Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer.
Genome-wide association studies (GWAS) provide a powerful means of identifying genetic variants that play a role in common diseases. Such studies present important ethical challenges. An increasing number of GWAS is taking place in lower income countries and there is a pressing need to identify the particular ethical challenges arising in such contexts. In this paper, we draw upon the experiences of the MalariaGEN Consortium to identify specific ethical issues raised by such research in Africa, Asia and Oceania.
Anopheles arabiensis is the major vector of malaria in Ethiopia. Malaria vector control in Ethiopia is based on selective indoor residual spraying using DDT, distribution of long lasting insecticide treated nets and environmental management of larval breeding habitats. DDT and pyrethroid insecticides are neurotoxins and have a similar mode of action on the sodium ion channel of insects. It was therefore necessary to verify the insecticide susceptibility status of An. arabiensis, to better understand the status of cross-resistance between DDT and the pyrethroids in this species as well as to detect a resistant gene.
The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer.
10 July 2008 in American Journal of Physical Anthropology
Breast cancer is the commonest cancer in Sudanese women. Reported genetic alterations in the form of mutations in tumor suppressors are low in frequencies and could not explain the peculiarities of the diseases including its focal nature. Potential contributors disease aetiology include oncogenic viruses such as Epstein-Barr virus (EBV), an established culprit of nasopharyngeal carcinoma, one of the most frequent cancers in Sudan.