Showing papers in "Journal of Cancer Research and Therapeutics in 2018"

Therapeutic approaches targeting cancer stem cells.

Abstract: Increasing studies have demonstrated that most tumors consisted a subpopulation of cells with stem cell properties, known as cancer stem cells (CSCs). Accumulating evidence indicated that CSCs may be critical driving force for several types of cancer. Hence, it was necessary to develop therapeutic approaches specifically targeting CSCs. In this review, first, the biological properties of CSCs were introduced, including the self-renewal and differentiation, high tumorigenesis and invasiveness, resistance to chemotherapy and radiotherapy, genetic and epigenetic variations. Meanwhile, CSCs-targeted therapeutic strategies were summarized, including targeting cell surface markers, signaling pathways, CSC niches, differentiation therapy, and drug resistance for CSCs. Furthermore, clinical trials on anti-CSCs therapies supported the efficacy of these therapies, as well as their combination with conventional chemotherapy and radiotherapy. CSCs could be significantly eradicated, eventually resulting in inhibited tumor growth, metastasis, and recurrence. Thus, selectively targeting CSCs with various agents may be a novel and promising therapeutic strategy against cancer.

Relationship between resilience, social support as well as anxiety/depression of lung cancer patients: A cross-sectional observation study.

Abstract: Objective: The mood of patients with lung carcinoma would be greatly influenced by the diagnosing and treating processes. This study was aimed to explore the effects of resilience between social assistance and anxiety/depression of patients with lung cancer, which may assist in clinical intervention. Design and Methods: A cross-sectional pilot study was conducted on lung cancer patients at Xiangya Hospital of Central South University, China. A total of 289 patients aged 25–81 years were included in this study. Results: Correlational analyses revealed that anxiety/depression was negatively associated with psychological resilience and each dimension of social assistance, including subjective support, objective support along with the supports utilization (P Conclusion: Lower psychological anxiety and depression would be experienced by lung cancer patients with higher resilience and social support. The level of anxiety and depression would be indirectly affected by social support through the mediation of resilience.

Expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors (2018 edition).

Abstract: Although surgical resection with curative intent is the main therapy for both primary and metastatic lung tumors, about 80% of lung cancers cannot be removed by surgery. Because most patients with unresectable lung cancer only receive limited benefits from traditional radiotherapy and chemotherapy, many novel local treatment modalities have emerged including local ablation therapy. The Minimally Invasive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association and Committee on Tumor Ablations, Chinese College of Interventionalists have organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures, describing the indications for candidates, assessing outcomes, and preventing postablation complications.

Checkpoint immunotherapy by nivolumab for treatment of metastatic melanoma.

Abstract: Clinical management of metastatic melanoma suffered historically from a lack of effective targeted and immunotherapies due to short-lived clinical responses. Recent advances in our understanding of tumor-immune signaling pathways, discovery of immunosuppressive checkpoints, and subsequent development of antibodies that target these checkpoints reverses the situation to some extent. Two antibodies ipilimumab and nivolumab gained Food and Drug administration approval for the treatment of metastatic melanoma and target two major immunosuppressive checkpoints cytotoxic T lymphocyte antigen and programmed cell death protein 1 (PD-1), respectively. Nivolumab binds to PD-1, prevents PD-1 interaction with ligand Programmed death ligand 1 (PD-L1), and thus releases the T-cell exhaustion events (such as T cell apoptosis, decrease in T cell proliferation, etc.) leading to buildup of potent tumor-specific immune response. Successful Phase I-III results with remarkable antitumor activity and safety led to approval of nivolumab against ipilimumab refractory metastatic melanoma. Nivolumab therapy is exciting in that it not only provides substantial benefit but also provides durable responses. This review focuses on the evolution of immunotherapy leading to nivolumab approval and its potential in treating melanoma either alone or in combination with other therapies.

Synergistic effect of thymoquinone and melatonin against breast cancer implanted in mice.

Abstract: 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.

Computed tomography-guided percutaneous microwave ablation for treatment of peripheral ground-glass opacity–Lung adenocarcinoma: A pilot study

Abstract: Purpose: The purpose of the study is to retrospectively evaluate the safety and efficacy of microwave ablation (MWA) for the treatment of ground-glass opacity (GGO)–lung adenocarcinoma. Materials and Methods: From December 2013 to June 2017, a total of 51 patients (22 males and 29 females, mean age of 69.4 ± 10.1 years) were included in this study, with 51 lung adenocarcinoma lesions showing GGO (mean long-axis diameter of 18.7 ± 6.05 mm). They received a total of 52 sessions of percutaneous computed tomography-guided (CT-guided) MWA. First, lung adenocarcinoma with GGO was histologically defined by needle biopsy under the guidance of CT. Second, the efficacy of CT-guided MWA was analyzed, including the feasibility, safety, 3 years local progression-free survival (LPFS), 3 years disease-specific survival, and 3 years overall survival (OS). Final, complications after MWA were also summarized. Results: The technical success rate was 100%, without MWA procedure-related death. At the median follow-up period (27.02, range: 7–45 months), the rates of 3 years LPFS, cancer-specific survival, and OS were 98%, 100%, and 96%, respectively. The complications after MWA included pneumothorax (48.1%, 25/52), hemoptysis (28.8%, 14/52), pleural effusion (23.1%, 12/52), and pulmonary infection (7.7%, 4/52). Conclusions: CT-guided percutaneous MWA was a feasible, safe, and effective therapeutic approach for treating GGO–lung adenocarcinoma.

Health-related quality of life: Impact of surgery and treatment modality in breast cancer

Abstract: Background: Breast cancer is the most common malignancy among women leading to serious sequelae on the health-related quality of life (HRQOL). Materials and Methods: This is a cross-sectional study. The Arabic version of EORTC QLQ-C30 (version 3) and EORTC QLQ-BR23 questionnaire was administered to a random sample of 172 Egyptian women with breast cancer. One hundred and nineteen patients had modified radical mastectomy (MRM) and 53 had breast conservative surgery (BCS). Results: The mean age was 50.32 years (±standard deviation [SD] = 8.54) with a mean period of 4.75 years (±SD 3.33) from surgery. The global health was poor (28.38 ± 11.7, 95% confidence interval [95% CI]: 30.71). Among the functional scales of QLQ-C30, social functioning scored the highest (87.91 ± 17.92, 95% CI: 91.64) whereas emotional functioning scored the lowest (59.61 ± 24.96, 95% CI: 64.66). The most distressing symptom on the symptom scales of QLQ-C30 was financial impact followed by fatigue and pain (mean: 57.87, 39.43, and 36.44). Using the disease-specific tools, it was found that body image and sexual functioning scored the lowest (mean 74.51 ± 13.21 and 74.45 ± 14.89, 95% CI: 77.27 and 77.55), respectively. On the symptom scale, arm symptoms scored the highest with a mean of 32.35 ± 23.22 (95% CI: 37.19). MRM patients had more favorable global health status and body image among the functional scale (P = 0.011, 0.027) due to social and religious issues. The functional scale was better in BCS with significant role function (P = 0.004). In the symptom scale, fatigue, pain, systemic side effects, and arm symptoms were statistically significant better in the BCS (P = 0.004, 0.006, 0.002, and 0.003, respectively). Conclusion: Egyptian breast cancer survivors reported lower overall global QOL. HRQOL is better in BCS in spite of good global health and body image in MRM.

Evaluation of circulating miR-21 and miR-222 as diagnostic biomarkers for gastric cancer

Abstract: Introduction: Gastric cancer is responsible for a large number of death worldwide and its high death rate is associated with a lack of noninvasive tools in GC diagnosis. MicroRNAs (miRNAs), as gene regulators, were shown to dysregulate in different types of cancer. Moreover, it is proven that miRNAs are stable in serum/plasma, so they can be used as a potential noninvasive marker in GC diagnosis. The objective of this study is to investigate the plasma miRNA expression in GC samples compared to controls as a potential biomarker in cancer diagnosis. Materials and Methods: Expression levels of miR-21 and miR-222 were assessed using quantitative real-time polymerase chain reaction in plasma of 30 GC patients and 30 healthy controls. Diagnostic value of selected miRNAs was evaluated using receiver operating characteristic curve. Target prediction was done using bioinformatics tools to investigate the signaling pathways and function of the selected miRNAs. Results: Our results demonstrated that the expression levels of miR-21 and miR-222 were significantly higher in GC plasma than in the controls (P Conclusion: Our results indicated that miR-21 and miR-222 in plasma samples can be served as a potential noninvasive tool in GC detection. Furthermore, the miRNA target prediction manifested that miR-21 and miR-222 involve in key processes associated with GC initiation and development.

The effects of gilaburu (Viburnum opulus) juice on experimentally induced Ehrlich ascites tumor in mice.

Abstract: Objective: The aim of study was to investigate anticancer effect of Viburnum opulus (VO) on Ehrlich ascites carcinoma (EAC) bearing mice that treated with different concentrations of VO. Materials and Methods: For tumor transplantation; mice were inoculated with 1 × 106 EAC cells intraperitoneally and than divided into five groups (n = 9). Two hours after inoculation; experimental groups were treated daily with VO extract at doses of 1000 mg/kg, 2000 mg/kg, 4000 mg/kg. Results: Extracts obtained from gilaburu juice can have hinder effect on tumor cell growth. Conclusion: As far as we known, this is the first study about in vivo antitumoral activity of VOon Ehrlich ascites tumor model, and consequently VO extract exhibited anticancer activity against EAC-bearing mice.

Circulating microRNA-21 as a prognostic, biological marker in cholangiocarcinoma.

Abstract: Aims: The prognosis of cholangiocarcinoma (CCA) is generally poor because there is a lack of effective diagnostic tools including laboratory assessments and imageological examination. Therefore, a novel biological marker (biomarker) to effectively diagnose cancer is highly desirable in clinical. Previously, serum microRNAs as biomarkers of cancers have been reported. However, it was still unclear about the clinical significance of serum microRNA-21 (miR-21) expression levels for CCA. Materials and Methods: The serum samples were separately collected from fifty patients of CCA, 15 patients of hepatolithiasis, and 15 healthy volunteers; quantitative real-time polymerase chain reaction was used for measuring miR-21 expression level in serum. The clinicopathological data were recorded before patients discharged. Results: In the CCA serum, the expression level of miR-21 significantly upregulated (P 0.05 for both). Furthermore, the miR-21 level was significant difference between pre- and post-operative serum (P Conclusions: This study suggested that serum miR-21 was a promising biomarker for diagnosing the late stage CCA and would have potential to be a useful prognostic biomarker of CCA.

Dynamic changes of T-cell subsets and their relation with tumor recurrence after microwave ablation in patients with hepatocellular carcinoma

Abstract: Aims: Thermal ablation can evoke an immune response, which may have effects on the prognosis of patients with hepatocellular carcinoma (HCC). Our aim is to investigate the changes of circulating T-cell subsets after microwave ablation (MWA) and to explore the risk factors of tumor recurrence in patients with hepatitis B virus (HBV)-related HCC. Methods: Thirty patients with HBV-related HCC were enrolled in this study. The blood samples were collected both before and after MWA (24 h, 72 h, and 1 month after MWA). The distributions of Th17 cells, regulatory Treg-cells, CD4+ T-cells, CD8+ T-cells, and CD3+ T-cells were determined by flow cytometer. The potential-related factors of tumor recurrence were analyzed by logistic regression. Results: The levels of circulating T-cell subsets, except for Th17 cells, were relatively stable after MWA. The frequency of Th17 cells increased from 3.98% ± 2.40% before treatment to 5.53% ±3.27% 24 h after treatment. Eight of 30 patients had a tumor recurrence. The results of logistic regression suggested that among 11 candidates, only the level of Th17 cells was the risk factor of tumor recurrence. To remove the interference from other factors, seven patients with tumor(s) >3 cm or alpha-fetoprotein >400 ng/mL were excluded in another parallel logistic regression. The results of such regression clearly demonstrated that circulating Th17 cells is indeed a related factor of tumor recurrence. Conclusions: Thermal ablation may evoke a transitional immune response by increasing the frequency of Th17 cells. Patients with high levels of baseline circulating Th17 cells, instead of the transient elevation of Th17 cells induced by MWA, are at the risk of tumor recurrence.

Medical expenditure for liver cancer in urban China: A 10-year multicenter retrospective survey (2002-2011).

Abstract: Objective: This study aims to understand the medical expenditure for liver cancer during 2002-2011 in urban areas of China. Materials and Methods: This is a retrospective study. Based on a stratified cluster sampling method, a medical expenditure survey collected basic personal information from related medical records. Two-tailed independent sample t-test, variance analysis, and Student–Newman–Keuls Tests were used in cost analysis for the corresponding data types. Results: A total of 12,342 liver cancer patients were included in the analysis. Overall average medical expenditure per case for liver cancer diagnosis and treatment in China has increased from ¥21, 950 to ¥40, 386 over the study period. For each liver cancer patient diagnosed between 2009 and 2011, the average expenditures were 29,332 CNY for stage I, 35,754 CNY for stage II, 34,288 CNY for stage III, and 30,275 CNY for stage IV diseases (P Discussion: As a major cancer in China, liver cancer accounts for a large portion of health economic burden and its medical expenditure is heavy for families. Early diagnosis and treatment for liver cancer will save medical expenditure. Conclusion: The economic burden of liver cancer is high in China and related medical expenditure has increased.

Role of dexmedetomidine in reducing the incidence of postoperative cognitive dysfunction caused by sevoflurane inhalation anesthesia in elderly patients with esophageal carcinoma

Abstract: Background: Sevoflurane anesthesia is a high-risk factor for postoperative cognitive dysfunction (POCD) in elderly patients. Recently, some studies demonstrated that dexmedetomidine (DEX) could reduce the incidence of POCD caused by sevoflurane anesthesia. We hypothesized that DEX could reduce the incidence of POCD caused by sevoflurane anesthesia through decreasing plasma interleukin (IL-6) and tumor necrosis factor (TNF)-α concentrations. Materials and Methods: A total of 120 patients aged 65–75 years scheduled for esophageal carcinoma resection were randomly assigned to four groups. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to measure patients' cognitive function the day before operation and the 1st, 3rd, and 7th postoperative days. The plasma TNF-α, IL-6, and S100 β protein concentrations were measured by ELISA 10 min before anesthesia administration and the 1st, 3rd, and 7th postoperative days. Results: There were no significant differences in the demographic or clinical characteristics or perioperative hemodynamic status in all groups. Compared with Group M + P, the MMSE and MoCA scores were significantly lower and the plasma TNF-α, IL-6, and S100 β protein concentrations were significantly higher in Group M + S at the 1st, 3rd, and 7th postoperative days (P Conclusion: The POCD incidence was higher in elderly patients receiving sevoflurane anesthesia and DEX could alleviate POCD in these patients through decreasing plasma TNF-α and IL-6 concentrations.

Synergistic effect of temozolomide and thymoquinone on human glioblastoma multiforme cell line (U87MG)

Abstract: Aims: Temozolomide (TMZ) is an alkylating agent used for glioblastoma multiforme (GBM) treatment. Nevertheless, resistance to TMZ is a major obstacle to successful treatment of this cancer. The aim of the present study was to investigate the effects of TMZ and thymoquinone (TQ) on U87MG cell line. Materials and Methods: The effect of TMZ and/or TQ on viability and invasion potential of U87MG cells was evaluated using various techniques including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase activity, cell invasion, migration, and adhesion assays. Enzyme-linked immunosorbent assay and polymerase chain reaction were used to study the expression and secretion of matrix metalloproteinases (MMPs). Results: Combination of TMZ and TQ had a synergistic cytotoxic effect on U87MG cells. TMZ and/or TQ significantly reduced the potential of U87MG cells invasion. In addition, after treating with TMZ and/or TQ, there was a decrease in the levels of matrix matrix metalloproteinase 2 nad 9 (MMP 2 and 9) expression and secretion in U87MG cells. Conclusions: The combination of TMZ and TQ may emerge as a promising strategy for the successful treatment of GBM.

Expert consensus statement on computed tomography-guided 125I radioactive seeds permanent interstitial brachytherapy

Abstract: The aim of this study is to develop expert consensus statement for recommendations of patient selection criteria, prescription dose, and procedure of computed tomography (CT)-guided 125I radioactive seeds permanent interstitial brachytherapy. Members of Chinese medical association radiation oncology branch, Chinese medical association radiation therapy professional committee, Chinese cancer society minimally invasive surgery branch seed therapy group, Chinese geriatric cancer society minimally invasive surgery branch, Beijing medical association radiation oncology professional committee, China northern radioactive seeds brachytherapy group formed a committee, which consists of physician members who come from the department of radiation oncology, surgery, intervention, internal medicine, ultrasound, and nuclear medicine. The leader of the group organized experts to write the first draft based on clinical experience and literature review and then sent the draft to the commissioner for consultation, finally reached a consensus. Guidelines for patient selection criteria, prescription dose of 125I seed for different kinds of carcinomas, activity of per seed, and workflow of CT-guided permanent interstitial radioactive seed implantation (RSI) are presented in this study. The procedure of CT-guided RSI comprised eight steps: indication selection, preoperative preparation, preoperative CT simulation and position setup, preplan, intraoperative needle insertion, RSI, postoperative dosimetric evaluation, and follow-up. Patient selection criteria are developed. Guidelines for prescription dose of 125I seed for different kinds of carcinomas, activity of per seed, and workflow of CT-guided permanent interstitial RSI are provided.

Long noncoding RNAs in cervical cancer.

Abstract: This is a review about long noncoding RNAs (lncRNAs) and cervical cancer, especially the crucial regulating role played by lncRNAs on cervical cancer. LncRNAs are a big family with popular investigation in the last years. LncRNAs, as its noncoding proteins, once were considered to be useless RNAs without much more concern. However, much more attention was paid with the unique relationships between lncRNAs and disease. Especially, lncRNAs were evaluated and found its modifying and regulating functions in the process of cancer development. In this review, we summarize the characteristics of certain lncRNAs which are crucial for cervical cancer, find their mechanisms, and provide more possible direction for following evaluations including the point for target treatment.

The anti-cancer efficacies of diffractaic, lobaric, and usnic acid: In vitro inhibition of glioma.

Abstract: Aims: Glioblastoma multiforme (GBM) shows the most aggressive invasion among primary brain tumors. In spite of the standard therapy methods such as surgery, radiotherapy, and chemotherapy, the mortalities are high in GBM patients owing to side effects. Some lichen secondary metabolites that have many bioactive functions exhibited anti-cancer efficacy toward many cancer types. The present study was undertaken to investigate proliferation change, oxidative status and DNA damage potentials of human U87MG-GBM, and primary rat cerebral cortex (PRCC) cells exposed to three lichen secondary metabolites. Materials and Methods: Different concentrations of lichen secondary metabolites including diffractaic acid (DA), lobaric acid (LA), and (+)-usnic acid (UA) were used for the treatments. PRCC cells were obtained from Sprague Dawley® rats. U87MG cell line was preferred as GBM cells. Results: The results showed that lactate dehydrogenase and 8-hydroxy-2'-deoxyguanosine levels increased in PRCC and U87MG cells in a clear dose-dependent manner. Inhibitory concentration 50% (IC50) values of LA, DA, and UA were calculated as 9.08, 122.26, 132.69 mg/L for PRCC cells and 5.77, 35.67, 41.55 mg/L for U87MG cells, respectively. Concentration of 10 mg/L of DA and UA demonstrated high anti-oxidant capacity on healthy PRCC cells. Conclusions: Overall, obtained data indicated that LA was highly toxic on GBM and PRCC cells. However, DA and then UA had high anti-oxidant capacity on PRCC cells. These results suggest that further studies that will be held on LA may play a critical role in GBM treatment.

Expression level of long noncoding RNA H19 in plasma of patients with nonsmall cell lung cancer and its clinical significance.

Abstract: Objective: This study was aimed to explore the expression level of long noncoding RNA H19 in the plasma of patients with nonsmall cell lung cancer (NSCLC) and its clinical significance. Methods: A total of 66 NSCLC patients (case group) and 31 patients with benign lung disease (control group) admitted from February 2015 to February 2017 were included in this study. Real-time polymerase chain reaction assay was applied to examine the relative expression level of long noncoding RNA H19 in the plasma of the two groups. The relationship between H19 expression and clinical, pathological features was explored. Receiver-operating characteristic (ROC) curve was applied to evaluate the clinical value of plasma H19 as a tumor marker in the auxiliary diagnosis of NSCLC. Results: The relative expression levels of plasma H19 inpatients from NSCLC group and benign lung disease group were 5.62 ± 2.02 (ΔCt) and 7.74 ± 2.75 (ΔCt), respectively. The NSCLC group presented with significantly higher levels than that of the benign disease group (P 0.05). With the serum H19 as a diagnosis reference, the diagnostic sensitivity of NSCLC was 67.74%, and the specificity was 63.08%. The area under the ROC curve was 0.73, and the diagnostic cutoff value was 6.62. Conclusion: Plasma level of H19 in NSCLC patients was significantly increased, which could be applied as a serological marker for the auxiliary diagnosis of NSCLC.

Assessment of accuracy of out‑of‑field dose calculations by TiGRT treatment planning system in radiotherapy

Abstract: Aim: The objective was to quantify the accuracy of dose calculation for out-of-field regions by the commercially available TiGRT version 1.2 (LinaTech, Sunnyvale, CA, USA) treatment planning system (TPS) for a clinical treatment delivered on a Siemens Primus with the single energy of 6 MV. Materials and Methods: Two tangential open fields were planned by TiGRT TPS to irradiate the left breast of a RANDO phantom. Dose values to out-of-field points were calculated by TiGRT TPS. A RANDO phantom was then irradiated, and dose values at set points were measured using thermoluminescent detectors-100 (TLDs-100) which were located within the phantom. Finally, the TLD-measured dose was compared to the TPS-calculated dose and the accuracy of TPS calculations at different distances from the field edge was quantified. Results: The measurements showed that TiGRT TPS generally underestimated the dose of out-of-field points and this underestimation worsened for regions relatively close to the treatment field edge. The mean underestimation of out-of-field doses was 39%. Nevertheless, the accuracy of dose calculation by this TPS for most in-field regions was within tolerance. Conclusion: This study highlights the limitations of TiGRT TPSs in calculating of the out-of-field dose. It should be noted that out-of-field data for this TPS should only be applied with a certain understanding of the accuracy of calculated dose outside the treatment field. Therefore, using the TPS-calculated dose could lead to an underestimation of secondary cancer risk as well as a weak clinical decision for patients with implantable cardiac pacemakers or pregnant patients.

Epigenetic deregulations of Wnt/β-catenin and transforming growth factor beta-Smad pathways in esophageal cancer: Outcome of DNA methylation

Abstract: Background: Promoter methylation of tumor suppressor genes (TSGs) is a well-reported portent in carcinogenesis; hence, it is worthy to investigate this in high-risk Northeast population of India. The study was designed to investigate methylation status of 94 TSGs in esophageal squamous cell carcinoma (ESCC). Further, the effect of OPCML promoter methylation on gene expression was analyzed by immunohistochemistry. Moreover, in silico protein–protein interactions were examined among 8 TSGs identified in the present study and 23 epigenetically regulated genes reported previously by our group in ESCC. Materials and Methods: Methylation profiling was carried out by polymerase chain reaction array and OPCML protein expression was examined by tissue microarray-based immunohistochemistry. Results: OPCML, NEUROG1, TERT, and WT1 genes were found hypermethylated and SCGB3A1, CDH1, THBS1, and VEGFA were hypomethylated in Grade 2 tumor. No significant change in OPCML expression was observed among control, Grade 1, and Grade 2 tumor. Conclusively, hypermethylation of the studied OPCML promoter in Grade 2 tumor produced no effect on expression. Unexpectedly, OPCML expression was downregulated in Grade 3 tumor in comparison to other groups signifying that downregulation of OPCML expression may lead to higher grade of tumor formation at the time of diagnosis of ESCC in patients. Significant interactions at protein level were found as VEGFA:PTK2, CTNNB1:CDH1, CTNNB1:VEGFA, CTNNB1:NEUROG1, CTNND2:CDH1, and CTNNB1:TERT. These interactions are pertinent to Wnt/β-catenin and TGF-β-Smad pathways. Conclusions: Deranged OPCML expression may lead to high-grade ESCC as well as epigenetically regulated genes, that is, CDH1, CTNNB1, CTNND2, THBS1, PTK2, WT1, OPCML, TGFB1, and SMAD4 may alter the Wnt/β-catenin and TGF-β-Smad pathways in ESCC. Further study of these genes could be useful to understand the molecular pathology of ESCC with respect to epithelial-mesenchymal transition (EMT) mediated by Wnt/β-catenin and TGF-β signaling pathways.

Clinical significance of interleukin-6 in diagnosis of lung, oral, esophageal, and gall bladder carcinomas.

Abstract: 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: 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.

Programmed death 1 Ligand 1 expression in breast cancer and its association with patients' clinical parameters.

Abstract: Objective: To evaluate the expression of programmed death 1 ligand 1 (PD-L1) in the cancer tissues and tumor-adjacent normal tissues of patients with invasive ductal carcinoma of the breast and to analyze the relationship between the expression of PD-L1 and the clinicopathological features of patients. Materials and Methods: This study included 112 cases of patients with invasive ductal carcinoma of breast who received surgical treatment from March 2012 to February 2016 in Xuzhou Cancer Hospital. The clinical materials of included patients were retrospectively analyzed. The immunohistochemical assay and real-time polymerase chain reaction (PCR) assay were applied to examine the expression of mRNA and protein of PD-L1 in breast cancer specimens of 112 cases and paired tumor-adjacent tissue specimens of 57 cases. The relationship between PD-L1 protein expression and clinicopathological features of patients was analyzed. Results: PD-L1 protein was mainly expressed in the cytoplasm. The positive rate of PD-L1 expression in invasive ductal carcinoma was 19.6% (22/112), and the positive rate of PD-L1 expression of tumor-adjacent normal tissues was 3.5% (2/57), indicating that the positive rate of PD-L1 expression of cancerous tissues was significantly higher than that of in tumor-adjacent normal tissues (P 0.05) while it was related with lymph node metastasis, the clinic staging, and histopathological grading (P Conclusion: The expression of PD-L1 in breast-invasive ductal carcinoma was significantly increased, and it was related to histological grading, clinical staging, and lymph node metastasis of breast cancer. PD-L1 may be a significant marker for the prognosis of breast cancer patients.

Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer.

Abstract: Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma, is one of the most challenging tumor entities worldwide, which is characterized as a highly aggressive disease with dismal overall prognosis. Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy, and radiotherapy. In many cases, surgical resection is not possible due to the advanced stage at diagnosis and poor responses to current treatments, therefore, treatment alternatives have to be performed. However, brachytherapy through radioactive 125I seeds (RIS) implantation into pancreatic cancer has been first applied in unresectable carcinoma and made accuracy curative effects. Therapeutic procedures of RIS implantation for pancreatic carcinoma were not identical in domestic medical centers, making it hard to achieve homogeneity and affecting the efficacy seriously at last. To maximize the benefits of RIS for patients with pancreatic cancer, Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee and Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, Radioactive Seed Therapy Branch organized and helped establish China expert consensus on RIS implantation for the treatment of pancreatic cancer, to provide a reference for clinical practices.

The value of serum survivin level in early diagnosis of cancer.

Abstract: Objective: Survivin is one of the apoptosis inhibitor proteins, and it plays a key role in tumor angiogenesis and cancer progression. This study was conducted to investigate the serum level of survivin to determine its diagnostic value in cancer patients. Materials and Methods: Blood samples were taken from cancer patients (n = 67) prior to surgery or chemo/radiotherapy and age-matched healthy volunteers (n = 23). The serum levels of survivin were analyzed by enzyme-linked immunosorbent assays. The difference in serum levels between patients and control was evaluated by using statistical methods. Correlation between the serum levels of survivin and clinicopathological features of cancer patients were also evaluated. Results: The diagnoses of patients were breast cancer (49.3%), colon cancer (25.4%), ovarian cancer (14.9%), and other cancers (10.4%). Serum survivin levels were significantly higher in cancer patients than healthy subjects (196.23 pg/ml vs. 117.73 pg/ml, respectively, P = 0.019). No significant relations were found between serum survivin level and demographic characteristics of cancer. The optimal cut-off value of serum survivin was determined at >120.8 pg/ml, and its serum levels above this cut-off value were associated with 4.198 times increased risk of cancer. Conclusion: Our study results may suggest that high serum survivin levels can show 4 times increased risk of cancer in a subject with a high suspicion of cancer. Furthermore, survivin level was not influenced with demographic characteristics of breast, gastric, colorectal, prostate, ovarian cancer, and glioblastome multiforme.

miR-146a is deregulated in gastric cancer

Abstract: Background: Gastric cancer is one of the most significant reasons for cancer-related death. miR-146a is one of the dysregulated factors associated with gastric tumorigenesis. However, deregulation of this microRNA (miRNA) has become controversial. Moreover, the inflammation-mediating role of this miRNA implies that miR-146a might be dysregulated by gastric cancer-related pathogens, such as Helicobacter pylori. However, the dysregulation of miR-146a in H. pylori-infected gastric tumors has not been widely studied. Objectives: We aimed to analyze the expression level of miR-146a in gastric cancer tissues and then to assess any potential association between miR-146a and H. pylori infection and other clinical characteristics. Materials and Methods: miR-146a expression level was quantitatively studied by reverse transcription quantitative polymerase chain reaction, in 144 fresh tissues including 44 normal and 100 gastric cancer samples. Results: A dramatic overexpression of miR-146a was observed in primary gastric tumors. miR-146a showed lower expression in progressed tumors with greater stages and lymph node metastasis. Conclusion: miR-146a is highly expressed in primary gastric tumor independent of H. pylori infection. It is highly expressed in the lower stages and lymph node-negative tumors. It might suggest the importance of upregulation and downregulation of this miRNA in the initiating/promoting and progressive steps of gastric tumorigenesis, respectively.

Breast cancer tumor type recognition using graph feature selection technique and radial basis function neural network with optimal structure.

Abstract: Context: Breast cancer is a major cause of mortality in young women in the developing countries. Early diagnosis is the key to improve survival rate in cancer patients. Aims: In this paper an intelligent system is proposed to breast cancer tumor type recognition. Settings and Design: The proposed system includes three main module: The feature selection module, the classifier module and the optimization module. Feature selection plays an important role in pattern recognition systems. The better selection of features usually results in higher accuracy rate. Methods and Material: In the proposed system we used a new graph based feature selection approach to select the best features. In the classifier module, the radial basis function neural network (RBFNN)is used as classifier. In RBF training, the number of RBFs and their respective centers and widths (Spread) have very important role in its performance. Therefore, artificial bee colony (ABC) algorithm is proposed for selecting appropriate parameters of the classifier. Statistical Analysis Used: The RBFNN with optimal structure and the selected feature classified the tumors with 99.59% accuracy. Results: The proposed system is tested on Wisconsin breast cancer database (WBCD) and the simulation results show that the recommended system exhibits a high accuracy. Conclusions: The proposed system has a high recognition accuracy and therefore we recommend the proposed system for breast cancer tumor type recognition.

Up-regulated expression of miR-155 in human colonic cancer.

Abstract: Objective: The aim of this study is to investigate the expression of miR-155 in colonic cancer tissue and to assess the potential predictive value of miR-155 in colonic cancer patients. Materials and Methods: From March to September of 2011, we included 57 patients with primary colonic cancer who underwent curative surgical resection. Total RNAs were extracted from colonic cancer tissues and adjacent normal tissues. Then the expression of miR-155 in colonic cancer and paracancerous tissues was investigated using real time quantitative reverse transcription-polymerase chain reaction. And the relationship between miR-155 expression level and the clinical, pathological parameters of colonic cancer was analyzed. Results: The relative expression level of miR-155 in colonic cancer tissues was significantly higher than that in paracancerous tissues and related to tumor-node-metastasis staging, tumor invasion, metastasis, and differentiation. Conclusion: The expression of miR-155 is up-regulated in colonic cancer tissues. MiR-155 may acts as proto-oncogenes involved in carcinogenesis, development, and invasion of colon cancer making it a potential target for gene therapy of colon cancer.

miR-150 contributes to the radioresistance in nasopharyngeal carcinoma cells by targeting glycogen synthase kinase-3β

Abstract: Introduction: Radiotherapy has been the primary treatment for nasopharyngeal carcinoma (NPC), but the NPC radiocurability was severely limited with the radioresistance. The research suggested the important role of miRNAs in cancer therapeutic response. Materials and Methods: A radioresistant NPC cell line CNE-2R, we exposed CNE-2 cells to a range of radiation doses. Levels of miR-150 were measured by quantitative reverse-transcriptase polymerase chain reaction in CNE-2R and CNE-2 cells. Results: In this study, a cell line CNE-2R derived from parental CNE-2 was established via being exposed to stepwise escalated radiation dose. The expression of miR-150 was upregulated in CNE-2R cells. The radioresistance of CNE-2R cells was reversed after inhibiting miR-150 with specific inhibitor, while the radioresistance of CNE-2 cells was enhanced after the overexpression of miR-150. MiR-150b elicited these responses by directly targeting GSK3β. Moreover, GSK3β protein expression was downregulated in CNE-2R cells and restored GSK3β expression increased radiosensitivity of CNE-2R cells. Importantly, the negative correlation between miR-150 expression and GSK3β protein level was confirmed in the NPC tissues. High miR-150 expression and low GSK3β protein level were associated with poor prognosis in NPC patients. Conclusion: Our findings suggested that miR-150-GSK3β axis may be a novel candidate for developing rational therapeutic strategies for NPC treatment.

The epidemiological and histological trend of bladder cancer in Iran.

Abstract: Introduction: Bladder cancer is the ninth common cancer in the world, the third common cancer among men in the Arabic and Western Asian countries, and the second in some regions of Iran (a country in the Middle East). There was no study on the epidemiological and histological trend of bladder cancer in Iran. This study aimed to the epidemiological and histological trend of bladder cancer in Iran. Materials and Methods: In this study, data were extracted from annual cancer registry reports of Iranian Ministry of Health between 2003 and 2008. Standardized incidence rates were calculated using the world standard population and incidence rate was calculated by age groups, sex, and histological type. Data on epidemiologic trend and histology were analyzed using Joinpoint software package. Results: A total of 23,291 cases were reported. Almost 17.70% (4127 cases) were women and 82.30% (19,170 cases) men. The sex ratio (male to female) was 4.65. Joinpoint analysis showed the significant increased trend of age-standardized incidence rate (ASIR) for both sexes. The annual percentage change of standardized incidence rate was 11.5 (confidence interval [CI]: 9.0–14.0) in women and 10.8 (CI: 8.0–13.6) in men. Two histological types of transitional cell carcinoma (TCC), not otherwise specified and papillary TCC included 43.89% and 49.86% of all cancer cases, respectively. Conclusion: According to this study the trend of ASIR of bladder cancer in Iran is rising, so it is necessary to conduct further researches in future to provide accurate information on the cancer and investigate related risk factors and implement prevention programs in Iran.