Autophagy is one of the survival processes of cancer cells, especially in stressful conditions such as starvation, hypoxia and chemotherapeutic agents. However, its roles in tumor survival have not yet been fully elucidated. Here, we found for the first time that JAK2/STAT3 was activated in HeLa cells when they were starved or treated with rapamycin. STAT3 activation was associated with autophagic processes, because it was completely inhibited by 3-methyladenine, partially inhibited by knockdown of molecules associated with autophagic processes and blocked by antioxidants, DPI, a Nox inhibitor and knockdown of p22 phox, indicating that ROS generated by Nox that was activated during autophagic processes activated JAK2/STAT3 pathway. Activated STAT3 directly bound to IL6 promoter and increased IL6 mRNA and protein secretion. Finally, the conditioned media, which included IL6, from starved HeLa cells promoted cancer cell survival in both normal and starved conditions, confirmed by clonogenic, proliferation and cell death assays. These data together indicate that the autophagic process in cancer cells can contribute to their survival by JAk2/STAT3 activation and subsequent secretion of growth factors.
Background/AimsWe investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting.MethodsIn total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy.ResultsAll patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects.ConclusionsA limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Robotic thyroidectomy using BABA may be a technically feasible and safe procedure comparable to conventional open surgery especially in node-negative patients.
Deregulation and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian (or mechanistic) target of rapamycin (mTOR) pathway have a major role in proliferation and cell survival in breast cancer. However, as single agents, mTOR inhibitors have had modest antitumor efficacy. In this study, we evaluated the effects of vertical inhibition of mTOR and Akt in breast cancer cell lines and xenografts. We assessed the effects of mTOR inhibitor rapamycin and Akt inhibitor MK-2206, given as single drugs or in combination, on cell signaling, cell proliferation and apoptosis in a panel of cancer cell lines in vitro. The antitumor efficacy was tested in vivo. We demonstrated that MK-2206 inhibited Akt phosphorylation, cell proliferation and apoptosis in a dose-dependent manner in breast cancer cell lines. Rapamycin inhibited S6 phosphorylation and cell proliferation, and resulted in lower levels of apoptosis induction. Furthermore, the combination treatment inhibited phosphorylation of Akt and S6, synergistically inhibited proliferation and induced apoptosis with a higher efficacy. In vivo combination inhibited tumor growth more than either agent alone. Our data suggest that a combination of Akt and mTOR inhibitors have greater antitumor activity in breast cancer cells, which may be a viable approach to treat patients.
PurposeThe improvement of intraoperative parathyroid hormone (IOPTH) assay and localization studies has enabled a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). The aim of this study is to analyze the demographics, clinical presentations, and surgical outcomes of the pHPT patients who received surgical management with versus without IOPTH.MethodsAnalysis of a database was performed on 53 patients who underwent parathyroidectomy for pHPT from 2004 to 2013. Preoperative localization was done by both sestamibi scan and ultrasonography. We divided the patients into two groups (without IOPTH versus with IOPTH) and analyzed the surgical outcomes statistically between two groups.ResultsThe concordance rate of Technetium 99m sestamibi scan and ultrasonography was 73.6% and 90.6%, respectively. The overall cure rate of group 1 (without IOPTH) was 94.9% and that of group 2 (with IOPTH) was 100%. The decline of PTH at postoperative 5 minutes and 10 minutes was 75.2% ± 14.9% and 84.9% ± 8.6% in cured patients. On the other hand, that of noncured patients at 5 minutes and 10 minutes was 17.2% ± 9.7% and 8.2% ± 2.2%. There was a significant difference in the drop rate of IOPTH between cured and persistent patients (P < 0.01). Pathological examination showed adenoma in 41 of 53 patients (77.4%) and hyperplasia in 10 of 53 patients (18.9%).ConclusionEven though the localization studies were successful, IOPTH monitoring is essential to avoid a surgical failure in MIP.
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