Background: We had previously reported that the Suppression Subtractive Hybridization (SSH) approach was relevant for the isolation of new mammalian genes involved in oogenesis and early follicle development. Some of these transcripts might be potential new oocyte and granulosa cell markers. We have now characterized one of them, named TOPAZ1 for the Testis and Ovary-specific PAZ domain gene.
Principal Findings: Sheep and mouse TOPAZ1 mRNA have 4,803 bp and 4,962 bp open reading frames (20 exons), respectively, and encode putative TOPAZ1 proteins containing 1,600 and 1653 amino acids. They possess PAZ and CCCH domains. In sheep, TOPAZ1 mRNA is preferentially expressed in females during fetal life with a peak during prophase I of meiosis, and in males during adulthood. In the mouse, Topaz1 is a germ cell-specific gene. TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis.
Conclusions: We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206057 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026950 | PLOS |
Background: The addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy.
View Article and Find Full Text PDFFront Oncol
November 2024
Eastern Hepatobiliary Surgical Hospital, Naval Military Medical University, Shanghai, China.
Background: Advanced biliary tract cancer (BTC) is associated with a poor prognosis and limited options for second-line treatment. The TOPAZ-1 and KEYNOTE-966 trials have demonstrated the benefits of combining immune checkpoint inhibitors (ICIs) with chemotherapy in treating BTC. However, the efficacy of FOLFOX as a second-line therapy is limited, highlighting the need for more effective treatment approaches.
View Article and Find Full Text PDFWorld J Clin Cases
December 2024
Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa 277-8577, Japan.
Background: The combination of immune checkpoint inhibitors and chemotherapy has shown promising results for the treatment of advanced biliary tract cancer (BTC). Based on the results of the TOPAZ-1 trial, a gemcitabine and cisplatin plus durvalumab (GCD) regimen was recently approved as first-line therapy for patients with advanced BTC. However, post-GCD conversion surgery has not been previously studied.
View Article and Find Full Text PDFIntroduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes.
Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine, plus durvalumab.
JCO Glob Oncol
December 2024
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.
Purpose: Biliary tract cancers (BTCs) are usually diagnosed in advanced stages, where treatment options are either palliative chemotherapy and/or best supportive care. The breakthrough results of the TOPAZ-1 trial demonstrated a 24% decrease in risk of death at 2 years with the addition of durvalumab to chemotherapy.
Materials And Methods: This was a multicenter retrospective cohort study conducted across 14 institutions in India.
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