| 1. |
|
|
| 2. |
|
|
| 3. |
- Hussain, Showket, et al.
(författare)
-
Association of cyclin D1 gene polymorphisms with risk of esophageal squamous cell carcinoma in Kashmir Valley : a high risk area
- 2011
-
Ingår i: Molecular Carcinogenesis. - : Wiley-Blackwell. - 0899-1987 .- 1098-2744. ; 50:7, s. 487-98
-
Tidskriftsartikel (refereegranskat)abstract
- Investigation of potential association of SNPs (G870A, rs9344; G1722C, rs678653) of cyclin D1 gene (CCND1) with susceptibility to esophageal squamous cell carcinoma (ESCC) in Kashmir valley (India). The study included 302 subjects comprising 151 ESCC cases and 151 controls. PCR-RFLP and direct sequencing were employed for genotyping. The G870A polymorphism, the individuals carrying GA + AA genotype was having 2.80-fold increased risk for development of ESCC (OR 2.8, 95% CI = 1.77-4.4; P = 0.0001) compared to GG genotype. Further a significantly higher risk was observed in individuals who consume >3 cups per day of salted tea (OR = 5.1; 95% CI = 1.6-16.7; P = 0.0016) and had smoking habits (OR = 6.3; 95% CI = 2.9-13.9; P = 0.0005). We also demonstrate for the first time in CCND1 1722 locus, the CC genotype was strongly associated with increased risk of developing ESCC (OR = 2.58; 95% CI = 1.61-4.15; P = 0.0001). In addition, the frequency of polymorphic C allele was also found to be higher in cases (OR = 1.92; 95% CI = 1.37-2.69; P = 0.0002). There appears to be an influence of CCND1 G870A/G1772C genotypes on genetic susceptibility to ESCC.
|
|
| 4. |
- Hussain, Showket, et al.
(författare)
-
Methylation-mediated gene silencing of suppressor of cytokine signaling-1 (SOCS-1) gene in esophageal squamous cell carcinoma patients of Kashmir valley
- 2011
-
Ingår i: Journal of Receptor and Signal Transduction Research. - : Informa Healthcare. - 1079-9893 .- 1532-4281. ; 31:2, s. 147-56
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir. The negative regulation of tumor suppressor gene leading to change in signaling pathway is one of the major mechanisms responsible for tumorigenic transformation.OBJECTIVE: In the present study, the role of silencing of suppressor of cytokine signaling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway, was analyzed in ESCC.METHODS: The expression pattern of SOCS-1 gene was analyzed in esophageal tumor biopsies although normal adjacent tissues that served as controls. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, methylation-specific PCR (MSP), and human papillomavirus (HPV) detection were performed to assess the expression pattern and promoter methylation of SOCS-1 gene including HPV status in a total of 75 surgically resected tissue specimens.RESULTS: Compared with the level of SOCS-1 expression in normal tissues, 53% (40/75) of the tumor tissues expressed either undetectable or reduced SOCS-1 expression (>50% loss of expression), which was significantly associated with advanced clinical stage or severe histopathological grade of the disease (P < 0.01). Aberrant promoter methylation of the SOCS-1 gene was found in 45% (34/75) of the esophageal tumor tissues, which was also found to be significantly associated with advanced stage of esophageal carcinoma (P < 0.01). The prevalence of HPV infection was found in 19% of tumor cases, whereas no HPV could be detected in any of the normal adjacent tissues.CONCLUSION: Transcriptional inactivation of SOCS-1 gene, primarily due to its promoter hypermethylation although HPV infection, may play an important role in esophageal carcinogenesis in Kashmir.
|
|
| 5. |
|
|
| 6. |
- Singh, Neha, et al.
(författare)
-
Downregulation of tumor suppressor gene PML in uterine cervical carcinogenesis : impact of human papillomavirus infection (HPV)
- 2013
-
Ingår i: Gynecologic Oncology. - : Elsevier. - 0090-8258 .- 1095-6859. ; 128:3, s. 420-6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Cervical cancer is a leading gynecological cancer in Indian women and is caused due to infection with high risk human pappilloma virus (HR-HPV) 16 and 18. It has been well documented that PML (promyelocytic leukemia) enhances viral infectivity and plays a crucial role in antiviral response mechanisms. The aim of the present study was to evaluate the role of PML gene with context to HPV infection in cervical carcinogenesis.METHODS: The expression pattern of PML was analyzed by western blotting and immunohistochemistry in a total of 170 fresh surgically resected cervical tissue specimens comprising precancer (n=12), cancer (n=118) and normal controls (n=40) recruited from PGIMER, Chandigarh, India. HPV status was analyzed by L1 consensus PCR followed by type specific PCR for HR-HPV types 16 and 18 and low risk types 6 and 11.RESULTS: A significant downregulation of PML protein was observed in the majority of cervical cancer and precancer cases 68% (89/130) compared to normal controls. The loss of expression pattern of PML gene was significantly increased with severity of disease both clinically and pathologically (p<0.001). HPV infection was detected in the majority of cancer cases 96% (113/118) and in 83% (10/12) of precancer lesions whereas no infection could be detected in normal controls. Interestingly, all the 68% (89/130) cervical cancer cases that showed downregulation of PML were HPV infected (p=0.0001).CONCLUSION: Taken together, these observations suggest that the downregulation of PML gene and its synergism with HPV infection may play an important role and may serve as a new marker for early diagnosis and therapeutic intervention for cervical carcinogenesis.
|
|
| 7. |
- Singh, Neha, et al.
(författare)
-
Implication of high risk Human papillomavirus HR-HPV infection in prostate cancer in Indian population- A pioneering case-control analysis
- 2015
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is the second most common cancer with sexual history as a consistent risk factor. This is the pioneering study that evaluates the frequency of HPV infection in prostate cancer in India. Ninety five (95) histopathologically confirmed cancer and fifty five (55) BPH from Indian population were analyzed for HPV infection using a pair of consensus sequence primer followed by type specific PCRs for both high-risk and low-risk HPV types. The data demonstrate HPV infection in 41% of prostate tumor biopsies and 20% in BPH. Subsequent PCR- based HPV typing using type - specific primers revealed 32% were infected with HPV type 16 whereas 6% were found to be positive for HPV type 18, while in BPH controls only 5% of the BPH controls were infected with HPV 16 and this difference was highly significant (p = 0.0004). Significant proportion of HPV infected (74%) cases belonged to stage III and IV (p < 0.001) with a high Gleason score ≥8 (p = 0.003). The study represents for the first time the incidence of HPV infection in prostate cancer in Indian population and strengthens the hypothesis that HPV infection could be one of the co factor associated with progression of prostate cancer.
|
|
| 8. |
- Singh, Neha, et al.
(författare)
-
Overexpression of signal transducer and activator of transcription (STAT-3 and STAT-5) transcription factors and alteration of suppressor of cytokine signaling (SOCS-1) protein in prostate cancer
- 2012
-
Ingår i: Journal of Receptor and Signal Transduction Research. - : Informa Healthcare. - 1079-9893 .- 1532-4281. ; 32:6, s. 321-7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer is a leading cause of mortality in men worldwide especially in developing countries like India. The molecular mechanisms of the oncogenic signaling pathway(s) that are involved in prostate carcinogenesis play a crucial role in disease progression and persistence. There is an important role of signal transducer and activator of transcriptions (STATs) particularly STAT-3 and STAT-5 and its negative regulator suppressor of cytokine signaling-1 (SOCS-1).METHODS: In the present study, the expression and localization of STAT and SOCS-1 proteins in prostate cancer by immunohistochemistry in a total of 150 formalin-fixed, paraffin-embedded human prostate tissues of different grade obtained by radical prostatectomies or transurethral resection.RESULTS: A significantly strong STAT-3 expression pattern in 68% (65/95) prostate cancer cases as compared to 12% (5/55) in benign prostatic hyperplasia (BPH) controls (P < 0.001) was observed. Interestingly the SOCS-1 expression was found to be significantly elevated in prostate cancer cases (P < 0.001).CONCLUSIONS: The present study demonstrates overexpression of STAT-3 and STAT-5 proteins and a contrasting role of SOCS-1 in prostate cancer. These results suggest a critical association between altered expression of STAT-3 and STAT-5 with SOCS-1 and indicate its potential role as a negative regulator independent of JAK-STAT pathway in tumorigenic transformation of prostate tissue. The results of the present report focuses on the fundamental differences in major oncogenic signaling cascades between benign and malignant form of prostate tissue that plays a crucial role in prostate cancer biology.
|
|
| 9. |
|
|
| 10. |
- Sobti, R. C., et al.
(författare)
-
Aberrant promoter methylation and loss of suppressor of cytokine signalling-1 gene expression in the development of uterine cervical carcinogenesis
- 2011
-
Ingår i: Cellular Oncology. - : Springer Science and Business Media LLC. - 2211-3428 .- 2211-3436. ; 34:6, s. 533-43
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cervical cancer is a leading cause of cancer related deaths in women worldwide caused due to infection of high-risk human papillomaviruses. As JAK/STAT signalling pathway has been shown to play an important role during carcinogenesis, we studied the role of silencing of Suppressor of Cytokine Signalling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway in cervical cancer.METHODS: The expression pattern of SOCS-1 mRNA and protein was analyzed in different stages of cervical tumor biopsies while normal cervical tissues served as controls. RT-PCR, immunohistochemistry and methylation-specific PCR (MSP) were performed to assess the expression pattern and promoter methylation of SOCS-1 gene in a total of 120 fresh surgically resected cervical tissue specimens comprising precancer (n = 12), cancer (n = 78) and normal controls (n = 30).RESULTS: Compared with expression of SOCS-1 in normal tissues, 64% of the tumor tissues expressed either undetectable or reduced expression. Aberrant promoter methylation of SOCS-1 was found in 61% of the cervical tumor tissues. SOCS-1 expression and methylation were significantly associated with severity of the disease (p < 0.01).CONCLUSION: We demonstrate for the first time the transcriptional inactivation of SOCS-1 gene due to hypermethylation and synergism with HPV infection which may play an important role in cervical carcinoma.
|
|
