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2.
Int J Gynecol Cancer ; 29(1): 53-59, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640684

RESUMO

OBJECTIVE: To identify factors that affect successful adaptation of sentinel lymph node mapping and those that lead to unintended adipose-only sentinel lymph node identification. METHODS: Surgical and pathological data were prospectively collected on patients with endometrial cancer who underwent sentinel lymph node mapping with indocyanine green with or without pelvic and/or para-aortic lymph node dissection between November 2013 and April 2017. All mapping cases were performed with the robotic system. Adipose-only specimens were defined as a sentinel lymph node without a pathologically identified lymph node after ultrastaging. RESULTS: A total of 202 patients were included: 83% had endometrioid pathology, 12% serous, 3% carcinosarcoma, and 2% clear cell, with mixed pathology noted in 2%. The bilateral sentinel lymph node detection rate was 66%, and the rate of mapping at least a unilateral sentinel lymph node was 86%. Neither the bilateral nor the unilateral sentinel lymph node mapping rate changed with increased surgeon experience. The rate of adipose-only sentinel lymph node identification was more frequent when comparing the first 10 cases (37%), cases 11 - 30 (28%), and > 30 cases (9%) (P = 0.006). Body mass index > 30 kg/m2, uterine fibroids, The International Federation of Gynecology and Obstetrics (FIGO) grade, and histology were not found to have a statistically significant impact on either sentinel lymph node identification or adipose-only sentinel lymph node identification. Adipose-only sentinel lymph nodes were more likely with increased time from cervical injection to identification of the sentinel lymph node in the right hemipelvis. The median range was 28 min (14-73) for true sentinel lymph node identification vs 33 min (23-74) for adipose-only sentinel lymph node identification (P = 0.02). CONCLUSION: Patient and surgeon factors did not impact the identification of sentinel lymph nodes over time. Adipose-only sentinel lymph nodes were more frequently identified in the initial cases and represent a potential complication to adapting sentinel lymph node biopsy without lymphadenectomy. The increase in adipose-only sentinel lymph node identification that was associated with time from cervical injection may represent delayed or disrupted uptake of indocyanine green.


Assuntos
Tecido Adiposo/patologia , Algoritmos , Neoplasias do Endométrio/patologia , Verde de Indocianina , Linfonodo Sentinela/patologia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Tecido Adiposo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Corantes , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Histerectomia , Excisão de Linfonodo , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos , Linfonodo Sentinela/cirurgia
3.
Stat Biosci ; 9(1): 1-12, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28966695

RESUMO

Despite improvements in operative management and therapies, overall survival rates in advanced ovarian cancer have remained largely unchanged over the past three decades. Although it is possible to identify high-risk patients following surgery, the knowledge does not provide information about the genomic aberrations conferring risk, or the implications for treatment. To address these challenges, we developed an integrative pathway-index model and applied it to messenger RNA expression from 458 patients with serous ovarian carcinoma from the Cancer Genome Atlas project. The biomarker derived from this approach, IPI59, contains 59 genes from six pathways. As we demonstrate using independent datasets from six studies, IPI59 is strongly associated with overall and progression-free survival, and also identifies high-risk patients who may benefit from enhanced adjuvant therapy.

4.
Int J Gynecol Cancer ; 18(6): 1194-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18217964

RESUMO

The goal of this study was to determine the factors associated with response to platinum retreatment in patients with platinum-resistant ovarian cancer. A review of patients with epithelial ovarian cancer retreated with cisplatin or carboplatin between 2002 and 2004 was performed. The platinum-free interval (PFI) and treatment-free interval (TFI) were determined for each patient. Response was based on serial CA125 levels using a modification of the Rustin criteria. Patients with clinical benefit ([CB] those who attained at least stable disease) were compared to patients with disease progression (PD). An analysis was performed to determine factors associated with CB in platinum-resistant patients retreated with platinum. Of 48 patients identified, 37 were evaluable included in this analysis. CB was observed in 27 (73%) while disease progression was noted in 10 (27%) women. The PFI was longer in those women who achieved CB (12.3 vs 6.9 months; P = 0.02). The TFI was 7.1 months for patients benefited from platinum retreatment vs 3.5 months for those with disease progression (P = 0.06). There was no statistically significant difference in the number of cytotoxic agents between the time of platinum retreatment and the prior platinum regimen (2 vs 1.5 months; P = 0.61). A prolonged PFI was associated with an improved chance of achieving CB with platinum retreatment. There was no association between the response to platinum retreatment and the number of intervening cytotoxic agents utilized. Further prospective study is warranted to define the optimal timing of platinum retreatment.


Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Compostos de Platina/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Prognóstico , Proteínas/metabolismo , Falha de Tratamento
5.
Int J Gynecol Cancer ; 18(3): 400-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17645510

RESUMO

While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3-5 toxicities occurred in 15 (24%) patients, including grade 3-4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3-5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy.


Assuntos
Anemia/induzido quimicamente , Anticorpos Monoclonais/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Neoplasias Ovarianas/patologia , Adulto , Idoso , Análise de Variância , Anemia/epidemiologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Modelos Logísticos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neutropenia/epidemiologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Ovariectomia , Valor Preditivo dos Testes , Probabilidade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
6.
Int J Gynecol Cancer ; 16(2): 562-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16681726

RESUMO

The purpose of this study was to evaluate gene expression patterns in human cervical tumors by extent of lymph node metastases at diagnosis. Pretreatment whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging was performed in eight patients with invasive squamous cell carcinoma of the cervix to evaluate the extent of lymph nodes metastases. Pretreatment tumor tissue samples were subjected to laser-capture microdissection, and isolated RNA was linearly amplified and hybridized to Affymetrix Human U95A GeneChip microarrays. Molecular FDG-PET imaging revealed that three patients had lymph node involvement in the supraclavicular region and five patients did not. Microarray data were segregated into two groups based on the extent of regional lymph node involvement. Supervised clustering analysis identified 75 of about 12,000 gene transcripts represented on the array whose average expression was at least threefold different. We identified 12 of the 75 transcripts that demonstrated a statistically significant difference in expression between the two patient groups (P < 0.05). Five transcripts were upregulated and seven downregulated. Both overall and cause-specific survivals were different between these two patient groups (P= 0.006). This limited data set identified candidate biomarkers of extent of lymph node metastases that correlated with poor survival outcome.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Neoplasias/genética , Neoplasias do Colo do Útero/genética , Adulto , Carcinoma de Células Escamosas/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Neoplasias do Colo do Útero/diagnóstico por imagem
7.
Oncogene ; 25(39): 5436-45, 2006 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-16607278

RESUMO

POU2F3 (OCT11, Skn-1a) is a keratinocyte-specific POU transcription factor whose expression is tied to squamous epithelial stratification. It is also a candidate tumor suppressor gene in cervical cancer (CC) because it lies in a critical loss of heterozygosity region on 11q23.3 in that cancer, and its expression is lost in more than 50% of CC tumors and cell lines. We now report that the loss of POU2F3 expression is tied to the hypermethylation of CpG islands in the POU2F3 promoter. Bisulfite sequencing analysis revealed that methylation of specific CpG sites (-287 to -70 bp) correlated with POU2F3 expression, which could be reactivated with a demethylating agent. Combined bisulfite restriction analysis revealed aberrant methylation of the POU2F3 promoter in 18 of 46 (39%) cervical tumors but never in normal epithelium. POU2F3 expression was downregulated and inversely correlated with promoter hypermethylation in 10 out of 11 CC cell lines. Immunohistochemical analysis on a cervical tissue microarray detected POU2F3 protein in the epithelium above the basal layer. As the disease progressed, expression also decreased, especially in invasive squamous cell cancer (70% loss). Thus, aberrant DNA methylation of the CpG island in POU2F3 promoter appears to play a key role in silencing this gene expression in human CC. The results suggested that POU2F3 might be one of the CC-related tumor suppressor genes, which are disrupted by both epigenetic and genetic mechanisms.


Assuntos
Proteínas de Homeodomínio/genética , Fatores do Domínio POU/genética , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/genética , Adenocarcinoma/genética , Biópsia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Metilação de DNA , Primers do DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Genes Supressores de Tumor , Genoma Humano , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento por Restrição
8.
Surg Endosc ; 18(9): 1331-4, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15803231

RESUMO

BACKGROUND: We assessed the feasibility of outpatient laparoscopic splenectomy, as performed by an experienced laparoscopic term and combined with optimal anesthesia. METHODS: Inclusion criteria in the study was limited to patients not hospitalized before the procedure who had hematological or neoplastic indications for splenectomy and were classified as American Society of Anesthesiologists (ASA) I-III. They received general intravenous anesthesia with propofol and remifentanil and were given keterolac, propacetamol, droperidol, and ondansetron as prophylaxis against postoperative pain and nausea. Laparoscopic splenectomy was performed via three trocars. The specimen was removed via an incision in the left iliac fossa. RESULTS: Ten of the 12 patients were discharged 3-6 h postoperatively; the other two were admitted primarily to hospital. One was readmitted due to a fever, which was finally explained by measles. The median operative times was 58 min (range, 45-135). Patient satisfaction was excellent in nine and intermediate in two cases; it was poor in one case, due to postoperative pain. CONCLUSION: Laparoscopic splenectomy can be completed in a relatively short time; therefore, it is feasible, safe, and satisfactory for most patients as an outpatient procedure.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Laparoscopia/efeitos adversos , Satisfação do Paciente , Esplenectomia/efeitos adversos , Esplenectomia/métodos , Adolescente , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança
9.
Gynecol Oncol ; 91(2): 318-25, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14599861

RESUMO

OBJECTIVES: This Phase II, multicenter, open-label study was conducted to assess the efficacy and tolerability of ZD9331, a novel direct-acting thymidylate synthase inhibitor, in heavily pretreated patients with ovarian cancer. METHODS: The study recruited 44 women with ovarian cancer or primary peritoneal cancer previously treated with platinum therapy and paclitaxel and with progressive disease after, or intolerance to, topotecan administered as the most recent therapy. ZD9331 was administered as an intravenous infusion at 130 mg/m(2) on Days 1 and 8 of 3-week cycles, until objective evidence of disease progression. A cutoff date of 3 months after the last patient received the first dose was set for data collection. RESULTS: Patients received a mean of 3.3 cycles of ZD9331 and a total of 143 cycles were administered. Among the 42 patients evaluated for best overall tumor response, one achieved a complete response and two achieved a partial response, giving an objective tumor response rate of 7%. The complete response occurred at Day 15 of Cycle 2 in a patient receiving ZD9331 as her eighth-line therapy. Seven patients had stable disease, giving a disease control rate of 23%. Thirty-one patients (71%) had disease progression and the median time to progression was 53 days. Most patients (89%) experienced drug-related adverse events, most commonly nausea (73%), vomiting (48%), and neutropenia (50%). Six patients (14%) were withdrawn from treatment due to adverse events. CONCLUSIONS: The preliminary evidence of efficacy and acceptable tolerability of ZD9331 in this heavily pretreated population with ovarian cancer warrants further investigation, especially in a less heavily pretreated patient population.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Quinazolinas/efeitos adversos
10.
Gynecol Oncol ; 90(3): 560-5, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-13678724

RESUMO

OBJECTIVE: Low red blood cell folate levels have been associated with hypomethylation of DNA in dysplastic tissue and an increased risk for cervical intraepithelial neoplasia in human papillomavirus (HPV)-infected women. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme regulating the metabolism of folate and methionine, the important components of DNA synthesis and methylation. Two common genetic polymorphisms, causing reduced MTHFR activity, have been identified. Therefore, the goal of this study was to evaluate these MTHFR variations as risk factors for invasive cervical cancer. METHODS: To overcome the failure to properly match cases and controls that can cause false-positive inferences due to population stratification and unrecognized variables in a traditional case-control study, a family-based transmission/disequilibrium test (TDT) was used. We obtained samples from nuclear families of 102 women with invasive cervical cancer (ICC). One polymorphism was typed by a PCR-RFLP method, while a template-directed dye-terminator assay was developed for the other. RESULTS AND CONCLUSIONS: We were unable to confirm a strong association of MTHFR polymorphisms and ICC using family-based controls and a transmission/disequilibrium test. The overall results of the TDT showed chi(2) (1 df) of 0.28 (P = 0.60) for exon 4, chi(2) (1 df) of 0.81(P = 0.37) for exon 7, and chi(2) (3 df) of 2.56 (P = 0.46) for the haplotype, meaning that there was no transmission of those alleles significantly in excess of Mendelian expectations to affected women. In addition, there was no effect of these variants with increased parity or infection with high-risk-type human papillomavirus.


Assuntos
Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Neoplasias do Colo do Útero/enzimologia , Adulto , Alelos , Feminino , Humanos , Desequilíbrio de Ligação , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Polimorfismo Genético , Neoplasias do Colo do Útero/genética
11.
Ann Oncol ; 13(11): 1819-25, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12419757

RESUMO

BACKGROUND: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies. PATIENTS AND METHODS: Twenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of rubitecan at 0.75 mg/m(2)/day administered orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) administered intravenously on days 1 and 8 of a 21-day cycle. RESULTS: The MTD was defined as rubitecan 1 mg/m(2) administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m(2) administered intravenously over 30 min days 1 and 8, given every 21 days. Dose-limiting toxicity was myelosuppression including neutropenia and thrombocytopenia. Other side effects included diarrhea, nausea, vomiting and fatigue. Five patients with stable disease were observed among 18 evaluable patients. CONCLUSIONS: The recommended phase II dose is rubitecan 1 mg/m(2) given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Camptotecina/análogos & derivados , Desoxicitidina/análogos & derivados , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Biópsia por Agulha , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Metástase Linfática , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias/mortalidade , Neoplasias/patologia , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Gencitabina
12.
Gynecol Oncol ; 86(1): 62-8, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12079302

RESUMO

OBJECTIVE: MLH1 methylation is associated with the microsatellite instability (MSI) phenotype in endometrial cancer and atypical endometrial hyperplasia, a premalignant precursor to carcinoma. The observation that methylation is also seen in atypical endometrial hyperplasia without MSI suggests that methylation is an early event in endometrial tumorigenesis. Our objective was to determine if methylation is always present in MSI-positive atypical hyperplasia concomitant with MSI-positive, methylation-positive carcinoma. METHODS: We used laser capture microdissection to study MLH1 methylation and MSI in a large series of endometrial cancer cases that had previously been shown to have methylation and the MSI-high (MSI-H) phenotype. We resampled areas of carcinoma from 27 patients along with 51 foci of concomitant atypical endometrial hyperplasia. RESULTS: Consistent with previous reports, we saw MLH1 methylation in areas of atypical endometrial hyperplasia that did not show MSI. In addition, we noted that 18% of the MSI-H atypical endometrial hyperplasia DNAs lacked methylation of critical cytosines in the MLH1 promoter. Immunohistochemistry studies showed that these MSI-H unmethylated foci of atypical endometrial hyperplasia failed to express MLH1, as did regions of simple hyperplasia. CONCLUSION: Methylation of the MLH1 promoter is an early event in endometrial tumorigenesis. Given that not all MSI-positive tissues had methylation at cytosines -229 and -231, it appears that methylation may not be required for MLH1 silencing and loss of mismatch repair.


Assuntos
Metilação de DNA , Reparo do DNA , Hiperplasia Endometrial/genética , Neoplasias do Endométrio/genética , Repetições de Microssatélites/genética , Proteínas de Neoplasias/genética , Proteínas Adaptadoras de Transdução de Sinal , Pareamento Incorreto de Bases , Proteínas de Transporte , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Proteína 1 Homóloga a MutL , Proteínas de Neoplasias/biossíntese , Proteínas Nucleares , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Regiões Promotoras Genéticas
13.
Mol Pathol ; 55(3): 153-5, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12032225

RESUMO

AIMS: To investigate the involvement of the RB2/p130 gene in the pathogenesis of sporadic ovarian cancer in addition to head and neck squamous cell carcinoma (HNSCC). METHODS: Paired tumour and patient matched normal DNA samples from 43 sporadic ovarian tumours and 39 normal/tumour HNSCC DNA samples were screened. The mutation screen used polymerase chain reaction (PCR) amplification followed by single strand conformation polymorphism analysis and direct sequencing of the PCR products. Exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus) were analysed for mutations. These exons were chosen because most of the point mutations in RB2/p130 are located in the C-terminal region and mutations in these exons have been identified previously in nasopharyngeal carcinomas and primary lung tumours. RESULTS: No abnormal band shifts were seen in the samples analysed, and no bands directly sequenced revealed the presence of mutations. CONCLUSIONS: Genetic alterations in the RB2/p130 gene (exons 19-22) are unlikely to be involved directly in the pathogenesis of sporadic ovarian cancer or HNSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Mutação , Neoplasias Ovarianas/genética , Fosfoproteínas/genética , Proteínas , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Humanos , Reação em Cadeia da Polimerase/métodos , Polimorfismo Conformacional de Fita Simples , Proteína do Retinoblastoma/genética , Proteína p130 Retinoblastoma-Like
14.
Gynecol Oncol ; 83(3): 533-6, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11733967

RESUMO

OBJECTIVE: We set out to determine the factors that predict subcutaneous implanted central venous port function. Specifically, we sought to determine whether the location of the catheter tip is correlated with port failure. METHODS: A review of all gynecologic oncology patients who underwent initial port placement between 1993 and 1998 was undertaken. The initial chest radiograph following port placement was reviewed, and the venous location of the catheter tip was recorded. Patients were followed until port removal, death, or the last documentation of port function. RESULTS: Two hundred thirty-six patients underwent port placement during the study period. The majority of patients (97%) had their port placed for intravenous chemotherapy. The median time of port duration in patients with a functional port was 21.6 months. Forty of the 236 ports (17%) were removed because of device malfunction. Catheter tips were located in the central venous system in 164 (69%) cases and outside of the central venous system in 72 (31%) cases. Removal secondary to malfunction was significantly higher when the catheter tip was located outside of the central venous system (30/72 (42%) versus 10/164 (6%), P = 0.001). By life-table analysis, ports removed for malfunction with their tips located centrally had a significantly longer median duration of functional use than those whose tips were located peripherally (78 versus 44 months, P = 0.0001). CONCLUSIONS: The rate of port removal secondary to malfunction is significantly less if the catheter tip is located in the central venous system. Confirmation of the location of the catheter tip is imperative for the long-term function of a subcutaneous implanted central venous port.


Assuntos
Cateterismo Venoso Central/métodos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/normas , Falha de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico
16.
Genes Chromosomes Cancer ; 32(4): 295-301, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11746970

RESUMO

We set out to determine the relative timing of loss of DNA mismatch repair and KRAS2 mutation in endometrial tumorigenesis. We studied endometrial carcinoma (CA) and synchronous atypical endometrial hyperplasia (AEH), the premalignant precursor of endometrial cancer. Carcinoma and hyperplasia were investigated for loss of mismatch repair as evidenced by microsatellite instability (MSI) and for KRAS2 mutations. Endometrial cancers previously shown to be MSI-positive were evaluated for KRAS2 codon 12 and 13 mutations. DNA was isolated from foci of AEH concomitant with, but physically remote from, the cancers by use of tissues prepared by laser capture microdissection (LCM). The AEH DNAs were then assessed for MSI and KRAS2 mutations. Of 210 endometrial CAs investigated, 51 (26%) were MSI-positive, and among those, 21 (41%) arose concomitantly with AEH. Of 41 foci of AEH (mean, two foci per patient) investigated, 34 (83%) were MSI-positive. KRAS2 mutations were seen in 5/51 (10%) MSI-positive carcinomas. From the five patients informative for both KRAS2 mutation and MSI, 10 foci of AEH were available for investigation. All 10 AEH specimens (100%) were MSI-positive, and six (60%) had the KRAS2 mutation present in the coexisting CA. The observation that some MSI-positive AEH specimens lack the KRAS2 mutation seen in the coexisting CA supports a model in which loss of DNA mismatch repair precedes KRAS2 mutation. However, in addition to the absence of KRAS2 mutations in AEH, we discovered mutations in LCM hyperplasia and carcinoma specimens that were not present in the portion of the cancers originally investigated. These discordant genotypes suggest genetic heterogeneity in endometrial hyperplasia and concomitant cancer.


Assuntos
Pareamento Incorreto de Bases/genética , Carcinoma/genética , Reparo do DNA/genética , Neoplasias do Endométrio/genética , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Progressão da Doença , Hiperplasia Endometrial/genética , Neoplasias do Endométrio/etiologia , Feminino , Genótipo , Humanos , Fenótipo , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras
17.
Mol Pathol ; 54(4): 240-3, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11477138

RESUMO

AIMS: To investigate the possible role of mutations in the transforming growth factor beta receptor type II gene (TGFBRII) in ovarian cancer and its relation to microsatellite instability (MSI), 43 sporadic ovarian tumours were analysed for mutations over the entire coding region of the TGFBRII gene. METHODS: Mutational analysis was performed using the polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) gel analysis, and direct sequencing. MSI analysis included both mononucleotide and dinucleotide microsatellite markers used for radiolabelling and gene scanning. RESULTS: No pathogenic mutations were detected, although sequencing of the polyadenine (poly A) tract in exon 3 using conventional techniques revealed a spurious frameshift mutation that was not present in the same samples analysed using a proofreading Taq polymerase. MSI analysis demonstrated an MSI negative phenotype in 40 of the 43 tumours. None of the three MSI positive tumours demonstrated MSI for mononucleotide markers only. CONCLUSIONS: These findings suggest that: (1) MSI (both conventional and mononucleotide) is infrequent in ovarian cancer and (2) inactivation of the MSH2, MLH1, and MSH6 mismatch repair genes and TGFBR2 gene mutations do not play a major role in ovarian cancer tumorigenesis. The spurious TGFBR2 frameshift mutations detected by sequencing after conventional PCR underline the importance of confirming putative mutations in repetitive sequences by alternative methods.


Assuntos
Repetições de Microssatélites , Neoplasias Ovarianas/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Pareamento Incorreto de Bases , Análise Mutacional de DNA , Reparo do DNA , Feminino , Humanos , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo II
18.
J Am Coll Nutr ; 20(3): 247-54, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11444421

RESUMO

BACKGROUND: Fortification of cereal-grain products was introduced in 1941 when iron and three vitamins were added to flour and bread. Ready-to-eat cereals were fortified at about the same time. These fortifications have contributed to increased dietary iron intake and reductions in iron deficiency anemia in the US. In 1996, FDA finalized rules for fortification of specific enriched cereal-grain products with folic acid. This measure was instituted to increase the folate intakes of women of child-bearing age and thereby reduce the risk of having a pregnancy affected with a neural tube birth defect. However, with recent increases in fortification, public health officials in the US are concemed that excess intake of specific nutrients such as iron and folic acid may result in toxic manifestations. OBJECTIVE: Our objective was to measure iron and total folate content in breakfast cereals and compare assay to label values for % Daily Value. We also determined by weight the amount of a ready-to-eat breakfast cereal adults would eat and compared this to the labeled serving size, for which the reference amount for this cereal per eating occasion was 1 cup or 30 g. DESIGN: Twenty-nine breakfast cereals were analyzed for iron content using the bathophenanthroline reaction. Twenty-eight cereals were analyzed for total folate, utilizing a microbiological assay with tri-enzyme digestion. Serving size quantities were estimated in seventy-two adults who regularly ate breakfast cereal and were asked to fill a 16 or 22 cm round bowl with the amount of cereal that they would consume for breakfast. RESULTS: When the labeled value was compared to the assayed value for iron content 21 of the 29 breakfast cereals were 120% or more of the label value and 8 cereals were 150% or more of the label value. Overall, analyzed values for iron ranged from 80% to 190% of label values. Analyzed values for folate ranged from 98% to 320% of label values. For 14 of 28 cereals, analyzed values exceeded label declarations by more than 150%. Bran-containing cereals contained the highest amounts of folate relative to their label declarations. The median analyzed serving size for the breakfast cereal was 47 g for females, 61 g for males with a combined median of 56 g as compared to the label value of 30 g. CONCLUSIONS: Analyzed values of iron and folic acid in breakfast cereals were considerably higher than labeled values. For adults, the amount of cereal actually consumed was approximately 200% of the labeled serving size. When the quantity of cereal consumed is more than the labeled serving size and when the levels of iron and folate are higher than declared, the intake of both will be significantly greater than the labeled values. It will be important to continue monitoring serum ferritin and folate levels in NHANES IV, since daily consumption of breakfast cereals may contribute to excessive intakes of iron and folate.


Assuntos
Grão Comestível/química , Ácido Fólico/administração & dosagem , Alimentos Fortificados/análise , Ferro/administração & dosagem , Feminino , Ácido Fólico/efeitos adversos , Ácido Fólico/análise , Rotulagem de Alimentos , Humanos , Ferro/efeitos adversos , Ferro/análise , Masculino , Política Nutricional , Necessidades Nutricionais , Estados Unidos
19.
J AOAC Int ; 84(3): 805-13, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11417645

RESUMO

There is currently no official method for the analysis of fatty acids (including trans fatty acids) in infant formulas. AOAC Official Method 996.01 for Fat Analysis in Cereal Products was extended to the analysis of milk-based infant formula Standard Reference Material (SRM)1846 to determine its applicability for use with infant formulas. Following the analysis of SRM 1846, 2 infant formulas, one milk-based liquid and one soy-based powdered infant formula, were analyzed for total fatty acid composition. Fatty acid methyl esters were prepared and analyzed by gas chromatography. The results of the analysis of SRM 1846 show that the mean analyzed values were highly reproducible as indicated by low coefficients of variation (CV). The CVs were <5% for the major fatty acids. Mean analyzed values for individual fatty acids in SRM 1846 were within +/- 1 standard deviation of the certificate values. The analyzed value for total fat as triglycerides (26.27 +/- 0.25%) agreed well with the certificate value (27.1 +/- 0.59%). Analyses of infant formulas showed that the concentrations of linoleic acid and fat meet the requirements for such formulas.


Assuntos
Análise de Alimentos/métodos , Análise de Alimentos/normas , Alimentos Infantis/análise , Animais , Cromatografia Gasosa , Ácidos Graxos/análise , Humanos , Lactente , Ácidos Linoleicos/análise , Ácidos Linolênicos/análise , Leite , Padrões de Referência , Reprodutibilidade dos Testes , Glycine max , Triglicerídeos/análise
20.
Hum Pathol ; 32(5): 475-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11381364

RESUMO

We have previously demonstrated a strong relationship between loss of heterozygosity (LOH) at chromosome 11q23.3 and the presence of extensive tumor plugs in lymphvascular spaces (LVS) in stage 1B cervical carcinoma, suggesting that genes at this locus may regulate vasculoinvasion. This study examined LOH at 11q23.3 in microdissected tumor plugs within LVS and in metastatic foci in lymph nodes (MFLN), as well as corresponding invasive tumor and adjacent cervical intraepithelial neoplasia (CIN) 3 in stage 1B squamous cell carcinoma. Of 49 invasive carcinomas, 38.8% had LOH at 11q23.3. Of 36 tumor plugs in LVS, 39% had LOH at 11q23.3. Twenty percent of 15 MFLN demonstrated LOH at 11q23.3. Patients with LOH at 11q23.3 are significantly more likely to have disease recurrence than patients without LOH at 11q23.3 (P =.02). Of 10 foci of CIN 3, none showed LOH at 11q23.3. Although unlikely to have an impact early in carcinogenesis, tumor-suppressor genes located in the region of 11q23.3 appear to be important in tumor progression, facilitating lymphvascular space invasion and, by inference, spread to lymph nodes in squamous cell carcinoma of the cervix.


Assuntos
Vasos Sanguíneos/patologia , Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 11 , Perda de Heterozigosidade , Metástase Neoplásica , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/análise , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Grupos Raciais , Neoplasias do Colo do Útero/patologia
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