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1.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612653

RESUMO

To understand chemoresistance in the context of cancer stem cells (CSC), a cisplatin resistance model was developed using a high-grade serous ovarian cancer patient-derived, cisplatin-sensitive sample, PDX4. As a molecular subtype-specific stem-like cell line, PDX4 was selected for its representative features, including its histopathological and BRCA2 mutation status, and exposed to cisplatin in vitro. In the cisplatin-resistant cells, transcriptomics were carried out, and cell morphology, protein expression, and functional status were characterized. Additionally, potential signaling pathways involved in cisplatin resistance were explored. Our findings reveal the presence of distinct molecular signatures and phenotypic changes in cisplatin-resistant PDX4 compared to their sensitive counterparts. Surprisingly, we observed that chemoresistance was not inherently linked with increased stemness. In fact, although resistant cells expressed a combination of EMT and stemness markers, functional assays revealed that they were less proliferative, migratory, and clonogenic-features indicative of an underlying complex mechanism for cell survival. Furthermore, DNA damage tolerance and cellular stress management pathways were enriched. This novel, syngeneic model provides a valuable platform for investigating the underlying mechanisms of cisplatin resistance in a clinically relevant context, contributing to the development of targeted therapies tailored to combat resistance in stem-like ovarian cancer.


Assuntos
Neoplasias Ovarianas , Platina , Humanos , Feminino , Platina/farmacologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário
2.
Gynecol Oncol ; 169: 125-130, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36577267

RESUMO

OBJECTIVES: The current study aimed to explore attitudes toward genetic germline testing and intentions to test in Latinas from Southern California. We hypothesized that patients' acculturation and education levels, as well as comfort with health care providers, are positively associated with attitudes and intentions toward genetic testing. METHODS: A survey was offered concurrently to Latinx female patients at a gynecologic oncology practice and to unaffiliated Latinx community members. The survey assessed demographics, structural, psychosocial, and acculturation factors and genetic testing attitudes and intentions via validated scales. RESULTS: Of 148 surveys collected, 66% of responders had low levels of acculturation. 50% of women had government-subsidized insurance; 22% had no schooling in the US. 67% of participants did not carry a diagnosis of cancer. Women with higher acculturation levels were more likely to consider genetic testing (rs = 0.54, p = .001). Higher acculturated women and less acculturated women under 50 were more likely to consider testing if it had been recommended by a female, trusted, or Hispanic/Latinx provider (rs = 0.22, p = .01, rs = 0.27, p = .003 and rs = 0.19, p = .003, respectively) or if there was a recent cancer diagnosis (self or family, rs = 0.19, p = .03). Overall, education correlated with intention to test. The more education outside of the US, the less negative was the attitude toward being tested (rs = -0.41, p = .002). CONCLUSIONS: Direct experiences with cancer, more schooling and higher acculturation coupled with provider characteristics determined if Latinas were more open to testing. Provider characteristics mattered: having a female, Latinx, Spanish speaking provider was important for genetic testing decision-making. These findings are particularly pertinent in areas with high Latinx populations.


Assuntos
Aculturação , Testes Genéticos , Hispânico ou Latino , Feminino , Humanos , Escolaridade , Inquéritos e Questionários
3.
J Surg Res ; 292: 150-157, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37619500

RESUMO

INTRODUCTION: To complete a culturally appropriate translation of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Cervical Cancer module (QLQ-CX24) from English to Chichewa (one of the official languages of Malawi) in preparation for postsurgical outcomes research in rural Malawian cervical cancer patients. METHODS: Following the EORTC translation procedure manual, two distinct forward translations from English were reconciled into a preliminary Chichewa translation, followed by two distinct back-translations to English. The English back-translation was reconciled and the translation report sent for discussion and proofreading by EORTC; this was followed by pilot testing. All translators were physicians fluent in English and Chichewa. RESULTS: Of 24 questions in QLQ-CX24, three had prior translations available; all three required revision to clarify tense or wording. Three discussion exchanges with EORTC refined the translation and ensured faithfulness to the original English meaning; proofreaders contributed minor changes. Pilot testing was completed on 10 female patients (three with cervical cancer, four suspicious cervical lesions, and three screening only). Three patients were illiterate. During pilot testing, translation of question 46 (Q46) was misunderstood as referring to vaginal discharge instead of feeling "feminine". The remaining questions were understood, with minor feedback for six questions. Final revision of Q46 yielded a phrase describing "feminine" as "appearance or activities as a woman". Concepts comparable to "feminine" were absent in the Chichewa language/regional Malawian culture. The final revision of Q46 was pilot-tested on five patients (three illiterate) and found acceptable. CONCLUSIONS: Translation of the QLQ-CX24 module was completed successfully and revealed absence of the modern concept of femininity in Chichewa language and regional Malawian culture. Care should be taken when creating and translating healthcare-related documents for surgical research to ensure broad applicability across cultures.

4.
Gynecol Obstet Invest ; 85(3): 214-221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203957

RESUMO

OBJECTIVE: Germline BRCA mutation rates in the Latina population are yet to be well described. We aimed to quantitate the rates of referral for genetic testing in qualifying women and testing completion rates in a population of women presenting for gynecologic oncology care. Results were then stratified by ethnic/racial background. METHODS: Charts of new patients evaluated at a comprehensive cancer center in Southern California were reviewed. Patients qualifying for genetic testing in accordance with NCCN Guidelines version 1.2017 for breast and/or ovarian cancer genetic assessment were identified. The actual rates of prescriptions for genetic testing placed, testing completion rates, test results, as well as patients' family history were abstracted. Data were analyzed with chi-square tests. RESULTS: Five hundred and seventy-two of 2,053 patients met testing criteria, and 256/572 (45%) were prescribed testing in accordance with the guidelines. By ethnicity, testing was prescribed in 44% of Non-Hispanic White (NHW), 44% of Latina, 46% of African-American, and 60% of Asian (p = 0.6) patients. Testing was completed in 65% of NHW, 66% of Latina, 65% of African-American, and 67% of Asian patients (p = 0.97). Completion rates were low overall: 28% of those who met testing criteria were tested (p = 0.85). Pathogenic BRCA mutations were found in 29% of NHW and 21% of Latina, 45% of African-American, and 20% of Asian patients (p = 0.4). CONCLUSIONS: There was no difference by ethnicity in rates of testing prescription, completion, or presence of BRCA mutations. Overall, testing rates were suboptimal. BRCA mutations were found in large percentage of Latinas (21%). Further studies are underway to identify barriers to testing prescriptions and completion for Latina women.


Assuntos
Proteína BRCA1/análise , Proteína BRCA2/análise , Neoplasias da Mama/etnologia , Detecção Precoce de Câncer/estatística & dados numéricos , Hispânico ou Latino/genética , Neoplasias Ovarianas/etnologia , Adulto , Negro ou Afro-Americano/genética , Povo Asiático/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , California/epidemiologia , Etnicidade/genética , Feminino , Testes Genéticos/estatística & dados numéricos , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Encaminhamento e Consulta/estatística & dados numéricos , População Branca/genética
5.
Gynecol Oncol ; 152(3): 540-547, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30665615

RESUMO

Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.


Assuntos
Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/estatística & dados numéricos , Feminino , Humanos , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/mortalidade
6.
Gynecol Obstet Invest ; 83(1): 83-89, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28399524

RESUMO

AIMS: The study aimed to do the following: (1) describe progression free survival (PFS) and overall survival (OS) of women with cervical cancer presenting with occult supraclavicular lymph node (SCLN) metastases, identified by positron emission tomography CT (PET-CT) and (2) compare OS of patients with isolated SCLN metastases to that of patients with SCLN and extranodal metastatic disease. METHODS: Patients were identified retrospectively. Treatment intent was abstracted. PFS and OS in the high-dose chemo-radiotherapy (RT), palliative RT, and supportive treatment groups, as well as OS of patients with SCLN metastases only vs. SCLN and extranodal metastases were calculated. RESULTS: Fourteen patients received high-dose chemo-RT, 32 received palliative RT, and 6 received supportive care (n = 52). Median PFS was 3 months in high-dose chemo-RT group and 1 month in palliative RT (p = ns). Median OS was 12 months in high-dose chemo-RT group, 7 months in palliative RT group, and 2 months in palliative care group (p = 0.05). OS was significantly different between patients with isolated SCLN disease vs. SCLN and extranodal disease, that is, 10.5 vs. 3 months (p = 0.009, χ2 = 6.9). CONCLUSIONS: In this limited analysis, median OS of cervical cancer patients with PET/CT-positive SCLN metastases was the longest when treated with high-dose chemo-RT. Patients with SCLN and extranodal metastases experienced significantly shorter OS, as compared to patients with SCLN only disease.


Assuntos
Linfonodos/diagnóstico por imagem , Cuidados Paliativos/estatística & dados numéricos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Quimiorradioterapia , Clavícula , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
7.
Int J Gynecol Cancer ; 27(3): 603-607, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28129243

RESUMO

OBJECTIVE: Sexual dysfunction can be a long-term issue for women with gynecologic cancer. This study assesses the extent of sexual and marital dysfunction women face following treatment of a gynecologic cancer. METHODS: A cross-sectional study of women with gynecologic cancer was conducted using a 181-item survey. Sexual dysfunction was measured by change in the Female Sexual Function Index score; marital dysfunction was measured by change in Intimate Bond Measure from prediagnosis to posttreatment. Paired t tests and Fisher exact test were used to compare women with dysfunction to those without dysfunction. RESULTS: Three hundred twenty women were enrolled (mean age, 56.0 [SD, 12.0] years). Among all women, sexual function declined from a score of 21.3 (SD, 10.4) prior to 15.3 (SD, 10.2) (P < 0.001), and sexual activity decreased from 6.1 (SD, 6.8) to 2.6 (SD, 4.9) times per month following treatment (P < 0.001). Among the 208 women who were sexually active at the time of study, sexual dysfunction after treatment was associated with younger age (50.9 [SD, 11.7] years to 57.3 [SD, 12.3] years), ovarian (40.7% vs 30.7%) or cervical (21.0% vs 10.2%) cancer diagnosis, chemotherapy treatment (72.8% vs 50.4%), and being in a relationship (97.3% vs 82.7%). Among women in relationships, 27% experienced marital dysfunction. CONCLUSIONS: Women who are younger, have an ovarian or cervical cancer diagnosis, receive chemotherapy, or are in a committed relationship are at particularly high risk of sexual dysfunction. These women should be provided information about the risks associated with their cancer treatment.


Assuntos
Relações Interpessoais , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/psicologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Psicogênicas/etiologia , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/psicologia , Estudos Transversais , Feminino , Humanos , Casamento , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Psicogênicas/psicologia , Neoplasias do Colo do Útero/tratamento farmacológico
8.
Gynecol Oncol ; 134(2): 233-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24952366

RESUMO

OBJECTIVES: Obese women have a high incidence of wound separation after gynecologic surgery. We explored the effect of a prospective care pathway on the incidence of wound complications. METHODS: Women with a body mass index (BMI) ≥30 kg/m(2) undergoing a gynecologic procedure by a gynecologic oncologist via a vertical abdominal incision were eligible. The surgical protocol required: skin and subcutaneous tissues to be incised using a scalpel or cutting electrocautery, fascial closure using #1 polydioxanone suture, placement of a 7 mm Jackson-Pratt drain below Camper's fascia, closure of Camper's fascia with 3-0 plain catgut suture and skin closure with staples. Wound complication was defined as the presence of either a wound infection or any separation. Demographic and perioperative data were analyzed using contingency tables. Univariable and multivariable regression models were used to identify predictors of wound complications. Patients were compared using a multivariable model to a historical group of obese patients to assess the efficacy of the care pathway. RESULTS: 105 women were enrolled with a median BMI of 38.1. Overall, 39 (37%) had a wound complication. Women with a BMI of 30-39.9 kg/m(2) had a significantly lower risk of wound complication as compared to those with a BMI >40 kg/m(2) (23% vs 59%, p<0.001). After controlling for factors associated with wound complications the prospective care pathway was associated with a significantly decreased wound complication rate in women with BMI <40 kg/m(2) (OR 0.40, 95% C.I.: 0.18-0.89). CONCLUSION: This surgical protocol leads to a decreased rate of wound complications among women with a BMI of 30-39.9 kg/m(2).


Assuntos
Procedimentos Cirúrgicos em Ginecologia , Obesidade/complicações , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Protocolos Clínicos , Procedimentos Clínicos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Deiscência da Ferida Operatória/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia
9.
Int J Gynecol Cancer ; 24(4): 806-12, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24670967

RESUMO

OBJECTIVES: Intensity-modulated radiation therapy (IMRT) is frequently utilized in the treatment of cervical cancer. Our study compared instances of pelvic fractures, osteonecrosis, and osteomyelitis posttreatment with conventional radiation therapy (RT) versus IMRT in patients with cervical carcinomas. METHODS: Eighty-three patients primarily treated with IMRT were case matched with 83 historical control subjects treated with conventional RT. Pretreatment and posttreatment computed tomography scans were reviewed. Logistic regression analysis was utilized to examine the effects of treatment type (conventional RT vs IMRT) on the occurrence of posttreatment pelvic bony structure complications while adjusting for confounders. RESULTS: In the IMRT group, 3 (4%) of 83 patients developed posttreatment sacral fractures (median follow-up, 51 months). In the conventional RT group, there were 14 pelvic girdle complications (17%): 9 fractures, 2 cases of osteonecrosis, and 3 cases of osteomyelitis (median follow-up, 43.5 months; odds ratio, 4.49 for conventional vs IMRT groups, P = 0.01; 95% confidence interval, 1.4-14.1). In addition, there were 4 cases of posttreatment osteoporosis in the conventional RT group. All patients with complications in the IMRT group and 11 of 13 in the conventional RT group were symptomatic. CONCLUSIONS: Intensity-modulated radiation therapy is associated with a lower risk for pelvic girdle complications than conventional RT.


Assuntos
Osteomielite/etiologia , Osteonecrose/etiologia , Pelve/patologia , Lesões por Radiação/etiologia , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias do Colo do Útero/radioterapia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteomielite/patologia , Osteonecrose/patologia , Pelve/efeitos da radiação , Prognóstico , Lesões por Radiação/patologia , Planejamento da Radioterapia Assistida por Computador , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia
10.
J Low Genit Tract Dis ; 18(1): 8-12, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23774079

RESUMO

OBJECTIVE: Our study evaluated whether buffering reduces pain from lidocaine injection for loop electrosurgical excisional procedures (LEEPs) of the cervix when compared to unbuffered lidocaine. METHODS: Women undergoing outpatient LEEPs were randomized to receive either buffered or unbuffered lidocaine. Participants, caregivers, and statisticians were blinded to treatment allocation. Pain was categorized as injection, procedure, or cramping pain. Severity of pain was reported using a Likert visual analog scale and compared using Mann-Whitney tests. RESULTS: Twenty-eight subjects received buffered lidocaine and 24 subjects received unbuffered lidocaine. The 2 groups were similar in regard to age, race, previous LEEP, anesthetic volume used, and loop size. Mean scores were similar between the nonbuffered and buffered groups for injection pain (25 vs 19, p = .13), procedure pain (27 vs 19, p = .08), and cramping pain (19 vs 18, p = .86). CONCLUSIONS: Pain scores with subepithelial lidocaine plus epinephrine for LEEP are low and are not significantly reduced by buffering the anesthetic.


Assuntos
Anestésicos Locais/administração & dosagem , Eletrocirurgia/métodos , Epinefrina/administração & dosagem , Lidocaína/administração & dosagem , Dor/induzido quimicamente , Neoplasias do Colo do Útero/cirurgia , Adolescente , Adulto , Anestésicos Locais/efeitos adversos , Soluções Tampão , Método Duplo-Cego , Epinefrina/efeitos adversos , Feminino , Humanos , Lidocaína/efeitos adversos , Pessoa de Meia-Idade , Dor/prevenção & controle , Adulto Jovem
12.
Gynecol Oncol ; 129(3): 528-32, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23474347

RESUMO

OBJECTIVES: The objectives of this study are to determine the utility of re-excision after a primary diagnosis of vulvar carcinoma by assessing the frequency of residual carcinoma found upon re-excision and to quantitate the wound breakdown and carcinoma recurrence rates. METHODS: We reviewed 1122 cases of VIN or vulvar carcinoma. Women who underwent re-excisional procedures, as part of their initial surgical treatment were identified. Associations between the margin status of the original excisional sample and histology of re-excision, as well as association between the depth of invasion upon initial excision and histology of re-excision were analyzed with Chi-square tests. RESULTS: We identified 84 evaluable patients, 72 with stage I disease, 4 with stage II, and 7 with stage III disease. Upon the initial excisional procedure, 33 patients (39%) had carcinoma-positive margins, 27 patients had VIN-positive margins (32%) and 24 patients (28%) had negative margins (>1mm). Upon re-excision, 1/24 (4%) patients with negative margins, 2/27 (7%) patients with VIN-positive margins, and 11/33 (33%) patients with carcinoma-positive margins were found to have carcinoma in the re-excision specimens (p<0.0001, χ(2)=31). Deeper tumor invasion of the initial excisional specimen (1-12mm) was associated with a higher chance of finding carcinoma upon re-excision (range 18-42%, depending on depth of invasion) (p=0.015, χ(2)=19). Nineteen patients (23%) had vulvar wound breakdown post re-excision. Twelve patients (15%) experienced recurrences. CONCLUSIONS: The yield of micro- or invasive carcinoma at re-excision is low, with a high wound breakdown rate. Re-excision should be considered for patients with margins positive for carcinoma, especially for women with deep invasion, while women with VIN or close but clear margins may be followed.


Assuntos
Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasia Residual , Reoperação , Vulva/patologia , Doenças da Vulva/patologia , Adulto Jovem
13.
Gynecol Oncol Rep ; 47: 101195, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37215243

RESUMO

Background: Extraovarian primary peritoneal carcinoma (EOPPC) is a rare form of epithelial adenocarcinoma arising from the peritoneal lining with little to no ovarian involvement. To date, very few cases of EOPPC with primary tumors outside of the peritoneum have been described, the majority of which present with a primary tumor in the retroperitoneum. No cases have been reported with primary presentation as a chest wall mass. Case report: This case describes a 64-year-old woman referred for the evaluation of PAX8 positive chest wall masses. Biopsies of these masses demonstrated tumor architecture that was predominantly micropapillary with rare psammomatous calcifications. Immunohistochemically, the tumor was PAX8, CK7, ER, MOC31, and BerEP4 positive, with a mutational pattern of p53. This was consistent with Mullerian adenocarcinoma markers and suggestive of high-grade serous carcinoma. The patient was diagnosed with a unique presentation of EOPPC and is currently alive at 36 months post initial diagnosis. She has been treated with a combination of diagnostic surgery, chemotherapy and radiation therapy. Conclusion: To the best of our knowledge, this is the first documented case of EOPPC presenting with a primary tumor of the chest wall. This case highlights the importance of pathology, immunohistology, and interdisciplinary collaboration in diagnosing and treating rare malignancies.

14.
Gynecol Oncol Rep ; 46: 101162, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36992982

RESUMO

Sweet Syndrome, or acute febrile neutrophilic dermatosis, is a rare inflammatory dermatologic disorder that can be spontaneous, associated with malignancy, or drug-induced. Reports of Sweet Syndrome in gynecologic oncology patients are sparse, and the majority are thought to be malignancy-associated. The case presented here represents the third case of drug-induced Sweet Syndrome in a gynecologic oncology patient. To the best of our knowledge, this is the first report of Sweet Syndrome after initiation of a poly (ADP-ribose) polymerase inhibitor (PARPi) for maintenance therapy in the treatment of high grade serous ovarian carcinoma (HGSOC). This represents one of the most severe dermatologic adverse effects of treatment with PARPi reported to date, requiring treatment discontinuation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38009093

RESUMO

Ovarian cancer remains the most lethal gynecologic malignancy in the USA. For over twenty years, epithelial-mesenchymal transition (EMT) has been characterized extensively in development and disease. The dysregulation of this process in cancer has been identified as a mechanism by which epithelial tumors become more aggressive, allowing them to survive and invade distant tissues. This occurs in part due to the increased expression of the EMT transcription factor, SNAI1 (Snail). In the case of epithelial ovarian cancer, Snail has been shown to contribute to cancer invasion, stemness, chemoresistance, and metabolic changes. Thus, in this review, we focus on summarizing current findings on the role of EMT (specifically, factors downstream of Snail) in determining ovarian cancer aggressiveness.

16.
Cancers (Basel) ; 15(19)2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37835384

RESUMO

We aimed to determine the incidence, treatment regimen, and treatment outcomes (including progression-free survival and overall survival) of gynecologic carcinosarcoma, a rare, aggressive, and understudied gynecologic malignancy. This retrospective review included all patients with gynecologic cancers diagnosed and treated at a single tertiary care comprehensive cancer center between January 2012 and May 2021. A total of 2116 patients were eligible for review, of which 84 cases were identified as carcinosarcoma: 66 were uterine (5.2% of uterine cancers), 17 were ovarian (3.6% of ovarian cancers), 1 was cervical (0.28% of cervical cancers), and 1 was untyped. Of the patients, 76.2% presented advanced-stage disease (stage III/IV) at the time of diagnosis. Minority patients were more likely to present with stage III/IV (p < 0.0001). The majority of patients underwent surgical resection followed by systemic chemotherapy with carboplatin and paclitaxel. The median PFS was 7.5 months. Of the patients, 55% were alive 1 year after diagnosis, and 45% were alive at 5 years. In the studied population, minorities were more likely to present with more advanced disease. The rate of gynecologic carcinosarcomas was consistent with historical reports.

17.
J Matern Fetal Neonatal Med ; 36(1): 2190840, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36927241

RESUMO

OBJECTIVE: Patients with suspected placenta accreta spectrum (PAS) disorder are often referred to specialized medical centers for antepartum management and definitive treatment via cesarean hysterectomy. In 2019, our institution formed the only multidisciplinary team for the management of PAS within two of the largest counties in California. The purpose of this study was to evaluate the effects of the multidisciplinary team on patient volume and surgical outcomes for patients with PAS. METHODS: This was a single center retrospective cohort study, based in the only tertiary referral center within two of the largest counties in California. Patients who underwent cesarean hysterectomy for suspected PAS from January 2014 to April 2021 were included and divided into two groups, based on management by the multidisciplinary team from January 2019 and onward or routine care prior to that time. The outcomes of interest were quantitative blood loss, total units of packed red blood cell transfusion, referral volume, and diagnostic accuracy as well as ICU admission, bladder injury, and postoperative length of stay. Furthermore, we wanted to determine if patient's distance to the hospital impacted outcomes. Normally distributed variables were compared between groups using the t-test. Categorical variables were compared between the two groups using the chi square test. RESULTS: A total of 114 patients were included in the cohort, 59 patients were from January 2014 to December 2018 and 55 patients were from January 2019 to April 2021. Since the establishment of the multidisciplinary center, there was a 2.5-fold increase in the total patient volume (0.8 case/month to 2 cases/month) and a 2.8-fold increase in the referred patient volume. Patients undergoing cesarean hysterectomy since the establishment of the multidisciplinary team had less quantitative blood loss (1500 mL vs 2000 mL, p = .005) and required less units of packed red blood cell transfusion (2 vs 4 units, p < .001). In addition, blood loss of ≥2000 mL decreased from 57.6% to 38.2% (p = .04) and diagnostic accuracy improved from 35.6% to 83.6% (p < .001). Furthermore, we found that patient distance to the hospital did not significantly impact surgical outcomes. CONCLUSIONS: Since the establishment of the multidisciplinary team, our center experienced an increase in PAS volume and was able to demonstrate a statistically significant improvement in patient outcomes.


Assuntos
Placenta Acreta , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Placenta Acreta/diagnóstico , Placenta Acreta/cirurgia , Transfusão de Eritrócitos , Centros de Atenção Terciária , Equipe de Assistência ao Paciente
18.
Gynecol Oncol ; 124(2): 340-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22005521

RESUMO

OBJECTIVES: The PTEN pseudogene, PTENP1, was recently shown to play a role in cell proliferation in a prostate cancer model. In the present study, we sought to determine whether PTENP1 is expressed in endometrial cancer (EMCA) cell lines and primary tumors along with the microRNAs (miRNAs) that are predicted to regulate PTEN and PTENP1 transcript levels. METHODS: RNA was prepared from six EMCA cell lines, three normal endometrial samples, and 61 primary tumors. TaqMan® RT-PCR was used to quantitate PTEN expression in all specimens and PTENP1 expression in cell lines, and normal endometrial (NE) samples. PTENP1 expression was evaluated using conventional RT-PCR in primary tumors. MicroRNA profiling was undertaken using NanoString(TM) technology in AN3CA and KLE cell lines. The relationship between PTEN transcript levels, PTENP1 expression, and PTEN mutation status was investigated. RESULTS: All NE samples, cell lines, and primary tumors expressed PTEN. PTENP1 transcript was expressed in NE, cell lines, and 34/61 (56%) primary tumors. The median relative PTEN level was 2.9 arbitrary expression units in PTENP1-positive tumors and 2.3 in PTENP1-negative tumors (p=0.09). PTEN levels in wild-type and haploinsufficient tumors were variable compared to PTEN-null tumors (p=0.015). Four microRNAs predicted to bind PTEN/PTENP1 ranked in the top 20 most abundant microRNA subtypes in the AN3CA and KLE cell lines. CONCLUSIONS: PTENP1 is expressed in NE and EMCA cell lines, as are PTEN/PTENP1 targeting inhibitory miRNAs (cell lines). Further studies are needed to evaluate the impact of PTEN/PTENP1/miRNA interactions on tumorigenesis regulation in EMCA.


Assuntos
Neoplasias do Endométrio/enzimologia , PTEN Fosfo-Hidrolase/genética , Pseudogenes , Proteínas Supressoras de Tumor/genética , Linhagem Celular Tumoral , Neoplasias do Endométrio/genética , Feminino , Humanos , MicroRNAs/biossíntese , MicroRNAs/genética , PTEN Fosfo-Hidrolase/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Supressoras de Tumor/biossíntese
19.
Front Oncol ; 12: 789910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463315

RESUMO

Objective: Women make up a majority of the gynecologic oncology workforce. Increasing the numbers of women in leadership has been proposed as a path towards professional gender equity. This study examined whether leadership gender and departmental infrastructure impact the work environment for women gynecologic oncologists. Methods: Members of a 472-member private Facebook group "Women of Gynecologic Oncology" (WGO) who self-identified as women gynecologic oncologists provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions using a REDcap survey platform. Results: Of 250 (53%) respondents to this survey, most were younger than age 50 years (93.6%); White (82.2%) and non-Hispanic (94.3%); married (84.7%); and parenting (75.2%). Practice environments included academic (n=152, 61.0%), hospital employed (n=57, 22.9%), and private practice (n=31, 12.4%), and 89.9% supervised trainees. A significant percent of respondents had experienced bullying (52.8%), gender discrimination (57%) and microaggressions (83%). Age, race, ethnicity, practice setting, or mentorship were not statistically significantly associated with these experiences. Reported perpetrators were varied and included colleagues (84%), patients (44%), staff (41%), administrators (18%), and trainees (16%). Prevalence of bullying (55.0 vs 47.7%, p=0.33), gender discrimination (59.1 vs 52.3%, p=0.33) and microaggressions (83.3 vs 83.0%, p=1.00) were similar irrespective of departmental leadership gender. Conclusions: Women gynecologic oncologists report a high prevalence of workplace bullying, gender discrimination and microaggressions regardless of the gender of their immediate leadership. Proactive and deliberate structural interventions to improve the work environment for surgeons who are women are urgently needed.

20.
Gynecol Oncol Rep ; 35: 100698, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33521220

RESUMO

OBJECTIVES: Osseous metastases (OM) in endometrial cancer (EMCA) are thought to be rare. This study aimed to address the gap in present knowledge by defining the rate of OM in endometrial cancer (EMCA) as stratified by histology and ascertaining the best diagnostic modality for detection. METHODS: 435 consecutive cases of EMCA evaluated in tertiary care setting were reviewed. Clinico-pathologic data were abstracted and analyzed. RESULTS: 18/403 patients were found to have OM (4.6%). Majority were detected by PET/CT (13/18 (72%)), with conventional CT scans missing the diagnoses otherwise made by PET/CT scans in 2/9 patients. Patients with type II EMCA were at higher risk of developing OM compared with patients with type I EMCA; 2/234 patients with type I EMCA (0.85%) developed OM, as compared to 16/167 patients with type II EMCA (9.58%), OR = 12.3. Patients with serous histology had significantly higher odds of developing OM when compared to patients with non-serous histologies (OR 4, p = 0.001, 95% CI 1.54 to 10.76). Kaplan Myer survival function and log-rank analysis showed that the presence of OM was a significant negative prognosticator of survival, with median overall survival (mOS) of 16 months in OM patients vs. mOS undefined in non-OM patients (p < 0.0001). DISCUSSION: Incidence of detected OM was clinically significant, with most cases identified by PET/CT scans. Patients with type II EMCA, and in particular serous histology, were at a significantly higher risk of developing OM. OM when present, is an indicator of aggressive cancer biology and poor prognosis. Further studies are needed to ascertain the mechanism of predisposition to OM formation in serous EMCA and to confirm PET/CT as modality of choice for detection of OM.

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