Institute of Cytology and Preventive Oncology ICMR

Greater Noida, India

Institute of Cytology and Preventive Oncology ICMR

Greater Noida, India
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Bharadwaj M.,Institute of Cytology and Preventive Oncology ICMR | Roy G.,Institute of Cytology and Preventive Oncology ICMR | Roy G.,Jamia Millia Islamia University | Dutta K.,Medical College Hospital | And 3 more authors.
Cancer and Metastasis Reviews | Year: 2013

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in many developing countries including India. Among the various etiological factors being implicated in the cause of HCC, the most important cause, however, is hepatitis B virus (HBV) infection. Among all HBV genes, HBx is the most critical carcinogenic component, the molecular mechanisms of which have not been completely elucidated. Despite its clinical significance, there exists a very elemental understanding of the molecular, cellular, and environmental mechanisms that drive disease pathogenesis in HCC infected with HBV. Furthermore, there are only limited therapeutic options, the clinical benefits of which are insignificant. Therefore, the quest for novel and effective therapeutic regimen against HBV-related HCC is of paramount importance. This review attempts to epitomize the current state of knowledge of this most common and dreaded liver neoplasm, highlighting the putative treatment avenues and therapeutic research strategies that need to be implemented with immediate effect for tackling HBV-related HCC that has plagued the medical and scientific fraternity for decades. Additionally, this review proposes a novel "five-point" management algorithm for HBV-related HCC apart from portraying the unmet needs, principal challenges, and scientific perspectives that are relevant to controlling this accelerating global health crisis. © 2012 Springer Science+Business Media New York.

Gupta S.,Institute of Cytology and Preventive Oncology ICMR | Sodhani P.,Institute of Cytology and Preventive Oncology ICMR | Singh V.,Institute of Cytology and Preventive Oncology ICMR | Sehgal A.,Institute of Cytology and Preventive Oncology ICMR
Diagnostic Cytopathology | Year: 2013

The study was undertaken to assess the utility of cervico-vaginal/vault cytology in the follow-up of women treated for cervical cancer and benign gynecological conditions. Records of 3,523 cervico-vaginal smears from 2,658 women who underwent hysterectomy and/or radiotherapy or chemotherapy, over a 10-year period were retrieved. Data was collected on type of treatment received, indication for hysterectomy, age of patient, presenting symptoms, stage of tumor, interval since treatment, cytology and biopsy results. The results of cytology versus other parameters were analyzed separately for women treated for cervical cancer and those hysterectomized for benign indications. Malignant cells were detected in 141/1949 (7.2%) follow-up smears from treated cervical cancer cases (140 recurrences and 1 VAIN). Around 92% of recurrences of cervical cancer were detected with in 2 years of follow-up and 75% of these women were symptomatic. Cytology first alerted the clinicians to a recurrence in a quarter of cases. On the other hand, VAIN was detected in 5/1079 (0.46%) vault smears from 997 women hysterectomized for benign gynecologic disease. All these women were asymptomatic and majority (80%) were detected in follow-up smears performed between 3 and 10 years. Vault cytology is an accurate tool to detect local recurrences/VAIN in women treated for cervical cancer or benign gynecological conditions. It may even first alert the clinicians to a possibility of recurrence. However, due to extremely low prevalence of VAIN/vaginal cancer, it seems unwarranted in women hysterectomized for benign indications, especially in resource constrained settings. Diagn. Cytopathol. 2013;41:762-766. © 2013 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Narain R.,Institute of Cytology and Preventive Oncology ICMR | Sardana S.,Institute of Cytology and Preventive Oncology ICMR | Gupta S.,Institute of Cytology and Preventive Oncology ICMR | Sehgal A.,Institute of Cytology and Preventive Oncology ICMR
Indian Journal of Medical Research | Year: 2011

Background &objectives: Tobacco use among school children is becoming a serious problem in developing countries. The early age of initiation underscores the urgent need to intervene and protect this vulnerable group from falling prey to this addiction. The present study was thus undertaken to assess the prevalence of tobacco habits among school children, determine the age of initiation of these habits, and compare the age of initiation between students who were more than 15 and ≤ 15 yr of age. Methods: Data on tobacco use were collected from 4786 students of class 7 to 12 (age: 11-19 yr) studying in different private and government schools of Noida city during July- December 2005, through cluster and random sampling using a self-administered questionnaire. Results: Any kind of tobacco use was found in 537 (11.2%) students; 419 (8.8%) were 'ever smokers (including current smokers)' 219 (4.6%) were 'ever tobacco chewers (including current chewers)', 179 (3.7%) were 'exclusive smokers' and 118 (2.5%) were 'exclusive tobacco chewers'. The mean age of initiation of these habits was around 12.4 yr. More than 50 per cent of tobacco chewers reported use of khaini at least once. Nearly 70 per cent of boys and 80 per cent of girls ≤ 15 yr initiated the habit of tobacco before the age of 11 yr. A significant early uptake of tobacco chewing was reported from private school students as compared to government school students (P<0.05). Interpretation & conclusions: Tobacco addiction is emerging as a big threat among children. Our findings indicate a recent downward shift in the age at initiation of tobacco uptake and rising prevalence among girls. Such data need to be collected from different parts of the country to develop anti-tobacco campaigns and take policy decision.

Singhal P.,Institute of Cytology and Preventive Oncology ICMR | Hussain S.,Institute of Cytology and Preventive Oncology ICMR | Thakur N.,Institute of Cytology and Preventive Oncology ICMR | Batra S.,LNJP Hospital | And 3 more authors.
DNA and Cell Biology | Year: 2013

Cervical cancer is one of the most common gynecological malignancies that causes a serious health problem worldwide. The aim of the present study was to analyze the association of p53 codon72 (arginine/proline) polymorphism (rs1042522) and Murine Double Minute 2 (MDM2) SNP309 T/G (rs2279744) with the advancement of cervical cancer by using polymerase chain reaction-restriction fragment length polymorphism method followed by direct sequencing. The frequencies of GG genotype at 309 position in the second promoter (P2) of MDM2 and Arginine in codon72 of p53 were found to be 3.5 (odds ratio [OR]=3.51; 95% confidence interval [CI]=1.93-6.4; p<0.0001) and 5 (OR=4.978; 95% CI=2.7-9.2; p<0.0001) fold higher, respectively, in cases than in the control. On gene-gene interactions between MDM2 and p53 polymorphisms, the frequency of MDM2 G/G and p53 Arg/Arg together was found to be 6.5-fold higher in cervical cancer patients compared with healthy controls (OR=6.497; 95% CI=2.987-14.13; p<0.0001). We found an association of p53 codon72 arginine and MDM2 SNP309 GG genotype with different clinical and histological grades, human papillomavirus (HPV) infection, and age at the time of diagnosis of cervical cancer. In conclusion, Arginine at codon72 of p53 and GG genotype at 309 in P2 of MDM2 together reveal a direct proportionality with the tumor grade of cervical cancer along with HPV infection in postmenopausal women. © Mary Ann Liebert, Inc.

Singh N.,Panjab University | Sobti R.C.,Panjab University | Suri V.,Post Graduate Institute of Medical Education and Research | Nijhawan R.,PGIMER | And 4 more authors.
Gynecologic Oncology | Year: 2013

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. © 2012 Elsevier Inc.

Singhal P.,Institute of Cytology and Preventive Oncology ICMR | Kumar A.,Institute of Cytology and Preventive Oncology ICMR | Bharadwaj S.,Guru Gobind Singh Indraprastha University | Hussain S.,Institute of Cytology and Preventive Oncology ICMR | Bharadwaj M.,Institute of Cytology and Preventive Oncology ICMR
Tumor Biology | Year: 2015

Aim: Cervical cancer is the most common gynecological malignancy in the developing countries like India. In addition to human papillomavirus (HPV) infection, host genetic factors play an important role in viral persistence and neoplastic growth. IL-10, a multifunctional cytokine, plays an active role to promote tumor growth in the presence of HPV. The present study aims to find out the impact of IL-10 promoter polymorphisms at -1082A/G (rs1800896), -819C/T (rs1800872), and -592C/A (rs1800871) sites along with IL-10 production and HPV infection in the progression of cervical cancer. Methods: We have genotyped a total of 506 subjects, 256 cases (208 cervical cancer + 48 precancer), and 250 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method followed by sequencing. IL-10 serum concentration was measured by enzyme-linked immunosorbent assay. Results: The frequency of IL-10 -592 variant genotype (AA) was found significantly reduced in cases as compare to controls while -1082 variant genotype (GG) was found ~4-fold higher risk of cervical cancer (p = <0.0001, OR = 3.667, 95 % CI = 2.329–5.773). On construction of haplotypes, GTC haplotype was emerged as a major risk haplotype while ACA haplotype was seemed as a marker for precancerous lesions. IL-10 serum concentration was observed higher in HPV-infected precancer and cancer cases. GTC haplotype was found to be coupled with higher serum concentration of IL-10 and HPV infection. Conclusion: IL-10 polymorphisms play a role in cervical cancer development and that GTC haplotype, which is closely related to its serum concentration, maybe a useful biomarker for HPV-mediated cervical cancer. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Prasad S.,and Reproductive Biology Center | Kumar Y.,and Reproductive Biology Center | Singhal M.,and Reproductive Biology Center | Sharma S.,Institute of Cytology and Preventive Oncology ICMR
Journal of Obstetrics and Gynecology of India | Year: 2014

Objective: To evaluate role of serum estradiol levels in predicting likelihood of pregnancy in women undergoing GnRH-a protocol in IVF-ET cycles. Design: A 3-year retrospective analysis of estradiol levels on down-regulated day 2, day 6, and day of hCG trigger and subsequent clinical pregnancy rates. Setting: A university hospital tertiary referral centre. Population or Sample: Women undergoing IVF treatment. Methods: Hormonal assessment on the down-regulated day 2, day 6, and day of hCG trigger. Main Outcome Measure(s): Comparison of hormonal profile, antral follicular count on day 2, endometrial thickness on day of trigger, and number of oocytes retrieved between pregnant and the non-pregnant group. The prediction of IVF success was based on the quantitative levels of estradiol on a specific day in down-regulated cycle. Result(s): The overall pregnancy rate was 32.25 % (50/160). Estradiol level on down-regulated day 2 was 31.9 ± 12.6 and on the day of trigger was 1,996.46 ± 1,252.36 in pregnant women, which was significantly higher as compared to estradiol levels in non-pregnant women (27.6 ± 12.3 and 1,525.1 ± 1,116.42, respectively). It was found to be a significant prognostic marker for successful IVF treatment. Estradiol levels on down-regulated day 6 were found to be non-significant between the two groups. Conclusion(s): Estradiol level on down-regulated day 2 of menstrual cycle and on the day of trigger was found to have a significant impact on the success of IVF-ET. © 2014 Federation of Obstetric & Gynecological Societies of India.

Gupta S.,Institute of Cytology and Preventive Oncology ICMR | Sodhani P.,Institute of Cytology and Preventive Oncology ICMR
Diagnostic Cytopathology | Year: 2012

The frequency of possible reasons for "atypical squamous cells" (ASC) overdiagnosis on Papanicolaou (Pap) smears was analyzed. Pap smears of 199 women with negative biopsy outcome after an ASC diagnosis were reviewed. Special attention was paid to presence of reproductive tract infections (RTIs), perimenopausal cells (PM cells), immature metaplastic cells, hormone-related alterations, and drying artefacts. Comparisons were made using Ï2 test between the two ASC qualifiers and also between premenopausal and peri/postmenopausal women. Possible reasons for ASC overdiagnosis could be assigned on Pap smear review in 88/199 (44.2%) negative biopsies. Overall, PM cells were the most frequent reason for ASC overdiagnosis, being present in 35/199 (17.6%) smears. RTIs were the next most common cause (14.6%). PM cells were the most significant confounding factors for persistent ASC undetermined significance (ASC-US) over interpretation (20.2%) while in none of the cases these were interpreted as ASC-H (P = 0.004). Of these, 32 smears belonged to peri/postmenopausal women while only three to premenopausal women (P < 0.001). Immature metaplastic cells were significantly more frequent cause of ASC-H rather than ASC-US interpretation (P = 0.007). RTIs and drying artefacts were more frequently overcalled as ASC-US (in premenopausal women) while hormonal changes were interpreted as ASC-H. Hormone related changes, immature metaplastic cells and drying artefacts more commonly resulted in ASC interpretation in peri/ postmenopausal smears. The results of this study suggest that diligent screening can substantially reduce ASC overdiagnosis, thereby reducing the referrals/ follow ups. © 2011 Wiley Periodicals, Inc.

Bhartiya D.,Institute of Cytology and Preventive Oncology ICMR | Chandramouli B.,Normal School of Pisa | Kumar N.,CSIR - Central Electrochemical Research Institute
Proteins: Structure, Function and Bioinformatics | Year: 2015

Plasmodium falciparum encounters frequent environmental challenges during its life cycle which makes productive protein folding immensely challenging for its metastable proteome. To identify the important components of protein folding machinery involved in maintaining P. falciparum proteome, we performed a proteome-wide phylogenetic profiling across various species. We found that except HSP110, the parasite lost all other cytosolic nucleotide exchange factors essential for regulating HSP70 which is the centrum of the protein folding network. Evolutionary and structural analysis shows that besides its canonical interaction with HSP70, PfHSP110 has acquired sequence insertions for additional dynamic interactions. Molecular co-evolution profile depicts that the co-evolving proteins of PfHSP110 belong to distinct pathways like genetic variation, DNA repair, fatty acid biosynthesis, protein modification/trafficking, molecular motions, and apoptosis. These proteins exhibit unique physiochemical properties like large size, high iso-electric point, low solubility, and antigenicity, hence require PfHSP110 chaperoning to attain functional state. Co-evolving protein interaction network suggests that PfHSP110 serves as an important hub to coordinate protein quality control, survival, and immune evasion pathways in the parasite. Overall, our findings highlight potential accessory roles of PfHSP110 that may provide survival advantage to the parasite during its lifecycle and febrile conditions. The data also open avenues for experimental validation of auxiliary functions of PfHSP110 and their exploration for design of better antimalarial strategies. © 2015 Wiley Periodicals, Inc.

Gupta S.,Institute of Cytology and Preventive Oncology ICMR | Sodhani P.,Institute of Cytology and Preventive Oncology ICMR | Jain S.,Maulana Azad Medical College
Journal of Cancer Research and Therapeutics | Year: 2012

Context: The diagnosis of metastatic cancer in fluids is of capital importance as, in most such instances, a rapid fatal outcome of the disease is anticipated. Aim: To determine the spectrum and cytomorphological features of the common and unusual malignancies presenting with effusions. Methods and Materials : A total of 11,562 effusion samples received for cytopathological examination over a 10-year period were analyzed retrospectively. Cytomorphological features of neoplastic effusions were studied. Special stains and immunocytochemistry (ICC) were performed to aid the diagnosis in difficult cases. Observations : The effusion samples comprised of pleural (5018), peritoneal (6340) and pericardial (204) fluids. A definitive diagnosis of classifiable malignancy could be given in 836 (7.3%) of these cases (5.7% adenocarcinomas and 1.6% uncommon malignancies). Adenocarcinoma was the most frequent cause of malignant pleural (70%) and peritoneal effusions (86.9%). The most common primary site for pleural metastasis was lung (35.7%), while for peritoneal metastasis, it was the ovary (54.3%). Among the uncommon neoplastic effusions, hematopoeitic malignancies were the most frequent, followed by squamous cell carcinomas. Primary malignant mesotheliomas were the most challenging to diagnose on effusion cytology. ICC was useful to arrive at a definitive diagnosis in difficult cases. Conclusions: Cytology is a useful tool to detect malignant effusions. However, in uncommon malignancies presenting as effusions, a detailed clinical history and ancillary investigations are often required to make a correct diagnosis.

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