75 research outputs found
4-(Morpholin-4-yl)-3-(trifluoromethyl)benzonitrile
In the title benzonitrile compound, C12H11F3N2O, an intramolecular C—H⋯F hydrogen bond generates an S(7) ring motif. The trifluoromethyl group is disordered over two orientations with a refined occupancy ratio of 0.549 (16):0.451 (16). The morpholine ring adopts a chair conformation. The benzene ring and mean plane of the morpholine ring make a dihedral angle of 58.04 (10)° with each other. In the crystal, molecules are connected by intermolecular C—H⋯F and C—H⋯O interactions to form R
2
2(8) ring motifs. These interactions also link the molecules into chains parallel to the [10] direction
Relation of COVID-19 with acute ischemic bowel disease: A retrospective observational study
Introduction: COVID-19 is a serious respiratory disease caused by SARS-CoV-2, aside from the respiratory system, the gastrointestinal system is the most common site of SARS-COV-2 infection. The study aimed to assess relation between COVID and ischemic bowel disease by analysing length of hospital stay and mortality rates between COVID and non-COVID groups.
Methods: The study was conducted from June 2020 to November 2021 in the surgical wards of Seth GS Medical College and KEM Hospital, Mumbai. Included patients presented to emergency room with acute abdomen which diagnosed as acute ischemic bowel disease during the period of study and then compared the outcomes between COVID and non-COVID groups.
Results: Out of 40 patients, 16 had no history of COVID and remaining 24 had either previous history of COVID or diagnosed presently with COVID. In both COVID and non-COVID population, distribution of comorbidities were almost equal exception being stroke, where both the cases had previous history of COVID, diabetes was the most common comorbidity in both the groups followed by hypertension. Patients with active COVID infection had higher mortality of 75% (3 out of 4) followed by patients with past history of infection with mortality rate of 65% (13 out of 20) whereas the mortality rate in non-COVID patients were 37.5% (6 out of 16).
Conclusion: Ischemic bowel disease among COVID-19 patients is rare, but its association with high mortality rates and prolonged length of stay necessitates clinical suspicion and prompt intervention
Paraneoplastic thrombocytosis in ovarian cancer
<p>Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that
platelets play in abetting cancer growth are unclear.</p>
<p>Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse
models of epithelial ovarian cancer were used to explore the underlying mechanisms
of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.</p>
<p>Results: Thrombocytosis was significantly associated with advanced disease and shortened
survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated
in patients who had thrombocytosis as compared with those who did not. In mouse
models, increased hepatic thrombopoietin synthesis in response to tumor-derived
interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumorderived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis
in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in
tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In
addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of
paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet
antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor
growth and angiogenesis.</p>
<p>Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic
thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have
therapeutic potential. </p>
Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem Ion Accelerator: An Experimental and Theoretical Approach
Proton being the easiest light ion to accelerate and achieve desired beam profile, has been pursued as a popular particulate radiation for therapy applications. In the present study, Saccharomyces cerevisiae D7 strain was used to estimate the RBE values of the 3 MeV proton beam, and an attempt was made to derive mathematical formula for calculating RBE value with respect to the dose. Dosimetry studies were carried out using Fricke dosimetry and Semiconductor Surface Barrier detector to calibrate the absorbed doses of Gamma chamber-1200 and Folded Tandem Ion Accelerator respectively. Gold standard cell survival assay and gene conversion assay were used to compare gamma and proton radiation induced cell death and genetic endpoint. Multi target single hit model was used to derive mathematical formula for RBE estimation. The results show a linear survival-dose response after proton radiation and sigmoid survival-dose response after gamma radiation treatment. The calculated RBE value from the survival and gene conversion studies was 1.60 and 3.93, respectively. The derived mathematical formula is very useful in calculating RBE value, which varies from 3.61 to 1.80 with increasing dose. The estimated RBE value from the mathematical formula is comparable with the experimental values. With the help of the present mathematical formulation, RBE value at any dose can be calculated in the exponential and sigmoidal regions of the survival curve without actually extending the experiment in that dose region, which is not possible using conventional methods
Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER
MicroRNAs are small regulatory RNAs that post-transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet the underlying mechanisms are not well understood. Here, we identify tumor hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced miRNA processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, miRNA biogenesis and tumor stem cell phenotypes that may underlie poor outcome in breast cancer
Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression
Abstract
Purpose: VEGF-targeted therapies have modest efficacy in cancerpatients, butacquiredresistance iscommon. Themechanisms underlying such resistance are poorly understood. Experimental Design: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance. Results: Using murine cancer models of adaptive resistance to anti-VEGF antibody (AVA), we found a previously unrecognized roleofmacrophagesinsuchresistance.Macrophageswereactively recruited to the tumor microenvironment and were responsible
for the emergence of AVA resistance. Depletion of macrophages following emergence of resistance halted tumor growth and prolonged survival of tumor-bearing mice. In a macrophagedeficient mouse model, resistance to AVA failed to develop, but could be induced by injection of macrophages. Downregulation of macrophage VEGFR-1 and VEGFR-3 expression accompanied upregulation of alternative angiogenic pathways, facilitating escape from anti-VEGF therapy. Conclusions: These findings provide a new understanding of the mechanisms underlying the modest efficacy of current antiangiogenesis therapies and identify new opportunities for combinationapproachesforovarianandothercancers. ClinCancerRes; 23(22); 7034–46. �2017 AACR
Hematogenous Metastasis of Ovarian Cancer: Rethinking Mode of Spread
SummaryOvarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin 1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis
Effect of the consumption on buriti oil on the metabolism of rats induced by iron overload
Erythropoietin Stimulates Tumor Growth via EphB4
While recombinant human erythropoietin (rhEpo) has been widely used to treat anemia in cancer patients, concerns about its adverse effects on patient survival have emerged. A lack of correlation between expression of the canonical EpoR and rhEpo’s effects on cancer cells prompted us to consider the existence of an alternative Epo receptor. Here, we identified EphB4 as an Epo receptor that triggers downstream signaling via STAT3 and promotes rhEpo induced tumor growth and progression. In human ovarian and breast cancer samples, expression of EphB4 rather than the canonical EpoR correlated with decreased disease-specific survival in rhEpo-treated patients. These results identify EphB4 as a critical mediator of erythropoietin-induced tumor progression and further provide clinically significant dimension to the biology of erythropoietin
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