Modulation of docetaxel-induced apoptosis and cell cycle arrest by all- trans retinoic acid in prostate cancer cells

We report that all- trans retinoic acid (ATRA) enhanced the toxicity of docetaxel against DU145 and LNCaP prostate cancer cells, and that the nature of the interaction between ATRA and docetaxel was highly synergistic. Docetaxel-induced apoptotic cell death was associated with phosphorylation and hence inactivation of Bcl-2. ATRA enhanced docetaxel-induced apoptosis and combined treatment with ATRA and docetaxel resulted in down-regulation of Bcl-2. Docetaxel caused phosphorylation and hence inactivation of cdc2 kinase result ing in G2/M arrest. ATRA inhibited docetaxel-induced phosphorylation of cdc2 resulting in activation of cdc2 kinase and partial reversal of the G2/M arrest. ATRA also inhibited docetaxel-induced activation of MAPK indicating that the effects of docetaxel and ATRA on cdc2 phosphorylation are dependent on MAPK. We conclude that ATRA synergistically enhances docetaxel toxicity by down-regulating Bcl-2 expression and partially reverses the docetaxel-induced G2/M arrest by inhibiting docetaxel-induced cdc2 phosphorylation in a pathway that is dependent on MAPK. © 2001 Cancer Research Campaign http://www.bjcancer.co

Analyzing the variability parameters of the landraces and varieties of little millet (Panicum sumatrense Roth ex Roem. & Schult.)

Little millet is one of the underutilized crops among the cereals, which is being cultivated by farmers of tribal agriculture. The landraces under cultivation possess excellent variability presenting good opportunities for selection. In view of this, the current study was carried out with 17 little millet landraces for 10 quantitative and nine qualitative traits. The study revealed the preponderance of additive gene action for all the 10 traits and hence effective selection could be done for their improvement. Higher to moderate ranges for PCV and GCV with minimum ECV for genetic variability for all the traits were observed. Among the nine qualitative traits, there were significant variations observed for inflorescence shape and panicle compactness. Hence, these traits could be utilized as major DUS descriptors in differentiating the little millet landraces in future. Further the PCA analysis exhibited three reliable principal components contributing to an overall variation of 74.54%. The traits such as days to 50% flowering, peduncle length and flag leaf length were the major positive contributors for variability across all the eigen vectors. These traits were found to exhibit a higher variability among the population and thus a rewarding selection and hybridization for improving these traits could be effected in future breeding programs. Among all the landraces and varieties chittan samai, perunsamai, ATL 1, CO 4 (samai), paakulam karunjamai and vellai samai could be further identified as desirable donors for improving the yield parameters in little millet breeding programs in future

Cancer effects of formaldehyde: a proposal for an indoor air guideline value

Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings

Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Recent scientific debate has focused on the potential for inhaled formaldehyde to cause lymphohematopoietic cancers, particularly leukemias, in humans. The concern stems from certain epidemiology studies reporting an association, although particulars of endpoints and dosimetry are inconsistent across studies and several other studies show no such effects. Animal studies generally report neither hematotoxicity nor leukemia associated with formaldehyde inhalation, and hematotoxicity studies in humans are inconsistent. Formaldehyde's reactivity has been thought to preclude systemic exposure following inhalation, and its apparent inability to reach and affect the target tissues attacked by known leukemogens has, heretofore, led to skepticism regarding its potential to cause human lymphohematopoietic cancers. Recently, however, potential modes of action for formaldehyde leukemogenesis have been hypothesized, and it has been suggested that formaldehyde be identified as a known human leukemogen. In this article, we apply our hypothesis-based weight-of-evidence (HBWoE) approach to evaluate the large body of evidence regarding formaldehyde and leukemogenesis, attending to how human, animal, and mode-of-action results inform one another. We trace the logic of inference within and across all studies, and articulate how one could account for the suite of available observations under the various proposed hypotheses. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the case fora causal association is weak and strains biological plausibility. Instead, apparent association between formaldehyde inhalation and leukemia in some human studies is better interpreted as due to chance or confounding

Identifying an indoor air exposure limit for formaldehyde considering both irritation and cancer hazards

Formaldehyde is a well-studied chemical and effects from inhalation exposures have been extensively characterized in numerous controlled studies with human volunteers, including asthmatics and other sensitive individuals, which provide a rich database on exposure concentrations that can reliably produce the symptoms of sensory irritation. Although individuals can differ in their sensitivity to odor and eye irritation, the majority of authoritative reviews of the formaldehyde literature have concluded that an air concentration of 0.3 ppm will provide protection from eye irritation for virtually everyone. A weight of evidence-based formaldehyde exposure limit of 0.1 ppm (100 ppb) is recommended as an indoor air level for all individuals for odor detection and sensory irritation. It has recently been suggested by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), and the US Environmental Protection Agency (US EPA) that formaldehyde is causally associated with nasopharyngeal cancer (NPC) and leukemia. This has led US EPA to conclude that irritation is not the most sensitive toxic endpoint and that carcinogenicity should dictate how to establish exposure limits for formaldehyde. In this review, a number of lines of reasoning and substantial scientific evidence are described and discussed, which leads to a conclusion that neither point of contact nor systemic effects of any type, including NPC or leukemia, are causally associated with exposure to formaldehyde. This conclusion supports the view that the equivocal epidemiology studies that suggest otherwise are almost certainly flawed by identified or yet to be unidentified confounding variables. Thus, this assessment concludes that a formaldehyde indoor air limit of 0.1 ppm should protect even particularly susceptible individuals from both irritation effects and any potential cancer hazard

NYU-DOE Pressurized Fluidized Bed Combustor Facility

New York University (NYU), under a Department of Energy (DOE) Contract, has designed and constructed a sub-pilot scale Pressurized Fluidized-Bed Combustor (PFBC) Facility at the Antonio Ferri Laboratories, Westbury, Long Island. The basic feature of this Experimental Research Facility is a well-instrumented, 30-inch diameter coal combustor capable of operating up to 10 atm and provided with a liberal number of ports, making it a versatile unit for study of fundamental in-bed phenomena. Additionally, the overall design features make it a flexible facility for solving a variety of industrial research problems. The main objectives of the facility are two-fold: (1) to perform research in important areas of Pressurized Fluidized-Bed Combustion like low-grade fuel combustion under pressure; and (2) to provide the PFBC community with a experimental research tool for basic and applied research in order to accelerate the commercialization of this technology. New York University will initially test the facility of burning low-grade fuels under pressure. During the test program, emphasis will be placed on burning North Dakota lignite under pressures up to 7 atm. The performance of lignite with regard to its feeding, combustion efficiency, sulfur adsorption and sorbent requirements will be investigated. This report describes the various systems of the PFBC facility and operating procedures, and presents an outline of the test program planned for the facility. Other details are provided in the Equipment and Maintenance Manual, Test Program and Data Acquisition Manual, and Training Manual