The aim of the present study was to determine the most meaningful preoperative prognostic factor of cancer-related death in ovarian cancer patients by comparing potentially prognostic systemic inflammatory response (SIR) markers. The levels of fibrinogen, albumin, C-reactive protein (CRP), and serum cancer antigen-125 (CA-125) and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were evaluated in 190 ovarian cancer patients to identify predictors of overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analyses. Patients with a PLR >203 had a shorter PFS and OS than the patients in PLR ≤203 group (11 vs. 24 months and 28 vs. 64 months). Univariate analyses revealed that tumor stage, postoperative residual tumor mass, ascites, and the levels of all SIR markers were associated with PFS and OS. Multivariate analysis revealed that PLR was independently associated with PFS (hazard ratio [HR] 1.852, 95% confidence interval [CI] 1.271-2.697, P = 0.001) and OS (HR 2.158, 95%CI 1.468-3.171, P< 0.001), as well as tumor stage and postoperative residual tumor mass. In contrast, fibrinogen remained significant only for PFS (HR 1.724, 95%CI 1.197-2.482, P = 0.003). Patients with a PLR >203 were more prone to have advanced tumor stage (P = 0.002), postoperative residual tumor mass >2 cm (P = 0.032), malignant ascites (P < 0.001), and all the other elevated SIR markers (P < 0.001). Preoperative PLR is superior to other SIR markers (CA-125, NLR, fibrinogen, CRP, and albumin) as a predictor of survival in ovarian cancer patients.
BackgroundIntra-tumoral hypoxia and increases in extracellular level of transforming growth factor β1 (TGF-β1), which are common findings in cancer, are associated with an increased risk of metastasis and mortality. Moreover, metastasis is the leading cause of death of patients with cervical cancer. PLOD2 is an intracellular enzyme required for the biogenesis of collagen and its expression can be induced by hypoxia and TGF-β1. Specifically, PLOD2 is up-regulated in several types of cancer, including cervical cancer, and is associated with cancer metastasis. Thus, in this research, we aimed to investigate the role of PLOD2 in the motility of cervical cancer cells and to show the molecular mechanism underlying this effect.MethodssiRNA was used to knockdown PLOD2 in the cervical cancer cell lines HeLa and SiHa. The ability of cells to migrate and invade, their adhesion to type I collagen, and their capacity for epithelial-to-mesenchymal transition (ΕΜΤ) and focal adhesion formation were analyzed. Gene expression changes were validated by qRT-PCR, Western blotting and Immunocytochemistry. The morphological status of cells was examined using phalloidin staining. Differences in PLOD2 expression among patients with cervical cancer were identified by referring to public databases, including Oncomine and TCGA.ResultsHypoxia and TGF-β1 enhanced the expression of PLOD2 in HeLa and SiHa cells, and knockdown of PLOD2 inhibited cell motility and EMT. Moreover, the depletion of PLOD2 attenuated hypoxia-mediated cell migration and invasion and inhibited TGF-β1-induced phenotypic EMT-like changes by preventing β-catenin from entering the nucleus. In addition, PLOD2 depletion decreased cell adhesion to extracellular collagen by inhibiting the formation of focal adhesions. Moreover, a database analysis showed that PLOD2 expression is associated with human cervical cancer progression.ConclusionsOverall, our results indicated that hypoxia- and TGF-β1-induced PLOD2 expression promotes the migratory, invasive and adhesive capacities of cervical cancer cells by participating in TGF-β1 induced EMT and the formation of focal adhesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-017-0420-z) contains supplementary material, which is available to authorized users.
Stomatin‐like protein 2 (STOML2 or SLP‐2) is an oncogenic anti‐apoptotic protein that is upregulated in several types of cancer, including cervical cancer. However, the mechanisms responsible for the SLP‐2 anti‐apoptotic function remain poorly understood. Here, we show that siRNA‐mediated SLP‐2 suppression decreases growth of human cervical cancer HELA and SIHA cells, and increases cisplatin‐induced apoptosis through activation of MEK/ERK signaling and suppression of the mitochondrial pathway. The inhibition of the mitochondrial pathway is mediated by increasing the mitochondrial Ca2+ concentration and mitochondrial membrane potential, thereby downregulating p‐MEK and p‐ERK levels, upregulating the Bax/Bcl‐2 ratio, increasing cytochrome C release from mitochondria into the cytosol, and upregulating levels of cleaved‐caspase 9, cleaved‐caspase 3, and cleaved poly ADP‐ribose polymerase (PARP). Overexpression of SLP‐2 using adenovirus‐STOML2 has the opposite effect: it upregulates p‐MEK and p‐ERK and downregulates the Bax/Bcl‐2 ratio and levels of cleaved‐caspase 9 to caspase 9, cleaved‐caspase 3 to caspase 3, and cleaved‐PARP to PARP in cisplatin‐treated cells. These data show that SLP‐2 inhibits cisplatin‐induced apoptosis by activating the MEK/ERK signaling and inhibiting the mitochondrial apoptosis pathway in cervical cancer cells.
Tumor-associated lymphocytes (TALs) have been successfully isolated from ascites and solid tumors, however the clinical use of TALs in treating ovarian cancer (OC) has not yet been reported. The present study investigated the efficacy and toxicity of TALs in the presence or absence of chemotherapy in OC patients with malignant ascites (MA). A total of 32 patients were enrolled in this study. A total of 8 patients received treatment with TALs alone (TALs group), 11 patients received combined treatment of TALs and chemotherapy (combination group) and 13 patients received chemotherapy alone (chemotherapy group). The endpoints included Karnofsky performance status (KPS), ascites-associated symptoms (AAS), time to progression (TTP) and overall survival (OS). Compared with the TALs and chemotherapy group, the KPS and AAS in the combination group significantly improved following treatment. Patients in the TALs group (37.5%) and chemotherapy group (53.8%) achieved significantly fewer objective response rates of ascites compared with those in the combination group (90.9%). Furthermore, combination therapy significantly extended TTP (13 months) compared with TALs alone (1 month, P<0.001), and chemotherapy alone (6 months, P=0.027). Similar results were observed for OS between the combination group and the TALs group (25 vs. 7 months, P<0.001). The present study therefore demonstrates that combined therapy of TALs and chemotherapy is safe, feasible, and more effective than chemotherapy or TALs alone in controlling MA and improving the quality of life for OC patients.
Magnesium alloys have been known as the next generation material for lightweight body structures. Pulsating hydroforming is an effective method to improve magnesium alloy sheet forming performance, and the formed parts are characterized by lightweight, high-specific strength and stiffness. The deformation performance of magnesium alloy sheet AZ31B with a thickness of 0.6 mm under pulsating hydroforming has been investigated by means of experimental study, numerical simulation and theoretical analysis. The results show that under the same maximum hydraulic pressure, compared with simple linear loading, the magnesium alloy forming parts with pulsating hydraulic loading not only have better wall thickness uniformity and larger bulging height but also can delay the occurrence of fracture, improve the forming performance and ultimate the forming ability of magnesium alloy sheet. A new evaluation index is proposed to simplify the comprehensive forming performance of magnesium alloy parts with different amplitudes and frequencies more accurately, which can also be applied to determine the optimal forming parameters of magnesium alloy sheet AZ31B in the pulsating loading condition.
Background: As known, there is a high correlation between Helicobacter pylori infection and gastric carcinoma. Objectives: Concerning the important role of adhesin HpaA of H. pylori in the infection process, we aimed to explore whether HpaA promotes gastric cancer metastasis. Methods: In this study, the levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection were compared with post-treatment condition. The levels of IL-21 from CD4+ T cells and culture supernatants with the recombinant HpaA treatment were detected, and then the levels of MMP-2, MMP-9, and metastasis were detected and verified via AGS cells co-cultured with aforesaid CD4+ T cells. Results: Our results showed that higher levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection than without H.pylori infection. Adhesin HpaA induced more IL-21 via CD4+ T cells, and IL-21 induced high MMP-2 and MMP-9 via AGS cells. In particular, HpaA caused this serial reaction to improve the migration of AGS cells, and aptamer HA6 (our previous report) and anti-IL-21 mcAb reduced the above phenomenon remarkably. Conclusions: In summary, our research suggested that adhesin HpaA plays a significant role in the process of gastric carcinoma cell metastasis via IL-21 from HpaA-induced T cells, and aptamer HA6 may be a potential therapeutic agent for H. pylori treatment.
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