doctor to detect prostate abnormalities. Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted in the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum, but the only test that can fully confirm the diagnosis of prostate cancer is a biopsy, the removal of small pieces of the prostate for microscopic examination.


title: Prostate cancer

text: Ultrasound and magnetic resonance imaging (MRI) are the two main imaging methods used for prostate cancer detection.


title: Prostate cancer

text: On MRI, the central and transitional zones both have lower T2 signal than the peripheral zone. Since the central and transitional zones cannot be distinguished from each other, they can be best described as the central gland on MRI. Thus, the peripheral gland has a higher signal on T2WI than the central gland. In the peripheral gland, prostate cancer appears as a low-intensity lesion. However, in the central gland, low-intensity lesions cannot be distinguished from the low-intensity central gland. Diffusion restriction is instrumental in identifying and characterizing central gland lesions. Combined diffusion-weighted (DW) imaging and dynamic contrast-enhanced MRI for distinguish malignant from benign prostate lesions can be used. The merged images, of DW and MRI with dynamic contrast enhancement, can visualise areas with low signal intensity and fast wash-out effect - characteristic of carcinomas. Lymphadenopathy can be seen best on postcontrast, fat-suppressed T1WI. Other regions can be described on MRI. The anterior fibromuscular stroma and the prostate capsule along the posterior and lateral prostate have a low T2WI signal, in contrast with the bright signal of the peripheral zone. Extraprostatic extension can be seen with disruption of capsule integrity.


title: Prostate cancer

text: As of 2011, MRI was used to identify targets for prostate biopsy using fusion MRI with ultrasound (US) or MRI-guidance alone. An MRI alone will correctly identify 91% of men with clinically significant prostate cancer but will misclassify 63% of men at risk for prostate cancer as having clinically significant prostate cancer. An MRI-targeted biopsy will correctly identify 80% of men with prostate cancer. However, it will classify 6% of men at risk for prostate cancer as having clinically significant prostate cancer. Detection of clinically insignificant cancer has been shown to be decreased when MRI-targeted biopsy is combined with standard biopsy for men with positive results on MRI, as compared with a standard biopsy method.


title: Prostate cancer

text: Following an MRI, regions of interest within the scan which may be cancer are often graded on a likelihood scale between 1 and 5. One such scale is the prostate imaging-reporting and data system (PI-RADS) scale which defines standards of clinical service for multiparametric MRI (mpMRI), including image creation and reporting. PI-RADS version 2 scoring has shown a specificity and sensitivity of 73% and 95%, respectively, for detection of prostate cancer.


title: Prostate cancer

text: When an MRI is used to decide whether to do a biopsy in men who have had a prior biopsy, it is 5% more likely to make a correct diagnosis than a standard biopsy and is 12% more likely to be correct for men who may or may not have had a prior biopsy. In men who have had a negative biopsy, this combination is 44% more likely to lead to a correct diagnosis.


title: Prostate cancer

text: Prostate MRI is also used for surgical planning for robotic prostatectomy. It helps surgeons decide whether to resect or spare the neurovascular bundle, determine return to urinary continence, and help assess surgical difficulty. MRI is used in other types of treatment planning, for both focal therapy and radiotherapy. MRI can also be used to target areas for research sampling in biobanking.


title: Prostate cancer

text: The biological properties which determine whether or not a tumour is visible on MRI is poorly understood. One theory is that tumour cells undergo several genetic changes during transformation which alter the cellular rate of growth and formation of new blood vessels, leading to tumours with more aggressive histological patterns, hypoxic regions and increased cell density among other features. Having larger, more dense tumours with changes in blood vessel distributions may feasibly alter signal on MRI through restriction of water and/or fluid movement.


title: Prostate cancer

text: Some studies have linked the presence of rare histological patterns within the tumour such as cribriform pattern. Although recent research suggests there is a number of histopathological features which may influence tumour detection by MRI. At a genetic level, prostate cancer visibility on MRI seems to be linked with genetic features of aggressive disease including processes such as cell proliferation, tumour hypoxia and DNA damage. The gene changes consistently observed in MRI-visible tumours include loss of tumour suppressor PTEN, increased expression of proliferation associated genes CENPF, AGR2 and growth factor GDF15 as well as a number of other genes. Changes in these pathways and genes may facilitate increased tumour growth, changes in vasculature and density which ultimately change the signal on MRI.


title: Prostate cancer

text: Ultrasound imaging can be obtained transrectally and is used during prostate biopsies. Prostate cancer can be seen as a hypoechoic lesion in 60% of cases. The other 40% of cancerous lesions are either hyperechoic or isoechoic. On Color Doppler, the lesions appear hypervascular.


title: Prostate cancer

text: If cancer is suspected, a biopsy is offered expediently. During a biopsy, a urologist or radiologist obtains tissue samples from the prostate via either the rectum or the perineum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Systematic biopsies correctly identify 63% of men as having clinically significant prostate cancer but will miss the rest. For men at risk for prostate cancer, biopsy will not misclassify any of the men as having clinically significant prostate cancer.


title: Prostate cancer

text: Antibiotics should be used to prevent complications such as fever, urinary tract infections, and sepsis even if the most appropriate course or dose is undefined. About 55% of men report discomfort during prostate biopsy.


title: Prostate cancer

text: A histopathologic diagnosis mainly includes assessment of whether a cancer exists, as well as any subdiagnosis, if possible. Histopathologic subdiagnosis has implications for the possibility and methodology of Gleason scoring. The most common histopathological subdiagnosis is acinar adenocarcinoma, constituting 93% of diagnoses. The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar adenocarcinoma.


title: Prostate cancer

text: Alkaline phosphatase is more elevated in metastatic than non-metastatic cells. High levels of alkaline phosphatase is associated with a significant decrease in survival.


title: Prostate cancer

text: The Gleason grading system is used to help evaluate the prognosis and helps guide therapy. A Gleason score is based upon the tumor's appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 through 10, with a higher number indicating greater risks and higher mortality.


title: Prostate cancer

text: In 2014, the International Society of Urological Pathology (ISUP) provided a new prostate cancer grading system called the ISUP scores.


title: Prostate cancer

text: Tissue samples can be stained for the presence of PSA and other tumor markers to determine the origin of malignant cells that have metastasized.


title: Prostate cancer

text: Small cell carcinoma is a rare (1%) type that cannot be diagnosed using PSA. researchers were investigating ways to screen for this type, because it is quick to metastasize.


title: Prostate cancer

text: The oncoprotein BCL-2 is associated with the development of androgen-independent prostate cancer, due to its high levels of expression in androgen-independent tumours in advanced stages. The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression.


title: Prostate cancer

text: An important part of evaluating prostate cancer is determining the stage, or degree of spread. Knowing the stage helps define prognosis and is useful when selecting therapies. The most common system is the four-stage TNM system (abbreviated from tumor/nodes/metastases). Its components include the size of the tumor, the number of involved lymph nodes, and the presence of any other metastases. In the United Kingdom the Cambridge Prognostic Group (CPG) is used for categorising prostate cancer into 5 risk groups (CPG1 to CPG5).


title: Prostate cancer

text: The most important distinction made by any staging system is whether the cancer is confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have metastasized. Several tests can be used to look for evidence of spread. Medical specialty professional organizations recommend against the use of PET scans, CT scans, or bone scans when a physician stages early prostate cancer with low risk for metastasis. Those tests would be appropriate in cases such as when a CT scan evaluates spread within the pelvis, a bone scan looks for spread to the bones, and endorectal coil magnetic resonance imaging evaluates the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to "increased" bone density in the areas of bone metastasis—the reverse of what is found in many other metastatic cancers. Approved radiopharmaceutical diagnostic agents used in PET: fluciclovine (2016), Ga 68 PSMA-11 (2020), piflufolastat (2021).


title: Prostate cancer

text: After a biopsy, a pathologist examines the samples under a microscope. If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The pathologist assigns a Gleason number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method.


title: Prostate cancer

text: In men with high-risk localised prostate cancer, staging with PSMA PET/CT may be appropriate to detect nodal or distant metastatic spread. In 2020, a randomised phase 3 trial compared Gallium-68 PSMA PET/CT to standard imaging (CT and bone scan). It reported superior accuracy of Gallium-68 PSMA-11 PET/CT (92% vs 65%), higher significant change in management (28% vs 15%), less equivocal/uncertain imaging findings (7% vs 23%) and lower radiation exposure (10 msV vs 19 mSv). The study concluded that PSMA PET/CT is a suitable replacement for conventional imaging.


title: Prostate cancer

text: The data on the relationship between diet and prostate cancer are poor. However, the rate of prostate cancer is linked to the consumption of the Western diet. Little if any evidence associates trans fat, saturated fat, and carbohydrate intake and prostate cancer. Evidence does not support a role for omega-3 fatty acids in preventing prostate cancer. Vitamin supplements appear to have no effect and some may increase the risk. High supplemental calcium intake has been linked to advanced prostate cancer.


title: Prostate cancer

text: Fish may lower prostate-cancer deaths, but does not appear to affect occurrence. Some evidence supports lower rates of prostate cancer with a vegetarian diet, lycopene, selenium cruciferous vegetables, soy, beans and/or other legumes.


title: Prostate cancer

text: In those who are regularly screened, 5-alpha-reductase inhibitors (finasteride and dutasteride) reduce the overall risk of prostate cancer. Data are insufficient to determine if they affect fatality risk and they may increase the chance of more serious cases.


title: Prostate cancer

text: Prostate cancer screening searches for cancers in those without symptoms. Options include the digital rectal exam and the PSA blood test. Such screening is controversial, and for many, may lead to unnecessary disruption and possibly harmful consequences. Harms of population-based screening, primarily due to overdiagnosis (the detection of latent cancers that would have otherwise not been discovered) may outweigh the benefits. Others recommend shared decision-making, an approach where screening may occur after a physician consultation.


title: Prostate cancer

text: The United States Preventive Services Task Force (USPSTF) suggests the decision whether to have PSA screening be based on consultation with a physician for men 55 to 69 years of age. USPSTF recommends against PSA screening after age 70. The Centers for Disease Control and Prevention endorsed USPSTF's conclusion. The American Society of Clinical Oncology and the American College of Physicians discourage screening for those who are expected to live less than 10–15 years, while those with a greater life expectancy a decision should individually balance the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment."


title: Prostate cancer

text: American Urological Association (AUA 2013) guidelines call for weighing the uncertain benefits of screening against the known harms associated with diagnostic tests and treatment. The AUA recommends that shared decision-making should control screening for those 55 to 69, and that screening should occur no more often than every two years. In the United Kingdom as of 2018, no program existed to screen for prostate cancer.


title: Prostate cancer

text: The first decision is whether treatment is needed. Low-grade forms found in elderly men often grow so slowly that treatment is not required. Treatment may be inappropriate if a person has other serious health problems or is not expected to live long enough for symptoms to appear. Approaches in which treatment is postponed are termed "expectant management". Expectant management is divided into two approaches: Watchful waiting, which has palliative intent (aims to treat symptoms only), and active surveillance, which has curative intent (aims to prevent the cancer from advancing).


title: Prostate cancer

text: Which option is best depends on disease stage, the Gleason score, and the PSA level. Other important factors are age, general health and a person's views about potential treatments and their possible side effects. Because most treatments can have significant side effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. A 2017 review found that more research focused on person-centered outcomes is needed to guide patients. A combination of treatment options is often recommended.


title: Prostate cancer

text: Guidelines for specific clinical situations require estimation of life expectancy. As average life expectancy increases due to advances in the treatment of other diseases, more patients will live long enough for their prostate cancer to express symptoms. An 18-item questionnaire was proposed to learn whether patients have adequate knowledge and understanding of their treatment options. In one 2015 study, most of those who were newly diagnosed correctly answered fewer than half of the questions.


title: Prostate cancer

text: The widespread use of PSA screening in the US has resulted in diagnosis at earlier age and cancer stage, but almost all cases are still diagnosed after age 65, while about 25% are diagnosed after age 75. Though US National Comprehensive Cancer Network guidelines recommend using life expectancy to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy or radiation therapy and are instead treated with hormonal therapy or watchful waiting.


title: Prostate cancer

text: Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. The tumor is carefully observed over time, with the intention of initiating treatment if signs of progression appear. Active surveillance is "not" synonymous with watchful waiting, a term which implies no treatment or specific program of monitoring, with the assumption that only palliative treatment would be used if advanced, symptomatic disease develops.


title: Prostate cancer

text: Active surveillance involves monitoring the tumor for growth or symptoms, which trigger treatment. The monitoring process may involve PSA tests, digital rectal examination, or repeated biopsies every few months. The goal of active surveillance is to postpone treatment, and avoid overtreatment and its side effects, given a slow-growing or self-limited tumor that in most people is unlikely to cause problems. This approach is not used for aggressive cancers, and may cause anxiety for people who wrongly believe that all cancers are deadly or that their condition is life-threatening. Between 50 and 75% of patients die from other causes without experiencing prostate symptoms. In localized disease, based on long-term follow-up, radical prostatectomy results in significantly improved oncological outcomes when compared with watchful waiting. Prostatectomy is associated with increased rates of urinary incontinence and erectile dysfunction, but these findings are based primarily on men diagnosed before widespread PSA screening and cannot be highly generalized. When compared to active monitoring/surveillance, on follow-up at ten years, radical prostatectomy probably has similar outcomes for disease-specific survival and probably reduces risk of disease progression and spreading. Urinary and sexual function are probably decreased in patients treated with radical prostatectomy.


title: Prostate cancer

text: Both surgical and nonsurgical treatments are available, but treatment can be difficult, and combinations can be used. Treatment by external beam radiation therapy, brachytherapy, cryosurgery, HIFU -->, and prostatectomy are, in general, offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for metastatic disease. Exceptions include local or metastasis-directed therapy with radiation may be used for advanced tumors with limited metastasis. Hormonal therapy is used for some early-stage tumors. Cryotherapy (the process of freezing the tumor), hormonal therapy, and chemotherapy may be offered if initial treatment fails and the cancer progresses. Sipuleucel-T, a cancer vaccine, was reported to offer a four-month increase in survival in metastatic prostate cancer, but the marketing authorisation for it was withdrawn on 19 May 2015.


title: Prostate cancer

text: If radiation therapy fails, radical prostatectomy may be an option, though it is a technically challenging surgery. However, radiation therapy "after" surgical failure may have many complications. It is associated with a small increase in bladder and colon cancer. Radiotherapy and surgery appear to result in similar outcomes with respect to bowel, erectile and urinary function after five years.


title: Prostate cancer

text: Non-surgical treatment may involve radiation therapy, chemotherapy, hormonal therapy, external beam radiation therapy, and particle therapy, high-intensity focused ultrasound, or some combination.


title: Prostate cancer

text: Prostate cancer that persists when testosterone levels are lowered by hormonal therapy is called castrate-resistant prostate cancer (CRPC). Many early-stage cancers need normal levels of testosterone to grow, but CRPC does not. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term CRPC emerged because these cancers show reliance upon hormones, particularly testosterone, for androgen receptor activation.


title: Prostate cancer

text: The cancer chemotherapeutic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. A second-line chemotherapy treatment is cabazitaxel. A combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC.


title: Prostate cancer

text: Immunotherapy treatment with sipuleucel-T in CRPC appeared to increase survival by four months. However, marketing authorisation for sipuleucel-T was withdrawn on 19 May 2015. The second line hormonal therapy abiraterone increases survival by about 4.6 months. Enzalutamide is another second line hormonal agent with a five-month survival advantage. Both abiraterone and enzalutamide are currently in clinical trials in those with CRPC who have not previously received chemotherapy.


title: Prostate cancer

text: Not all patients respond to androgen signaling-blocking drugs. Certain cells with characteristics resembling stem cells remain unaffected. Therefore, the desire to improve CRPC outcomes resulted in increasing doses or combination therapy with synergistic androgen-signaling blocking agents. But even these combination will not affect stem-like cells that do not exhibit androgen signaling.


title: Prostate cancer

text: For patients with metastatic prostate cancer that has spread to their bones, doctors use a variety of bone-modifying agents to prevent skeletal complications and support the formation of new bone mass. Zoledronic acid (a bisphosphonate) and denosumab (a RANK-ligand-inhibitor) appear to be effective agents, but are associated with more frequent and serious adverse events.


title: Prostate cancer

text: Radical prostatectomy is considered the mainstay of surgical treatment of prostate cancer, where the surgeon removes the prostate, seminal vesicles, and surrounding lymph nodes. It can be done by an open technique (a skin incision at the lower abdomen), or laparoscopically. Radical retropubic prostatectomy is the most commonly used open surgical technique. Robotic-assisted prostatectomy has become common. Men with localized prostate cancer, having laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy, might have shorter stays in the hospital and get fewer blood transfusions than men undergoing open radical prostatectomy. How these treatments compare with regard to overall survival or recurrence-free survival is unknown.


title: Prostate cancer

text: Transurethral resection of the prostate is the standard surgical treatment for benign enlargement of the prostate. In prostate cancer, this procedure can be used to relieve symptoms of urinary retention caused by a large prostate tumor, but it is not used to treat the cancer itself. The procedure is done under spinal anesthesia, a resectoscope is inserted inside the penis and the extra prostatic tissue is cut to clear the way for the urine to pass.


title: Prostate cancer

text: The two main complications encountered after prostatectomy and prostate radiotherapy are erectile dysfunction and urinary incontinence, mainly stress-type. Most men regain continence within 6 to 12 months after the operation, so doctors usually wait at least one year before resorting to invasive treatments.


title: Prostate cancer

text: Stress urinary incontinence usually happens after prostate surgery or radiation therapy due to factors that include damage to the urethral sphincter or surrounding tissue and nerves. The prostate surrounds the urethra, a muscular tube that closes the urinary bladder. Any of the mentioned reasons can lead to incompetent closure of the urethra and hence incontinence. Initial therapy includes bladder training, lifestyle changes, kegel exercises, and the use of incontinence pads. More invasive surgical treatment can include the insertion of a urethral sling or an artificial urinary sphincter, which is a mechanical device that mimics the function of the urethral sphincter, and is activated manually by the patient through a switch implanted in the scrotum. The latter is considered the gold standard in patients with moderate or severe stress urinary incontinence.


title: Prostate cancer

text: Erectile dysfunction happens in different degrees in nearly all men who undergo prostate cancer treatment, including radiotherapy or surgery; however, within one year, most of them will notice improvement. If nerves were damaged, this progress may not take place. Pharmacological treatment includes PDE-5 inhibitors such as viagra or cialis, or injectable intracavernous drugs injected directly into the penis (prostaglandin E1 and vasoactive drug mixtures). Other nonpharmacological therapy includes vacuum constriction devices and penile implants.


title: Prostate cancer

text: Psychological interventions such as psychoeducation, cognitive behavioural therapy (CBT) and mindfulness are recommended for the management of mental and emotional complications of disease symptoms and those associated with active treatment. Due to limited research and inadequate methodological rigor of published literature, solid recommendations cannot be made on the effectiveness of mindfulness in men with prostate cancer.


title: Prostate cancer

text: Many prostate cancers are not destined to be lethal, and most men will ultimately not die as a result of the disease. Mortality varies widely across geography and other elements. In the United States, five-year survival rates range from 29% (distant metastases) to 100% (local or regional tumors). In Japan, the fatality rate rose to 8.6/100,000 in 2000. In India in the 1990s, half of those diagnosed with local cancer died within 19 years. One study reported that African-Americans have 50–60 times more deaths than found in Shanghai, China. In Nigeria, 2% of men develop prostate cancer, and 64% of them are dead after 2 years. Most Nigerian men present with metastatic disease with a typical survival of 40 months.


title: Prostate cancer

text: In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are the stage, pretherapy PSA level, and Gleason score. The higher the grade and the stage, the poorer the prognosis. Nomograms can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients. A complicating factor is that the majority of patients have multiple independent tumor foci upon diagnosis, and these foci have independent genetic changes and molecular features. Because of this extensive inter-focal heterogeneity, it is a risk that the prognostication is set based on the wrong tumor focus.


title: Prostate cancer

text: An important aspect of decision making on the value of treatment is how to balance prognosis from prostate cancer with other causes of mortality and the morbidity of treatment. The PREDICT Prostate algorithm (https://prostate.predict.nhs.uk) is a multivariable prognostic model that provides individualised cancer-specific and overall long-term survival estimates in early stage non-metastatic PCa patients. In addition to the use of routinely available preoperative clinical-pathological variables such as PSA, biopsy Gleason score (ISUP grade group), and clinical T-stage, the PREDICT Prostate tool also includes the impact of patient characteristics (age and comorbidity status) and radical treatment (radical prostatectomy or radiotherapy) on survival. The tool provides patients with estimated survival rates after treatment in the context of absolute mortality rate, which allows patients to make an informed decision as to the value of treatment and its potential side effects. Thurtle et al. performed an external validation of their previously published PREDICT Prostate model. The tool outperformed other widely used models and was proven to have high c-indices for all-cause and PCa-specific mortality, and the model calibration was good and remained accurate within the treatment subgroups. Recent work has also shown that it significantly alters clinician treatment recommendations and improves patients confidence in decision making and in their understanding of mortality risks from a new prostate cancer diagnosis Predict Prostate is endorsed for use as a decision aid for prostate cancer by the UK National Institute for Health and Care Excellence


title: Prostate cancer

text: Androgen ablation therapy causes remission in 80–90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy. How androgen-independence is established and how it re-establishes progression is unclear.


title: Prostate cancer

text: Several tools are available to help predict outcomes, such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some include the number or percentage of biopsy cores positive, age, and/or other information.


title: Prostate cancer

text: Life expectancy projections are averages for an entire male population, and many medical and lifestyle factors modify these numbers. For example, studies have shown that a 40-year-old man will lose 3.1 years of life if he is overweight (BMI 25–29) and 5.8 years of life if he is obese (BMI 30 or more), compared to men of normal weight. If he is both overweight and a smoker, he will lose 6.7 years, and if obese and a smoker, he will lose 13.7 years.


title: Prostate cancer

text: No evidence shows that either surgery or beam radiation has an advantage over the other in this regard. The lower death rates reported with surgery appear to occur because surgery is more likely to be offered to younger men with less severe cancers. Insufficient information is available to determine whether seed radiation extends life more readily than the other treatments, but data so far do not suggest that it does.


title: Prostate cancer

text: Men with low-grade disease (Gleason 2–4) were unlikely to die of prostate cancer within 15 years of diagnosis. Older men (age 70–75) with low-grade disease had a roughly 20% overall survival at 15 years due to deaths from competing causes. Men with high-grade disease (Gleason 8–10) experienced high mortality within 15 years of diagnosis, regardless of their age.


title: Prostate cancer

text: As of 2012, prostate cancer is the second-most frequently diagnosed cancer (at 15% of all male cancers) and the sixth leading cause of cancer death in males worldwide. In 2010, prostate cancer resulted in 256,000 deaths, up from 156,000 deaths in 1990. Rates of prostate cancer vary widely. Rates vary widely between countries. It is least common in South and East Asia, and more common in Europe, North America, Australia, and New Zealand. Prostate cancer is least common among Asian men and most common among black men, with white men in between.


title: Prostate cancer

text: The average annual incidence rate of prostate cancer between 1988 and 1992 among Chinese men in the United States was 15 times higher than that of their counterparts living in Shanghai and Tianjin, but these high rates may be affected by higher rates of detection. Many suggest that prostate cancer may be under-reported, yet benign prostatic hyperplasia incidence in China and Japan is similar to rates in Western countries.


title: Prostate cancer

text: Prostate cancer is the third-leading cause of cancer death in men, exceeded by lung cancer and colorectal cancer. It accounts for 19% of all male cancers and 9% of male cancer-related deaths.


title: Prostate cancer

text: Age-adjusted incidence rates increased steadily from 1975 through 1992, with particularly dramatic increases associated with the spread of PSA screening in the late 1980s, later followed by a fall in incidence. A decline in early-stage incidence rates from 2011 to 2012 (19%) in men aged 50 years and older persisted through 2013 (6%).


title: Prostate cancer

text: Declines in mortality rates in certain jurisdictions may reflect the interaction of PSA screening and improved treatment. The estimated lifetime risk is about 14.0%, and the lifetime mortality risk is 2.6%.


title: Prostate cancer

text: Between 2005 and 2011, the proportion of disease diagnosed at a locoregional stage was 93% for whites and 92% for African Americans; the proportion of disease diagnosed at a late stage was 4% for European Americans and 5% for African Americans.


title: Prostate cancer

text: Prostate cancer is more common in the African American population than the European American population. An autopsy study of White and Asian men also found an increase in occult prostate cancer with age, reaching nearly 60% in men older than 80 years. More than 50% of cancers in Asian men and 25% of cancers in White men had a Gleason score of 7 or greater, suggesting that Gleason score may be an imprecise indicator of clinically insignificant cases.


title: Prostate cancer

text: Prostate cancer is the third-leading type of cancer in Canadian men. In 2016, around 4,000 died and 21,600 men were diagnosed with prostate cancer.


title: Prostate cancer

text: In Europe in 2012, it was the third-most diagnosed cancer after breast and colorectal cancers at 417,000 cases.


title: Prostate cancer

text: In the United Kingdom, it is the second-most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year, of which around 10,000 are fatal.


title: Prostate cancer

text: The prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538. Prostate cancer was identified in 1853. It was initially considered a rare disease, probably because of shorter life expectancies and poorer detection methods in the 19th century. The first treatments were surgeries to relieve urinary obstruction.


title: Prostate cancer

text: Removal of the gland was first described in 1851, and radical perineal prostatectomy was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital.


title: Prostate cancer

text: Surgical removal of the testes (orchiectomy) to treat prostate cancer was first performed in the 1890s, with limited success. Transurethral resection of the prostate (TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh. This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.


title: Prostate cancer

text: In 1941, Charles B. Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer. This discovery of "chemical castration" won Huggins the 1966 Nobel Prize in Physiology or Medicine. The role of the gonadotropin-releasing hormone (GnRH) in reproduction was determined by Andrzej W. Schally and Roger Guillemin, who shared the 1977 Nobel Prize in Physiology or Medicine for this work. GnRH receptor agonists, such as leuprorelin and goserelin, were subsequently developed and used to treat prostate cancer.


title: Prostate cancer

text: Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants. External beam radiotherapy became more popular as stronger [X-ray] radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds (for prostate cancer) was first described in 1983.


title: Prostate cancer

text: Systemic chemotherapy for prostate cancer was first studied in the 1970s. The initial regimen of cyclophosphamide and 5-fluorouracil was quickly joined by regimens using other systemic chemotherapy drugs.


title: Prostate cancer

text: Enzalutamide gained FDA approval in 2012 for the treatment of castration-resistant prostate cancer (CRPC). Alpharadin won FDA approval in 2013, under the priority review program.


title: Prostate cancer

text: In 2006, a previously unknown retrovirus, Xenotropic MuLV-related virus (XMRV), was associated with human prostate tumors, but "PLOS Pathogens" retracted the article in 2012.


title: Prostate cancer

text: Men with prostate cancer generally encounter significant disparities in awareness, funding, media coverage, and research—and therefore, inferior treatment and poorer outcomes—compared to other cancers of equal prevalence. In 2001, "The Guardian" noted that Britain had 3,000 nurses specializing in breast cancer, compared to a single nurse for prostate cancer. Waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.


title: Prostate cancer

text: A 2007 report by the U.S.-based National Prostate Cancer Coalition stated that prostate cancer drugs were outnumbered seven to one by breast cancer drugs. "The Times" also noted an "anti-male bias in cancer funding" with a four-to-one discrepancy in the United Kingdom by both the government and by cancer charities such as Cancer Research UK. Critics cite such figures when claiming that women's health is favored over men's health.


title: Prostate cancer

text: Disparities extend into detection, with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs. For example, a 2007 report found 49 U.S. states mandate insurance coverage for routine breast cancer screening, compared to 28 for prostate cancer.


title: Prostate cancer

text: Prostate cancer experiences significantly less media coverage than other, equally prevalent cancers, outcovered 2.6:1 by breast cancer.


title: Prostate cancer

text: Prostate Cancer Awareness Month takes place in September in a number of countries. A light blue ribbon is used to promote the cause.


title: Prostate cancer

text: "Castration-resitant prostate cancer" is prostate cancer that progresses despite androgen depletion therapy.


title: Prostate cancer

text: PARP inhibitor olaparib is an approved breast/ovarian cancer drug that is undergoing clinical trials. Also in trials for CRPC are : checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC.


title: Prostate cancer

text: All medications for CRPC block androgen receptor (AR) signaling via direct or indirect targeting of the AR ligand binding domain (LBD). AR belongs to the steroid nuclear receptor family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important for disease progression. Molecules that could successfully target alternative domains have emerged. Such therapies could provide an advantage; particularly in treating prostate cancers that are resistant to current therapies.


title: Prostate cancer

text: Arachidonate 5-lipoxygenase has been identified as playing a significant role in the survival of prostate cancer cells. Medications that target this enzyme are undergoing development. In particular, arachidonate 5-lipoxygenase inhibitors produce massive, rapid programmed cell death in prostate cancer cells.


title: Prostate cancer

text: Galectin-3 is another potential target. Aberrant glycan profiles have been described in prostate cancer, and studies have found specific links between the galectin signature and prostate cancer.


title: Prostate cancer

text: The PIM kinase family is another potential target for selective inhibition. A number of related drugs are under development. It has been suggested the most promising approach may be to co-target this family with other pathways including PI3K.


title: Prostate cancer

text: Scientists have established prostate cancer cell lines to investigate disease progression. LNCaP, PC-3 (PC3), and DU-145 (DU145) are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express AR, but PC-3 and DU-145 cells express very little or no AR.


title: Prostate cancer

text: The proliferation of LNCaP cells is androgen-dependent but the proliferation of PC-3 and DU-145 cells is androgen-insensitive. Elevation of AR expression is often observed in advanced prostate tumors in patients. Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These androgen-independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen treatment. Paradoxically, androgens inhibit the proliferation of these androgen-independent prostate cancer cells.


title: Prostate cancer

text: One active research area and non-clinically applied investigations involves non-invasive methods of tumor detection. A molecular test that detects the presence of cell-associated PCA3 mRNA in fluid obtained from the prostate and first-void urine sample is under investigation. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. The test result is currently reported as a specimen ratio of PCA3 mRNA to PSA mRNA.


title: Prostate cancer

text: The PCA3 test attempts to help decide whether, in men suspected of having prostate cancer (especially if an initial biopsy fails to explain the elevated serum PSA), a biopsy/rebiopsy is needed. The higher the expression of PCA3 in the sample, the greater the likelihood of a positive biopsy. The CDC's Evaluation of Genomic Applications in Practice and Prevention Working Group discourages clinical use.


title: Internet Protocol

text: The Internet Protocol (IP) is the network layer communications protocol in the Internet protocol suite for relaying datagrams across network boundaries. Its routing function enables internetworking, and essentially establishes the Internet.


title: Internet Protocol

text: IP has the task of delivering packets from the source host to the destination host solely based on the IP addresses in the packet headers. For this purpose, IP defines packet structures that encapsulate the data to be delivered. It also defines addressing methods that are used to label the datagram with source and destination information.


title: Internet Protocol

text: IP was the connectionless datagram service in the original Transmission Control Program introduced by Vint Cerf and Bob Kahn in 1974, which was complemented by a connection-oriented service that became the basis for the Transmission Control Protocol (TCP). The Internet protocol suite is therefore often referred to as "TCP/IP".


title: Internet Protocol

text: The first major version of IP, Internet Protocol Version 4 (IPv4), is the dominant protocol of the Internet. Its successor is Internet Protocol Version 6 (IPv6), which has been in increasing deployment on the public Internet since c. 2006.


title: Internet Protocol

text: The Internet Protocol is responsible for addressing host interfaces, encapsulating data into datagrams (including fragmentation and reassembly) and routing datagrams from a source host interface to a destination host interface across one or more IP networks. For these purposes, the Internet Protocol defines the format of packets and provides an addressing system.


title: Internet Protocol

text: Each datagram has two components: a header and a payload. The IP header includes source IP address, destination IP address, and other metadata needed to route and deliver the datagram. The payload is the data that is transported. This method of nesting the data payload in a packet with a header is called encapsulation.


title: Internet Protocol

text: IP addressing entails the assignment of IP addresses and associated parameters to host interfaces. The address space is divided into subnetworks, involving the designation of network prefixes. IP routing is performed by all hosts, as well as routers, whose main function is to transport packets across network boundaries. Routers communicate with one another via specially designed routing protocols, either interior gateway protocols or exterior gateway protocols, as needed for the topology of the network.


title: Internet Protocol

text: In May 1974, the Institute of Electrical and Electronics Engineers (IEEE) published a paper entitled "A Protocol for Packet Network Intercommunication". The paper's authors, Vint Cerf and Bob Kahn, described an internetworking protocol for sharing resources using packet switching among network nodes. A central control component of this model was the "Transmission Control Program" that incorporated both connection-oriented links and datagram services between hosts. The monolithic Transmission Control Program was later divided into a modular architecture consisting of the Transmission Control Protocol and User Datagram Protocol at the transport layer and the Internet Protocol at the internet layer. The model became known as the "Department of Defense (DoD) Internet Model" and "Internet protocol suite", and informally as "TCP/IP".


title: Internet Protocol

text: IP versions 1 to 3 were experimental versions, designed between 1973 and 1978. The following Internet Experiment Note (IEN) documents describe version 3 of the Internet Protocol, prior to the modern version of IPv4:


title: Internet Protocol

text: The dominant internetworking protocol in the Internet Layer in use is IPv4; the number 4 identifies the protocol version, carried in every IP datagram. IPv4 is described in (1981).


title: Internet Protocol

text: Versions 2 and 3, and a draft of version 4, allowed an address length of up to 128 bits, but this was mistakenly reduced to 32 bits in the final version of IPv4.


title: Internet Protocol

text: Version number 5 was used by the Internet Stream Protocol, an experimental streaming protocol that was not adopted.


title: Internet Protocol

text: The successor to IPv4 is IPv6. IPv6 was a result of several years of experimentation and dialog during which various protocol models were proposed, such as TP/IX (), PIP () and TUBA (TCP and UDP with Bigger Addresses, ). Its most prominent difference from version 4 is the size of the addresses. While IPv4 uses 32 bits for addressing, yielding c. 4.3 billion () addresses, IPv6 uses 128-bit addresses providing c. addresses. Although adoption of IPv6 has been slow, , most countries in the world show significant adoption of IPv6, with over 35% of Google's traffic being carried over IPv6 connections.


title: Internet Protocol

text: The assignment of the new protocol as IPv6 was uncertain until due diligence assured that IPv6 had not been used previously. Other Internet Layer protocols have been assigned version numbers, such as 7 ("IP/TX"), 8 and 9 ("historic"). Notably, on April 1, 1994, the IETF published an April Fools' Day joke about IPv9. IPv9 was also used in an alternate proposed address space expansion called TUBA. A 2004 Chinese proposal for an "IPv9" protocol appears to be unrelated to all of these, and is not endorsed by the IETF.


title: Internet Protocol

text: The design of the Internet protocol suite adheres to the end-to-end principle, a concept adapted from the CYCLADES project. Under the end-to-end principle, the network infrastructure is considered inherently unreliable at any single network element or transmission medium and is dynamic in terms of the availability of links and nodes. No central monitoring or performance measurement facility exists that tracks or maintains the state of the network. For the benefit of reducing network complexity, the intelligence in the network is purposely located in the end nodes.


title: Internet Protocol

text: As a consequence of this design, the Internet Protocol only provides best-effort delivery and its service is characterized as unreliable. In network architectural parlance, it is a connectionless protocol, in contrast to connection-oriented communication. Various fault conditions may occur, such as data corruption, packet loss and duplication. Because routing is dynamic, meaning every packet is treated independently, and because the network maintains no state based on the path of prior packets, different packets may be routed to the same destination via different paths, resulting in out-of-order delivery to the receiver.


title: Internet Protocol

text: All fault conditions in the network must be detected and compensated by the participating end nodes. The upper layer protocols of the Internet protocol suite are responsible for resolving reliability issues. For example, a host may buffer network data to ensure correct ordering before the data is delivered to an application.


title: Internet Protocol

text: IPv4 provides safeguards to ensure that the header of an IP packet is error-free. A routing node discards packets that fail a header checksum test. Although the Internet Control Message Protocol (ICMP) provides notification of errors, a routing node is not required to notify either end node of errors. IPv6, by contrast, operates without header checksums, since current link layer technology is assumed to provide sufficient error detection.


title: Internet Protocol

text: The dynamic nature of the Internet and the diversity of its components provide no guarantee that any particular path is actually capable of, or suitable for, performing the data transmission requested. One of the technical constraints is the size of data packets possible on a given link. Facilities exist to examine the maximum transmission unit (MTU) size of the local link and Path MTU Discovery can be used for the entire intended path to the destination.


title: Internet Protocol

text: The IPv4 internetworking layer automatically fragments a datagram into smaller units for transmission when the link MTU is exceeded. IP provides re-ordering of fragments received out of order. An IPv6 network does not perform fragmentation in network elements, but requires end hosts and higher-layer protocols to avoid exceeding the path MTU.


title: Internet Protocol

text: The Transmission Control Protocol (TCP) is an example of a protocol that adjusts its segment size to be smaller than the MTU. The User Datagram Protocol (UDP) and ICMP disregard MTU size, thereby forcing IP to fragment oversized datagrams.