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1.
Neoplasia ; 29: 100800, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35500546

RESUMO

Dietary patterns contribute to cancer risk. Separately, microbial factors influence the development of several cancers. However, the interaction of diet and the microbiome and their joint contribution to cancer treatment response needs more research. The microbiome significantly impacts drug metabolism, immune activation, and response to immunotherapy. One of the critical factors affecting the microbiome structure and function is diet. Data demonstrate that the diet and microbiome composition affects the immune response. Moreover, malnutrition is a significant confounder to cancer therapy response. There is little understanding of the interaction of malnutrition with the microbiome in the context of cancer. This review aims to address the current knowledge of dietary intake patterns and malnutrition among cancer patients and the impact on treatment outcomes. Second, this review will provide evidence linking the microbiome to cancer treatment response and provide evidence of the potentially strong effect that diet could have on this interaction. This review will formulate critical questions that will need further research to understand the diet-microbiome relationship in cancer treatment response and directions for future research to guide us to precision nutrition therapy to improve cancer outcomes.


Assuntos
Microbioma Gastrointestinal , Desnutrição , Microbiota , Neoplasias , Dieta , Microbioma Gastrointestinal/fisiologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Estado Nutricional
2.
J Cancer Educ ; 34(2): 357-362, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29280059

RESUMO

Human papilloma virus (HPV) vaccination rates lag behind other vaccines, primarily because of weak provider recommendations, and are associated with nearly 30,000 new cancer diagnoses a year. Educating medical students about HPV using active, team-centered learning may increase assimilation of information and may increase vaccination rates. A team-based learning (TBL) module focused on HPV for first-year medical students about HPV will better increase knowledge and likeliness to vaccinate than traditional education methods. Baseline HPV knowledge in medical students across Texas was assessed by surveying all 4-year undergraduate medical schools. Students at one medical school then participated in a week-long TBL focused on basic and clinical concepts relating to HPV, and then were re-surveyed upon completion of the course module. At baseline assessment, first-year student at the intervention site performed at the same level as first-year medical students across the state of Texas on knowledge and satisfaction with their HPV-related medical school education. After the TBL implementation, students performed significantly better than similar-year students and equal to graduating seniors, on knowledge of HPV- and HPV-related cancers, and report significantly higher satisfaction with education measures. Students at the intervention site were significantly more likely to recommend the HPV vaccination in future practice. Short-term knowledge and willingness to recommend vaccination are improved with a targeted HPV TBL early in medical education, which may provide a basis of knowledge that could translate into improved vaccination rates.


Assuntos
Competência Clínica , Educação de Graduação em Medicina/métodos , Vacinas contra Papillomavirus , Grupo Associado , Estudantes de Medicina , Adulto , Feminino , Humanos , Masculino , Texas , Adulto Jovem
3.
Gynecol Oncol Rep ; 26: 14-16, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30148199

RESUMO

Cervical cancer is the most common gynecologic malignancy worldwide and the third most common gynecologic cancer in the USA. Improved screening methods such as liquid-based cytology accompanied by Human Papilloma Virus (HPV) co-testing have contributed to a declining incidence of cervical cancer. There are approximately 13,000 new cases per year in the United States, accounting for 4200 deaths (Siegel et al., 2011). Pelvic organ prolapse increases with age, obesity and parity. In the absence of bothersome urinary, gastrointestinal or pressure symptoms, patients may choose conservative management options. The index patient was a 72 year old woman with a known history of pelvic organ prolapse who had been managed by her primary physician for 7 years until she developed new-onset vaginal bleeding. One month following worsening prolapse and increased vaginal bleeding she presented to the emergency department and was evaluated. On physical examination the cervix appeared as an 8 cm exophytic fungating mass extruding from the vagina and bled easily from areas of apparent necrosis. Multiple biopsies confirmed an invasive squamous cell carcinoma. The patient underwent the insertion of a Gelhorn pessary and perineorrhaphy to reduce her procidentia, cystocele and enterocele. Chemotherapy with Cisplatin and radiation therapy in the form of brachytherapy and external beam radiation therapy were then administered with curative intent. Cervical cancer complicating a uterine procidentia in an elderly patient is a rare occurrence in the United States and requires a multidisciplinary approach involving a urogynecologist, a gynecologic oncologist and a radiation oncologist. Nonetheless, in carefully selected patients, the outcome can be successful.

4.
Matern Child Health J ; 22(12): 1738-1742, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29992373

RESUMO

Introduction Early prenatal care can improve pregnancy outcomes, reduce complications, and ensure a healthier pregnancy. Unfortunately, many pregnant women do not seek early care. This research provides a framework for improving prenatal care in a low income community-based obstetrics clinic. Methods A multi-disciplinary quality improvement initiative was implemented at a large federally qualified health clinic in Houston, Texas to improve the rate of early entry into prenatal care by identifying barriers through patient surveys, focus groups, stakeholder feedback, and improving processes to reduce these barriers. Results A significant increase in early prenatal care was achieved by redesigning operational and clinical processes to improve access to care, expand patient education and outreach, increase resources, extend hours of operation, and increase presumptive insurance eligibility. Three months post implementation, an increase of 44.5% (p < 0.001) occurred in patients who had a prenatal visit in the first trimester. Patients with early prenatal care had better obstetrical and neonatal outcomes; however, the results were not statistically significant likely due to the small sample size. Discussion This quality improvement project provides various strategies and resources for other community-based clinics to consider when seeking improvement in their rates of early prenatal care.


Assuntos
Acessibilidade aos Serviços de Saúde , Seguro Saúde , Área Carente de Assistência Médica , Pobreza , Cuidado Pré-Natal/estatística & dados numéricos , Melhoria de Qualidade , Definição da Elegibilidade , Feminino , Humanos , Gravidez , Resultado da Gravidez , Cuidado Pré-Natal/organização & administração , Avaliação de Programas e Projetos de Saúde , Texas , Populações Vulneráveis
5.
MedEdPORTAL ; 14: 10787, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30800987

RESUMO

Introduction: Human papillomavirus (HPV) is associated with 30,000 cancer diagnoses a year, but the HPV vaccination is administered less frequently than other vaccinations. Future providers are a potential target for improving rates, and this flipped classroom module was developed to educate future vaccinators on HPV virology, vaccination, and clinical management. Methods: Designed as a clinical correlation for a basic science curriculum on introductory virology and immunology, this weeklong module consisted of a 1-hour lecture and case presentation, assigned articles, and a 90-minute wrap-up session including individual and group quizzes over the assigned material, a group clinical application exercise, and a 20-minute lecture on the case and real-world applications. A pre-/posttest survey was done on general knowledge of HPV, satisfaction with education, and willingness to recommend vaccination for HPV. Results: This module was designed for first-year students, 491 of whom have performed well in it. Pre-/posttest surveys of 243 students indicated that they significantly improved their knowledge of HPV (from 66.3% premodule to 86.3% postmodule, p <.001) and their satisfaction with medical education on vaccination-related topics, as well as increasing their willingness to recommend vaccination (from 58% premodule to 100% postmodule, p <.001). Discussion: This module is an effective and satisfactory way to teach first-year medical students about HPV and HPV vaccination and improves reported willingness to recommend vaccination. With limited resources available to effectively teach HPV vaccination to preclinical medical students, this module fills a gap.


Assuntos
Infecções por Papillomavirus/terapia , Estudantes de Medicina/estatística & dados numéricos , Educação de Graduação em Medicina/métodos , Avaliação Educacional/métodos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/fisiopatologia , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/uso terapêutico , Inquéritos e Questionários
6.
Histopathology ; 71(3): 480-487, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28417598

RESUMO

AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally related to and originate from the low-grade endometrioid carcinoma remains unclear. The aim of this study was to use massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low-grade and high-grade components. METHODS AND RESULTS: DNA samples extracted from each tumour component (low-grade endometrioid, high-grade anaplastic and high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing with the 410-gene Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay. Somatic single nucleotide variants, small insertions and deletions, and copy number alterations were detected with state-of-the-art bioinformatics algorithms, and validated with orthogonal methods. The endometrioid carcinoma and the associated high-grade components shared copy number alterations and four clonal mutations, including SMARCA4 mutations, which resulted in loss of BRG1 protein expression. Subclonal mutations and mutations restricted to single components were also identified, such as distinct TP53 mutations restricted to each histological component. CONCLUSIONS: Histologically distinct components of ovarian endometrioid carcinomas may show intratumour genetic heterogeneity but be clonally related, harbouring a complex clonal composition. In the present case, SMARCA4 mutations were probably early events, whereas TP53 somatic mutations were acquired later in evolution.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Idoso , Carcinoma Epitelial do Ovário , Análise Mutacional de DNA , Feminino , Humanos
7.
BJU Int ; 114(6): 844-51, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26010047

RESUMO

OBJECTIVE: To estimate the effect of radiation therapy (RT) administered for uterine cancer (UtC) on bladder cancer (BC) incidence, tumour characteristics at presentation, and mortality. PATIENTS AND METHODS: In this retrospective cohort study, records of 56 681 patients diagnosed with UtC as their first primary malignancy during 1980-2005 were obtained from the Surveillance, Epidemiology and End-Results (SEER) database. Follow-up for incident BC ended on 31 December 2008. Occurrences of BC diagnoses and BC deaths in patients with UtC managed with or without RT were summarised with counts and person-time incidence rates (counts divided by person-years of observation). Age adjustment of rates was performed by direct standardisation. Incident BC cases were described in terms of histological types, grades and stages. RESULTS: With a mean follow-up of 15 years, BC was diagnosed in 146 (0.93%) of 15 726 patients with UtC managed with RT, and in 197 (0.48%) of 40 955 patients with UtC managed without RT, with an age-adjusted rate ratio of 2.0 (95% confidence interval [CI] 1.6-2.5). Fatal BC occurred in 39 (0.25%) and 36 (0.09%) of patients with UtC managed with vs without RT, respectively, with an age-adjusted rate ratio of 2.9 (95% CI 1.8-4.6). Incident BC cases diagnosed in patients with UtC managed with vs without RT had similar distributions of histological types, grades, and stages. CONCLUSIONS: Use of RT for UtC is associated with increased BC incidence and mortality later in life. Heightened awareness should help identify women with new voiding symptoms or haematuria, all of which should be fully evaluated.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias Uterinas/radioterapia , Idoso , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias Uterinas/patologia
8.
World J Oncol ; 5(5-6): 228-231, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29147409

RESUMO

Uterine cervical cancers customarily spread by local extension to the adjacent viscera or through lymphatic embolization to the retroperitoneal lymph nodes. Distant hematogenous spread particularly to the brain is an uncommon and late event which heralds a poor prognosis. We report a case of uterine squamous cell carcinoma of the cervix with unusual simultaneous presentation of cavernous sinus metastasis and multiple brain metastases while reviewing the current literature on this clinical entity.

9.
J Gynecol Surg ; 29(4): 174-178, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24761131

RESUMO

Background: While robotic surgery for gynecologic indications received U.S. government approval in 2005, and has been rapidly and widely adopted, it is currently unclear how often this approach to hysterectomy is utilized. Objective: The aim of this research was to assess length of stay (LOS), mortality, indications, and current use of robotic hysterectomy, compared to other types of hysterectomy. Methods: A retrospective study of hysterectomies performed in New York State (NYS) in 2011 was performed. Data, including indication for surgery, age, procedure, LOS, and discharge status were obtained from the NYS Department of Health Statewide Planning and Research Cooperative System (SPARCS). Outcome Measures: LOS and mortality rate, were calculated according to institution, procedure, and indication for surgery. Results: For 22073 hysterectomies performed in NYS, the mean LOS was 2.9 days, and there were 29 (0.13%) deaths. The mean LOS for abdominal (12774 cases, 3.9 days) hysterectomies was longer than for laparoscopic (3927 cases, 1.6 days), robotic (2814 cases, 1.6 days), or vaginal (2558 cases, 1.7 days) hysterectomies (p<0.05). The adjusted mortality rates for abdominal (0.20%), laparoscopic (0.03%), robotic (0.07%), and vaginal (0.04%) hysterectomies were not significantly different. Overall, robotic surgery was performed in 29% of hospitals, by 11% of physicians and in 13% of cases. A robotic approach was utilized in 35% of patients with uterine cancer, 13% with endometriosis, 11% with excessive bleeding, 8% with leiomyomata, and 8% with pelvic relaxation. Conclusions: Despite the advantages in reduced LOS for robotic and other minimally invasive types of hysterectomies, the abdominal route is still predominant in most institutions. (J GYNECOL SURG XX:1).

11.
Gynecol Oncol ; 123(2): 208-13, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21821278

RESUMO

OBJECTIVE: To determine the prognostic significance of location of lymph node metastasis and extranodal disease for women with stage IIIC endometrial cancer. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Statistical analysis used Chi-square test, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: A total of 2559 women were identified; 1453 stage IIIC1, and with 906 stage IIIC2 tumors. Compared to stage IIIC1; more stage IIIC2 patients demonstrated high-risk factors such as grade III disease (p<0.001), unfavorable histologic types (p=0.01), concurrent disease at other extrauterine sites (p<0.001), and greater than two positive lymph nodes (p<0.001). While the 5-year disease specific survival was comparable (p>0.05) among node positive patients found to have positive peritoneal cytology (44.0%), adnexal/serosal metastasis (42.9%), and vaginal/parametrial involvement (41.8%); it differed individually in all three categories from those with nodal metastasis alone (67.0%, p<0.001). Among women with extranodal disease, the location of nodal metastasis had no effect on survival (HR=0.92; 95% CI, 0.74-1.14). For women with node only stage IIIC tumors, those patients with positive para-aortic nodes were more likely to die from their tumors (HR=1.40; 95% CI, 1.12-1.75). CONCLUSION(S): Location of lymph node metastasis is prognostic in patients with nodal disease alone, and not in those with extranodal disease. Extranodal disease is associated with a poor prognosis and should be regarded in conjunction with location of lymph node metastasis for risk-stratification in stage IIIC endometrial cancer.


Assuntos
Neoplasias do Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Programa de SEER
12.
Int J Gynecol Cancer ; 21(9): 1606-12, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21720252

RESUMO

OBJECTIVES: (1) To determine the significance of positive peritoneal cytology and pelvic versus para-aortic lymph node involvement in uterine carcinosarcoma. (2) To evaluate the impact of isolated retroperitoneal lymph node involvement (IIIC-N) versus retroperitoneal lymph node involvement plus other evidence of extrauterine disease spread (IIIC-N+) on survival in patients with stage IIIC uterine carcinosarcoma. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Statistical analysis used χ, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: A total of 690 women were identified. When comparing overall survival between patients with disease spread to uterine serosa and/or adnexa and those with positive peritoneal cytology, there was no significant difference (25.4% vs 15.5%, P = 0.2). However, although the 5-year overall survival was comparable between patients with positive pelvic lymph nodes and those with positive para-aortic lymph nodes (22.1% vs 25.4%, P = 1.0), it was significantly worse in stage IIIC-N(+) compared to stage IIIC-N patients (15.0% vs 33.4%, P < 0.001). Only patient's age (P < 0.001), race (P = 0.03), stage (P < 0.03), and lymphadenectomy (P < 0.001) were independent predictors of survival after adjusting for other contributing factors. In addition, the results of unadjusted analysis concerning the survival difference between different stage groups were confirmed on multivariate analysis. CONCLUSIONS: Positive peritoneal cytology is associated with poor prognosis in uterine carcinosarcoma, comparable to current International Federation of Gynecology and Obstetrics stage IIIA classification of disease. Although there does not seem to be a significant survival difference between patients with positive pelvic versus those with para-aortic lymph nodes, the prognosis seems to be much worse in patients with stage IIIC uterine carcinosarcoma with other evidence of extrauterine disease spread, suggesting the need for more aggressive therapy.


Assuntos
Carcinossarcoma/patologia , Neoplasias Uterinas/patologia , Idoso , Carcinossarcoma/epidemiologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Cavidade Peritoneal/patologia , Modelos de Riscos Proporcionais , Espaço Retroperitoneal/patologia , Programa de SEER , Estados Unidos/epidemiologia , Neoplasias Uterinas/epidemiologia
13.
Int J Gynecol Cancer ; 21(4): 711-6, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21412165

RESUMO

OBJECTIVE: (1) To determine the correlation of 2008 International Federation of Gynecology and Obstetrics staging system with survival in patients with stage IIA cervical cancer, (2) to elucidate the treatment patterns in stage IIA1 and stage IIA2 cervical cancer, and (3) to investigate whether radical hysterectomy or radiation influenced overall survival. METHODS: Data were extracted from the Surveillance, Epidemiology and End Results database between 1988 and 2005. Statistical analysis used χ test, Kaplan-Meier method, Cox regression, and logistic regression. RESULTS: Of the 560 women, 271 (48.4%) had stage IIA1, and 289 (51.6%) had stage IIA2 cervical cancer. Stage IIA2 patients were younger than stage IIA1 patients (mean age, 49 years vs 54 years; P = 0.01). Stage IIA1, compared with stage IIA2, differed significantly regarding the administration of primary radiation (47.2% vs 64.7%, P < 0.001) and adjuvant radiation (60.5% vs 77.5%, P = 0.006). The following variables were significantly associated with the performance of radical hysterectomy: patient age, 65 years or younger, tumor size, ≤ 2 cm or lesser, high tumor grade, and nonsquamous tumor histology. The incidence of adjuvant radiation after radical hysterectomy was high (48% [tumor size, ≤ 2 cm] to 86% [tumor size, >6 cm]). The 5-year overall survival was not significantly different between stages IIA1 and IIA2 (65.8% vs 59.5%, P = 0.2). Only patient age (P = 0.01), tumor size (P = 0.02), and lymph node status (P = 0.002) were independent predictors of survival. When controlled for other contributing factors, there was no significant difference in survival between patients treated by radical hysterectomy and primary radiation. CONCLUSIONS: The 2008 International Federation of Gynecology and Obstetrics staging criteria is not an independent predictor of survival in stage IIA cervical cancer. Given the equivalent efficacy of radical hysterectomy and radiation, attention should be paid to the high risk of adjuvant radiation in these patients.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias/métodos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Programa de SEER , Análise de Sobrevida , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
14.
Gynecol Oncol ; 121(1): 143-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21269668

RESUMO

OBJECTIVES: To determine the practice patterns of members of Society of Gynecologic Oncologists (SGO) in different clinical situations involving the intra-operative detection of nodal metastasis in early stage cervical cancer. METHODS: A study questionnaire was mailed to the current members of SGO (n=874). Data were collected using an internet survey database. Frequency distributions were determined, and non parametric tests were performed. RESULTS: Thirty percent SGO members responded (n=274). Only 38.6% routinely performed an intra-operative frozen section evaluation of the lymph nodes. Of these; most (79%) did not abort the radical hysterectomy (RH) for an isolated microscopically positive pelvic lymph node. The likelihood of aborting RH for microscopic nodal involvement increased however with number of positive pelvic lymph nodes (21% with 1, 40% with 2-3, and 61% with >3 positive pelvic lymph nodes), involvement of para-aortic lymph nodes (61%), or bilaterally positive lymph nodes (54%). Similarly, a large number did not complete the RH due to gross involvement of pelvic (45%) or para-aortic lymph node/s (69%). Most (90%) completed the lymphadenectomy before aborting RH. When completing RH, the majority tailored its extent to perform a less radical resection. Variables significantly associated with the likelihood of completing RH in different clinical situations included: location of current practice (West), practice type (private), years in practice (>15 years), and number of cases seen per year (>10/month). CONCLUSION: Practice patterns of SGO members are considerably diverse, which is reflective of the conflicting evidence available in the literature. Well designed studies are required to determine the best overall approach.


Assuntos
Linfonodos/patologia , Padrões de Prática Médica , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Feminino , Secções Congeladas , Humanos , Histerectomia/métodos , Cuidados Intraoperatórios/métodos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
15.
Breast Cancer Res Treat ; 129(2): 411-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21063905

RESUMO

The c-fms proto-oncogene encoded CSF-1 receptor and its ligand represent a feedback loop, which in a paracrine manner, is well known to promote spread of breast cancers. The role of the autocrine feedback loop in promotion of breast tumor behavior, in particular in vitro, is less well understood. The physiologic stimulation of c-fms expression by glucocorticoids (GCs) in vitro and in vivo magnifies the tumor promoting effect seen in these cells from activated c-fms signaling by CSF-1. Targeted molecular therapy against c-fms could therefore abrogate both complementary feedback loops. Using breast cancer cells endogenously co-expressing receptor and ligand, we used complementary approaches to inhibit c-fms expression and function within this autocrine pathway in the context of GC stimulation. Silencing RNA (shRNA), antisense oligonucleotide therapy (AON), and inhibition of c-fms signaling, were all used to quantitate inhibition of GC-stimulated adhesion, motility, and invasion of human breast cancer cells in vitro. shRNA to c-fms downregulated GC-stimulated c-fms mRNA by fourfold over controls, correlating with over twofold reduction in cellular invasiveness. AON therapy was also able to inhibit GC stimulation of c-fms mRNA, and resulted in threefold less invasiveness and 1.5 to 2-fold reductions in adhesion and motility. Finally, the small-molecule c-fms inhibitor Ki20227 was able to decrease in a dose-response manner, breast cancer cell invasion by up to fourfold. Inhibition of this receptor/ligand pair may have clinical utility in inhibition of the autocrine as well as the known paracrine interactions in breast cancer, thus further supporting use of targeted therapies in this disease.


Assuntos
Comunicação Autócrina/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Comunicação Autócrina/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Invasividade Neoplásica , Oligonucleotídeos Antissenso/metabolismo , Fenótipo , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proto-Oncogene Mas , Interferência de RNA , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Tiazóis/farmacologia , Transfecção
16.
Int J Gynecol Cancer ; 19(5): 856-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19574773

RESUMO

OBJECTIVES: Central nervous system metastases are believed to be becoming more clinically evident as long-term survival for epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC) has improved. Our objective was to report our experience with managing brain metastatic disease (BMD) in patients with EOC and PPC. METHODS: A retrospective review was performed on patients with EOC and PPC diagnosed with BMD from 1983 to 2007 at our institution. RESULTS: Twenty-four patients were identified. Patients with multiple brain lesions (n = 16) had a shorter median time to diagnosis of BMD than patients with single lesions (n = 8; 22.5 vs 39 months). Radiation therapy was included in the treatment of BMD for 19 patients (78%). Fourteen patients received whole-brain radiation therapy (WBRT) only (survival, 6 months [range, 1-51 months]). Three patients received a combination of gamma knife radiosurgery and WBRT (survival, 20 months [range, 17-67 months]), and 1 patient received gamma knife radiosurgery alone (survival, 10 months). Four patients underwent craniotomy with 3 receiving postoperative WBRT (survival, 8.5 months [range, 2-97 months]). Two patients elected for palliative care only. The median survival from the diagnosis of BMD was 8.5 months (range, 1-97 months) with a 42% 1-year survival and 16% 2-year survival. Patients with single lesions had a significantly longer survival than patients with multiple lesions (17 months [range, 3-97 months] vs 6 months [range, 3-67 months], respectively). CONCLUSIONS: Our report provides the largest single-institution experience of brain metastasis from EOC and PPC in patients receiving predominantly platinum and paclitaxel therapy. Patients with BMD from EOC and PPC have a poor prognosis overall; however, prolonged survival is possible in a small subset of patients.


Assuntos
Neoplasias Encefálicas/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/secundário , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Adulto , Idoso , Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante , Terapia Combinada , Irradiação Craniana , Craniotomia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Prognóstico , Radiocirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
Neoplasia ; 11(2): 136-44, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19177198

RESUMO

Coexpression of the macrophage colony-stimulating factor (CSF-1) and its receptor (CSF-1R) in metastatic ovarian cancer specimens is a predictor of poor outcome in epithelial ovarian cancer. This suggests that an autocrine loop is produced by which ovarian tumors can secrete CSF-1 stimulating the CSF-1R resulting in a more aggressive phenotype. Our current work sought to validate this autocrine stimulation model using stable transfection of a 4-kb CSF-1 construct into otherwise nonvirulent Bix3 ovarian cancer cells. A representative clone, Bix3T8.2, produced a 72-fold increase in CSF-1 gene transcription rate (by nuclear run-off assays) and a 57-fold increase in secreted CSF-1 protein (by sandwich ELISA), compared to parent cells. Comparison of Bix3T8.2 invasion, adhesion, and motility in vitro and metastasis in vivo were made to parental and transfectant controls. Up to 12-fold higher invasiveness was seen with Bix3T8.2 and 2- and 6-fold higher adhesion and motility, respectively, over controls in vitro. In nude mice, i.p. injection of Bix3T8.2 produced a wide array of visceral, nodal, and distant metastasis with a degree of enhanced tumor burden not seen in any of the 10 mice inoculated with transfectant control cells. Complete absence of tumor take distinguished 40% of mice implanted with transfectant control cells. Disruption of this autocrine loop using antisense oligomer therapy against CSF-1R and 3' untranslated region knockdown of CSF-1 protein resulted in reversal of in vitro and in vivo tumor phenotypes. This CSF-1 feedback loop offers a model by which novel biologic therapies can potentially target multiple levels of this pathway.


Assuntos
Transformação Celular Neoplásica , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Metástase Neoplásica/patologia , Neoplasias Ovarianas/patologia , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Adesão Celular , Movimento Celular , Transformação Celular Neoplásica/genética , Feminino , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Oligonucleotídeos Antissenso/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Fenótipo , Receptor de Fator Estimulador de Colônias de Macrófagos/efeitos dos fármacos , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Células Tumorais Cultivadas
18.
Teach Learn Med ; 21(1): 15-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19130381

RESUMO

BACKGROUND: Reflection is a learning tool increasingly being used in medical education. It has not been well studied as a method of communicating resident rotation goals and objectives. PURPOSE: The purpose was to study the effect of monthly resident reflection on achieving curriculum goals. METHODS: During the first half of the 2005-06 academic year, obstetrics/gynecology residents at a community hospital received curriculum goals in a traditional written manner. During the second 6 months, the same trainees underwent 1-hr monthly structured reflection sessions on the rotation goals and objectives. RESULTS: Sixteen residents were studied. Compared to control, residents reported the rotation goals as better defined during reflection months. More trainees rated reflection as more valuable than the didactic time it replaced. All 16 residents documented more cumulative procedures in the Accreditation Council for Graduate Medical Education operative log Web site during reflection months for each of the three major categories; there was a mean increased number of procedures logged in Obstetrics (23.1 +/- 14.0, p < .001), Gynecology (18.3 +/- 10.9, p < .001), and Primary Care (21.1 +/- 23.5, p = .003). Overall, there was a mean of 62.6 +/- 32.1 (p < .001) more procedures entered during the reflection period, which translated to an 18% increase. CONCLUSIONS: Structured monthly reflection may lead to a higher success of achieving rotation goals.


Assuntos
Objetivos , Internato e Residência , Estudantes de Medicina/psicologia , Pensamento , Currículo , Coleta de Dados , Ginecologia/educação , Humanos , Internato e Residência/organização & administração , Obstetrícia/educação , Estudos Prospectivos , Texas
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