30 research outputs found

    The common and uncommon cestodal infestation encountered in routine histopathological practice from a semi-urban population in south India and their public health importance.

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    Parasites are encountered uncommonly in routine histopathologic practice. Among them, cestodes form a major bulk. Cysticercosis heads the list forming the bulk of cases followed by Hydatidosis and Sparganosis. Microscopic identification of inflammation with surrounding reactions along with other morphological features forms the mainstay of diagnosis of parasitic diseases on histopathology. Identification of the parasites on histopathological examination would reduce the cost-diagnosis ratio avoiding expensive serological investigation

    Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

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    PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). RESULTS: ATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC(50) levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH(2)-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis. CONCLUSION: These data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance

    Chitosan nanoparticle-mediated delivery of miRNA-34a decreases prostate tumor growth in the bone and its expression induces non-canonical autophagy

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    While several new therapies are FDA-approved for bone-metastatic prostate cancer (PCa), patient survival has only improved marginally. Here, we report that chitosan nanoparticle-mediated delivery of miR-34a, a tumor suppressive microRNA that downregulates multiple gene products involved in PCa progression and metastasis, inhibited prostate tumor growth and preserved bone integrity in a xenograft model representative of established PCa bone metastasis. Expression of miR-34a induced apoptosis in PCa cells, and, in accord with downregulation of targets associated with PCa growth, including MET and Axl and c-Myc, also induced a form of non-canonical autophagy that is independent of Beclin-1, ATG4, ATG5 and ATG7. MiR-34a-induced autophagy is anti-proliferative in prostate cancer cells, as blocking apoptosis still resulted in growth inhibition of tumor cells. Thus, combined effects of autophagy and apoptosis are responsible for miR-34a-mediated prostate tumor growth inhibition, and have translational impact, as this non-canonical form of autophagy is tumor inhibitory. Together, these results provide a new understanding of the biological effects of miR-34a and highlight the clinical potential for miR-34a delivery as a treatment for bone metastatic prostate cancer

    A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.

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    Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumor-associated endothelial cells, with a higher expression correlating with favorable prognosis. Importantly, ELTD1 silencing impairs endothelial sprouting and vessel formation in vitro and in vivo, drastically reducing tumor growth and greatly improving survival. Collectively, these results provide insight into the regulation of tumor angiogenesis and highlight ELTD1 as key player in blood vessel formation

    International incidence of childhood cancer, 2001-10: A population-based registry study

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    The value of systematic pattern analysis in FNAC of breast lesions: 225 cases with cytohistological correlation

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    Background : Fine needle aspiration cytology (FNAC) has a high rating in the assessment of breast lesions. Various methods have been used to diagnose cytology of breast lesions. Aims : Present study was undertaken to evaluate the feasibility of application of systematic pattern analysis based on morphology in diagnosing breast aspirates. Materials and Methods : This is a retrospective study of FNAC of the breast done over a period of 4 years in a tertiary care centre. A total of 225 cases of breast lesions for which FNAC was done with histological follow-up were included in the study. Breast aspirates were provisionally diagnosed based on systematic pattern analysis. Aspirates were grouped into six categories based on predominant cellular pattern, and correlation between cytological and histological diagnosis was assessed. Results : Application of pattern analysis on FNAC of breast lesions in our study had a sensitivity of 94.5%, specificity of 98%, diagnostic accuracy of 97%, positive predictive value of 95.8%, and negative predictive value of 97.4%. Conclusions : Systematic pattern analysis based on morphology of FNAC smears was found to be highly reliable and could be easily reproducible in the assessment of breast masses

    An Audit of Requests for Fresh Frozen Plasma in a Tertiary Care Center in South India

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    Aim: To audit the fresh frozen plasma (FFP) usage with an insight into various guidelines. Materials and Methods: The blood bank records pertaining to FFP usage in patients admitted in our medical college hospital were retrospectively reviewed for 2 years for usage of FFP in various departments and evaluated for appropriateness of usage based on various guidelines, which included the 2013 guidelines published by the National Health and Medical Research Council and the Australasian Society for Blood Transfusion. Results: A total of 785 units of FFPs were transfused to 207 patients during the study period. The appropriate usage was found to be 59.3%, and the usage was most appropriate in massive transfusions. Conclusion: This study highlights the nonadherence to guidelines among clinicians which is mainly due to lack of knowledge of appropriate usage

    Synthesis, characterization crystal and molecular structure studies of 5-(3-methylbenzoyl)-4-methyl-1,3,4,5-tetrahydro-2h-1,5-benzodiazepin-2-one: hirshfeld surface analysis and DFT calculations

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    Benzodiazepines derivatives have been reported for their broad spectrum of biological applications. These derivatives are also being investigated for their supporting activity against human cancers. The title compound 5-(3-Methylbenzoyl)-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one has been synthesized, characterized using 1H NMR, 13C NMR, IR techniques and finally the structure was confirmed by single crystal X-ray diffraction studies. The single crystals of the compound were obtained using ethanol as crystallization solvent. The compound C18H18N2O2 crystallizes in the orthorhombic crystal system with P212121 space group. The crystal structure of the title compound is stabilized by Nsingle bondH路路路O intermolecular hydrogen bond and p路路路p interactions. The structure also exhibits one dimensional chain stacking along a-axis through intermolecular interactions. These molecular interactions were then quantified using Hirshfeld surface analysis to understand their nature of involvement in interaction with other molecules. The analysis of the fingerprint plots revealed that the H鈥 (58.7%) interactions has the major contribution to the total molecular surface. Further, the electronic properties of the title compound were studied by computing the frontier molecular orbital energies using density functional theory calculations with B3LYP/6-311 + G (d, p) level basis set. Finally, the molecular electrostatic potential map was generated and the chemical reactive sites were identified to understand the molecular surface properties
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