LncRNA SNHG6 knockdown inhibits cisplatin resistance and progression of gastric cancer through miR-1297/BCL-2 axis

Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelia-mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were upregulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment.  Keywords: Gastric cancer, cisplatin resistance, lncRNA SNHG6, miR-1297, BCL-2

RELATIONSHIP BETWEEN HELMINTHASIS AND GASTRIC CANCER: A SYSTEMATIC REVIEW

Introduction: helminths are parasitic worms able to produce diverse clinical manifestations in humans, mainly in the gut. Gastric cancer its a high incidence entity in Colombia, being the highland regions where its incidence is the highest in comparison with the lower incidence coastal region. From the above it is intended to determine the relationship between helminthiasis and the development of gastric cancer. Methodology: A systematic review was performed in four databases for studies evaluating the relationship between helminthiasis and the development of gastric cancer. Results: We included 16 articles from 929 records, with 11 articles reporting a positive relationship and 5 articles with negative relationship. Conclusions: Parasitic infections of the gastrointestinal tract by helminths promote TH-2 type immune responses and decrease TH-1 type that are involved in the progression of precancerous lesions associated with Helicobacter pylori infection. Keywords: Gastric cancer, Helminthiases, inflammation.

HIPK2 reduces the resistance of gastric cancer cells to cisplatin via p53 pathway

Purpose: To uncover the functional effect of homologous domain-associated protein kinase 2 (HIPK2) on the viability of cisplatin (DDP)-resistant gastric cancer (GC) cells and elucidate the possible mechanism of action.Methods: The effect of DDP on GC viability and apoptotic rate was evaluated using MTT and flow cytometry (FCM) assays. The potential effect of HIPK2 on DDP sensitivity and cell apoptosis was investigated in the presence of cisplatin while the effect of HIPK2 on p53 activation was determined by immunoblot assay.Results: HIPK2 expression was decreased in DDP-resistant GC cell while upregulation of HIPK2 reduced growth, but promoted apoptosis in DDP-resistant GC cells. Further investigations showed that HIPK2 promoted p53 activation, while suppression of p53 weakened the inhibitory effect of HIPK2 on DDP-resistance in GC cells.Conclusion: The results suggest that HIPK2 is a promising and important therapeutic factor for the regulation of the resistance of GC cells to DDP. Thus, may have a role to play in the management of gastric cancer Keywords: Gastric cancer, Cisplatin, HIPK2, Homologous domain-associated protein kinase 2, p53 pathway, Therapeutic target

Quinolinone inhibits proliferation of gastric cancer cells and induces their apoptosis via down-regulation of the expression of pro-oncogene c-Myc

Purpose: To determine the anti-proliferative potential of quinolinone against gastric cancer cells, and the underlying mechanism of action.Methods: Quinolinone-mediated proliferative changes were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while its effect on apoptosis was determined by flow cytometry. Transwell and wound healing assays were used for the determination of the effect of quinolinone on cell invasion and migration. The effect of quinolinone on protein expression levels were assayed with western blotting.Results: Quinolinone caused reduction in gastric cancer cell viability, but it had no effect on normal (GES-1) cells. Treatment with 8 μM quinolinone reduced the viability of SNU-5 and SGC-7901 cells to 32 and 27 %, respectively. Moreover, 8 μM quinolinone induced 67.90 and 71.54 % apoptosis in SNU-5 and SGC-7901 cells, respectively. Quinolinone significantly increased the population of cells in G1 phase, and suppressed migration potential (p < 0.05). Furthermore, in quinolinone-treated cells, the expression levels of p-PI3K, c-Myc and p-AKT were much lower than those in untreated cells (p < 0.05). Quinolinone also downregulated the expressions of MMP-2 and MMP-9, while it upregulated p21 expression in SNU-5 and SGC-7901 cells.Conclusion: Quinolinone suppresses the growth of SNU-5 and SGC-7901 gastric cancer cells via cell cycle arrest, induction of apoptosis and downregulation of the expressions of c-Myc and metalloproteinases. Thus, quinolinone may be developed as a potential drug candidate for the treatment of gastric cancer. Keywords: Gastric cancer, Apoptosis, Metalloproteinases, Phosphorylation

Evaluation changes in indicators of oncological service in gastric cancer in Kazakhstan

About 1.8 million new cases of gastric cancer (GC) are predicted and it is expected that about 1.4 million human will die from this pathology, according to the forecasts of the International Agency for Research on Cancer in 2040. To this aim, an analysis studying the indicators of the oncological service for GC also makes it possible to evaluate the ongoing anti-cancer measures in the Republic of Kazakhstan. Aim. Evaluate some indicators of the oncological service at GC in Kazakhstan in 2009 to 2018. Material and methods. The research material was data from the Ministry of Health of the Republic of Kazakhstan – annual form No. 7 and 35 regarding GC (ICD 10-C50) for 2009 2018 – incidence, mortality, early diagnosis, neglect, morphological verification. A retrospective study using descriptive and analytical methods of biomedical statistics was used as the main method. Results and discussion. For 2009-2018, 27,468 new cases of GC were registered in the republic for the first time and 19,672 deaths from this pathology were registered. The average annual crude incidence rate of GC was 16.1±0.20/0000 (95% CI=15.7-16.5) and decreased in dynamics from 16.8±0.30/0000 (2009) to 15.1±0.30/0000 in 2018, the difference was statistically significant (t=4.01 and p=0.000). In dynamics, mortality rates from GC tended to statistically significant (t=12.02 and p=0.000) decrease from 14.0±0.30/0000 (2009) to 8.9±0.20/0000 in 2018 year, and the average annual crude mortality rate from GC was 11.6±0.60/0000 (95% CI=10.5-12.7). The research of the study period reveals a trend: early diagnosis indicators (specific weight of patients with I-II stage) improved from 24.5% (2009) to 41.3% in 2018, and accordingly the specific weight of neglected patients significantly decreased with stage III (from 46.2% to 41.1%) and with stage IV (from 29.3% to 17.5%). The morphological verification indicators for GC over the studied years improved from 85.1% to 95.0%. Conclusion. An analysis of the indicators of the oncological service in GC revealed an improvement in morphological verification and early diagnosis, a decrease in neglect and mortality rates, which is undoubtedly associated with ongoing anti-cancer measures in Kazakhstan, in particular with the screening, which was carried out in 2012-2016. Keywords: gastric cancer, incidence, mortality, early diagnosis, neglect, morphological verification.

ADAR expression and copy number variation in patients with advanced gastric cancer

Background Gastric cancer (GC) is a world health problem and it is the third leading cause of cancer deaths worldwide. The current practice for prognosis assessment in GC is based on radiological and pathological criteria and they may not result in an accurate prognosis. The aim of this study is to evaluate expression and copy number variation of the ADAR gene in advanced GC and clarify its correlation with survival and histopathological characteristics. Methods Forty two patients with stage III and IV GC were included in this study. ADAR gene expression and copy number variation were measured by real-time PCR and Quantitative multiplex fluorescent-PCR, respectively. Survival analysis performed based on the Kaplan–Meier method and Mantel–Cox test. Results ADAR mRNA was significantly overexpressed in the tumor tissues when compared to the adjacent normal tissues (p <0.01). Also, ADAR expression level in stage IV was higher than stage III. 40% of patients showed amplification in ADAR gene and there was a positive correlation between ADAR copy number and expression. Increased ADAR expression was clearly correlated with poorer survival outcomes and Mantel–Cox test showed statistically significant differences between low and high expression groups (p <0.0001). ADAR overexpression and amplification were significantly associated with metastasis, size and stage of tumor. Conclusions Together, our data indicate that amplification leads to over expression of ADAR and it could be used as a prognostic biomarker for disease progression, especially for the metastatic process in GC. Keywords Gastric cancer, ADAR gene, Overexpression, Amplification, Prognosis

Estratificación de riesgo del cáncer gástrico, Cuba 2000-2015

La estratificación epidemiológica de riesgo ofrece la oportunidad de actuar proactivamente, diseñando intervenciones de cuidados sanitarios específicos adecuadas al nivel de necesidad de los distintos grupos de personas. Con el objetivo de estratificar la mortalidad por cáncer gástrico según provincias de residencia y caracterizar algunas variables sociodemográficas, se realizó un estudio ecológico de series temporales. El universo estuvo conformado por los 12.781 fallecidos del país cuya causa básica de muerte recogida en el certificado de defunción fue el cáncer gástrico en el período 2000-2015. Se calcularon indicadores: razón, porcentajes, tasas de mortalidad brutas y específicas, por edad y sexo, por 100 000 habitantes. La estratificación por provincias se clasificó en bajo, moderado y alto. En el período de estudio se registraron 12 781 defunciones, 78,4 % correspondieron a los adultos mayores de 60 años, el sexo masculino con 61,8 %. Las provincias de mayor riesgo en el cuatrienio 2011-2015: Cienfuegos (10,1), Guantánamo (9,7) y Villa Clara (9,45). Se concluye que la estratificación de riesgo a nivel provincial presentó variaciones importantes en el período de estudio. Los adultos mayores de 60 años del sexo masculino tienen mayor riesgo de morir por cáncer gástrico. Palabras clave: Cáncer gástrico, estratificación, riesgo, tasa bruta de mortalidad. Abstract Epidemiological risk stratification offers the opportunity to act proactively, designing specific health care interventions appropriate to the level of need of different groups of people. In order to stratify mortality from gastric cancer according to provinces of residence and characterize some sociodemographic variables, an ecological study of time series was carried out. The universe consisted of the 12,781 deaths in the country whose basic cause of death included in the death certificate was gastric cancer in the 2000-2015 period. Indicators were calculated: reason, percentages, gross and specific mortality rates, by age and sex, per 100,000 inhabitants. Stratification by provinces was classified as low, moderate and high. In the study period, 12,781 deaths were recorded, 78.4 % corresponded to adults over 60 years, the male sex with 61.8 %. The provinces with the highest risk in the four-year period 2011-2015: Cienfuegos (10.1), Guantánamo (9.7) and Villa Clara (9.45). Conclusions Risk stratification at the provincial level showed important variations in the study period. Adults over 60 years of age are at greater risk of dying from gastric cancer. Keywords: Gastric cancer, stratification, risk, gross mortality rate.

Evolución de la mortalidad por cáncer gástrico en el adulto mayor Cuba 1987-2015

El cáncer gástrico afecta principalmente a las personas de edad avanzada. Con el objetivo de caracterizar la evolución de la mortalidad por cáncer gástrico en el adulto mayor en Cuba durante los años 1987-2015, según variables sociodemográficas seleccionadas, se realizó un estudio ecológico de series temporales. El universo estuvo conformado por 16713 fallecidos mayores de 60 años en Cuba, cuya causa de muerte registrada en el certificado de defunción fue el cáncer gástrico. Se analizaron tasas anuales crudas y ajustadas por grupos de edad y sexo. Predominó el sexo masculino con 62,3 % y el grupo de edad de 70-79 años con 37,1 %, mayor frecuencia de morir en hombre 1,6:1. El 38,6 % de los fallecidos tenía color de la piel blanca, más frecuente en el sexo masculino. Fue evidente que a la hora de la muerte predominó la condición de fallecidos sin parejas estables en 57,4 %. Las tasas de mortalidad ajustadas por grupos de edad aumentan después de la octava década de la vida. La evolución de la mortalidad por cáncer gástrico durante los últimos 28 años muestra una tendencia ascendente a predominio del sexo masculino, se hace necesario diseñar e implementar programas de detección precoz que vayan dirigidos a la disminución de la mortalidad en los adultos mayores. Palabras clave: Cáncer gástrico, adulto mayor, tasa de mortalidad, tasa bruta de mortalidad y tasa ajustada de mortalidad. Abstract Gastric cancer affects mainly the elderly. Objective: to characterize the evolution of mortality due to gastric cancer in the elderly. Cuba 1987-2015 according to selected sociodemographic variables. Method: ecological study of time series. Universe: 16713 deaths in the country over 60 years whose basic cause of death recorded in the death certificate was gastric cancer. Crude annual rates adjusted for age and sex groups were analyzed. Results: male sex predominated with 62.3 % and the age group of 70-79 years with 37.1 %, higher frequency of death in male 1.6: 1. 38.6 % of the deceased had white skin color, more frequent in the male sex. It was evident that at the time of death the condition of deceased without stable partners predominated in 57.4 %. Mortality rates adjusted for age groups increase after the eighth decade of life. Conclusion: the evolution of mortality from gastric cancer during the last 28 years shows an ascending tendency to predominance of the male sex, it is necessary to design and implement early detection programs that are aimed at reducing mortality in the elderly. Keywords: Gastric cancer, older adult, mortality rate, crude and adjusted rates.

LONG - TERM RESULTS FROM CURABLE GASTRECTOMY AND D2, D3 LYMPHADENECTOMY IN GASTRIC CANCER TREATMENT

Objectives: Evaluation of pathological characteristics, motality rate and five-year survival rate from curable gastrectomy and D2, D3 lymphadenectomy in gastric cancer at Hue Centre Hospital. Materials and methods: Consist of 119 patients underwent curable gastrectomy and D2, D3 lymphadenectomy from May 2005 to May 2012. Results: Age: average 56.2 ± 11.8 (19-81), male/female 1.83/1. Distal subtotal gastrectomy 88.24%, total gastrectomy 7.56%, proximal subtotal gastrectomy 4.2% Lymphadenectomy: D2 62.18%, D3 37.82%. TNM classification: first stage 4.20%, second stage 29.41%, third stage 61.34% và fourth stage 5.04%. Intraoperative splenic rupture was the most common 5.88%, overall five-year survival rate 28.8%, overall D2 five-year survival rate 47.9%; overall D3 five-year survival rate 63.1% (not significant with p = 0.1137) and non relatively operative motality. Conclusion: Curable gastrectomy and D2, D3 lymphadenectomy in gastric cancer is safety, five-year survival rate is long-term, and oncologically effective procedure. Keywords: Gastric cancer, Gastrectomy, D2, D3 Lymphadenectomy. Key words: Gastric cancer, Gastrectomy, D2, D3 Lymphadenectomy