Kirti Srivastava

Background Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear protein involved in the DNA repair pathway. The aim of this investigation was to assess the association of PARP1 polymorphisms with PARP1 expression and cervical cancer susceptibility in North Indian women. Methods and results This was a case-control study comprised of 141 cervical cancer patients and 147 healthy controls. The PCR-RFLP was performed for genotypic distribution. The qRT-PCR and immunohistochemistry were performed to check PARP1 gene and protein expression, respectively. The homozygous CC (rs1136410) in the genotype model was found to be significant (P = 0.002); however, the interval of the odds ratio was wide, thereby leading to an unstable association. In the additive model, the association was significant, but the odds ratio was less than 2, whereas the dominant model was significantly correlated with cervical cancer with a high odds ratio (P = 0.002; OR = 2.34). The heterozygous CT (rs7527192) was associated with cervical cancer in the genotype model (OR = 2.37). The dominant and additive models were also significantly associated with cervical cancer, conferring a 2.71 and 2.36 times higher risk. The gene and protein expression of PARP1 was higher in cervical cancer patients. There was an association of CC genotype (rs1136410) and PARP1 expression as per the Kruskal-Wallis test, but no such association was found in rs7527192 polymorphism. Conclusions The findings suggest that rs7527192 may be associated with cervical cancer susceptibility in this cohort, and rs1136410 influences the PARP1 expression; however, independent validation in larger, multiethnic, and functionally characterized cohorts with HPV adjustment is required.

Purpose The MGMT (O⁶-methylguanine-DNA methyltransferase) gene plays a crucial role in repairing DNA damage caused by alkylating agents, including those used in chemotherapy. Genetic and epigenetic alterations can influence the regulation of MGMT gene, which in turn may impact the response to concomitant chemoradiotherapy (CRT) in cervical cancer. The present study was undertaken to evaluate the correlation of such variations in MGMT gene with the treatment outcome of concomitant chemoradiotherapy (CRT) in cervical cancer. Methods A total of 460 study subjects (240 controls and 220 patients) were subjected to genotypic analysis of MGMT gene variants rs12917(T/C) and rs2308327(A/G) by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Out of them, 48 each of controls and patients were analyzed for promoter methylation and expression by methylation-specific PCR and real-time PCR, respectively. Patients (n = 48) were followed up and evaluated for treatment (CRT) outcome. Statistical analyses were done using GraphPad (9.0) and SPSS version 18.0. Results Individuals with GG genotype, G allele of rs2308327, and haplotype ‘TA’ of both variants showed a significant increase in the development of cervical cancer (P ≤ 0.05). In epigenetic regulation, there was a significant hypermethylation of MGMT gene and down-regulation of their expression in patients compared to control individuals. In treatment outcome of CRT, GG genotype of rs2308327(A/G) gene variant showed better response and GG + AG was significantly associated with vital status (alive). Unmethylated MGMT gene showed better median overall survival up to 25 months significant in comparison to methylated MGMT promoter. Conclusion Gene variant rs2308327(A/G) and promoter hypermethylation regulated MGMT gene can be a good prognostic for treatment response in cervical cancer patients.

Eccrine spiroadenoma arises from adnexal tissue of skin and is usually benign, slow growing and may remain static for decades [1]. Dabska et al. first defined the term malignant eccrine spiroadenoma (MES) in 1972, since then around 100 cases of MES have been found (Alejandra de Andrés Gómez. Malignant eccrine breast spiroadenoma. A case report and literature review [2]). Its very rare kind of tumor can arise either from transformation in benign lesion or can arise de novo. Here we are reporting a case of malignant spiroadenoma arising from transformation of benign lesion, its pathology and treatment.

Background: BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. Methods: Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [− 20%; 20%]. Results: In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(− 8.05)-19.89%], thus, they lied within predetermined equivalence margins [− 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC_0–504, С_mах, Т_max, T_1/2. Analysis of C_trough did not reveal any significant inter-group differences as well. Conclusions: Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug. Trial registration: The trial was registered with ClinicalTrials.gov (Study Number NCT01764022). The date of registration was January 9, 2013.