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1.
Front Genet ; 13: 863956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734436

RESUMO

Background: Ovarian cancer (OC) is gynecologic cancer with the highest mortality rate. It is estimated that 13-17% of ovarian cancers are due to heritable mutations in BRCA1 and BRCA2. The BRCA1 (BRCA1-Del ex9-12) Mexican founder mutation is responsible for 28-35% of the cases with ovarian cancer. The aim was to describe the PFS of OC patients treated with olaparib, emphasizing patients carrying the Mexican founder mutation (BRCA1-Del ex9-12). Methods: In this observational study, of 107 patients with BRCAm, 35 patients were treated with olaparib from November 2016 to May 2021 at the Ovarian Cancer Program (COE) of Mexico; patient information was extracted from electronic medical records. Results: Of 311 patients, 107 (34.4%) were with BRCAm; 71.9% (77/107) were with BRCA1, of which 27.3% (21/77) were with BRCA1-Del ex9-12, and 28.1% (30/107) were with BRCA2 mutations. Only 35 patients received olaparib treatment, and the median follow-up was 12.87 months. The PFS of BRCA1-Del ex9-12 was NR (non-reach); however, 73% of the patients received the treatment at 36 vs. 11.59 months (95% CI; 10.43-12.75) in patients with other BRCAm (p = 0.008). Almost 50% of patients required dose reduction due to toxicity; the most frequent adverse events were hematological in 76.5% and gastrointestinal in 4%. Conclusion: Mexican OC BRCA1-Del ex9-12 patients treated with olaparib had a significant increase in PFS regardless of the line of treatment compared to other mutations in BRCA.

2.
J Ovarian Res ; 13(1): 86, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32718331

RESUMO

BACKGROUND: The current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence. RESULTS: MMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (-) in stroma displayed a significant reduction of survival. CONCLUSIONS: The presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Ovarianas/patologia , Receptores Androgênicos/metabolismo , Adulto , Carcinoma Epitelial do Ovário/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Prognóstico , Estudos Retrospectivos , Células Estromais/metabolismo , Células Estromais/patologia , Análise de Sobrevida
3.
J Ovarian Res ; 12(1): 15, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736825

RESUMO

BACKGROUND: Ovarian cancer is the most lethal of all gynecologic malignancies. The relationship between sexual steroids receptors and ovarian cancer progression has been largely evaluated. The presence of progesterone receptors has been associated with an increase of a disease-free period and overall survival in patients with ovarian carcinoma. In the present study, primary cultures of ovarian carcinoma obtained from 35 patients diagnosed with epithelial ovarian cancer were evaluated for cell survival after treatment with 10- 8 M of 17ß-estradiol, progesterone, testosterone and dihydrotestosterone. RESULTS: The results were analyzed considering histological subtypes: low grade serous, high grade serous, endometrioid and mucinous carcinoma; clear cell carcinoma was not included due to failure in obtaining successful cultures of this subtype. A significant reduction of cell survival was observed after progesterone treatment in endometrioid ovarian carcinoma. Changes were not observed in low grade serous, high grade serous and mucinous carcinoma. The effect of progesterone was related to the presence of progesterone receptor (PR), a 43% reduction in the cell number was observed in PR (+) endometrioid ovarian carcinoma. CONCLUSIONS: This study supports the importance of progesterone and the presence of progesterone receptor in the reduction of ovarian cancer progression in the endometrioid ovarian carcinoma.


Assuntos
Antineoplásicos Hormonais/farmacologia , Carcinoma Endometrioide/patologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Ovarianas/patologia , Progesterona/farmacologia , Adulto , Carcinoma Endometrioide/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Estudos Prospectivos , Receptores de Progesterona/metabolismo , Receptores de Esteroides/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos
4.
Endocr Connect ; 7(9): 1006-1012, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30012649

RESUMO

The significance of the presence of androgen receptor (AR), estrogen receptor alpha (ER) and progesterone receptor (PR) in ovarian cancer patient survival has been a matter of numerous studies. This study was aimed to describe the expression profile of the three sexual steroid receptors in high-grade serous, endometrioid, mucinous and low-grade serous ovarian carcinoma and its association to the proliferation index in patients with primary ovarian carcinoma diagnosis, before any treatment. Eighty-one samples were obtained from the National Institute of Cancerology in Mexico City and were evaluated for the presence of AR, ER, PR and Ki67 by immunohistochemistry. The four subtypes of ovarian carcinoma displays a specific profile of the eight possible combinations of the steroid receptors with significant differences within the profile and the histological subtypes. High-grade serous carcinoma was characterized by a high frequency of both, triple-negative and AR+ ER- PR+ profiles. Endometrioid carcinoma presented a higher frequency of triple-positive profile. The presence of only AR+ profile was not observed in the endometrioid tumors. The relationship of the receptor profile with the proliferation index in the tumor epithelium shows that the expression of only ER is associated to a reduced proliferation index in endometrioid carcinoma. Steroid hormone receptor expression and co-expression could help characterize ovarian carcinoma.

5.
Rev Invest Clin ; 70(3): 112-116, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29943771

RESUMO

Mexico has seen an increase in cancer prevalence in its entire population as well as particular age ranges, predominantly the older segment. The most frequently reported pelvic cancers in Mexico are cervical, endometrial, bladder, prostate, rectum, and anal canal. Approximately 80% of the population diagnosed with pelvic cancers present with locally advanced tumors and require concomitant chemoradiotherapy, sequential chemoradiotherapy, or radiotherapy alone. The toxicity of any of these treatment modalities may be manifested as intestinal injury, a significant problem that can compromise the response to treatment, the patient's nutritional state, quality of life, and survival. In this article, we will approach key aspects in nutrition as well as the epidemiological characteristics and toxicities in patients affected by these pelvic tumors.


Assuntos
Gastroenteropatias/etiologia , Neoplasias Pélvicas/terapia , Qualidade de Vida , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Gastroenteropatias/fisiopatologia , Humanos , México/epidemiologia , Neoplasias Pélvicas/epidemiologia , Neoplasias Pélvicas/patologia , Prevalência , Lesões por Radiação/epidemiologia , Lesões por Radiação/fisiopatologia
6.
J Ovarian Res ; 9(1): 41, 2016 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-27388275

RESUMO

BACKGROUND: Serum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma. This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerología-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate. RESULTS: The abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 ≤ 500 U/mL was 2.28, 95 % CI 1.08-4.84, P = 0.032. CONCLUSIONS: Clinical stage associated with pretreatment absolute values of CA125 should be considered as prognostic factor in EOC patients. Values of CA125 higher than 500 U/mL in high grade serous carcinoma with FIGO stage III resulted in an enhanced survival rate of the patients.


Assuntos
Biomarcadores Tumorais , Antígeno Ca-125/sangue , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
7.
Iran J Pathol ; 11(4): 399-408, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28855932

RESUMO

BACKGROUND: Phyllodes tumor (PT) of the breast in Hispanic patients is more frequently reported with large tumors and with more borderline/malignant subtypes compared with other populations. The objective of this study was to describe characteristics of patients with PT and to identify differences among subtypes in a Mexican population. METHODS: A retrospective study was conducted on patients with PT. Sociodemographic, histopathologic, and treatment characteristics were compared among subtypes, including only surgically treated cases due the complete surgical-specimen study requirement for appropriate WHO classification. RESULTS: During 10 years, 346 PT were diagnosed; only 307 were included (305 patients), with a mean age of 41.7 yr. Self-detected lump took place in 91.8%, usually discovered 6 months previously, with median tumor size of 4.5 cm. Local wide excisions were done in 213 (69.8%) and mastectomies in 92 (30.1%). Immediate breast reconstruction took place in 38% and oncoplastic procedures in 23%. PT were classified as benign in 222 (72.3%) cases, borderline in 50 (16.2%), and malignant in 35 (11.4%), with pathological tumor size of 4.2, 5.4, and 8.7 cm, respectively (P<0.001). Patients with malignant PT were older (48 yr), with more diabetics (14.3%), less breastfeeding (37.1%), more smokers (17.1%), with more postmenopausal cases (42.9%), and older age at menopause (51.5 years) compared with the remaining subtypes (P<0.05). Relapse occurred in 8.2% of patients with follow-up. CONCLUSION: In comparison with other Hispanic publications, these Mexican patients had similar age, with smaller tumors, modestly higher benign PT, fewer malignant PT, and lower documented relapse cases.

8.
J Oncol ; 2014: 307317, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24864143

RESUMO

Introduction. Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach for peritoneal carcinomatosis. However, high rates of complications are associated with CS and HIPEC due to treatment complexity; that is why some patients need stabilization and surveillance for complications in the intensive care unit. Objective. This study analyzed that ICU stay is necessary after HIPEC. Methods. 39 patients with peritoneal carcinomatosis were treated according to strict selection criteria with CS and HIPEC, with closed technique, and the chemotherapy administered were cisplatin 25 mg/m(2)/L and mitomycin C 3.3 mg/m(2)/L for 90-minutes at 40.5°C. Results. 26 (67%) of the 39 patients were transferred to the ICU. Major postoperative complications were seen in 14/26 patients (53%). The mean time on surgical procedures was 7.06 hours (range 5-9 hours). The mean blood loss was 939 ml (range 100-3700 ml). The mean time stay in the ICU was 2.7 days. Conclusion. CS with HIPEC for the treatment of PC results in low mortality and high morbidity. Therefore, ICU stay directly following HIPEC should not be standardized, but should preferably be based on the extent or resections performed and individual patient characteristics and risk factors. Late complications were comparable to those reported after large abdominal surgery without HIPEC.

9.
Gac Med Mex ; 150 Suppl 2: 161-70, 2014 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-25643776

RESUMO

INTRODUCTION: Breast cancer is heterogeneous, with different responses to NC even within similar histology and stages. OBJECTIVE: To evaluate clinical/pathological response to NC according to different tumor subtypes in Mexican breast cancer patients. PATIENTS AND METHODS: Retrospective study of patients with breast cancer stages II-III, and complete immunohistochemistry (IHC), such as hormonal receptors HER2 and Ki67, treated with NC and surgery. Descriptive and comparative analyses between different intrinsic subtypes were performed. RESULTS: A total of 117 patients were included with 48.6 ± 10.6 years of age, stage II (24%), and III (76%). We identified 20 (17.1%) cases of luminal A, 37 (31.6%) luminal B HER2-, 13 (11.1%) luminal B HER2+, 12 (10.3%) HER2+, and 35 (29.9%) triple negative. Clinical complete response (tumor and lymph nodes) in luminal A was 10%, in luminal B HER2- 10.8%, luminal B HER2+ 15.4%, HER2+ 25%, and in triple negative 14.3%. Conservative surgeries were done in 9 (7.7%) patients. There is a weak positive association between Ki67 expression and tumor clinical response. Pathological complete response occurred in 8 (6.83%) cases, being more frequent in luminal B HER2+ patients (23%). CONCLUSIONS: Pathological complete responses were more often in luminal B HER2+ cases.

10.
J Ovarian Res ; 6(1): 85, 2013 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-24279585

RESUMO

BACKGROUND: The importance of surface epithelium and epithelial inclusion cysts in the ovary arises from studies demonstrating that these structures are susceptible to epithelial ovarian cancer development. The expression of estrogen receptor alpha (ER alpha), androgen receptor (AR), in epithelial cells of the ovary from premenopausal and postmenopausal women is interesting because sexual steroid hormones are involved in cell growth and differentiation. METHODS: The presence of ER alpha, AR, and the orphan G protein-coupled receptor 30 (GPR30) was demonstrated by immunofluorescence in ovaries obtained from 79 pre and postmenopausal patients, undergoing histero-salpingo-oophorectomy for proliferative gynecological diseases. The proportion of patients that displayed positive reaction for estrogen and androgen receptors in epithelial cells of the ovary was evaluated according to menopausal status and associated pathology. RESULTS: The proportion of patients that displayed a positive receptor expression in the epithelial cells of the ovarian surface and cortical inclusion cysts shows that ER alpha is present in 20 of 79 patients (0.25), AR in 33 of 79 (0.42) and GPR30 in 38 of 55 (0.69). There are no differences in ER alpha, AR, and GPR30 expression between pre and postmenopausal patients and considering the associated pathology, proportions for ER alpha and GPR30 are similar. The patients with cervical cancer show a higher proportion of AR expression in epithelial cells of the ovary, which is statistically significant (P < 0.01) compared with patients with other proliferative diseases. CONCLUSIONS: The presence of ER alpha, AR, and GPR30 in the surface epithelial ovarian cells and its derivatives are observed with a proportion that is specific for each receptor. The proportion of expression for these receptors in the epithelial cells of the ovary does not change after menopause. The proportion of ovaries with AR positive epithelial cells in patients with cervical squamous carcinoma is higher compared with other gynecological pathologies.

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