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Feb 2022 DOI 10.14302/issn.2379-8572.joa-22-4072
Mario Biava PierCorresponding author
Centro Medico Turati, Piazza Cavour 1, Milano (MI)
This translational paper discusses differentiation‑stage factors from zebrafish embryos as epigenetic regulators with potential to reverse neurosensory hearing loss. It outlines experimental evidence, delivery concepts, and research gaps.
Jun 2021 DOI 10.14302/issn.2689-4602.jes-21-3868
O. Henderson JeffreyCorresponding author
Department of Science and Mathematics, Judson University, Elgin, IL 60123, USA
Hox genes, their conserved derivatives, and the pathways responsible for their expression have been extensively studied in the fruit fly, Drosophila melanogaster;the experimentation done in the Drosophila model system has given developmental biologists tools to better understand the role and significance of Hox genes and their derivatives in anterior-posterior axis determination in the Drosophila embryo. Along with this, Drosophila research opened up the door to investigation on the conservation of Hox genes between vertebrates and invertebrates. Comparative embryology in mice, chickens, pufferfish, and zebrafish have shown conserved Hox gene expression patterns specifically along the anterior-posterior axis. Recently, comparative analysis performed on dorsal-ventral axis formation showed that patterning and segmentation of the spinal cord is influenced by the action of Hox genes as well. This review will briefly consider the evolution of the vertebrate brain and the evolution and conservation of Hox genes in regulating hindbrain patterning and spinal cord development.
Feb 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2581
Khan AshrafCorresponding author
Departments of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA 01605, USA
We report the case of a 75 year-old female with past history of ampullary adenocarcinoma presenting with a rapidly enlarging breast mass, initially misclassified on fine needle aspiration as a probable sarcoma, which was ultimately diagnosed as melanoma on resection in the absence of a known cutaneous primary lesion. Next-generation sequencing (NGS) of the tumor revealed a mutation in the Smoothened oncogene (SMO) of unknown significance and wild-type BRAF. To our knowledge, SMO mutation in melanoma of any site has not been previously reported, though the effectiveness of SMO inhibitors has been studied in both in vivo and in vitro models of melanoma. Currently, these inhibitors have not been studied in SMO mutant melanoma. The patient declined further therapy after resection due to multiple comorbidities. She expired two years after presenting with the breast mass from complications of high grade urothelial carcinoma.
Nov 2018 DOI 10.14302/issn.2689-5773.jcdp-18-2435
Bajaj AnubhaCorresponding author
Consultant Histopathologist
Theobjective of reviewing Hairy Cell Leukaemia may be achieved by emphasising the condition as a category of chronic lymphocytic leukaemia with hair like protrusions of the cytoplasm situated on the aberrant B cell surface. An infrequent disorder, hairy cell leukaemia contributes an estimated 2% of lymphoid malignancies with a male predominance ( M:F ::4-5:1). A majority (90%) of instances depict a mutant immunoglobulin heavy chain variable region (IGHV). The haematopoietic stem cells (HSCs) elucidate a B raf proto-oncogene( BRAF V600E gene- 7q34). An enlarged spleen may be discerned along with pancytopenia as a presenting symptom. The morphology of specific hairy cell leukaemia may be on account of an in vitro interaction of primary hairy cells with BRAF genes and MEK inhibitors, which incite a prominent MEK - ERK dephosphorylation, thereby curtailing transcriptional outpourings of the RAS- RAF- MEK-ERK pathway. Bone marrow aspiration or bone marrow trephine biopsy may be inadequate for diagnosis in 30%-50% individuals on account of extensive fibrosis and the bone marrow sections depict a characteristic interstitial infiltration of leukaemia cells.. Reticulin stains exhibit broad, dense reticulum fibres surrounding the individual or aggregates of leukaemia cells with fibrotic extensions into the abutting bone marrow. The immune reactivity of classic hairy cell leukaemia is concurrent CD19+ CD20+,CD 11c+, CD25+, CD103+ and CD123+. Immune staining for CD20+, annexin 1 and VE1 (a BRAF V600E stain) validates the diagnosis and analyses the extent of malignant bone marrow infiltration. Application of inhibitors of BRAF V600E gene is efficacious in patients resistant to standard therapy. An enlarged spleen beyond 3 centimetres of the left costal margin, a white blood cell count greater than 10000 cells/µL , circulating hairy cells in the peripheral blood greater than 5000 cells/µL and a β 2 micro-globulin level exceeding twice the normal range of 3 µg/ml delineate an inferior outcome with resistance to purine analogues (PNAs). CD38+ elucidation ensures a worse prognosis as does the lack of an IGHV mutation with a reduced overall survival,. A lack of BRAF genetic mutation in 10% -20% of hairy cell leukaemia comprises of inferior prognosis.
Apr 2017 DOI 10.14302/issn.2372-6601.jhor-17-1463
Szablewska SylwiaCorresponding author
Nicolaus Copernicus University, Faculty of Health Sciences; Department of Oncology, Radiotherapy and Ginecologic Oncology, Poland
Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells. In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment. In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.