The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.

Circular RNA Cdr1as Upregulates SCAI to Suppress Cisplatin Resistance in Ovarian Cancer via miR-1270 Suppression.

As more is learned about the development of cervical cancer, the value of annual Pap smear screening for all women is being questioned. This study was conducted to investigate whether women at higher risk for the development of cervical cancer could be identified by testing for the presence of human papillomavirus (HPV) in the cervical smear. These women could be followed annually, and the interval between screening Pap smears for women at lower risk could be increased. Study participants were women enrolled in the Kaiser Permanente healthcare plan in Portland, Oregon, who underwent annual Pap smear screening between April 1989, and November 1990. More than 20,000 women (20,810 of 23,702) had satisfactory cervical smears with sufficient samples for HPV testing, which was conducted using a polymerase chain reaction-based method with MYO9/11 primers. Most women (83.6%) had at least one follow-up smear during the study period; however, women with atypical squamous cells (ASC) or worse had more smears than women with normal results (mean, 4.4 vs. 3.3). Follow-up was conducted more or less annually for a total period of 122 months. HPV results were not used in deciding patient management. Ninety-six percent of the 20,810 baseline Pap smears were diagnosed as negative (N = 20,156). Thirteen percent of these patients tested positive for HPV. The baseline smears of 654 of the 20,810 women (3.1%) were classified as ASC or worse. Of these 654 smears, 417 (63.8%) were positive for HPV. One hundred seventy-eight women had a cytologic diagnosis of a low-grade squamous intraepithelial lesion or worse; of these, 143 (80.3%) tested positive for HPV. During the 10 years of follow-up, 171 patients developed cervical intraepithelial neoplasia (CIN) 3 or cervical cancer. The baseline smear was normal in 112 of these women and ASC or worse in 59 (34.5%). Only half (49.2%) of the 58 patients diagnosed within the first 45 months of follow-up had an abnormal baseline smear. During this first 45 months, 7.85% of the women whose initial Pap test was at least ASC were diagnosed with CIN 3 or cancer. The cumulative incidence at 10 years of follow-up was 10.2%. Sixty of the 171 women with CIN 3 or cervical cancer had a negative baseline HPV test. Of the 118 women who were diagnosed during the first 45 months of follow-up, 89 (79.4%) were HPV positive initially. The cumulative incidence of CIN 3 or cancer among the group with a positive baseline HPV test was 6.92% over 10 years but only 1.73% at 45 months. The risk of developing CIN 3 or cancer remained elevated throughout the study in those women with a positive baseline HPV test. The predictive ability of the baseline Pap smear diminished as the follow-up interval increased. Fifteen percent of the patients (N = 3216) had a positive Pap smear, a positive HPV test, or both at the initial examination. One hundred twenty-three (71.9%) were among the 171 women who developed CIN 3 or cancer. Eighty-six percent (102 of 123) of the patients who were diagnosed within the first 45 months were positive with at least one of the screening studies. The cumulative incidence over 45 months for women who had positive HPV testing and/or abnormal Pap smear results was 4.54%. Women with negative results in both screening tests had a cumulative risk of 0.16% for the same period. At 10 years the cumulative risk incidence for these two groups was 6.83% and 0.79%, respectively, yielding a negative predictive value of 99.1% for combined testing.

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Baseline Cytology, Human Papillomavirus Testing, and Risk for Cervical Neoplasia: A 10-Year Cohort Analysis

The aim of this study was to explore the roles of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) on cisplatin resistance in ovarian cancer and the underlying mechanisms. We investigated the expression of lncRNAs in 3 paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of UCA1 in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then we examined the effects of UCA1 on cisplatin resistance in vitro and in vivo. In this study, UCA1 was observed to be upregulated in cisplatin-resistant patient tissues and cell lines. Knockdown of UCA1 inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed UCA1 promoted the miR-143 expression and miR-143 could bind to the predicted binding site of UCA1. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. Importantly, we demonstrated that UCA1 was upregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that UCA1 modulates cisplatin resistance through the miR-143/FOSL2 pathway in ovarian cancer.

lncRNA UCA1 Mediates Resistance to Cisplatin by Regulating the miR-143/FOSL2-Signaling Pathway in Ovarian Cancer.

Recent developments in genetics and molecular biology have classified breast cancer into subtypes based on tumor markers of estrogen (ER), progesterone (PR) and human epidermal growth Factor-2 receptors (Her-2), with the basal-like (ER−, PR−, Her2−) subtype commonly referred to as “triple negative” breast cancer (TNBC) being the most aggressive. Prior studies have provided evidence that higher socio-economic status (SES) is associated with increased breast cancer risk, likely due to hormone related risk factors such as parity and hormonal contraceptive use. However, it is unclear if the relationship between SES and overall breast cancer incidence exists within each subtype, and if this association varies by race/ethnicity. Analysis was based on data obtained from the SEER database linked to 2008–2012 American Community Survey data, and restricted to women diagnosed with breast cancer in 2010. The NCI SES census tract SES index based on measures of income, poverty, unemployment, occupational class, education and house value, was examined and categorized into quintiles. Age-adjusted incidence rate ratios were calculated comparing the lowest to the highest SES groups by subtype, separately for each race/ethnic group. We identified 47,586 women with breast cancer diagnosed in 2010. The majority was diagnosed with Her2−/HR+ tumors (73 %), while 12 % had triple negative tumors (TNBC). There was a significant trend of higher incidence with increasing SES for Her2−/HR+ (IRR Highest vs. Lowest SES: 1.32, 95 % CI 1.27–1.39; p value trend: 0.01) and Her2+/HR+ tumors (IRR Highest vs. Lowest SES: 1.46, 95 % CI 1.27–1.68; p value trend: 0.01) among White cases. There was no association between SES and incidence of HR− subtypes (Her2+/HR− or TNBC). Similar associations were observed among Black, Hispanic and Asian or Pacific Islander cases. The positive association between SES and breast cancer incidence is primarily driven by hormone receptor positive tumors. To the extent that neighborhood SES is a proxy for individual SES, future studies are still needed to identify etiologic risk factors for other breast cancer subtypes.

/pdf/socioeconomic-status-and-incidence-of-breast-cancer-by-220ls5e1gm.pdf

Socioeconomic status and incidence of breast cancer by hormone receptor subtype

Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and suppressed in vitro angiogenesis in a concentration-dependent manner. GA downregulated AKT phosphorylation as well as HIF-1α expression but promoted PTEN expression. The luciferase assay results suggest that the PTEN/AKT/HIF-1α pathway accounts for the inhibitory effect of GA on VEGF expression and in vitro angiogenesis. These findings provide strong support for the high potential of GA in the prevention and therapy of ovarian cancer.

/pdf/gallic-acid-a-phenolic-compound-exerts-anti-angiogenic-welp1zwo88.pdf

Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells

Epithelial ovarian cancer is the fifth most common cancer in women. It is usually diagnosed at an advanced stage and is the leading cause of death from gynecologic cancers in women. The overall survival rate at five years is 50% and its treatment is still poor. We need new treatments for patients with recurrent ovarian cancer who are incurable with current management. We review the effectiveness of new biological agents and morbidity and mortality of cytoreductive surgery. Since the hyperthermic increases the effectiveness of chemotherapy and the chance of survival, hyperthermic intraperitoneal chemotherapy has been proven to be a promising option, however it still requires further study to be the standard treatment.

/pdf/management-of-recurrent-epithelial-ovarian-cancer-39hpdpef2x.pdf

Management of recurrent epithelial ovarian cancer.

Primary cervical cancer screening Abstract Cervicouterine cancer screening with citology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher

/pdf/deteccion-primaria-del-cancer-cervicouterino-1tb74gqma8.pdf

Detección primaria del cáncer cervicouterino

Breast Cancer is a heterogeneous disease, progressive, currently, are classified according to in pattern of gene expression luminal A, luminal B, basal and HER-2neu + and Triple-negative, 75% to 80% have receptors positive hormonal and 15% to 20% are positive for hER-2neu and 10% to 20% are triple negative, with hormone receptor negative and HER2-neu and their diagnostic is made by exclusion, the Metabolic Syndrome is related to a higher incidence of these cancers where the insulin-leptin axisadiponectin are implicated in carcinogenesis.

/pdf/metabolic-syndrome-in-breast-cancer-4tzjp4u6lr.pdf

Metabolic syndrome in breast cancer

This is a retrospective, descriptive study of women with histologic diagnostic of malignant tumor or germinal cells done in 15 patients from 1993-1998 in the Oncologic Gynecologic Service of the Hospital Juárez de Mexico: eight were dysgerminomas (53.3%), three (20%) endodermal sinus tumors and four (26.6%) inmature teratomas. The study involves 15 patents (12-32 years average 22 years. Nine (60%) were in early stage (II of FIGO) six (40% were in early stage (III FIGO). Tumoral size 12-20 cm average 16 cm. Main symptoms were: abdominal pain, abdominal distention, and abdominal pelvic tumor. α-fetoprotein was used as tumoral marker for follow-up. Surgical treatment was palliative in 12 (80%), radical in three (20%); 15 patients (100%) received adjuvant chemotherapy on Cisplatin and only 1 patient (6.6%) received radiotherapy; the end of this study 14 women are still alive without evidence of tumoral activity and 1 (6.6%) with endodermal sinus tumor died. Germinal cells tumors have a good prognosis when they have favorable response to chemotherapy which is good in women in fertile age mainly when tumor is in early stage.

/pdf/tumor-de-celulas-germinales-de-ovario-presentacion-clinica-y-2ykuuvym4k.pdf

Tumor de células germinales de ovario. Presentación clínica y su tratamiento en 15 casos

Cancer screening programs have been successful in reducing the incidence and mortality due to cervical cancer. For more than a decade, the human papillomavirus test has been recommended as part of these programs, however, Pap tests is not currently recommended for women 65 years of age who participated adequately in screening programs, continuing with these screening programs is not needed. Screening programs will be different in special populations at greatest risk where tests are frequently needed or use of alternative methods.

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Víctor Manuel Vargas-Aguilar

Papers

Management of recurrent epithelial ovarian cancer.

Detección primaria del cáncer cervicouterino

Metabolic syndrome in breast cancer

Tumor de células germinales de ovario. Presentación clínica y su tratamiento en 15 casos

Nuevas directrices en la detección oportuna del cáncer cervicouterino