In recent years, cancer has become the most common human disease worldwide, and great attentions have been paid to clarifying the carcinogenesis and identifying new effective antitumor therapy. Although great progress has been made in this research field, human malignant diseases could still not be radically cured. Thunder god vine is a herbal medicine, which has proved to exert efficient antitumor activity in various human cancers such as lung cancer, pancreatic cancer, and colon cancer. In vivo and in vitro experiments showed that thunder god vine extract triptolide could inhibit tumor cell proliferation, cell migration, and cell invasion. Here, we overviewed the functional role of triptolide in human malignancies and its promising therapeutic potential in treating such deadly diseases.

Objectives: To study the transforming growth factor beta (TGF-β) signaling pathway in interactions with estrogen receptor alpha (ERα) signaling pathway mediating the growth of human uterine leiomyoma (UL) activated by phenolic environmental estrogens (EEs). Methods: The subcultured UL cells were used to determine the validation of TGF-β3 for the viability of human UL cells using CCK-8 assay, mRNA expressions of ERα, and c-fos by quantitative reverse transcription polymerase chain reaction method, and expressions of p-Smad3, SnoN, and c-fos proteins by Western blot assay in each treatment group. Results: Compared with each of EEs or TGF-β3 treatment, slightly decrease in the proliferation rate of UL was detected in the coexistence of each EE with TGF-β3. Interestingly, mRNA expressions of ERα and c-fos reduced in the setting of coexistence of TGF-β3 and EEs. Somehow, the expression of p-Smad3 and c-fos proteins significantly decreased in each of E2, bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) group, as well as the expression of SnoN protein significantly reduced only in BPA and NP groups, followed by TGF-β3 treatment. With the overlaid action of ICI 182,780, the expression of p-Smad3 protein significantly increased in OP group, but slightly increased in E2, BPA, NP, and OP groups. However, compared with the control group, the expression of SnoN and c-fos proteins significantly decreased in the same setting. Conclusion: Both ERα signaling pathway and TGF-β signaling pathway have different roles in governing UL cell proliferation. The phenolic EEs can be a promoter to the proliferation of UL cells, which is mediated by ERα signaling pathway and cross-talked with TGF-β signaling pathway.

Aims: Several studies evaluated the association between myeloperoxidase (MPO) -463 G/A polymorphism and the risk of lung cancer. However, the results were not stable. Materials and Methods: Online electronic databases (PubMed, EMBASE, and Wanfang database) were searched. The strength of association between the MPO -463 G/A polymorphism and lung cancer risk was assessed by calculating odds ratios (OR) with 95% confidence interval (CI). Results: A total of 22 studies with 7420 cases and 9132 controls on the association between MPO -463 G/A polymorphism and lung cancer risk were included for this meta-analysis. MPO -463 G/A polymorphism was associated with a significantly decreased risk of lung cancer (OR = 0.91; 95% CI: 0.85–0.98; I ² = 25%). In the race subgroup analysis, Asians with MPO -463 G/A polymorphism had decreased lung cancer risk (OR = 0.81; 95% CI: 0.70–0.93; I ² = 0%). However, Caucasians did not show significant result (OR = 0.93; 95% CI: 0.86–1.02; I ² = 36%). In the subgroup analysis according to source of control, both population-based studies and hospital-based studies were marginally significantly associated with decreased risk of lung cancer (OR = 0.90; 95% CI: 0.82–1.00; I ² = 41% and OR = 0.91; 95% CI: 0.82–1.01; I ² = 0%). Conclusion: The present meta-analysis suggested that the MPO -463 G/A polymorphism carriers had a protective role in lung cancer.

Background: Lymph node status is important in staging colorectal cancer. The use of combination treatment for pathological T3N0 (pT3N0) rectal cancer patients has been controversial. We aimed to explore the prognostic significance of the total number of lymph nodes harvested from pT3N0 rectal cancer patients. Methods: Between June 2004 and November 2011, 289 pT3N0 rectal cancer patients who received total mesorectal excision (TME) with or without postoperative chemotherapy were retrospectively reviewed. The main independent variable was the total number of harvested lymph nodes, and the endpoints included local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). Results: The patients had a median of 13 lymph nodes harvested. When compared with patients who had < 12 lymph nodes harvested, patients who had ≥12 lymph nodes harvested had higher 5-year LRFS (84.7% vs. 98.0%, P < 0.001), DFS (71.4% vs. 86.8%, P < 0.001), and OS (77.6% vs. 94.9%, P < 0.001) rates. Multivariate analysis demonstrated that the patients who had ≥12 lymph nodes harvested had a significantly lower risks of local relapse (hazard ratio [HR], 0.099; P < 0.001), treatment failure (HR: 0.291; P < 0.001), and death (HR: 0.231; P < 0.001) when compared with patients who had <12 lymph nodes harvested. Conclusions: The number of lymph nodes harvested was independently associated with local relapse, treatment failure, and OS rates in pT3N0 rectal cancer patients who received initial TME with or without postoperative chemotherapy. Postoperative radiotherapy should not be omitted for pT3N0 rectal cancer patients who had <12 lymph nodes harvested.

Aim: To explore the expression of microRNA-106b (miRNA-106b) in nonsmall cell lung cancer (NSCLC). Settings and Design: miRNAs are short regulatory RNAs that negatively modulate gene expression at the posttranscriptional level, and are deeply involved in the pathogenesis of several types of cancer. miRNA-106b has been shown to play an oncogenic role in tumor progression. The expression of miRNA-106b is detected in this study. Subjects and Methods: Quantitative reverse transcription polymerase chain reaction and Northern blotting were used to detect the expression level of miRNA-106b in 200 NSCLC samples. Statistical Analysis Used: All statistical analyses were performed using SPSS 16.0 software. Results were statistically evaluated using the Kruskal–Wallis test and Mann–Whitney U-test. Survival curves were estimated by the Kaplan–Meier method and P < 0.05 was considered to be statistically significant. Results: miRNA-106b expression is increased in NSCLC tissues. Statistical analysis showed that overexpression of miRNA-106b was strongly associated with lymph node metastasis, stage of tumor node metastasis classification, and poor prognosis. Moreover, there was a significant difference in the miRNA-106b expression levels between smoking and nonsmoking patients. Multivariate Cox regression analysis showed that miRNA-106b was an independent prognostic factor for NSCLC patients. Conclusions: These data suggest that aberrantly expressed miRNA-106b may contribute to the development of NSCLC.

Background: Interleukin (IL)-17A and IL-17F are inflammatory cytokines mainly produced by T helper 17 cells. IL-17A is known to be protumorigenic while IL-17F has a protective role in cancer. A number of studies have been conducted to determine the association between polymorphisms of IL-17AG197A (rs2275913) and IL-17FA7488G (rs763780) and risk of cancers. No studies have yet to be conducted to genotype the IL-17AG197A polymorphism in colorectal cancer (CRC). Objective: To assess the association of IL-17AG197A and IL-17FA7488G polymorphisms with CRC risk. Materials and Methods: We performed the genotyping by polymerase chain reaction-restriction fragment length polymorphism method on blood samples from 80 healthy individuals and paraffin-embedded tumor tissues from 70 CRC patients. Results: Our study showed that IL-17A197AA genotype was significantly associated with an increased CRC risk with odds ratios of 6.08 (95% confidence interval [CI]: 2.25–16.42, P < 0.001) and 2.80 (95% CI: 1.23–6.35, P = 0.014), in comparison with GG and AG genotypes, respectively. However, IL-17FA7488G polymorphism was not significantly associated with CRC risk (P = 0.102). No significant association of IL-17AG197A and IL-17FA7488G polymorphisms with patient and tumor variables was found. Conclusion: This report from Malaysia shows the relationship of IL-17A197AA genotype with susceptibility to CRC.

Aims: Several studies evaluated the association between peroxisome proliferators-activated receptor gamma (PPARγ) Pro12Ala (rs1801282), and His477His (rs3856806) polymorphisms and the risk of colorectal cancer (CRC). However, the results were not stable. Materials and Methods: We searched databases containing PubMed and EMBASE. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Results: A significantly decreased CRC risk was found for PPARγ Pro12Ala polymorphism (OR = 0.88, 95% CI 0.83–0.94, P < 0.0001). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.89, 95% CI 0.83–0.95, P = 0.0003) but not in Asian population (OR = 0.76, 95% CI 0.57–1.02, P = 0.07). In the subgroup analysis by CRC location, significantly decreased risks were found in rectal cancer (OR = 0.88, 95% CI 0.77–1.00, P = 0.05) and colon cancer (OR = 0.82, 95% CI 0.73–0.92, P = 0.0008). In addition, a significantly decreased CRC risk was also detected for PPARγ His477His polymorphism (OR = 0.66, 95% CI 0.44–1.00, P = 0.05). In the subgroup analysis by race, a significantly decreased risk was found in the Caucasian population (OR = 0.43, 95% CI 0.26–0.69, P = 0.0006) but not in Asian population (OR = 0.95, 95% CI 0.73–1.25, P = 0.72). Conclusions: PPARγ Pro12Ala and His477His polymorphisms might be associated with susceptibility of CRC.

Objective: Our study aims to investigate the expression of human epidermal growth factor receptor 2 (HER-2), Janus-activated kinase/signal transducer, and activator of transcription 3-suppressor of cytokine signaling 3 (JAK/STAT3-SOCS3) pathway in gastric cancer (GC) and its relationship with clinicopathological features and prognosis of GC. Materials and Methods: A total of 105 GC patients who underwent surgical resection were enrolled for our study, and corresponding 60 normal tissues adjacent to carcinoma (>10 cm from the carcinoma tissues) as control groups. Spearman correlation analysis was applied for correlation analysis among HER-2, STAT3, and SOCS3. Kaplan–Meier method and Cox proportional hazard model were applied for investigating the associations among HER-2, STAT3 and SOCS3 expressions and prognosis of GC patients. Results: The expressions of HER-2 and STAT3 in GC tissues were increased, but SOCS3 expression showed an evident decrease with the change of depth of invasion, lymph node metastasis (LNM), and tumor node metastasis staging (all P < 0.05). The result of Spearman correlation analysis showed a positive correlation between HER-2 and STAT3 (r = 0.216, P < 0.05), while a negative correlation was observed between STAT3 and SOCS3 (r = –0.237, P < 0.05). Kaplan–Meier analysis results showed that the survival time of HER-2 and STAT3 negative group were both higher than their positive group (both P < 0.001), nevertheless, the survival time of SOCS3 negative group was lower than positive group (P < 0.001). Cox regression multivariate analysis indicated HER-2, STAT3, SOCS3, LNM, and depth of invasion were independent prognostic factors influenced the prognosis of GC (all P < 0.001). Conclusion: Our study revealed that HER-2 may participates in the development, invasion and metastasis of GC by affecting the JAK/STAT3 pathway. HER-2, STAT3, and SOCS3 serve as reference indexes for the prognosis of GC patients.

Introduction: Fine-needle aspiration was once done in suspected malignant thyroid nodules more than 5 mm in diameter. Five millimeter has been applied in many studies as the cut off tumor size in recent years. In this study, we would like to analyze the clinicopathological and ultrasonographic features of papillary thyroid microcarcinoma (PTMC) ≤5 mm and >5 mm with the aim of finding out the diagnostic value of ultrasonography. Subjects and Methods: A total of 291 patients from January 2012 to October 2014 who underwent an ultrasound examination and were postoperatively diagnosed as PTMC were enrolled in the study. The patients were divided into Group A (≤5 mm) and Group B (>5 mm, ≤10 mm) based on diameter. The clinicopathological and ultrasonographic features of the two groups were statistically analyzed. Results: In total, 291 thyroid tumors were analyzed in 291 patients. In patients who were identified with multiple tumors, the largest nodule in size was used for analysis. PTMC >5 mm in diameter were found with a higher incidence of lymph node metastasis and advanced tumor-node-metastasis (TNM) Stage (III/IV) with a significant difference, also with a larger part of multiple tumors compared to PTMC <5 mm. Of all the ultrasonographic features studied, calcification and peripheral halo were more significantly correlated with PTMC >5 mm. The presence of vascularity and blood supply were both associated with the tumor size. Conclusion: Larger tumor size of PTMC is more likely to involve in lymph node metastasis and advanced TNM stage. Correlation of tumor size with calcification, peripheral halo, vascularity, and blood supply do exist in PTMC. Ultrasound is of great value in the evaluation of PTMC.

Aim: To test the anticancer potential of a combination of thymoquinone (TQ) and melatonin (MLT) against breast cancer implanted in mice. Materials and Methods: The antiproliferative activity of TQ, MLT, and their combination was tested against mouse epithelial breast cancer cell line (EMT6/P) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The combination index (CI) was calculated using isobolographic method. Balb/C mice were transplanted with EMT6/P cell line and in vivo antitumor activity was assessed for TQ, MLT, and their combination. Changes in tumor size were measured for each treatment. Histological examination of tumor sections was performed using standard hematoxylin/eosin staining protocol and TUNEL colorimetric assay was used to test the apoptosis induction ability for all treatments. Immunohistochemical staining was used to detect vascular endothelial growth factor (VEGF) expression in tumor section and ELISA was used to measure serum levels of interferon gamma (INF-γ) and interleukin-4. Serum levels of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used as biomarkers of hepatotoxicity of the combination therapy. Results: Synergistic anticancer effect was observed between TQ and MLT with CI value of 0.552. The combination of TQ and MLT caused a significant decrease in tumor size with a percentage cure of 60%. The combination therapy induced extensive necrosis, increased apoptosis rate, and decreased VEGF expression in tumor sections. Serum levels of INF-γ were increased in mice treated with combination therapy and AST and ALT levels were close to their normal values. Conclusions: The combination TQ and MLT act synergistically to inhibit breast cancer implanted in mice. The anticancer effect of this combination is mediated by induction of apoptosis, angiogenesis inhibition, and activation of T helper 1 anticancer immune response.

Aim of Study: Nasopharyngeal carcinoma (NPC) is by far the most common malignant tumor of the nasopharynx and is suggested to be related to immune system dysfunction. T cells play a central role in the cell-mediated immunity. However, how the T cells vary during the NPC treatment is still unclear. Materials and Methods: We divided the NPC patients into previously untreated, partial remission, complete remission, and relapse groups. Healthy controls were those without any autoimmune diseases, cancer, or recent infection. We used flow cytometry to detect the changes in T cell subsets. Results: We found the quantity (%) of CD4⁺ CD25⁺ CD127^low/− Treg regulatory T cells and CD8⁺ CD28⁻ T cells were obviously increased in NPC previously untreated, partial remission, and relapse groups. There was no difference in these two subsets between complete remission groups and healthy controls. In addition, the quantity (%) of CD3⁺ CD4⁺ and CD8⁺ CD28⁺ effector T cells were reduced in NPC previously untreated, partial remission, and relapse groups. There was no difference in these two subsets between complete remission groups and healthy controls. Conclusions: Our research determines the changes of T cell subsets in different stages of NPC.

Background: Lactate formation is upregulated in tumor cells by lactate dehydrogenase (LDH). High serum LDH level is linked to many malignancies with poorer survival, but tumor LDH has not been well investigated in small cell lung cancer (SCLC). Patients and Methods: The study was performed in 120 cases of SCLC confirmed by pathological examination. The evaluation of treatment response to chemotherapy was based on response evaluation criteria in solid tumors criteria. The serum LDH levels were determined at diagnosis and follow-up visits. The distribution and differences in LDH change and the chemotherapeutic response rate was evaluated by using χ ² tests. Receiver operating characteristic curves were calculated to select the cut-off level of an increase in LDH indicating significant progression. The correlation of time of serum LDH normalization, time-to-progression (TTP), and overall survival (OS) were analyzed by Pearson correlation. Influence of increasing LDH on survival was calculated using the Kaplan–Meier method. Results: At diagnosis, significant differences in LDH levels were found between the groups with limited or extensive. In contrast to the limited-stage group, the extensive-stage group showed significantly decreased the level of LDH after the first-line chemotherapy. In patients whose diseases progressed, LDH levels were significantly higher in the last 1-month period preceding progression compared with the level at the progression. In the follow-up, we found that prolonging periods of serum LDH normalization were co-related to TTP and OS significantly. An increase in LDH by at least 51.5 U/L was found to be associated to a significantly higher probability of disease progression, and patients with initial increased LDH had a significantly reduced probability of survival. Conclusions: LDH is validated for its potential usefulness as markers for monitoring treatment response in SCLC and also suitable for discriminating between disease and disease-free periods.

Background: Nonsmall cell lung cancer (NSCLC) is one of the leading incidence and mortality of malignant tumors worldwide. While aberrant DNA methylation is a frequent event occurred during NSCLC carcinogenesis and development, therefore holding the potential to predict the process of tumor development. This study aims to explore the feasibility of gene nidogen 2 (NID2) as the diagnostic biomarker for NSCLC. Materials and Methods: Quantitative methylation specific polymerase chain reaction of NID2 has been done among the following sample panels: For tissue methylation evaluation, we collected 96 cases of NSCLC versus 18 cases of noncancerous lung lesions (NCLLs); 46 from the 96 NSCLC patients also provided DNA of bronchoalveolar lavage (BAL) and plasma sample, the methylation status of which are assessed against 12 cases of NCLL for BAL and 30 cases of NCLL for plasma samples, respectively. Results: The methylation rate of NID2 in NSCLC versus NCLL is evaluated as: In tissue 59.40% versus 16.67%, (P = 0.0001); in BAL 30.43% versus 16.67% (P = 0.1640); in plasma 45.65% versus 20.00% (P = 0.0191). Conclusions: Our study revealed the frequent occurrence of aberrant NID2 methylation in NSCLC and peripheral blood, which might be useful as a biomarker to predict NSCLC or to screen the high-risk population for NSCLC.

Aim of Study: To analyze the function of keratinocyte growth factor (KGF) and it ligand fibroblast growth factor receptor 2-IIIb (FGFR2-IIIb) in the epithelial ovarian cancer (EOC) progression. Materials and Methods: In this study, the protein KGF and corresponding ligand FGFR2-IIIb expression were detected in both normal epithelial ovarian tissues and in EOC tissues. Seventy-one ovarian tumor tissues were examined for KGF and FGFR2-IIIb expression by immunohistochemistry; seven normal epithelial ovarian tissues as control were examined. By using a monoclonal antibody to inhibit KGF activation, we tested KGF-induced EOC cells invasion ability. By means of Western blot, we tested extracellular signal-regulated kinase (ERK), phosphorylation ERK, myosin light chain (MLC), and phosphorylation MLC with or without KGF protein. Results: We found that the expression FGFR2-IIIb increased in EOC cells and tissues comparing with its normal counterpart, and the expression of KGF protein decreased or undetectable in human EOC cells and tissues comparing with its normal part. The effect of KGF in promoting EOC cell invasion was blocked by an FGFR2-IIIb antibody. We further discovered that KGF upregulated ERK and MLC phosphorylation in the highly invasive ovarian cancer cell line HO8910PM. Therefore, regarding the highly invasive ovarian cancer cells, we speculated that KGF might promote proliferation and invasion through the ERK-MLC pathway. Conclusions: These results suggest that KGF might play an important role in the progression of ovarian cancer and could be an attractive target for ovarian cancer therapy.

Aim of Study: The current meta-analysis investigated the correlation between breast cancer type 1 (BRCA1) promoter methylation and the clinicopathological features of breast cancer (BC). Materials and Methods: An electronic literature search was performed to identify and select cohort studies, by employing stringent inclusion and exclusion criteria, for data relevant to promoter methylation of BRCA1 and BC. Statistical analysis of the extracted data was performed using comprehensive meta-analysis 2.0 software (CMA 2.0) (Biostat Inc., Englewood, New Jersey, USA). Results: A total of 125 published studies were retrieved from the literature search, and finally, 18 cohort studies meeting our inclusion criteria were incorporated into our meta-analysis. The 18 studies contained a total of 3213 BC patients. Meta-analysis results revealed that BRCA1 promoter methylation in BC patients with high and moderately differentiated tumors (I-II) was significantly lower than patients with poorly-differentiation tumors (III) (odds ratio [OR] =0.450, 95% confidence interval [95% CI] =0.241–0.838, P = 0.012). BRCA1 promoter methylation in BC patients with lymph node (LN) metastasis was significantly higher than patients without LN metastasis (OR = 2.244, 95% CI = 1.278–3.940, P = 0.005). The results of ethnicity-based subgroup analysis showed a significant difference in histological grade of BC on Asians, LN metastasis of BC in Asians and Caucasians, subtypes of BC in Caucasians, and age at diagnosis of BC patients in Caucasians (all P < 0.05). Conclusions: Our meta-analysis revealed that BRCA1 promoter methylation status is linked to tumor grade and LN metastasis of BC.

Aim: The aims of this study are to evaluate the serum levels of paraoxonase (PON) and arylesterase (ARE) in breast cancer (BC) patients; to determine their relationship with chemotherapy requirements in BC; and to find a cut-off value to assess subjects with a higher risk of BC. Subjects and Methods: A total of 40 BC patients and 33 age-matched healthy women were included in this study. Beside other biochemical parameters, participants' serum PON and ARE levels were determined and analyzed. Results: Serum PON and ARE levels were found decreased in sera of the patients (96.44 ± 21 and 159.75 ± 15.75 U/L, respectively)compared to controls (158.39 ± 23.04 and 239.33 ± 32.98 U/L, respectively) (P = 0.001 for both). Subgroup analysis of the BC patients revealed that both serum PON and ARE levels were lower in patients who needed neoadjuvant chemotherapy (NAC), compared to those who did not (P = 0.024 and 0.02, respectively). We determined a cut-off value of PON according to the receiver operating characteristic curve analysis as 131.2 U/L (sensitivity 97.5% and specificity 93.9%). Conclusion: BC patients have lower serum PON and ARE levels than healthy controls. Also, serum ARE levels (but not PON) were negatively correlated with body mass index in BC patients. Both serum PON and ARE levels were lower in patients who needed NAC than in patients who did not need such therapy.

Objective: We aim to investigate whether the breast cancer metastasis suppressor gene, breast cancer metastasis suppressor 1 (BRMS1), is correlated with clinicopathological features of breast cancer or not. Materials and Methods: Following a stringent inclusion and exclusion criteria, case-control studies related to the association between BRMS1 and breast cancer were selected from articles retrieved by electronic database searches. All statistical analyses were performed by Stata version 12.0 (Stata Corp, College Station, TX, USA). Results: A total of 12 studies were ultimately included in this meta-analysis. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower compared with normal breast tissues (odds ratio [OR] =0.08, 95% confidence interval [CI] =0.04–0.15, P < 0.001). The BRMS1 protein in metastatic breast cancer tissue was lower than that in nonmetastatic breast cancer tissue (OR = 0.20, 95% CI = 0.13–0.29, P < 0.001), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1, 2 was found to be higher than TNM stages 3, 4 (OR = 4.62, 95% CI = 2.77–7.70, P < 0.001). With respect to breast cancer types, BRMS1 protein in all the three major types of breast cancer was lower than the normal tissues. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. Conclusion: Our meta-analysis results showed that reduced BRMS1 expression level was significantly associated with clinicopathological features of breast cancer, suggesting that loss of expression or reduced levels of BRMS1 might be a strong indicator of the metastatic capacity of breast cancer, with poor prognosis.

Background and Objective: Investigations on the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and prostate cancer risk are conflicting. This meta-analysis was conducted to assess the relationship between ACE I/D gene polymorphism and prostate cancer risk. Materials and Methods: Reports were identified from PubMed, Cochrane Library, and China Biological Medicine (CBM)-disc (CBM database) on December 30, 2014, and eligible studies were recruited. Results: ACE I/D gene polymorphism was not associated with prostate cancer risk for overall populations in this meta-analysis (D allele: Odds ratio [OR] =1.56, 95% confidence interval [95% CI]: 1.00–2.46, P = 0.05; DD genotype: OR = 1.74, 95% CI: 0.95–3.20, P = 0.07; II genotype: OR = 0.67, 95% CI: 0.39–1.15, P = 0.15). Furthermore, the association of ACE I/D gene polymorphism with colorectal cancer risk was not found for the Caucasians. Interestingly, ACE I/D gene polymorphism was associated with prostate cancer risk for the Asian population and Latino population. Conclusions: There was an association between ACE I/D gene polymorphism and prostate cancer risk for the Asians and Latino population in this meta-analysis. However, more investigations should be performed to confirm this relationship.

Aim: We investigated the association of WNT inhibitory factor-1 (WIF-1) gene methylation with the pathogenesis of multiple human tumors, using a meta-analysis based approach. Materials and Methods: Electronic databases and manual search was additionally employed to retrieve relevant published literature. The cohort studies relating to tumor and WIF-1 were screened based on predefined selection criteria, and all extracted data from the selected studies were analyzed through STATA software. Results: Sixteen studies were finally enrolled in our study involved 1112 tumor samples and 612 adjacent normal samples. The study result showed that WIF-1 gene methylations in tumor tissues were significantly higher compared with adjacent/normal tissues. The result of subgroup analysis on ethnicity revealed that in the Caucasians, Asians, and Africans, the methylation status of WIF-1 gene in tumor tissues was higher than adjacent/normal tissues. Further subgroup analysis on disease types revealed that WIF-1 gene methylation status is a widespread phenomenon that is, observed in tumor tissues of patients with multiple human tumors compared with that in adjacent/normal tissues. Interestingly, there was no significant difference in WIF-1 gene methylation between tumor tissues among patients with lung cancer, gastric cancer, astrocytoma, and adjacent/normal tissues, indicating the WIF-1 gene methylation not a general nonspecific phenomenon. Conclusion: WIF-1 gene methylation in tumor tissues was significantly more frequent as compared to that in adjacent normal tissues, indicating that WIF-1 gene methylation may be an important event in the pathogenesis of multiple human tumors.

Aim of Study: Proanthocyanidin-rich longan flower extract (LFP) has been previously shown to inhibit the proliferation and anchorage-independent growth in soft agar of two colorectal carcinoma (CRC) cells in vitro. In this report, we further examined the effects of LFP in a CRC spheroid model. Materials and Methods: A liquid-overlay assay employing HT-29 spheroids was used to evaluate the effects of LFP on cancer cell tumorigenesis, viability, and apoptosis. Associated effects on signaling path ways (epidermal growth factor receptor [EGFR], Akt) and apoptotic regulators were measured using Western blot. Results: Treatment with LFP up to 200 μg/ml inhibited tumor growth in a dose-dependent manner and induced prominent apoptosis as measured by annexin V staining. Cells treated with LFP showed decreased EGFR and Akt phosphorylation with decreased expression of B-cell lymphoma 2. Conclusion: The ability of LFP to induce apoptosis in CRC spheroids warrants further investigation of its composition and identification of tumor-active components.

Purpose: To investigate the values of gemstone spectral imaging (GSI)-dual-energy computed tomography (DECT) in differentiation of renal cell carcinoma (RCC) and minimal-fat renal angiomyolipoma (MF-RAML). Patients and Methods: Twenty-one patients with ischemic RCC and 19 patients with MF-RAML were enrolled in this study. GSI was performed on them, and the spectrum signs were analyzed. Results: I(H₂O), H₂O(I), I(fat), and fat(I) concentrations, normalized I concentration, and effective atomic number of corticomedullary phase and parenchymal phase in enhanced GSI-DECT in ischemic RCC group were all significantly lower than those in MF-RAML group (P < 0.05). CT value and absolute slope rate of spectral attenuation curve in two phases in ischemic RCC group were also significantly lower than those in MF-RAML group (P < 0.05). Conclusion: GSI-DECT has provided a new idea and method for differential diagnosis of ischemic RCC and MF-RAML, with high-clinical values.

Background: Lung cancer is sometimes difficult to differentiate from benign lung diseases with nodular shadow in imaging scan. In these cases, exploratory operation is needed for the patients with highly suspected malignant disease. Therefore, there is an urgent demand to differentiate the benign lung disease from malignant lung nodules rather than invasive method. Aim: We evaluated the diagnostic value of two tumor markers in distinguishing operable lung cancer from benign lung disease. Materials and Methods: The serum levels of carcinoembryonic antigen (CEA) and CYFRA 21-1 were retrospectively analyzed in 236 lung cancer patients and 44 patients with benign lung disease. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Results: We found that the average level of tumor marker in operable lung cancer patients was higher than those in patients with benign lung disease. CYFRA 21-1 sensitivity and specificity for lung cancer diagnosis was 37.3% and 90.9%, respectively, while that for CEA was 22.0% and 90.9%. The combined value for the sensitivity and specificity of these two tumor markers was 47.5% and 81.8%, respectively. Conclusion: Our results indicate that the combination of these two tumor markers resulted in higher sensitivity compared to use CYFRA 21-1 or CEA along. Given its lower sensitivity and higher specificity, positive CYFRA 21-1 or positive CEA strongly supports lung cancer in patients with nodular shadow in imaging scan.

Aims: Previous studies have found that long noncoding RNA taurine upregulated gene 1 (TUG1) can regulate osteosarcoma cells apoptosis and proliferation; the aim of this study was to investigate the clinical significance of TUG1 in osteosarcoma. Subjects and Methods: The expression of TUG1 was detected by real-time and quantitative polymerase chain reaction assay in 94 pairs of tumor tissues and corresponding noncancerous bone tissues of osteosarcoma patients. Its correlations with clinicopathologic features were analyzed, and the significance of TUG1 as a prognostic factor was determined. Results: This study shows that the expression of TUG1 in osteosarcoma tissues was significantly higher than that in adjacent normal bone tissues. Upregulation of TUG1 was significantly correlated with the larger tumor size and advanced tumor-node-metastases stage of osteosarcoma patients. Kaplan–Meier curve showed a decreased overall survival time of osteosarcoma patients with high TUG1 expression. Moreover, univariate and multivariate analyses suggested that low-expression level of TUG1 was an independent poor prognostic indicator for osteosarcoma patients. Conclusions: In conclusion, our data support TUG1 as a potential prognostic predictor and gene therapy target with its high expression in tumor tissues and its association with carcinogenesis and progression in osteosarcoma.

Purpose: We reported the patterns of care for a cohort of Chinese patients with nonsmall cell lung cancer (NSCLC) and examined the characteristics of those patients who did not receive cancer-specific treatment. Materials and Methods: This was a prospective cohort study. The study population was patients with first primary NSCLC diagnosed and admitted to Hebei Cancer Hospital in Hebei Province in China from January 2004 to December 2005. Logistic regression was used to examine factors associated with no cancer-specific treatment. Cox proportional hazard regression was used to examine the effects of cancer treatment on survival. Results: Of 579 NSCLC patients included in the study, 73.4% were male, 84.3% died by the end of the study after 7 years follow-up, 40.1% were diagnosed at a late stage of disease, and 33.7% had unknown disease stage. Over half (50.8%) of the patients received palliative care, 23.8% for curative care, and 25.4% did not receive any cancer-specific treatment. The probability of not receiving cancer-specific treatment was significantly higher for those who diagnosed at older age (odds ratio [OR] =3.01, 95% confidence interval [95% CI]: 1.79–5.06), had unknown stage at diagnosis (OR = 2.77, 95% CI: 1.41–5.47), or had unclassified histological type (OR = 3.48, 95% CI: 1.94-6.21). After adjusted for other factors, patients received anti-cancer treatment had significantly lower risk of dying from NSCLC P < 0.0001) compared with patients who did not receive any cancer-specific treatment. Conclusions: Despite the benefits of anti-cancer treatments confirmed in this study, over a quarter patients did not receive any such treatment. Finding the reasons for the patients who did not receive cancer-specific treatment may improve the quality of patient care in this population.

Aim of Study: The present study was designed to investigate the application of positron images from photonuclear reactions to verify the location of targeted radiation in vivo. Materials and Methods: The phantom study was conducted with distilled water, porcine muscle, porcine adipose tissue, and graphite; these subjects were irradiated separately with 50 MV photons generated by an MM50 Racetrack Microtron. The positron emission activity was measured using a Geiger counter, and the radioactive decay curves for each of the irradiated materials were then established. The positron emission tomography (PET) images of the three tissue models were also achieved using the same radiation conditions. The in vivo PET imaging study was also conducted in tumor-bearing rabbits. Results: Our results demonstrated that the PET imaging could be used to verify the position of the irradiation field in vivo. The dose distribution images of photonuclear reactions of ¹¹ C and ¹⁵ O were uniform, using 2-Gy 50 MV photons. Conclusions: The factors influencing the half-life of radiation activity in various tissues were different from the first order kinetic reaction in physics.

Objective: In this study, we showed a modified method for the isolation of cancer stem cells (CSCs) using a combination of differential adhesion method and serum-free culture medium (SFM) method. Materials and Methods: Trypsin-sensitive cells and trypsin-resistant cells were isolated from MB49, EJ, and SK-OV-3 cells using a combination of differential adhesion method and SFM method. The CSCs markers expression of trypsin-resistant cells was verified by the flow cytometry, the Western blotting, and the quantitative polymerase chain reaction. Functional comparisons were verified by the resistance to chemotherapy assay, the transwell assay, and the tumor xenograft formation assay. Results: Trypsin-resistant cells were isolated successfully. They were identified with high expression of CSCs markers and possessed higher resistance to chemotherapy, greater migration in vitro and stronger tumorigenic abilities in vivo. Conclusion: Trypsin-resistant cells showed specific CSCs characterizations. They were able to be isolated successfully with a modified method by a combination of differential adhesion method and SFM method.

Objective: Sunitinib/sorafenib (SU/SO), dendritic cells (DCs), or DC-cytokine-induced killer (CIK) could significantly prolong progression-free survival (PFS), 3-year overall survival (OS), or 5-year OS for patients with metastatic renal cell carcinoma (mRCC). We retrospectively analyzed the clinical efficacy between SU/SO combined with DC-CIK and SU/SO monotherapy in treating renal cell carcinoma (RCC) patients with metastasis after radical nephrectomy. Materials and Methods: All patients (n = 34) with postoperative mRCC in our hospital from January 2009 to January 2014 were received either SU/SO monotherapy (Group 1, n = 15) or in combination with DC-CIK (Group 2, n = 19). A retrospective study was based on the primary endpoint (PFS) and secondary endpoint (OS). Results: At a median follow-up of 19.5 months, in Group 2, as compared with in Group 1, the median PFS was significantly longer (28.0 vs. 11.0 months, P = 0.03). Moreover, the 3-year OS was higher (57.1% vs. 28.6%). The cases of progressive diseases (PDs) and deaths were less in Group 2 than that in Group 1 (PD: 8 vs. 9, deaths: 3 vs. 5); however, the cases of stable diseases were more (11 vs. 6). In addition, the 3-year OS was higher in SU + DC-CIK group than that in SO + DC-CIK group (63.36% vs. 50%). There was no significant difference for PFS between SO + DC-CIK group and SU single agent group. Conclusions: SU/SO with DC-CIK could significantly prolong the median PFS, improve the 3-year OS rate, prolong the 3-year OS. It is likely to be a new approach for mRCC after radical nephrectomy.

Objective: The aim of this study is to investigate the clinical value of serum B7 homologous body 4 (B7-H4) protein detection for the diagnosis of ovarian cancer (OC) in Chinese Han women by pooling published data. Methods: A systematic literature search was conducted in Cochrane Library, PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure databases. The bivariate model was utilized to calculate the pooled estimates. Publication bias was assessed by using funnel plots and Deek's test. Results: After the review, ten publications were found to meet our inclusion criteria. The overall diagnostic sensitivity and specificity of B7-H4 in OC were 0.782 (95% confidence interval [CI]: 0.732–0.825) and 0.870 (95% CI: 0.804–0.916), respectively. The area under summary receiver operating characteristic curves was 0.86 (95% CI: 0.83–0.89). No significant publication bias was observed in the included studies. Conclusion: Serum B7-H4 detection, either alone or in combination with carbohydrate antigen 125, has an acceptable value in the diagnosis of OC.

Objective: To systematically review the efficacy and safety of low molecular weight heparin (LMWH) in treating patients with lung cancer received chemotherapy. Materials and Methods: Databases including PubMed, The Cochrane Library, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched for the randomized controlled trials (RCTs) about LMWH in treating patients with lung cancer received chemotherapy from the establishment to May 31, 2015. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data, and assessed quality of the included studies. Meta-analysis was then performed by using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) software. Results: A total of eight RCTs involving 952 patients were finally included. Meta-analysis showed that compared with the control group, LMWH significantly improved the 1- and 2-year overall survival (OS) rates of the patients with lung cancer received chemotherapy (risk ratio [RR] =1.65, 95% confidence interval [95% CI] [1.20–2.26], P = 0.002; RR = 2.63, 95% CI [1.40–4.94], P = 0.003, respectively), and significantly reduced the incidence of venous thromboembolism (VTE) (RR = 0.40, 95% CI [0.23–0.69], P = 0.001), not significantly increased the incidence of major bleeding events and thrombocytopenia (RR = 1.29, 95% CI [0.57–2.96], P = 0.54; RR = 0.86, 95% CI [0.69–1.07], P = 0.18, respectively), and not significantly improved the overall response rate (RR = 1.24, 95% CI [0.98–1.57], P = 0.07). Conclusion: LMWH improves the 1- and 2-year OS rates of the patients with lung cancer received chemotherapy and reduces the incidence of VTE, not increase the incidence of major bleeding events and thrombocytopenia. These show that there is a certain effect of LMWH, and the security is good.

Background and Aim: To investigate the value of peripheral blood plasma levels of septin-9 and clusterin protein in the diagnosis of epithelial ovarian cancer (EOC). Materials and Methods: The peripheral blood plasma samples were obtained from 137 EOC patients, 12 borderline ovarian tumor patients, 10 benign ovarian tumor patients, 41 benign pelvic lesion patients, and 58 healthy women. The peripheral plasma septin-9 and clusterin proteins levels were measured by enzyme-linked immunosorbent assay. The power of test was evaluated with the area under the receiver operating characteristic curve (ROC) (AUC). Results: The mean levels of plasma septin-9 and clusterin in EOC patients were significantly higher than that in healthy women (P = 0.002, P = 0.021). The mean levels of plasma septin-9 in benign pelvic lesion patients were significantly higher than that in healthy women (P = 0.007). The mean levels of plasma septin-9 in epithelial ovarian carcinoma patients with tumor family history or distant metastases were significantly higher than that of patients without (P = 0.040, P = 0.025). The AUC of septin-9 protein was 0.712, when the optimal cut-off point was 0.28, the sensitivity and diagnostic specificity were 82.5% and 50.0%, respectively; the AUC of clusterin was 0.636, and when the optimal cut-off point was 87.96 ng/ml, the sensitivity and diagnostic specificity was 71.5% and 41.4%, respectively. Conclusion: The plasma levels of septin-9 and clusterin in ovarian cancer patients were abnormally elevated, which might be used as potential candidates of peripheral blood tumor biomarkers for early diagnosis of EOC and septin-9 might be related to distal metastases of EOC. The septin-9 might play the promotion role, which protein level relates to not only the distal metastases but also the prognosis of EOC. Due to the limit of sample volume, further enlargement of the sample size and set up of the follow-up system is in need to in-depth study the relationship between plasma protein concentration with the distal metastases, and further explore its correlation with the prognosis of EOC.

Context: Radiotherapy is the commonly used therapeutic modality for inoperable cancer types. We investigated chemoradiotherapy (CRT) effects on the Na ⁺/K ⁺-ATPase enzyme. Aims: The aim of the present study was to determine the usefulness of Na ⁺/K ⁺-ATPase enzyme as a prognostic factor and as a potential target for increasing the CRT response of nonsmall cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). Settings and Design: We prospectively evaluated 30 patients (all were treated with CRT) and 20 healthy controls. Subjects and Methods: Blood samples were taken before and after the completion of CRT from the patients and once from the control group. Erythrocyte membranes were isolated and Na ⁺/K ⁺-ATPase enzyme activities were measured. Statistical Analysis Used: The statistical significance was calculated using the one-way analysis of variance test and the Tukey's test. Results: Na ⁺/K ⁺-ATPase activity levels were increased in the patient groups before completion of CRT CRT, when compared to the control group. A significant decrease in Na ⁺/K ⁺-ATPase activity was noted in the patient groups after the completion of CRT when compared to before CRT, but the activity remained higher than in the control group. No relationship was noted between survival and Na ⁺/K ⁺-ATPase activity in NSCLC and GBM patients. Conclusion: Levels of Na ⁺/K ⁺-ATPase activity were initially high in patients with NSCLC and GBM, and decreased after the completion of CRT. This supports a linkage between the altered activity of Na ⁺/K ⁺-ATPase and the treatment effects of CRT. The observed change in Na ⁺/K ⁺-ATPase activity in cancer patients receiving CRT suggests that targeting this enzyme could represent a novel mean of combatting NSCLC and GBM.

Introduction: Recurrent pulmonary metastasis is common in sarcoma patients following the first pulmonary metastasectomy. Repeated pulmonary metastasectomy (RPM) may be a possible treatment method, but it has several unfavorable aspects. The clinical efficiency of RPM has not been established, as previous studies have reached inconsistent results. Materials and Methods: Comprehensively literature searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. All eligible articles were included according to inclusion criteria. Then, a meta-analysis was conducted to clarify the clinical efficiency of RPM. Results: A total of 9 articles with 464 patients were included. We found that sarcoma patients with recurrent pulmonary metastasis that underwent RPM had significantly better overall survival (hazard ratio = 0.59; 95% confidence interval, 0.44–0.81; P = 0.001). No significant publication bias was found. Sensitivity analysis showed the results were stable. Conclusion: Selected sarcoma patients with recurrent pulmonary metastasis following the first pulmonary metastasectomy could still benefit from RPM, despite its unfavorable aspects.

Aim of Study: The CYP3A5*3 allele (A6986G transition in intron 3) is the major member of cytochrome P450 subfamily, which plays a pivotal role in exogenous carcinogens of liver. Variation of the CYP3A5*3 (rs776746 A > G) can lead to oxidation and inactivation of testosterone, which may result in individual susceptibility to prostate cancer. Methods: All eligible published studies about association between CYP3A5*3 polymorphisms and prostate cancer risk were searched in PubMed, Embase, Web of Science, and Cochrane Library, for the period up to August 2015. Odds ratios (ORs) together with 95% confidence intervals (95% CIs) were used to access the strength of the association. Results: Six case–control studies including 2522 cancer patients and 2444 healthy controls were finally included. The meta-analysis results suggested that CYP3A5*3 polymorphisms were significantly associated with an increased risk of prostate cancer under two genetic models (GG + AG vs. AA: OR = 1.53, 95% CI = 1.23–1.90, P = 0.000; GG vs. AA: OR = 1.46, 95% CI = 1.14–1.87, P = 0.000). Further subgroup analysis according to ethnicity indicated that CYP3A5*3 polymorphism may increase the risks of prostate cancer among African (G allele vs. A allele: OR = 1.34, 95% CI = 1.14–1.57, P = 0.000; GG + AG vs. AA: OR = 1.606, 95% CI = 1.27–2.04, P = 0.000). Sensitivity analysis indicated a reliable result and publication bias suggested no strong publication bias under the genetic models. Conclusion: Our data support that the CYP3A5*3 polymorphism may be associated with increased risk of prostate cancer, particularly in African populations. Large and well-designed studies are needed to validate this association.

Objective: Osteosarcoma is the most common malignant bone tumor that occurs in children and adolescents. Various studies have investigated the role of serum alkaline phosphatase (ALP) level in patients with osteosarcoma but report conflicting findings. Thus, a meta-analysis to assess its prognostic value more precisely is conducted. Materials and Methods: Pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) was used to assess the prognostic role of serum ALP level. Eleven studies published between 1993 and 2013 with a total of 1336 osteosarcoma patients were included. Results: Overall, the pooled HR for all 11 eligible studies evaluating high ALP level on OS was 1.60 (95% CI: 1.38–1.86). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg's (0.553) and Egger's (0.382) test also did not suggest evidence for publication bias. Conclusion: This meta-analysis suggests that high serum ALP level is obviously associated with lower OS rate in patients with osteosarcoma, and it is an effective biomarker of prognosis.

Objective: Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. The discovery of new therapies against HCC is highly dependable on finding molecules which play essential roles in cancer development. The objective of this study was to evaluate the activity of gamma secretase (γ-secretase), and the antitumor effects of a γ-secretase inhibitor (GSI) in HCC. Methods: The expression of presenilin 1 (PS1), a core component of γ-secretase, was examined by Western blot. Activity of γ-secretase was measured by a luciferase-based reporter system, and cancer cells were transfected either with PS1 dominant negative mutant (PS1D385A) or treated with GSI. Results: Expression of PS1 was increased in HCC tissue and several HCC cell lines, which were accompanied by elevated γ-secretase activity. Cell colony formation and cell proliferation were decreased upon treatment with GSI but not with PS1D385A transfection. Conclusion: GSIs may be appealing candidates for the development of new therapies against HCC.

Purpose: The balance between T helper (Th) cells Th1- and Th2-related cytokines plays a key role in the clinical process of acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). The objective of this study was to assess the status of Th1/Th2 cytokines in patients with ACS and T2D or IGT. Methods: A total of 201 ACS patients were enrolled in the study. All ACS patients were divided into three groups: Group I-patients with normal glucose tolerance (NGT), Group II-patients with IGT and Group III-patients with T2D. We measured circulating Th1/Th2-type cytokines (interleukin [IL]-4, IL-13, interferon-gamma [IFN-γ], and tumor-necrosis factor-alpha [TNF-α]) using enzyme-linked immunosorbent assay and calculated the ratio of Th1/Th2. Results: Significant elevations in serum levels of IL-4, IL-13, IFN-γ, and TNF-α were found in ACS-T2D and ACS-IGT groups compared to that in both ACS-NGT group and healthy individuals. Higher serum levels of IL-4, IL-13, and TNF-α were found in ACS-NGT group than that in the control group. Furthermore, IL-4 and IFN-γ concentrations were significantly higher in ACS-T2D patients than in ACS-IGT patients. IFN-γ/IL-4, IFN-γ/IL-13, and TNF-α/IL-4 ratios as markers of Th1/Th2 ratio were significantly higher for the ACS-T2D group and ACS-IGT group as compared to that in the ACS-NGT group and control group (P < 0.05). Conclusion: Shifts in the balance of Th1/Th2 toward a predominance of Th1 may represent more severe inflammatory status in ACS patients with type T2D or IGT.

Objective: To quantitatively investigate the effect of GSTP1 hypermethylation on hepatocellular carcinoma (HCC) using a meta-analysis of available case–control studies. Materials and Methods: Previous studies have primarily evaluated the incidence of GSTP1 hypermethylation in HCC and corresponding control groups, and compared the incidence of GSTP1 hypermethylation in tumor tissues, pericancer liver tissues, normal liver issues, and nontumor liver tissues with that in other diseases. Data regarding publication information, study characteristics, and incidence of GSTP1 hypermethylation in both groups were collected from these studies and summarized. Eleven studies, including 546 cases of HCC and 575 nontumor cases, were identified for meta-analysis. Results: Statistically significant odds ratios (ORs) of GSTP1 hypermethylation were obtained from tumor tissues and nontumorous liver tissues of HCC patients (OR 2.63, 95% confidence interval [CI]: 1.77–3.89%, P < 0.0001), tumor tissues of HCC patients, healthy liver tissues of patients with other diseases (OR 7.29, 95% CI: 2.87–18.51%, P < 0.0001), tumor tissues of HCC patients, and liver tissues of patients with nontumorous liver diseases (OR 2.13, 95% CI: 1.10–4.13%, P < 0.05). The pooled analysis showed significantly increased ORs of GSTP1 hypermethylation (OR 2.21, 95% CI: 1.01–4.84%, P < 0.05) from HCC tissues and cirrhotic tissues. Conclusions: The results of this meta-analysis suggest that GSTP1 hypermethylation induces the inactivation of GSTP1 gene, plays an important role in hepatocarcinogenesis, and is associated with an increased risk of HCC.

Aims: Several studies suggested that miR-499 rs3746444 polymorphism was associated with the risk of hepatocellular carcinoma (HCC). However, other studies did not confirm the result. To derive a more comprehensive estimation of the association between miR-499 rs3746444 polymorphism and HCC risk, we conducted a meta-analysis. Materials and Methods: PUBMED, COCHRANE, and WEB OF SCIENCE databases were retrieved for the association studies focused on the relationship between miR-499 rs3746444 polymorphism and the risk of HCC. The strength of the associations between miR-499 rs3746444 polymorphism and the risk of HCC was measured by odds ratios (ORs) with 95% confidence intervals (CIs). Results: A statistically significant association between miR-499 rs3746444 polymorphism and the risk of HCC was fond (OR = 1.26; 95% CI, 1.04–1.52; P = 0.02). In the subgroup analysis of race, Asian population with miR-499 rs3746444 polymorphism showed increased HCC risk (OR = 1.29; 95% CI, 1.03–1.62; P = 0.03). In the subgroup analysis of hepatitis virus status, patients with HBV and miR-499 rs3746444 polymorphism showed increased HCC risk (OR = 1.38; 95% CI, 1.17–1.64; P = 0.0002). In the subgroup analysis of source of control, both hospital- and population-based studies found significant results (OR = 1.46; 95% CI, 1.12–1.90; P = 0.005; OR = 1.19; 95% CI, 1.01–1.40; P = 0.04). Conclusions: This meta-analysis suggested that mir-499 rs3746444 polymorphism was associated with an increased HCC risk.

Background: Insulin receptor substrate 1 (IRS-1) has been known to be an associated factor with breast cancer progression. However, there has been little study with respect to the relationship between the expression of IRS-1 and breast cancer prognosis in clinical practice. In this study, we evaluated the impact of the estrogen receptor (ER) and IRS-1 on the recurrence and survival of breast cancer patients. Methods: We analyzed the pathologic finding of 376 tissue samples from breast cancer patients who received proper treatment between January 1990 and December 2006 using the tissue microarray. We measured the expression of ER and IRS-1 by immunohistochemistry staining and analyzed the difference of recurrence and survival rate in each subgroup of ER and IRS-1. Results: Our results show that there is a significant difference of disease-free survival (DFS) according to ER and IRS-1 subgroups with both univariate and multivariate analyses. Specifically, ER-positive and IRS-1-positive breast cancer samples showed improved DFS compared to ER-positive and IRS-1-negative breast cancer (adjusted hazard ratio: 2.17; 95% confidence interval: 1.15–4.09; P = 0.01). There was a difference of overall survival according to ER and IRS-1 subgroups by univariate analysis (P = 0.01), but not by multivariate analysis (P = 0.36). Conclusion: ER and IRS-1 subgroups appear to be critical factors for the prediction of breast cancer recurrence. In particular, we suggest that the patients who have ER-positive and IRS-1-negative breast cancer undergo more aggressive treatment because they have poorer prognoses.

Background/Objective: It has been reported that Krüppel like factor 6 intervening sequence (KLF6 IVS) 1-27 G > A might be associated with cancer susceptibility. Here, we conducted a meta-analysis to summarize and clarify this association. Materials and Methods/Main Results: A systematic search of studies on the association between KLF6 IVS 1-27 G > A, and cancer susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. Seven articles were included in our meta-analysis. Overall and in prostate cancer, population-based subgroup overall and Caucasian subgroup overall, no evidence was found for the association between KLF6 IVS 1-27 G > A polymorphism and cancer susceptibility in any genetic model and the results showed stability in sensitivity analyses. Conclusions: KLF6 IVS 1-27 G > A may not be associated with cancer susceptibility, especially the susceptibility of unselected prostate cancer. However, there was insufficient data to fully confirm the association between KLF6 IVS 1-27 G > A and familial prostate cancer, sporadic prostate cancer, gastric cancer, and cancers from different ethnicity, and the results should be interpreted with caution.

Aim: This study was conducted to investigate the anti-tumor effects of the Chinese traditional herb phenolic alkaloids of menispermum dauricum (PAMD) on gastric cancer both in vitro and in vivo. Materials and Methods: Cell apoptosis was detected in cultured SGC-7901 cells after administration of a different dose of PAMD. Gastric cancer model was established by single i.p. injection of SGC-7901 cells in the mice (n = 60). Then, animals were received high dose (20 mg/kg), medial dose (10 mg/kg), and low dose (5 mg/kg) of PAMD. Mice received 5-floxuridine was set as positive controls and received normal saline was as blank controls. Effects of PAMD on tumor growth were evaluated by tumor inhibition rate. Tumor tissues were collected from mice and detected for the expression of several genes P53, B-cell CLL/lymphoma 2 (BCL-2), BCL-2-associated X protein (BAX), CASPASE-3, K-RAS by real-time polymerase chain reaction, and Western blot. In addition, tumor cell changes were observed under transmission electron microscopy. Results: The apoptosis index in PAMD at high- and medial-dose group was significantly higher than that in blank control group (P < 0.01). PAMD at different dose could significantly decrease the tumor weight compared to the blank control group (P < 0.01). In addition, PAMD could obviously increase BAX and caspase-3 expression as well as decrease K-RAS expression when compared to the blank control treatment (P < 0.01). Furthermore, PAMD could induce tumor cell morphology changes. Conclusions: PAMD could suppress gastric tumor growth in vivo, possibly through increasing the expression of pro-apoptotic genes expression then leading to cell apoptosis and inhibiting oncogenic K-RAS expression.

Objective: Cancer patients with bone marrow metastases are rare and dismal. The study was to identify the clinical features and prognostic factors in cancer patients with bone marrow metastases. Patients and Methods: A total of 30 patients with bone marrow metastases were reviewed between September 2007 and September 2013. Bone marrow metastases were identified by bone marrow aspiration. Results: The median age was 56.5 years (range, 8–85 years). The two most common primary tumor sites were the stomach (7, 23.3%), breast (5, 16.7%). Bone metastases (27, 90.0%) were the most common concurrent metastases. The most common cause for bone marrow aspiration was anemia and thrombocytopenia (10, 33.3%). The median survival time was 3 months (range, 0.5–82 months). Patients with good performance status (n = 19) had a longer median survival time than patients with poor performance status (n = 11) (8 months vs. 1 months, P = 0.041). Patients with primary unknown origin (n = 5) had a significantly shorter overall survival time than patients with known origin (n = 25) (1 month vs. 6 months = 0.010). The median survival time was 9 months in the systemic therapy group (n = 21) and 1 month in the best supportive care group (n = 9) (P = 0.000). Conclusion: To make primary origin clear and start systemic antitumor therapy is beneficial for patients with bone marrow metastases.

Aims: Some studies investigated the association between CCND1 rs9344 polymorphism and hepatocellular carcinoma (HCC) risk. However, the results were inconclusive. Thus, we did a meta-analysis to determine this relationship. Materials and Methods: Relevant studies were systematically searched using the PubMed, CNKI, and EMBASE databases. The strength of the association was calculated with the odds ratio (OR) and respective 95% confidence intervals (Cis). Results: We investigated the association between CCND1 rs9344 polymorphism and HCC risk in the dominant models. The result of this meta-analysis showed that CCND1 rs9344 polymorphism did not significantly associated with HCC risk (OR = 1.09; 95% CI 0.88–1.34). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with HCC risk in Caucasians (OR = 1.55; 95% CI, 1.05–2.29). However, we did not find any significant association between this polymorphism and HCC risk in Asians (OR = 0.91; 95% CI, 0.71–1.18). Conclusions: This meta-analysis suggested that CCND1 rs9344 polymorphism might be associated with the risk of HCC among Caucasians.

Aim: The aim of this study is to investigate the mechanism of baicalein in inducing human liver cell line SMMC-7721 apoptosis. Materials and Methods: Twenty micromoles baicalein or 10 μM LY294002 was adopted to treat SMMC-7721 cells. Cell proliferation was tested by cell counting kit-8 assay. Cell cycle was determined by flow cytometry and cyclin D1 expression. Cell apoptosis was detected by annexin V/propidium iodide double staining. Phosphatidyl inositol 3-kinase (PI3K)/Akt signaling pathway was assessed by real-time polymerase chain reaction and Western blot. Results: Baicalein suppressed liver cancer cell SMMC-7721 proliferation and induced cell apoptosis together with LY294002. Baicalein blocked cell cycle in G0–G1 phase and downregulated cyclin D1 level. Baicalein and LY294002 significantly suppressed PI3K/Akt signaling pathway-related molecule activity at both mRNA and protein levels (P < 0.05). Conclusion: Baicalein can inhibit liver cancer cell proliferation and promote cell apoptosis by affecting PI3K/Akt signaling pathway together with LY294002.

Aim of the Study: Results on the relationship between cytotoxic T-lymphocyte antigen 4 (CTLA4) +49A/G (rs231775) gene polymorphism and colorectal cancer risk are still debated. This meta-analysis was performed to assess the association between CTLA4 +49A/G and colorectal cancer risk. Materials and Methods: The relevant studies were searched from PubMed, Cochrane Library, and China Biological Medicine Database-disc, and eligible investigations were included and synthesized using meta-analysis method. Results: Eleven studies were recruited into this meta-analysis for the association of CTLA4 A/G gene polymorphism and colorectal cancer risk, consisting of 1802 colorectal cancer patients and 2939 controls. G allele was a risk factor for the colorectal cancer risk, and AA genotype might be a protective factor against colorectal cancer risk in overall populations (G allele: Odds ratio [OR] = 1.19, 95% confidence interval [CI]: 1.03–1.38, P = 0.02; AA genotype: OR = 0.63, 95% CI: 0.47–0.84, P = 0.002). However, the GG genotype was not associated with colorectal cancer risk in overall populations. Conclusion: The association between CTLA4 G allele/AA genotype and colorectal cancer risk was found in this meta-analysis.

Primary pulmonary epithelioid angiosarcoma is an extremely rare malignancy. Herein, we report the case of an elderly Chinese patient with primary pulmonary epithelioid angiosarcoma. The 72-year-old man presented with a 1-month history of persistent hemoptysis and left chest pain and weight loss of 3 kg. A chest computed tomography (CT) scan revealed two masses (maximum size 3.0 cm × 2.0 cm and 0.8 cm × 0.5 cm) in right lower lobe. We performed a left thoracotomy for tumor resection. Pathological examination showed that there was a significant amount of hemorrhage, fibrinous exudates, degeneration, and necrosis. With immunohistochemical analysis, tumor cells had strong expression of CD34, FLI-1, vimentin. Morphological and immunohistochemical findings supported the diagnosis of epithelioid angiosarcoma.

Cardiac side effects of targeted chemotherapy agents are getting more and more important topic nowadays. However, the studies on this topic are limited. Because multiple agent chemotherapy is not a common treatment option, it is hard to establish controlled study groups (as before chemotherapy and after chemotherapy); further, cancer, itself, may cause cardiac side effects and uncertainty of the symptoms may be associated with previous clinical situation before chemotherapy. For all that, we may get information to a certain degree about the side effects of these agents by analyzing case reports. These side effects have a broad spectrum from asymptomatic rhythm alterations to acute cardiac death. In this case report, we aim to discuss asymptomatic ventricular bigeminal rhythm, which is proved by electrocardiography, of our patient during treated by trastuzumab.

The objective of the study was to highlight the significance of surgical treatment for esophageal carcinoma after distal gastrectomy and provide suitable surgical options. A patient with esophageal carcinoma and previous distal partial gastrectomy was treated by replacing the esophagus with remnant stomach and moving the spleen into the thoracic cavity. We then systematically reviewed the literature on the treatment of such conditions. Postoperative recovery went well. During the 2-year follow-up, the patient did not complain any discomfort and had no signs of metastasis or recurrence. For esophageal carcinoma patients who have undergone distal gastrectomy, surgery should remain an option. For patients whose carcinoma is in the lower part of the esophagus or who are frail but had an early diagnosis, surgery to replace the esophagus with remnant stomach and relocation of the spleen into the thoracic cavity should be considered.

Adult fibrosarcoma (FS) of the maxillary sinus and the cranial base is a rare soft tissue sarcoma which is clinically characterized by a high frequency of local repeated recurrence if not excised widely. At present, the standard treatment option for FS is surgical resection. Here, we report a case of a 46-year-old male with a 5 months history recurrent FS of the maxillary sinus. The patient possessed an enormous mass in the right maxillofacial region extending to the cranial base, as observed by computed tomography. Histologically, the lessions were composed of hypercellular cells with heterogenous groups. The recurrence and pathologically heterogenous groups of FS lead to therapeutic complexities. Due to the challenging anatomy in head and neck region, it is crucial to define the lesion areas and weigh the balance between life quality and functional reconstruction.

Occult thyroid carcinoma is mostly discovered by autopsy or by other causes of thyroid surgery. To the best of our knowledge, there have been only a few reports concerning the situation that cervical mass was the initial manifestation of occult papillary thyroid carcinoma. The three patients in our report were all admitted to hospital because of the masses on their necks. Although pathology reports showed the nodal presence of thyroid cancer, we did not find the primary tumor on the same side of thyroid. We reported the clinical data of patients, including chief complaint, ultrasonography, computed tomography, and pathology results. We attempt to raise awareness regarding this particular disease and as a reference for clinical diagnosis and treatment. Examinations are needed to confirm the diagnosis for occult cancer of the thyroid. Surgical procedure is the major treatment method at present.