Τρίτη 19 Απριλίου 2016

Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect

Publication date: Available online 19 April 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Ahitagni Biswas, Pramod Kumar Julka
Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the importance of awareness and timely identification and management of this dermatological toxicity in patients undergoing bleomycin based combination chemotherapy.



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Effect of methyl butyrate aroma on the survival and viability of human breast cancer cells in vitro

Publication date: Available online 19 April 2016
Source:Journal of the Egyptian National Cancer Institute
Author(s): Mohsin Ali Khan, Rumana Ahmad, A.N. Srivastava
BackgroundAroma can have far reaching effects on mind, body and soul. Pleasant aromas are known to have a soothing effect on the mind and are known to relieve stress and enhance concentration. Recently, it been demonstrated that aroma may also have some curative effects as well as benefits and can be used both for prophylaxis and therapy of diseases. Our aim was to test our hypothesis whether aroma can cure or prevent cancer. Methyl butyrate (MB) is the methyl ester of butyric acid having a characteristic sweet and fruity odor like that of apples and pineapples. It occurs in many plant products in minute quantities and in pineapple oil.MethodsIn the present study, the effect of aroma of MB has been evaluated on human breast cancer cell line MDA-MB-231 in vitro. The percentage viability of the cell line was determined by using Trypan blue dye exclusion assay.ResultsIt was found that MB at a concentration of 0.01M was effective in causing considerable cytotoxicity (40%) in breast cancer cells (without even coming in contact with cells) while at 0.02M, % cytotoxicity was found to be 50%. Mechanism of action of MB on cancer cells was investigated by acridine orange–ethidium bromide assays using fluorescence microscopy and DNA fragmentation assay. MB aroma appeared to induce necrosis in cancer cells exposed to it.ConclusionNo study involving the effect of aroma/smell on cancer cells has ever been reported before and warrants further investigation on other cancer and normal cell lines.



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Pembrolizumab Shows Promise in Patients with Rare Form of Skin Cancer

In a small clinical trial, more than half of the patients with an aggressive form of skin cancer called Merkel cell carcinoma responded to the drug pembrolizumab (Keytruda®), which strengthens the immune response against cancer. Overall, the responses have been longer-lasting than those typically seen in patients with this very rare cancer who have received chemotherapy.

The 26 patients in this phase II trial had an advanced form of the disease, and none had received prior systemic treatment. Among the 25 patients who could be evaluated, 14 patients (56 percent) had a complete or partial response, Paul Nghiem, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center reported on April 19 at the annual meeting of the American Association for Cancer Research (AACR) in New Orleans.



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Elderly ovarian cancer patients: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO)

Publication date: June 2016
Source:European Journal of Cancer, Volume 60
Author(s): H. Woopen, G. Inci, R. Richter, R. Chekerov, F. Ismaeel, J. Sehouli
BackgroundBarriers for optimal treatment and enrolment in clinical trials are the physicians' perceptions towards age, comorbidities and fear of toxicity as well as the eligibility criteria of clinical trials. There is a high need to gain more knowledge about this patient group in order to optimize treatment. We aimed to evaluate the influence of age above 65 years on comorbidities, comedication, grade III/IV toxicity, prior discontinuation of chemotherapy and survival.Patients and methodsAn individual participant data meta-analysis of three phase II/III studies ('Tower', 'Topotecan phase III' and 'Hector') of the North-Eastern German Society of Gynecological Oncology including 1213 patients with recurrent ovarian cancer was conducted using logistic regression and Cox regression analysis.ResultsMedian age at diagnosis was 59 years. The patient group ≥65 years included 349 versus 864 patients younger than 65 years. Cardiovascular disease and diabetes were more frequent in the older age group (p < 0.001 and p = 0.001). Haematological and cardiovascular grade III/IV toxicities were more often seen in patients above 65 years, while non-haematological toxicity was not (p = 0.03, odds ratio [OR] 1.35; p = 0.04, OR 1.83; and p = 0.90, OR 0.98, respectively). There was no difference in prior discontinuation of treatment in multivariate analysis. Cox regression showed a trend towards poorer progression-free survival (p = 0.053, hazard ratio 1.143) in the older age group.ConclusionHaematological and cardiovascular toxicities are more frequent in elderly patients. However, this did not influence prior discontinuation of therapy. Elderly patients should not be deprived of adequate chemotherapy or excluded from clinical studies just because of their age. Thorough geriatric assessment and monitoring is mandatory.



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Corrigendum to “Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer” [Eur J Cancer 53 (2016) 51–64]

Publication date: Available online 19 April 2016
Source:European Journal of Cancer
Author(s): Sandrina Lambrechts, Dominiek Smeets, Matthieu Moisse, Elena Ioana Braicu, Adriaan Vanderstichele, Hui Zhao, Els Van Nieuwenhuysen, Els Berns, Jalid Sehouli, Robert Zeillinger, Silvia Darb-Esfahani, Dan Cacsire Castillo-Tong, Diether Lambrechts, Ignace Vergote




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Tumor control with PD-1 inhibition in a patient with concurrent metastatic melanoma and renal cell carcinoma

Abstract

Blockade of the immunological checkpoint programmed death 1 (PD-1) using monoclonal antibodies has shown robust anti-tumor activity across a broad range of solid and hematological malignancies including melanoma and renal cell carcinoma (RCC). Characteristic markers such as the presence of tumor infiltrating lymphocytes, PD-L1 status, and mutational load may be equally or even more important in predicting clinical benefit from PD-1 pathway blockade than tumor histology. This case of a patient with concurrent metastatic melanoma and metastatic RCC, both of which were controlled for more than a year after a single dose of the anti-PD-1 antibody pembrolizumab, illustrates the potential to simultaneously treat distinct immunogenic tumors with anti-PD-1 agents.



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Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Abstract

The N-methyl-d-aspartate receptor (NMDAr) is particularly vulnerable to aging. The GluN2B subunit of the NMDAr, compared to other NMDAr subunits, suffers the greatest losses of expression in the aging brain, especially in the frontal cortex. While expression levels of GluN2B mRNA and protein in the aged brain are well documented, there has been little investigation into age-related posttranslational modifications of the subunit. In this study, we explored some of the mechanisms that may promote differences in the NMDAr complex in the frontal cortex of aged animals. Two ages of mice, 3 and 24 months, were behaviorally tested in the Morris water maze. The frontal cortex and hippocampus from each mouse were subjected to differential centrifugation followed by solubilization in Triton X-100. Proteins from Triton-insoluble membranes, Triton-soluble membranes, and intracellular membranes/cytosol were examined by Western blot. Higher levels of GluN2B tyrosine 1472 phosphorylation in frontal cortex synaptic fractions of old mice were associated with better reference learning but poorer cognitive flexibility. Levels of GluN2B phosphotyrosine 1336 remained steady, but there were greater levels of the calpain-induced 115 kDa GluN2B cleavage product on extrasynaptic membranes in these old good learners. There was an age-related increase in calpain activity, but it was not associated with better learning. These data highlight a unique aging change for aged mice with good spatial learning that might be detrimental to cognitive flexibility. This study also suggests that higher levels of truncated GluN2B on extrasynaptic membranes are not deleterious to spatial memory in aged mice.



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The Herbal Medicine Utrica Dioica Inhibits Proliferation of Colorectal Cancer Cell Line by Inducing Apoptosis and Arrest at the G2/M Phase

Abstract

Background

One of the major causes of cancer death internationally and the third most prevalent cancer in the world has been diagnosed with colorectal cancer. Although current routine treatments of cancer have been successful in some extent, mortality caused by adverse effects of these strategies is still raising. Medicinal plants are potential sources of anticancer compounds and can be exploited as a powerful complementary tool. This study aimed to investigate the cytotoxic effects of nettle extract on mouse colorectal cancer cells, HCT.

Materials and Methods

In the present study, to evaluate the cytotoxicity of nettle extract, MTT assay and trypan blue were performed. Subsequently, DNA fragmentation and TUNEL test was carried out for determination of apoptosis. Real-time PCR test was used to quantify the expression of Caspase-3, Caspase-9, and Bcl-2 which is involved in apoptosis regulation. Finally, cell cycle analysis was conducted by using flow cytometry.

Results

The results of MTT assay showed that the dichloromethane extract of U. dioica extract significantly destroyed cancer cells HCT-116. DNA fragmentation and TUNEL test demonstrated that Utrica extract elicited apoptotic response in the cancer cells. The messenger RNA (mRNA) expression levels of Caspase-3 and Caspase-9 markedly increased, while the Bcl-2 gene was conversely downregulated. Findings of flow cytometry confirmed that cell cycle arrest has occurred at the G2 phase.

Conclusion

Taken together, our experiment showed that subjecting HCT-116 cells to dichloromethane extract of nettle (U. dioica), increases turnover of these cells. Thus, it may be a useful agent in the treatment of colorectal cancer.



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Issue Information - Ed Board



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Issue Information - TOC



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Importance of surgical margins in rectal cancer

Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter-saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs. J. Surg. Oncol. 2016;113:323–332. © 2016 Wiley Periodicals, Inc.



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Erratum to: Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study



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Risk of interactions between complementary and alternative medicine and medication for comorbidities in patients with melanoma

Abstract

Complementary and alternative medicine (CAM) is used widely among cancer patients. Beside the risk of interaction with cancer therapies, interactions with treatment for comorbidities are an underestimated problem. The aim of this study was to assess prevalence of interactions between CAM and drugs for comorbidities from a large CAM usage survey on melanoma patients and to classify herb–drug interactions with regard to their potential to harm. Consecutive melanoma outpatients of seven skin cancer centers were asked to complete a standardized CAM questionnaire including questions to their CAM use and their taken medication for comorbidities and cancer. Each combination of conventional drugs and complementary substances was evaluated for their potential of interaction. 1089 questionnaires were eligible for evaluation. From these, 61.6 % of patients reported taking drugs regularly from which 34.4 % used biological-based CAM methods. Risk evaluation for interaction was possible for 180 CAM users who listed the names or substances they took for comorbidities. From those patients, we found 37.2 % at risk of interaction of their co-consumption of conventional and complementary drugs. Almost all patients using Chinese herbs were at risk (88.6 %). With a high rate of CAM usage at risk of interactions between CAM drugs and drugs taken for comorbidities, implementation of a regular assessment of CAM usage and drugs for comorbidities is mandatory in cancer care.



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A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women

Publication date: June 2016
Source:Cancer Epidemiology, Volume 42
Author(s): Liang Chen, Zhigang Duan, Lesley Tinker, Haleh Sangi-Haghpeykar, Howard Strickler, Gloria Y.F. Ho, Marc J. Gunter, Thomas Rohan, Craig Logsdon, Donna L. White, Kathryn Royse, Hashem B. El-Serag, Li Jiao
ObjectivesReceptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand Nε-(carboxymethyl)-lysine (CML) and trigger dysregulation of adipokines and chronic inflammation. Soluble RAGE (sRAGE) mitigates the detrimental effect of RAGE. We examined the associations between circulating levels of CML-AGE and sRAGE and colorectal cancer (CRC).MethodsIn a case-cohort study of the Women's Health Initiative Study, blood levels of CML-AGE and sRAGE were measured using ELISA. We used multivariable Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CRC in relation to quartiles (Q) of biomarker levels.ResultsAverage follow-up was 7.8 years for 444 cases and 805 subcohort members. In the subcohort, CML-AGE and sRAGE were inversely correlated with BMI (P values<0.0001). Levels of CML-AGE and sRAGE were not associated with CRC. In BMI-specific analysis, the association between sRAGE and CRC was observed. Among women with BMI≥25kg/m2, those with highest levels of sRAGE had significantly lower risk for CRC as compared to women with lowest levels of sRAGE (HRQ4versusQ1: 0.39; 95% CI: 0.17–0.91). This inverse association was not observed among women with BMI <25kg/m2 (P value for interaction=0.01).ConclusionsAmong postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.



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Associations between prior HPV4 vaccine doses and cervical cancer screening participation

Publication date: June 2016
Source:Cancer Epidemiology, Volume 42
Author(s): Stephanie D. Boone, Christina M. Pinkston, Kathy B. Baumgartner, Richard N. Baumgartner, Sean M. Harper, Aaron J. Bonham, Christopher A. Paynter, Diane M. Harper
BackgroundCervical cancer screening, regardless of HPV vaccination, is a cornerstone of cancer prevention. This study evaluated associations between prior HPV vaccine doses and initiation and continued participation of screening by age at vaccination.MethodsUsing electronic medical records for a safety net healthcare system (Truman Medical Center), women aged 14–26y vaccinated (n=1123) between 07/01/2006 and 10/1/2009 were randomly selected and matched on birth year and health campus to unvaccinated (n=1123) women. Frequency of screening was determined through 07/01/2013. Hazard ratios (HR) for screening were estimated using Cox proportional hazards regression.ResultsScreening rates were higher after vaccination: unvaccinated (53%), first (62%), second (59%) or third (61%) doses. Women who initiated screening were less likely to complete the vaccine series, regardless of age. Women receiving one dose were more likely than unvaccinated women to initiate screening (HR=2.98 95% Confidence Interval (CI):2.45–3.61) and were more likely to screen than those receiving two (1 vs. 2, HR=2.94 95% CI:2.09–4.14) or three doses (1 vs. 3, HR=3.15 95% CI:2.21–4.48). Compared to unvaccinated women, women <21y who completed 3-doses were 1.8-times more likely to screen at ≥21y, whereas vaccinated women ≥21y were more likely to screen regardless of number of doses (p<0.0001).ConclusionsWomen who were vaccinated were more likely to screen than unvaccinated women; screening rate was highest after and occurred closest to the first vaccine dose. Research evaluating the efficacy of a one-dose vaccine is warranted and may provide both higher vaccination and screening rates.



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Helicobacter pylori infection and oesophageal adenocarcinoma

Publication date: Available online 18 April 2016
Source:Cancer Epidemiology
Author(s): Jannis Kountouras, Stergios A. Polyzos, Chistos Zeglinas, Panagiotis Katsinelos, Nikolaos Giorgakis, Elizabeth Vardaka, Constantinos Kountouras, Fotini Artemaki, Dimitri Tzivras, Eyaggelos Kazakos, Elena Tsiaousi, Georgia Deretzi




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Feasibility of laparoscopic total proctocolectomy with ileal pouch–anal anastomosis and total colectomy with ileorectal anastomosis for familial adenomatous polyposis: results of a nationwide multicenter study

Abstract

Background

Data supporting the safety and feasibility of laparoscopic total proctocolectomy with ileal pouch–anal anastomosis (TPC-IPAA) and total colectomy with ileorectal anastomosis (TC-IRA) for patients with familial adenomatous polyposis (FAP) are limited. The aim of this study was to clarify the feasibility and morbidity of laparoscopic TPC-IPAA and TC-IRA for patients with FAP, using a large Japanese multicenter dataset.

Methods

Data on 256 patients with FAP who underwent TPC-IPAA (n = 171) or TC-IRA (n = 85) at 23 institutions between the years 2000 and 2012 were collected. Short- and long-term clinical outcomes were compared between laparoscopic and open approaches for each procedure.

Results

Among the 256 patients with FAP, a total of 126 patients underwent laparoscopic surgery, consisting of 74 laparoscopic TPC-IPAAs and 52 laparoscopic TC-IRAs. The proportion of the FAP patients who underwent laparoscopic surgery increased during the study period, reaching 79 % of all TPC-IPAAs and 82 % of all TC-IRAs in the final two years covered by the data. In both TPC-IPAA and TC-IRA, the laparoscopic approach was associated with a longer operative duration but a similarly low postoperative morbidity and comparably adequate anal function compared with the open approach. The overall survival and the incidence of desmoid tumor were also comparable between the laparoscopic and open approaches in both procedures.

Conclusions

Laparoscopic TPC-IPAA and TC-IRA are both feasible options—with low rates of morbidity, good functional outcomes, and excellent overall survival rates—in patients with FAP. Since the data indicate that laparoscopic TPC-IPAA and TC-IRA are feasible, they also support the recent increase in laparoscopic surgery for patients with FAP in Japan.



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Infantile Fibrosarcoma With NTRK3–ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101

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Infantile fibrosarcoma (IFS) is a rare pediatric cancer typically presenting in the first 2 years of life. Surgical resection is usually curative and chemotherapy is active against gross residual disease. However, when recurrences occur, therapeutic options are limited. We report a case of refractory IFS with constitutive activation of the tropomyosin-related kinase (TRK) signaling pathway from an ETS variant gene 6–neurotrophin 3 receptor gene (ETV6–NTRK3) gene fusion. The patient enrolled in a pediatric Phase 1 trial of LOXO-101, an experimental, highly selective inhibitor of TRK. The patient experienced a rapid, radiographic response, demonstrating the potential for LOXO-101 to provide benefit for IFS harboring NTRK gene fusions.



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Identification of stromal ColXα1 and tumor-infiltrating lymphocytes as putative predictive markers of neoadjuvant therapy in estrogen receptor-positive/HER2-positive breast cancer

Abstract

Background

The influence of the tumor microenvironment and tumor-stromal interactions on the heterogeneity of response within breast cancer subtypes have just begun to be explored. This study focuses on patients with estrogen receptor-positive/human epidermal growth factor receptor 2-positive (ER+/HER2+) breast cancer receiving neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel predictive biomarkers by combining gene expression analysis and immunohistochemistry with pathologic response.

Methods

We performed gene expression profiling on pre-NAC+H tumor samples from responding (no or minimal residual disease at surgery) and non-responding patients. Gene set enrichment analysis identified potentially relevant pathways, and immunohistochemical staining of pre-treatment biopsies was used to measure protein levels of those pathways, which were correlated with pathologic response in both univariate and multivariate analysis.

Results

Increased expression of genes encoding for stromal collagens, including Col10A1, and reduced expression of immune-associated genes, reflecting lower levels of total tumor-infiltrating lymphocytes (TILs), were strongly associated with poor pathologic response. Lower TILs in tumor biopsies correlated with reduced likelihood of achieving an optimal pathologic response, but increased expression of the Col10A1 gene product, colXα1, had greater predictive value than stromal abundance for poor response (OR = 18.9, p = 0.003), and the combination of increased colXα1 expression and low TILs was significantly associated with poor response in multivariate analysis. ROC analysis suggests strong specificity and sensitivity for this combination in predicting treatment response.

Conclusions

Increased expression of stromal colXα1 and low TILs correlate with poor pathologic response in ER+/HER2+ breast tumors. Further studies are needed to confirm their predictive value and impact on long-term outcomes, and to determine whether this collagen exerts a protective effect on the cancer cells or simply reflects other factors within the tumor microenvironment.



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Improvement of ablative margins by the intraoperative use of CEUS-CT/MR image fusion in hepatocellular carcinoma

Abstract

Background

To assess whether intraoperative use of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion can accurately evaluate ablative margin (AM) and guide supplementary ablation to improve AM after hepatocellular carcinoma (HCC) ablation.

Methods

Ninety-eight patients with 126 HCCs designated to undergo thermal ablation treatment were enrolled in this prospective study. CEUS-CT/MR image fusion was performed intraoperatively to evaluate whether 5-mm AM was covered by the ablative area. If possible, supplementary ablation was applied at the site of inadequate AM. The CEUS image quality, the time used for CEUS-CT/MR image fusion and the success rate of image fusion were recorded. Local tumor progression (LTP) was observed during follow-up. Clinical factors including AM were examined to identify risk factors for LTP.

Results

The success rate of image fusion was 96.2 % (126/131), and the duration required for image fusion was 4.9 ± 2.0 (3–13) min. The CEUS image quality was good in 36.1 % (53/147) and medium in 63.9 % (94/147) of the cases. By supplementary ablation, 21.8 % (12/55) of lesions with inadequate AMs became adequate AMs. During follow-up, there were 5 LTPs in lesions with inadequate AMs and 1 LTP in lesions with adequate AMs. Multivariate analysis showed that AM was the only independent risk factor for LTP (hazard ratio, 9.167; 95 % confidence interval, 1.070–78.571; p = 0.043).

Conclusion

CEUS-CT/MR image fusion is feasible for intraoperative use and can serve as an accurate method to evaluate AMs and guide supplementary ablation to lower inadequate AMs.



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Erratum to: Generation of an algorithm based on minimal gene sets to clinically subtype triple negative breast cancer patients



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Survivin protein expression is involved in the progression of non-small cell lung cancer in Asians: a meta-analysis

Abstract

Background

Surviving expression might serve as a prognostic biomarker predicting the clinical outcome of non-small cell lung cancer (NSCLC). The study was conducted to explore the potential correlation of survivin protein expression with NSCLC and its clinicopathologic characteristics.

Methods

PubMed, Medline, Cochrane Library, CNKI and Wanfang database were searched through January 2016 with a set of inclusion and exclusion criteria. Data was extracted from these articles and all statistical analysis was conducted by using Stata 12.0.

Results

A total of 28 literatures (14 studies in Chinese and 14 studies in English) were enrolled in this meta-analysis, including 3206 NSCLC patients and 816 normal controls. The result of meta-analysis demonstrated a significant difference of survivin positive expression between NSCLC patients and normal controls (RR = 7.16, 95 % CI = 4.63-11.07, P < 0.001). To investigate the relationship of survivin expression and clinicopathologic characteristics, we performed a meta-analysis in NSCLC patients. Our results indicates survivin expression was associated with histological differentiation, tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM) (RR = 0.80, 95 % CI = 0.73-0.87, P < 0.001; RR = 0.75, 95 % CI = 0.67-0.84, P < 0.001; RR = 1.14, 95 % CI = 1.01-1.29, P = 0.035, respectively), but not pathological type and tumor size. (RR = 1.00, 95 % CI = 0.93-1.07, P = 0.983; RR = 0.95, 95 % CI = 0.86-1.05, P = 0.336, respectively).

Conclusion

Higher expression of survivin in NSCLC patients was found when compared to normal controls. Survivin expression was associated with the clinicopathologic characteristics of NSCLC and may serves as an important biomarker for NSCLC progression.



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Violation of Bans on Tobacco Advertising and Promotion at Points of Sale in Viet Nam: Trend from 2009 - 2015.

Violation of Bans on Tobacco Advertising and Promotion at Points of Sale in Viet Nam: Trend from 2009 - 2015.

Asian Pac J Cancer Prev. 2016;17 Suppl:91-6

Authors: Huong le TT, Long TK, Son PX, Huyen do P, Linh PT, Bich NN, Lam NX, Anh le V, Tuyet-Hanh TT

Abstract
Comprehensive bans on tobacco advertising and promotion were introduced through tobacco control legislation in Viet Nam, but it has been established that violations of the bans are very common. This study was conducted to explore the trend in violations of bans on tobacco advertising and promotion at points of sale in Viet Nam in the past six years and to explore any differences in the violation situations before and after the Law on Tobacco Control came into effect on 1st May 2013. Quantitative data were collected through observation of violations of the bans on tobacco advertising and promotion at points of sale in 10 provinces throughout Viet Nam in four survey rounds (2009, 2010, 2011, and 2015). Variation in violation prevalence over time was examined by chi-square test using a Bonferini method. Binary logistic regression was employed to identify the factors that may have influences on different types of violation. A level of significance of p<0.05 was used for all tests in this article. The most common form of violation was the display of more than one pack/one carton of a cigarette brand. Violation of bans on tobacco advertising increased while violations on promotion ban and on displaying tobacco decreased through time. Some factors associated with the tobacco advertising and promotion bans included surveyed years, types of points of sale, regions and areas where the points of sale were located. The enforcement of the bans did not improve even after the issuance and the enactment of the Law on Tobacco Control. This suggests that the monitoring and enforcement of bans on tobacco advertising and promotion at points of sale should be strengthened. Penalties should be strictly applied for violators as indicated in the current tobacco control legislation.

PMID: 27087189 [PubMed - in process]



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Potential Impact of Graphic Health Warnings on Cigarette Packages in Reducing Cigarette Demand and Smoking-Related Deaths in Vietnam.

Potential Impact of Graphic Health Warnings on Cigarette Packages in Reducing Cigarette Demand and Smoking-Related Deaths in Vietnam.

Asian Pac J Cancer Prev. 2016;17 Suppl:85-90

Authors: Minh HV, Chung le H, Giang KB, Duc DM, Hinh ND, Mai VQ, Cuong NM, Manh PD, Duc HA, Yang JC

Abstract
Two years after implementation of the graphic health warning intervention in Vietnam, it is very important to evaluate the intervention's potential impact. The objective of this paper was to predict effects of graphic health warnings on cigarette packages, particularly in reducing cigarette demand and smoking-associated deaths in Vietnam. In this study, a discrete choice experiment (DCE) method was used to evaluate the potential impact of graphic tobacco health warnings on smoking demand. To predict the impact of GHWs on reducing premature deaths associated with smoking, we constructed different static models. We adapted the method developed by University of Toronto, Canada and found that GHWs had statistically significant impact on reducing cigarette demand (up to 10.1% through images of lung damage), resulting in an overall decrease of smoking prevalence in Vietnam. We also found that between 428,417- 646,098 premature deaths would be prevented as a result of the GHW intervention. The potential impact of the GHW labels on reducing premature smoking-associated deaths in Vietnam were shown to be stronger among lower socio-economic groups.

PMID: 27087188 [PubMed - in process]



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Relative Importance of Different Attributes of Graphic Health Warnings on Tobacco Packages in Viet Nam.

Relative Importance of Different Attributes of Graphic Health Warnings on Tobacco Packages in Viet Nam.

Asian Pac J Cancer Prev. 2016;17 Suppl:79-84

Authors: Giang KB, Chung le H, Minh HV, Kien VD, Giap VV, Hinh ND, Cuong NM, Manh PD, Duc HA, Yang JC

Abstract
Graphic health warnings (GHW) on tobacco packages have proven to be effective in increasing quit attempts among smokers and reducing initial smoking among adolescents. This research aimed to examine the relative importance of different attributes of graphic health warnings on tobacco packages in Viet Nam. A discrete choice experimental (DCE) design was applied with a conditional logit model. In addition, a ranking method was used to list from the least to the most dreadful GHW labels. With the results from DCE model, graphic type was shown to be the most important attribute, followed by cost and coverage area of GHW. The least important attribute was position of the GHW. Among 5 graphic types (internal lung cancer image, external damaged teeth, abstract image, human suffering image and text), the image of lung cancer was found to have the strongest influence on both smokers and non-smokers. With ranking method, the image of throat cancer and heart diseases were considered the most dreadful images. GHWs should be designed with these attributes in mind, to maximise influence on purchase among both smokers and non-smokers.

PMID: 27087187 [PubMed - in process]



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Changes in Vietnamese Male Smokers' Reactions Towards New Pictorial Cigarette Pack Warnings Over Time.

Changes in Vietnamese Male Smokers' Reactions Towards New Pictorial Cigarette Pack Warnings Over Time.

Asian Pac J Cancer Prev. 2016;17 Suppl:71-8

Authors: Ngan TT, Anh le V, My NT, Bich NN

Abstract
Printing of pictorial health warnings (PHWs) on cigarette packages became obligatory by the Vietnam Law on Prevention and Control of Tobacco Harm in May 2013. Literature from high-income countries suggests that PHWs motivate smokers to quit smoking although their long-term effects have been questioned due to reduction of impact over time. This study aimed to assess the salience of PHWs and smokers' reactions towards PHWs over time. In May 2014 and May 2015, a cross-sectional questionnaire-based household survey was administered to respectively 1,462 and 1,509 Vietnamese male smokers aged 18 to 35. The result showed that salience of the PHWs 2 years after the implementation was higher than at the point of 1 year after the implementation. The proportion of respondents who tried to avoid noting the PHWs was reduced from 35% in wave 1 to 23% in wave 2. However, "Tried to avoid looking/thinking about the PHWs" increased 1.5 times the odds of presenting quit intention compared to those respondents who did not try to avoid looking/thinking about the PHWs (OR=1.5; 95%CI: 1.2-2.0). In conclusion, avoidance regarding PHWs may not work as a barrier when aiming at a higher level of quit intention. Salience of the PHWs may increase in the period shortly after their introduction onto packs but can be expected to decrease with time. In other words, it might be advisable to change or renew PHWs after a period of implementation to maintain their beneficial effects.

PMID: 27087186 [PubMed - in process]



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Students' Knowledge and Attitudes Towards Smoke-Free Universities: Changes Since Enactment of Vietnamese Tobacco Control Legislation.

Students' Knowledge and Attitudes Towards Smoke-Free Universities: Changes Since Enactment of Vietnamese Tobacco Control Legislation.

Asian Pac J Cancer Prev. 2016;17 Suppl:65-70

Authors: Bich NN, Cook M, Johnstone K, Capra M, Lan VT

Abstract
BACKGROUND: In 2013, legislation in Vietnam regulated smoking in public areas. Included was a ban on indoor smoking at universities.
OBJECTIVE: Since awareness and attitude are moderators of the effectiveness of smokefree policy, ou aim was to assess changes in students' knowledge and attitude tosecond hand smoke (SHS) and awareness and support of smoke-free legislation at four Vietnamese universities, one year after legislative changes.
METHODS: A two-phase cross sectional study of undergraduate students using self-administered questionnaires (based on the Global Adult Tobacco Survey and the Thrasher survey) was conducted at the introduction of the legislation and one year thereafter.
RESULTS: One-year post legislation there were significant increases in knowledge of smoke-free legislation and awareness of universities as smoke-free environments. There was a significant increase in knowledge of harmful effects of SHS on diseases such as examples in the heart and lung, including lung cancer, and miscarriage. Students expressed strong support of smoke-free environments in universities, hospitals, schools, workplaces, public transport, libraries, cinemas and theatres; support was also increased post legislation. Changes were seen in attitude to SHS, and rights of non-smokers and smokers.
CONCLUSIONS: Positive changes have occurred in knowledge and attitude toward smoke-free environments and SHS in universities since enactment of Vietnamese tobacco control legislation.

PMID: 27087185 [PubMed - in process]



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Changes in Co-Occurrence of Smoking and Harmful Drinking among Youth: a Study from the Chi Linh Demographic - Epidemiological Surveillance System in Vietnam, 2006-2013.

Changes in Co-Occurrence of Smoking and Harmful Drinking among Youth: a Study from the Chi Linh Demographic - Epidemiological Surveillance System in Vietnam, 2006-2013.

Asian Pac J Cancer Prev. 2016;17 Suppl:55-63

Authors: Duc DM, Vui le T, Quynh NT, Minh HV

Abstract
Smoking and harmful drinking dramatically increase health risks but little is known about their cooccurrence and factors that influence this co-habit, limiting development and implementation of appropriately targeted prevention interventions. This study was conducted among youth aged 10-24 years old in the Chi Linh Demographic - Epidemiological Surveillance System (CHILILAB DESS). The total numbers in the first, second and third rounds in 2006, 2009 and 2013 were 12,406, 10,211, and 7,654, respectively. A random-effects logit model controlling for both time-variant and time-invariant variables was applied to explore factors associated with current smoking, harmful drinking, and occurrence of smoking and harmful drinking together. We found dramatically increasing trends in current smoking, harmful drinking and co-occurrence among youth. Our results indicate similar health problems among youth in peri-urban areas in Vietnam. Demographic characteristics (older age, being male, being unmarried, and having informal work) appeared to be predictors for smoking and drinking behaviour. Besides, peer and family members had significant influence on smoking, whereas having a close-friend who was smoking was the most important variable. The results suggested that smoking and harmful drinking should not be solved with separate, stand-alone interventions but rather with integrated efforts.

PMID: 27087184 [PubMed - in process]



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Exposure to Tobacco Advertising and Promotion among School Children Aged 13-15 in Vietnam - an Overview from GYTS 2014.

Exposure to Tobacco Advertising and Promotion among School Children Aged 13-15 in Vietnam - an Overview from GYTS 2014.

Asian Pac J Cancer Prev. 2016;17 Suppl:49-53

Authors: Long TK, Son PX, Giang KB, Hai PT, Huyen DT, Khue LN, Nga PT, Lam NT, Minh HV, Huong le TT

Abstract
Evidence shows that tobacco advertising and promotion activities may increase tobacco consumption and usage, especially in youth. Despite the regulation on prohibiting advertisement of any tobacco product, tobacco advertisement and promotion activities are still common in Vietnam. This article presents current exposure to tobacco advertising and promotion (TAP) among school children aged 13 to 15 years in Vietnam in 2014 and potential influencing factors. Data from the Global Youth Tobacco Survey 2014 in Vietnam covering 3,430 school aged children were used. Both descriptive and analytical statistics were carried out with Stata 13 statistical software. Binary logistic regression was applied to explain the exposure to TAP among youth and examine relationships with individual factors. A significance level of p<0.05 and sampling weights were used in all of the computations. In the past 30 days, 48.6% of the students experienced exposure to at least 1 type of tobacco advertising or promotion. Wearing or otherwise using products related to tobacco was the most exposure TAP type reported by students (22.3%). The internet (22.1), points of sales (19.2) and social events (11.5) were three places that students aged 13-15 frequently were exposed to TAP. Binary logistic results showed that gender (female vs male) (OR = 0.61, 95%CI: 0.52 - 0.71), susceptibility to smoking (OR = 2.12, 95%CI: 1.53 - 2.92), closest friends' smoked (OR = 1.43, 95%CI: 1.2 - 1.7) and parents smoking status (OR = 2.83, 95%CI: 1.6 - 5.01) were significantly associated with TAP exposure among school-aged children. The research findings should contribute to effective implementation of measures for preventing and controlling tobacco use among students aged 13-15 in Viet Nam.

PMID: 27087183 [PubMed - in process]



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Trends in Second-Hand Tobacco Smoke Exposure Levels at Home among Viet Nam School Children Aged 13-15 and Associated Factors.

Trends in Second-Hand Tobacco Smoke Exposure Levels at Home among Viet Nam School Children Aged 13-15 and Associated Factors.

Asian Pac J Cancer Prev. 2016;17 Suppl:43-7

Authors: Lam NT, Nga PT, Minh HV, Giang KB, Hai PT, Huyen DT, Linh NT, Van DK, Khue LN

Abstract
Second-hand tobacco smoke (SHS) exposure at home, especially among children, is a serious issue in Viet Nam. During the past decade, much effort has been taken for tobacco control in the country, including various prgorammes aiming to reduce SHS exposure among adults and children. This article analysed trends and factors associated with SHS exposure at home among school children aged 13-15 in Viet Nam, using the Global Youth Tobacco Surveys conducted in 2007 and 2014. Descriptive and inferential statistical methods with logistic regression were applied. Overall, there was a significant reduction in the level of exposure, from 58.5% (95%CI: 57.6-59.3) in 2007 to 47.1% (95%CI: 45.4-48.8) in 2014. Of the associated factors, having one or both parents smoking was significantly associated with the highest odds of SHS exposure at home (OR=5.0; 95%CI: 4.2-6.1). Conversely, having a mother with a college or higher education level was found to be a protective factor (OR=0.5; 95%CI: 0.3-0.8).

PMID: 27087182 [PubMed - in process]



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Knowledge and Attitude Towards Tobacco Smoking among 13-15 Year-Old School Children in Viet Nam - Findings from GYTS 2014.

Knowledge and Attitude Towards Tobacco Smoking among 13-15 Year-Old School Children in Viet Nam - Findings from GYTS 2014.

Asian Pac J Cancer Prev. 2016;17 Suppl:37-42

Authors: Huong NT, Kien NT, Giang KB, Minh HV, Hai PT, Huyen DT, Khue LN, Linh NT, Lam NT, Nga PT

Abstract
Studies have shown that smoking is a learnt behavior, often initiated during adolescence. This paper aims to describe tobacco-related knowledge, attitude and associations among school adolescents aged 13-15 with exposure to anti-smoking information. Using data from the Global Youth Tobacco Survey (GYTS) in Viet Nam, 2014, knowledge was measured through 4 questions about tobacco use, and attitude was assessed through 3 questions on personal, social and environmental aspects. Students giving most anti-tobacco responses to all questions were considered as having correct knowledge or appropriate attitude or both. Access to anti-smoking information was determined by exposure to any media messages on tobacco control during the past 30 days and teaching in school about the danger of tobacco use during the past 12 months. A substantial percentage of students thought that being near others who smoke might be harmful to them and smoking is harmful to health (89.4% and 89.6% respectively). However, only 46.4% reported that it is definitely difficult to quit smoking and 66.9% thought that smoking for only 1 or 2 years, once stopped, is harmful to health. Slightly more than half of the respondents reported appropriate attitude that young smokers have fewer friends than others and smoking makes them less attractive and less comfortable at social events. Noticing anti-smoking messages in the media together with having lessons in school about the dangers of tobacco substantially increased the likelihood of having correct knowledge, appropriate attitude and both. Despite relatively high awareness about smoking harms, effective educational communication is still highly needed to improve the level of comprehensive knowledge and an appropriate attitude regarding tobacco use.

PMID: 27087181 [PubMed - in process]



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Access to Anti-smoking Information among School Children and its Potential Impact on Preventing Smoking Initiation: Results from the Global Youth Tobacco Use Survey (GYTS) 2014 in Viet Nam.

Access to Anti-smoking Information among School Children and its Potential Impact on Preventing Smoking Initiation: Results from the Global Youth Tobacco Use Survey (GYTS) 2014 in Viet Nam.

Asian Pac J Cancer Prev. 2016;17 Suppl:31-6

Authors: Minh HV, Minh HV, Giang KB, Hai PT, Hoang TD, Huyen DT, Khue LN, Linh NT, Lam NT, Nga PT

Abstract
Scientific evidence on all aspects of smoking amongst youth is very important for designing appropriate interventions to reduce smoking among this vulnerable population. This paper describes current access to antismoking information among school children aged 13 to 15 years in Vietnam in 2014 and examines its potential impact on preventing smoking initiation. The data used in this paper were obtained from the 2014 Global Youth Tobacco Survey (GYTS) in Vietnam. Students were asked questions about their level of awareness of anti-smoking information from various sources in the past 30 days and about lessons in school regarding the dangers of tobacco use during the last 12 months. Those who have never smoked were asked "whether or not they thought about avoiding cigarettes because of health warnings on cigarette packages" and answers were analyzed in combination with data on access to anti-smoking information from other sources. The prevalence of exposure to antismoking campaigns was high among school children in Viet Nam: 55.3% of current smokers reported thoughts of smoking cessation because of health warnings on cigarette packages; 60.5% of never smokers avoided initiating smoking because of the same health warnings. The potential impact of graphic health warnings to prevent school-aged children from smoking initiation would be stronger if there was concurrent access to anti-smoking programs on the dangers of tobacco use in schools. However, school education for tobacco prevention and control has not been as strong as expected. A more comprehensive school curriculum on tobacco prevention and control is recommended to reinforce antismoking messages among school children.

PMID: 27087180 [PubMed - in process]



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Tobacco Access and Availability for Vietnamese School Children (aged 13-15): Results from the Global Youth Tobacco Use Survey (GYTS) 2014 in Viet Nam.

Tobacco Access and Availability for Vietnamese School Children (aged 13-15): Results from the Global Youth Tobacco Use Survey (GYTS) 2014 in Viet Nam.

Asian Pac J Cancer Prev. 2016;17 Suppl:25-9

Authors: Anh le TK, Quyen BT, Minh HV, Giang KB, Hai PT, Huyen DT, Khue LN, Lam NT, Nga PT

Abstract
Efforts to reduce tobacco use among school children need to be based on understanding of access to cigarettes by these subjects because previous studies indicated that enforcement of laws for controlling tobacco sales seems to not affect teen/school children because they can obtain cigarettes from different sources. This paper aims to describe access to and availability of cigarettes among school students (aged 13-15 years old) according to the data from GYTS Vietnam 2014. In GYTS, a national school-based survey of students of grades 8-10, our findings showed that about 15% school children are current smokers who smoke at home, and that they could easily buy cigarettes from stores (63.2%), or someone else (27.8%), or street vendors (9%). Notably, over 85% of school children answered that they were not refused because of their age. This high percentage was nearly the same in the North (85.7%), the Centre (92.5%), and the South (89.7%) of Viet Nam. These findings show that it is quite easy for school children to obtain cigarettes and this is a crucial challenge for policy makers aiming to reduce tobacco use among youth in general and school-age students in particular.

PMID: 27087179 [PubMed - in process]



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Cigarette Smoking among Adolescents aged 13-15 in Viet Nam and Correlates of Current Cigarette Smoking: Results from GYTS 2014 Data.

Cigarette Smoking among Adolescents aged 13-15 in Viet Nam and Correlates of Current Cigarette Smoking: Results from GYTS 2014 Data.

Asian Pac J Cancer Prev. 2016;17 Suppl:17-23

Authors: Huong le T, Vu NT, Dung NN, Xuan le TT, Giang KB, Hai PT, Huyen DT, Khue LN, Lam NT, Minh HV, Nga PT

Abstract
The aim of this paper is to report the rate of current and ever cigarette smoking and explore correlates of current cigarette smoking among adolescents aged 13-15 in Viet Nam. This analysis was derived from GYTS survey, which comprised of 3,430 adolescents aged 13-15, conducted in 2014 in 13 cities and provinces of Viet Nam. We calculated the weighted rates of current and ever cigarette smoking and reported patterns of smoking behavior. We also performed logistic regression to explore correlates of current cigarette smoking behavior. The weighted rate of ever cigarette smoking was 9.5% (95% confidence interval (CI): 8.5 %-10.5%), in which the weighted rate among males (15.4%; 95% CI: 13.6%-17.0%) was higher than that among females (4.2%; 95% CI: 3.3%-5.1%). The weighted rate of current cigarette smoking was relatively low at 2.5% (95%CI: 2.0%- 3.0%) with higher weighted rate among males (4.9%; 95% CI: 3.8%-5.9%) compared to the corresponding figure among females (0.2%; 95% CI: 0.0 %-0.5%). Current cigarette smoking was significantly higher among males than females, in students aged 15 versus 13 years old, and in students who had several or all close friends smoking and students with daily observation of smoking at school. For greater smoking reduction outcomes, we recommend that tobacco interventions for adolescents should consider targeting more male students at older ages, establish stricter adherence to school-based banning of cigarette smoking, engage both smoking and nonsmoking adolescents and empower adolescents to resist peer smoking influence as well as changing their norms or beliefs towards smoking benefits.

PMID: 27087178 [PubMed - in process]



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Methodology for the Global Youth Tobacco Use Survey (GYST), Vietnam, 2014.

Methodology for the Global Youth Tobacco Use Survey (GYST), Vietnam, 2014.

Asian Pac J Cancer Prev. 2016;17 Suppl:11-5

Authors: Giang KB, Minh HV, Hai PT, Huyen DT, Khue LN, Linh NT, Lam NT, Nga PT, Hoat LN

Abstract
Viet Nam is a country with the highest rate of adult male smokers in the world. In 2010, the percentage of adult male smokers was 47.4%. Each year in Viet Nam, there are 40,000 lives lost from tobacco-related diseases. The Global Tobacco Youth Survey is an international standardized survey that has been conducted in more than 140 countries. To provide evidence for tobacco control, Viet Nam already conducted two rounds of GYTS in 2003 and 2007. The GYTS in 2014 is the survey's third iteration. This paper aims to document key methodological details and socio-demographic characteristics of the respondents included in the 2014 GYTS in Viet Nam. This survey followed international protocol and was conducted in 13 provinces representative of 6 geographical regions. A total of 3,430 school children, aged 13 to 15 years used a standardized answer sheet to answer 76 questions about seven tobacco-related topics, including prevalence of tobacco use, environmental tobacco smoke, access and availability, media and advertisement, cessation, knowledge and attitudes, tobaccorelated school curriculum. This GYTS provides valid and reliable data for monitoring tobacco use among youth in Vietnam and is recommended to be regularly repeated.

PMID: 27087177 [PubMed - in process]



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Tobacco Control Policies in Vietnam: Review on MPOWER Implementation Progress and Challenges.

Tobacco Control Policies in Vietnam: Review on MPOWER Implementation Progress and Challenges.

Asian Pac J Cancer Prev. 2016;17 Suppl:1-9

Authors: Minh HV, Ngan TT, Mai VQ, My NT, Chung le H, Kien VD, Anh TT, Ngoc NB, Giap VV, Cuong NM, Manh PD, Giang KB

Abstract
In Vietnam, the WHO Framework Convention on Tobacco Control (WHO FCTC) took effect in March 2005 while MPOWER has been implemented since 2008. This paper describes the progress and challenges of implementation of the MPOWER package in Vietnam. We can report that, in term of monitoring, Vietnam is very active in the Global Tobacco Surveillance System, completing two rounds of the Global Adult Tobacco Survey (GATS) and three rounds of the Global Youth Tobacco Survey (GYTS). To protect people from tobacco smoke, Vietnam has issued and enforced a law requiring comprehensive smoking bans at workplaces and public places since 2013. Tobacco advertising and promotion are also prohibited with the exception of points of sale displays of tobacco products. Violations come in the form of promotion girls, corporate social responsibility activities from tobacco manufacturers and packages displayed by retail vendors. Vietnam is one of the 77 countries that require pictorial health warnings to be printed on cigarette packages to warn about the danger of tobacco and the warnings have been implemented effectively. Cigarette tax is 70% of factory price which is equal to less than 45% of retail price and much lower than the recommendation of WHO. However, Vietnam is one of the very few countries that require manufacturers and importers to make "compulsory contributions" at 1-2% of the factory price of cigarettes sold in Vietnam for the establishment of a Tobacco Control Fund (TCF). The TCF is being operated well. In 2015, 67 units of 63 provinces/cities, 22 ministries and political-social organizations and 6 hospitals received funding from TCF to implement a wide range of tobacco control activities. Cessation services have been starting with a a toll-free quit-line but need to be further strengthened. In conclusion, Vietnam has constantly put efforts into the tobacco control field with high commitment from the government, scientists and activists. Though several remarkable achievements have been gained, many challenges remain. To overcome those challenges, implementation strategies that take into account the contextual factors and social determinants of tobacco use in Vietnam are needed.

PMID: 27087176 [PubMed - in process]



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Iron depletion enhances the effect of sorafenib in hepatocarcinoma.

Related Articles

Iron depletion enhances the effect of sorafenib in hepatocarcinoma.

Cancer Biol Ther. 2016 Apr 18;:0

Authors: Urano S, Ohara T, Noma K, Katsube R, Ninomiya T, Tomono Y, Tazawa H, Kagawa S, Shirakawa Y, Kimura F, Nouso K, Matsukawa A, Yamamoto K, Fujiwara T

Abstract
Human hepatocellular carcinoma (HCC) is known to have a poor prognosis. Sorafenib, a molecular targeted drug, is most commonly used for HCC treatment. However, its effect on HCC is limited in clinical use and therefore new strategies regarding sorafenib treatment are required. Iron overload is known to be associated with progression of chronic hepatitis and increased risk of HCC. We previously reported that iron depletion inhibited cancer cell proliferation and conversely induced angiogenesis. Indeed iron depletion therapy including iron chelator needs to be combined with anti-angiogenic drug for its anti-cancer effect. Since sorafenib has an anti-angiogenic effect by its inhibitory targeting VEGFR, we hypothesized that sorafenib could complement the anti-cancer effect of iron depletion. We retrospectively analyzed the relationship between the efficacy of sorafenib and serum iron-related markers in clinical HCC patients. In clinical cases, overall survival was prolonged in total iron binding capacity (TIBC) high- and ferritin low-patients. This result suggested that the low iron-pooled patients, who could have a potential of more angiogenic properties in/around HCC tumors, could be adequate for sorafenib treatment. We determined the effect of sorafenib (Nexavar®) and/or deferasirox (EXJADE®) on cancer cell viability, and on cell signaling of human hepatocarcinoma HepG2 and HLE cells. Both iron depletion by deferasirox and sorafenib revealed insufficient cytotoxic effect by each monotherapy, however, on the basis of increased angiogenesis by iron depletion, the addition of deferasirox enhanced anti-proliferative effect of sorafenib. Deferasirox was confirmed to increase vascular endothelial growth factor (VEGF) secretion into cellular supernatants by ELISA analysis. In in vivo study sorafenib combined with deferasirox also enhanced sorafenib-induced apoptosis. These results suggested that sorafenib combined with deferasirox could be a novel combination chemotherapy for HCC.

PMID: 27089255 [PubMed - as supplied by publisher]



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Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.

Related Articles

Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.

Cancer Biol Ther. 2016 Apr 18;:0

Authors: Zhou S, Zhao Z, Lin Y, Gong S, Li F, Pan J, Li X, Gao Z, Zhao AZ

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis among all malignancies and is resistant to almost all current therapies. Attenuated Salmonella typhimurium strain VNP20009 has been deployed as powerful anticancer agent in a variety of animal cancer models, and previous phase 1 clinical trials have proven its safety profiles. However, thus far, little is known about its effect on PDAC. Here, we established CFPAC-1 cell lines expressing an mKate2 protein and thus emitting far-red fluorescence in the subsequent xenograft implant. VNP20009 strain was further engineered to carry a luciferase cDNA, which catalyzes the light-emitting reaction to allow the observation of salmonella distribution and accumulation within tumor with live imaging. Using such VNP20009 strain and intratumoral delivery, we could reduce the growth of pancreatic cancer by inducing apoptosis and severe necrosis in a dosage dependent manner. Consistent with this finding, intratumoral delivery of VNP20009 also increase caspase-3 activity and the expression of Bax protein. In summary, we revealed that VNP20009 is a promising bacterial agent for the treatment of PDAC, and that we have established a dual fluorescent imaging system as a valuable tool for noninvasive live imaging of solid tumor and engineered bacterial drug.

PMID: 27089121 [PubMed - as supplied by publisher]



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Iron depletion enhances the effect of sorafenib in hepatocarcinoma.

Iron depletion enhances the effect of sorafenib in hepatocarcinoma.

Cancer Biol Ther. 2016 Apr 18;:0

Authors: Urano S, Ohara T, Noma K, Katsube R, Ninomiya T, Tomono Y, Tazawa H, Kagawa S, Shirakawa Y, Kimura F, Nouso K, Matsukawa A, Yamamoto K, Fujiwara T

Abstract
Human hepatocellular carcinoma (HCC) is known to have a poor prognosis. Sorafenib, a molecular targeted drug, is most commonly used for HCC treatment. However, its effect on HCC is limited in clinical use and therefore new strategies regarding sorafenib treatment are required. Iron overload is known to be associated with progression of chronic hepatitis and increased risk of HCC. We previously reported that iron depletion inhibited cancer cell proliferation and conversely induced angiogenesis. Indeed iron depletion therapy including iron chelator needs to be combined with anti-angiogenic drug for its anti-cancer effect. Since sorafenib has an anti-angiogenic effect by its inhibitory targeting VEGFR, we hypothesized that sorafenib could complement the anti-cancer effect of iron depletion. We retrospectively analyzed the relationship between the efficacy of sorafenib and serum iron-related markers in clinical HCC patients. In clinical cases, overall survival was prolonged in total iron binding capacity (TIBC) high- and ferritin low-patients. This result suggested that the low iron-pooled patients, who could have a potential of more angiogenic properties in/around HCC tumors, could be adequate for sorafenib treatment. We determined the effect of sorafenib (Nexavar®) and/or deferasirox (EXJADE®) on cancer cell viability, and on cell signaling of human hepatocarcinoma HepG2 and HLE cells. Both iron depletion by deferasirox and sorafenib revealed insufficient cytotoxic effect by each monotherapy, however, on the basis of increased angiogenesis by iron depletion, the addition of deferasirox enhanced anti-proliferative effect of sorafenib. Deferasirox was confirmed to increase vascular endothelial growth factor (VEGF) secretion into cellular supernatants by ELISA analysis. In in vivo study sorafenib combined with deferasirox also enhanced sorafenib-induced apoptosis. These results suggested that sorafenib combined with deferasirox could be a novel combination chemotherapy for HCC.

PMID: 27089255 [PubMed - as supplied by publisher]



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Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.

Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.

Cancer Biol Ther. 2016 Apr 18;:0

Authors: Zhou S, Zhao Z, Lin Y, Gong S, Li F, Pan J, Li X, Gao Z, Zhao AZ

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis among all malignancies and is resistant to almost all current therapies. Attenuated Salmonella typhimurium strain VNP20009 has been deployed as powerful anticancer agent in a variety of animal cancer models, and previous phase 1 clinical trials have proven its safety profiles. However, thus far, little is known about its effect on PDAC. Here, we established CFPAC-1 cell lines expressing an mKate2 protein and thus emitting far-red fluorescence in the subsequent xenograft implant. VNP20009 strain was further engineered to carry a luciferase cDNA, which catalyzes the light-emitting reaction to allow the observation of salmonella distribution and accumulation within tumor with live imaging. Using such VNP20009 strain and intratumoral delivery, we could reduce the growth of pancreatic cancer by inducing apoptosis and severe necrosis in a dosage dependent manner. Consistent with this finding, intratumoral delivery of VNP20009 also increase caspase-3 activity and the expression of Bax protein. In summary, we revealed that VNP20009 is a promising bacterial agent for the treatment of PDAC, and that we have established a dual fluorescent imaging system as a valuable tool for noninvasive live imaging of solid tumor and engineered bacterial drug.

PMID: 27089121 [PubMed - as supplied by publisher]



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Iron depletion enhances the effect of sorafenib in hepatocarcinoma.

Iron depletion enhances the effect of sorafenib in hepatocarcinoma.

Cancer Biol Ther. 2016 Apr 18;:0

Authors: Urano S, Ohara T, Noma K, Katsube R, Ninomiya T, Tomono Y, Tazawa H, Kagawa S, Shirakawa Y, Kimura F, Nouso K, Matsukawa A, Yamamoto K, Fujiwara T

Abstract
Human hepatocellular carcinoma (HCC) is known to have a poor prognosis. Sorafenib, a molecular targeted drug, is most commonly used for HCC treatment. However, its effect on HCC is limited in clinical use and therefore new strategies regarding sorafenib treatment are required. Iron overload is known to be associated with progression of chronic hepatitis and increased risk of HCC. We previously reported that iron depletion inhibited cancer cell proliferation and conversely induced angiogenesis. Indeed iron depletion therapy including iron chelator needs to be combined with anti-angiogenic drug for its anti-cancer effect. Since sorafenib has an anti-angiogenic effect by its inhibitory targeting VEGFR, we hypothesized that sorafenib could complement the anti-cancer effect of iron depletion. We retrospectively analyzed the relationship between the efficacy of sorafenib and serum iron-related markers in clinical HCC patients. In clinical cases, overall survival was prolonged in total iron binding capacity (TIBC) high- and ferritin low-patients. This result suggested that the low iron-pooled patients, who could have a potential of more angiogenic properties in/around HCC tumors, could be adequate for sorafenib treatment. We determined the effect of sorafenib (Nexavar®) and/or deferasirox (EXJADE®) on cancer cell viability, and on cell signaling of human hepatocarcinoma HepG2 and HLE cells. Both iron depletion by deferasirox and sorafenib revealed insufficient cytotoxic effect by each monotherapy, however, on the basis of increased angiogenesis by iron depletion, the addition of deferasirox enhanced anti-proliferative effect of sorafenib. Deferasirox was confirmed to increase vascular endothelial growth factor (VEGF) secretion into cellular supernatants by ELISA analysis. In in vivo study sorafenib combined with deferasirox also enhanced sorafenib-induced apoptosis. These results suggested that sorafenib combined with deferasirox could be a novel combination chemotherapy for HCC.

PMID: 27089255 [PubMed - as supplied by publisher]



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Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.

Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system.

Cancer Biol Ther. 2016 Apr 18;:0

Authors: Zhou S, Zhao Z, Lin Y, Gong S, Li F, Pan J, Li X, Gao Z, Zhao AZ

Abstract
Pancreatic ductal adenocarcinoma (PDAC) has the poorest prognosis among all malignancies and is resistant to almost all current therapies. Attenuated Salmonella typhimurium strain VNP20009 has been deployed as powerful anticancer agent in a variety of animal cancer models, and previous phase 1 clinical trials have proven its safety profiles. However, thus far, little is known about its effect on PDAC. Here, we established CFPAC-1 cell lines expressing an mKate2 protein and thus emitting far-red fluorescence in the subsequent xenograft implant. VNP20009 strain was further engineered to carry a luciferase cDNA, which catalyzes the light-emitting reaction to allow the observation of salmonella distribution and accumulation within tumor with live imaging. Using such VNP20009 strain and intratumoral delivery, we could reduce the growth of pancreatic cancer by inducing apoptosis and severe necrosis in a dosage dependent manner. Consistent with this finding, intratumoral delivery of VNP20009 also increase caspase-3 activity and the expression of Bax protein. In summary, we revealed that VNP20009 is a promising bacterial agent for the treatment of PDAC, and that we have established a dual fluorescent imaging system as a valuable tool for noninvasive live imaging of solid tumor and engineered bacterial drug.

PMID: 27089121 [PubMed - as supplied by publisher]



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