RESUMEN
OBJECTIVE: To determine the efficacy of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian carcinoma and related malignancies. METHODS: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤2. Dalantercept was administered subcutaneously at 1.2â¯mg/kg every 3â¯weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was the probability of response ≤0.10 and the probability of 6-month progression-free survival without receipt of non-protocol therapy (event-free survival at 6â¯months, EFS6) ≤0.15, using RECIST 1.1 criteria. RESULTS: The first stage was closed after enrollment of 30 participants with median age of 56.5â¯years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval <6â¯months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1-29). There were six treatment-related grade 3 AEs and no grade ≥4 AEs. There were no objective responses. EFS6 was reached in 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%). CONCLUSIONS: Though safe, dalantercept as administered had limited efficacy in this patient population overall.
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Receptores de Activinas Tipo II/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Receptores de Activinas Tipo II/efectos adversos , Adulto , Anciano , Antineoplásicos/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Persona de Mediana Edad , Neoplasia Residual , Proteínas Recombinantes de Fusión/efectos adversos , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
OBJECTIVES: To review the extent of health disparities in gynecologic cancer care and outcomes and to propose recommendations to help counteract the disparities. METHODS: We searched the electronic databases PubMed and the Cochrane Library. We included studies demonstrating quantifiable differences by race and ethnicity in the incidence, treatment, and survival of gynecologic cancers in the United States (US). Most studies relied on retrospective data. We focused on differences between Black and White women, because of the limited number of studies on non-Black women. RESULTS: White women have a higher incidence of ovarian cancer compared to Black women. However, the all-cause ovarian cancer mortality in Black women is 1.3 times higher than that of White women. Endometrial and cervical cancer mortality in Black women is twice that of White women. The etiology of these disparities is multifaceted. However, much of the evidence suggests that equal care leads to equal outcomes for Black women diagnosed with gynecologic cancers. Underlying molecular factors may play an additional role in aggressive tumor biology and endometrial cancer disparities. CONCLUSION: Gynecologic cancer disparities exist between Black and White women. The literature is limited by the lack of large prospective trials and adequate numbers of non-Black racial and ethnic groups. We conclude with recommendations for continued research and a multifaceted approach to eliminate gynecologic cancer disparities.
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Comités Consultivos , Negro o Afroamericano/estadística & datos numéricos , Neoplasias de los Genitales Femeninos/etnología , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Población Blanca/estadística & datos numéricos , Femenino , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/terapia , Humanos , Estados UnidosRESUMEN
The glycation of protein and nucleic acids that occurs as a consequence of hyperglycemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs after the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal, and disruption of mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear owing to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells, and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography-tandem mass spectrometry, enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycemia both in cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging.
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Diabetes Mellitus Tipo 1/metabolismo , Glioxal/análisis , Hiperglucemia/metabolismo , Mitocondrias Hepáticas/metabolismo , Sondas Moleculares/síntesis química , Piruvaldehído/análisis , Animales , Bovinos , Línea Celular , Cromatografía Liquida , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/patología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Glioxal/metabolismo , Hiperglucemia/diagnóstico , Hiperglucemia/patología , Ratones , Mitocondrias Hepáticas/patología , Mioblastos/metabolismo , Mioblastos/patología , Compuestos Organofosforados/química , Estrés Oxidativo , Fenilendiaminas/química , Piruvaldehído/metabolismo , Ratas , Espectrometría de Masas en TándemRESUMEN
Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H(2)O(2)) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H(2)O(2) derives from superoxide (O(2)(.)), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O(2)(.) production, such as may occur under nutrient excess and low ATP demand, the increase in O(2)() and H(2)O(2) may provide feedback signals to modulate mitochondrial metabolism.
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Peróxido de Hidrógeno/metabolismo , Mitocondrias Cardíacas/enzimología , Proteínas Mitocondriales/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Complejo Piruvato Deshidrogenasa/metabolismo , Superóxidos/metabolismo , Adenosina Trifosfato/biosíntesis , Animales , Ciclo del Ácido Cítrico/fisiología , Células HEK293 , Humanos , Mitocondrias Cardíacas/genética , Proteínas Mitocondriales/genética , Proteínas Serina-Treonina Quinasas/genética , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Complejo Piruvato Deshidrogenasa/genética , Ratas , Transducción de Señal/fisiologíaRESUMEN
The current epidemic of the metabolic syndrome in the developed world is largely due to overnutrition and lack of physical activity. However, the underlying causes by which chronic overnutrition interacts with genotype and physical inactivity to generate the metabolic syndrome phenotype are complex, and include multiple metabolic and physiological alterations. Mitochondrial oxidative stress has been suggested to contribute to the metabolic syndrome, but the mechanisms and significance are unclear. Here we review how disruption of mitochondrial metabolism and increased oxidative stress may occur during overnutrition coupled with limited physical activity. From this we suggest a unifying hypothesis to integrate what is known about mitochondrial involvement in the metabolic syndrome that points to testable hypotheses and novel therapeutic approaches.
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Síndrome Metabólico/metabolismo , Mitocondrias/metabolismo , Animales , Humanos , Estrés Oxidativo/genética , Estrés Oxidativo/fisiologíaRESUMEN
OBJECTIVES: To review populations of women in the United States at high risk for cervical cancer, assess known reasons for existing outcome disparities, and discuss potential strategies to reduce barriers to HPV vaccination and current strategies for cervical cancer prevention. METHODS: An expert forum conducted September 12-13, 2008, by the Society of Gynecologic Oncologists including 56 experts in cervical cancer and titled "Future strategies of cervical cancer prevention: what do we need to do now to prepare?" RESULTS: Although epidemiological data is useful and necessary to identify populations at high risk for cervical cancer, an understanding of the knowledge and attitudes regarding HPV and cervical cancer prevention of racial/ethnic groups and sub-groups within racial/ethnic categories is critical for the implementation of effective targeted and effective educational efforts. Inequities in cervical cancer screening, diagnosis and treatment and HPV vaccination may arise from a number of barriers including access to healthcare, cultural beliefs, and limited awareness of options. CONCLUSIONS: Initiatives to promote uptake of prophylactic HPV vaccination that target high-risk women need to be implemented before existing disparities widen. Although acceptability of HPV vaccination is promising, uptake is still low among low-income populations and specific racial/ethnic minorities. To address limited vaccine uptake it may be beneficial to establish national/state guidelines as well as culturally relevant interventions at the individual and community levels. The successful implementation of multiple integrated initiatives on HPV awareness, knowledge, and vaccination will diminish existing disparities in cervical cancer incidence and mortality.
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Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Aceptación de la Atención de Salud , Neoplasias del Cuello Uterino/prevención & control , Vacunación/métodos , Vacunación/psicología , Femenino , Humanos , Infecciones por Papillomavirus/epidemiología , Estados Unidos/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virologíaRESUMEN
Oregovomab is a monoclonal antibody that recognizes CA125 and forms circulating immune complexes that can elicit immunity against both tumor antigen and tumor. This study was designed to assess combining this immunotherapy at 2 dosing schedules with front-line chemotherapy in patients with advanced ovarian cancer. Forty patients with stage III/IV carcinomas were randomized to receive a 2 mg oregovomab infusion either the same day [simultaneous infusion (SIM)] or 1 week after [1-week delayed (OWD)] standard carboplatin-paclitaxel chemotherapy at cycles 1, 3, and 5, then quarterly for up to 11 antibody doses. The primary end point was antibody response to oregovomab. Secondary end points included cellular immune response, response rate to front-line treatment, and progression-free survival. A different immune response pattern was observed between the SIM arm and the OWD arm, baseline plasma cytokines were balanced. Humoral immunity occurred more rapidly (P=0.0033) and with greater magnitude in the SIM arm. Absolute lymphocyte counts decreased in the SIM arm at cycles 3 and 5 compared with baseline. Treatment emergent CA125-specific cellular immunity was measured more commonly with SIM (P=0.04) and clinical parameters directionally favored this schedule. The immune responses were stronger than those measured in a previous maintenance monoimmunotherapy protocol. Immunotherapy-associated toxicity was minimal in this study. Front-line chemotherapy with carboplatin-paclitaxel has immune adjuvant properties when combined with oregovomab immunotherapy; however, schedule is important. SIM strategies of carboplatin and paclitaxel should be further studied with oregovomab and other antigen-specific cancer immunotherapy approaches.
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Adyuvantes Inmunológicos/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/efectos adversos , Antígeno Ca-125/sangre , Carboplatino/efectos adversos , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Esquema de Medicación , Femenino , Humanos , Inmunoterapia , Interferón gamma/inmunología , Interferón gamma/metabolismo , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Paclitaxel/efectos adversosRESUMEN
OBJECTIVE: The recent approval of a vaccine to prevent HPV infection is an important advance in cervical cancer prevention. This article is intended to provide gynecologic oncologists with a comprehensive background in modern cervical cancer prevention strategies. METHODS: We describe and contrast the quadrivalent and bivalent vaccines. More established cervical cancer prevention strategies are reviewed, with comments on the impact of HPV vaccination. Clinical guidance is provided for use of the approved quadrivalent vaccine. Safety and side effects of both vaccines are reviewed and future questions and challenges are explored. RESULTS: It is vitally important that both vaccinated and unvaccinated women continue to fully engage in cervical cancer prevention, including cervical cancer screening, follow-up of abnormal screens, and treatment of premalignant lesions. A quadrivalent virus-like particle vaccine has now been approved for use in girls and women ages 9 to 26. A bivalent vaccine may be available soon. Vaccine efficacy in clinical trials has been outstanding, with 100% protection against HPV-type-specific cervical intraepithelial neoplasia (CIN) II and III. CONCLUSIONS: Comprehensive cervical cancer protection now includes prophylactic vaccination for girls and young women in addition to screening and treatment of premalignant changes. Gynecologic oncologists will continue to play an important role in promoting optimal prevention practices.
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Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Femenino , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Humanos , Infecciones Tumorales por Virus/prevención & control , Neoplasias del Cuello Uterino/virología , Frotis VaginalRESUMEN
PURPOSE: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. METHODS AND MATERIALS: We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m(2)/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and > or =40 Gy (V(10), V(20), V(30), and V(40), respectively) was calculated. HT was graded according to the Radiation Therapy Oncology Group system. Multivariate regression models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. RESULTS: Increased pelvic BM V(10) (BM-V(10)) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V(10) > or =90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V(10) <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V(30) and V(40) were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. CONCLUSION: The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.
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Médula Ósea/efectos de la radiación , Enfermedades Hematológicas/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Anemia/sangre , Anemia/etiología , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Médula Ósea/efectos de los fármacos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Terapia Combinada/métodos , Femenino , Cabeza Femoral/efectos de la radiación , Enfermedades Hematológicas/sangre , Humanos , Ilion/efectos de la radiación , Leucopenia/sangre , Leucopenia/etiología , Región Lumbosacra/efectos de la radiación , Persona de Mediana Edad , Neutropenia/sangre , Neutropenia/etiología , Fármacos Sensibilizantes a Radiaciones/administración & dosificación , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Dosificación Radioterapéutica , Sacro/efectos de la radiación , Trombocitopenia/sangre , Trombocitopenia/etiología , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
BACKGROUND: Ovarian carcinoma is a devastating disease because patients are diagnosed with advanced disease at presentation and five-year survival ranges from 5-20%. Salvage therapy becomes important for survival in those patients with recurrent disease. There are a variety of agents with relatively similar response rates; however, side effects may limit choice. Pegylated liposomal doxorubicin was found to be less toxic but as effective as other agents. Cardiotoxicity continues to be a concern with long-term antracycline use. CASES: We present three cases of women diagnosed with advanced ovarian carcinoma. Each patient initially underwent optimal cytoreductive surgery, however, developed recurrent disease and were treated with pegylated liposomal doxorubicin. One patient remains disease-free following complete response. Two patients were maintained on pegylated liposomal doxorubicin with stable disease for 18 and 34 months, respectively. These cases demonstrate that pegylated liposomal doxorubicin can be used for extended periods of time without cardiotoxicity. CONCLUSION: The adverse events were few with cumulative doses as high as 1,360 mg/m2. These cases show that pegylated liposomal doxorubicin may be a promising agent in recurrent ovarian carcinoma. We recognize the limitations of our data. The results need to be confirmed in a larger group of patients.
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Antibióticos Antineoplásicos/uso terapéutico , Doxorrubicina/análogos & derivados , Neoplasias Ováricas/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Anciano , Antibióticos Antineoplásicos/efectos adversos , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Polietilenglicoles/efectos adversos , Terapia Recuperativa , Factores de TiempoRESUMEN
OBJECTIVE: To estimate the risk of high-grade cervical disease among teenage women with abnormal cytology. METHODS: Retrospective analysis of a prospectively collected database of females undergoing colposcopy for abnormal screening cytology in an urban dysplasia clinic. RESULTS: Among 211 eligible teens, high-grade squamous intraepithelial lesions were found in 17 (8%) on referral cytology and 4 (2%) on repeat cytology. High-grade cervical intraepithelial neoplasia was found in colposcopic biopsy specimens 30 (15%) of young women; no patient had cancer. Age, referral Pap, ethnicity, parity, HIV serostatus, history of other sexually transmitted infections, smoking, oral contraceptive use condom use, use of medroxyprogesterone, age at first intercourse, and the number of years since first intercourse did not predict increasing risk of high-grade cervical intraepithelial neoplasia (CIN). In logistic regression, both number of partners > or = 5 (p = 0.003) and a finding of any squamous intraepithelial lesion in a Pap test repeated at colposcopy (p = 0.025) were significant predictors of CIN 2,3, though the predictive value of the model was weak (R = 0.12). CONCLUSION: Only 15% of teens with abnormal cytology have high-grade CIN. Colposcopy may be most appropriate for those with multiple partners and squamous intraepithelial lesions on repeat Pap.
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Tamizaje Masivo , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Adolescente , Adulto , Biopsia , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Chicago , Colposcopía , Citodiagnóstico , Femenino , Humanos , Modelos Logísticos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Frotis VaginalRESUMEN
OBJECTIVE: To define the risk of high-grade cervical intraepithelial neoplasia (CIN 2,3) among women with unsatisfactory colposcopy results who underwent a loop electrosurgical excision procedure. METHODS: Loop electrosurgical excision procedures were performed for clinical indications by residents supervised by attending obstetrician-gynecologists at an urban public hospital referral clinic. Specimens obtained between July 1, 1996, and April 30, 2002, were retrieved retrospectively after grading and recording in an institutional database. The endpoint of interest was high-grade cervical disease, a composite of CIN 2, CIN 3, and cancer, in excision specimens. RESULTS: Of 169 evaluable patients, five (3%) had cancer. High-grade disease was found in 6 of 21 patients (29%) without a colposcopic lesion, in 13 of 33 patients (36%) with only koilocytosis on colposcopic biopsy, in 15 of 55 patients (27%) with CIN 1, in 13 of 25 patients (54%) with CIN 2, and in 26 of 35 patients (74%) with CIN 3 (p < 0.001). High-grade disease was associated with the grade of referral cytologic results, cytologic analysis repeated at colposcopy, and colposcopic biopsy (p < 0.001 for all). Limiting excision to women with cytologic results at the time of colposcopy read as atypical squamous cells of undetermined significance or worse yielded a high-grade disease prevalence of 12%, with a sensitivity of 92%, specificity 46%, negative predictive value 88%, and positive predictive value 56%. Referral cytologic results, colposcopic biopsy, age, and endocervical curettage results did not seem to identify women at low risk for high-grade disease. CONCLUSIONS: Women with negative cytologic results at the time of colposcopy have a low risk for high-grade disease and may avoid a loop electrosurgical excision procedure despite unsatisfactory colposcopy.
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Cuello del Útero/patología , Colposcopía , Electrocirugia , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Biopsia , Bases de Datos Factuales , Femenino , Humanos , Valor Predictivo de las Pruebas , Riesgo , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patologíaRESUMEN
PURPOSE: The purpose of this pilot study was to evaluate the efficacy of the clitoral therapy device (Eros Therapy) in alleviating sexual dysfunction in irradiated cervical cancer patients. METHODS AND MATERIALS: Eligible patients had a history of cervical cancer treated with radiotherapy and self-reported sexual dysfunction of sexual arousal and/or orgasmic disorders. Patients used the noninvasive, nonpharmacologic clitoral therapy device using a hand-held, battery-powered vacuum to cause clitoral engorgement four times weekly for 3 months during foreplay and self-stimulation. Study instruments included the Female Sexual Function Index, Derogatis Interview for Sexual Functioning, and Dyadic Adjustment Scale. The outcome evaluation was performed at 3 months. RESULTS: Between 2001 and 2002, 15 women were enrolled and 13 completed the study. The median patient age and radiotherapy-enrollment interval was 43.5 years and 2 years, respectively. At baseline, all patients reported symptoms of sexual arousal and/or orgasmic disorders, and some also had sexual desire and pain disorders. At 3 months, statistically significant improvements were seen in all domains tested, including sexual desire, arousal, lubrication, orgasm, sexual satisfaction, and reduced pain. The median Female Sexual Function Index total score increased from 17 to 29.4 (maximal score, 36; p <0.001). The median Derogatis Interview for Sexual Functioning total raw score increased from 46 to 95 (maximal score, 118; p <0.001). At baseline, the Derogatis Interview for Sexual Functioning total T-score corresponded to the bottom 10th percentile of normal sexual functioning. At 3 months, the total T-score placed the patients at the normalcy cutoff. Gynecologic examinations revealed improved mucosal color and moisture and vaginal elasticity and decreased bleeding and ulceration. CONCLUSION: Our results from this pilot study suggest that the clitoral therapy device may alleviate sexual dysfunction in irradiated cervical cancer patients. A randomized, controlled trial is warranted to assess the full benefits of this approach.
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Clítoris/fisiología , Modalidades de Fisioterapia/instrumentación , Disfunciones Sexuales Fisiológicas/terapia , Disfunciones Sexuales Psicológicas/terapia , Neoplasias del Cuello Uterino/radioterapia , Adulto , Clítoris/irrigación sanguínea , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Persona de Mediana Edad , Orgasmo , Proyectos Piloto , Succión/instrumentación , Resultado del TratamientoRESUMEN
To identify changes in gene expression in serous epithelial ovarian cancers (SEOC), we utilized cDNA microarrays consisting of 2382 genes with cancer related properties to analyze tumors from 20 patients with defined clinical out-comes. The significance analysis of microarrays method was used to determine differentially expressed genes, leading to the identification of 134 up-regulated and 231 down-regulated genes overall. By increasing the stringency of the statistical selection criteria, 41 over-expressed and 51 under-expressed genes were identified. The median duration of follow-up of the 20 patients was 16.8 months with a median progression free survival of 7.0 months. We found 11 genes that were differentially over-expressed in patients with recurrent disease, and 3 genes (homo sapiens mRNA for Ins P3 5-phophatase, lipoma HMGIC fusion partner-like 2 and CD63 melanoma 1 antigen) in patients who were dead of disease. Subsequently, we examined the distribution of the differentially expressed genes in the cDNA library database from adult human tumor and normal tissues using the DigiNorthern method to identify a subset of genes with relatively restricted tissue distribution. Finally, protein expression of 5 selected genes were further examined using immunohistochemistry applied on a tissue microarray prepared from an independent panel of 93 SEOC tissues. The results provided validation for 2 under-expressed genes (E2F transcription factor 5 and CK14) and 3 over-expressed genes (Bcl2-like 1, COX-2, CD63). Our study demonstrates differential gene expression in clinically distinct groups of SEOC using cDNA microarray. These genes may potentially be useful as biomarkers and/or targets for therapeutic intervention.
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Carcinoma/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas/genética , Adulto , Anciano , Antígenos CD/análisis , Carcinoma/diagnóstico , Carcinoma/metabolismo , Ciclooxigenasa 2 , Regulación hacia Abajo , Factor de Transcripción E2F5 , Femenino , Perfilación de la Expresión Génica , Biblioteca de Genes , Humanos , Inmunoquímica , Isoenzimas/análisis , Proteínas de la Membrana , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/metabolismo , Glicoproteínas de Membrana Plaquetaria/análisis , Prostaglandina-Endoperóxido Sintasas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Membrana Serosa/patología , Tetraspanina 30 , Distribución Tisular/genética , Factores de Transcripción/análisis , Regulación hacia Arriba , Proteína bcl-XRESUMEN
BACKGROUND: Primary primitive neuroectodermal (pPNET) tumors rarely occur in adults, and they very rarely present as primary tumors of the uterus. Only 12 reported cases of pPNET of the uterus have been published in the English literature. We report two additional cases treated at the Roswell Park Cancer Institute, Buffalo, NY, between 1999 and 2002. CASES: Two postmenopausal patients presenting with abnormal uterine bleeding underwent endometrial biopsy, and subsequently staging laparotomy. The diagnosis of pPNET in both cases was confirmed only by extensive immunohistochemical analysis of the tumors. One patient with disease confined to an endometrial polyp received no adjuvant therapy, while the second patient with extrauterine disease received adjuvant pelvic radiation followed by chemotherapy. CONCLUSIONS: The diagnosis of pPNET of the uterus may be a challenge. Features of diagnostic significance include positive staining with neuron-specific enolase, presence of neurosecretory granules, and positive staining with the MIC-2 gene. Currently, there is no uniformity in the treatment of these cases since the majority of the patients reported to date have had surgery, chemotherapy, and/or radiation therapy.
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Tumores Neuroectodérmicos Periféricos Primitivos/patología , Neoplasias Uterinas/patología , Anciano , Femenino , Humanos , Tumores Neuroectodérmicos Periféricos Primitivos/terapia , Neoplasias Uterinas/terapiaRESUMEN
We previously reported that prostate derived Ets transcription factor (PDEF) is a breast tumor-associated molecule. To obtain further insights into PDEF expression in other human tumor types, a cDNA library database from human adult normal and tumor tissues was compiled and searched for PDEF distribution. The results showed that PDEF is present at relative higher frequencies in the cDNA libraries from brain, breast, lung and ovarian tumors in comparison to those from the corresponding normal tissues. RT/PCR analysis of PDEF expression in ovarian tumors confirmed that PDEF is expressed in 36 out of 51 (71%) ovarian tumors. Further comparison of the distribution of PDEF with other widely recognized cancer-associated molecules showed that PDEF has more restricted distributions than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin and telomerase in cDNA libraries from brain (except survivin), breast, lung and ovarian tumors. These data together show a better tumor-association for PDEF and suggest that PDEF is a more suitable target for developing specific cancer therapies.
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Proteínas Proto-Oncogénicas/metabolismo , Factores de Transcripción/metabolismo , ADN Complementario/genética , Bases de Datos Factuales , Femenino , Biblioteca de Genes , Humanos , Masculino , Neoplasias Ováricas , Ovario , Próstata , Unión Proteica , Proteínas Tirosina Quinasas/aislamiento & purificación , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/aislamiento & purificación , Proteínas Proto-Oncogénicas c-ets , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/aislamiento & purificaciónRESUMEN
OBJECTIVE: The aim of this study was to determine the strength of the correlation between colposcopic impression and biopsy histology. METHODS: In an urban referral clinic, colposcopy and directed biopsy were performed between July 1, 1996, and December 31, 1999, by residents supervised by board-certified attending obstetrician-gynecologists. Impression and biopsy were graded as benign, suggesting condyloma or koilocytosis, cervical intraepithelial neoplasia (CIN) grades 1-3, or cancer. The significance of association was assessed by chi(2) testing and the strength by kappa statistics. RESULTS: Colposcopies were performed on 2825 women, with colposcopic impression and biopsy grade known for 2112. Exact agreement was found in only 893 (37%) women, but results agreed within one grade in 1203 (75%). The association between impression and histology was significant (P < 0.001), but the strength of the correlation was poor (0.20). The positive predictive value of any colposcopic abnormality for any histologic abnormality was 80%. The negative predictive value of a benign colposcopic impression was 68%. The sensitivity of colposcopy with a threshold of any lesion detected was 89%, and the specificity was 52%. The sensitivity for CIN 2/3 was 56%. CONCLUSION: Colposcopy is imprecise, although useful in estimating lesion grade. Management decisions require biopsy.
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Biopsia/métodos , Colposcopía/métodos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Displasia del Cuello del Útero/patologíaRESUMEN
OBJECTIVE: To enhance the yield of endocervical curettage (ECC) by defining risks for abnormality. STUDY DESIGN: Demographic and medical information collected at colposcopy and subsequent histology were reviewed retrospectively. Statistical analysis was by t and chi 2 tests. RESULTS: Among 2,287 women undergoing ECC at colposcopy, in only 105 (5%) did positive ECC require excisional therapy that would not otherwise have been recommended. Women with positive ECC were older (mean, 39.0 vs. 33.2 years; P < .001) and of higher parity (mean, 3.0 vs. 2.0 births; P < .001), with earlier first intercourse (at 16.6 vs. 17.2 years, P = .006), more unsatisfactory colposcopy (148 [27%] of 545 women with unsatisfactory colposcopy vs. 183 [12%] of 1,523 women with satisfactory colposcopy; P < .001) and more colposcopic impressions of cervical intraepithelial neoplasia (CIN) 2-3 (163 [51%] of 323 vs. 443 [25.6%] of 1,730 women with low grade or a negative impression; P < .001). The likelihood of missed CIN 2-3 was 0.4%, with no missed cancers among women with satisfactory colposcopy and either a normal colposcopic impression (1/254) or nulliparity (2/474). CONCLUSION: ECC identifies otherwise-undetected preinvasive and invasive lesions but may be avoided in women with satisfactory colposcopy who are nulliparous or have no colposcopic lesions.
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Colposcopía/métodos , Dilatación y Legrado Uterino/estadística & datos numéricos , Anamnesis/estadística & datos numéricos , Selección de Paciente , Lesiones Precancerosas/patología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Distribución por Edad , Biopsia con Aguja , Estudios de Cohortes , Dilatación y Legrado Uterino/métodos , Femenino , Humanos , Persona de Mediana Edad , Prevalencia , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/epidemiología , Displasia del Cuello del Útero/epidemiologíaRESUMEN
Cell viability, autolysis and lipolysis were studied in Cheddar cheese made using Lactococcus lactis subsp. cremoris AM2 or Lactococcus lactis subsp. cremoris HP. Cheddar cheese was made in triplicate over a 3 month period and ripened for 238 days at 8 degrees C. Cell viability in cheese was lower for AM2 (a non-bitter strain) than for strain HP (a bitter strain). Autolysis, monitored by the level of the intracellular marker enzyme, lactate dehydrogenase (EC 1.1.1.27) in cheese 'juice' extracted by hydraulic pressure, was much greater in the cheese made using AM2 than that made with HP. Lipolysis was determined by the increase during ripening of individual free fatty acids (FFA) from butyric (C4:0) to linolenic acid (C18:3) measured using a high performance liquid chromatographic technique. Levels of individual FFA from butyric (C4:0) to linolenic (C18:3) acids increased significantly (P<0.05) during ripening in cheeses made with either starter culture. Palmitic (C16:0) and oleic (C18:1) acids were the most abundant FFA throughout ripening in all cheeses. Levels of caprylic (C8:0), myristic (C14:0), palmitic (C16:0) and stearic (C18:0) acids were significantly higher (P<0.05) in cheeses manufactured with Lc. lactis subsp. cremoris AM2 than in cheeses manufactured with Lc. lactis subsp. cremoris HP. Differences in levels of lipolysis between strains was not due to differences in the specific lipolytic or esterolytic activities in cell free extracts of the strains as measured by activity on triolein (lipase) and p-nitrophenylbutyrate (esterase) substrates. Therefore, evidence is provided for a relationship between the extent of starter cell autolysis and the level of lipolysis during Cheddar cheese ripening.