• Title/Summary/Keyword: SHER

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Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley

  • Wani, Majid;Afroze, Dil;Makhdoomi, Muzamil;Hamid, Iqra;Wani, Bilal;Bhat, Gulzar;Wani, Rauf;Wani, Khursheed
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4177-4181
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    • 2012
  • Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age ($mean{\pm}S.D$) $50{\pm}11.4$ years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001).We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.

Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer

  • Pandith, Arshad A;Hussain, Aashaq;Khan, Mosin S;Shah, Zafar A;Wani, M Saleem;Siddiqi, Mushtaq A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2787-2793
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    • 2016
  • Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

ADA Levels in Body Fluids as the Preferred Test to Rule Out Tuberculosis in Limited-resource Settings: Data from a Tertiary Care Hospital in Northern India

  • Rasool, Rafia;Rashid, Gowhar;Mir, Shafat Ahmad;Rather, Tahseen Bilal;Mudassar, Syed
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.3
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    • pp.167-172
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    • 2022
  • In clinical practice, the diagnosis of tuberculosis (TB) continues to be a challenge. The goal of this study was to evaluate the reliability and impact of adenosine deaminase (ADA) enzyme testing as a biochemical marker in the continued management of suspected tuberculosis in a limited resource setting hospital. The retrospective data were collected from 2018 to 2021 and comprised the results of all ADA test assays done in the laboratory. All types of body fluids received for ADA testing were analyzed. Over the course of two years, 1461 samples for ADA assay testing were received. The average age of the study population was 56.69±11.7 years, with males accounting for the majority of the subjects (55.72%). Pleural fluid (N=817, 55.92%) was the most common type of sample received for the ADA assay. 114 (13.95%) of the 817 pleural fluid samples were found to be positive. A survey was conducted to obtain physician's response regarding reliability on ADA testing. 100% of them reported the supportive role of ADA levels in the workup of patients with suspected tuberculosis. In a limited resource setting, the ADA test, in conjunction with clinical and other laboratory findings, can help physicians to initiate early treatment in hospitals for the benefit of patients.

IL-1β Polymorphism and Expression Associated with Decreased Risk of Gastric Carcinoma: a Case Control Study in the Ethnic Kashmiri Population, India

  • Irtiza, Syed;Samie, Amat Us;Ali, Shakir;Siddiqi, Mushtaq A;Naqash, Sameer H;Sameer, Aga Syed
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1987-1992
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    • 2015
  • The aim of this research was to investigate the possible association between gastric carcinoma (GC) and polymorphisms of the IL-$1{\beta}$ gene in the Kashmiri population using peripheral blood DNA from 150 gastric carcinoma cases and 250 population controls with detailed data for clinicopathological characteristics of the disease. Two SNPs in the IL-$1{\beta}$ gene were selected for this study. Expression of IL-$1{\beta}$ was studied in 50 gastric carcinoma cases using immunohistochemistry and RT-PCR and then correlated with genotype. The frequency of the IL-$1{\beta}$-511 C allele was significantly higher in the GC case group (53.3%) than in controls (45.4%) with an odds ratio (OR) of 0.73 and a P value of 0.03. Multivariate regression analysis showed associations of gastric carcinoma with mutant form of IL-$1{\beta}$-511 TT (OR 0.309; P value <0.001) and the CC genotype of IL-$1{\beta}$-31 (OR 0.313; P value of 0.002). Haplotype analysis of IL-$1{\beta}$-31 and IL-$1{\beta}$-511 showed decreased association of IL-$1{\beta}$-31 T with IL-$1{\beta}$-511 C with gastric carcinoma (OR 0.728; P value 0.03). Expression study of 50 samples by immunohistochemistry (IHC) and RT-PCR showed association with grade III and stage III+IV. After correlating the expression with polymorphism no association was found.

Lack of Influence of MGMT Codon Leu84Phe and Codon Ileu143Val Polymorphisms on Esophageal Cancer Risk in the Kashmir Valley

  • Shah, Mohd A.;Shaffi, Sheikh M.;Lone, Ghulam Nabi;Jan, Syed Mudassar
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3047-3052
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    • 2012
  • The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.

5'-CpG Island Promoter Hypermethylation of the CAV-1 Gene in Breast Cancer Patients of Kashmir

  • Syeed, Nidda;Hussain, Firdous;Husain, Syed Akhtar;Siddiqi, Mushtaq A.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.371-376
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    • 2012
  • Background: Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signalling. Aberrant promoter methylation of CAV-1 is associated with inactivation of expression. We previously observed CAV-1 mutations in breast cancers and therefore devised this study to examine the hypermethylation status of the promoter region of CAV-1 with reference to breast cancer progression and development. Methods: Hypermethylation status of CAV-1 was analyzed by methylation specific PCR. Loss of expression of the CAV-1 gene was further evaluated by semi-quantitative rt-PCR. Results: 28/130 (21.5%) breast cancer cases showed promoter hypermethylation with reduced CAV-1 expression levels when compared with adjacent normal breast tissue. CAV-1 gene hypermethylation was significantly related to menopausal status, histopathological grade and age. Conclusion: The rationale of our study is that CAV-1 gene is transcriptionally repressed in breast cancer cells due to hypermethylation. Our results reveal that promoter hypermethylation and loss of expression of the CAV-1 gene is an important alternative mechanism for inactivation of CAV-1 leading to complete gene silencing.

Metastatic Lymphadenopathy in Kashmir Valley: A Clinicopathological Study

  • Qadri, Sumyra Khurshid;Hamdani, Nissar Hussain;Shah, Parveen;Baba, Khalil Mohammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.419-422
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    • 2014
  • Background: Lymphadenopathy is a common presentation in both benign and malignant diseases which need to be diagnosed without delay. Fine needle aspiration cytology (FNAC) helps us diagnose a disease and follow its course, including the response to therapy. Aim: This study aimed to analyze the clinicopathological features of metastatic lymphadenopathy and the diagnostic utility of FNAC in our setting. Materials and Methods: This two-year prospective study included all the patients with metastatic lymphadenopathy, diagnosed with FNAC. Results: A total of 412 cases (male:female ratio, 1.3:1; age range, 3 to 90 years) were studied. Supraclavicular lymph nodes were involved most commonly (50.5%). The commonest metastatic tumor was squamous cell carcinoma in general (30.1%) and in males (37.6%), and infiltrating ductal carcinoma (25.3%) in females. Lung, with 64 (15.5%) cases followed by esophagus, 60 (14.6%) cases; breast, 49 (11.9%) cases; skin, 32 (7.8%) cases; and stomach, 25 (6.1%) cases were the most common primary sites of malignancy. In 69 patients, excision biopsy was performed. Histopathological findings correlated well with that of cytology in all these cases. Conclusions: FNAC is an important tool in the diagnostic work up of metastatic lymphadenopathy, which in the hands of an experienced and skilful cytopathologist can avoid the need for excision biopsy.

N-Nitrosodimethylamine in the Kashmiri Diet and Possible Roles in the High Incidence of Gastrointestinal Cancers

  • Chikan, Naveed A.;Shabir, Nadeem;Shaffi, Sheikh;Mir, Manzoor R.;Patel, Trupti N.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.1077-1079
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    • 2012
  • The Kashmiri population is culturally distinct with special dietary features owing to the temperate climatic conditions of Kashmir valley. This has habituated the population to preserve food in smoked, pickled and sundried forms which include considerable amounts of $N$-nitroso compounds (NOCs). These are known to cause cytotoxicity, DNA damage, mutation, unscheduled DNA synthesis and DNA methylation. All of these changes at molecular level are known to contribute to the pathogenesis of cancer. One of the prominent NOCs found in Kashmiri food is $N$-Nitrosodimethylamine (NDMA). Here we review the occurrence of NDMA in sundried foods, dried fish, kehwa, traditional pickle, $Brassica$ $oleracia$ and $tobbaco$. We also discuss its possible role in the high prevalence of gastrointestinal cancers in Kashmir.

Estimation of runoff coefficient through impervious covers analysis using long-term outflow simulation (장기유출 모의를 통한 도시유역 불투수율에 따른 유출계수 변화)

  • Kim, Young-Ran;Hwang, Sung-Hwan
    • Journal of Korean Society of Water and Wastewater
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    • v.28 no.6
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    • pp.635-645
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    • 2014
  • The changes of rainfall pattern and impervious covers have increased disaster risks in urbanized areas. Impervious covers such as roads and building roofs have been dramatically increased. So, it is falling the ability safety of flood defense equipments to exist. Runoff coefficient means ratio of runoff by whole rainfall which is able to directly contribute at surface runoff during rainfall event. The application of accurate runoff coefficients is very important in sewer pipelines design. This study has been performed to estimate runoff characteristics change which are applicable to the process of sewer pipelines design or various public facilities design. It has used the SHER model, a long-term runoff model, to analyze the impact of a rising impervious covers on runoff coefficient change. It thus analyzed the long-term runoff to analyze rainfall basins extraction. Consequently, it was found that impervious surfaces could be a important factor for urban flood control. We could suggest the application of accurate runoff coefficients in accordance to the land Impervious covers. The average increase rates of runoff coefficients increased 0.011 for 1% increase of impervious covers. By having the application of the results, we could improve plans for facilities design.

Yield Response of Bushbean (Phaseolus vulgaris L.) to Doses of Fertilizers and Sowing Times in Bangladesh

  • Ullah M.J.;Hossain H.M.M. Tariq;Baqque M.A.
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.51 no.6
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    • pp.491-496
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    • 2006
  • The present study was initiated to explore the yield potential of bushbean by exploiting the interaction of variety, sowing time, and fertilizers containing N, P, and K Two varieties namely BARI Bushbean 1 and BARI Bushbean 2, three levels of fertilizer viz. control ($N_{0}P_{0}K_{0}$), medium ($N_{20}P_{30}K_{30}$), high ($N_{40}P_{60}K_{60}$) and three sowing times (November 15, December 1 and December 15) were considered as treatment variables. Among the varieties, BARI Bushbean 2 always showed better performance for most of the yield and yield attributes duly attributed by the application of fertilizers ${\circleda}$ N: P: K = 40: 60: 60 respectively. The highest seed yield (1375.17 kg/ha) was recorded when the crop was sown on the $15^{th}$ November with the supplemented soil nutrition status as above. The influence of sowing times indicate that there is a gradual trend of decreasing in seed yield and other associated parameters after first sowing ($15^{th}\;November$). The results of this study suggest that the multi-locational trial under varied sowing times with soil nutrition might potentially increase the long-term adaptation of bushbean in Bangladesh.