Emergence of rare and low abundant anaerobic gut Firmicutes is associated with a significant downfall of Klebsiella in human colon cancer.

Gut bacterial dysbiosis has been linked to several gastrointestinal diseases, including deadly colorectal cancer (CRC), a leading cause of mortality in cancer patients. However, perturbation in gut bacteriome during colon cancer (CC, devoid of colorectal malignancy) remains poorly explored. Here, 16S rRNA gene amplicon sequencing was carried out for fecal DNA samples targeted to hypervariable V3-V4 region by employing MiSeq platform to explore the gut bacterial community shift in CC patients. While alpha diversity indices predicted high species richness and diversity, beta diversity showed marked gut bacterial compositional dissimilarity in CC versus healthy controls (HC, n = 10 each). We observed a significant (p < 0.05, Wilcoxon Rank-Sum test) emergence of low-abundant anaerobic taxa, including Parvimonas and Peptostreptococcus, in addition to Subdoligranulum, Coprococcus, Holdemanella, Solobacterium, Bilophila, Blautia, Dorea, Moryella and several unidentified taxa, mainly affiliated to Firmicutes, in CC patients. In addition, we also traced the emergence of putative probiotic taxon Slackia, belonging to Actinomycetota, in CC patients. The emergence of anaerobic Firmicutes in CC is accompanied by a significant (p < 0.05) decline in the Klebsiella, as determined through linear discriminant analysis effect size (LEfSe) and heat tree analyses. Shifts in core microbiome and variation in network correlation were also witnessed. Taken together, this study highlighted a significant and consistent emergence of rare anaerobic Firmicutes suggesting possible anaerobiosis driving gut microbial community shift, which could be exploited in designing diagnostic and therapeutic tools targeted to CC.

Proteogenomic examination of esophageal squamous cell carcinoma (ESCC): new lines of inquiry.

Introduction: Esophageal squamous cell carcinoma (ESCC), a histopathologic subtype of esophageal cancer is a major cause of cancer-related morbidity and mortality worldwide. This is primarily because patients are diagnosed at an advanced stage by the time symptoms appear. The genomics and mass spectrometry-based proteomics continue to provide important leads toward biomarker discovery for ESCC. However, such leads are yet to be translated into clinical utilities. Areas covered: We gathered information pertaining to proteomics and proteogenomics efforts in ESCC from the literature search until 2020. An overview of omics approaches to discover the candidate biomarkers for ESCC were highlighted. We present a summary of recent investigations of alterations in the level of gene and protein expression observed in biological samples including body fluids, tissue/biopsy and in vitro-based models. Expert opinion: A large number of protein-based biomarkers and therapeutic targets are being used in cancer therapy. Several candidates are being developed as diagnostics and prognostics for the management of cancers. High-resolution proteomic and proteogenomic approaches offer an efficient way to identify additional candidate biomarkers for diagnosis, monitoring of disease progression, prediction of response to chemo and radiotherapy. Some of these biomarkers can also be developed as therapeutic targets.

Fabrication and characterizations of simvastatin-containing mesoporous bioactive glass and molybdenum disulfide scaffold for bone tissue engineering.

Due to the limitations of the current treatment approaches of allograft and autograft techniques, treating bone disorders is a significant challenge. To address these shortcomings, a novel biomaterial composite is required. This study presents the preparation and fabrication of a novel biomaterial composite scaffold that combines poly (D, L-lactide-co-glycolide) (PLGA), mesoporous bioactive glass (MBG), molybdenum disulfide (MoS2), and simvastatin (Sim) to address the limitations of current bone grafting techniques of autograft and allograft. The fabricated scaffold of PLGA-MBG-MoS2-Sim composites was developed using a low-cost hydraulic press and salt leaching method, and scanning electron microscopy (SEM) analysis confirmed the scaffolds have a pore size between 143 and 240 µm. The protein adsorption for fabricated scaffolds was increased at 24 h. The water adsorption and retention studies showed significant results on the PLGA-MBG-MoS2-Sim composite scaffold. The biodegradation studies of the PLGA-MBG-MoS2-Sim composite scaffold have shown 54% after 28 days. In vitro, bioactivity evaluation utilizing simulated body fluid studies confirmed the development of bone mineral hydroxyapatite on the scaffolds, which was characterized using x-ray diffraction, Fourier transform infrared, and SEM analysis. Furthermore, the PLGA-MBG-MoS2-Sim composite scaffold is biocompatible with C3H10T1/2 cells and expresses more alkaline phosphatase and mineralization activity. Additionally, in vivo research showed that PLGA-MBG-MoS2-Sim stimulates a higher rate of bone regeneration. These findings highlight the fabricated PLGA-MBG-MoS2-Sim composite scaffold presents a promising solution for the limitations of current bone grafting techniques.

An assembly of TROP2-mediated signaling events.

Trophoblast cell surface antigen 2 (TROP2) is a calcium-transducing transmembrane protein mainly involved in embryo development. The aberrant expression of TROP2 is observed in numerous cancers, including triple-negative breast cancer, gastric, colorectal, pancreatic, squamous cell carcinoma of the oral cavity, and prostate cancers. The main signaling pathways mediated by TROP2 are calcium signaling, PI3K/AKT, JAK/STAT, MAPKs, and ß-catenin signaling. However, collective information about the TROP2-mediated signaling pathway is not available for visualization or analysis. In this study, we constructed a TROP2 signaling map with respect to its role in different cancers. The data curation was done manually by following the NetPath annotation criteria. The described map consists of different molecular events, including 8 activation/inhibition, 16 enzyme catalysis, 19 gene regulations, 12 molecular associations, 39 induced-protein expressions, and 2 protein translocation. The data of the TROP2 pathway map is made freely accessible through the WikiPathways Database ( https://www.wikipathways.org/index.php/Pathway:WP5300 ). Development of TROP2 signaling pathway map.

Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.

PURPOSE: The purpose of this study was to understand the impact of population diversity and geographic variation on tumor mutation burden (TMB) scores across cancers and its implication on stratification of patients for immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: This retrospective study used whole-exome sequencing (WES) to profile 1,233 Indian patients with cancer across 30 different cancer types and to estimate their TMB scores. A WES-based pipeline was adopted, along with an indigenously developed strategy for arriving at true somatic mutations. A robust unsupervised machine learning approach was used to understand the distribution of TMB scores across different populations and within the population. RESULTS: The results of the study showed a biphasic distribution of TMB scores in most cancers, with different threshold scores across cancer types. Patients with cancer in India had higher TMB scores compared with the Caucasian patients. We also observed that the TMB score value at 90th percentile (predicting high efficacy to ICI) was high in four different cancer types (sarcoma, ovary, head and neck, and breast) in the Indian cohort as compared with The Cancer Genome Atlas or public cohort. However, in lung and colorectal cancers, the TMB score distribution was similar between the two population cohorts. CONCLUSION: The findings of this study indicate that it is crucial to benchmark both cancer-specific and population-specific TMB distributions to establish a TMB threshold for each cancer in various populations. Additional prospective studies on much larger population across different cancers are warranted to validate this observation to become the standard of care.

A multi-cellular molecular signaling and functional network map of C-C motif chemokine ligand 18 (CCL18): a chemokine with immunosuppressive and pro-tumor functions.

The C-C Motif Chemokine Ligand 18 (CCL18) is a beta-chemokine sub-family member with immunomodulatory functions in primates. CCL18-dependent migration and epithelial-to-mesenchymal transition of oral squamous cell carcinoma, squamous cell carcinoma of head and neck, breast cancer, hepatocellular carcinoma, non-small cell lung carcinoma, ovarian cancer, pancreatic ductal carcinoma and bladder cancer cells are well-established. In the tumor niche, tumor-associated macrophages produce CCL18 and its overexpression is correlated with reduced patient survival in multiple cancers. Although multiple receptors including C-C chemokine receptor type 3 (CCR3), type 6 (CCR6), type 8 (CCR8) and G-protein coupled estrogen receptor (GPER1) are reported for CCL18, the Phosphatidylinositol Transfer Protein, Membrane-Associated 3 (PITPNM3) receptor is currently considered as its predominant receptor. Characterization of the molecular events and check points associated with the immunosuppressive and cancer progression support functions induced by CCL18 for their potential towards therapeutic applications is an area of active research. Hence, in this study, we assembled 917 signaling events reported to be induced by CCL18 through their studied receptors in diverse cell types as an integrated knowledgebase for reference, data integration and gene-set enrichment analysis of global transcriptomic and/or proteomics datasets.

Omics Data Mining for multiPTMs in Oral Cancer: Cellular Proteome and Secretome of Chronic Tobacco-Treated Oral Keratinocytes.

Oral cancer is common worldwide but lacks robust diagnostics and therapeutics. Lifestyle factors, such as tobacco chewing and smoking, are significantly associated with oral cancers. Mapping the changes in the global proteome, secretome and post-translational modifications (PTMs) during tobacco exposure of oral keratinocytes hold great potential for understanding the mechanisms of oral carcinogenesis, not to mention for innovation toward clinical interventions in the future. On the other hand, although advances in mass spectrometry (MS)-based techniques have enabled the deep mining of complex proteomes, a large portion of the mass spectrometric data remains unassigned. These unassigned spectral data can be researched for multiple post-translational modifications (multiPTMs). Using data mining of publicly available proteomics data, we report, in this study, a multiPTM analysis of high-resolution MS-derived datasets on cellular proteome and secretome of chronic tobacco-treated oral keratinocytes. We identified 800 PTM sites in 496 proteins. Among them, 43 PTM sites in 37 proteins were found to be differentially expressed, accounting for their protein-level expression. Enrichment analysis of the proteins with altered phosphosite expression and the known kinases of these phosphosites discovered the overrepresentation of certain biological processes such as splicing and hemidesmosome assembly. These findings contribute to a deeper understanding of omics level changes in chronic tobacco-treated oral keratinocytes, and by extension, pathophysiology of oral cancers.

Clinical Profile and Quality of Life Assessment of Oral Cancer Patients Following Nasolabial Flap Reconstruction Surgery.

To evaluate the quality of life (QOL) of oral cancer patients who had undergone surgical reconstruction with nasolabial flap. A cross-sectional study was conducted over a period of 1 year at a tertiary care hospital and 128 subjects were included. The subjective assessment of quality of life using The University of Washington QOL Questionnaire including physical, socio-emotional, composite and overall QOL, Objective assessment of functional mouth opening and Nasolabial crease scar assessment using Vancouver scar scale was done. Majority of the subjects, 98.4% were male. Maximum cases were involving the lower gingivobuccal complex and retromolar trigone followed by buccal mucosa. Majority of the tumors were T2, 53.1% followed by T1, 18.8%. Statistically significant (p < 0.05) difference was found in relation to age, tumor size (T1, T2, T3), absence of adjuvant radiation therapy, presence or absence of neck dissection, tumor site; buccal mucosa and lower gingivobuccal complex plus retromolar trigone and intact bone status in physical functional, social-emotional subscores, composite score and overall QOL assessment. Improved mouth opening postoperatively was statistically significant (p < 0.05) in T1 and T2 lesions of buccal mucosa and lower gingivobuccal complex plus retromolar trigone who did not receive radiation and with intact bone status. Majority of the cases, 36.7% had a nasolabial crease scar score 2. Nasolabial flap is a viable option in the reconstruction of small and medium sized oral defects with good quality of life (QOL) outcome and objective outcome as depicted by significantly improved mouth opening. The aesthetic outcome of nasolabial crease scar is good in our study.

A network map of netrin receptor UNC5B-mediated signaling.

UNC-5 Homolog B (UNC5B) is a member of the dependence receptor family. This family of receptors can induce two opposite intracellular signaling cascades depending on the presence or absence of the ligand and is thus capable of driving two opposing processes. UNC5B signaling has been implicated in several cancers, where it induces cell death in the absence of its ligand Netrin-1 and promotes cell survival in its presence. In addition, inhibition of Netrin-1 ligand has been reported to decrease invasiveness and angiogenesis in tumors. UNC5B signaling pathway has also been reported to be involved in several processes such as neural development, developmental angiogenesis and inflammatory processes. However, literature pertaining to UNC5B signaling is scarce and scattered. Considering the importance of UNC5B signaling, we developed a resource of signaling events mediated by UNC5B. Using data mined from published literature, we compiled an integrated pathway map consisting of 88 UNC5B-mediated signaling events and 55 proteins. These signaling events include 27 protein-protein interaction events, 33 catalytic events involving various post-translational modifications, 9 events of UNC5B-mediated protein activation/inhibition, 27 gene regulation events and 2 events of translocation. This pathway resource has been made available to the research community through NetPath ( http://www.netpath.org /), a manually curated resource of signaling pathways (Database URL: http://www.netpath.org/pathways?path_id=NetPath_172 ). The current resource provides a foundation for the understanding of UNC5B-mediated cellular responses. The development of resource will serve researchers to explore the mechanisms of UNC-5B signaling in cancers.

Laparoscopic Management of Colonic Diverticular Disease and its Complications: an Analysis.

Dense inflammatory reactions, loss of tissue planes and sepsis make surgical treatment of diverticulitis complex and difficult. Experience with laparoscopic management of this disease is scanty in our country. This study aims to assess the pattern of presentation, the site of involvement and complications of diverticulitis coli. This study also aims to audit the results of laparoscopic approach for complicated colonic diverticulitis. A retrospective analysis of all patients who had laparoscopic management of complicated diverticulitis patients from August 2007 to October 2014 was done from the database. The site of involvement, extent and presence or absence of complications of diverticular disease was noted. The surgical approach, intraoperative parameters and short-term outcome measures were analysed. There were 38 (8.8 %) patients with diverticular disease out of 427 patients who had laparoscopic colorectal surgery in the study period with a median age of 59 years. Out of 38 patients, 50 % had comorbid conditions. Internal fistulae were seen in 9 (23.6 %) patients, 6 with colovesical and 3 with colovaginal fistulae. Elective laparoscopic colectomy with primary anastomosis was done in 34 (89 %) cases of which, and 10 (26 %) patients had abscess on presentation requiring drainage. Four patients required emergency laparoscopic surgery of which primary resection and anastomosis was done in 3 (7.8 %), and Hartmann's operation was done in 1 (2.6 %) patient. Two patients required stoma. The morbidity was seen in 15 % cases, and the mean hospital stay was 9.54 days. Laparoscopic approach for diverticular disease and its complication is feasible and safe. Careful selection of patients, judicious use of diverting stoma and appropriate selection of the procedure help to achieve good results even in those with septic complications and fistulising disease.

Neoplastic Parkinsonism: An illustrative case report.

Non-Hodgkin's lymphoma of T-cell types are rare neoplasms. Central nervous system metastasis is unusual. We are reporting a patient with peripheral T-cell lymphoma unspecified who had extra nodal metastasis into the brain that manifested with extrapyramidal dysfunction. The clinical presentation was exceptional in that the course was indolent and patient had no overt extra neural manifestations of malignancy for nearly 3 years after the onset of Parkinsonism. Striking brain imaging late in the disease supported by pathological findings enabled the diagnosis of this rare condition.