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Table of Contents
October 2016
Volume 3 | Issue 2
Page Nos. 123-240
Online since Wednesday, September 5, 2018
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EDITORIAL
Editorial
p. 123
Dhananjaya Saranath, Aparna Khanna
DOI
:10.4103/2349-3666.240608
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REVIEW ARTICLES
Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene
p. 130
Rajashree Kadam, Tanuja Teni
DOI
:10.4103/2349-3666.240609
Clusterin (CLU), a heterodimeric and sulfated glycoprotein has been associated with various physiological functions. This molecular chaperone protein is ubiquitously expressed in diverse tissues and conserved across species. Differences in subcellular localization and possible existence of different CLU isoforms may contribute to its functional diversity. Increased or decreased expression of CLU has been observed in several cancers versus normal tissues and hence its role in tumorigenesis is controversial. Evidences from several studies imply that CLU may have a dual role as a tumor suppressor gene or an oncogene depending on the signal and cellular context. CLU possibly exerts its oncogenic role by inhibiting apoptosis, activating autophagy and modulating several signaling pathways like IGF-1/IGFR, EGFR, NF-kB, PI3K/AKT, TGFp and select miRNAs. CLU may exert its tumor suppressive effects by regulating cell cycle and inducing apoptosis. In cancer, loss of heterozygosity (LOH), copy number loss at CLU locus, epigenetic modifications and expression of select miRNAs may lead to the downregulation of CLU. Custirsen (OGX-011), a second generation antisense oligonucleotide that inhibits CLU expression and increases sensitivity of cancer cells to chemotherapeutic drugs, is currently in phase III clinical trials. CLU is an attractive target in several cancers, however for effective targeting, it is essential to know whether it acts as an oncogene or a tumor suppressor gene in a specific tissue/cellular context. The current review attempts to discuss the two contrasting roles of CLU in cancer and associated regulatory mechanisms. This review also sheds light on the complex CLU splice variants, the varied functional attributes supporting the dual roles in cancer and limitations of the CLU research that warrant attention.
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Chemoprotectants in cancer chemotherapy: An update
p. 157
Abhishek Basu, Arin Bhattacharjee, Sudin Bhattacharya
DOI
:10.4103/2349-3666.240610
Cancer chemotherapeutic agents play an integral part in the management of patients with malignancy. However, chemotherapy is associated with significant toxicity with an adverse impact on the health of the patients. As a result the therapeutic outcome is influenced due to the inability to deliver sufficient dose-intensive therapy leading to treatment delays or cessation. Chemoprotectants have been developed in order to mitigate the toxicity associated with chemotherapeutic agents by providing organ-specific protection to normal tissues, without compromising the antitumor efficacy. The current review highlights chemoprotectants in the management of chemotherapeutics-associated toxicity, such as: amifostine, aprepitant, dexrazoxane, filgrastim, sargramostim, mesna, oprelvekin, palifermin, recombinant human erythropoietin etc. Additionally, the present status on the concurrent use of chemoprotectants in combination with chemotherapeutic agents, with focus on their safety is included. The advantageous role of these cytoprotective agents combined with chemotherapy remains controversial in clinical studies due to moderate protective efficacy for normal tissues and organs, risk of concomitant tumor protection and adverse reactions. Besides, the number of successful agents is rather small. Therefore, identification of novel approaches and chemoprotectants holds potential for better management of cancer with chemotherapy.
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Oral feeding with Arachidonic Acid (AA) and Docosahexanoic Acid (DHA) help in better recovery of haematopoiesis in sub-lethally irradiated mice
p. 182
Kedar Limbkar, Vaijayanti Kale, Lalita Limaye
DOI
:10.4103/2349-3666.240611
Haematopoiesis is severely hampered after exposure to ionizing radiations. Role of polyunsaturated fatty acids (PUFAs) during embryonic development as well as during various physiological processes is well established. However, few studies on their effect on haematopoiesis are reported. Hence, we studied the effect of oral administration of PUFAs-AA/DHA on haematopoiesis of sub-lethally irradiated mice. To determine the optimal dose for haematopoiesis, non-irradiated healthy mice were orally fed with different doses of AA/DHA daily for ten days. Additionally, mice were sub lethally irradiated and kept for ten days on normal diet. Further, sub-lethally irradiated mice were orally fed with optimal dose of AA/DHA for ten days. Mice from the experiments were sacrificed after ten days and their bone marrow cells were harvested and analyzed for their total nucleated cell (TNC) count, side population (SP) and lin-Sca-1
+
c-kit
+
(LSK) phenotype. Peripheral blood collected from this set of mice was subjected to hemogram analysis. Daily dose of 8 mg AA/DHA for ten days was assessed as optimal for enhancing BM-MNCs and primitive HSCs in non-irradiated mice. Significant depletion in BM-MNCs, SP and LSK cells was observed in sub lethally irradiated mice compared to un-irradiated control mice. Feeding with DHA or AA in sub lethally irradiated mice showed significantly higher number of BM-MNCs and increased percentage of SP and LSK cells, suggesting that DHA and AA resulted in better recovery of hematopoietically compromised mice. The data indicated that DHA or AA may serve as useful dietary supplements in patients exposed to irradiation.
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Mathematical modeling of viral epidemics: A review
p. 195
Pratip Shil
DOI
:10.4103/2349-3666.240612
Mathematical models to describe transmission and propagation of diseases have gained momentum over the last hundred years. Formulated mathematical models are currently applied to understandthe epidemiology of various diseases including viral diseases viz Influenza, SARS, measles, etc. With the emergence of advanced computing tools, designing mathematical models and generating simulations (numerical solutions) have become feasible. There is an enormous scope for using mathematical models in studying epidemiology of viral diseases through transmission dynamics of outbreaks and in evaluating or predicting the effects of interventions and vaccinations. The influenza pandemic of 2009 and the recent Ebola epidemics of 2014-15 have generated renewed interest in mathematical modelling of epidemics. Here we present a review of the various mathematical models and their applications in the study of virus driven epidemics.
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Recent advances in the treatment of Malaria
p. 216
Sohal Satish, Jayashree Puttur, Evans Coutinho, Premlata Ambre, Santosh R Nandan
DOI
:10.4103/2349-3666.240613
Malaria is an infectious disease caused by protozoan parasites belonging to the
Plasmodium
species. The disease has been a major cause of mortality and morbidity, especially in populations of African and SouthEast Asian countries. A well-developed treatment regimen including the artemisinins as a potent antimalarial and other safety preventive measures have played a major role in reducing global burden of malaria over the years. However, recent reports of drug resistance against the artemisinins should be a wakeup call, for the artemisinins have been the mainstay towards the treatment of the disease in recent past. There is a need for newer antimalarials that can be active on more than one stage of the parasite life cycle. These may be complementary to the artemisinins and may also help in keeping a check on the menace of drug resistance. The current review focuses on clinical drug candidates with activity against more than one stages of the malarial parasite life cycle.
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RESEARCH ARTICLE
Biomagnetic interaction of functionalized iron oxide nanoparticles with bovine serum albumin
p. 229
Mayank Gupta, Sudeshna Chandra
DOI
:10.4103/2349-3666.240614
Functionalized iron oxide (magnetic) nanoparticles are promising candidate for detection and sensing of target molecule as they can be manipulated and detected through magnetic interactions. The biological recognition moiety of the functionalized coating results in binding of the target analyte which causes a change in the interaction of the nanoparticles under the influence of an external magnetic field. This forms the basis of the fabrication of a bio-magnetic sensor. The current study reports the use of three different macromolecules viz. glycol chitosan (GC), poly ethylene glycol methyl ether (PEGME) and poly sodium stereo-4 sulphate (PSSNa) to functionalize and cap the magnetic nanoparticles. The magnetic nanoparticles were characterized using FTIR, XRD, TEM and TGA to evaluate their structural and surface properties. TEM showed spherical nanoparticles with mean size of ~11, 12 and 13 nm for GC, PEGME and PSSNa-MNPs respectively. TGA evaluates the weight loss of the modified MNPs and confirms the coating on the surface of the MNPs. Bovine serum albumin (BSA) was immobilized on the functionalized MNPs and detection studies were carried out using AC susceptibility studies on a physical property measurement system. Detection of BSA immobilized MNPs was exhibited at 300 K by the measurement of the imaginary part of the magnetic susceptibility over a frequency range and is based on the changes of dynamic magnetic properties of the MNPs, making use of the Brownian relaxation.
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