There is increasing evidence that host inflammatory responses play an important role in the development and progression of cancers. There are some data that cancer is associated not only with inflammation at the site of the lesion, but also with dysregulations of the host overall systemic immune response. In the case of cervical cancer, inflammation is an important factor associated with the development, progression, and potential metastasis of the disease. What is unclear still in the potential for modifications of host responses to human papillomaviruses (HPV)a known causative agent of CC, that could be induced by cigarette smoking. In particular, it remains to be determined how the inflammation induced by HPV infection could impact on CC incidence/severity. In this prospective study, serum levels of 10 cytokines were evaluated using Multiplex and ELISA assays. The samples were the sera of 43 CC patients and 60 healthy (NILM) controls. All outcomes were evaluated in relation to host HPV and to their smoking status. The results in indicated that serum sTREM-1, TNFa, IFNb, IL-1b, and IL-6 levels were significantly increased in CC (HPVþ) patients compared to healthy NILM controls. A similar trend was observed for IL-10 and IL-2 levels. Within the two groups, differences in cytokine levels between smokers and never smokers were not remarkable. The findings here support the hypothesized role of systemic inflammation in the pathophysiology of CC.
Our study aimed to evaluate the distribution of genotypes and allele frequencies of IL-6 597A/G (rs1800797) and 174G/C (rs1800795) polymorphisms in HPV infected and uninfected healthy women and cervical cancer patients. A PCR based Multiplex HPV genotyping test kit was used for in vitro detection and differentiation of high risk HPV genotypes. Genotyping of two polymorphisms, IL-6 597A/G (rs1800797) and 174G/C (rs1800795), was performed using the KASP genotyping assay kit. Cervical cancer patients were more likely to be HPV positive than control patients. Allele C of IL-6 rs1800795 was associated with a higher risk of cervical cancer by 2.26-fold and genotype CC by 5.37-fold. Genotype CC of IL-6 rs1800795 was more frequent in the HPV positive group compared with the HPV negative group (p = 0.002). Allele G of IL-6 rs1800797 was more frequently found in women with HPV16/HPV18 compared to other HPV types (p = 0.045). Women with AA genotypes of IL-6 rs1800797 were less frequently infected with HPV16/HPV18 compared to other HPV types (p = 0.045). The major finding of the study is the significant association of C allele and CC genotype of IL-6 1800795 gene with cervical cancer in the Lithuanian population. Genotype CC of IL-6 rs1800795 has a significant association with HPV infection as well.
Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.
The aim was to estimate changes in the resistance rates of Pseudomonas aeruginosa (P. aeruginosa) strains isolated from patients treated in intensive care units of the largest university hospital. Materials and Methods. Isolates were identified with the Phoenix ID system (Becton Dickinson, USA). The minimum inhibitory concentration (MIC) of ceftazidime, ciprofloxacin, and amikacin were determined by the E-test and evaluated following the recommendations of the Clinical Laboratory Standards Institute. Results. In 2003, the proportion of P. aeruginosa strains resistant to piperacillin was greatest followed by strains resistant gentamicin and ciprofloxacin. In 2008, the resistance rates markedly changed being the highest to ciprofloxacin. An increase in the resistance rates to ciprofloxacin (+24%, P<0.001) and ceftazidime (+8.3%, P<0.05) was documented. In 2003, there were 66.7% of P. aeruginosa strains sensitive to all antibiotics tested, and this percentage decreased to 47.5% in 2008 (P<0.05). During the study, a significant increase in the median MICs for ciprofloxacin and amikacin was observed (P<0.001); however, no significant change was documented for ceftazidime. Conclusions. P. aeruginosa remains an important nosocomial pathogen with relatively high overall resistance to antimicrobial agents, and the resistance level is increasing.
Introduction/Background Classification of lymph node metastases according to the size into macrometastases > 2 mm (MAC), micrometastases 0.2 -2 mm (MIC) and isolated tumour cells <0.2 mm (ITC) was adopted from breast cancer. In cervical cancer, MAC is well established as one of the main prognostic factors, while the impact of MIC and ITC has been subject of controversy. Given the fact, that the size of nodal metastasis is a continual variable, we sought to identify a potential cut-off value for the minimal size of metastasis that is not associated with a negative prognostic impact. Methodology Data of 967 cervical cancer patients, T1a1 L1-T2b stages, after primary surgical treatment with curative intent, including SLN biopsy followed by pathological ultrastaging, were obtained from the SCANN (Surveillance in Cervical CANcer) study. Iterative testing was performed for all subgroups of nodal metastases with upper size cut-offs ranging from 0.01 to 1.0 mm in 0.01 mm intervals. DFS in each subgroup was compared with the N0 cohort and the rest of the N1 group (> cut-off) using Log rank test. Results When the subgroups were analyzed by the defined cut-off values, we found that disease-free survival was significantly shorter in subgroups with metastases !0.4 mm in diameter compared with the N0 subgroup (hazard ratio 2.311, P=.04; see figure 1a). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). Also, no cut-off could be identified to separate a subcohort of small nodal metastases with significantly better prognosis than the rest of the N1 cohort (see figure 1b).
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