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Abstract : 8-Cl-cAMP, “The Old Dog with New Tricks”: A Review
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Abstract: Current chemotherapeutic drugs act for the most part by killing cancer cells directly. Treatment with these drugs often can be harmful to normal cells and may cause incomplete elimination of the target cells, resulting in the recurrence of the disease. To coop with current treatments the path of biomodulation rather than cytotoxicity, has been seen in the role of cAMP in normal versus malignant cells. It has been found that an increase of cAMP levels in normal cells stimulates proliferation, and that in the same time cancerous cells are inhibited to proliferate. This inverted reaction has given the momentum for synthesis of various cAMP analogues and investigation of there antitumor activity. A number of analogues, such as 8-PIP-cAMP, 8-Br-CAMP or 8-HA–cAMP showed efficacy only in millimolar concentrations. Only one of them, 8-Cl-cAMP as specific analogue has achieved inhibition of proliferation and stimulation of apoptosis of malignant cells in low or micromole concentrations. Still, 25 years later the mechanism of action of 8-clcAMP has not been fully elucidated or defined. This review is to challenge these mechanisms of action and to set a view of the nature of 8-Cl-cAMP action. Keywords: 8-Cl-cAMP, PKA cAMP-dependent protein kinase, biomodulation. Download Full Article |
Abstract : The Role of Exosomes and its Cargos in Drug Resistance of Cancer
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Abstract: Chemotherapy is one of the main therapies in cancer and plays an important role in controlling tumor progression, which can offer a longer overall survival (OS) for patients. But as the accumulation of drugs used in vivo, cancer cells develop drug resistance, even multi-drug resistance (MDR), that can cause failure of the whole therapy. The similar phenomenon can be observed in vitro. There are several mechanisms of drug resistance such as drug efflux, mediated by extracellular vesicles. Exosomes, a subset of extracellular vesicles (EVs), can be secreted by many types of cells and transfer proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. Particularly cancer cells secrete more exosomes than healthy cells and resistance cells secrete more exosomes than sensitive cells. Exosomes have function of intercellular communication and molecular transfer, both associated with tumor growth, invasion, metastasis, angiogenesis, and drug resistance. In this paper, we will review the current knowledge regarding the emerging roles of exosomes and its cargo in drug resistance. Keywords: Exosomes, drug resistance, drug efflux, antibody, miRNAs, lncRNA, P-glycoprotein, EMT. Download Full Article |
Abstract : Isoreserpine Reverses Multidrug Resistance Mediated by ABCB1
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Abstract: One of the major obstacles to successful cancer chemotherapy is the development of multidrug resistance (MDR) that is associated with the overexpression of ATP-binding cassette (ABC) drug transporter ABCB1 (P-glycoprotein/ MDR1). Currently, the most efficient way to overcome ABCB1-mediated MDR in cancer is by direct inhibition of ABCB1 function. Many drugs with known biological activities have been discovered to inhibit the function of ABCB1 and reverse ABCB1-mediated MDR in cancers. However, clinical trial results suggested that many of these clinically active drugs should not be used as ABCB1 modulators due to direct toxicity or undesirable side effects. In this study, we demonstrated that isoreserpine, an indole alkaloid with relatively low toxicity, can significantly inhibit ABCB1-mediated efflux of calcein-AM, a known substrate of ABCB1, in a dose-dependent manner. Moreover, we showed that at non-toxic concentrations, isoreserpine potently reversed ABCB1-mediated resistance to doxorubicin and colchicine in ABCB1-overexpressing human KB-V-1 epidermal cancer cells. Collectively, our findings revealed that by inhibiting the transport function of ABCB1, isoreserpine can restore drug sensitivity of ABCB1-overexpressing cells to conventional chemotherapeutic drugs. In conclusion, isoreserpine should be further developed into a promising reversal agent for the treatment of MDR in ABCB1-overexpressing cancers. Keywords: Multidrug resistance, Isoreserpine, ABCB1. Download Full Article |
Abstract : Histo-Epidemiological Profile of Digestive Cancers in Togo
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Abstract: Background:The frequency of digestive cancers is increasing since the last ten years. The aim of the study was to determine the epidemiologic and histologic aspects of digestive cancers in Togo. Method: We conducted a descriptive cross-sectional study focused on digestive cancers cases diagnosed from 1995 throughout 2014 (20 years) at the pathology laboratory of the Lomé teaching hospital. We included all digestive samples (biopsy, excision, surgical specimens) collected and sent to the pathology laboratory from 1994 to 2013 using data from the records of the laboratory. Results: We have collected 1306 cases of digestive cancers (20.4%). The annual incidence was 65.3 cases. The sex-ratio (M/F) was 1.5. The mean age was47.8 years. The most common locations were the stomach (35.3%) and the esophagus (27.3%). The adenocarcinoma was predominant in the stomach (84.4%), the rectum (70.2%), and the colon (86.3%). The squamous cell carcinoma was commonly found at the esophagus (94.8%). The lymphomas were observed in the small intestine (53.4%). Conclusion: Digestive cancers are frequent in Togo and occur in young adults. The stomach cancer is the most common cancer Keywords: Digestive cancers, epidemiology, histology, Togo. Download Full Article |
