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The Role of Suppressors of Cytokine Signalling in Human Neoplasms
Walid Sasi,Anup K. Sharma,Kefah Mokbel
Molecular Biology International , 2014, DOI: 10.1155/2014/630797
Abstract: Suppressors of cytokine signalling 1–7 (SOCS1–7) and cytokine-inducible SH2-containing protein (CIS) are a group of intracellular proteins that are well known as JAK-STAT and several other signalling pathways negative feedback regulators. More recently several members have been identified as tumour suppressors and dysregulation of their biological roles in controlling cytokine and growth factor signalling may contribute to the development of many solid organ and haematological malignancies. This review explores their biological functions and their possible tumour suppressing role in human neoplasms. 1. Cytokines and Their Signalling Pathways Cytokines are a large family of secreted soluble glycoproteins that regulate cellular growth and differentiation which are part of fundamental biological processes including embryonic development, immunity, wound healing, and haematopoiesis. Cytokines carry information about the biological status to target cells by interacting with receptors on the cell surface. Cellular responses to cytokine stimulation depend on the type of cytokine and the nature of the target cell and include proliferation, differentiation, effector function, and survival [1, 2]. Cytokines activate multiple intracellular signalling pathways in order to produce their physiological effects. One of the most studied pathways is that involving the receptor-associated janus kinases (JAKs) and the latent cytoplasmic transcription factors signal transducers and activators of transcription (STATs) [3, 4]. Genetic deletion experiments in mice have demonstrated that this pathway is critical for the actions of specific cytokines. For example, STAT1 is absolutely required for the actions of interferons, STAT4 is absolutely necessary for the actions of interleukin-12 (IL-12), STAT6 is required for the actions of interleukin-4 (IL-4), and JAK3 is required for the actions of cytokines that use the common γ receptor [5]. This cascade requires strict cellular control and loss of regulation can promote tumorigenesis and chronic inflammation. The threshold, magnitude, and specific responses elicited by cytokine stimulation are regulated by numerous mechanisms including tyrosine phosphatases, receptor internalisation, proteasomal degradation of signalling adaptor molecules, soluble receptor antagonists, and specific inhibitors, including the protein inhibitors of activated STATs (PIAS) and suppressor of cytokine signalling (SOCS) proteins. The expression of SOCS proteins can be induced by cytokine stimulation, and they not only serve to interfere with signalling
Capsular synovial metaplasia mimicking silicone leak of a breast prosthesis: a case report
Sarah Krishnanandan, Ali Abbassian, Anup K Sharma, Giles Cunnick
Journal of Medical Case Reports , 2008, DOI: 10.1186/1752-1947-2-277
Abstract: A 25-year-old woman had undergone bilateral breast augmentation for cosmetic reasons. One implant was subsequently subjected to two attempts at expansion to correct asymmetry. The patient was later found to have a large quantity of viscous fluid around the port of that same prosthesis. Histological assessment of the implant had consequently confirmed capsular synovial metaplasia. This had initially caused the suspicion of a silicone 'bleed' from the implant and had resulted in an unnecessary explantation.Capsular synovial metaplasia should be ruled out before the removal of breast implants where a leak is suspected. Manipulation and expansion of an implant may be risk factors for the development of synovial metaplasia.Synovial metaplasia around prostheses is regarded as a transitional phenomenon [1]. We describe the case of a patient in whom, at the time of removal of a prosthetic port, the quantity of viscous fluid produced as a result of metaplasia caused us to suspect that a silicone bleed had occurred. This resulted in what later appeared to have been the unnecessary explantation of her implant.A fit and healthy 25-year-old Caucasian woman presented with asymmetry and gross bilateral tubular deformity of the breasts. Subsequently, a bilateral breast reconstruction with 350 cc Becker？ (Mentor, UK) implants was performed. At the time of surgery, 200 ml of saline was used to inflate both implants. The left implant was further inflated 1 and 5 months later using 80 ml of normal saline on both occasions, to optimize symmetry.One year later, both ports were removed as a day case procedure. At that time, the right port was removed without complication. However, the left port was surrounded by a viscous fluid simulating implant rupture. A silicone gel bleed was suspected and another operation was planned where the left prosthesis was replaced with another permanent implant. The fluid and a sample of the periprosthetic capsule were sent for histological review. Histologi
Bilateral Florid Papillomatosis of the Nipple: An Unusual Indicator for Metachronous Breast Cancer Development—A Case Report
Walid Sasi,Dibyesh Banerjee,Kefah Mokbel,Anup K. Sharma
Case Reports in Oncological Medicine , 2014, DOI: 10.1155/2014/432609
Abstract: Adenoma or florid papillomatosis of the nipple (FPN) is a rare benign disease which has histopathological features similar to those of a mammary papillary carcinoma. Here, we report a rare case of bilateral florid papillomatosis of the nipple and breast cancer, with a literature review. 1. Introduction Adenoma or florid papillomatosis of the nipple (FPN) is a rare benign disease which clinically resembles Paget’s disease of the nipple and has histopathological features similar to those of a mammary papillary carcinoma [1]. In this report, we discuss a rare case of bilateral florid papillomatosis of the nipple with unilateral breast cancer, followed by a brief literature review. 2. Case Report A 63-year-old Caucasian woman presented to our breast clinic with a cracked right nipple and a chronic yellow discharge for 1 year. She had a left side mastectomy with Latissimus Dorsi flap reconstruction 2 years ago for breast cancer. Histopathological examination of the left mastectomy specimen reported features of left nipple florid papillomatosis along with multifocal ductal carcinoma in situ with apocrine features and microinvasive changes. Twelve years prior to that, she had a benign cyst removed from her left breast. Her mother died of ovarian cancer. Findings on clinical examination were those of eczematous-like changes of her right nipple with crusting and nipple inversion. A yellow discharge could be expressed on examination and no palpable lumps were found in her right breast or either axillae. Her right breast mammogram showed heterogeneous glandular parenchyma which was unchanged compared to previous examinations. No new suspicious mammographic features were identified. The patient has subsequently undergone a major (total) duct excision with a specimen size of ？mm. Histology of the breast tissue included major nipple ducts in the breast tissue, several of which showed florid epithelial hyperplasia with papillary hyperplasia in some areas (Figure 1). Ducts expanded and occluded by solid sheets of cells with focal necrosis were also seen, with periductal fibrosis (Figure 2). Apocrine changes were focally seen (Figure 3). In the first 3 sequential slices, there appeared to be a fairly well-defined nodule suggesting a major duct (or nipple) adenoma. Immunostaining showed strong membranous staining with CK 5/6, indicating preservation of basal/myoepithelial layer (Figures 4 and 5). The features were those of a subareolar sclerosing duct papillomatosis (florid papillomatosis of the nipple). The presence of solid areas with central necrosis and similar
Developing synergy regression models with space-borne ALOS PALSAR and Landsat TM sensors for retrieving tropical forest biomass
Anup K Das,C Jeganathan,L K L K Sharma,M S Nathawat,Shiv Mohan,Suman Sinha
- , 2016,
Abstract:
Identification of Medicinally Active Ingredient in Ultradiluted Digitalis purpurea: Fluorescence Spectroscopic and Cyclic-Voltammetric Study
Anup Sharma,Bulbul Purkait
Journal of Analytical Methods in Chemistry , 2012, DOI: 10.1155/2012/109058
Abstract: Serially diluted and agitated (SAD) drugs available commercially are in use with great faith because of the astonishing results they produce. The scientific viewpoint attached to the centuries-old therapy with SAD drugs, as in homeopathy, remained doubtful for want of appropriate research and insufficient evidence base. The conflicting points related to SAD drug mostly related to the level of concentrations/dilutions, use of drug in contradictory clinical conditions compared to the modern system of medicine, identification of medicinally active ingredient in concentrations and dilutions used in commercially available SAD drugs, and lack of laboratory-based pharmacological data vis-à-vis modern medicine. Modus operandi of SAD drug is also unknown. To address some of these issues an analytical study was carried out wherein commercially available SAD drug Digitalis purpurea, commonly used in different systems of medicine, was put to test. Various concentrations of commercially available Digitalis purpurea were analyzed using analytical methods: cyclic voltammetry, emission spectroscopy, and UV-VIS spectroscopy. These analytical methods apparently identified the medicinal ingredients and effect of serial dilution in commercial preparation of the drugs.
Energy in Commercially Available Ultra-Diluted Natural Cardiotropic Drug Digitalis purpurea: An UV Spectroscopic Study
Anup Sharma,Bulbul Purkait
Research Journal of Pharmacology , 2013,
Abstract: Ultra diluted drugs have a statistically significant medicinal effect compare to placebo but it is still unknown how they work. Extract of foxglove plant, Digitalis purpurea, Scrophulariaceae, an effective cardiotropic natural product, is one such compound, which is used by almost all prevalent systems of medicine. As a natural cardiotropic drug it is presumed to have an energy component involved in producing the effect. Since the effect of Digitalis purpurea depends on concentration and dilution, it motivated us to carry out a systematic study to explore an energy entity in less than micro volume, commercially available drug Digitalis purpurea, diluted with aqueous ethanol. The diluent and cleaning agent used was free from any possible contaminant whatsoever. We report a preliminary UV spectroscopy analysis on the effect of serial ultra dilution in the medicinal plant extract Digitalis purpurea. Well-known technique of UV spectroscopy has been used for identification/characterization and analytical evaluation of the medicinally active ingredients of Digitalis purpurea. The experimental results, although preliminary, provide significant and reliable information showing standard UV spectral absorption peak within expected range. It also shows, the diluted out effect on the active component of the drug Digitalis purpurea and provides information to compute energy on serial dilution of drugs. It is found that 4.5 eV is required to dislodge the bond in the group. The eV content of a drug may become important issue for pharmacological and posological considerations.
Quality Assessment of Serially Ultradiluted and Agitated Drug Digitalis purpurea by Emission Spectroscopy and Clinical Analysis of Its Effect on the Heart Rate of Indian Bufo melanostictus
Anup Sharma,Bulbul Purkait
Journal of Pharmaceutics , 2013, DOI: 10.1155/2013/571464
Abstract: The investigation of ultradiluted (homeopathic) drugs is extremely interesting and challenging, and from that point of view this study shows novelty. A study of in vivo changes in heart rate of the Indian Bufo melanostictus caused by commercially available serially ultra-diluted and agitated extract of Digitalis purpurea has been tried in order to understand their pharmacological role. RR interval (of ECG) was compared after intraperitoneal administration of serially diluted and agitated Digitalis purpurea extract, diluent rectified spirit, and Digoxin in anesthetized animals. The study revealed statistically significant changes in the heart rate after application of these drugs except in case of Digoxin and the 200th serial dilution of Digitalis purpurea. The duration of RR intervals after application of the drugs was corroborative of the effect of Digoxin and Digitalis purpurea extract up to 30th dilution. Emission spectra were obtained for the experimental ultra-diluted Digitalis purpurea extract and Digoxin to identify and characterize them. The observed RR pattern and emission spectra show an association. The quality assessment of the commercial ultra-diluted organic drugs obtained from natural products may be initiated by monitoring in vivo studies on animal models. 1. Introduction Exploration of in vivo effect of commercially available serially ultradiluted (with rectified spirit) and agitated drugs (SAD) is required [1], to understand their pharmacological role. Although “drug proving” studies of the effect of ultradiluted drugs on humans have been done, these studies did not deliver enough supporting laboratory evidence to show its relationship with ultradiluted drug. Myths regarding ultradiluted drugs continue. Myths are that homeopathic drugs available readily across the counter, specially the ultradiluted ones, are placebo and do not cause physiological and toxicological changes. The medical and scientific fraternity cast aspersions on the role of homeopathic medicine because of paradigmatic differences [1]. Hence, the assessments of the quality of SAD in terms of their physiological and toxicological effectiveness are aspects that need attention. The investigation of homeopathic drugs is extremely interesting and challenging. This motivated us to take up the study, which was conducted in two parts: first, an in vivo observation of the cardiac effect produced by the serially ultradiluted and agitated Digitalis purpurea extract and the purest known comparable drug Digoxin and,second, the fluoroscopic analysis of these drugs by identification
Cross-Talk between Malarial Cysteine Proteases and Falstatin: The BC Loop as a Hot-Spot Target
Srinivasan Sundararaj, Ajay K. Saxena, Ruby Sharma, Kapil Vashisht, Supriya Sharma, Anup Anvikar, Rajnikant Dixit, Philip J. Rosenthal, Kailash C. Pandey
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093008
Abstract: Cysteine proteases play a crucial role in the development of the human malaria parasites Plasmodium falciparum and Plasmodium vivax. Our earlier studies demonstrated that these enzymes are equipped with specific domains for defined functions and further suggested the mechanism of activation of cysteine proteases. The activities of these proteases are regulated by a new class of endogenous inhibitors of cysteine proteases (ICPs). Structural studies of the ICPs of Trypanosoma cruzi (chagasin) and Plasmodium berghei (PbICP) indicated that three loops (termed BC, DE, and FG) are crucial for binding to target proteases. Falstatin, an ICP of P. falciparum, appears to play a crucial role in invasion of erythrocytes and hepatocytes. However, the mechanism of inhibition of cysteine proteases by falstatin has not been established. Our study suggests that falstatin is the first known ICP to function as a multimeric protein. Using site-directed mutagenesis, hemoglobin hydrolysis assays and peptide inhibition studies, we demonstrate that the BC loop, but not the DE or FG loops, inhibits cysteine proteases of P. falciparum and P. vivax via hydrogen bonds. These results suggest that the BC loop of falstatin acts as a hot-spot target for inhibiting malarial cysteine proteases. This finding suggests new strategies for the development of anti-malarial agents based on protease-inhibitor interactions.
Effect of Ambient Humidity on the Transmission of UV/Visible Light through Model Human Epidermis  [PDF]
Carlton Farley III, Aschalew Kassu, Sandra Sadate, Anup Sharma
Open Journal of Applied Sciences (OJAppS) , 2016, DOI: 10.4236/ojapps.2016.63016
Abstract: Transmission of light through model human epidermal samples is investigated at four different wavelengths and at varying ambient humidity. Light from light emitting diodes (LEDs) is used for transmission measurements through the samples at a UVA wavelength of 365 nm, and visible wavelengths of 460 nm, 500 nm, and 595 nm. Ambient air-humidity is varied between 20% and 100%. Results show that for high ambient humidity, near 100%, transmission of light through the epidermis is higher than at low ambient humidity, 60% or lower. These results are explained with a simple model of epidermis as a turbid medium and the effect of adsorbed water in reducing light-scattering by refractive-index-matching. Biological implications of increased light-transmission through epidermis at high ambient humidity are discussed.
Laser Micro-Printing of Dye-Molecules on Polymeric Surfaces  [PDF]
Wesley Sims, Aschalew Kassu, Carlton Farley, Anup Sharma
Open Journal of Applied Sciences (OJAppS) , 2016, DOI: 10.4236/ojapps.2016.67043
Abstract: We describe a technique for micro-patterning and immobilization of dyes on polymer substrates using a low-power visible laser for dye-excitation. Deposits from an aqueous medium containing the dye can be attached at any desired spot on the substrate simply by exposing the area to laser light. The area of the laser beam can control the spot-size of immobilized dye, in the range of 10 - 100 microns. The immobilization technique is characterized by micro-printing numerals, alphabets and patterns on polybutadiene substrates with Rhodamine (Rh6G) dye. Adsorption of laser-excited dye molecules within the polymer appears to be the mechanism for laser-printing technique.
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