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1.
Cell Stress Chaperones ; 22(6): 811-822, 2017 11.
Article in English | MEDLINE | ID: mdl-28608263

ABSTRACT

Neoadjuvant (or induction) chemotherapy can be used for cervical cancer patients with locally advanced disease; this treatment is followed by radical surgery and/or radiation therapy. Cisplatin is considered to be the most active platinum agent drug for this cancer, with a response rate of 20%. In order to understand how the cisplatin treatment affects the stress response, in this work, we performed an exploratory study to analyze a number of stress proteins before and after cisplatin neoadjuvant chemotherapy. The study involved 14 patients; the pre- and post-chemotherapy paired biopsies were examined by hematoxylin and eosin staining and by immunohistochemistry. The proteins evaluated were p53, P16/INK4A, MSH2, nuclear protein transcriptional regulator 1 (NUPR1), and HSPB1 (total: HSPB1/t and phosphorylated: HSPB1/p). These proteins were selected because there is previous evidence of their relationship with drug resistance. The formation of platinum-DNA adducts was also studied. There was a great variation in the expression levels of the mentioned proteins in the pre-chemotherapy biopsies. After chemotherapy, p53 was not significantly affected by cisplatin, as well as P16/INK4A and MSH2 while nuclear NUPR1 content tended to decrease (p = 0.056). Cytoplasmic HSPB1/t expression levels decreased significantly following cisplatin therapy while nuclear HSPB1/t and HSPB1/p tended to increase. Since the most significant changes following chemotherapy appeared in the HSPB1 expression levels, the changes were confirmed by Western blot. The platinum-DNA adducts were observed in HeLa cell in apoptosis; however, in the tumor samples, the platinum-DNA adducts were observed in morphologically healthy tumor cells; these cells displayed nuclear HSPB1/p. Further mechanistic studies should be performed to reveal how HSPB1/p is related with drug resistance. When the correlations of the markers with the response to neoadjuvant chemotherapy were examined, only high pre-chemotherapy levels of cytoplasmic HSPB1/p correlated with a poor clinical and pathological response to neoadjuvant cisplatin chemotherapy (p = 0.056) suggesting that this marker could be useful opening its study in a larger number of cases.


Subject(s)
Biomarkers, Tumor/genetics , Cisplatin/adverse effects , HSP27 Heat-Shock Proteins/genetics , Uterine Cervical Neoplasms/drug therapy , Adult , Aged , Cisplatin/administration & dosage , DNA Adducts/genetics , DNA Damage/drug effects , DNA Damage/genetics , DNA Repair/drug effects , DNA Repair/genetics , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , HeLa Cells , Heat-Shock Proteins , Humans , Middle Aged , Molecular Chaperones , Neoadjuvant Therapy/adverse effects , Tumor Suppressor Protein p53/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology
2.
Oncol Rep ; 33(5): 2521-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25738832

ABSTRACT

Cervical cancer is the second most common cancer among women in Argentina and the mortality rate is not declining despite opportunistic screening. Free-of-charge human papillomavirus (HPV) vaccination of 11-year-old girls was introduced in 2011. Parental acceptance of HPV vaccination is considered to be of great importance for HPV vaccine uptake. However, little is known regarding this factor in Argentina. The aim of the present study was to explore maternal HPV vaccination acceptance, willingness to pay for HPV vaccination and correlates of this willingness, awareness of HPV and HPV-associated disease and behaviors and attitudes associated with HPV vaccination acceptance. A total of 180 mothers of girls aged 9-15 years comprised this quantitative, cross-sectional, survey-based study, conducted at two hospitals in the Mendoza Province. Correlates of willingness to pay for HPV vaccination were obtained using multivariable logistic regression models. Maternal HPV vaccination acceptance was 90%, and 60% of mothers were willing to pay for HPV vaccination. Mothers who were gainfully employed and had a higher disposable household income were significantly more willing to pay for HPV vaccination [odds ratio (OR)=2.54, 95% confidence interval (CI) 1.01-6.38; OR=3.28, 95% CI 1.36-7.94, respectively], as were mothers who were aware of cervical cancer prior to the study (OR=3.22, 95% CI 1.02-10.14). Only one in 10 mothers were informed that HPV vaccination does not offer complete protection against cervical cancer. In conclusion, the present study showed high maternal HPV vaccination acceptance, although acceptance decreased when vaccination was not free-of-charge. Continuous public education campaigns are needed to improve knowledge of HPV, HPV vaccines and HPV-associated disease.


Subject(s)
Papillomaviridae/immunology , Papillomavirus Infections/immunology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/immunology , Uterine Cervical Neoplasms/immunology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Immunization/methods , Middle Aged , Nuclear Family , Papillomavirus Infections/epidemiology , Prevalence , Surveys and Questionnaires , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Vaccination/methods , Young Adult
3.
Int J Oncol ; 43(4): 1310-8, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23877491

ABSTRACT

Cervical cancer is the second most common cancer among women in Argentina and the mortality has remained unchanged for the last 30 years. The 2011 national implementation of human papillomavirus (HPV) vaccination will be a key component of future cervical cancer prevention. Vaccination of young adult women is not included in the program, although these women could also benefit from the vaccine, especially in underserved areas with a high prevalence of HPV. However, research on acceptance of HPV vaccination within this group is scarce. The aim of this study was to investigate acceptance of HPV vaccination, the correlation between acceptance and cost, as well as other factors and perceptions of HPV vaccination among young adult women in Argentina. In total, 174 young women aged 18-30 years were included in this quantitative cross-sectional hospital-based study in a low resource area of the Mendoza Province, conducted through structured questionnaire-based interviews. Multinomial logistic regression models were used to investigate correlates of acceptance. Acceptance of HPV vaccination was high if it was free (95%) and even if it was not (75%). A significant positive association was found between acceptance and belief in vaccine safety (p=0.01) and between acceptance and not being a welfare recipient (p=0.00). Nearly half the participants incorrectly believed that they would be fully protected against cervical cancer after vaccination. Our findings suggest that acceptance of HPV vaccination is high among young women in a high-risk, relatively underserved area, even if vaccination is not free. Extensive misconceptions about the vaccine, however, highlight the need for further education about HPV vaccination.


Subject(s)
Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Papillomavirus Vaccines/administration & dosage , Prevalence , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Logistic Models , Papillomavirus Infections/prevention & control , Patient Acceptance of Health Care , Surveys and Questionnaires , Uterine Cervical Neoplasms , Vaccination , Young Adult
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