Asish Patel

Mucins and associated glycan signatures in colon adenoma- carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

Development of biomarkers that detect early stage resectable premalignant lesions of colon can provide critical aid in the prevention of colorectal cancer. Recent lines of evidence suggest the utility of mucin expression to predict malignant transformation of colon pre-neoplastic lesions. In this study, we investigated the combined expression of multiple mucins and mucin-associated glycans during the adenoma-carcinoma sequence of colon cancer progression. Further, we evaluated their applicability as markers for differentiating adenomas/adenocarcinomas from hyperplastic polyps. Immunohistochemical analyses performed on colon disease tissue microarrays revealed downregulation of MUC2 and MUC4 expression (p < 0.0001) while MUC1 and MUC5AC expressions were upregulated (p = 0.01) during adenoma-adenocarcinoma progression. Expression of MUC17 was downregulated in inflamed tissues compared to normal tissues, but its increased expression differentiated adenomas (p = 0.0028) and adenocarcinomas (p = 0.025) from inflammation. Glycan epitope-Tn/STn on MUC1 showed higher expression in hyperplastic polyps (p = 0.023), adenomas (p = 0.042) and adenocarcinomas (p = 0.0096) compared to normal tissues. Multivariate regression analyses indicated that a combination of MUC2, MUC5AC, and MUC17 could effectively discriminate adenoma-adenocarcinoma from hyperplastic polyps. Altogether, a combined analysis of altered mucins and mucin-associated glycans is a useful approach to distinguish premalignant/malignant lesions of colon from benign polyps.

The training and certification of surgical oncologists globally.

BackgroundThe global cancer burden (GCB) is expected to rise significantly during the next few decades with most of the new cancers and cancer-related deaths afflicting the low- to middle-income countries. The ability to tackle this rising GCB requires the presence of an adequately trained surgical oncology workforce, which is dependent on credible training pathways and sustainable certification pipelines. The purpose of this article is to review briefly the training patterns and certification requirements for surgical oncologists globally by sampling representative countries across all regions of the world.MethodsA thorough literature search was conducted using multiple websites of credible national/global organizations as well as the websites of individual countries. Countries from select regions in the world were included (based on the World Health Organization regions and Human Development Index) in the analysis to determine the prevalent trends in the training of surgical oncologists globally.ResultsSeveral trends and significant differences were noted in the training patterns of surgical oncologists globally. The presence or absence of domestic surgical oncology fellowships had an inverse correlation to the income level of the country. Countries without domestic fellowships usually relied on high-income foreign destinations for their training.ConclusionsThe results of the analysis demonstrated significant variability in training of surgical oncologists globally. Despite the diversity, we noticed some general trends based on which some recommendations were put forth for increasing the global surgical oncology workforce.

Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance

Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies.

A Combination of MUC5AC and CA19-9 Improves the Diagnosis of Pancreatic Cancer: A Multicenter Study

OBJECTIVES:Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets.METHODS:The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n=346) was used to evaluate the diagnostic (n=241) and predictive (n=105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n=94) and the University of Pittsburgh Medical Center (n=321).RESULTS:Tissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2 ng/ml, IQR: 23.9–382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7 ng/ml, IQR: 87.7–948.6) were significantly higher compared with (P-value ≤0.0001) benign controls (BC) (7.2 ng/ml, IQR: 0.4–26.5) and (P-value ≤0.0001) chronic pancreatitis (CP) controls (8.4 ng/ml, IQR: 1.5–19.2). In the diagnostic training set (n=241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value < 0.001) the diagnostic accuracy for differentiating resectable cases from controls.CONCLUSIONS:MUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

The American Society of Peritoneal Surface Malignancies Multi-Institution evaluation of 1,051 advanced ovarian cancer patients undergoing cytoreductive surgery and HIPEC: An introduction of the peritoneal surface disease severity score

Standard treatment for ovarian epithelial cancer (OEC) consists of cytoreductive surgery (CRS) and a platinum–taxane chemotherapy combination. There is increasing interest in evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage IIIC/IV disease. The peritoneal surface disease severity score (PSDSS) was introduced as a basis to improve patient selection for this therapy in OEC.

Genetic Variants of Mucins: Unexplored Conundrum.

Alternative gene splicing, occurring ubiquitously in multicellular organisms can produce several protein isoforms with putatively different functions. The enormously extended genomic structure of mucin genes characterized by the presence of multiple exons encoding various domains may result in functionally diverse repertoire of mucin proteins due to alternative splicing. Splice variants (Svs) and mutations in mucin genes have been observed in various cancers and shown to participate in cancer progression and metastasis. Although several mucin Svs have been identified, their potential functions remain largely unexplored with the exception of the Svs of MUC1 and MUC4. A few studies have examined the expression of MUC1 and MUC4 Svs in cancer and indicated their potential involvement in promoting cancer cell proliferation, invasion, migration, angiogenesis and inflammation. Herein we review the current understanding of mucin Svs in cancer and inflammation and discuss the potential impact of splicing in generating a functionally diverse repertoire of mucin gene products. We also performed mutational analysis of mucin genes across five major cancer types in International Cancer Genome Consortium database and found unequal mutational rates across the panel of cancer-associated mucins. Although the functional role of mucins in the pathobiology of various malignancies and their utility as diagnostic and therapeutic targets remain undisputed, these attributes need to be reevaluated in light of the potentially unique functions of disease-specific genetic variants of mucins. Thus, the expressional and functional characterization of the genetic variants of mucins may provide avenues to fully exploit their potential as novel biomarkers and therapeutic targets.

Re: The American Society of Peritoneal Surface Malignancies Multi-Institution Evaluation of 1,051 Advanced Ovarian Cancer Patients Undergoing Cytoreductive Surgery and HIPEC: An Introduction of the Peritoneal Surface Disease Severity Score. Journal of Surgical Oncology 2016;114(7):779–784.

1Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska 2Department of Gastrointestinal Surgery, Ghent University Hospital Belgium, Gent, Belgium 3National Cancer Institute of Milan, Milan, Italy 4Department of Gynecologic Oncology, Aegean Obstetrics and Gynecology Education and Research Hospital, Izmir, Turkey 5Department of Surgery, Wake Forest University Baptist Medical Center, Winston Salem, North Carolina 6Unit of Oncological and Pancreatic Surgery, Department of General and Digestive Surgery, University Hospital Reina Sofia, Cordoba, Spain 7 Service de Chirurgie Générale et Oncologique, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France 8Department of Surgical Oncology, St. Agnes Hospital, Baltimore, Maryland

Diagnostic potential of mucins in pancreatic juice for pancreatic cancer.

222 Background: Pancreatic juice remains an underutilized resource for diagnosing pancreatic cancer. Mucins are high molecular weight glycoproteins differentially upregulated in pancreatic cancer, and we hypothesize that their profile in pancreatic juice may have diagnostic potential. Methods: Pancreatic juice was obtained during endoscopy from non-healthy non-pancreatic control (NHPC, n = 57), chronic pancreatitis (CP, n = 23), and pancreatic cancer (PC, n = 23) patients. Sandwich ELISA was used to detect MUC1, MUC4, MUC5AC, CA125, and CA19-9. Kruskal-Wallis test and Wilcoxon rank sum test for group and pairwise comparison was done with p < 0.05 as significant. Logistic regression with ROC curve modeling of log transformed data was done for each biomarker individually and in combination to determine odds ratio (OR), sensitivity (SN), and specificity (SP) for PC. Results: PC vs NHPC: MUC5AC had the best individual performance for diagnosing PC with an OR = 2.78 (95% CI = 1.51-5.13), AUC = 0.81, and optima...

Borderline Resectable Pancreatic Cancer

Borderline resectable pancreatic cancer (BRPC) is an evolving diagnostic entity that blurs the distinction between resectable and locally advanced pancreatic cancer (Varadhachary et al. Ann Surg Oncol 13:1035–1046, 2006). Until recently the management of this disease has been poorly defined; however, consensus guidelines have been developed regarding the proper management of this diagnostic entity. Recent studies have shown that if appropriately identified and treated, this subset of disease can have outcomes similar to pancreatic cancer that is defined as resectable (Laurence et al. J Gastrointest Surg 15:2059–2069, 2011). The aim of this review is to outline the current consensus on definitions, workup and management of BRPC, and also provide a summary of issues that require progress as defined by the International Study Group of Pancreatic Surgery (ISGPS).

Abundance of mango leaf gall midge in relation to major abiotic factors and crop stages

September 14-15, 2012 Volume 1 Issue 2 63 Agrotechnol ISSN:2168-9881 AGT, an open access journal C oriented production systems have become important in the agribusiness sector. A change regarding the need for differentiation has occurred in the perception of companies, producers, distribution channels and other players involved in the production of agribusiness commodities. There is a discussion on how to achieve it. The use of branding which is understood as the process involved in creating and promoting strong brands is a way to obtain differentiation. The creation and promotion of strong brands for Indian agribusiness is an important aspect for the strategies of Indian agribusiness companies, farmers and agri entrepreneurs and exporters for entering as well as create a competitive advantage in the domestic and global market .Build strong brands could be a useful way to escape standard market prices for commodities, creating value, providing income for all links involved in the production chain. With the increasing trend towards the use of branded products and in this new environment of consumers seeking for quality, origin certification, confidence attributes, and for more organic and green production standards, there are huge possibilities for creation of brands that meet this kind of demand. India’s geographical location, its natural resources, and expertise in the production of certain agribusiness commodities, allows the country an opportunity for adding and creating competitive value to many domestic products.This paper quoting Indian and International examples intends to suggest propositions regarding the use of branding strategies in agribusiness commodities, concepts such as Co-branding, Branding Ecosystem and Ingredient Branding as well as problems associated with branding.Arecanut well known for consumption of its fruit (bettle nut) as a masticator in India and in the middle and Far East is being tried for utilizing its leaf sheath as an alternative fodder for animal. India has the highest producer area under cultivation of arecanut in the world and is mostly grown in southern part and in the north-eastern region of the country. Considering its higher economic profitability, many farmers have replaced it with paddy cultivation, resulting in shortage of paddy straw for its use as animal fodder. Recently the arecanut sheath has been investigated for use as a dry fodder for cattle, and an alternative to paddy straw. The arecanut tree sheds about 10 leaves (sheaths) per year hence total production of sheaths is around 4380 sheaths per year per hectare. The size of this areca sheath is about 20-35 cm feet wide and 30-120 cm length. The available machineries for chaff making have been tried to chop the arecanut sheath into suitable fodder size. However due to physical and biological characteristics of the sheath, none of them were found suitable to get desired size. A factorial experiment was therefore conducted using texture analyzer to study the cutting characteristics of the arecanut sheath for proper size reduction. Three different cutting con figurations were evaluated for cutting energy requirements, peak cutting forces required and the quality of cut obtained. A two dimensional shearing configuration was found to be suitable for size reduction of arecanut sheath with peak cutting force of 350 N. The inclination angle of cutter knife and speed of cut were not found to be significantly affecting the phenomenon of cutting.Agri-2012 September 14-15, 2012 Volume 1 Issue 2 29 Agrotechnol ISSN:2168-9881 AGT, an open access journal T ever increasing demand for large numbers of laboratory reared insects for bioassays has necessitated the development of efficient and economical methods for mass production of insect pests. Several methods have been developed for artificial rearing of cotton bollworm/legume pod borer, Helicoverpa armigera. However, it is difficult to maintain the culture of this insect in the laboratory for more than five generations because of onset of pathogen infection, and inbreeding depression resulting in reduce fecundity and egg hatching. Therefore, the present studies were planned to overcome the problems faced in maintaining the culture of H. armigera on a long-term basis under laboratory conditions. We evaluate plastic cups, glass vials, and cell well plates for maintaining the culture of this insect. The larval survival was significantly greater in insects reared individually in cellwells (95.33%), followed by glass vials (79.33 %), and poor in plastic cups and Petri plates where the insects were reared in groups. The weights of the larvae were also more in insects reared in cell wells, although the differences between different methods were not significant. The indigenously available cell well plates were quite suitable for rearing H. armigera, and these are amenable to surface sterilization, reusable, and hence, suitable for mass rearing of H. armigera.September 14-15, 2012 Volume 1 Issue 2 77 Agrotechnol ISSN:2168-9881 AGT, an open access journal B in agricultural systems is under pressure worldwide. The loss of genetic resources due to their declining use in modern agriculture has resulted in major concerns about the future vulnerability of agricultural production and related pest and disease risks and food security. Climate change and increasingly dramatic shifts in land use threaten to exacerbate the existing biodiversity crisis. Various international conventions have addressed this topic; this has moved the conservation and sustainable use of genetic resources issue to the top of the international development agenda. Over the past decade, a series of important steps have been taken to protect agro biodiversity in particular, which mainly includes the plant genetic resources on which agriculture depends. These and further efforts are vital for enabling countries and communities to meet their food needs, for improving rural livelihoods, and ultimately for protecting the well-being of all people now and in the future. A prerequisite for conserving biodiversity is proper identification and establishment of identity of a particular entity. Taxonomical characterization is a tedious and time consuming task, especially for plant species with long life cycle. DNA bar-coding is emerging as a preferred global standard in molecular taxonomy, which promises to bring a significant level of automation, standardization and high-throughput data analysis for identification of biological entity. The need for a rapid, accurate, identification of closely related genotypes can be achieved by DNA based identification system .Assessment of diversity by using molecular markers has recently been proposed and demonstrated on a large scale through the use of a short DNA sequence. DNA bar-coding has already proved useful for identification of animal species. In plants it is only beginning to attract the attention of the DNA bar-coding community.September 14-15, 2012 Volume 1 Issue 2 59 Agrotechnol ISSN:2168-9881 AGT, an open access journal I tropical and sub-tropical Island climate, coconut is the major plantation crop cultivated throughout the Islands as a source to sustain the small livelihood to the small and marginal family. Copra is produced after drying coconut either through sun drying or other traditional method “Machan”. Again, due to adverse effect of heavy rainfall (2800-3500mm), temperature (25-32oC) and relative humidity (75-95%) year round, high microbial infection to the product is observed, causing low quality of copra leading to lower income to the producers. Moreover, the traditional method of producing copra is quite tedious, fetching lower remuneration price in the domestic market. Keeping in view, a biomass fired copra dryer has been designed, developed and tested in the Island conditions at Port Blair, Andaman and Nicobar Islands, India which is located at 11° 40’ N and 92° 46’ E. The aim was to increase in employment generation to the rural households who are engaged with traditional method of copra production. The capacity of dryer is 1000 coconuts per batch using MS frame (2.4 m x 1.2 m x 1.6 m). The drying bed made of M.S bar grill kept at a height of 1 meter above the ground level. The results indicated that the biomass fired dryer took 20hrs including 3 hrs of preheating time to reduce the initial moisture content of 55 % (w.b) to the safe final moisture content of 6% (w.b) where as in comparision to solar dryer and open sun drying, it saves 37 % and 50% of total drying time respectively. The average temperature recorded in the drying chamber was 50-55 0C. The dryer About 80 kg of fuel is used and it requires three man powers to obtain better quality copra. The coconut shell may be used for fuel which saves manpower and energy, thereby enhancing net return to the farmers.