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The ATP binding cassette (ABC) transporters, first discovered as high-affinity nutrient importers in bacteria, rose to prominence when their ability to confer multidrug resistance (MDR) to cancer cells was realized. The most characterized human permeability glycoprotein (P-gp) is a dominant exporter of anti-cancer drugs and its overexpression is directly linked to MDR. The overexpression of drug efflux pumps belonging to the ABC superfamily is also a frequent cause of resistance to antifungals. Fungi has a battery of ABC proteins, but in variable numbers and at different subcellular locations. These proteins perform many critical functions, from serving as gatekeepers for xenobiotic cleansing to translocating various structurally unrelated cargoes, including lipids, fatty acids, ions, peptides, sterols, metabolites and toxins. Their emerging additional roles in cellular physiology and virulence call for attention to analyze and re-examine their divergent functions in yeast. In brief, this review traces the history of ABC transporters in yeast and discusses their typical physiological functions that go beyond their well-known role as antifungal drug efflux pumps.Very limited progress has been made in the management of advanced melanoma, especially melanoma of uveal origin. Lactamase β (LACTB) is a novel tumor suppressor; however, its biological function in melanoma remains unknown. Herein we demonstrated markedly lower LACTB expression levels in melanoma tissues and cell lines. Overexpression of LACTB suppressed the proliferation, migration and invasion of melanoma cells in vitro. Mechanistically, LACTB inhibited the activity of yes-associated protein (YAP). We showed that the level of phospho-YAP (Serine 127) was increased upon LACTB overexpression, which prevented the translocation of YAP to the nucleus. Further, LACTB could directly bind to PP1A and attenuate the interaction between PP1A and YAP, resulting in decreased YAP dephosphorylation and inactivation in a LATS1-independent manner. Additionally, transfection of phosphorylation-defective YAP mutants reversed LACTB-induced tumor suppression. Upstream, we demonstrated that SOX10 binds to the LACTB promoter and negatively regulates its transcription. Overexpression of LACTB also suppressed the tumorigenicity and lung metastasis of MUM2B uveal melanoma cells in vivo. Taken together, our findings indicate a novel SOX10/LACTB/PP1A signaling cascade that renders YAP inactive and modulates melanoma progression, offering a new therapeutic target for melanoma treatment.Tumor neoantigens play an important role in current cancer immunotherapies. The most commonly studied class of tumor neoantigens contains those derived from single-nucleotide variants (SNVs) and insertions or deletions (Indels). However, gene fusions are also ideal sources of tumor neoantigens, as they can form new open reading frames (ORFs). Compared with SNV and Indel (SNV&Indel) neoantigens, fusion gene neoantigens tend to be more immunogenic, have more targets per mutation, and are more broadly shared across different cancer types. As a result, they are an important class of tumor neoantigens and emerging targets for cancer immunotherapies, with uses as prognostic biomarkers of immune checkpoint blockade (ICB) and in the development of tumor vaccines, adoptive cell therapies and tumor immune microenvironment modulation. https://www.selleckchem.com/products/ro-3306.html In this review, we introduce the chromosomal basis and characteristics of gene fusions. Then, we summarize the predictive tools, mutation burden and immunogenicity of gene fusion neoantigens. Further, we discuss applications and future improvements of gene fusion neoantigens with respect to current cancer immunotherapies and novel developments in cancer treatment.Hepatitis B Virus (HBV) infection is a leading cause of chronic liver cirrhosis and hepatocellular carcinoma (HCC) with an estimated 400 million people infected worldwide. The precise molecular mechanisms underlying HBV replication and tumorigenesis have remained largely uncharacterized due to the lack of a primary cell model to study HBV, a virus that exhibits stringent host species and cell-type specificity. Organoid technology has recently emerged as a powerful tool to investigate human diseases in a primary 3D cell-culture system that maintains the organisation and functionality of the tissue of origin. In this review, we describe the utilisation of human liver organoid platforms to study HBV. We first present the different categories of liver organoids and their demonstrated ability to support the complete HBV replication cycle. We then discuss the potential applications of liver organoids in investigating HBV infection and replication, related tumorigenesis and novel HBV-directed therapies. Liver organoids can be genetically modified, patient-derived, expanded and biobanked, thereby serving as a clinically-relevant, human, primary cell-derived platform to investigate HBV. Finally, we provide insights into the future applications of this powerful technology in the context of HBV-infection and HCC. Single-incision laparoscopic surgery (SILS) is an exciting new modality in the field of minimal access surgery. This case illustrates the feasibility of single-incision laparoscopic surgery for uterine pathology in the pediatric and adolescent population. A 19-year-old girl presented with pelvic pain. Transabdominal pelvic ultrasound and magnetic resonance imaging revealed multiple fibroids with rapid enlargement over a year. In collaboration with the Minimally Invasive Gynecologic Surgery team, single incision laparoscopic myomectomy was performed with satisfactory results. Complex uterine pathology can be managed with minimally invasive surgery with excellent clinical outcomes. SILS is a rapidly developing field that may represent the future of laparoscopic surgery and can be used to treat reproductive pathology in the pediatric and adolescent population. Complex uterine pathology can be managed with minimally invasive surgery with excellent clinical outcomes. SILS is a rapidly developing field that may represent the future of laparoscopic surgery and can be used to treat reproductive pathology in the pediatric and adolescent population.
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