38365589
Quantification of tumour initiating effect of jute batching oil and its distillates over mouse skin.
In order to identify the tumour initiating constituent(s) of a mineral oil, jute batching oil (JBO), used in the processing of jute fibres, it was fractionally distilled in various boiling range fractions. The latter were then subjected to in vivo assessment of their aryl hydrocarbon hydroxylase (AHH) inducing potential in mouse epidermis. Fractions with almost similar AHH inducing potential were regrouped and studied for their tumour initiating potential over mouse skin following two-stage initiation-promotion protocol and using 12-O-tetradecanoyl phorbol-13-acetate (TPA) as tumour promoter. It was noticed that: (1) JBO as initiator, provoked local development of benign skin tumours over mouse back; (2) fractions of JBO boiling below 335 degrees C and above 399 degrees C accounted for most of the tumour initiating potential of the oil; (3) the histological features of the tumours (i.e. benign papillomas and keratoacanthomas) initiated by these fractions were similar to those developed after being initiated with unfractionated or reconstituted JBO; (4) removal of these fractions from JBO may be attempted which could decontaminate the batch oil from most of its tumorigenic components and make it safer for industrial use.
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.
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.
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.
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.
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.
1834760
The true incidence of placental mesenchymal dysplasia.
8134220
Prognostic factors in ovarian cancer: how close are we to a complete picture?
Prognostic factors in ovarian cancer: how close are we to a complete picture? Ovarian cancer is the fourth most common cause of cancer-related death in women, but is the most lethal of the gynaeco-logical malignancies with 30–40% overall survival at 5 years [1]. This is in part because the majority of patients with ova-rian cancer present with advanced disease, and treatment options at presentation are confined to a combination of debulking surgery and platinum based chemotherapy, which are only partially effective [2]. Consequently, almost all patients with advanced disease ultimately relapse and die of their disease. Advances in the management of these patients are therefore urgently required. Prognostic factors are defined as phenotypes which correlate with overall survival. In general prognostic factors reflect the intrinsic biology of a tumour (e.g. histological subtype, grade), disease extent (e.g. stage) and/or the capacity of a patient to cope with the morbidity associated with the tumour and treatment (e.g. performance status). As well as these pretreatment factors, others which may impact on outcome include the treatment received by a patient (e.g. optimal surgical cytore-duction, platinum-based chemotherapy), and the effect of treatment on the tumour (e.g. complete response) or the patient (e.g. myelosuppression). As clinical tools, prognostic factors can potentially help in individualising treatment for patients. In properly staged early disease (stage Ia/b), patients have a better prognosis and the benefits of adjuvant chemotherapy may be confined to those with adverse features (e.g. histological subtype or grade) [3]. In this context a prognostic factor with a good positive or negative predictive value for individual patients, would be useful in deciding which patients should receive chemotherapy and those for whom the toxicity was not justified. In contrast, in advanced disease, the majority of patients benefit from paclitaxel –carboplatin chemotherapy and debulking surgery. As there are no established alternatives for patients with either good or poor prognosis, pretreatment prognostic stratification has little influence on clinical management [2]. Instead, pre-treatment markers predictive of response or resistance to individual cytotoxic drugs would be more useful in this context for treatment selection. As research tools, prognostic factors can help identify subgroups of patients with especially poor prognosis and alert us to the need to develop alternative treatment strategies for these patients, while in clinical trials prognostic factors are used to balance patients between treatment arms to minimise the risk of confounding. Prognostic factor studies can also provide useful insights into …
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.
25760349
Antihypertensive agents and arterial stiffness: relevance to reducing cardiovascular risk in the chronic kidney disease patient.
PURPOSE OF REVIEW
Arterial stiffness is a sign of diffuse adventitial macrovascular disease. The purpose of the present review is to discuss, in patients with chronic kidney disease, the pathophysiology of increased arterial stiffness, the role of antihypertensive therapy on reduction of arterial stiffness, and the clinical ways by which the prognostication of cardiovascular disease in patients with chronic kidney disease can be refined using arterial stiffness monitoring.


RECENT FINDINGS
Arterial stiffness is increased with increasing prevalence of traditional cardiovascular risk factors. In patients with chronic kidney disease some unique factors further increase the risk of arterial stiffness, and include volume overload, activation of the renin-angiotensin system, anemia, and dysregulated mineral metabolism. Arterial stiffness is increased even in patients with early-stage chronic kidney disease. Blood pressure reduction when accompanied by a reduction in arterial stiffness is associated with improved prognosis. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can preferentially improve arterial stiffness, which may be an additional mechanism of cardiovascular protection with these agents.


SUMMARY
The impact of improvement in arterial stiffness with antihypertensive agents on cardiovascular outcomes needs well designed clinical trials.
556786
A novel mode of dimerization via formation of a glutamate anhydride crosslink in a protein crystal structure.
Acid anhydrides are formed by removal of water, are very active, and can react with water to form the original binary components.