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Background. FGF signaling is critical to controlling various cancers. Nevertheless, the functions of FGF-related genes in PCa are still unknown. Objective. The objective of this study is to build a FGF-related signature that was capable of accurately predicting PCa survival and prognosis for BCR. Methods. The univariate and multivariate Cox regression, infiltrating immune cells, LASSO, and GSEA analyses were carried out to build a prognostic model. Results. A FGF-related signature that consists of PIK3CA and SOS1 was developed for the purpose of predicting PCa prognosis, and all patients were categorized into low- and high-risk groups. In comparison to the low-risk group, high-risk score patients had poorer BCR survival. This signature’s predictive power has been investigated utilizing the AUC of the ROC curves. The risk score has been shown to be an independent prognostic factor by multivariate analysis. The four enriched pathways of the high-risk group were obtained by gene set enrichment analysis (GSEA) and found to be associated with the tumorigenesis and development of PCa, including focal adhesion, TGF-β signaling pathway, adherens junction, and ECM receptor interaction. The high-risk groups had considerably higher levels of immune status and tumor immune cell infiltration, suggesting a more favorable response to immune checkpoint inhibitors. IHC found that the expression of the two FGF-related genes in the predictive signature was extremely different in PCa tissues. Conclusion. To summarize, our FGF-related risk signature may effectively predict and diagnose PCa, indicating that in PCa patients, they are potential therapeutic targets and promising prognostic biomarkers.

Background The minichromosome maintenance (MCM) protein complex is important for DNA replication. Moreover, the expression of specific MCM complex components has been associated with the survival of hepatocellular carcinoma (HCC) patients. However, the expression and functional roles of minichromosome maintenance complex component 4 (MCM4) in HCC development and progression have not yet been explored. We analyzed the expression and clinical significance of MCM4, including its association with liver cancer patient survival. Methods Oncomine, UALCAN, and HCCDB (a database of HCC expression atlas) were used to characterize the expression of MCM4 in tumor and normal tissues. The expression of MCM4 at the protein level was confirmed based on immunohistochemistry (IHC) data obtained from the Human Protein Atlas (HPA) database. The level of MCM4 was measured in tumor and adjacent normal tissues by RT-qPCR, western blot and IHC staining. The copy number alterations (CNAs) and mutations in MCM4 were analyzed by cBioPortal, whereas the co-expression genes of MCM4 in HCC were obtained from Oncomine, and used for gene ontology and pathway analysis via the NetworkAnalyst 3.0 tool, to explore the predictive signaling pathway in HCC. Results The levels of MCM4 messenger (m)RNA and protein were found to be significantly higher in liver cancer tissues than in normal liver tissues. Kaplan-Meier analysis showed that the upregulation of MCM4 was significantly negatively correlated with the survival of HCC patients. Conclusions Our data suggest that MCM4 may be used as a potential prognostic marker and therapeutic target for HCC.

Background The aim of this study was to evaluate the efficacy and safety of trastuzumab, combined with the FLOT regimen, in the perioperative treatment of resectable HER-2-positive advanced gastric cancer. Methods Overall, 45 patients were divided into two groups; 29 patients in the experimental group were treated with trastuzumab combined with FLOT and 16 patients in the control group were treated with FLOT alone. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), tumor regression grade (TRG), surgical margin, side effects, and overall survival. Results In the experimental and control groups, ORR was 72.4% and 43.8% (p=0.226), DCR was 89.7% and 87.5%, R0 resection rate was 96.5% and 93.7%, total/subtotal tumor regression grade was 17.2% and 6.3%, partial tumor regression grade was 27.6% and 18.7% (p=0.468), and 2-year survival rate was 78.1% and 73.9% (p=0.932), respectively. The common side effects were agranulocytosis and vomiting. There was no significant difference between the two groups. Conclusion Trastuzumab combined with FLOT has a good curative effect and safety profile in the perioperative treatment of patients with resectable HER-2-positive advanced gastric cancer. In addition, trastuzumab + FLOT had the same result as FLOT alone, as there was no significant benefit with the addition of T in the group studied.

BACKGROUND: The minichromosome maintenance (MCM) protein complex is important for DNA replication. Moreover, the expression of specific MCM complex components has been associated with the survival of hepatocellular carcinoma (HCC) patients. However, the expression and functional roles of minichromosome maintenance complex component 4 (MCM4) in HCC development and progression have not yet been explored. We analyzed the expression and clinical significance of MCM4, including its association with liver cancer patient survival. METHODS: Oncomine, UALCAN, and HCCDB (a database of HCC expression atlas) were used to characterize the expression of MCM4 in tumor and normal tissues. The expression of MCM4 at the protein level was confirmed based on immunohistochemistry (IHC) data obtained from the Human Protein Atlas (HPA) database. The level of MCM4 was measured in tumor and adjacent normal tissues by RT-qPCR, western blot and IHC staining. The copy number alterations (CNAs) and mutations in MCM4 were analyzed by cBioPortal, whereas the co-expression genes of MCM4 in HCC were obtained from Oncomine, and used for gene ontology and pathway analysis via the NetworkAnalyst 3.0 tool, to explore the predictive signaling pathway in HCC. RESULTS: The levels of MCM4 messenger (m)RNA and protein were found to be significantly higher in liver cancer tissues than in normal liver tissues. Kaplan-Meier analysis showed that the upregulation of MCM4 was significantly negatively correlated with the survival of HCC patients. CONCLUSIONS: Our data suggest that MCM4 may be used as a potential prognostic marker and therapeutic target for HCC.

The purpose of this study was to analyze the characteristics, diagnosis and treatment principles and prognosis of multiple primary cancers (MPC).A total of 77 patients with MPC admitted in the Central Hospital of Changsha from December 2013 to December 2018 were enrolled in this retrospective analysis. The survival of these 77 patients with complete follow-up data was calculated.There were 77 patients with multiple primary cancers, including 70 patients with double primary cancers, 6 patients with three primary cancers, and 1 patient with four primary cancers. Among the 77 MPC patients, there were 4 synchronous carcinomas (SC), 58 metachronous carcinomas (MC), and 15 unknown cases. The 3, 5, and 10-year overall survival rates of 77 patients with follow-up data were 86.5%, 18.2%, and 12.9%, respectively. The median survival time of 4 SC and 58 MC patients was 12 months and 108 months, respectively. The median survival time was 48.5 months in 23 patients with an interval of less than 5 years, and 108 months in 29 patients with first and second primary cancers whose interval was more than 5 years. The median survival time of 26 patients with second primary lung cancer was 84 months, and that of 23 patients with second primary non-lung cancer was 156 months.MPCs are more likely to occur in the colorectum, and the prognosis of patients with metachronous cancer is better than that of patients with synchronous cancer. The longer the interval between two cancers, the better the prognosis will be. The prognosis of the second primary non-lung cancer patients is better than that of the lung cancer patients.

Nasopharyngeal carcinoma (NPC) has a high incidence and mortality rate, particularly in Southern China. Apogossypolone (ApoG2) is a novel derivative of gossypol with antitumor activity and less toxicity. The human NPC CNE-2 cell line was studied in the in vitro model; whilst 4 week-old male nude mice (BALB/c-nu) were inoculated subcutaneously with CNE-2 cells, and xenograft tumors were studied in the in vivo model. Graded concentrations of ApoG2 were used in treatment studies. In ApoG2-treated and control in vitro and in vivo tumor cells, cell apoptosis, and autophagy were evaluated and quantified using fluorescent and transmission electron microscopy and flow cytometry. Hoechst-33258 fluorescence staining was used to evaluate apoptosis in treated and non-treated cell culture and xenograft NPC cells. Western blotting was performed on lysed tumor cells using primary antibodies to B-cell lymphoma-2 (Bcl-2), beclin-1, and β-actin, and flow cytometry results indicated cell apoptosis rates of 3.90±0.34 and 19.52±1.18% in the control and ApoG2-treated cells, respectively (F=485.294, P

Supplemental Material, Ethical_review for miR-331-3p Inhibits Proliferation and Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Targeting elf4B-PI3K-AKT Pathway by Zhang Xuefang, Zheng Ruinian, Jiang Liji, Zhang Chun, Zheng Qiaolan, Jia Jun, Chen Yuming and Huang Junrong in Technology in Cancer Research & Treatment

Long non-coding RNA (lncRNA) is an important member of non-coding RNA family and emerging evidence has indicated that it plays a pivotal role in many physiological and pathological processes. The lncRNA X inactive specific transcript (XIST) is a potential tumour suppressor in some types of cancers. However, the expression and function of XIST in breast cancer remain largely unclear. The objective of this study was to evaluate the expression and biological role of XIST in breast cancer. The results showed that XIST was significantly down-regulated in breast cancer tissues and cell lines. Further functional analysis indicated that overexpression of XIST remarkably inhibited breast cancer cell growth, migration, and invasion. The results of luciferase reporter assays verified that miR-155 was a direct target of XIST in breast cancer. Moreover, caudal-type homeobox 1 (CDX1) was identified as a direct target of miR-155 and miR-155/CDX1 rescued the effects of XIST in breast cancer cells. Taken together, our results suggest that XIST is down-regulated in breast cancer and suppresses breast cancer cell growth, migration, and invasion via the miR-155/CDX1 axis.

The present study investigated the effects of curcumin (Cur) on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control), 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05). The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05), and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05). Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.

In this study, we sought to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA; experimental group) versus RFA treatment (control group) in patients receiving palliative treatment for hepatocellular carcinoma. To summarize the available evidence, we used the Review Manager 5.1 software to perform a meta-analysis of English-language articles published in public databases prior to 2014. Based on 6 studies that met the inclusion criteria, a total of 531 (experimental group, 272; control group, 259) patients with hepatocellular carcinoma were included in the meta-analysis. The meta-analysis demonstrated that the experimental group had a higher 3-year survival rate [risk ratios (RRs) = 1.41; 95% confidence interval (CI) = 1.03-1.94; P0.05] and a higher 2-year survival rate (RR = 1.11; 95%CI = 1.01-1.23; P0.05) than the control group. In the overall meta-analysis, the overall RRs were 2.02 (95%CI = 1.40-2.91; P0.05) and 1.63 (95%CI = 1.06-2.51; P0.05) for 3- and 5-year recurrence-free survival, respectively. Furthermore, the overall meta-analysis showed an overall RR of 0.75 (95%CI = 0.60-0.93; P0.05) for the incidence of tumor progression and an overall RR of 1.19 (95%CI = 0.33-4.33; P0.05) for the major complication rate. In a sensitivity analysis, the above mentioned meta-analytic estimates were unchanged by the removal of 1 study at a time. The meta-analysis suggested that the experimental group had a higher survival rate, a higher recurrence-free survival rate, and a lower incidence of tumor progression than the corresponding control group.

Aging is a multifactorial process characterized by the progressive deterioration of physiological functions. Among the multiple molecular mechanisms, microRNAs (miRNAs) have increasingly been implicated in the regulation of Aging process. However, the contribution of miRNAs to physiological Aging and the underlying mechanisms remain elusive. We herein performed high‐throughput analysis using miRNA and mRNA microarray in the physiological Aging mouse, attempted to deepen into the understanding of the effects of miRNAs on Aging process at the “network” level. The data showed that various p53 responsive miRNAs, including miR‐124, miR‐34a and miR‐29a/b/c, were up‐regulated in Aging mouse compared with that in Young mouse. Further investigation unraveled that similar as miR‐34a and miR‐29, miR‐124 significantly promoted cellular senescence. As expected, mRNA microarray and gene co‐expression network analysis unveiled that the most down‐regulated mRNAs were enriched in the regulatory pathways of cell proliferation. Fascinatingly, among these down‐regulated mRNAs, Ccna2 stood out as a common target of several p53 responsive miRNAs (miR‐124 and miR‐29), which functioned as the antagonist of p21 in cell cycle regulation. Silencing of Ccna2 remarkably triggered the cellular senescence, while Ccna2 overexpression delayed cellular senescence and significantly reversed the senescence‐induction effect of miR‐124 and miR‐29. Moreover, these p53 responsive miRNAs were significantly up‐regulated during the senescence process of p21‐deficient cells; overexpression of p53 responsive miRNAs or knockdown of Ccna2 evidently accelerated the cellular senescence in the absence of p21. Taken together, our data suggested that the p53/miRNAs/Ccna2 pathway might serve as a novel senescence modulator independent of p53/p21 pathway.

Sonodynamic therapy (SDT) is a promising new approach for cancer therapy. The aim of this study was to investigate the tumor affinity of chlorin e6, a photosensitizer, and its sonodynamic effects on NSCLC.Human lung adenocarcinoma cells SPCA-1 and mice bearing SPCA-1 tumor xenograft were exposed to ultrasound in the presence or absence of chlorin e6. Chlorin e6 distribution was detected by laser scan confocal microscope. Cell apoptosis and necrosis were studied by flow cytometry analysis. Tumor size and weight were measured after different treatments.The concentration of chlorin e6 in tumor tissue was remarkably higher than that in normal muscle near tumor, and the difference was greatest at 18h (the fluorescence intensity was 5.38-fold higher in tumor than in muscle, P0.05). In vivo, ultrasound (0.4-1.6W/cm(2)) or chlorin e6 (10-40mg/kg) alone had no remarkable anti-tumor effects, but the combination of ultrasound (1.6W/cm(2)) with chlorin e6 (SDT) hampered tumor growth significantly (P0.05). Intraperitoneal injection of 40mg/kg chlorin e6 exerted no notable side effect on blood, liver and kidney function. Flow cytometry analysis showed that chlorin e6-mediated sonodynamic effect was mainly through the induction of cell necrosis.Chlorin e6 is a promising sonosensitizer and chlorin e6-mediated SDT may provide a new approach for NSCLC therapy.

Nasopharyngeal carcinoma (NPC) has a high incidence and mortality rate, particularly in Southern China. Apogossypolone (ApoG2) is a novel derivative of gossypol with antitumor activity and less toxicity. The human NPC CNE-2 cell line was studied in the in vitro model; whilst 4 week-old male nude mice (BALB/c-nu) were inoculated subcutaneously with CNE-2 cells, and xenograft tumors were studied in the in vivo model. Graded concentrations of ApoG2 were used in treatment studies. In ApoG2-treated and control in vitro and in vivo tumor cells, cell apoptosis, and autophagy were evaluated and quantified using fluorescent and transmission electron microscopy and flow cytometry. Hoechst-33258 fluorescence staining was used to evaluate apoptosis in treated and non-treated cell culture and xenograft NPC cells. Western blotting was performed on lysed tumor cells using primary antibodies to B-cell lymphoma-2 (Bcl-2), beclin-1, and β-actin, and flow cytometry results indicated cell apoptosis rates of 3.90±0.34 and 19.52±1.18% in the control and ApoG2-treated cells, respectively (F=485.294, P

The clinical benefits provided by using combined taxanes and anthracyclines in first-line chemotherapy for metastatic breast carcinoma (MBC) remain uncertain. This meta-analysis compares the benefits of using a combination of anthracyclines along with taxanes versus using single-agent-based chemotherapeutic regimens in the treatment of MBC. Relevant clinical trials as well as abstracts from articles presented at major cancer conferences were searched in various databases including PubMed, Embase, and Cochrane Library. The relevant studies had a primary endpoint of overall survival (OS) and secondary endpoints that included progression-free survival (PFS), time-to-treatment failure (TTF), time to progression (TTP), objective response rate (ORR), disease control rate (DCR), and safety. The hazard ratios of OS, PFS, TTF, and TTP, the odds ratios of ORR and DCR, and the risk ratios (RRs) for grades 1–2 and 3–4 toxicities were extracted from the retrieved studies and analyzed using various statistical methods. Meta-analytic estimates were derived from a random-effect model. Fifteen trials were included in the final meta-analysis, and the results suggest that chemotherapy with combined anthracyclines and taxanes does not significantly improve the OS of MBC patients when compared with the OS achieved using separate taxane or anthracycline-based regimens. Compared with taxane-based regimens, combined taxane along with anthracycline regimens failed to significantly improve TTP, ORR, or DCR, but did significantly improve TTP and ORR when compared with anthracycline-based regimens. Furthermore, both individual taxane-based and anthracycline-based regimens produced fewer toxic reactions compared to combined taxane along with anthracycline regimens. Taxane-based regimens had lower RRs for side effects of neutropenia, infection/febrile neutropenia, nausea, and vomiting, whereas patients receiving anthracycline-based regimens had lower RRs for neutropenia, infection/febrile neutropenia, anorexia, stomatitis/mucosal inflammation, diarrhea, and sensory neuropathy. In contrast, patients receiving taxane-based regimens were at higher RRs for hand–foot syndrome and diarrhea, whereas patients receiving anthracycline-based regimens had higher RRs for nausea and vomiting. A taxane-based treatment regimen may be a better option than a combined taxane/anthracycline regimen for managing patients with advanced breast cancer, as it produces equivalent clinical outcomes and has less toxicity compared to other similar regimens.