30834959
Kava, a Tonic for Relieving the Irrational Development of Natural Preventive Agents
The last two decades have witnessed explosive growth in the study of natural and other cancer chemopreventive agents ([1][1], [2][2]). Extensive preclinical data have been generated for natural agents, and many (such as green tea, curcumin, phenyl isothiocyanate, indole-3-carbinol, silibinin,
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.
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.
6837472
Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.
Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.
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.
5785486
Identification of the site of photocross-linking formed in the absence of magnesium nucleotide from SH2 (Cys-697) in myosin subfragment 1 labeled with 4'-maleimidylbenzophenone.
The site of photocross-linking between Cys-697 (SH2), prelabeled with 4'-[14C]maleimidylbenzophenone, and the 50-kDa segment of myosin S1 on irradiation in the absence of nucleotide has been determined by isolation of the 20-50-kDa adduct and subsequent tryptic proteolysis. Isolation and partial sequencing of the radioactively labeled peptide indicate that the site of cross-linking is Arg-239. This result indicates that, in the absence of nucleotide, Arg-239 resides at about 1.0 nm from SH2 and, on the basis of the recent work of Sutoh and Hiratsuka (Sutoh, K. and Hiratsuka T. (1988) Biochemistry 27, 2964-2969) places Arg-239 at no more than 1.45 nm from either Lys-184 or Lys-189 of the nucleotide-binding "glycine-rich" loop prior to the binding of nucleotide.
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.
8887497
Does ferric gluconate lower epoetin requirements in hemodialysis patients with high ferritin levels?
The 6-week Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated that the administration of intravenous iron improved anemia in patients on hemodialysis who had high ferritin levels (500–1,200 ng/ml [1,124–2,696 pmol/l]) and were receiving adequate epoetin doses, disproving previous beliefs that intravenous iron does not benefit patients with ferritin levels >500 ng/ml. This commentary discusses the DRIVE-II study, an observational 6-week extension study reported by Kapoian et al. that was designed to measure the impact of prior iron administration on subsequent epoetin dose. The extension study found that the epoetin dose requirement decreased significantly in patients who had received intravenous iron during DRIVE, but did not change in control patients. Although the results are promising, long-term studies with hard end points such as stroke, myocardial infarction, hospitalization for heart failure, and death are needed to confirm the safety of the intravenous iron regimen.
11810102
Epidemiology of Interdialytic Ambulatory Hypertension and the Role of Volume Excess
Background: The epidemiology of hypertension among hemodialysis (HD) patients is difficult to describe accurately because of difficulties in the assessment of blood pressure (BP). Methods: Using 44-hour interdialytic ambulatory BP measurements, we describe the epidemiology of hypertension in a cohort of 369 patients. To seek correlates of hypertension control, antihypertensive agents were withdrawn among patients with controlled hypertension and ambulatory BP monitoring was repeated. Results: Hypertension (defined as an average ambulatory systolic BP ≧135 mm Hg or diastolic BP ≧85 mm Hg, or the use of antihypertensive medications) was prevalent in 82% of the patients and independently associated with epoetin use, lower body mass index and fewer years on dialysis. Although 89% of the patients were being treated, hypertension was controlled adequately in only 38%. Poor control was independently associated with greater antihypertensive drug use. Inferior vena cava (IVC) diameter in expiration was associated with increased risk of poorly controlled hypertension both in cross-sectional analysis and after withdrawal of antihypertensive drugs. Conclusions: Interdialytic hypertension is highly prevalent and difficult to control among HD patients. End-expiration IVC diameter is associated with poor control of hypertension in cross-sectional analyses as well as after washout of antihypertensive drugs. Among HD patients, an attractive target for improving hypertension control appears to be the reduction of extracellular fluid volume.
38466120
Novel therapeutic agents in ovarian cancer.
AIMS
Epithelial ovarian cancer is responsible for 4% of all cancer deaths in women, and the five-year overall survival of patients with advanced disease is 30-40%. Treatment currently comprises a combination of surgery and chemotherapy with carboplatin and paclitaxel. The main reason for treatment failure is that the majority of patients present with advanced disease, and current drugs are unable to effect a cure even in chemosensitive patients. This article systematically reviews novel therapeutic strategies that have been evaluated in patients with ovarian cancer in the last 5 years.


METHODS
Pubmed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed) and American Society of Clinical Oncology Annual conference abstracts were searched using the terms "(phase I OR phase II OR phase III OR phase 1 OR phase 2 OR phase 3) AND (ovary OR ovarian) AND (cancer OR carcinoma)" from January 2000 to May 2005 to identify studies for potential inclusion in this review. Reviews of novel therapies in ovarian cancer were also used to identify additional clinical trials.


FINDINGS
A wide range of therapeutic strategies are currently being evaluated in ovarian cancer. These include novel cytotoxics, small molecule inhibitors, monoclonal antibodies, gene therapy and immuno-therapy strategies. The rationale for the development of these agents includes enhancement of efficacy by targeting novel biological pathways, re-sensitisation to existing drugs, simplification of drug administration and/or reduction of drug-toxicity.


CONCLUSIONS
Current developments have the potential to result in substantial improvements in the outlook for women with ovarian cancer.
3038618
Is the mortality higher in the pulmonary vs the extrapulmonary ARDS? A meta analysis.
BACKGROUND AND AIM
ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups.


METHODS
We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models.


RESULTS
Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I(2), 50.9%; 95% CI, 21.3 to 66.2%; chi(2) statistic, 67.22; p = 0.0004).


CONCLUSIONS
The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.