In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to "likely pathogenic". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Quality of information regarding abnormal uterine bleeding available online.

INTRODUCTION: The Internet and electronic devices with Internet access allow for a greater fluidity of information and speed of communication, especially in the field of health. Abnormal uterine bleeding (AUB) affects approximately 3-30% of women and can negatively impact their health and quality of life. Information regarding AUB that is available on the Internet may not be clear or accurate, rendering it difficult to understand and likely to result in delayed medical evaluation, which subsequently leads to worsening of the AUB. OBJECTIVE: To evaluate the quality of the information regarding AUB currently available on the Internet, including information regarding treatments. METHODS: The Google Trends website was searched for the most widely used English terms related to AUB. The identified descriptors were searched individually on the Google, Yahoo!, and Bing search engines. The first 10 results of each search were pre-selected and evaluated for inclusion in this study. Selected websites were categorically divided into two groups (news/magazine and academic) and individually analyzed by three experts using the DISCERN quality criteria (reliability, general quality, and quality of information) and the presence or absence of the Health on the Net Foundation Code of Conduct (HONcode®) seal. RESULTS: Of the 168 websites included in this study, 60.1% were allocated to the news/magazine group and 39.9% were allocated to the academic group. Over half of the websites (54.2%) did not have the HONcode® quality seal. Websites in the academic group were more likely to include accurate information regarding AUB with greater reliability than websites in the news/magazine group. There were no statistical differences regarding the general quality of the websites. Most websites were rated as either moderate quality (70.8%) or low quality (28.6%). The HONcode® criterion was found to be a confounding factor of the analyses, as the grouping and quality results of websites without this seal were significantly associated. In addition, websites in the news/magazines group were 6.7 times more likely to provide low quality information than websites in the academic group (odds ratio: 6.7; 95% confidence interval: 2.1-21.4). CONCLUSION: The information regarding AUB that is available on the Internet is of low to moderate quality. Academic websites present more reliable information of greater quality. The presence of the HONcode® seal is considered important to determine the quality of the content of a website, especially for news/magazine websites, and may help Internet users identify websites that contain more reliable information. Algorithms and applications that categorize the quality of information and the reliability of health content may be useful tools that can help patients clarify their symptoms for several conditions including AUB.

Evaluating the quality of HPV vaccine-related information on the Portuguese Internet.

Human papillomavirus (HPV) is considered the second largest human carcinogen after tobacco and is responsible for 5% of all cancers, 10% of cancers in women, and 15% of all cancers in developing countries. Among these, cervical cancer is the most prevalent. An HPV vaccine has recently been developed to provide primary protection against the viral infection. In 2014, Brazil's National Immunization Program (Programa Nacional de Imunizações, PNI) started making a quadrivalent vaccine available to the public. However, after 2014, the vaccine coverage dropped and did not reach the PNI's targets. Among other factors, this low uptake was due to the quality of information on the Internet. Using Google Trends, the main search terms used to search for vaccine-related information on the Internet were identified. The content of the identified websites was analyzed using the DISCERN instrument and their reach was determined using their page authority score. Most of the texts analyzed were not of high quality. The data that most commonly reach the lay public are from sites that lack scientific rigor. We found a weak correlation between the DISCERN and page authority scores. Based on our analysis, we inferred that the information that reaches the user is not always the most accurate and can lead to harmful decisions on vaccination. The content that reaches the user most easily is not always of sound quality. New analyses are important, especially on the impact of social networks that present even fewer criteria in publications and are more easily accessible.

Breaking Bad News in Obstetrics and Gynecology: We Must Talk About It.

Breaking bad news is common in obstetrics and gynecology (ob-gyn). However, it is difficult, and few doctors receive training on how to deal with this situation. This narrative review aims to gather, analyze, and synthesize part of the knowledge on the area, focused on Ob-Gyn. Among the 16 selected articles, two are randomized controlled intervention studies, and most studies refer to obstetrics. The results found by us pointed out that simulation, feedback/debriefing, lectures, and protocols could improve doctors' performance in communicating bad news. For patients, the context and how the information is transmitted seem to impact more than the content of the news. Ob-Gyn doctors could benefit from specific protocols and education, given the specialty's particularities. There is a lack of evidence about the most effective way to conduct such training. Finding validated ways to quantify and classify studies' results in the area, which would allow for the objective analysis of outcomes, is one of the biggest challenges concerning this topic.

Dar más notícias é comum em obstetrícia e ginecologia. Porém, é difícil e poucos médicos recebem treinamento sobre como lidar com essa situação. Esta revisão narrativa tem como objetivo reunir, analisar e sintetizar parte do conhecimento sobre a área, com foco na obstetrícia. Dentre os 16 artigos selecionados, dois são estudos de intervenção randomizados e controlados, e a maioria dos estudos refere-se à obstetrícia. Os resultados encontrados ressaltaram que simulação, feedback/entrevistas, palestras e protocolos podem melhorar o desempenho dos médicos na comunicação de más notícias. Para os pacientes, o contexto e como as informações são transmitidas parecem ter maior impacto do que o conteúdo das notícias. Os obstetras e ginecologistas poderiam se beneficiar de cursos e protocolos específicos, dadas as particularidades da especialidade. Faltam evidências sobre a forma mais eficaz de realizar esse treinamento. Encontrar formas validadas de quantificar e classificar os resultados dos estudos na área, permitindo uma análise objetiva dos resultados, é um dos maiores desafios neste tema.

Identification of best housekeeping genes for the normalization of RT-qPCR in human cell lines.

The identification of the best reference gene is a critical step to evaluate the relative change in mRNA expression of a target gene by RT-qPCR. In this work, we evaluated nineteen genes of different functional classes using Real Time Human Reference Gene Panel (Roche Applied Sciences), to identify the internal housekeeping genes (HKGs) most suitable for gene expression normalization data in human cell lines. Normal cell lines CCD-19LU (lung fibroblast), HEK-293 (epithelial cell of embryonic kidney), WI-26 VA4 (lung fibroblast), and human cancer cells, BT-549 (breast cancer), Hs 578T (breast cancer), MACL-1 (breast cancer), HeLa (cervical carcinoma), U-87 MG (glioblastoma/astrocytoma), RKO-AS45-1 (colorectal carcinoma), and TOV-21G (ovarian adenocarcinoma) were cultivated according to manufacturer's protocol. Twelve candidate reference genes were commonly expressed in five cell lines (CCD-19Lu, HEK-293, RKO-AS45-1, TOV-21G, and U-87 MG). To verify the expression stability, we used the RefFinder web tool, which integrates data from the computational programs Normfinder, BestKeeper, geNorm, and the comparative Delta-Ct method. The ACTB was the most stable reference gene to the CCD-19Lu and HEK-293 cells. The best combination of HKGs for the RKO-AS45-1 and TOV-21G cell lines were B2M/GAPDH and PBGD/B2M, respectively. For the U-87 MG cells, GAPDH and IPO8 were the most suitable HKGs. Thus, our findings showed that it is crucial to use the right HKGs to precise normalize gene expression levels in cancer studies, once a suitable HKG for one cell type cannot be to the other.

Evaluation of the quality of information available on the internet on vaginal meshes.

OBJECTIVE: The objective of this study was to evaluate the quality of information on the internet about vaginal meshes available to the general population. STUDY DESIGN: The terms "vaginal sling," "sling vagina," "vaginal mesh," "mesh vagina," "vaginal tape," and "tape vagina" were used every time on three major search engines, and the first 10 websites retrieved by each search engine were selected and evaluated using the DISCERN questionnaire. The websites were divided into four categories based on the type of agency that created the website. These included websites created by private health institutions, non-private health institutions, and non-health institutions and websites for encyclopedias, libraries, articles and scientific papers. They were compared in terms of the reliability, information quality, and total DISCERN score. RESULTS: The survey yielded 98 different websites; after applying the exclusion criteria, 62 sites were selected. Websites for articles, magazines, libraries, and encyclopedias and those by non-private health services had significantly high scores for the reliability dimension of the DISCERN tool as compared to the other two website categories (p < 0.05). Regarding the quality of information, websites for non-specific health services and those for articles, magazines, libraries, and encyclopedias presented significantly lower scores as compared to the other two website categories. Websites for non-specific health services had significantly lower average total DISCERN points when compared to other website categories. The websites for private health services and those for articles, magazines, libraries, and encyclopedias had significantly lower DISCERN scores than the websites for non-private health services did. CONCLUSION: Our findings showed that the quality of information regarding vaginal meshes on the first 10 websites on major search engines was moderate.

HSPA1A, HSPA1L and TRAP1 heat shock genes may be associated with prognosis in ovarian epithelial cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with the presence of chemoresistance contributing to the poor prognosis. Heat Shock Proteins (HSPs) genes are activated in response to pathophysiological stress and serve a role in a variety of stages in carcinogenesis, acting primarily as anti-apoptotic agents and in chemotherapy resistance in a variety of tumor types. The current study evaluated the HSP gene expression profile in women with ovarian cancer (OC) and their correlation with clinical and pathological aspects of patients with OC. A total of 51 patients included in the current study were divided into four groups: Primary Epithelial Ovarian Cancer (EOC; n=14), metastatic EOC (n=11), ovarian serous cystadenoma (n=7) and no evidence of ovarian malignancy or control groups (n=19). RNA extraction and reverse transcription-quantitative (RT-q) PCR was then performed on the samples obtained. RT-qPCR was performed to compare TNF receptor associated protein 1 (TRAP1), heat shock protein family (HSP) HSPB1, HSPD1, HSPA1A and HSPA1L expression in primary and metastatic EOCs. TRAP1, HSPB1, HSPD1, HSPA1A and HSPA1L gene expression did not differ among groups. HSPA1A, HSPA1L and TRAP1 were revealed to be underexpressed in the primary and metastatic EOC groups, with HSPA1L exhibiting the lowest expression. TRAP1 expression was higher in tumors at stages I/II compared with those at stages III/IV. No correlation was exhibited between HSP expression and age, menarche, menopause, parity, period after menopause initiation, cytoreduction, CA-125 or overall and disease-free survival. HSPA1A was negatively correlated with the risk of mortality from OC. The results indicated that the downregulation of HSPA1A, HSPA1L and TRAP1 could be associated with the clinical prognostic features of women with EOC.

Extremely brief mindfulness interventions for women undergoing breast biopsies: a randomized controlled trial.

PURPOSE: Mindfulness-based programs can reduce stress and help practitioners to have positive attitudes in their daily lives. This randomized controlled trial evaluated the impact of brief Mindfulness interventions on quantitative and qualitative stress parameters in patients undergoing imaging-guided breast biopsies. METHODS: Eighty-two women undergoing percutaneous imaging-guided breast biopsy were randomized into two groups: MBI group or standard care group. One week before the biopsy procedure, on the waiting room and during the biopsy procedure, the MBI group was exposed to mindfulness techniques and the standard care group received supportive dialogue from the biopsy team. Participants completed questionnaires measuring depression, anxiety and stress, demographics, and medical history, besides evaluating their pain experience through a visual analogue scale for pain and had their systolic and diastolic blood pressure, initial and final temperate, heart rate, oxygen saturation, and salivary cortisol measured. RESULTS: Participation in the mindfulness intervention group was associated with reduced levels of perceived stress, blood pressure, heart rate, and oxygen saturation compared to participation in the standard care group (P values < 0.05). No difference was observed regarding salivary cortisol levels, peripheral temperature, and pain perception between the two studied groups. CONCLUSION: Results indicate that an extremely brief mindfulness intervention is a feasible intervention, suggesting that Mindfulness-based programs may be beneficial to reduce discomfort in acutely stressful settings.

Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44+/high/CD24-/low/CD117-/low/CD146-/low/ALDH1low profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44+/high/CD24+/high/ CD117-/low/CD146-/low/ALDH1low profile in both culture models, although the tumorsphere model showed a significant increase in CD24+/high subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24+/high cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

Barriers and myths that limit the use of intrauterine contraception in nulliparous women: a survey of Brazilian gynaecologists.

OBJECTIVE: To understand the extent to which barriers and misperceptions about intrauterine contraception (IUC) remain among Brazilian gynaecologists, particularly for nulliparous women. METHODS: An online survey was developed to assess Brazilian gynaecologists' knowledge and attitudes towards IUC. Data collected included demographic and professional data, main barriers when considering IUC for women in general and/or nulliparous women, attitudes towards inclusion of IUC in contraceptive counselling, and opinions on what could increase IUC prescription for nulliparous women. A question regarding knowledge about WHO medical eligibility criteria (WHO MEC) was also included in the survey. RESULTS: 101 gynaecologists completed the survey. The insertion rate in nulliparous women was 79.2%. Brazilian gynaecologists were more likely to consider IUC in counselling or provide it on request for parous than for nulliparous women (p<0.05) and perceived more complications in nulliparous women. 74.2% of gynaecologists recognised a higher risk of pelvic inflammatory disease (PID)/infertility associated with IUC use in nulliparous women than in parous women. Difficult and painful insertion were also relevant for 83.2% and 77.3% of the gynaecologists, respectively. Respondents showed a high level of awareness of the WHO MEC classification. CONCLUSIONS: The three most commonly reported barriers to considering IUC as a contraceptive option for nulliparous woman were concerns about PID and difficult or painful insertion. The challenge is to ensure that gynaecologists understand the evidence and do not disregard IUC as a potential option for nulliparous women.

The rate of recurrent BRCA1, BRCA2, and TP53 mutations in the general population, and unselected ovarian cancer cases, in Belo Horizonte, Brazil.

In Brazil, several recurring mutations in BRCA1 and BRCA2 and a TP53 mutation (R337H) have been reported in high risk breast cancer cases. We hypothesized that these recurring mutations may also be detected in the general population and ovarian cancer cases in the state of Minas Gerais. To test this notion, participants were recruited from the outpatient and the Gynecological clinic in the UFMG Medical Center in Belo Horizonte, Minas Gerais, Brazil. BRCA1 (c.68_69delAG, c.5266dupC, c.181T>G, c.4034delA, c.5123C>A), BRCA2 (c.5946delT, c.8537_8538delAG, 4936_4939delGAAA), the c.156_157insAlu* BRCA2 and the c.1010G>A *TP53 mutation were genotyped using validated techniques. Overall, 513 cancer free participants (273 men) (mean age 47.7 ± 15.1 years) and 103 ovarian cancer cases (mean age at diagnosis 58.7 ± 9.6 years) were studied. None of the participants were found to carry any of the genotyped mutations. We conclude that the recurring mutations in BRCA1, BRCA2 and TP53 cannot be detected in the general population or consecutive ovarian cancer cases in this geographical region in Brazil.

Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro.

PURPOSES: To determine the basic expression of ABC transporters in an epithelial ovarian cancer cell line, and to investigate whether low concentrations of acetaminophen and ibuprofen inhibited the growth of this cell line in vitro. METHODS: TOV-21 G cells were exposed to different concentrations of acetaminophen (1.5 to 15 µg/mL) and ibuprofen (2.0 to 20 µg/mL) for 24 to 48 hours. The cellular growth was assessed using a cell viability assay. Cellular morphology was determined by fluorescence microscopy. The gene expression profile of ABC transporters was determined by assessing a panel including 42 genes of the ABC transporter superfamily. RESULTS: We observed a significant decrease in TOV-21 G cell growth after exposure to 15 µg/mL of acetaminophen for 24 (p=0.02) and 48 hours (p=0.01), or to 20 µg/mL of ibuprofen for 48 hours (p=0.04). Assessing the morphology of TOV-21 G cells did not reveal evidence of extensive apoptosis. TOV-21 G cells had a reduced expression of the genes ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 within the ABC transporter superfamily. CONCLUSIONS: This study provides in vitro evidence of inhibitory effects of growth in therapeutic concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally, TOV-21 G cells presented a reduced expression of the ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 transporters.

Single CpG island methylation is not sufficient to maintain the silenced expression of CASPASE-8 apoptosis-related gene among women with epithelial ovarian cancer.

Despite impressive research efforts, the biology of epithelial ovarian cancer (EOC) remains poorly understood and alterations in the expression of CASPASE-8 contribute to a worse tumor prognosis. This study assesses the methylation of the CpG island within the CASPASE-8 promoter and CASPASE-8 gene expression both in cystadenoma tumors and in primary and metastatic EOC. DNA and RNA were obtained from women with normal ovarian tissues (n=18), ovarian serous cystadenoma tumors (n=11) and EOC (n=16) using Trizol(®). The methylation frequency of the CpG island in the CASPASE-8 promoter was assessed using the methylation-specific PCR assay after DNA bisulfite conversion. Quantitative PCR was performed to quantify the relative levels of CASPASE-8 in each sample. The differences between samples with each group were evaluated using the Mann-Whitney U and Kruskal-Wallis tests as indicated. Hemimethylation of the CASPASE-8 promoter was found in 11.8% of the normal ovary samples, 20% of the cystadenoma tumors and 20% of the metastatic EOC, while methylation of the CASPASE-8 promoter was absent in the EOC primary tissues (P=0.047). An increased CASPASE-8 expression level was observed in all tumor groups. Significant differences were observed in the CASPASE-8 expression levels when compared with all ovarian tumor groups (P=0.0278). Promoter DNA methylation did not associate with expression levels of CASPASE-8, suggesting the presence of other mechanisms in relation to gene expression control in EOC; thus providing a better understanding of this complex disease.

Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors.

OBJECTIVE: This study assesses TRAIL-R2 (TNF-related apoptosis-inducing ligand receptor 2) and BCL2 (B cell CLL/lymphoma 2) expression as well as CpG island methylation within the TRAIL-R2 promoter in ovarian serous tumors and primary and metastatic serous EOC (epithelial ovarian cancer). METHODS: RNA and DNA were obtained from women with normal ovarian tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and serous EOC (n = 16) using Trizol®. Quantitative PCR was performed to quantify the relative levels of TRAIL-R2 and BCL2. The methylation frequency of the TRAIL-R3 promoter was assessed using a methylation-specific PCR assay after DNA bisulfite conversion. Differences between the groups were evaluated using the χ (2), Mann-Whitney U or Kruskal-Wallis tests, as indicated. RESULTS: We identified TRAIL-R2 and BCL2 mRNA expressed in all ovarian tumor groups, and there were significant differences between the groups. Both genes had low expression levels in ovarian serous cystadenoma and primary EOC tumors when compared with metastatic EOC. Methylation of the TRAIL-R2 promoter was frequently observed in all groups; however, there were no statistically significant associations. CONCLUSIONS: Primary EOC is associated with lower TRAIL-R2 and BCL2 expression levels, while metastatic EOC is associated with higher expression of these genes. Promoter DNA methylation was not related to this finding, suggesting there are other mechanisms involved in transcriptional control.

N-acetylglucosaminidase, myeloperoxidase and vascular endothelial growth factor serum levels in breast cancer patients.

Inflammatory cells surround breast carcinomas and may act promoting tumor development or stimulating anti-tumor immunity. N-acetylglucosaminidase (NAG) has been employed to detect macrophage accumulation/activation. Myeloperoxidase (MPO) is considered a marker for neutrophils activity/accumulation. Vascular Endothelial Growth Factor (VEGF) is as strong pro-angiogenic cytokine. The aim of this study was to measure the systemic inflammatory response by measuring serum levels of NAG, MPO and VEGF in women diagnosed with breast cancer and associate this response to the peritumoral inflammatory infiltrate and to prognostic factors. Serum samples obtained from women with no evidence of disease (n=31) and with breast cancer (n=68) were analyzed for the activities of NAG, MPO and VEGF by enzymatic assay. Serum levels of NAG and VEGF were higher in healthy volunteers (P<0.0001) and serum levels of MPO were higher in patients with breast cancer (P=0.002). Serum levels of NAG were positively correlated to serum levels of MPO and VEGF (P<0.0001 and P=0.0012, respectively) and MPO and VEGF serum levels had also a positive correlation (P=0.0018). The inflammatory infiltrate was not associated to serum levels of the inflammatory markers, and higher levels of MPO were associated to lymphovascular invasion negativity (P=0.0175).

Assessment of chemokine serum levels in epithelial ovarian cancer patients.

AIMS AND BACKGROUND: The study was undertaken to investigate CCL2/MCP-1, CCL3/ MIP-1α, CCL4/MIP-1ß, CCL5/RANTES and CXCL8/IL-8 women with epithelial ovarian cancer. METHODS AND STUDY DESIGN: Sixteen patients diagnosed with epithelial ovarian cancer and 18 healthy women with no evidence of malign neoplasia (control group) aged from 23 to 89 years (mean ± SEM, 58.7 ± 2.3) were included. The epithelial ovarian cancer patients underwent laparotomy and debulking surgery. Chemokines serum levels were measured by cytometric bead array. Statistical analysis was performed using Mann-Whitney and Kendall's tau. P <0.05 was considered statistically significant for all analyses. RESULTS: The tumor staging (FIGO) was classified into: I in 4 cases (25%), III in 5 cases (31.3%) and stage IV in 7 cases (43.8%). Sera chemokine dosages of CCL2/MCP-1 and CCL4/MIP-1ß were lower in epithelial ovarian cancer patients than in the control group (P = 0.021 and P = 0.030, respectively). No significant difference between groups was observed in the levels of CCL3/MIP-1α, CCL5/RANTES and CXCL8/IL-8. No association between the chemokines analyzed and tumor stage was found. The serum level of CCL4/MIP-1ß was correlated with CA-125. CONCLUSIONS: The study of serum levels of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES and CXCL8/IL-8 chemokines in epithelial ovarian cancer patients identified a down-regulation in CCL2/MCP-1 and CCL4/MIP-1ß, which suggests that the two chemokines may play an important role in the pathophysiology of ovarian cancer.