The manifestations of cancerous phenotypes necessitate alterations at different levels of information-flow from genome to proteome. The molecular alterations at different information processing levels serve as the basis for the cancer phenotype to emerge. To understand the underlying mechanisms that drive the acquisition of cancer hallmarks it is required to interrogate cancer cells using multiple levels of information flow represented by different omics-such as genomics, epigenomics, transcriptomics, and proteomics. The advantage of multi-omics data integration comes with a trade-off in the form of an added layer of complexity originating from inherently diverse types of omics-datasets that may pose a challenge to integrate the omics-data in a biologically meaningful manner. The plethora of cancer-specific online omics-data resources, if able to be integrated efficiently and systematically, may facilitate the generation of new biological insights for cancer research. In this review, we provide a comprehensive overview of the online single-and multi-omics resources that are dedicated to cancer. We catalog various online omics-data resources such as The Cancer Genome Atlas (TCGA) along with various TCGA-associated data portals and tools for multi-omics analysis and visualization, the International Cancer Genome Consortium (ICGC), Catalogue of Somatic Mutations in Cancer (COSMIC), The Pathology Atlas, Gene Expression Omnibus (GEO), and PRoteomics IDEntifications (PRIDE). By comparing the strengths and limitations of the respective online resources, we aim to highlight the current biological and technological challenges and possible strategies to overcome these challenges. We outline the available schemes for the integration of the multi-omics dimensions for stratifying cancer patients and biomarker prediction based on the integrated molecular-signatures of cancer. Finally, we propose the multi-omics driven systems-biology approaches to realize the potential of precision onco-medicine as the
Background: The dengue-infected patients with or without hemorrhagic manifestations, typically exhibit moderate to severe thrombocytopenia. A thrombopoietin receptor agonist À eltrombopag has been efficacious in correcting thrombocytopenia in patients with various pathological conditions including immune thrombocytopenia, chronic liver disease, and severe aplastic anemia. This study investigated the efficacy and safety of eltrombopag to correct dengue-mediated thrombocytopenia. Methods: In this open-label, randomized controlled phase-II trial, patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) having platelet (PLT) count lower than 100 £ 10 9 /L without comorbidity, pregnancy, and liver abnormalities were enrolled in Dhaka Medical College Hospital, Better Life Hospital and AMZ hospital, Dhaka, Bangladesh. Between October 10, 2019, and December 30, 2019, 123 DF and DHF patients were assessed for eligibility to be enrolled in the trial. Fourteen patients were excluded as they failed to fulfill the inclusion criteria (N = 6) or refused to participate in the trial (N = 8). Finally, 109 patients were randomly assigned to either Group 1, (N = 36), Group 2 (N = 37), or Control-group (N = 36) in a 1:1:1 ratio. Two doses of eltrombopag-25 mg/day and 50 mg/day were administered to Group-1 and Group-2 patients, respectively whereas the control-group patients received standard dengue treatment without eltrombopag. The management of all enrolled patients was according to WHO guidelines. The randomization procedure was performed by using a computerized system (STATA Inc.). CBC and immature platelet fraction (IPF) were monitored from Day-0 to Day-7. Absolute immature platelet count (A-IPC) was calculated from PLT count and IPF for each patient. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured on Day-0 and Day-4 and an Ultrasonogram (USG) of the abdomen was performed on Day-4 and Day-7 for each patient. The efficacy of eltrombopag as the primary outcome of the trial was investigated by the proportion of patients with recovered platelet count receiving eltrombopag with corrected platelet count (platelet count above the lower normal limit: 150 £ 10 9 /L) on Day-7 of the enrollment as compared to the Control-group. As the secondary outcomes, the reduction of bleeding tendency in response to eltrombopag as well as the safety of eltrombopag in dengue patients were assessed. The safety was evaluated in case of adverse events, liver function enzymes AST/ALT levels and USG. This trial is registered with the international clinical trial registry, number SLCTR/2019/037. Results: A total of 101 patients including 77 DF and 24 DHF patients completed the trial as eight patients left the trial without completing the follow-up. Patients of the different groups were compared with respect to mean age (26 §8, 30 §10 and 30 §9 years for, Group-1,-2 and Control-group, respectively) (p-value= 0.23) and basal PLT count (Group-1: 58 §24 £ 10 9 ; Group-2: 52 §29 £ 10 9 and control-group: 55 §30 £ ...
Background: Surgical removal of gall bladder for its diseases is common. However, not much is known about the incidence of incidental carcinoma in such patients in our population. Objective of current study was to analyze the different pathological entities of post-operative gall bladder specimen with particular emphasis on incidental carcinoma. Methods: This retrospective study was carried out at a multi-specialty hospital in eastern India from the pathology records for the period from August 2005 to July 2008. The records were analyzed for gender, age group distribution, and pathological types with different histology. Results: Out of 863 records, chronic cholecystitis 51.2% was the most common histology and malignancy was seen in 2.7% (23/863) both pre-operative and post-operative diagnosis. In the neoplastic group incidental carcinoma was diagnosed in 1.9% (17/23) of cases Conclusion: Histopathological examination of gallbladder specimen helps to identify non-neoplastic conditions with its complications and also, for the detection of incidental carcinoma. Thorough sampling of all gallbladder specimens is a must to detect focal neoplastic changes.
This large multicentre study of peritonitis offers insights into the aetiology and outcomes of infectious complications of chronic PD in India that are germane to clinical decision-making.
The proteotranscriptomic landscape depends on the transcription, mRNA-turnover, translation, and regulated-destruction of proteins. Gene-specific mRNA-to-protein correlation is the consequence of the dynamic interplays of the different regulatory processes of proteotranscriptomic landscape. So far, the critical impact of mRNA and protein stability on their subsequent correlation on a global scale remained unresolved. Whether the mRNA-to-protein correlations are constrained by their stability and conserved across mammalian species including human is unknown. Moreover, whether the stability-dependent correlation pattern is altered in the tumor has not been explored. To establish the quantitative relationship between stability and correlation between mRNA and protein levels, we performed a multi-omics data integration study across mammalian systems including diverse types of human tissues and cell lines in a genome-wide manner. The current study illuminated an important aspect of the mammalian proteotranscriptomic landscape by providing evidence that stability-constrained mRNA-to-protein correlation follows a hierarchical pattern that remains conserved across different tissues and mammalian species. By analyzing the tumor and non-tumor tissues, we further illustrated that mRNA-to-protein correlations deviate in tumor tissues. By gene-centric analysis, we harnessed the hierarchical correlation patterns to identify altered mRNA-to-protein correlation in tumors and characterized the tumor correlation-enhancing and -repressing genes. We elucidated the transcriptional regulatory circuits controlling the correlation-enhancing and -repressing genes that are associated with metabolic reprogramming and cancer-associated pathways in tumor tissue. By tightly controlling the mRNA-to-protein correlation of specific genes, the transcriptional regulatory circuits may enable the tumor cells to evolve in varying tumor microenvironment. The mRNA-to-protein correlation analysis thus can serve as a unique approach to identify the pathways prioritized by the tumor cells at different clinical stages. The component of transcriptional regulatory circuits identified by the current study can serve as potential candidates for stage-dependent anticancer therapy.
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