Pretreatment radiomic analysis using CECT can potentially provide important information regarding the therapeutic response to PLDRT for GCACM, improving risk stratification.
The aim of the present study was to determine the effects of the insulin-like growth factor 1 (IGF-1)/phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/Akt/forkhead box (FoxO) signaling pathway on male reproduction in rats subjected to water immersion and restraint stress (WRS). Sperm morphology, sperm malformation rate, and serum testosterone concentration were analyzed following WRS. In addition, the expression levels and immunolocalization of IGF-1, PTEN, Akt and FoxO proteins, as well as the rate of cell apoptosis in rat testes, were investigated. The results indicated that sperm malformation rate, serum testosterone concentration, and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells were increased in the testes after WRS. Furthermore, IGF-1 and FoxO1 proteins were predominantly localized in the sperm cytoplasm during the late stages of spermatogenesis. FoxO1 protein was also localized in Leydig cell cytoplasm. PTEN and total Akt proteins were predominantly expressed in the cytoplasm of Leydig cells and spermatogonia. PTEN protein was also detected in vascular endothelial cells. In addition, IGF-1, PTEN, Akt1, Akt2, FoxO3 and FoxO4 gene expression levels were upregulated following WRS, and peaked after 7 h of WRS. During the recovery period, the expression levels of these genes gradually returned to normal levels. The present study demonstrated that WRS induced sperm damage in the testes. In addition, the results indicated that the IGF-1/PTEN/Akt/FoxO signaling pathway may serve an anti-stress role in the testes of rats subjected to WRS.
Biliary tract cancer (BTC) is an uncommon and aggressive neoplasm, with most patients presenting in an advanced stage. Systemic chemotherapy is the limited treatment available but is unsatisfactory, while targeted therapy is still awaiting validation from clinical trials. Given the potential effect of immune checkpoint inhibitors (ICIs) in the treatment of BTC, this review aims to summarize the evidence-based benefits and predictive biomarkers for using inhibitors of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) ligand, or programmed cell death protein-1 and its ligand (PD-1 and PD-L1) as monotherapy or combined with other anti-tumor therapies, while also pointing out certain pitfalls with the use of ICIs which need to be addressed.
Background
The standard treatment for advanced gastric/gastroesophageal junction cancer (AGC/GEJC) is palliative chemotherapy combined with targeted therapy. The SOX regimen (S-1 plus oxaliplatin) is recommended as neoadjuvant or palliative first-line chemotherapy in Asian patients. Apatinib, an oral VEGFR tyrosine kinase inhibitor, is associated with additional survival benefit as third- or subsequent-line therapy. However, the median overall survival time of AGC/GEJC is only 8–11 months in the West and 13–17 months in East Asia/Japan, even with the application of anti-angiogenic agents. Hence, the multimodal and individual management of patients is challenging standards to improve prognosis, including the preferential use of low-dose anti-angiogenic drugs and immunotherapy, as well as the application of multi-disciplinary treatment (MDT)-directed conversion therapy.
Methods/Design
This single-center study was designed to combine low-dose apatinib with camrelizumab plus the SOX regimen in diagnosed potentially resectable and initially unresectable AGC/GEJC. This a prospective, open-label, single-arm, dose escalation and extension phase Ib clinical trial, conducted in Jiangsu Province Hospital, beginning from June 2020. All patients will first receive this combined regimen (3 weeks/cycle) for at most eight cycles, then apatinib and camrelizumab in maintenance therapy until disease progression, intolerable toxicity, death, a maximum 2 years of treatment or discontinuation for any reason. Follow-up and evaluation will be carried out regularly. If surgery is allowed by MDT discussions, oral apatinib will be discontinued during the last preoperative cycle. The primary endpoints are the objective response rate and maximum tolerated dose according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) and the Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 5.0).
Discussion
This study will assess the response and side effects of AGC/GEJC patients in the use of low-dose apatinib combined with camrelizumab and the SOX regimen, and this combined therapy is expected to be a feasible and optimized first-line treatment option. In addition, this study will provide robust evidence and novel ideas for conversion therapy.
Trial Registration
ChiCTR.gov.cn: ChiCTR2000034109.
The use of hepatic artery infusion (HAI) as a regional therapy against liver metastasis has rarely been reported in gastric cancer. This study aimed to evaluate the efficacy and safety of HAI oxaliplatin plus oral S-1 chemotherapy in first-line palliative therapy for gastric cancer with multiple liver metastases (GCLM). Methods: We reviewed the records of five patients with GCLM who received HAI oxaliplatin (70-80 mg/m 2 2 hrs d1,15) administered via a port-catheter system and S-1 with oral (35-40 mg/m 2 twice daily for d1-14, 28 days for one cycle). Follow-up examination and efficacy evaluation were executed periodically. Results: Until the 4th cycle response evaluation, the local effective rate and control rate were 40% and 80%, respectively; only one patient developed progression. HAI chemotherapy had a better local control against liver metastases (median progression-free survival: hepatic, 8.8 months vs. extrahepatic, 6.2 months), accompanied by less systemic toxicity, decreased tumour markers and symptomatic relief. Conclusion: HAI oxaliplatin plus oral S-1 chemotherapy can be considered as a new choice of first-line treatment for GCLM, which is also a good approach for controlling extrahepatic lesions with less adverse events.
Background: Neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX regimen) has shown promising results in pathological response rate and survival rate in patients with locally advanced resectable gastric cancer (LAGC). We previously carried out the SPACE study to assess efficacy and safety of low-dose apatinib combined with camrelizumab and the SOX regimen as a first-line treatment of advanced gastric/ gastroesophageal junction adenocarcinoma (AGC/GEJC). The preliminary results demonstrated a high objective response rate. However, the SPACE study was conducted in patients with AGC, but the efficacy of LAGC patients is not yet known. The SPACE-neo study is designed to investigate whether this combination could improve outcomes in patients with locally advanced gastric/gastroesophageal junction cancer (LAGC/ GEJC) as neoadjuvant therapy.Methods: SPACE-neo is a prospective, open-label, single-arm study conducted in China at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital). Thirty-two patients with human epidermal growth factor receptor 2 (HER2)-negative or HER2-unknown LAGC/GEJC confirmed by histopathology or cytology will be recruited. Included patients shall be clinically staged as M0 and either T3 to T4 or N+ assessed by ultrasound endoscopy and thoracoabdominal-enhanced computed tomography or magnetic resonance imaging. The patients will receive three cycles of this combined regimen as a neoadjuvant treatment. Each patient will receive screening visits within 2 weeks before the first cycle and planned visits before every cycle of treatment. Key monitoring data include imaging data, pathological findings, and adverse events associated with neoadjuvant and surgical treatment. The primary endpoints are major pathological response (MPR) and safety. MPR is the proportion of patients whose residual tumor cells
e16508 Background: Gastric cancer with multiple liver metastases (GCLM) is associated with a high disease burden with synchronous or metachronous tumour invasions of other organs. In order to improve patient outcome, this study combined hepatic artery infusion (HAI) oxaliplatin with oral S-1 chemotherapy as a first-line palliative therapy. The aim is to assess efficacy and safety of this combination mode. Methods: We reviewed the records of ten patients with GCLM who received HAI oxaliplatin (70-80 mg/m2 2h d1,15) administered via a port-catheter system and S-1 with oral (35-40 mg/m2 twice daily for d1-14, 28 days for one cycle). Follow-up examination and efficacy evaluation were executed periodically. Results: Until the 4th cycle response evaluation, the local effective rate and control rate was 60% and 90% respectively, only one patient developed progression. HAI oxaliplatin plus oral S-1 chemotherapy had a better local control against hepatic metastases (median progression-free survival: hepatic, 9.0 months vs. extrahepatic, 6.5 months), which showed potential benefit of the combination regimen in gaining local tumour control, maintaining function and improving life quality. Conclusions: HAI oxaliplatin plus oral S-1 chemotherapy can be regarded as an optimized treatment strategy for GCLM, which is also a crucial way for controlling of extrahepatic lesions without much systemic toxicity.
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