Advances in prophylactic cancer vaccine research

Prophylactic vaccination against human cancer provides a unique opportunity to prevent human suffering for individuals at risk for tumor development. Appropriate vaccines may pose slightly different requirements than vaccines intended for therapeutic use. Prophylactic vaccines will need to prevent tumors far into the future, emphasizing the need to establish solid tumor-specific immunologic memory. Another important issue associated with prophylactic cancer vaccines is the identification of appropriate populations for vaccination. Individuals at risk may include those exposed to oncogenic viruses, those with occupational exposure to tumor promoting agents, and individuals with a family history of cancer. This paper addresses the specific challenges posed to the exciting field of prophylactic cancer vaccine research.     

Effects of Aroclor 1254 on femoral bone metabolism in adult male Wistar rats

Environmental pollutants that disrupt endocrine system might also affect the modeling and remodeling of bone. Environmental factors, irrespective of age and sex contribute for the development of secondary osteoporosis. Polychlorinated biphenyls have adverse effects on various organs including bone. The present study was designed to investigate the effects of PCB (Aroclor 1254) on femur bone and the ameliorative role of vitamin C or E. In this regard, four groups of adult male albino rats were used as control, PCB (2mg/kgb.wt.), PCB+vitamin C (100mg/kgb.wt.) and PCB+vitamin E (50mg/kgb.wt.). The bone formation markers (ALP, Collagen), bone resorption marker (TRAP), antioxidant enzymes (SOD, GPX and GST) and lipid peroxidation in the femur were studied. Aroclor 1254 treatment decreased the ALP activity and collagen, but increased the TRAP activity and lipid peroxidation. While it decreased the SOD and GPX activity, GST was unaltered. Interestingly, simultaneous administration of vitamin C or E prevented the adverse effects of Aroclor 1254 in the femur. In conclusion, the present investigation suggests that Aroclor 1254 induced oxidative stress affects femoral bone metabolism. However, vitamin C or vitamin E protected the femur from the oxidative stress.     

Gender modulation of Ca(2+) uptake in cardiac mitochondria

BACKGROUND: Mitochondrial calcium overload is an important factor in defining ischemia/reperfusion injury. Since pre-menopausal women are relatively protected from ischemia and heart disease, we tested the hypothesis that gender differences alter Ca(2+) handling in rat cardiac mitochondria. METHODS: Using cardiac mitochondria isolated from male, female, and ovariectomized Sprague-Dawley rats, we measured mitochondrial calcium transport, redox state, and membrane potential (Deltapsi(m)) during exposure to a calcium bolus. Redox state was modulated using either succinate (S) or succinate and pyruvate (SP) as substrates. RESULTS: Net Ca(2+) uptake rates were significantly lower in female than male mitochondria using SP, substrate conditions that resulted in a lower redox state (NADH/NAD(+)). Inhibition of the mitochondrial transition pore (MTP) using cyclosporin A showed significantly lower net Ca(2+) uptake in both substrate solutions when mitochondria from female and ovariectomized animals were compared to males, a finding consistent with gender modulation of the mitochondrial uniporter. Blockade of the Ca(2+) uniporter by ruthenium red abolished gender or substrate solution differences in calcium release. While there were no significant differences in resting Deltapsi(m), or Deltapsi(m) following Ca(2+) addition, 80% of female samples recovered from Ca(2+)-induced depolarization compared to 57% and 43% of male and ovariectomized animals, respectively. CONCLUSIONS: Mitochondria from female hearts have lower Ca(2+) uptake rates under physiologic substrate solutions (succinate/pyruvate) and are able to appropriately maintain DeltaYm under conditions of high [Ca(2+)]. These differences are consistent with gender modulation of the Ca(2+) uniporter and may be a mechanism by which female myocardium suffers less injury with ischemia/reperfusion.     

Acute tobacco smoke exposure promotes mitochondrial permeability transition in rat heart

Chronic exposure to tobacco smoke is known to impair mitochondrial function. However, the effect of acute tobacco smoke exposure (ATSE) in vivo, as might occur in social settings, on mitochondrial function and calcium handling of cardiac cells has not been examined. It was hypothesized that ATSE might adversely modify mitochondrial function as reflected in mitochondrial energetics, membrane potential, and calcium transport. Mitochondria were isolated from the hearts of adult rats either exposed to 6 h of environmental tobacco smoke ( approximately 60 mg/mm3 tobacco smoke particles) or sham exposure. To model a calcium stress similar to ischemia/reperfusion, mitochondria were exposed to a Ca2+ bolus with measurement of membrane potential, energetics, Ca2+uptake and release, and redox state. ATSE mitochondria were characterized by significantly higher ADP-stimulated ATP production and a more reduced redox state (NADH ratio) under basal conditions without observed changes in resting Psim. Exposure of ATSE mitochondria to Ca2+stress resulted in significantly more rapid depolarization of Psim. The initial rate of Ca2+uptake was not altered in ATSE mitochondria, but CsA-sensitive Ca2+ release was significantly increased. ATSE does not significantly alter resting mitochondrial function. However, ATSE modifies the response of cardiac mitochondria to calcium stress, resulting in a more rapid depolarization and subsequent release of Ca2+ via the mitochondrial permeability transition (MPT).     

Current scenario of 1,4-diazepines as potent biomolecules--a mini review

The aim of this review is precisely to give a comprehensive account of the large volume of work carried out on 1,4-diazepines regardless of the degree of unsaturation in the diazepine system. This review mainly emphasizes recent work on the diazepines also including earlier work.     

Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts – in vitro

Di-2-ethyl hexyl phthalate (DEHP), an industrial plasticizer and a ubiquitous environmental contaminant, is an established endocrine disruptor (ED). Increasing evidences indicate that some EDs interfere with osteoblast differentiation and function. In the present study, we investigated the effects of DEHP on the expression of cell cycle proteins, differentiation markers, Runx2 and its co-activator TAZ in osteoblasts derived from neonatal rat calvaria. A significant decrease in protein levels of cyclin D1 and CDK-2 was found at high dosage of DEHP (100 μM) after 24 h treatment. DEHP treatment caused a significant decrease in ALP mRNA. While DEHP treatment significantly decreased the TAZ at mRNA and protein levels, it decreased only the Runx2protein levels. Histochemical localization of ALP, collagen and mineralized nodules studied from cells treated with DEHP (10 and 100 μM) for 21 days revealed a drastic decrease in collagen, ALP and mineralization. In conclusion, DEHP affected differentiation of neonatal rat calvarial osteoblasts and mineralization of matrix secreted by these cells.     

Cissus quadrangularis augments IGF system components in human osteoblast like SaOS-2 cells

Osteoporosis is a public health problem which is associated with significant morbidity and mortality. Growth factors are produced locally in the bone and control cellular events such as induction of bone growth. Signaling through the Insulin-like growth factor (IGF)-I receptor (IGF-IR) by locally synthesized IGF - I or IGF-II in osteoblast is considered crucial for normal development and for bone remodeling. Traditional use of Cissus quadrangularis (C. quadrangularis) in the treatment of bone disorders have been documented, however its regulatory effects on IGF system components remain largely unknown. The present study is employed to delineate the effects of ethanolic extract of C. quadrangularis on the regulation of IGF system components in human osteoblast like SaOS-2 cells. RT-PCR analysis revealed an increase in the mRNA expression of IGF-I, IGF-II, IGF-IR in cells treated with C. quadrangularis when compared with control cells. The mRNA expression of IGF binding protein-3 (IGFBP-3) did not differ significantly between control and C. quadrangularis treated cells. Immunoradiometric analysis revealed increased levels of IGF-I, IGF-II and IGFBP-3 in the conditioned medium of C. quadrangularis treated cultures when compared with control. Western blotting analysis revealed increase in protein levels of IGF-IR in cells treated with C. quadrangularis. These results indicate positive regulation of C. quadrangularis on the IGF system components of human osteoblast like SaOS-2 cells.