Aim: Clinical success of the proteasome inhibitor bortezomib for multiple myeloma (MM) treatment highlights the potential of therapeutically targeting the ubiquitin (Ub) + proteasome system. However, bortezomib treatment invariably leads to therapeutic resistance through mechanisms that remain elusive and that limit long-term clinical efficacy. We hypothesized that individual E3 Ub ligases were differentially expressed in MM patients that did or did not respond to bortezomib. E3 ligases bind intracellular protein substrates leading to their subsequent ubiquitination that then triggers proteasomal degradation of the substrate. The aim of the present study was to analyze the gene expression profiles (GEPs) from MM patients and identify E3 Ub ligases that correlated with clinical response to bortezomib. Methods: MM tumor cells were collected by bone marrow biopsy from newly diagnosed patients, and RNA isolated and GEPs were correlated with individual patient response to bortezomib. Results: Expression of the E3 Ub ligase Skp1-Cullin-1-F-box (SCF)-Skp2 was significantly increased in MM patients that did not respond to bortezomib. However, SCF-Skp2 expression was not increased in GEPs from patients that did not respond to other anti-myeloma agents. Conclusion: Drugs that target the E3 Ub ligase SCF-Skp2 may overcome bortezomib resistance and display refined specificity with reduced adverse toxicities.

Aim: The glycolytic enzyme, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), mediates shifts in glycolytic flux and is important for glioblastoma cell survival. This study aimed to identify micro-RNAs that alter PFKFB4 expression to regulate glioblastoma cell survival. Methods: Western blot analyses, luciferase reporter assays, and public database analyses were used to predict and validate the regulation of PFKFB4 mRNA expression by miR-505 in glioblastoma. Cell growth and apoptosis assays were performed to determine the effects of miR-505 on the growth and survival of primary glioblastoma stem-like cells (GSCs) and established glioblastoma cell lines. In addition, the correlations between patient survival and the expression of miR-505 and PFKFB4 mRNA in glioblastoma specimens were examined. Results: Using micro-RNA target prediction programs, a miR-505 binding site in the 3'-UTR of the PFKFB4 mRNA transcript was identified, and query of a public CLIP-Seq database indicated that PFKFB4 binds this site in living cells. It was found that fusion of the PFKFB4 3'-UTR to luciferase conferred regulation of luciferase activity by PFKFB4. In addition, Western blots revealed that miR-505 significantly decreased PFKFB4 protein expression in established glioblastoma cell lines and primary GSCs. Enforced PFKFB4 overexpression increased the growth of primary GSCs and established glioblastoma multiforme cell lines, and miR-505 antagonized this effect. By downregulating PFKFB4, miR-505 increased production of reactive oxygen species, thereby repressing glioblastoma cell growth and promoting glioblastoma cell death. Importantly, patient survival was positively correlated with miR-505 expression and negatively correlated with PFKFB4 mRNA expression in primary glioblastoma specimens. Conclusion: It was showed that miR-505 downregulates PFKFB4 expression in glioblastoma, thereby decreasing glioblastoma cell survival. Targeting PFKFB4 via miR-505 may represent a promising therapeutic approach in glioblastoma.

Aim: Fine needle aspiration cytology (FNAC) for cytodiagnosis of various lesions is routinely used in many centers. In bone, however, FNAC has not been widely applied because of concerns about its diagnostic accuracy. The present study aims to determine the value of FNAC in the diagnosis of bone tumors. Methods: It was a progressive observational study conducted over a period of one year, undertaken on suspected bone tumor cases in Acharya Vinoba Bhave Rural Hospital, Wardha, India. The material obtained was smeared on glass slides and stained with Giemsa stain. Results: A total of 36 cases were studied, of which diagnostic material was adequately obtained in 32 cases (88.88%). The sensitivity (92.85%) and specificity (94.44%) of FNAC were high, with an accuracy of 93.75%, which is similar to findings in other studies. Conclusion: FNAC plays a vital role in diagnosing bone tumors. It is a rapid, easy, cheap, and minimum invasive outpatient department procedure. However histopathology is still important in diagnosing bone tumors that are unclear or undiagnosed on FNAC since histopathology gives a complete architectural pattern of tissue.

Histone H2A and H2B ubiquitination represents a widely used mechanism for a variety of regulatory transcriptional programs. In this review, structural and functional studies of histone H2A and histone H2B deubiquitinase (DUB), DUB including 2A-DUB, BRCA1-associated protein-1, USP3, UBP8, and USP16, and their role in developmental disease and carcinogenesis were recapitulated. Also the progress in developing small molecular inhibitors targeting DUBs and their application in colon cancer, B-cell lymphoma, and multiple myeloma were summarized. Overall, the study seek to strengthen the understanding on how these DUBs contribute to normal and malignant tissue development thus aiding in improving the design of therapeutic strategies used for diagnosis and prognosis of the disease.

Glioblastoma multiforme (GBM) is a heterogeneous group of tumors, each with its own distinct molecular and genetic signatures. This heterogeneity is a major clinical hurdle for classifying tumors and for devising effective personalized therapies targeting the disease pathways. Herein, the primary genetic and epigenetic alterations in GBM that have been used as therapeutic targets in clinical settings nowadays, with or without clinical benefits for patients, as well as the future directions for developing novel strategies were discussed.

B-acute lymphoblastic leukemia (B-ALL) often presents with pancytopenia/bicytopenia, with thrombocytopenia being the most important parameter. The case of a 12-year-old child with bicytopenia on peripheral smear was presented. On bone marrow examination, 85% morphologically lymphoid blasts, negative for myeloperoxidase, and periodic-acid Schiff on cytochemistry were found. The blasts suppressed the erythroid population but not the megakaryocytic population. On flow cytometry, a diagnosis of common-ALL-antigen positive B-precursor ALL was concluded. To conclude, ALL cannot be excluded in patients who present with a normal platelet count. A bone marrow aspirate is crucial in patients with bi/pancytopenia.