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Angiogenesis in Control and Progression of Lung Cancer (This article was withdrawn as requested by the authors at March 24, 2015))
No full textLung cancer is the major cause of cancer-related mortality worldwide owing to its late-stage detection and aggressive behavior. Epidemiologically, several genetic and epigenetic factors contribute to the development of lung cancer. Angiogenesis, a critical process in tumor progression has become an important target for anti-cancer therapy particularly in lung cancer. Besides commercially available angiogenic inhibitors, numerous anti-angiogenic therapies have been developed to limit tumor growth, although, most of them have not proved beneficial in terms of long-term survival. Despite, logical advances in treatment strategies, NSCLC still remains a major health concern due to poor prognosis of the diseases state. This calls for a comprehensive analysis of signaling processes governing tumor angiogenesis and treatment options available thereof for development of a sustainable strategy to control cancer. In this review, several aspects of lung cancer have been discussed starting from its pathological characterization to the development of modern therapeutics
Linking Cancer Metabolism and Innate Immunosurveillance: Modulation of Gamma-Delta T Cell-mediated Tumor Cell Recognition by the Key Metabolic Regulator AMPK
No full textThere is accumulating evidence demonstrating that gd T cells comprise an important arm of innate cancer immunosurveillance governed by intracellular accumulation of mevalonate pathway products. In contrast to optimized in vitro conditions, growing tumors in vivo are exposed to nutrient deprivation/hypoxia both activating the key energy metabolism regulator adenosine monophosphate activated protein kinase (AMPK). Upon activation, AMPK increase catabolic ATP-generating processes such as uptake and oxidation of glucose and fatty acids but inhibit ATP-consuming biosynthetic processes such as protein synthesis and cholesterol production (mevalonate pathway). This correlation prompted us to investigate the effects of AMPK activation (mimicked by the synthetic AMP-analogue 5-aminoimidazole-4-carboxamide riboside (=AICAR) or by the anti-diabetic drug metformin on tumor cell recognition by Vg9Vd2 T cells.We found that Vg9Vd2 T cells exhibited significant decreased up-regulation of activation markers in response to AICAR or metformin pre-treated target tumor cell lines (Daudi, RPMI 8226 and the farnesylpyrophphosphate synthase (FPPS)-knockdown cell line Raji AS22) as compared to untreated tumor cells. In addition, AMPK activation in tumor cells reduced the ability of Vg9Vd2 T cells to produce pro-inflammatory cytokines (IFN-g, TNF-a). As determined by phospho-specific flow cytometry analysis, either AICAR or metformin treatment resulted in increased phosphorylation and therefore inactivation of the AMPK target enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, subsequently lowering intracellular mevalonate pathway products critical for activation of Vg9Vd2 T cells. Thus, this data demonstrates for the first time an impact of cancer metabolism on immune recognition facilitating tumor escape
Antimutagenic Potential of Probiotic Lactobacillus sporogenes Using Ames assay
Get PDFObjective: Probiotic are beneficial microbial nutrition supplements which have useful effects on human health by conserving of bowel microbial balance. There are many studies that have been recommended the use of probiotic products as cancer risk reducer. The aim of present study was to investigate antimutagenic potential of Probiotic Lactobacillus sporogenes against TA98 and TA100 strain of Salmonella typhimurium.Material and Methods: Ames test was used in the present investigation to evaluate antimutagenic activity in TA98 and TA100 strains of Salmonella typhimurium using direct acting mutagens (Sodium azide) and different concentration of Probiotic L.Sporogenes (25, 50, 100 and 500 μg/0.1 ml/plate).Results: Probiotic Lactobacillus sporogenes showed significant antimutagenicity against mutagen sodium azide in TA98 and TA100 tester strains whereas it showed antimutagenicity result in inhibition of 93-97% and 62-88% of his+ revertants induced by sodium azide in TA98 and TA100 strains respectively.Conclusion: The antimutagenicity of Probiotic Lactobacillus sporogenes the observed in the present study implies chemopreventive pharmacological importance of Probiotic Lactobacillus sporogenes and encourages its use as a biotherapeutic agent
Papillary carcinoma breast in male patient - A rare presentation
Get PDFIntroduction - Male breast carcinoma is rare, accounting for 1% of all malignancies in men and around 1% of all cases of breast carcinoma. Intracystic papillary carcinoma accounts for 0.5–1% of all breast cancers. It generally has good prognosis in women with almost 100% reported 10 year survival rate.Similar data for male patients is not available as the disease is extremely rare.Presentation of Case - A 52 year-old male patient presented with a swelling in his left breast. Swelling had gradually increased in size. On examination, a well-circumscribed swelling was palpable in retro aerolar region with nipple retraction. Mass was not fixed to underlying pectoralis muscle.A large mobile axillary lymph node was palpable. Fine needle aspiration was done, which reported “atypical ductal hyperplasia”. A core biopsy was done which displayed features of intracystic papillary carcinoma. A left modified radical mastectomy was carried out with axillary dissection. The biopsy report of the specimen confirmed the diagnosis of intracystic papillary carcinoma, tumor deposits were seen in lymph nodes. Adjuvant chemotherapy was given postoperatively. Patient recovered well.Conclusion - Intracystic papillary carcinoma is a rare malignancy of breast .It carries an excellent prognosis with upto 100% ten years survival rates reported in females.Surgery with chemotherapy has remained mainstay of treatment but due to rarity of the male breast cancer as such and Intracystic papillary carcinoma in particular, there are no clear guidelines for its management. Further analysis of this disease is needed for its better understanding and management.
Overview of Diverse Pharmacological Activities of Substituted Coumarins: Compounds with Therapeutic Potentials
Get PDFCoumarins are well known plant derived natural product which is extensively used as a biological active compound. Coumarins have attracted considerable attention of medicinal chemists and pharmacologists and have been demonstrated to bear many pharmacological activities. Natural and synthetic coumarins were verified to have antioxidant, antiinflammatory, anticoagulation, estrogenic, dermal photosensitizing, vasodilator, molluscicidal, anti helmentic, sedative, hypnotic, analgesic, hypothermic, antimicrobial, anticancer, anticonvulsant, antihyperlipidemic, tyrosinase inhibitor and anti-parkinsonism and antiulcer activities. This review is based on recent studies of coumarins and coumarin related compounds. Therefore the focus will be on their pharmacological importance along with the various synthesis methods. The aim of the paper is to review the available information on substituted coumarins
Biological Potential of Substituted Thiadiazole Compounds
Get PDFHeterocyclic compounds are present in most biologically active molecules. The chemistry of heterocyclic compounds has been an interesting field of study. Heterocyclic nucleus 1,3,4-thiadiazole constitutes constitutes an important class of compounds for drug development. The novel thiadiazoles and investigation of their chemical and biological behavior have gained more importance in recent decades. There has been intense investigation of different classes of thiadiazole compounds, many of which possess extensive pharmacological activities. The 1,3,4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. 1,3,4-Thiadiazole nucleus exhibited remarkable pharmacological activities Such as antibacterial, antifungal, antitubercular, antiviral, antileishmanial, anti-inflammatory, analgesic, antidepressant, anticonvulsant, anticancer, antioxidant, antidiabetic, molluscicidal, antihypertensive, diuretic. So far, modifications of the thiadiazole ring have proven highly effective with improved potency and lesser toxicity. The present review highlights the recently synthesized thiadiazole possessing important biological activities
Investigation on Poly(acrylate-co-acrylamide)/polyanilineConducting Hydrogel
Get PDFIn the present work, conducting poly(acrylate-co-acrylamide)/polyaniline (PAANa-co-AM/PANI) hydrogel was synthesized and its structural and electrical properties were studied in detail. The composite material was prepared by two step interpenetrating network solution polymerization of aniline inside the poly(acrylate-co-acrylamide) hydrogel matrix. The polymerization reactions were carried out in aqueous medium and in the presence of ammonium persulphate (APS) as initiator and N, N’-methylene bisacrylamide (NMBA) as crosslinker. Effects of crosslinker, initiator, aniline monomer, acrylamide amount and particle size of superabsorbent polymer on the synthesis and conductivity of (PAANa-co-AM/PANI) hydrogel were studied in detail. The structure and morphological analysis was done using Fourier Transform Infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) techniqes. The conductivity of P(AANa-co-AM)/PANI was found as high as 0.81 mS cm-1 with optimized synthesis conditions
Comparative Evaluation of Modified Furlow Palatoplasty and Intravelar Veloplasty in Cleft Palate Repair
Get PDFIntroduction: The purpose of this study was to comparatively assess the two techniques of cleft palate repair i.e. Kriens intravelar veloplasty (IVV) and modified Furlow Palatoplasty (MFP) for post-operative fistula formation, wound dehiscence at suture line, nasal regurgitation, velopharyngeal insufficiency, soft palate lengthening and speech.Method: This prospective study was conducted on 60 patients having primary cleft palate. They were assigned either to IVV group or MFP group randomly so that both the groups consisted of 30 patients each. The two groups were operated under general anesthesia. Measurements at the time of operation were made with the help of soft ruler and Castroviejo caliper. Follow up of patient's was done 1 week, 1 month, 3 month, 6 months and complication is present was noted. Five year post operatively speech was recorded and assessed by the speech language pathologist. Post-operative Nasoendoscopy was also performed to assess the velopharyngeal insufficiency.Result: The MFP group showed more percentage elongation of the soft palate and less incidence of post-operative palatal fistula formation than IVV group. Total speech scores were superior in MFP patients but the differences were less robust. Velopharyngeal incompetence was present in both groups but was less severe in MFP group than the IVV group. Conclusion: The MFP group showed comparatively superior results than the IVV group but required an increased surgical time. Therefore MFP can be used as an alternative technique for cleft palate repair
Conservation Analysis of HIV-1 Protein Sequences Reveal Potential Drug Binding Sites: A Case of Viral Protein U and Protease
Get PDFThe HIV-1 viral protein U (Vpu) and protease play a pivotal role in the infectious lifecycle of human immunodeficiency virus-1. The objective of this study is to find the degree of conservation of the viral protein U (Vpu) and protease protein and to detect conserved binding sites, which might be used as target sites for potential anti-Vpu and anti-protease drugs. The conservation analysis was based on 4231 amino acid sequences for Vpu and 13,457 amino acid sequences for protease. The conservation analysis revealed a number of conserved and variable residues. The universally conserved residues identified in this study might be involved in either structure stabilizing or protein-protein interactions. The novel conserved potential binding sites which have been identified are: Vpu (Ile39, Arg45, Ile46 and Gly71) and protease (Pro9, Thr80 and Asn83). Along with conservational analysis, structural analysis revealed novel binding sites, namely four conserved sites on Vpu (Arg49, Ala50, Ser53, Gly54, Gly59; Glu56, Ser57, Asp60; Glu56, Gly71; Glu48, Glu51, Asp52, Gly54-Glu56) and single novel conserved site on protease (Thr4, Trp6 and Arg87, Asn88, Thr91, Gln92). The outcome of this study provides the basis for developing anti-Vpu and anti-protease drugs which have abridged potential to induce drug resistance through mutations
Financing of Entrepreneurs in India: a New Dimension under Islamic Finance
Get PDFFinancing is one of the basic requirements of a project which Entrepreneur needs to start. Project financing is both for short term and long term. The sources from which the Entrepreneur can meet their financial needs for their project vary from country to country. In some countries, Institutions dealing in providing finance to Entrepreneurs share profits and losses and in some countries (like India) only profits are shared and losses are transferred to entrepreneurs. The former is called Mudarabah financing, which is currently working in more than 300 institutions in the world. Under this type of financing, risk is also shared and not transferred to entrepreneurs. This type of financing has shown tremendous success as far as entrepreneurship is concerned. While taking the pros and cons of this type of financing, the paper provides a comprehensive detail about its prospects and problems, as far as Indian entrepreneurship is concerned. It is explained in the paper how entrepreneurs can be through Islamic finance. As there are six ways for financing the entrepreneurs and all are explained in this paper