33705616
Anticancer potential of silymarin: from bench to bed side.
Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects, silymarin exhibits antitumor activity against human tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers.
36556551
Glutathione S-transferase-dependent conjugation of leukotriene A4-methyl ester to leukotriene C4-methyl ester in mammalian skin.
The glutathione S-transferase (GST)-dependent conjugation of reduced glutathione (GSH) with leukotriene A4 (LTA4)-methyl ester in rodent and human skin was investigated. Incubation of [3H]LTA4-methyl ester (1 nmole, approximately 200,000 dpm) with cytosol prepared from rat, mouse and human skin or with affinity purified GST from rat skin cytosol in the presence of GSH resulted in the formation of LTC4-methyl ester. Maximum enzyme activity was observed in rat skin followed by mouse and human skin. With heat-denatured cytosol or in the absence of GSH, the product formation was negligible. GST purified from rat skin cytosol by GSH-agarose affinity chromatography exhibited a several-fold increase in the specific activity of enzyme with 1-chloro-2,4-dinitrobenzene (55-fold), ethacrynic acid (67-fold) and LTA4-methyl ester (12-fold) as substrates. Western blot analysis of the affinity purified GST indicated a predominant expression of the Pi class of GST isozyme followed by Mu and Alpha classes of isozymes. The formation of LTC4-methyl ester was established by its radioactivity profile on high pressure liquid chromatography and absorption spectroscopy. These results suggest that, in addition to xenobiotic metabolism, cutaneous GSTs may also be capable of metabolizing physiological substrates such as LTA4.
46117096
ras protein p21 processing enzyme farnesyltransferase in chemical carcinogen-induced murine skin tumors.
Farnesylation of ras protein p21 is crucial for the protein's membrane localization, which is essential for its cell-transforming activity, which in turn is thought to be critical for the ultimate induction of cancer. The cytosolic enzyme farnesyltransferase plays a major role in posttranslational modification of p21, but the level of farnesyltransferase activity in mammalian tumors and its relationship to the processing of cytosolic p21 that leads to tumorigenesis are unknown. We report here that farnesyltransferase activity was significantly higher in chemical carcinogen-induced benign skin papillomas in SENCAR mice than in the epidermises of control animals. The enzyme is primarily epidermal in origin, and kinetic studies with cytosol from epidermis and papillomas showed that the reaction was linear with respect to time, substrate concentration, and protein content. Skin papillomas showed significantly elevated levels of both cytosolic and membrane-bound Ha-ras p21, whereas far lesser cytosolic and almost negligible amounts of membrane-bound p21 were present in the epidermis of control mice. There was a positive correlation between increased enzyme activity in papilloma cytosol and the processing of overexpressed cytosolic Ha-ras p21 for its localization to membrane.
37464296
Introduction to Special Issue on Molecular Basis for Cancer Prevention with Bioactive Food Components in Nutrition and Cancer--an International Journal.
The advance of technology and understanding of the process of cancer development suggests that the reported lesser incidence and death due to cancer in countries other than the Western and European countries might also be due to under- diagnosed and under-represented cases. Further, increases in life span as well as ignorance about the disease puts populations in South and South East Asian countries at higher risk to develop cancer. With the increasing rate of cancer incidence every year in non -Western countries, cancer is estimated to become the deadliest disease in coming decades. Conventional chemo- and radio-therapies during the past three decades have not been able to contain the disease, and also have serious side effects. Many natural agents, especially small molecules from plants are non-toxic, easily available and may have anticancer potential. Thus, screening phytochemicals as anticancer agents could be a better approach in cancer prevention and treatment. This chemoprevention approach may have translational significance for prevention and treatment of cancer. 
 
Therefore to emphasize the potential role of phytochemicals in cancer prevention and therapy, it was our privilege to host the International Symposium on Recent Advances in Cancer Research: Therapeutics to Chemoprevention, at Central University of Gujarat (CUG), Gandhinagar. The conference was co-organized by the University of Colorado Denver, USA; University of Pittsburgh, USA; University of Oklahoma, USA, during 8–9 February, 2012. Modern biological strategies, specifically the latest developments for the targeted prevention and treatment of cancer via dietary, natural and synthetic agents were discussed in detail. The symposium also emphasized the translational aspect of cancer chemoprevention strategies for various cancers. 
 
The symposium deliberations include the ideas for combinatorial chemoprevention by phytochemicals as a promising approach for cancer control and emerging trends for the use of herbal radio-modulators to sensitize the cancer cells for apoptotic cell death. Many bioactive phytochemicals such as silibinin, benzyl isothiocyanate, anthocyanidins, nexrutine, tocopherol, etc. were discussed for their in vivo efficacy in animal tumor models, associated mechanisms and translational potential. Targeting tumor microenvironment with small molecules was found promising and having translational potential for prostate and breast cancer chemoprevention. 
 
The novel work and ideas presented at the symposium were helpful in guiding the research orientation of scientists, especially the young researchers who will be benefitted at all levels of their career development. Since chemoprevention of cancer is becoming an attractive approach for controlling cancer, we felt that the deliberations of this symposium should reach to the wider section of the researchers. Therefore, it was planned to bring out a special issue on Molecular Basis for Cancer Prevention with Bioactive Food Components in Nutrition and Cancer – An International Journal. We appreciate the researchers for contributing their novel work and ideas to this special issue. We are grateful to the Editor of Nutrition and Cancer – An International Journal, for his initiative to bring out this special issue on this relevant topic. We believe that this volume will be enlightening for the researchers working in the area of cancer chemoprevention.
32720111
Assessment of some tumorigenic risks associated with fresh and used cutting oil.
35457752
Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes.
Nordihydroguaiaretic acid (NDGA), a plant lignan and phenolic antioxidant, is a known lipoxygenase inhibitor. In this study, we investigated the effect of NDGA on rat epidermal and hepatic monooxygenase activity and its interaction with rat hepatic microsomal cytochrome P-450. The addition of NDGA to epidermal microsomes prepared from control and 3-methylcholanthrene (3-MC)-pretreated rats and hepatic microsomal preparations from control, 3-MC-pretreated, and phenobarbital (PB)-pretreated rats resulted in a concentration-dependent inhibition of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (ERD) activities. The 50% inhibitory dose for NDGA ranged from 4.1 x 10(-5) to 13.1 x 10(-5) M for AHH and ERD activities in these microsomal preparations. The addition of NDGA to hepatic microsomes prepared from PB-pretreated rats resulted in spectral changes characterized by absorbance maxima at 380 nm and minima at 414 nm, typical of type I binding difference spectra. It also showed time- and concentration-dependent inhibition of the binding of carbon monoxide to dithionite or NADPH-reduced cytochrome P-450. We speculate that perhaps hydroxyl groups present in NDGA play an important role in inhibiting the monooxygenase activity and suggest that NDGA may have potential as an antimutagen and/or anticarcinogen. Furthermore, caution must be exercised in elucidating the role of lipoxygenase in metabolic pathways based solely on the criterion of inhibition by NDGA.
5792982
Therapeutic potential of Curcuma longa, the golden spice of India, in drug discovery for ophthalmic diseases
Background: Curcuma longa is among the most commonly used spices in India and other Asian countries. The herb has also been used in Ayurveda and other traditional systems of medicine for the prevention and treatment of a variety of ailments. Curcuminoids are the major chemical constituents of C. longa that are of medicinal importance. Today, a large body of scientific evidence exists to indicate potential therapeutic benefits of C. longa. Several preclinical and clinical studies have investigated the pharmacological properties of C. longa and results indicate strong therapeutic potential for anti-inflammatory, antioxidant, antibacterial, anticancer and many other properties. Objective: This review summarizes the scientific evidences showing possible benefits of C. longa in a variety of ophthalmic diseases. Conclusion: Although the putative mechanism(s), molecular targets and range of therapeutic applications have been researched widely, further investigations are needed to explore the true therapeutic potential and future of curcuminoids as novel drug molecules in ophthalmic diseases.
205184982
Short-term vitamin D receptor activation increases serum creatinine due to increased production with no effect on the glomerular filtration rate.
Vitamin D receptor activation has been associated with increased serum creatinine and reduced estimated glomerular filtration rates, raising concerns that its use may be detrimental to kidney function. Here we studied the effect of vitamin D receptor activation on serum creatinine, creatinine generation, and its clearance. We measured baseline serum creatinine and 24-h urine creatinine in 16 patients with chronic kidney disease. The measurements were repeated every day for 7 days, during which time the patients received 2 μg paricalcitol, an orally active vitamin D receptor activator, every morning. At 4 days after stopping the vitamin analog, measurements were continued for 3 days. Geometric mean parathyroid hormone levels decreased from 77 pg/ml at baseline to 43 pg/ml at the end of treatment and significantly rebounded to 87 pg/ml following paricalcitol withdrawal, thereby supporting the biological efficacy of the analog dose used. With this therapy, the serum creatinine significantly increased at a rate of 0.010 mg/dl/day and urine creatinine at a rate of 17.6 mg/day. Creatinine and iothalamate clearances did not change, whereas urine albumin decreased insignificantly. Thus, short-term vitamin D receptor activation increases creatinine generation and serum creatinine, but it does not influence the glomerular filtration rate.
10080320
Unfavourable results with distraction in craniofacial skeleton
Distraction osteogenesis has revolutionised the management of craniofacial abnormalities. The technique however requires precise planning, patient selection, execution and follow-up to achieve consistent and positive results and to avoid unfavourable results. The unfavourable results with craniofacial distraction stem from many factors ranging from improper patient selection, planning and use of inappropriate distraction device and vector. The present study analyses the current standards and techniques of distraction and details in depth the various errors and complications that may occur due to this technique. The commonly observed complications of distraction have been detailed along with measures and suggestions to avoid them in clinical practice.
205448049
Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with acute severe asthma in a respiratory intensive care unit in North India.
The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in chronic asthma has been reported in various studies. However, no study has systematically evaluated the occurrence of Aspergillus hypersensitivity (AH) and ABPA in acute severe asthma (ASA). The aim of this study was to investigate the occurrence of AH and ABPA in patients with ASA. All patients with ASA admitted to the respiratory intensive care unit (ICU) of this institute underwent a prospective evaluation for ABPA using Aspergillus skin test (AST) as a screening tool. Patients with positive AST were labelled as AH and were further investigated for ABPA. Patients with ASA were compared with historical control group of 755 outpatient bronchial asthma patients previously reported. Of the 357 ICU admissions, 57 (43 females, 14 males; mean age 43.5 years) patients were admitted with a diagnosis of ASA. The occurrence of AH was 50.9% [95% confidence interval (CI) 38.3-63.4; 29/57 patients] whereas the prevalence of ABPA was 38.6% (95% CI 27.1-51.6; 22/57 patients) in patients with ASA. The occurrence of AH and ABPA was significantly higher in the ASA group compared with the outpatient bronchial asthma group (38.5% and 20.5%, respectively). The prevalence of serological ABPA (ABPA without central bronchiectasis) was also higher in the ASA group compared with the outpatient bronchial asthma group (45.4% vs. 23.9%). The occurrence of AH and ABPA is very high in patients with acute asthma admitted to a respiratory ICU. Furthermore, the occurrence of high percentage of serological ABPA calls for the use of AST as a routine screening tool for ABPA in all patients with acute asthma at discharge.
21255298
Effects of statins on renal function.
This report reviews data on the development of proteinuria in patients with chronic kidney disease who are treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for dyslipidemia. Although subgroup analyses of statin trials have shown cardiovascular benefits in subjects with chronic kidney disease, concern about statin-induced proteinuria remains high. Experimental studies have suggested that the proteinuria seen with statin treatment results from the inhibition of receptor-mediated endocytosis, the likely mechanism of protein uptake in proximal tubular cells. Transient proteinuria may signify little more than the effective inhibition of cholesterol synthesis at this site. The blockade of protein trafficking in tubular cells is thought to reduce inflammation, slow fibrosis, and diminish proteinuria in the long term. Post hoc analyses of large clinical trials in subjects without overt renal disease have generally supported this notion, showing that statins most benefit patients with the greatest baseline renal deficits. Statins have also been shown to preserve glomerular filtration rate and reduce proteinuria in subjects with nondiabetic renal disease. In conclusion, in the absence of prospective, randomized trials in renally impaired patients, the collective evidence indicates that statin therapy may slow the decrease in renal function that generally attends atherosclerotic disease. The incidence of proteinuria with potent statins is only 1% to 2% when these drugs are given in recommended doses. Several large trials are currently under way to examine the safety and efficacy of statins in renally compromised patients at high risk for cardiovascular disease.