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BACKGROUND: Chemotherapy-induced alopecia (CIA) is a common and emotionally-taxing side effect of chemotherapy, including taxane agents used frequently in treatment of gynecologic cancers. Scalp hypothermia, also known as "cold caps", is a possible method to prevent severe CIA, studied primarily in the breast cancer population. OBJECTIVES: To compile existing data on scalp hypothermia in cancer patients receiving taxane chemotherapy in order to investigate its application to the gynecologic cancer population. SEARCH STRATEGY: MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and Cochrane were searched through January 31, 2023. SELECTION CRITERIA: Full-text manuscripts reporting on the results of scalp hypothermia in patients receiving taxane-based chemotherapy. DATA COLLECTION AND ANALYSIS: Binomial proportions were summed, and random-effects meta-analyses performed. MAIN RESULTS: From 1424 records, we included 31 studies, representing 14 different countries. Only 5 studies included gynecologic cancer patients. We extracted the outcome of the proportion of patients with <50% hair loss. Among 2179 included patients, 60.7% were reported to have <50% hair loss (meta-analysis: 60.6%, 95% confidence interval [CI] 54.9-66.1%). Among the 28 studies reporting only on taxane-based chemotherapy, the rate of <50% hair loss was 60.0% (meta-analysis: 60.9%, (95% CI: 54.9-66.7%). In comparative studies, hair loss was significantly less in patients who received scalp hypothermia versus those who did not (49.3% versus 0% with <50% hair loss; OR 40.3, 95% CI: 10.5-154.8). Scalp cooling achieved <50% hair loss in patients receiving paclitaxel (67.7%; meta-analysis 69.9%, 95% CI 64.1-75.4%) and docetaxel (57.1%; meta-analysis 60.5%, 95% CI 50.0-71.6%). Meta-analysis on patient satisfaction in regard to scalp cooling found a satisfaction rate of 78.9% (95% CI 69.1-87.4%). CONCLUSION: Scalp hypothermia may be an effective method to reduce some cases of CIA due to taxane chemotherapy, especially paclitaxel. More trials need to be done to determine the precise effects of scalp hypothermia in gynecologic cancer patients.
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OBJECTIVE: The treatment for high risk or recurrent gestational trophoblastic neoplasia (GTN) is a highly toxic multi-agent chemotherapy. For patients with progressive or recurrent GTN, checkpoint inhibitors have demonstrated anti-tumor activity; however, identification of novel therapies for GTN remain an unmet need. Therefore, we sought to characterize the molecular landscape of GTN to identify potential therapeutic targets. METHODS: GTN samples were analyzed using a combination of molecular - next-generation sequencing (NGS) or whole exome sequencing (WES)- and protein- Immunohistochemistry (IHC) analyses. GTN samples encompassed complete moles, choriocarcinoma, epithelioid trophoblastic tumors (ETT), and placental site trophoblastic tumors (PSTT). RESULTS: We analyzed 30 cases of GTN including 15 choriocarcinoma, 7 ETT, 5 PSTT, 1 invasive mole and 2 mixed histologies. The median age was 41.5. GTN samples were found to be PD-L1 positive (92.3%), tumor mutational burden (TMB) low (92.8%), and microsatellite stable (MSS) (100%). Forty-six percent of choriocarcinoma specimens contained a genomic alteration including TP53 (33%) and homologous recombination repair (HRR) (13%) genes. Alterations in RTK-RAS pathway signaling was present in 40% of ETT cases. CONCLUSIONS: The high rate of PD-L1 positivity in this real-world database and reported in prior literature support continued clinical trial development evaluating immunotherapy for treatment of GTN. Other potential targeted treatments identified include Wee1, PARP and MEK inhibitors based on molecular alterations in TP53, HRR genes, and RTK-RAS pathways respectively.
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Doença Trofoblástica Gestacional , Humanos , Feminino , Doença Trofoblástica Gestacional/genética , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/patologia , Adulto , Gravidez , Pessoa de Meia-Idade , Sequenciamento do Exoma , Sequenciamento de Nucleotídeos em Larga Escala , Terapia de Alvo Molecular/métodos , Antígeno B7-H1/genética , Antígeno B7-H1/antagonistas & inibidores , Adulto Jovem , Coriocarcinoma/genética , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologiaRESUMO
OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.
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Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: To determine the clinical and prognostic significance of CA-125 trends prior to, during, and after chemotherapy in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients were enrolled in a phase III randomized trial (GOG 157) following upfront surgery for grade 3 stage IA/IB, stage IC, or stage II disease, and had been treated with either three or six cycles of carboplatin/paclitaxel. Kaplan-Meier method and Cox proportional hazards model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 350 patients, the median pre-chemotherapy CA-125 was 65 (IQR: 31-129). 71% of Whites had an elevated CA-125 compared to 47% of non-Whites (p = 0.006). Following the first cycle of chemotherapy, 74% of those with elevated CA-125 had normalization. Those who had normalization of CA-125 after 1 cycle had significantly better 5-year RFS (81% vs. 65%, p = 0.003) and OS (87% vs. 75%, p = 0.009) compared to those who did not normalize (defined as ≤35 U/mL). The pattern of CA-125 change following chemotherapy cycle 1, from normal to normal vs. elevated to normal vs. elevated to elevated had corresponding RFS of 87% vs. 80% vs. 68% (p = 0.013), and OS of 92% vs. 88% vs. 77% (p = 0.009). However, the percent decline (p = 0.993) and absolute nadir normal value of CA-125 (0-10 vs. 11-35 U/mL) were not predictive of outcome (p = 0.4). CONCLUSIONS: Normal baseline CA125 and normalization of this biomarker after the first cycle of chemotherapy were associated with better survival in high-risk early-stage epithelial ovarian cancer patients.
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Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Antígeno Ca-125 , Carboplatina , PaclitaxelRESUMO
PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
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Recidiva Local de Neoplasia/patologia , Nomogramas , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Neoplasias do Colo do Útero/cirurgiaRESUMO
To identify the differentiating features in clinical presentation, management, and maternal/fetal outcome in complete hydatidiform mole and coexistent fetus compared with placental mesenchymal dysplasia. Between 1997 and 2015, five women with complete hydatidiform mole and coexistent fetus and four women with placental mesenchymal dysplasia were managed at the University of California San Francisco. Clinical features were analyzed and compared with previously published data. Of the five cases of complete hydatidiform mole and coexistent fetus, two had live births. ß-hCG levels were > 200,000 IU/L in all cases. On imaging, a clear plane between the cystic component and the placenta favored a diagnosis of complete hydatidiform mole and coexistent fetus. None of the patients went on to develop gestational trophoblastic neoplasia (GTN), with a range of follow-up from 2 to 38 months. Combining this data with previously published work, the live birth rate in these cases was 38.8%, the rate of persistent GTN was 36.2%, and the rate of persistent GTN in patients with reported live births was 27%. Of the four cases of placental mesenchymal dysplasia, all four had live births. One patient developed HELLP syndrome and intrauterine growth restriction; the remaining three were asymptomatic. Maternal symptoms, fetal anomalies, ß-hCG level, and placental growth pattern on imaging may help differentiate between complete hydatidiform mole and coexistent fetus and placental mesenchymal dysplasia. There was not an increased risk of gestational trophoblastic neoplasia in patients with complete hydatidiform mole and coexistent fetus who opted to continue with pregnancy.
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OBJECTIVE: Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology. METHODS: Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (relative risk (RR)=30-60), RAD51C (RR=5.0), or ATM (RR=1.5-2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ2 testing for statistical analyses, comparing results according to mutation type and demographic information. RESULTS: A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, and 40% would perform a risk reducing salpingo-oophorectomy prior to menopause in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. For the postmenopausal woman, 98%, 85%, and 42% would proceed with risk reducing salpingo-oophorectomy in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. Response distribution for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes (p<0.001). CONCLUSIONS: Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a BRCA1, RAD51C, and ATM mutation, earlier and more frequently in the setting of a BRCA1 mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.
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Carcinoma Epitelial do Ovário/prevenção & controle , Ginecologia/métodos , Neoplasias Ovarianas/prevenção & controle , Adulto , Fatores Etários , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma Epitelial do Ovário/genética , Proteínas de Ligação a DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Padrões de Prática Médica/estatística & dados numéricos , Fatores de Risco , Salpingo-Ooforectomia/estatística & dados numéricos , Inquéritos e Questionários , Ubiquitina-Proteína LigasesRESUMO
In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of preterm delivery, hemorrhage, and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The messenger RNA (mRNA) encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly up-regulated molecule in PAS samples. Overexpression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up-regulate a cancer-like proinvasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.
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Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Regulação da Expressão Gênica , Placenta Acreta/metabolismo , Trofoblastos/metabolismo , Regulação para Cima , Feminino , Humanos , Miométrio , Placenta/patologia , Placenta Acreta/genética , Placenta Acreta/patologia , Pré-Eclâmpsia , Gravidez , Transcriptoma , Útero/patologiaRESUMO
OBJECTIVE: To assess the frequency of chromosome testing after first trimester miscarriage as well as to investigate patient experiences. STUDY DESIGN: An anonymous online questionnaire was developed and made available. Inclusion criteria were female, age ≥ 18, first trimester miscarriage, occurrence of miscarriage within the past year, miscarriage care provided in the United States, and survey completion. RESULTS: Of the 980 women who started the survey, 448 met inclusion criteria. Of those, 37 participants had chromosome testing on the miscarriage specimen. Of those who did not have testing, 66% said they wished they had done so at the time of miscarriage, and 67% said they would still want testing if it were available today. There was no correlation between patient age and chromosome testing. Chromosome testing increased in frequency with higher number of miscarriages, although the low number of women with chromosome testing limits our ability to draw definitive conclusions. On average, providers needed to spend 15-20 minutes with patients for them to feel like it was "enough time." CONCLUSION: In this national survey we found that chromosome testing is performed in approximately 8% of first trimester miscarriages. Our data indicate that the majority of patients experiencing first trimester miscarriage desire chromosome testing.
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Aborto Espontâneo/genética , Cariotipagem/estatística & dados numéricos , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Etnicidade , Feminino , Idade Gestacional , Humanos , Masculino , Gravidez , Primeiro Trimestre da Gravidez , Inquéritos e Questionários , Estados UnidosRESUMO
â¢Pericardial effusion may be present early in the disease process in patients with ovarian cancer.â¢Even a small pericardial effusion may become clinically apparent in the setting of concomitant pleural effusion(s).â¢Cardiac tamponade should be considered in the differential diagnosis of postoperative hemodynamic instability to facilitate timely intervention.
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OBJECTIVE: Although omentectomy is part of the staging and treatment of epithelial ovarian cancer (EOC), its performance in a patient with a grossly normal omentumacknowledging its role in debulking gross tumor depositshas never been definitively shown to improve survival. METHODS/MATERIALS: Using Surveillance, Epidemiology, and End Results data from 1998 to 2010, we identified patients with EOC and assessed their age, race, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, lymph node dissection, nodal findings, and performance of omentectomy. We compared disease-specific survival (DSS) based on the presence or absence of omentectomy using log-rank univariate analysis, Cox multivariate analysis, and Kaplan-Meier survival curves. RESULTS: A total of 20,975 patients with invasive EOC underwent surgical treatment. Initial univariate analysis indicated a lower mean DSS with performance of omentectomy. However, multivariate analysis demonstrated no significant association between DSS and performance of omentectomy (hazard ratio, 0.978; P = 0.506). The DSS was improved if lymphadenectomy was performed (hazard ratio, 0.60; P < 0.001). In recent years, there was a trend toward decreased performance of omentectomy.To look specifically at patients without bulky omental disease, a subset analysis was done looking at patients with stage I-IIIA disease who had had lymphadenectomy performed. There were 5454 patients in the group who underwent an omentectomy and 2404 patients in the group who did not. No difference in DSS was seen between the groups based on performance of omentectomy (P = 0.89). However, the analysis was limited by the lack of Surveillance, Epidemiology, and End Results data on the extent of omentectomy, amount of residual disease, and adjuvant chemotherapy. CONCLUSIONS: In this analysis, performance of omentectomy in patients with EOC without bulky disease (≤stage IIIA) did not seem to confer improvement in survival. A randomized control trial would be needed to fully address this question.
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Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Omento/cirurgia , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Programa de SEER , Taxa de Sobrevida , Adulto JovemRESUMO
Insulin causes the exocytic translocation of GLUT4 glucose transporters to stimulate glucose uptake in fat and muscle. Previous results support a model in which TUG traps GLUT4 in intracellular, insulin-responsive vesicles termed GLUT4 storage vesicles (GSVs). Insulin triggers TUG cleavage to release the GSVs; GLUT4 then recycles through endosomes during ongoing insulin exposure. The TUG C terminus binds a GSV anchoring site comprising Golgin-160 and possibly other proteins. Here, we report that the TUG C terminus is acetylated. The TUG C-terminal peptide bound the Golgin-160-associated protein, ACBD3 (acyl-CoA-binding domain-containing 3), and acetylation reduced binding of TUG to ACBD3 but not to Golgin-160. Mutation of the acetylated residues impaired insulin-responsive GLUT4 trafficking in 3T3-L1 adipocytes. ACBD3 overexpression enhanced the translocation of GSV cargos, GLUT4 and insulin-regulated aminopeptidase (IRAP), and ACBD3 was required for intracellular retention of these cargos in unstimulated cells. Sirtuin 2 (SIRT2), a NAD(+)-dependent deacetylase, bound TUG and deacetylated the TUG peptide. SIRT2 overexpression reduced TUG acetylation and redistributed GLUT4 and IRAP to the plasma membrane in 3T3-L1 adipocytes. Mutation of the acetylated residues in TUG abrogated these effects. In mice, SIRT2 deletion increased TUG acetylation and proteolytic processing. During glucose tolerance tests, glucose disposal was enhanced in SIRT2 knock-out mice, compared with wild type controls, without any effect on insulin concentrations. Together, these data support a model in which TUG acetylation modulates its interaction with Golgi matrix proteins and is regulated by SIRT2. Moreover, acetylation of TUG enhances its function to trap GSVs within unstimulated cells and enhances insulin-stimulated glucose uptake.
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Adipócitos/metabolismo , Proteínas de Transporte/fisiologia , Cistinil Aminopeptidase/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Sirtuína 2/metabolismo , Células 3T3-L1 , Acetilação , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Animais , Western Blotting , Membrana Celular/metabolismo , Células Cultivadas , Cistinil Aminopeptidase/genética , Citoplasma/metabolismo , Citometria de Fluxo , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Humanos , Imunoprecipitação , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transporte Proteico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 2/genéticaRESUMO
OBJECTIVE: This article reviews the literature concerning the function of the omentum and how omentectomy came to be part of the staging and treatment of epithelial ovarian cancer. METHODS: A review of the English language literature based on a MEDLINE (PubMed) database search using the key words: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers. RESULTS: Descriptions of the omentum can be found as far back as the time of the ancient Egyptians. An immunologic role of the omentum was confirmed in 1980s when "milky spots" were described. Omentectomy arrived as part of the ovarian cancer guidelines in the 1960s after observing that the omentum was a frequent site of metastasis and that patients with removal of all diseased tissue did better. The exact role of the omentum in immunology and cancer remains incompletely understood. CONCLUSIONS: Historically, occult omental metastases in otherwise early disease have led to the inclusion of omentectomy for the purpose of accurate staging and for a possible therapeutic benefit. Laboratory studies on the role in cancer of the omental fat and milky spots are controversial.
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Neoplasias Epiteliais e Glandulares/cirurgia , Omento/fisiologia , Omento/cirurgia , Neoplasias Ovarianas/cirurgia , Animais , Carcinoma Epitelial do Ovário , Modelos Animais de Doenças , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Omento/patologia , Neoplasias Ovarianas/patologiaRESUMO
OBJECTIVE: This article reviews the literature concerning the role of omentectomy in the staging and treatment of clinically apparent early stage epithelial ovarian cancer. METHODS: A review of the English language literature based on a MEDLINE (PubMed) database search using the keywords: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers. RESULTS: Historically, the realization that ovarian cancer cells have a predisposition to metastasize to the omentum has led to the inclusion of omentectomy, both for the purpose of accurate staging of ovarian cancer and for its possible therapeutic benefit. In apparently early stage epithelial ovarian cancer, microscopic disease in the omentum is found in 0-22% of the cases; however extra-ovarian disease isolated to the omentum is found in 2-7% of cases at most. There are no specific guidelines as to how much of the omentum should be removed, but pathology studies show that for the purpose of staging and detecting microscopic disease, omental biopsies are probably sufficient in a grossly normal appearing omentum. In cases where adjuvant chemotherapy is planned, the role of omentectomy appears to be primarily for staging, while its therapeutic role remains unclear in microscopic omental disease. CONCLUSIONS: In apparent early stage ovarian cancer, the presence of isolated omental metastases is relatively rare. For staging purposes in such cases, random omental biopsies rather than total omentectomy may suffice. Furthermore, chemotherapy appears to effectively treat microscopic disease and therefore if this is already planned the benefit of omentectomy is unclear.
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Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Omento/patologia , Omento/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Animais , Biópsia , Carcinoma Epitelial do Ovário , Feminino , Humanos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Degenerating myomas are common explanations for pain associated with abdominal masses in pregnancy. However, masses arising from other pelvic organs should be included in the differential diagnosis. CASE: We present a case of an abdominal mass in pregnancy that was originally misdiagnosed as a uterine leiomyoma. Attention to the patient's history along with judicious use of imaging modalities led to the correct diagnosis of urachal duct carcinoma. This was treated appropriately and resulted in a term vaginal delivery. We present a review of the literature on this tumor and its management in pregnancy. CONCLUSION: Urologic malignancies are rare but should be considered in the differential diagnosis for any woman presenting with pain and an abdominal mass in pregnancy. A multidisciplinary approach optimizes outcomes.
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Carcinoma de Células Escamosas/diagnóstico , Leiomioma/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Úraco/diagnóstico por imagem , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Anamnese , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/cirurgia , Ultrassonografia , Úraco/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
To promote glucose uptake into fat and muscle cells, insulin causes the translocation of GLUT4 glucose transporters from intracellular vesicles to the cell surface. Previous data support a model in which TUG traps GLUT4-containing vesicles and tethers them intracellularly in unstimulated cells and in which insulin mobilizes this pool of vesicles by releasing this tether. Here we show that TUG undergoes site-specific endoproteolytic cleavage, which separates a GLUT4-binding, N-terminal region of TUG from a C-terminal region previously suggested to bind an intracellular anchor. Cleavage is accelerated by insulin stimulation in 3T3-L1 adipocytes and is highly dependent upon adipocyte differentiation. The N-terminal TUG cleavage product has properties of a novel 18-kDa ubiquitin-like modifier, which we call TUGUL. The C-terminal product is observed at the expected size of 42 kDa and also as a 54-kDa form that is released from membranes into the cytosol. In transfected cells, intact TUG links GLUT4 to PIST and also binds Golgin-160 through its C-terminal region. PIST is an effector of TC10α, a GTPase previously shown to transmit an insulin signal required for GLUT4 translocation, and we show using RNAi that TC10α is required for TUG proteolytic processing. Finally, we demonstrate that a cleavage-resistant form of TUG does not support highly insulin-responsive GLUT4 translocation or glucose uptake in 3T3-L1 adipocytes. Together with previous results, these data support a model whereby insulin stimulates TUG cleavage to liberate GLUT4 storage vesicles from the Golgi matrix, which promotes GLUT4 translocation to the cell surface and enhances glucose uptake.
Assuntos
Adipócitos/metabolismo , Proteínas de Transporte/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Proteínas de Transporte/genética , Glucose/farmacocinética , Transportador de Glucose Tipo 4/genética , Complexo de Golgi/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Immunoblotting , Insulina/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Microscopia de Fluorescência , Dados de Sequência Molecular , Mutação , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Interferência de RNA , Homologia de Sequência de AminoácidosRESUMO
Biomineralization has mostly been studied in the class Anthozoa (Phylum Cnidaria), but very little is known about the evolution of the calcified skeleton in the class Hydrozoa or about the processes leading to its formation. The evolution of the calcified skeleton is here investigated in the hydrozoan family Hydractiniidae. A phylogenetic analysis of ribosomal, mitochondrial, and nuclear-protein-coding DNA sequences supported two independent origins of the calcified skeleton within the Hydractiniidae and indicates a case of parallel evolution, as suspected in the Anthozoa. Neither of the two origins of skeleton in the Hydractiniidae has led to either speciose or numerically abundant species, in contrast with other skeletonized hydrozoan families. Finally, we show that the origin of calcified skeletons in the Hydractiniidae is significantly correlated with the distribution of species with calcium carbonate granules within a polyp's gastrodermal cells. This suggests that the presence of these granules precedes the origin of a full skeleton.
Assuntos
Carbonato de Cálcio/metabolismo , Evolução Molecular , Hidrozoários/genética , Hidrozoários/metabolismo , Filogenia , Animais , Calcificação Fisiológica/genética , Calcificação Fisiológica/fisiologia , DNA/genética , Minerais , Análise de Sequência de DNARESUMO
Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.