ABSTRACT
BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that soluble forms of T-cell costimulatory molecules 4-1BB (s4-1BB) and OX40 (sOX40) interact with immune cells and may constitute a mechanism of immune evasion by tumors in various cancers. The role of the soluble forms of 4-1BB and OX40 in GC remains unclear. We aimed to examine the association between serum levels of s4-1BB and sOX40 and tumor progression in patients with GC. METHODS: Between 2017 and 2018, a cross-sectional study was performed with serum samples of 83 GC patients and 20 healthy controls. RESULTS: Patients with stage IV metastatic gastric cancer had significantly higher levels of soluble OX40 in comparison with stage III patients with lymph nodes metastasis (p = 0.0003) and stages I and II patients (p = 0.005), whereas the opposite was found for soluble 4-1BB levels, with lower levels being found in advanced stage III (p = 0.003) compared with initial stages I/II. CONCLUSIONS: The sOX40 and s4-1BB-mediated T cell interactions may be involved in antitumor immune responses in GC, possibly favoring tumor escape and progression. Serum levels of sOX40 and s4-1BB are associated with staging in GC and may constitute biomarkers for prognosis, as well as potential targets for immunotherapy.
ABSTRACT
Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models-including patient-derived xenograft (PDX), 3D, and monolayer primary cultures-we successfully replicated crucial molecular traits observed in the patient's tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like TSC2 and FGFR4. These models are helpful in assessing the potential for an in-depth exploration of this tumor's biology. This comprehensive approach holds promise in identifying potential therapeutic avenues for managing this exceedingly rare soft tissue sarcoma.
Subject(s)
Sarcoma , Animals , Humans , Male , Mice , Mutation , Penile Neoplasms/genetics , Penile Neoplasms/pathology , Sarcoma/genetics , Sarcoma/pathology , Tuberous Sclerosis Complex 2 Protein/genetics , Middle AgedABSTRACT
BACKGROUND: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS: The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS: It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.
