Treatment options for metastatic renal cell carcinoma (RCC) have been limited due to its resistance to chemotherapy and radiotherapy. Benefits from immunotherapeutic agents provide only a small subset of patients. During the past decade major advances have been made toward understanding the molecular basis of RCC development. Such acquired knowledge has offered unique opportunities for the development of molecular targeting agents. These agents are predominately small molecules or monoclonal antibodies that exert their action through modulation of protein activity or inhibition of amplified signals directly implicated in disease mechanism. To date, some of newly molecular targeted agents have entered advanced phases of clinical development, received marketing authorization by regulatory agencies and have opened a possibility of multiple treatment options. This article overviews current knowledge in RCC molecular pathology with recent clinical data, and discuss present strategies for future development of targeted therapies.
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http://dx.doi.org/10.2174/138161208784246252 | DOI Listing |
Jpn J Clin Oncol
January 2025
Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiode, Natori, Miyagi 981-1293, Japan.
A Japanese woman with Li-Fraumeni syndrome in her 40s underwent comprehensive genetic profiling accompanied by germline data using the Oncoguide NCC Oncopanel, but no germline pathogenic variants in the tumor suppressor gene TP53 were detected. However, careful examination of additional data in the report suggested the presence of a large TP53 deletion. Custom targeting next-generation sequencing and nanopore sequencing revealed a 3.
View Article and Find Full Text PDFAnn Emerg Med
January 2025
Division of Medical Toxicology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Study Objective: The osmol gap can help detect and manage those with toxic alcohol exposure, and it is altered by all alcohols including ethanol. The optimal correction for ethanol that would allow accurate detection of an alternative alcohol is unclear.
Methods: We conducted a prospective cohort study to assess baseline variations in osmol gap, and then to assess the validity of 2 commonly used coefficients (correction factors) for ethanol.
Mol Ther
January 2025
Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.
View Article and Find Full Text PDFEnviron Microbiome
January 2025
Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.
Background: Recovery of degraded coral reefs is reliant upon the recruitment of coral larvae, yet the mechanisms behind coral larval settlement are not well understood, especially for non-acroporid species. Biofilms associated with reef substrates, such as coral rubble or crustose coralline algae, can induce coral larval settlement; however, the specific biochemical cues and the microorganisms that produce them remain largely unknown. Here, we assessed larval settlement responses in five non-acroporid broadcast-spawning coral species in the families Merulinidae, Lobophyllidae and Poritidae to biofilms developed in aquaria for either one or two months under light and dark treatments.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
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