Purpose: The occurrence of neutropenia following chemotherapy makes the management of myelosuppression important. The main objective of this study was to evaluate whether the decrease of peripheral blood monocytes was a potential indicator to predict the occurrence of neutropenia. Patients and Methods: We retrospectively reviewed the medical records of 103 chemotherapy patients who underwent neutropenia. A paired sample t-test was used to assess whether the number of days when monocyte initial decrease/are in nadir/final increase was significantly less than that of the neutrophils. The baseline of monocyte percentage and the decrease rate of neutrophil were analyzed by the bivariate correlation (two-tailed). Moreover, the grade of neutropenia and the baseline of monocyte percentage (divided into <5% and ≥5%) were examined by the Chi-square test for correlations. Results: Our study showed that the change trend of monocyte count was the same as that of neutrophil count and that the number of days when monocytes initial decrease/are in nadir/final increase was significantly less than that of neutrophils, respectively. The time of initial decrease in monocyte count was 1.39 days earlier; the nadir in monocyte count occurred 3.81 days earlier, and the final increase in monocyte count was 2.36 days earlier than that in neutrophil count. In addition, there was an inverse correlation between the decrease rate of neutrophil and the baseline of monocyte percentage according to the analysis of bivariate correlation (Pearson correlation = –0.241, P = 0.0142). Unfortunately, there was no significant correlation between the baseline of monocyte percentage and the grade of neutropenia examined with the Chi-square test (P = 0.7401). Conclusion: Our study shows the increase or decrease in monocyte count is a significant potential indicator to predict the occurrence of neutropenia, and it is also a predictor to guide the next monitoring time of neutrophil count and the treatment of granulocyte-colony stimulating factor.

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Background: The aim of this retrospective study was to investigate the clinicopathological characteristics of patients with signet-ring cell carcinoma (SRCC) of the stomach, and the efficacy of the modified docetaxel, cisplatin, and fluorouracil (mDCF) chemotherapy regimen. Patients and Methods: Sixty-five patients diagnosed with metastatic or recurrent SRCC and treated with at least one course of mDCF regimen as the first-line treatment at our hospital July 2007 and January 2015, were included in this study. The mDCF protocol comprised docetaxel at 60 mg/m²/day (day 1), cisplatin at 60 mg/m²/day (day 1), and 5-fluorouracil at 600 mg/m²/day (days 1–5) for every 3 weeks. Results: The median age was 53 years (range, 25–69 years). The most frequent sites of metastasis were the peritoneum (50.8%) and liver (21.5%). The median number of chemotherapy courses was six. In assessing 61 patients for response evaluation, one patient (1.6%) achieved a complete response, and 36 (59.0%) achieved a partial response. Fifteen patients (24.6%) had stable disease and nine (14.8%) had progressive disease. Grades 3–4 hematological toxicity revealed anemia in three (4.6%) patients, thrombocytopenia in two (3.1%), and neutropenia in five (7.7%). Grades 3–4 nonhematological side effects revealed nausea and vomiting in four (6.1%) patients and mucositis in one (1.5%). The overall survival (OS) and progression-free survival (PFS) were 10.4 months (95% confidence interval [95% CI], 8.9–12.0) and 6.1 months (95% CI, 5.1–7.0), respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of 2 and a high pretreatment carcinoembryonic antigen level were statistically significant. Conclusions: mDCF is an effective regimen in patients with SRCC of the stomach who have ECOG performance score of 0–1 when the PFS, OS, and tumor response rate are considered. Further prospective studies including more patients should be conducted on this subject.

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Objective: To critically assess the effectiveness and safety of acupuncture for treating hot flashes (HFs) among breast cancer (BC) patients, and to get much more highly compelling evidence then to guide clinical practice. Methods: Comprehensive systematic literature searches were carried out for identifying randomized controlled trials and observational studies (OSs) published before January 2015. The meta-analysis (MA) was performed by Review Manager 5 software if data could be merged routinely, if not descriptions would be given. Results: A total of 18 studies were eligible ultimately. With respect to HFs frequency, the MA during treatment showed a significant difference (MD = –1.78, 95% confidence intervals [95% CIs]: –3.42-–0.14), but no statistical differences were observed when posttreatment or follow-up period. While electroacupuncture versus applied relaxation, they both helped to promote HFs markedly but did not reveal statistically significance between them. Referring to Kupperman's index, all the treatment brought out great assistance when compared with baseline conditions, and there was significant difference between real acupuncture sham acupuncture (posttreatment: MD = –4.40, 95% CI: –6.77-–2.03; follow-up: MD = –4.30, 95% CI: –6.52-–2.08). In terms of OS, 7 prospective single arm studies focused on exploring the efficacy of traditional acupuncture, and all revealed moderate or great benefit for BC patients suffering from HFs. Conclusions: Acupuncture still appeared to be an efficacious therapeutic strategy, especially for the less/no side effects. Because of its widespread acceptance and encouraging effectiveness for improving HFs, much more high-quality studies are in need urgently.

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Aim: This randomized phase III trial compared hepatic arterial infusion (HAI) chemotherapy with 5-fluorouracil (5-FU) followed by uracil/tegafur (UFT) and leucovorin (LV) versus UFT/LV alone for patients with curatively resected liver metastases from colorectal cancer (CRC). Methods: The study was designed to include 280 patients to be randomized to receive either HAI with 5-FU followed by UFT/LV (Arm A) or UFT/LV alone (Arm B) to assess whether HAI chemotherapy improved disease-free survival (DFS). Results: Forty-four patients were randomized. Three-year DFS was relatively worse in the experimental arm although this difference was not statistically significant (43.5% in Arm A vs. 58% in Arm B; hazard ratio [HR], 1.304; P = 0.534). The experimental arm also tended to have a worse 3-year overall survival rate (80.2% in Arm A vs. 85.2% in Arm B; HR, 2.255; P = 0.192). There was no significant difference in the frequency of Grade 3 or higher toxicities between the two arms. Conclusion: Although this study was limited by a small sample size after early study termination, our analysis found that HAI with 5-FU followed by UFT/LV did not improve the DFS of patients with curatively resected liver metastases from CRC compared with UFT/LV alone. The future studies are necessary to evaluate the survival benefit of HAI in combination with newer systemic chemotherapeutic agents for patients with resectable liver metastases from CRC.

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Aims: To explore the biological roles of alpha-fetoprotein (AFP), a tumor-associated antigen in human hepatocellular carcinoma (HCC). Materials and Methods: After knockdown of AFP in HepG2 cells by transfection of specific Stealth™ RNAi, the expression of AFP were detected by reverse transcription polymerase chain reaction at mRNA level and by enzyme-linked immunosorbent assay at the protein level. Then, the effect of silenced AFP on cell proliferation was assessed by dimethylthiazolyl-2,5-diphenyl-tetrazolium bromide assay, and apoptosis assessment with Hoechst33258 and flow cytometry (double stain with fluorescein isothiocyanate/propidium iodide), the roles of AFP in the cell cycle regulation were assessed by flow cytometry. We also detected the expression of some key proteins related to apoptosis pathway by Western immunoblot analysis. Results: After the transfection for 48 h, the expression of AFP gene was almost abolished, the cell proliferation was inhibited by 47.61%, the number of cells undergoing early apoptosis was significantly increased to 59.47%; cell cycle was arrested with the increase of G0/G1 phase cells from 45.3% to 58.4%. Inhibition of AFP expression also results in decreasing of transforming growth factor-β (TGF-β), mutant P53 expression, and increasing of Bax/Bcl-2 ratio, activation of caspase-3. Conclusions: The results suggest that AFP may positively regulate cell proliferation by enhancing the apoptosis resistance via effect on TGF-β and p53/Bax/caspase-3 signaling pathway in HepG2 cells. As such, the knockdown of AFP gene should be further investigated in vivo as a novel approach to HCC treatment.

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Aim: This study aimed to investigate the key transcription factors (TFs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) associated with hepatocellular carcinoma (HCC). Materials and Methods: The datasets GSE31383 and GSE54238 were downloaded from Gene Expression Omnibus data repository. GSE31383 was used to screen differentially expressed miRNAs, and GSE54238 was used to screen differentially expressed messenger RNAs (mRNAs) and lncRNAs. ChipBase was used to identify TF-miRNA pairs. StarBase was selected to identify miRNA-mRNA and lncRNA-miRNA interactions. Kyoto Encyclopedia of Genes and Genomes pathway analysis was also conducted using Database for Annotation, Visualization, and Integrated Discovery tool. Results: A total of 2065 mRNAs, 1050 lncRNAs, and 26 miRNAs were identified to be divergently expressed in HCC compared with normal tissues. There were 338 miRNA-mRNA and 65 lncRNA-miRNA pairs with reverse expression trend. Besides 249 TF-miRNA relationships including differentially expressed miRNA were isolated. Among them, 11 TF-miRNA had the same expression trend. Furthermore, lncRNA-miRNA-mRNA and TF-miRNA-mRNA regulatory networks were constructed. hsa-miR-497, hsa-miR-195, and hsa-miR-424 were identified as hub nodes in these two networks. Hub TFs, such as TATA box binding protein-associated factor 1 (TAF1) and hepatocyte nuclear factor 4, alpha (HNF4α), and lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were also screened out in the network. Conclusions: Our findings highlight the regulatory networks among TFs, lncRNAs, miRNAs, and mRNAs in HCC. Several key molecules, such as hsa-miR-195, lncRNA MALAT1 and TFs TAF1 and HNF4α, may contribute to the progression of HCC.

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Large cell neuroendocrine carcinoma (LCNEC) of the prostate is extremely rare. Previously reported cases in the literature were almost exclusively developed in men receiving androgen deprivation therapy for prostate adenocarcinoma. We herein present a case of de novo LCNEC: A 66-year-old male was incidentally diagnosed as LCNEC after he underwent transurethral resection of prostate. The stage was T4N1M1. Therefore, the patient was treated with 6 cycles of cisplatin and etoposide in the following 6 months, which achieved a partial remission. He gave up the chance to eradicate the residual mass. Three months later, the tumor progressed rapidly. In conclusion, LCNEC is a rare prostate cancer. Our experience shows that chemotherapy with etoposide and cisplatin is effective to achieve a significant remission. However, LCNEC is highly malignant in nature, postchemotherapy surgery for the residual mass should be considered.

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Objective: To investigate the incidence, management, and outcome of a liver abscess after transarterial embolization/chemoembolization (TAE/TACE) therapy for hepatocellular carcinoma (HCC). Materials and Methods: From May 2007 to May 2014, all patients complicated with liver abscess following TAE/TACE for HCC were identified and analyzed at four medical centers. Results: During the study period, a total of 6984 TAE/TACE procedures were performed among 3129 patients, and a total of 23 patients developed liver abscess with the incidence of 0.33% (23/6984) per procedure. There were 21 males and 2 females, and mean age of 52.1 ± 12.1 years. The mean interval from last TAE/TACE procedure to the diagnosis of liver abscess was 12.9 ± 6.6 days. All the patients received intravenous antibiotics, with ten patients had a percutaneous drain, one each for percutaneous aspiration and surgery. Complications related to the liver abscess were hepatorrhexis and pleural effusion (n = 1), pleural effusion (n = 1), and obstructive jaundice (n = 1), all of which were resolved after conservative treatments. The serum alpha-fetoprotein (AFP) levels were significantly reduced at 6 months after treatment (P < 0.01) in 15 patients whose AFP > 400 ng/mL preprocedure. Complete or partial tumor response at 6 months after TAE/TACE was achieved in three and twenty patients, respectively; and 6 months survival was 100%. Conclusions: The incidence of a liver abscess after TAE/TACE is low; antibiotics therapy along was successful in about half patients, and percutaneous abscess aspiration/drainage were necessary in large size abscess and severely symptomatic patients; the outcomes are benign without worsening of the progression of underlying HCC.

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Aim: Although routine screening contributes to substantial reductions in cervical cancer morbidity and mortality, the low specificity of HPV detection and limited sensitivity of cervical cytology necessitates the application of more optimized markers, such as the newly-introduced p16/Ki-67 dual-staining method. Here we reviewed several studies to evaluate the performance of this method in cervical cancer screening. Methods: An electronic database search was performed on PubMed, Web of Science, CNKI and Wanfang Database for studies assessing p16/Ki-67 dual immunostaining in the diagnosis of high-grade cervical intraepithelial neoplasm (HGCIN) with abnormal cytological morphologies. Two reviewers screened literatures, extracted data and assessed the quality of the included studies independently. Meta-analysis was performed using ReV. Man 5.2 and Meta-DiSc 1.2 software packages. Results: The absolute sensitivity of p16/Ki-67 dual staining for diagnosing HGCIN ranged from 80% to 94%, while the sensitivity of triage method with hrHPV testing ranged from 78% to 96%. The specificity of p16/Ki-67 testing and hrHPV detection for predicting absence of CIN2+ ranged from 39% to 79% and 15% to 44%, respectively. Quantitative meta-analysis showed that the pooled sensitivity of p16/ki-67 dual staining is 0.88 [95'CI (0.86-0.90)], the pooled specificity is 0.58 [95'CI (0.56-0.60)]. For hrHPV testing, the pooled sensitivity and pooled specificity is 0.94 [95'CI (0.93-0.96)] and 0.32 [95'CI (0.29-0.34)], respectively. Conclusions: p16/Ki-67 dual immunostaining had comparable sensitivity and improved specificity in screening HGCIN or CC when compared with hrHPV detection. Further studies may be beneficial to assess the efficacy of this novel biomarker, which can be potentially used as one of the initial screening assays.

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Objective: To investigate the efficacy of Shenfu injection (SFI) in reducing chemotherapy-induced adverse effects in nonsmall cell lung cancer (NSCLC) patients by conducting a meta-analysis. Methods: A systematic review of Cochrane Library, PubMed, Embase, CNKI, Chinese Biomedical Literature Database, VIP, and Wanfang Database was performed from their inception to December 2015. Eligible studies were randomized controlled trials (RCTs) comparing chemotherapy with or without SFI for patients with NSCLC. The main outcomes were improvement in chemotherapy-induced grade 3/4 marrow suppression (leukopenia, neutropenia, anemia, and thrombocytopenia) or gastrointestinal toxicities (nausea and vomiting, diarrhea, and constipation), quality of life, and T-lymphocytes subsets. Results: Sixteen RCTs involving 948 patients were identified. Compared with chemotherapy alone, SFI plus chemotherapy had lower 3/4 grade toxicity for leukopenia (risk ratio [RR] 0.34; 95% confidence intervals [95% CIs] 0.21–0.55), thrombocytopenia (RR 0.36; 95% CI 0.19–0.71), anemia (RR 0.39; 95% CI 0.16–0.99), nausea and vomiting (RR 0.29; 95% CI 0.14–0.58), and diarrhea (RR 0.21; 95% CI 0.07–0.63), Moreover, SFI plus chemotherapy significantly increased Karnofsky Performance Status (weighted mean difference 11.34; 95% CI 7.26–15.42). Conclusions: Adjuvant treatment with SFI improves the quality of life, attenuates the chemotherapy-induced gastrointestinal toxicities and bone marrow suppression, thus improving compliance to chemotherapy in patients with NSCLC. As for limited English literature about SFI and NSCLC, only trials publishing in the Chinese were included in the meta-analysis. More well-designed multicenter RCTs are needed before a definitive conclusion can be drawn.

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Background: Breast cancer is the first noticeable disease in female patients. Long-term use of soybean (Glycine max) may prevent the progression of cancer. However, the molecular mechanism for the functions of soybean remains unclear. Histone demethylase JMJD5, an important epigenetic molecule, is overexpressed in the progression of breast cancer suggesting that soybean may ameliorate cancer by affecting the expression of JMJD5. Materials and Methods: To test the hypothesis, human breast cancer cell lines MCF-7 and MDA-MB-231 were treated with different concentrations of soybean and/or transfected with the plasmids pcDNA3.1-JMJD5 and pTZU6 + 1-shRNA-JMJD5. The growth rate was measured using xCELLigence real-time cell analysis. The level of JMJD5 was measured by using quantitative reverse transcription-polymerase chain reaction and Western blot. Results: Soybean showed significant inhibitory effects on the growth rates ofMCF-7 and MDA-MB-231 cells in a concentration-dependent way (P < 0.05). Meanwhile, the levels of JMJD5 were reduced with the increase of soybean concentration (P < 0.05). JMJD5 transfection increased the growth rates of MCF-7 and MDA-MB-231 by 25% and 40%. In contrast, the growth rates of MCF-7 and MDA-MB-231 cells were decreased by 17% and 23% after being transfected with JMJD5 shRNA. Soybean inhibited the growth rate of MCF-7 and MDA-MB-231 cells when they were transfected by JMJD5 gene but no for the cells transfected with JMJD5 shRNA. Conclusion: The complicated compositions of soybean will be beneficial to the therapy of breast cancer since its causes may be involved in multiple aspects. Soybean represses breast cancer development by downregulating the level of JMJD5.

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Objective: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with significant morbidity and mortality among cancer patients who received cytotoxic chemotherapy. The aim of current study was to elucidate the prevalence of HBV and HCV among large population of solid cancers and lymphoma and to compare them with large number of control group. Patients and Methods: Between 2000 and 2014, 8322 cancer patients who were admitted to Oncology Departments were evaluated retrospectively and 3890 patients in whom hepatitis serology were available were included in this study. Their results were compared with control group that consisted of 96,000 subjects. Results: In control groups, hepatitis B surface antigen (HBsAg) positivity rate was 3.3% and anti-HCV positivity rate was 0.84%. In cancer patients, HBsAg positivity rate was 3.65% and anti-HCV positivity rate was 1.2%. Neither HBsAg positivity rate nor anti-HCV positivity rate was statistically significant between groups (P = 0.12 and P = 0.09, respectively). HBsAg positivity rates of head and neck cancer (5.88%; P = 0.02), rectum (5.6%; P = 0.025), and gastric and esophagus cancer (5.88%; P = 0.025) were significantly higher than control groups. Anti-HCV positivity rate (2.5%; P = 0.0016) was significantly higher in lung cancer when compared with control group. Conclusion: The current study elucidated the prevalence of HBV and HCV among large population of solid cancers and lymphoma and we showed that hepatitis B and C positivity rates are significantly increased in certain solid tumors. Our findings should also be clarified with large prospective studies.

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Introduction: Chronic inflammation predisposes to cancer. Cytokines play an essential role in cancer pathogenesis. Interleukin-6 (IL-6) is a pleiotropic cytokine that enables growth and differentiation of tumors. The effects of IL-6 are mediated by signal transducers and activators of transcription 3 (STAT3). STAT3 deficiency reduced tumor incidence and growth while STAT3 hyperactivation has an opposite effect; also it negatively regulates p53 gene. IL-6/STAT3 signaling is crucial in carcinogenesis linked to inflammation. Increased IL-6 levels are observed in cancer. Studies investigating the role of IL-6 is limited. Aim: This study aims at determining IL-6 levels in lung, oral, esophageal, and gallbladder cancer patients. Materials and Methods: Subjects consisted of 175 patients with lung, oral, gall bladder, and esophageal cancers. The patients included 68 females and 107 males with an average age of 52 years. Fifty healthy individuals served as controls. IL-6 was detected by electrochemiluminescent immunoassay principle. Results: IL-6 values were determined in 175 (21 lung, 55 oral, 17 esophageal and 82 gallbladder) cancer patients. Of these, 147/175 (18 lung, 43 oral, 13 esophageal and 73 gallbladder) cancer patients (84%) showed higher IL-6 levels as compared to control group (normal range: <7 pg/ml). Conclusion: This indicates a significant correlation between IL-6 overexpression and cancer development, highlighting the significance of IL-6 in oral, lung, esophageal, and gallbladder carcinomas. IL-6 may be used as a tumor marker for cancer diagnosis. It may be a clinically significant predictor and may represent a target for cancer treatment. However, to definitely conclude this, further extensive studies would be required.

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Objective: Studies have investigated expression status of galectin-3 (Gal-3), but very little is known about the importance of circulating Gal-3 in patients with breast cancer (BC). The purpose of the study was to investigate the clinical significance and potential diagnostic value of plasma Gal-3 levels in patients with BC. Materials and Methods: Fifty-two patients with BC and 35 age-matched healthy controls were enrolled. Levels of Gal-3 were investigated in BC patients and healthy controls. Gal-3 levels were determined using ELISA method. Results: Serum Gal-3 levels were significantly higher in BC patients than in controls (P = 0.002). Gal-3 levels did not significantly differ according to patients' statuses of lymph node involvement, hormone receptor, lymphovascular invasion, e-cadherin, menopausal, stage, serum hemostatic markers (prothrombin time, partial thromboplastin time, and international normalized ratio), platelet counts, mean platelet volume, lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 15-3 values (P > 0.05 for all). A cut-off value of Gal-3 to predict BC was determined at ≥3.17 ng/ml with a sensitivity of 75.0%, a specificity of 65.71%, a positive and negative predictive values of 76.5 and 63.9%, respectively (area under the curve: 0.705 [95% confidence interval, 0.598–0.798], P = 0.0002). Conclusion: Serum Gal-3 levels were significantly higher in BC patients and did not significantly differ according to clinical and tumoral characteristics of patients. Furthermore, there was no difference in Gal-3 levels between BC patients with and without metastatic disease. Serum Gal-3 levels can be used as an adjunct to other diagnostic or screening tests for BC regardless of clinical and tumoral characteristics of patients.

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Objective: To investigate the prevalence and characteristics of gemcitabine-based chemotherapy-induced thrombocytopenia in Chinese patients with nonsmall cell lung cancer (NSCLC). Materials and Methods: Medical records of 197 patients with histologically proven NSCLC received gemcitabine-based chemotherapy from June 2011 to June 2013 in our hospital were collected. The relative risk factors were identified and evaluated by univariate and multivariate analyses. Results: The incidence of gemcitabine-based chemotherapy-induced thrombocytopenia in these NSCLC patients was 85.8%. Between thrombocytopenia and nonthrombocytopenia patients, in patients with thrombocytopenia and thrombocytopenia, we found Stage III/IV patients got more probabilities for thrombocytopenia (P < 0.01). In addition, patients who received gemcitabine and cisplatin (GP) regimen resulted in more thrombocytopenia than gemcitabine and carboplatin (GC) and other regimens (P < 0.001). In addition, majority of the thrombocytopenia patients presented thrombocytopenia in their first cycle (P < 0.001). Whereas, other potential risk factors such as age, gender, performance status value, diabetes mellitus or not, and other underlying disease (hypertension and hepatopathy) were not showed such significance in this study. Further, the multivariate analysis revealed that stage (odds ratio [OR] 7.113, P < 0.01) and chemotherapy cycles (OR 0.543, P < 0.01) were also statistically significant independent risk factors for gemcitabine-based chemotherapy-induced thrombocytopenia. Conclusion: This study shows that thrombocytopenia is common in Chinese NSCLC patients receiving gemcitabine-based regimens. Chemotherapy cycles and stage might be the important factors influencing the occurrence of gemcitabine-based regimens-induced thrombocytopenia.

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Objectives: The objective was to study the mechanisms of oral squamous cell carcinoma (OSCC). Materials and Methods: We analyzed microarrays of GSE23558 and GSE25103. GSE23558 and GSE25103 were downloaded from Gene Expression Omnibus. GSE23558 included 27 OSCC samples, 4 independent and 1 pooled normal samples. GSE25103 included 112 OSCC samples and ten normal samples. The differentially expressed genes (DEGs) and the risk single nucleotide polymorphisms (SNPs) separately were obtained by limma package and plink software. Then, candidate disease genes were screened from the common genes of the genes carrying SNPs and the DEGs using Fisher's combination method. Using TargetMine online tool, potential functions of the candidate disease genes were analyzed by functional and pathway enrichment analyses. Besides, protein–protein interaction (PPI) network of these genes was constructed by STRING and Cytoscape software. Furthermore, modules of PPI network were screened by the ClusterONE. Results: We screened 2353 DEGs and 35635 risk SNPs in OSCC samples compared with normal samples. Moreover, CA9 was the most significant upregulated genes. There were 754 candidate disease genes, including 299 upregulated (e.g., VEGFC and FAT1) and 455 downregulated genes. For the candidate disease genes, the enriched functions were mainly in biological process categories. Importantly, FN1 (degree = 42) and CCNA2 (degree = 38) had high degrees in the PPI network. Furthermore, FN1 and CCNA2 were separately involved in module 1 and module 2 of the PPI network. FN1, CCNA2, CA9, VEGFC, and FAT1 might affect OSCC. Conclusion: In general, our study obtained important genes implicated in OSCC.

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Context: Methotrexate (MTX) is a cytotoxic chemotherapeutic element for various inflammatory diseases. The cytotoxic effect of MTX is also seen in normal tissues having a high proliferation rate including gastrointestinal and bone marrow. Aims: The aim of this study was to find out whether oxidative damage could be relevant for MTX-induced toxicity in vivo using Wistar rats and to investigate the preventive potential of cactus cladodes. Materials and Methods: Adult and healthy male Wistar rats (200–250 g) were pretreated by ethanol fraction of cactus cladodes. Following a single dose of MTX (20 mg/kg), either vehicle (saline) or ethanolic (400 mg/kg) was administered intraperitoneally. All animals were killed 24 h after the intraperitoneal injection of MTX. Small intestine samples were collected for malondialdehyde (MDA) level, protein carbonyl generation, and peroxidase and catalase (CAT) activity measurement. The small intestine was also collected for histopathology analysis. Statistical Analysis Used: Each experiment was conducted in triplicate separately. Values were presented as a mean ± standard deviation. Differences were considered significant at P < 0.05. Results: Our results showed that MTX-induced significant alterations in oxidative stress markers noticed in the form of intestinal tissues damage, MDA level increased and protein carbonyls generation. CAT and peroxidase activities decreased with MTX administration. The combined treatment of MTX with cactus extracts showed a reduction of MTX-induced oxidative damage. Conclusions: It could be concluded that cactus cladodes extract was effective in protecting the small intestine against MTX-induced damage.

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Recurrent medulloblastoma has a very poor prognosis in children regardless of the treatment employed. We report the case of a 3-year-old child with recurrent refractory medulloblastoma who was treated with both bevacizumab and stereotactic radiosurgery (SRS). The boy was found to harbor a tumor in the cerebral posterior fossa in November 2010. Craniotomy was performed to remove the tumor completely. Postoperative pathological examination showed desmoplastic medulloblastoma. Craniospinal radiotherapy and chemotherapy were performed. Three years later, the boy suffered from constant headache again. Magnetic resonance imaging showed seeding of medulloblastoma in the posterior fossa as four masses with diameter ranging from 2 cm to 3 cm. To avoid overdose radiation, we used SRS and anti-angiogenesis therapy. Bevacizumab was given at 10 mg/kg for four times with an interval of 1 month. Gamma Knife (Leksell Gamma Knife^®, Elekta Instruments, Stockholm, Sweden) was used targeting at one lesion each time and performed for consecutive two times with bevacizumab therapy. Following this combined treatment, the lesions targeted with radiosurgery showed complete response with minimal toxicity in <1 month successively. The combined use of bevacizumab and SRS may represent a novel treatment against medulloblastoma in patients who are not surgical candidates, and should be investigated further. This is the first documented case of medulloblastoma treated with bevacizumab and SRS. Further clinical trials should be considered to evaluate the effectiveness of this strategy.

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Aim of Study: To investigate the apoptotic event of trichostatin A (TSA) and its associated mechanism in oral squamous cell carcinoma (OSCC) lines. Materials and Methods: HSC-3 and Ca9.22 cell lines were evaluated using a trypan blue exclusion assay, histone isolation, soft agar assay, live/dead assay, 4%,6-diamidino-2-phenylindole staining, JC-1 mitochondrial membrane potential (MMP) assay, and Western blot analysis to demonstrate the anticancer activity of TSA. Results: TSA decreased OSCC cell viability and proliferation without affecting the histone acetylation. TSA-induced caspase-dependent or -independent apoptosis according to cell types, TSA enhanced the expression levels of Bim protein by dephosphorylating ERK1/2 pathway in HSC-3 cells. TSA also damaged MMP and increased cytosolic apoptosis-inducing factor (AIF) in Ca9.22 cells. Conclusion: The present study suggests that TSA may be a potential anticancer drug candidate for the treatment of OSCC through the induction of apoptosis.

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Aim of Study: Recent studies have suggested neprilysin (NEP) play a key role in cigarette smoke-induced nonsmall-cell lung carcinoma; however, the detailed mechanism was still unclear. Here, we employed in vitro human bronchial epithelial BEAS-2B cells to investigate whether and how NEP involved in cigarette smoke condensate (CSC)-induced cancer occurrence. Materials and Methods: In vitro MTT and transwell assay was applied. Live cell imaging and staining were also employed. Results: In vitro data showed that CSC could increase BEAS-2B cell migration while NEP shRNA could block CSC-induced BEAS-2B cell hypermigration. By biotination and live cell staining, we found that after CSC treatment, cell surface NEP was increased while internalization trafficking was shifted from late endosome/lysosome pathway to recycling pathway. Finally, we found that surface NEP could bind to p120 catenin (p120ctn) for lysosome destination turnover while CSC treatment could change p120ctn membrane/cytosome distribution. Loss of p120ctn will subsequently change NEP trafficking and finally, increase its membrane distribution with a phenocopy manner as CSC. Conclusion: These data indicated under CSC treatment; losing of membrane p120ctn could upregulate surface NEP protein level and thus facilitate BEAS-2B cell migration.

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Choriocarcinoma syndrome is a life-threatening lysis syndrome caused by blood vessel rupture and subsequent tumor bleeding. We describe a case of pretreatment choriocarcinoma syndrome that developed in a 27-year-old man. He underwent a high orchiectomy at a local hospital and was diagnosed with metastatic testicular tumor given the high serum human chorionic gonadotropin levels (943,601 mIU/mL). Thus, he was referred to our institution. Although he had bulky lung metastases and alveolar bleeding, we were able to administer full-dose chemotherapy with etoposide and cisplatin. On day 3 of chemotherapy, he presented with severe hypoxia and worsening of alveolar bleeding. Thus, he underwent tracheal intubation at the Intensive Care Unit. Full-dose chemotherapy was continued, and the patient was extubated upon improvement. He is currently alive and continuing treatment at another hospital.

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Objective: The association between asthma and the risk of prostate cancer remains elusive. We aimed to evaluate the relationship between asthma and the onset of prostate cancer. Methods: We searched PubMed, Embase, and Cochrane databases for articles that assessed the association of asthma with the risk of prostate cancer through October 2015. We extracted odds ratio (OR) and calculated the corresponding 95% confidence interval (CI). We used random-effects models to calculate a pooled association between asthma and the risk of prostate cancer. Results: Fourteen studies were involved in the assessment of the association between asthma and prostate cancer risk. Asthma was not associated with the risk of prostate cancer in overall populations (OR 0.994, 95% CI 0.836–1.182), Caucasians (OR 0.922, 95% CI 0.825–1.030), and Asians (OR 5.022, 95% CI 0.415–60.793). The cumulative analysis also suggested a lack association between asthma and the risk of prostate cancer. Exclusion of any single study did not change the results significantly. No evidence of marked publication bias was observed. Conclusions: Our investigation indicated that asthma was not associated with prostate cancer risk in overall populations, Caucasians, and Asians.

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Malignant melanoma (MM) has a high potential of lymphatic and hematogeneous spread, and metastatic disease is always incurable with a high mortality. We present a rare phenomenon of MM metastasizing to the palatine tonsil.

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Acute myeloid leukemia has a rare subtype in French-American-British classification as M7 or acute megakaryoblastic leukemia. Chromosome abnormalities in cases with acute megakaryoblastic leukemia can affect their prognosis. Evaluation of these abnormalities and their impact are not fully elucidated. This case presentation is about 16 months female who has a rare abnormality (trisomy 3) alongside acute megakaryoblastic leukemia. The remarkable point is that her malignancy is as primary or non-Down syndrome acute megakaryoblastic leukemia. The author's suggestion through this case presentation is the necessity of drawing a cytogenetic profile, especially in cases with acute megakaryoblastic leukemia for better treatment strategies.

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Low-grade myofibroblastic sarcoma (LGMS) is a malignant tumor with myofibroblastic differentiation, which frequently occurs in the oral cavity and extremities. Here, we report a case of LGMS of the pancreas in a 44-year-old female presented to our hospital with recurrent upper abdominal pain. Computed tomography revealed a low-density solid tumor at the body of the pancreas. Distal pancreatectomy combined with splenectomy was performed. LGMS of the pancreas was diagnosed by the histological features together with immunohistochemical findings. The patient received adjuvant chemotherapy after surgery and remained asymptomatic for 5 years. Previous studies and our experience suggested that surgical excision with wide margins is the reasonable treatment of LGMS and adjuvant therapy may improve its prognosis.

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Aim of the Study: Although surgery is considered to be curative treatment, recurrence rates are high in gastric cancer. Adjuvant 5-fluorouracil (5-FU) based chemoradiotherapy has been shown to improve the prognosis. We compared tolerability and efficacy of the two different chemotherapy regimens; 5-FU/leucovorin (LV) versus cisplatin with capecitabine (XP) combined with radiotherapy (RT) in the adjuvant therapy of the lymph node positive locally advanced gastric cancer. Materials and Methods: Totally, 104 patients who underwent curative surgery with lymph node resection were evaluated, respectively. Patients were stratified two group based on the adjuvant chemoradiotherapy regimen. Group 1 (n = 46) received XP followed capecitabine with RT (XRT) then XP. Group 2 (n = 58) received 5-FU/LV combined with RT postoperatively. Two groups were compared based on clinicopathological parameters. Factors related with disease-free survival (DFS) and overall survival (OS) were analyzed. Results: Totally, 32 patients had recurrent disease, and there was no difference between two groups. While peritoneal metastasis was more common in XP arm, distant metastasis was commonly seen in 5-FU/LV arm. There was no significant difference between two groups in regard of Grade 3/4 toxicitis; hematologic toxicities were more in 5-FU/LV group than XP arm. In addition, dose modification because of toxicities were more frequent in 5-FU/LV arm (P = 0.003). For all groups, lymph node dissection type was related with DFS, surgical margin and recurrence were important for OS. Conclusion: XP-XRT regimen is well tolerated with lower toxicity compared the standard 5-FU/LV-RT. Although there is no difference with respect to outcome, patients with XP arm without the necessity of intravenous catheter admitted hospital less frequent than bolus5-FU/LV arm.

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Hemangioma of bone is a rare bone tumor accounting for <1% of all osseous tumors. Hemangiomas are common in skull and vertebrae but uncommon in rib. Rib hemangiomas may increase in size over a period and may cause symptoms due to increasing size. Preoperative diagnosis is not always possible due to overlapping radiological features between benign and malignant lesions. Use of preoperative aspiration and biopsy has their own risks and benefit. Excision of rib in case of monostotic rib lesions is the treatment of choice due to low risk of recurrence and no reported postoperative complications. We report a case of rib hemangioma which mimicked a malignancy preoperatively.

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Context: Pancreatic cancer in a common tumor in our country for which there are various treatment alternatives. Objective: Evaluate the effectiveness and safety of nab-paclitaxel and gemcitabine in everyday clinical practice. Settings and Design: Observational, retrospective study at a tertiary university hospital. Subjects and Methods: We included patients diagnosed of metastatic or locally advanced pancreatic cancer that were being treated with nab-paclitaxel and gemcitabine. We recorded response, progression-free survival (PFS), and overall survival (OS) rates together with toxicities. Statistical Analysis Used: We used SPSS program for Windows. We conducted descriptive statistics using averages, medians, standard deviations or ranges, and percentages. Results: We included 15 patients. At 3 months, there were no complete responses; 20% showed partial responses, and in 60% of patients, the disease stabilized. The median PFS was 8.9 months and the OS was 9.6. The most important adverse reactions were neutropenia, fatigue, and nausea/vomiting. Conclusions: The treatment regimen leads to increased survival in these patients with an acceptable toxicity profile.

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Ectopic extrarenal renin-producing tumor is a rare disease with approximately 30 case reports in English literature. We herein present the first case of renin-producing germ cell tumors in the pineal apparatus and mediastinum. A 26-year-old man who had undergone craniotomy for the treatment of pineal tumor was found to have hypertension at a regular visit postoperatively. Laboratory findings revealed high plasma levels of renin activity and that of aldosterone concentration. Chest computed tomography demonstrated a large tumor in the mediastinum. The pathological findings revealed the mediastinal germ cell tumor positive for renin. The present case suggests that for young patients presenting with hypertension with a mediastinal tumor, the possibility of a renin-producing tumor should be considered.

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Background: Embelin is an active compound identified as a novel X-linked inhibitor of apoptosis protein (XIAP) inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anticancer activities. However, the therapeutic effect of Embelin to human osteosarcoma is not yet determined. Objectives: In this study, we evaluated the sensitizing potential of Embelin on promoting apoptosis to cause osteosarcoma cell death and inhibiting its invasion. Methods: We uesd 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to detect the survival rates of osteosarcoma cells, Western blot to detect the expression of proteins in U-2 OS and MG63 cells, and fluorescence microscope to observe the morphology of apoptotic cells. Results: The survival of osteosarcoma cells decreased, When Embelin was used. Obvious condensed and flared fluorescence was observed, when used high-dose Embelin. There was an increase of caspase-3, cleaved caspase-3, caspase-8, and caspase-9 in Embelin group, while PI3K, AKt, p-AKt, X-linked inhibitor of apoptosis protein, and MMP-9 were downregulated. The invasion of Embelin application was significantly lower than that of the control application. Conclusion: Embelin promoted apoptosis via XIAP and PI3K/Akt signaling pathway. XIAP inhibitor Embelin inducing apoptosis could cause osteosarcoma cell death and inhibit its invasion.

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Objective: Although proteinuria has been increasingly reported in lung cancers, especially small cell lung cancer (SCLC), its clinical impact in patients with SCLC remains unknown. Materials and Methods: We analyzed patients with newly-diagnosed SCLC confirmed by clinical, radiological, and pathological features over a 7-year period. Pretreatment proteinuria was assessed by quantitative analysis of 24-h urine before receiving chemotherapy. The demographic, laboratory characteristics and its impact on survival outcome were evaluated. Results: There were 140 SCLC patients with the mean age of 70.2 years, extensive stage (89.3%), and male predominance (81.4%). Significant proteinuria (>300 mg/day) occurred in 17.4% (24/140) patients. Patients with proteinuria had significant higher serum blood urea nitrogen, lower total calcium, total protein, albumin levels, and lower creatinine clearance (Ccr) (24-h Ccr). Daily protein excretion was negatively correlated with serum total protein, albumin, and Ccr. Using a multivariable Cox proportional hazard model, proteinuria (hazard ratio, 1.943, 95% confidence interval 1.148–3.259, P = 0.010), along with poor performance status and serum albumin, were independent risk factors of all-cause mortality. Proteinuria was also associated with poor survival status (6.08 vs. 11.88 months, P < 0.001), especially in those who had severe proteinuria (>2 g/day). Conclusions: Proteinuria is not uncommon and associated with all-cause mortality in patients with SCLC.

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Objective: Conflicting data have been reported regarding the association between perioperative blood transfusion (PBT) and clinical outcomes for prostate cancer patients. We conducted a systematic review and meta-analysis to evaluate the impact of PBT on cancer survival and recurrence for patients who underwent radical prostatectomy (RP). Methods: A systematic review of PubMed, EMBASE, and Cochrane libraries was performed to identify all eligible studies that evaluate the association between PBT and clinical outcomes for prostate cancer patients undergoing RP. The analyzed outcomes were overall survival (OS) and recurrence-free survival (RFS) at 3, 5, and 10 years. Results: A total of eight articles met our criteria. Meta-analysis indicated that prostate cancer patients with PBT had decreased OS (hazard ratio [HR] =1.51, 95% confidence interval [CI], 1.22–1.85, P < 0.01; HR = 1.57, 95% CI, 1.33–1.85, P < 0.01; HR = 1.55, 95% CI, 1.03–2.33, P = 0.04) and RFS (HR = 1.67, 95% CI, 1.37–2.04, P < 0.01; HR = 1.42, 95% CI, 1.23–1.63, P < 0.01; HR = 1.37, 95% CI, 1.03–1.83, P = 0.03) at 3, 5, and 10 years after surgery compared with those without PBT. Conclusions: The findings from the current meta-analysis demonstrate that PBT was associated with adverse survival and recurrence outcomes for prostate cancer patients undergoing RP.

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Purpose: This study assessed whether our enhanced recovery after surgery (ERAS) program for distal pancreatectomy (DP) is safe and feasible. Patients and Methods: The subjects were patients who underwent consecutive DP between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization, and 30-day readmission rate. Our ERAS program included 12 elements (4 preoperative elements, 3 intraoperative elements, and 5 postoperative elements). Results: A total of 44 patients were studied. The overall incidence of morbidity was 29.5%, the incidence of mortality was 0%, and the incidence of readmission was 0%. Four preoperative elements and 3 intraoperative elements seemed feasible. Among the 5 postoperative elements, 4 elements seemed feasible, accounting 90%< performance rate however the early removal of catheters and drain seemed not feasible. The median postoperative hospital stay was 14 days (range: 8–39 days). The median postoperative hospital stay was 13 days (range: 8–27 days) in patients without postoperative complications while the median postoperative hospital stay was 26 days (range: 14–39 days) in patients with postoperative complications. Conclusion: This study results suggested that our ERAS program is safe and feasible in patients who undergo DP. However, achieving compliance on the postoperative element, especially the removal of catcher and drain, was more challenging.

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Objective: The aim of this is to compare the immunotherapeutic effects of human colorectal cancer antigen GA733-2 fused to the Fc fragment of antibody (GA733-2-Fc) and to Fc and endoplasmic reticulum (ER) retention motif KDEL (GA733-2-Fc-KDEL). Materials and Methods: Recombinant GA733-2-Fc and GA733-2-Fc-KDEL were produced from infiltrated Nicotiana benthamiana leaves and purified by affinity chromatography. Glycan structures were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The allergic and immunogenic responses of recombinant GA733-2-Fc and GA733-2-Fc-KDEL were estimated in an intraperitoneally immunized mouse. The tumor regression effect of recombinant GA733-2-Fc and GA733-2-Fc-KDEL was examined using a colorectal carcinoma CT-26 animal model. Results: Recombinant GA733-2-Fc contained plant-specific glycan structures including β(1,2)-xylose and α(1,3)-fucose whereas recombinant GA733-2-Fc-KDEL contained oligomannose type glycan structures. Mice immunized intraperitoneally with recombinant GA733-2-Fc and GA733-2-Fc-KDEL elicited strong GA733-2-Fc-specific immunoglobulin G (IgG) and IgA serum antibody responses. Recombinant GA733-2-Fc-KDEL reduced the production of GA733-2-Fc-specific IgE. Recombinant GA733-2-Fc-KDEL increased the production of interferon-γ. Intraperitoneal preimmunization with recombinant GA733-2-Fc and GA733-2-Fc-KDEL regressed tumor growth in a colorectal carcinoma CT-26 animal model. The tumor regression effect induced by recombinant GA733-2-Fc-KDEL was greater than that induced by recombinant GA733-2-Fc. The human and mouse colorectal carcinoma cell binding activities of recombinant GA733-2-Fc-KDEL-immunized sera were higher than those of recombinant GA733-2-Fc. Conclusions: Our results suggest that GA733-2-Fc conjugated to ER-retention motif KDEL is a more efficient antigen to prevent tumor growth induced by colorectal carcinoma and minimize an allergic response.

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Aim of Study: NM23, as a possible biomarker of prognosis in malignant tumors, has generated remarkable interest in this critical period of the high morbidity and mortality of malignancies. Thus, we launched this meta-analysis to investigate the predictive value of NM23 expression in patients with gastric cancer. Materials and Methods: We searched PubMed, Embase, and Web of Science for relevant articles. The pooled odds ratios (ORs) and corresponding 95% confidence interval (CI) were calculated to evaluate the prognostic value of NM23 expression in patients with gastric cancer and the association between NM23 expression and clinicopathological factors. We also performed subgroup analyses to find the source of heterogeneity. Results: Exactly, 2674 patients were pooled from 19 available studies in total. The incorporative OR combined by 11 studies with overall survival (OS) showed no significance (OR = 0.90, 95% CI: 0.51–1.58, P = 0.71). Although we failed to find any significance in N status and tumor node metastasis (TNM) staging (P = 0.23 and P = 0.74, respectively), elevated NM23 expression was related to well tumor differentiation (OR = 0.62, 95% CI: 0.41–0.95, P = 0.03). However, in the subgroup analyses, we could not find any potential source of heterogeneity. Conclusion: The results showed that statistically significant association was found between NM23 expression and the tumor differentiation of patients with gastric cancer, but no significance was found in OS, N status, and TNM staging. More and further researches should be conducted to reveal the prognostic value of NM23.

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Objective: Annexin A1 (ANXA1), a calcium-dependent phospholipid binding protein, is known to be regulated by microRNA-196a (miR-196a) in esophageal adenocarcinoma, and its high expression in tumor tissue is correlated with the poor prognosis of esophageal squamous cell carcinoma (ESCC). However, the role of ANXA1 in the serum of patients with ESCC remains unclear. Materials and Methods: In this study, we used enzyme-linked immunosorbent assay to evaluate the levels of ANXA1 and real-time polymerase chain reaction to detect the expression of miR-196a in the serum of ESCC patients (healthy donors as controls) and evaluated the relationship between ANXA1 and clinical outcomes. Results: The results showed that the level of serum ANXA1 in ESCC patients was significantly lower than that in controls (P = 0.001) but increased after chemoradiotherapy (P = 0.001). There was no correlation between the baseline level of serum ANXA1 and the short-term efficacy of treatment (P = 0.26) as well as the 1-year progression-free survival (PFS) (P = 0.094). However, there existed a significant correlation between the increases of serum ANXA1 expression and the 1-year PFS (P = 0.04). A higher increase (>2-fold of baseline) in the serum ANXA1 levels was correlated with a poorer PFS (hazard ratio = 3.096, 95% confidence interval 1.239–7.861). There was an inverse correlation between the expressions of miR-196a and ANXA1 in serum (Pearson's correlation of –0.54, P = 0.021). Conclusion: Our data revealed that the expression of serum ANXA1 in ESCC patients increases after chemoradiotherapy and the increased fold change in serum ANXA1 confers independent negative prognostic impact in ESCC. The higher the increase in serum ANXA1 levels, the poorer the outcome.

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Context: Proper preoperative staging is vital in the treatment of breast cancer patients. Fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and conventional diagnostic modalities including ultrasonography (US), mammography (MG), and magnetic resonance imaging (MRI) play a greater role. Aims: To evaluate the diagnostic accuracy of FDG-PET in detecting primary breast cancer as compared with US, MG, and MRI, and in axillary lymph nodes (ALNs) staging in Chinese women. Settings and Design: It is a study of diagnostic accuracy. Subjects and Methods: Thirty-one female patients, with biopsy established breast carcinoma, were recruited and analyzed retrospectively. All patients underwent ¹⁸F-FDG-PET, MG, US, and MRI. FDG-PET/CT for the diagnosis of primary breast cancer and detecting ALNs metastases were compared with MG, US, and MRI. Statistical Analysis Used: Sensitivity, specificity, positive-predictive value (PPV), and negative-predictive value (NPV) of FDG-PET imaging for primary breast cancers and ALN staging were analyzed using standard statistical analyses. Results: In 31 patients with cytologically established invasive breast carcinoma, the sensitivities of US, MG, MRI, and FDG-PET/CT were 90% (28/31), 84% (26/31), 97% (30/31), and 94% (29/31), respectively. The sensitivity, specificity, overall accuracy, PPV, and NPV of US, MRI, and FDG-PET/CT in ALN staging (maximum standardized uptake value cutoff at 1.5) were 80%, 86%, 84%, 80%, and 90%; 90%, 95%, 94%, 90%, and 95%; and 90%, 86%, 87%, 90%, and 95%, respectively. Conclusions: US and MRI should remain the first line for the diagnosis of breast cancer. Both MRI and FDG-PET/CT could accurately diagnose the primary breast cancer and stage the axilla lymph nodes, but further large population study is needed.

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Purpose: Pyruvate kinase M2 (PKM2) was found overexpressed in tumor cells and played a significant role in tumor formation and growth. We sought to explore the correlation of PKM2 expression with cell proliferation, invasion, and apoptosis in bladder cancer cell line. Materials and Methods: Real-time polymerase chain reaction and Western blot were performed to determine the expression level of PKM2 at mRNA and protein level. MTT and flow cytometry were respectively used to explore the proliferation, invasion, and apoptosis in bladder cancer cell line in vitro. Results: The results suggested that suppression of PKM2 significantly decreased the proliferation rate, invasive cell number, and migration ability of bladder cancer cells compared with blank group. Moreover, proteins such as MMP2 and MMP9 as well as P38 expression were also affected by the PKM2 expression changes. These results proved that PKM2 could be involved in the progression of bladder cancer by mitogen-activated protein kinases signaling pathway. Conclusion: The data presented in this study revealed that PKM2 up-regulation may promote the development and metastasis of bladder cancer through promoting cell proliferation, migration and invasion via MAPK signal pathway.

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Context: Results from recent molecular epidemiologic studies suggest that the timeless genes play a role in tumorigenesis, possibly by influencing cell cycle or other pathways relevant to cancer. Aims: The aim of this study was to explore the expression level of the timeless gene in human glioma. Subjects and Methods: Using immunohistochemical staining, methylation-specific polymerase chain reaction techniques, we examined the expression of the timeless gene in 94 gliomas. Statistical Analysis Used: The association between tumor grade and expression of the investigated proteins was assessed using the Spearman, Chi-square test, and two-sample t-test, included in the Statistical Package for the Social Science, version 13.0. Results: The expression levels of timeless mRNA in high-grade glioma were significantly different from the surrounding nontumor tissues (P < 0.01). The difference in the expression of timeless in low-grade gliomas and the surrounding nonglioma tissues was insignificant (P > 0.05). The intensity of immunoactivity for TIMELESS in high-grade gliomas was significantly higher than that of low-grade gliomas (r = −0.403, P = 0.012 < 0.05), nontumor tissues around high-grade gliomas (r = −0.376, P = 0.027 < 0.05), whereas there was no difference in the intensity of immunoactivity for TIMELESS between low-grade gliomas and the surrounding nontumor tissues (P > 0.05). Conclusions: The expression of timeless in high-grade gliomas was significantly higher than that of the low-grade gliomas and nonglioma. Therefore, we suggest that disturbances in timeless expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells and promoting carcinogenesis.

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Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Aim: To investigate the mechanisms of paclitaxel resistance in hepatocellular carcinoma cells and find promising molecular target for HCC therapy. Materials and Methods: To investigate the effects of FHL1 on chemo resistance in HCC cells, we generated FHL1 knock-down stable cell lines with HepG2 and SMMC7721 cells. Cell viability assay, colony formation and xenograft experiments assay were performed to detect effect of FHL1 on Paclitaxel or Oxaliplatin resistance in vitro and in vivo. Caspase activity assay was performed to explore the activation of caspase-3 and caspase-9 in paclitaxel treated FHL1-knockdown HepG2 cells. Result: In the present study we have investigated that four-and-a-half LIM protein 1 (FHL1), which plays an important role in the development of cancer, is associated with both the chemo resistance of hepatocellular carcinomas cells in vitro and in vivo. Knockdown of FHL1 significantly enhanced the sensitivity of paclitaxel, but had no effects on sensitivity of oxaliplatin. Moreover, knockdown of FHL1 promoted the activation of caspase-3 and caspase-9, which were induced by paclitaxel. Interestingly, FHL1 negatively regulates the chemo resistance of HCC in xenografted nude mice. Conclusion: FHL1 promote paclitaxel resistance in hepatocellular carcinomas cells through regulating apoptosis induced by paclitaxel, suggesting that FHL1 may be a promising molecular target for HCC therapy.

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Primitive neuroectodermal tumor (PNET) is an exceedingly rare type of malignant tumor. The diagnosis of pancreatic PNET is usually challenging for radiologists and surgeons, especially when an accurate preoperative diagnosis is needed. Herein, we report a case of a 36-year-old patient with a mass diagnosed as PNET in the head of the pancreas and present a literature review. Compared to previous literature reports, there were some imaging features observed by computed tomography (CT) in our case that might be helpful for a relatively accurate preoperative diagnosis. PNET should be considered preoperatively for soft-tissue neoplasms of the pancreas when the diagnosis of more common pancreatic tumors is not favored by signs in CT, especially in pediatric and adolescent populations. This case is the 20^th case of pancreatic PNET reported in literature.

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In general, paragangliomas are symptomatic tumors, which may be clinically taken for other tumors, benign or malignant lesions. Paragangliomas of the nasal cavity and paranasal sinuses are an extremely rare entity and what is even rarer is its association with ectopic adrenocorticotropic hormone production. We report this very rare case to highlight the rare association of Cushing's syndrome with nasal paraganglioma and the importance of total surgical resection in its treatment.

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Context: Survivin is an antiapoptotic protein with a role in tumorigenesis and suggested prognostic value in several proliferative diseases. Aims: This study aimed to examine the role of survivin as a prognostic marker in pancreatic adenocarcinoma (PDAC). Settings and Design: Fifty-one specimens of PDAC were assessed for survivin expression by immunohistochemistry. Subjects and Methods: Overall survival and 1-, 3-, and 5-year survival were retrieved retrospectively. Statistical Analysis Used: Bivariate analysis was conducted using Chi-square and Mann–Whitney U tests, while survival analysis was conducted using Kaplan–Meier statistics. Results: Of the 51 assessed cases, 49% were positive for survivin. Survivin expression was significantly correlated 1-year survival and overall survival, particularly in bcl-2 positive cases. Conclusions: Survivin may be implicated in the bcl-2 and p53 pathways and therefore in the biology of PDAC. Its potential use as a survival predictor and therapeutic target represent a promising field.

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Aims: Several studies suggested that diabetes mellitus (DM) was associated with the risk of glioma. However, other studies did not confirm the result. Therefore, I conducted this meta-analysis. Materials and Methods: I retrieved the PubMed, Embase, and Web of Science database, by adopting keywords “glioma,” and “diabetes,” “DM.” The strength of the associations between DM and the risk of glioma was measured by odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: Ten relevant studies were identified in the final analysis. A statistically significant association between DM and glioma risk was fond (OR = 0.84; 95% CI, 0.73–0.97; P = 0.02). In the subgroup analysis of age group, young population with DM showed decreased glioma risk (OR = 0.83; 95% CI, 0.70–0.98; P = 0.02), whereas old population with DM did not show a significant association (OR = 0.87; 95% CI, 0.65–1.16; P = 0.34). In the subgroup analysis of gender, male patients with DM showed decreased glioma risk (OR = 0.82; 95% CI, 0.68–0.99; P = 0.04), whereas female population with DM did not show a significant association (OR = 0.93; 95% CI, 0.70–1.24; P = 0.63). Conclusions: This meta-analysis suggested that DM may be associated with the reduced glioma risk.

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Thyroid abnormalities are found nearly 70% cases receiving sunitinib therapy. Mostly, patients suffer transient hypothyroidism rarely presents with overt acute symptoms requiring levothyroxine replacement. Onset is variable in published literature. We report a case of metastatic gastrointestinal stromal tumor receiving sunitinib with normal baseline thyroid function. The patient developed symptoms of acute severe hypothyroidism with high thyroid stimulating hormone level on the 4^th week of therapy. The patient responded with oral levothyroxine. clinical and biochemical parameter resolved rapidly. Patient receiving sunitinib warns baseline and subsequent surveillance of thyroid function (both clinical and biochemical). This rare dreadful condition reverts promptly with thyroxine replacement.

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Aims: Tat-interacting protein 30 (TIP30), a transcriptional repressor, possesses antitumor effect in different cancer cells. However, little is known about the function of TIP30 in bladder cancer till now. Materials and Methods: A TIP30-overexpressing plasmid was transfected into the bladder cancer cells (T24). The cell cycle and apoptosis were detected by flow cytometry. The cell proliferation was analyzed using the cell counting kit-8 assay. The migrative and invasive abilities of T24 cells were measured by the transwell assay. The expression of TIP30, cell cycle proteins, migration-related proteins, and cell apoptosis-related proteins was assessed by Western blotting. Results: The cell proliferation, migration, and invasion of T24 cells were inhibited by overexpression of TIP30. Moreover, the rate of cell apoptosis was increased by the overexpression of TIP30. The expression of cell cycle proteins, phosphorylated EGFR, p-Akt, Bcl-2, cyclin D, cyclin E), migration-related proteins (matrix metalloproteinases 2 [MMP2], MMP6, MMP9), were downregulated, and cell apoptosis-related proteins (bax, cleaved caspase3) were upregulated. Conclusions: These results suggest that TIP30, as a tumor suppressor in the bladder cancer, might be served as a target in cancer therapies in the future.

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Objective: The objective of this paper was to reveal hub pathways in primary mediastinal B-cell lymphoma (PMBL) based on multiple pathway crosstalk networks (PCNs) and give insight for its pathological mechanism. Materials and Methods: Based on gene expression data, pathway data and protein-protein interaction data, background PCN (BPCN) and tumor PCN (TPCN) of PMBL were constructed. The rank product algorithm was implemented to identify hub pathways of BPCN and TPCN. Finally, topological properties (degree, closeness, betweenness, and transitivity) of hub pathways were analyzed. Results: For BPCN, there were three hundred nodes and 42,239 edges, and the pathway pairs had great overlaps. TPCN was composed of 281 nodes and 12,700 cross-talks. A total of five hub pathways were identified, nonalcoholic fatty liver disease (NAFLD), tuberculosis, human T-lymphotropic virus type-I (HTLV-I) infection, hepatitis B, and Epstein–Barr virus infection. The topological properties for them were different from each other, further between PMBL and normal controls. Conclusion: We have identified five hub pathways for PMBL, such as NAFLD, HTLV-I infection, and Hepatitis B, which might be potential biomarkers for target therapy for PMBL.

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Introduction: Scutellaria baicalensis is commonly used in Asia as an herbal medicine to treat a variety of ailments, including cancer. Wogonoside, one major constituent of S. baicalensis, can be primarily converted to wogonin through deglycosylation via enteric microbiome metabolism. Materials and Methods: The antiproliferative effects of the glycoside (wogonoside) and its deglycosylated compound (wogonin) on a panel of human cancer cell lines from the most common solid tumors were evaluated using the MTS colorimetric assay. Cell cycle and apoptosis were determined using flow cytometry. Enzymatic activities of caspases were measured, and the interactions of wogonin and caspases were explored by a docking analysis. Results: Wogonoside did not have obvious antiproliferative effects on the cancer cells. In contrast, wogonin showed significant antiproliferative activities on all the tested cancer cells. Wogonin arrested the cells in the G1 phase and significantly induced cell apoptosis. The compound also activated the expression of caspases 3 and 9. The docking results suggest that the compound forms hydrogen bonds with Phe250 and Ser251, and π–π interactions with Phe256 in caspase 3, and with Asp228 in caspase 9. Conclusions: After wogonoside deglycosylation, wogonin significantly enhanced its anticancer potential as a potent anticancer compound derived from S. baicalensis.

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