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Dichotomy of Nitric Oxide in Cancer Biology and its Therapeutic Implications
Get PDFThe role of Nitric oxide, which is an important signalling molecule, has become an active and controversial area of research in cancer. Nitric oxide has been designated as “Double-edged sword” in Cancer as it has exhibited both pro-apoptotic and anti-apoptotic effects. Nitric oxide synthase (NOS) levels have been associated with contrasting effects of tumor suppression tumor progression. The discovery of generation of NO in mammalian tissues and its biological role in cancer has thrown light into tumor biology research. Through various studies conducted, it has become clear that concentration and time dependent regulation of Nitric oxide lead to tumor growth, cytostasis and cell death .The regulation of tumor growth by Nitric oxide represents an important new dimension in cancer research and understanding of mechanisms involved behind this process at molecular and cellular level is a major area of concern which will open up new avenues in Cancer Research and may help to provide new and better therapeutic interventions in diagnosis, treatment and cure of Cancer
Meat Consumption and Risk of Developing Esophageal Cancer: A Meta-analysis
Get PDFBackground: Meat has been linked as a risk factor for several cancers. Red meat and processed meat specifically have been suggested as risk factors for esophageal cancer, but this has not been established. We performed a meta-analysis to summarize available evidence from case-control and cohort studies on this topic.Methods: A systematic search of MEDLINE, PubMed, EMBASE was completed up until November, 2013. Studies were included that reported confirmed histological diagnosis of cancer, odds ratios (OR) or relative risks (RR) and confidence intervals (CI). Pooled ORs and 95% CIs were calculated for the effect of different meats on the development of esophageal cancer using a random effects model. Studies were assessed for heterogeneity and publication bias.Results: 29 studies were included in this analysis, involving 1,208,768 individuals with a total of 8,620 cases and 44,574 controls. High consumption rates were associated with development of cancer for red meat (OR 1.59; 95% CI 1.31-1.93), processed meat (OR 1.75; 95% CI 1.28-2.38), barbecued meat (OR 1.54; 95% CI 1.25–1.91) and overall (OR 1.26; 95% CI 1.11-1.43). Low and medium consumption rates were also significant for red and barbecued meat. High and medium consumption of white meat was significantly protective. High consumption of fish was also found to be protective (OR 0.73; 95% CI 0.55-0.95).Conclusions: Findings of this meta-analysis demonstrated red meat, processed meat and barbecued meat are likely to increase the risk of esophageal cancer in a dose dependent relationship. Fish and white meat were shown to have a protective effect
Primary T-cell Non – Hodgkin lymphoma of the Urinary Bladder Presenting as Haematuria and Bilateral Hydronephrosis: Report of a Rare Case
Get PDFIntroduction: Primary T cell lymphoma of the urinary bladder is extremely rare disease. Most of the lymphomas of urinary bladder are B-cell lymphomas. We encountered a case of T-cell lymphoma of the urinary bladder presenting as haematuria and bilateral hydronephrosis. Presentation of Case: A 42-year-old man was admitted to our hospital because of intermittent painful gross haematuria associated with bilateral loin pain and vomiting lasting for 3-4 weeks. Results of his general examination were normal. An ultrasonographic study and Computed Tomography (CT) of his abdomen and pelvis revealed bilateral gross hydro-ureteronephrosis with significantly thickened urinary bladder wall with large circumferential growth involving the entire bladder occluding both ureteric orifices with internal calcification. A cystoscopy procedure with Trans Urethral Resection of Bladder Tumour (TURBT) was performed. Postoperative microscopic examination and immunohistochemistry showed medium to large lymphocytes with hyperchromatic nuclei and strong expression of CD3 in the tumour cells and negativity for CD20 and cytokeratin. A diagnosis of T-cell non Hodgkin Lymphoma was entertained. Conclusion: Presentation of bilateral hydronephrosis with primary T cell lymphoma has not been reported previously. This sort of presentation can mimic other bladder malignancy and present a diagnostic challenge. An ancillary technique, Immunohistochemistry in our case, helped us arrive at the correct diagnosis and subsequent appropriate management
Vagal Nerve Schwannoma Clinically Mimicking Gastrointestinal Stromal Tumor: Report of a Case
Get PDFIntroduction: Mesenchymal tumors of the gastrointestinal (GI) tract are mainly comprised of a spectrum of spindle cell tumors which include gastrointestinal stromal tumors (GISTs), leiomyomas or leiomyosarcomas, and schwannomas. As all of these tumors of the GI are located in the submucosal layer of the bowell wall, differential diagnosis is very difficult. Histopathological evaluation using immunohistochemical staining is required for the definitive diagnosis.Presentation of case: A 20-year-old female patient was presented with an upper abdominal pain and dyspepsia since 2 months duration.This case is initially thought as GIST but finally diagnosed as vagal nerve schwannoma by histopathological evaluation after resection of the mass.Conclusion: Schwannomas should be considered in the differential diagnosis of other mesenchimal tumors, such as gastrointestinal stromal tumors and leiomyomas or leiomyosarcomas, indeed it can grow in any part of the peripheral nerves along the gastrointestinal tract. Histopathological evaluation including immunohistochemical staining is required for the definitive diagnosis
Automatic Detection of Vasculature from the Images of Human Retina Using CLAHE and Bitplane Decomposition
Get PDFRetinal blood vessel detection and extraction is an essential step in understanding several eye related pathologies. It is the key in automatic screening systems for retinal abnormalities. We present a novel yet simple approach to the detection and segmentation of vasculature from the fundus images of the human retina. For the detection and extraction of blood vessels, the green channel of the image is separated. The green channel is preprocessed for a better contrast by using contrast limited adaptive histogram equalization (CLAHE) and mathematical morphology. On applying bitplane decomposition, bitplane 2 is found to carry important information on the topology of retinal vasculature. A series of morphological operations on bitplane 2 segment the vasculature accurately. The proposed algorithm is computationally simple and does not require a prior knowledge of other retinal features like optic disc and macula. The algorithm has been evaluated on a subset of MESSIDOR and DRIVE image databases with various visual qualities. Robustness with respect to changes in the parameters of the algorithm has been examined.
A Novel Fibrinolytic Enzyme from Bacillus Sphaericus MTCC 3672: Optimization and Purification Studies
Get PDFA novel extracellular fibrinolytic enzyme was produced from Bacillus sphaericus MTCC 3672 for dissolving blood clots. Optimized fermentation parameters achieved by one factor at a time approach had demonstrated 2.85 fold increase in fibrinolytic activity i.e. from 3.5*104 U/l (basal media) to 9.98*104 U/l after 24 h of incubation in submerged fermentation. Statistical screening of six independent nutritional variables such as, glucose, yeast extract, NaCl, MgCl2, MnCl2, CaCl2 was studied using Plackett-Burman design. Amongst six variables, yeast extract was found to be significant factor affecting yield of a fibrinolytic enzyme. Furthermore, growth kinetics of biomass formation, enzyme production, and substrate utilization was evaluated by unstructured kinetic models and various biokinetic parameters such as µmax (0.37 1/h), Pr (0.12 1/h), YP/S (7.74 U/g) and YX/S (3.32 g/g) were determined. In purification step, ultrafiltered broth was purified with DEAE Cellulose anion exchange chromatography and Sephadex G100 gel filtration chromatography with 10 fold purity. In vitro fibrin clot degradation study had revealed significant breakdown of fibrin clot. The fibrinolytic activity of purified enzyme (7.5 mm) was found to be matching with marketed Nattolife® (8.0 mm) (nattokinase) and superior to Thromboflux® (0 mm) (streptokinase) formulations. Hence, efficient formulation containing purified fibrinolytic agent can be used for medical emergencies viz. myocardial infarction and deep vein thrombosis
Fascin-1 and Digestive System Carcinoma
Get PDFInvasion and metastasis are major reason for poor prognosis of digestive system carcinoma patients. Motility and migratory capacity are important in contributing to tumor cells’ invasion and metastasis. Fascin is one of actin cross-linking proteins and can participate in forming parallel actin bundles in cell protrusions. Fascin-1 is consequently involved in cell adhesion, motility, and signaling. In cultured cells, over-expression of fascin-1 can increase migration and invasion capacity of cells. Many studies show up-expressions of fascin-1 are significantly associated with worse prognosis, poor differentiation, TNM stage, positive for lymph node metastasis, and positive for distant metastasis in digestive system carcinoma patients. So fascin-1 may have prognostic value as an early biomarker for more aggressive digestive system carcinoma. This review provides detailed account of preclinical studies conducted to determine the utility of fascin-1 as a therapeutic and predictive agent in invasion and metastasis of carcinomas
Successful Rechallenge with Vemurafenib and Corticosteroids in a Patient with Vemurafenib Induced Liver Dysfunction, Previously Treated with Ipilimumab
Get PDFIntroduction: There are multiple new systemic therapies for patients with metastatic melanoma, including vemurafenib and ipilimumab. Because of this, more patients will be exposed to multiple medicines during their treatment course. Here we present the case of a successful rechallenge with vemurafenib and concurrent corticosteroids in a patient with vemurafenib responsive metastatic melanoma and vemurafenib induced liver dysfunction thought to be related to previous treatment of ipilimumab.Presentation of case: A 60-year-old woman with a history of stage 3 melanoma presented with metastases to her liver and lymph nodes, normal liver function tests (LFTs) and was started on ipilimumab. After her symptoms increased and her disease progressed, ipilimumab treatment was stopped and vemurafenib was initiated. She experienced good regression in her disease burden but subsequently experienced a grade 4 elevation in her LFTs, which resolved with a corticosteroid taper. Her disease responded well to a vemurafenib rechallenge at a reduced dose; however, she experienced another increase in her LFTs. By administering vemurafenib with corticosteroids concurrently, she achieved good tumor shrinkage without liver dysfunction.Conclusion: The reader should have an increased appreciation for the emerging adverse event profile of patients treated with multiple systemic metastatic melanoma therapies during their course and potential management strategies
Managing IT Operations in a Cloud-driven Enterprise: Case Studies
Get PDFEnterprise IT needs a new approach to manage processes, applications and infrastructure which are distributed across a mix of environments. In an Enterprise traditionally a request to deliver an application to business could take weeks or months due to decision-making functions, multiple approval bodies and processes that exist within IT departments. These delays in delivering a requested service can lead to dissatisfaction, with the result that the line-of-business group may seek alternative sources of IT capabilities. Also the complex IT infrastructure of these enterprises cannot keep up with the demand of new applications and services from an increasingly dispersed and mobile workforce which results in slower rollout of critical applications and services, limited resources, poor operation visibility and control. In such scenarios, it’s better to adopt cloud services to substitute for new application deployment otherwise most Enterprise IT organizations face the risk of losing 'market share' to the Public Cloud. Using Cloud Model the organizations should increase ROI, lower TCO and operate with seamless IT operations. It also helps to beat shadow IT and the practice of resource over-or under provisioning. In this research paper we have given two case studies where we migrated two Enterprise IT application to public clouds for the purpose of lower TCO and higher ROI. By migrating, the IT organizations improved IT agility, enterprise-class software for performance, security and control. In this paper, we also focus on the advantages and challenges while adopting cloud services
Down Regulation of Phosphatidylinositol Glycan Class S (PIGS) by siRNA Sensitizes HeLa Cells to UV and H2O2
Get PDFOur research group had recently found that an endoplasmic reticulum membrane protein, phosphatidylinositol glycan class S (PIGS), interacts with a protein involved in DNA repair, DNA polymerase beta (pol) (using yeast 2 hybrid system), suggesting a role of PIGS in base excision repair pathway. As an essential component of glycosylphosphatidylinositol (GPI) transamidase, PIGS helps many eukaryotic proteins to anchor on the cell surface. In the absence of PIGS, the carbonyl intermediate of GPI is not generated, and GPI biosynthesis remains incomplete. In order to further our understanding of the function of PIGS, we knocked down the gene by using siRNA technology in HeLa cells. The knocked down cell lines were tested for their sensitivity to ultraviolet (UV) radiation and hydrogen peroxide (H2O2) toxicity. The proliferation activity was compared by wound-healing assay. Apoptosis was studied by DNA fragmentation assay, colony forming assay, and caspase assay. Wound healing assay result indicates remarkably higher (1.5-2.7 times) proliferation rate of PIGS knocked down cells. The results from the sensitivity test to UV and H2O2, assessed using DNA fragmentation assay, show that PIGS siRNA cells are more sensitive than the control cells. Apoptosis of these sensitive cells is mediated by the release of cytochrome C in the cytosolic fraction followed by activation of caspase 9, 3 respectively. Therefore, in the future, RNAi technology may be used in the therapy of cervical cancer by depleting PIGS and then treating the patients with UV and H2O2