Madhu Srivastava

Impact of Toll-like receptors [TLR] 2 (−196 to −174 del) and TLR 4 (Asp299Gly, Thr399Ile) in cervical cancer susceptibility in North Indian women

OBJECTIVE(S) Targeting the Toll-like receptor (TLR) signaling pathway in elucidating the cellular and molecular mechanisms of human diseases, including cervical cancer, is gaining tremendous importance. The aim of our study was to identify the role of TLR 2(-196 to -174 del) and TLR 4(Asp299Gly and Thr399Ile) gene polymorphisms in cervical cancer susceptibility in North Indian women. METHODS For the study, blood samples were collected from histopathologically confirmed patients of cervical cancer (n=150) and unrelated, healthy female controls of similar ethnicity (n=150). Genomic DNA was extracted from peripheral blood leukocytes using salting-out method. TLR 2 and TLR 4 genotyping was done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism followed by 10% polyacrylamide gel electrophoresis. RESULTS TLR 2 del allele showed significant association (p=0.048, OR=1.6 [95%CI=1.00-2.51]) with cervical cancer susceptibility, while no significant association was found with TLR 4 (Asp299Gly and Thr399Ile). However, TLR 4 Thr/Ile genotype was found to be significantly associated with early stage (Stage II) of cervical cancer (p=0.044, OR=2.51 [95%CI=1.03-6.12]). Furthermore, TLR 2 ins/del genotype showed strong association (p=0.015, OR=1.95 [95%CI=1.14-3.33]) with tobacco usage in women with cervical cancer. CONCLUSION(S) Our study highlighted the involvement of TLR 2 (-196 to -174 del) and TLR 4 (Thr399Ile) gene polymorphisms in cervical cancer susceptibility. The TLR gene polymorphisms, upon further evaluation, may be helpful in elucidation of immunobiological mechanisms associated with cervical cancer susceptibility.

Cyclooxygenase-2 gene polymorphisms and risk of cervical cancer in a North Indian population.

Introduction: Single nucleotide polymorphisms in the cyclooxygenase-2 (COX-2) might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to cancer. This study sought to evaluate the effects of COX-2 +8473T/C (rs5275) and −765G/C (rs20417) gene polymorphisms on the risk of cervical cancer in women of Northern India. Methods: Peripheral blood samples were collected from 200 histopathologically confirmed patients with cervical cancer and 200 unrelated, healthy female controls of similar ethnicity. Questionnaire survey was conducted to comprehend the demographic data, smoking status, and cancer stage of patients. Polymerase chain reaction-based restriction fragment length polymorphism was used to detect the genotypes of the COX-2 gene. Results: Cyclooxygenase-2 +8473CC genotype was associated with a significantly reduced risk of cervical cancer (P = 0.036; odds ratio, 0.4; 95% confidence interval, 0.1−0.9), whereas COX-2 −765G/C polymorphism demonstrated no association. In addition, no significant association with clinical stages of cervical cancer and modulation of risk due to tobacco usage was observed in our study. Conclusions: Cyclooxygenase-2 +8473T/C gene polymorphism demonstrated protective effect in North Indian women. Further studies evaluating the role of COX-2 gene polymorphisms in ethnically diverse populations and a larger cohort may help in understanding the etiopathogenesis of cervical cancer in women worldwide.

Exploring new potentials and generating hypothesis for management of locally advanced head neck cancer: Analysis of pooled data from two phase II trials

BACKGROUND To study the long term results of two phase II concurrent chemoradiotherapy protocols and conduct pooled data analysis with special emphasis on nodal density. MATERIALS AND METHODS In the period from April 2001 to May 2003, phase II Mitomycin C (MMC) and late chemo-intensification (LCI) protocols were started in the same institute, enrolling 69 and 74 patients respectively. Long term results for these individual trials are reported along with pooled data analysis. RESULTS Median follow-up time for whole group, MMC protocol and LCI protocol was 43.8 months (SD619.8), 55 months (SD 618.5) and 47.5 months (SD 620.9) respectively. LRFS, DFS and OS at five years for whole group was 59.4, 43.5 and 47.1% respectively, for MMC protocol was 59.9, 45.5 and 49.5% respectively and for LCI, protocol was 53.6%, 41.5% and 44.4% respectively. Subgroup analysis revealed that MMC protocol was more effective than LCI protocol in terms of DFS and OS in patients with hypo dense nodes while opposite was true for Isodense nodes. Multivariate analysis revealed nodal density as an independent variable that had an impact on treatment outcome. Risk of death in patients with hypo dense nodes was 2.91 times that of Isodense nodes. CONCLUSIONS Innovative and pragmatic approach is required to address locally advanced head neck cancer. Long term results for MMC and LCI protocols are encouraging. Integrating the basic concepts of these protocols may help develop new protocols, which will facilitate the search for the optimal solution.

Comparitive study of efficacy, tolerability of four field box technique vs. two field anterior posterior technique in locally advanced carcinoma cervix--a prospective analysis.

Purpose: The pelvic failure rate decreases with increase in the radiation dose but the complications increase. The four field pelvic technique has a theoretical advantage of providing a higher tumor dose with less dose to the surrounding normal tissue thus reducing the complications. Result: Eighty-three patients completed treatment, 42 in Arm A and 41 in Arm B. The complete response achieved in the two groups was 85.75% and 87.8% (p = 0.67). Skin reactions were more in Arm B (p < 0.05). Grade II GIT symptoms were more common in both the groups (p = 0.75). Grade I GUT toxicity was the most common toxicity in both the arms (p = 0.38). The most common hematological toxicity in the two arms was of grade II (p = 0.78). Material and method: After satisfying the eligibility criteria histo-pathologically proven locally advanced carcinoma cancer cervix patients were randomized to four (Arm A) or two (Arm B) field techniques. Conclusions: Both two and four field box techniques are equally effective and feasible as stastically insignificant difference in the response rate and acute toxicities was observed in the two arms.

Target polarization/correlation effects on the near-threshold ionization of helium

The effect of target polarization by the projectile along with the electron - electron angular correlation in it on the angular distribution of triple differential cross section for the ionization of helium close to threshold is studied. The target polarization is estimated variationally and the cross section is calculated in the distorted-wave Born approximation with suitable effective charges for the asymptotic description of the final state at 26.6 eV incident energy with equal energy sharing. The target polarization/correlation is found to lead to a substantial change in the cross section. The agreement with experimental data in kinematical arrangement with is very good.

(e, 2e) triple differential cross section for ionization-excitation of helium

Simultaneous ionization and excitation of helium by electron impact is considered in an improved second Born approximation. The wave function of the low energy ejected electron is obtained in the field of residual He+ ion in 2s-state. The calculation has been done for the processe−+He→e−+He+(2s)+e− in the coplanar asymmetric geometry with Hartree-Fock wave function of Byron and Joachain for the helium ground state and the results are compared with the absolute experimental data of Dupreet al [J. Phys.B25, 259 (1992)] at ∼ 5.5 keV incident energy. Our results are found to increase the ratio of the recoil peak to binary peak intensity by about 30% over the first Born results and thus to bring it closer to the experimental data.