RESUMO
PRL-3 genomic copy number is increased in colorectal cancer (CRC), and PRL-3 expression is closely associated with lymph node and liver metastasis of CRC. However, the clinical significance of PRL-3 genomic gain for CRC remains obscure. Here, PRL-3 genomic status in 109 primary CRC tumors and in 44 CRC tumors that had metastasized to the liver, was quantified using real time PCR. Association of PRL-3 genomic status with clinicopathological factors and prognosis was assessed in detail. PRL-3 genomic gain was identified in 31 primary CRC (27.4 %) and was more frequently seen in stage III than in stage II (p = 0.025). Among the clinicopathological factors assessed, PRL-3 genomic gain was significantly associated with poorly differentiated histology (p = 0.0039). Moreover, CRC patients with PRL-3 genomic gain exhibited poorer prognosis than those with no gain in stage II-IV CRC (p = 0.017). PRL-3 genomic gain was identified in 18 (41 %) of the liver metastasis tumors, and this frequency of gain was significantly increased as compared to that of the corresponding primary CRCs (11 %) (p = 0.001). Our findings suggested that PRL-3 genomic gain may represent an aggressive phenotype of primary CRC, and may associate with liver metastasis.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Proteínas Tirosina Fosfatases/genética , Neoplasias Colorretais/mortalidade , Feminino , Dosagem de Genes , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo RealRESUMO
In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.
Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/terapia , Quimiorradioterapia/efeitos adversos , Leucemia Mieloide Aguda/etiologia , Neoplasias Hepáticas/terapia , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Ovarianas/terapia , Neoplasias das Glândulas Suprarrenais/secundário , Idoso , Neoplasias Ósseas/secundário , Carboplatina/administração & dosagem , Infarto Cerebral/etiologia , Evolução Fatal , Feminino , Humanos , Neoplasias Hepáticas/secundário , Células Neoplásicas Circulantes , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagemRESUMO
In recent years, Shimane University Hospital has begun to see patients with pelvic inflammatory disease (PID) which has become severe and chronic after insufficient conservative treatment in primary or secondary medical care facilities. Serious chronic tubo-ovarian abscess (TOA) is complicated by intraperitoneal inflammatory adhesions to surrounding organs, so that it is difficult to determine the original anatomical position of organs at surgery. Forcible synechotomy can result in damage to the adhering organs and insufficient drainage after surgery can cause recurrence of inflammation. In order to increase the chances for a successful surgical treatment, careful preparation, such as preoperative administration of antibiotics and ureteral stent insertion are necessary. In addition, the chances for recurrence of inflammation can be lessened by thorough intraperitoneal irrigation and insertion of a drainage tube.
Assuntos
Abscesso/cirurgia , Doenças das Tubas Uterinas/cirurgia , Doenças Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to determine whether combination S-1 plus cisplatin (CDDP) therapy, the most widely used therapy for Japanese patients with advanced gastric cancer, and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment. METHODS: Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were randomised into two groups: TSU-68 plus S-1/CDDP (group A) and S-1/CDDP (group B) groups. Both patient groups received identical S-1 and CDDP dosages. TSU-68 was orally administered for 35 consecutive days. Group B patients received S-1 orally twice daily for three consecutive weeks, followed by intravenous CDDP on day 8. The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS periods were 208 and 213 days in groups A and B, respectively (P=0.427). Median survival periods for groups A and B were 497.0 and 463.5 days, respectively (P=0.219). No statistically significant differences were noted for PFS, survival or the adverse event (AE) incidence rate. All AEs were expected according to previous reports for TSU-68, TS-1, and CDDP. CONCLUSION: Combination therapy involving TSU-68, S-1, and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers. However, factors related to therapeutic efficacy should be investigated further.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/farmacocinética , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Indóis/farmacocinética , Masculino , Pessoa de Meia-Idade , Oxindóis , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Ácido Oxônico/farmacocinética , Propionatos/administração & dosagem , Propionatos/efeitos adversos , Propionatos/farmacocinética , Pirróis , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Tegafur/farmacocinéticaRESUMO
The present report describes a rare case of a uterine perivascular epithelioid cell tumor (PEComa) arising from a polypoid adenomyoma. The patient, a 44-year-old woman with tuberous sclerosis, was incidentally found to have a uterine mass with malignant-appearing features on a computed tomography (CT) scan. Pathological examination of the hysterectomy specimen demonstrated that the tumor was composed of pale, spindle-shaped, epithelioid tumor cells which were positive for SMA and HMB-45. These findings were consistent with a PEComa arising from a polypoid adenomyoma.
Assuntos
Adenomioma/patologia , Neoplasias de Células Epitelioides Perivasculares/patologia , Pólipos/patologia , Neoplasias Uterinas/patologia , Adulto , Feminino , Humanos , Imuno-HistoquímicaRESUMO
BACKGROUND: This study examined the clinical significance of NAC1 and the expression level of its potential downstream target fatty acid synthase (FASN) in ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a potential therapeutic target. METHODS: NAC1 and FASN expression and NACC1 gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridisation, and clinical data collected by a retrospective chart review. C75, a FASN inhibitor, was used to assess whether this pathway represented a therapeutic target in OCCC. RESULTS: High NAC1 expression was most frequent in clear cell tumours (40.0%:24/60). NACC1 gene amplification was identified in none of the 58 OCCCs. The frequency of NACC1 gene amplification was significantly higher in the high-grade serous histology than in the clear cell histology (P<0.01). NAC1 expression was significantly correlated with FASN expression in both OCCC samples and OCCC cell lines. Either high NAC1 expression or high FASN expression significantly correlated with shorter progression-free and overall survival (P=0.002 and 0.0048). NAC1 overexpression stimulated FASN expression, and NAC1 silencing using siRNA decreased FASN expression in OCCC cell lines. Profound growth inhibition was observed in C75-treated carcinoma cells with FASN overexpression when compared with the response in carcinoma cells without FASN expression. CONCLUSION: These findings indicate that NAC1/FASN overexpression is critical to the growth and survival of a subset of OCCC. The FASN silencing by the C75-induced phenotypes depends on the expression status of the targeted cell line. Therefore, NAC1/FASN pathway-targeted therapy may benefit selected OCCC patients.
Assuntos
Adenocarcinoma de Células Claras/metabolismo , Ácido Graxo Sintases/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Repressoras/metabolismo , Adenocarcinoma de Células Claras/enzimologia , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Ácido Graxo Sintases/antagonistas & inibidores , Ácido Graxo Sintases/genética , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Terapia de Alvo Molecular , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Repressoras/genética , Estudos Retrospectivos , Transdução de SinaisRESUMO
BACKGROUND: This phase I first-in-human study was conducted in Japanese patients to investigate the safety, pharmacokinetics (PKs), and determine the maximum tolerated dose (MTD) of oral TAK-285, a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2. METHODS: The TAK-285 dose was escalated until MTD was determined. A second patient cohort received TAK-285 at the MTD for at least 4 weeks. RESULTS: In all, 26 patients received TAK-285 at doses ranging from 50 to 400 mg once daily (q.d.) or twice daily (b.i.d.); 20 patients made up the dose escalation cohort and the remaining 6 patients were the repeated administration cohort. TAK-285 was well tolerated. Dose-limiting toxicities noted in two patients who received 400 mg b.i.d. were grade 3 increases in aminotransferases and grade 3 decreased appetite. Consequently, the MTD was determined to be 300 mg b.i.d. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d. CONCLUSION: The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.
Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Hidroxibutiratos/uso terapêutico , Neoplasias/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Administração Oral , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Esquema de Medicação , Drogas em Investigação/uso terapêutico , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare microwave endometrial ablation (MEA) using a new curved applicator with conventional surgical procedures in 26 patients with menorrhagia. STUDY DESIGN: Ten patients received MEA and 16 patients received conventional surgical procedures. Using a visual analog scale (VAS). MEA patients rated their menorrhagia, dysmenorrhea, and feelings of satisfaction from the procedure. The patients' intraoperative blood loss, operating time, and length of hospital stay were compared. RESULTS: Following MEA, the VAS scores were significantly decreased in the MEA patients for menorrhagia (p < 0.0001) and dysmenorrhea (p = 0.0002). The average VAS score regarding feelings of satisfaction for MEA was 8.9 (full score = 10). Mean blood loss, operating time, and mean length of hospital stay were significantly decreased in the MEA group compared to the conventional surgical procedure group (p < 0.0001). CONCLUSION: MEA successfully controlled menorrhagia and achieved a high rate of satisfaction among patients.
Assuntos
Técnicas de Ablação Endometrial/métodos , Menorragia/cirurgia , Micro-Ondas/uso terapêutico , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Satisfação do PacienteRESUMO
Exaggerated placental site is defined as a non-neoplastic trophoblastic lesion featuring exuberant infiltration into the endometrium and myometrium by intermediate trophoblasts and syncytiotrophoblasts. Exaggerated placental site can occur following normal or ectopic pregnancy, abortion, or hydatidiform mole. We encountered a case of reactive exaggerated placental site seven months following normal pregnancy that clinically mimicked placental site trophoblastic tumor. Few reports have described the clinical course, histopathology and differential diagnosis of exaggerated placental site; we present our patient's case together with histopathological observations and review of related literature.
Assuntos
Doença Trofoblástica Gestacional/patologia , Imageamento por Ressonância Magnética , Tumor Trofoblástico de Localização Placentária/patologia , Trofoblastos/patologia , Doenças Uterinas/patologia , Adulto , Gonadotropina Coriônica/sangue , Diagnóstico Diferencial , Feminino , Doença Trofoblástica Gestacional/diagnóstico por imagem , Humanos , Gravidez , Tumor Trofoblástico de Localização Placentária/sangue , Tumor Trofoblástico de Localização Placentária/diagnóstico por imagem , Trofoblastos/diagnóstico por imagem , Ultrassonografia , Doenças Uterinas/sangue , Doenças Uterinas/diagnóstico por imagemRESUMO
Ovarian tumors of low malignant potential (LMP) appear to be intermediate between adenomas and ovarian carcinomas. Such tumors are often associated with a significantly better prognosis than for ovarian carcinomas. However, a subset of LMPs can progress and become lethal even in patients with early-stage disease. In order to seek sensitive diagnostic tools to monitor patients after surgical therapy, we performed a genome-wide scan for LOH in 37 early-stage mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reported to be associated with ovarian carcinoma. Fractional allelic loss (FAL) values were calculated as (loci scored with LOH)/(total informative loci) for each sample. With respect to tumor recurrence, high FAL values were more frequent in recurrent tumors than in non-recurrent tumors. Using the screening markers, FAL values for recurrent tumors were significantly higher than for non-recurrent tumors (19.8% vs 6.3%, respectively, p < 0.0001). Similar results were obtained using the hotspot markers (22.2% vs 7.1%, respectively, p < 0.0001). A significant correlation between FAL values obtained using screening markers and those based on hotspot markers was observed (R = 0.460, p = 0.003). Our findings suggest that a specific type of genetic instability (i.e., chromosomal instability, CIN) may exist in mucinous LMPs, and that this instability may indicate tumors with an aggressive biological nature. Therefore, FAL values may represent a new biomarker for risk prediction in early-stage mucinous LMP tumors.
Assuntos
Adenocarcinoma Mucinoso/genética , Perda de Heterozigosidade , Repetições de Microssatélites , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Adenocarcinoma Mucinoso/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Neoplasias Ovarianas/patologia , Análise de SobrevidaRESUMO
INTRODUCTION: A persistent primitive hypoglossal artery (PPHA) is a rare vascular anomaly and is usually asymptomatic. However, the PPHA may cause multi-territorial infarction when complicated by internal carotid artery (ICA) stenosis. CASE REPORT: We describe a 73-year-old male who simultaneously developed cerebral infarction in both carotid and vertebrobasilar territories due to ICA stenosis associated with an ipsilateral PPHA. The PPHA mainly provided blood flow to the vertebrobasilar territory in this case, because the bilateral vertebral arteries were markedly hypoplastic. He underwent carotid endarterectomy under internal shunting. Intraoperative multi-modality monitoring including angiography, motor evoked potential, and near infrared spectroscopy was very useful to avoid ischemic complications during surgery. The postoperative course was uneventful. CONCLUSION: It should be reminded that a persistent carotid-basilar anastomosis can cause multi-territorial cerebral infarction mimicking cardiogenic embolism and may be a candidate for aggressive prophylactic intervention, when occlusive lesions develop in the carotid artery. It is very important to monitor hemodynamic and/or electrophysiological status in both carotid and vertebrobasilar territories in order to perform carotid endarterectomy safely in such cases.
Assuntos
Artérias/anormalidades , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/métodos , Bulbo/irrigação sanguínea , Monitorização Intraoperatória/métodos , Idoso , Angiografia , Humanos , Masculino , Resultado do Tratamento , Insuficiência Vertebrobasilar/prevenção & controleRESUMO
BACKGROUND: Pleomorphic rhabdomyosarcoma (RMS) of gynecologic origin is an exceedingly rare, highly malignant tumor. Only a few cases have been reported in the last decades. CASE REPORT: A 60-year-old postmenopausal woman presented with a high LDH level of unknown origin. Ultimately, she was diagnosed with pleomorphic RMS. She underwent total hysterectomy, bilateral salpingo-oophorectomy, left pelvic and paraaortic lymphadenectomy and partial omentectomy. Surgery was followed by systemic chemotherapy and pelvic irradiation. Unfortunately, the patient did not respond to treatment. Her disease course correlated with the fluctuation of plasma LDH levels. Ultimately she died within 20 months of the diagnosis. CONCLUSION: It is important to have better insight and to set a standard multimodal treatment for adult RMS. In addition, plasma LDH levels can be considered as a prognostic marker for RMS, particularly in advanced stage.
Assuntos
L-Lactato Desidrogenase/sangue , Rabdomiossarcoma/patologia , Neoplasias Uterinas/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Rabdomiossarcoma/sangue , Rabdomiossarcoma/fisiopatologia , Neoplasias Uterinas/sangue , Neoplasias Uterinas/fisiopatologiaRESUMO
This study examined the status of KRAS and BRAF mutations, in relation to extracellular signal-regulated protein kinase (ERK) activation in 58 ovarian carcinomas to clarify the clinicopathological and prognostic significance of KRAS/BRAF mutations. Somatic mutations of either KRAS or BRAF were identified in 12 (20.6%) out of 58 ovarian carcinomas. The frequency of KRAS/BRAF mutations in conventional serous high-grade carcinomas (4.0% : 1/25) was significantly lower than that in the other histological type (32.3% : 10/31). Phosphorylated ERK1/2 (p-ERK1/2) expression was identified in 18 (38.2%) out of 45 ovarian carcinomas. KRAS/BRAF mutation was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage I, II (P<0.001), and p-ERK1/2 (P<0.001). No significant correlations between KRAS/BRAF mutations or p-ERK1/2 expression and overall survival were found in patients with ovarian carcinoma treated with platinum and taxane chemotherapy (P=0.2460, P=0.9339, respectively). Next, to clarify the roles of ERK1/2 activation in ovarian cancers harbouring KRAS or BRAF mutations, we inactivated ERK1/2 in ovarian cancer cells using CI-1040. Cl-1040 is a compound that selectively inhibits MAP kinase kinase (MEK), an upstream regulator of ERK1/2, and thus prevents ERK1/2 activation. Profound growth inhibition and apoptosis were observed in CI-1040-treated cancer cells with mutations in either KRAS or BRAF in comparison with the ovarian cancer cells containing wild-type sequences. This was evident in both in vitro and in vivo studies. The findings in this study indicate that an activated ERK1/2 pathway is critical to tumour growth and survival of ovarian cancers with KRAS or BRAF mutations. Furthermore, they suggest that the CI-1040-induced phenotypes depend on the mutational status of KRAS and BRAF in ovarian cancers. Therefore, ovarian cancer patients with KRAS or BRAF mutations may benefit from CI-1040 treatment.
Assuntos
Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Ativação Enzimática , Feminino , Humanos , Camundongos , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mutação/genética , Neoplasias Ovarianas/patologia , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Especificidade por Substrato , Taxa de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas ras/metabolismoRESUMO
BACKGROUND AND PURPOSE: The relationship of (11)C-methionine (MET) uptake and tumor activity in low-grade gliomas (those meeting the criteria for World Health Organization [WHO] grade II gliomas) remains uncertain. The aim of this study was to compare MET uptake in low-grade gliomas and to analyze whether MET positron-emission tomography (PET) can estimate tumor viability and provide evidence of malignant transformation. MATERIALS AND METHODS: We studied glioma metabolic activity in 49 consecutive patients with newly diagnosed grade II gliomas by using MET PET before surgical resection. On MET PET, we measured tumor/normal brain uptake ratio (T/N ratio) in 21 diffuse astrocytomas (DAs), 12 oligodendrogliomas (ODs), and 16 oligoastrocytomas (OAs). We compared MET T/N ratio among these 3 tumors and investigated possible correlation with proliferative activity, as measured by Mib-1 labeling index (LI). RESULTS: MET T/N ratios of DA, OD, and OA were 2.11 +/- 0.87, 3.75 +/- 1.43, and 2.76 +/- 1.27, respectively. The MET T/N ratio of OD was significantly higher than that of DA (P < .005). In comparison of MET T/N ratios with the Mib-1 LI, a significant correlation was shown in DA (r = 0.63; P < .005) but not in OD and OA. CONCLUSION: MET uptake in DAs may be closely associated with tumor viability, which depends on increased amino acid transport by an activated carrier-mediated system. DAs with lower MET uptake were considered more quiescent lesions, whereas DA with higher MET uptake may act more aggressively.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Glioma/diagnóstico por imagem , Glioma/metabolismo , Metionina/farmacocinética , Adulto , Radioisótopos de Carbono/farmacocinética , Feminino , Humanos , Masculino , Invasividade Neoplásica , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
BACKGROUND AND PURPOSE: Positron-emission tomography (PET) is a useful tool in oncology. The aim of this study was to assess the metabolic activity of gliomas using (11)C-methionine (MET), [(18)F] fluorodeoxyglucose (FDG), and (11)C-choline (CHO) PET and to explore the correlation between the metabolic activity and histopathologic features. MATERIALS AND METHODS: PET examinations were performed for 95 primary gliomas (37 grade II, 37 grade III, and 21 grade IV). We measured the tumor/normal brain uptake ratio (T/N ratio) on each PET and investigated the correlations among the tracer uptake, tumor grade, tumor type, and tumor proliferation activity. In addition, we compared the ease of visual evaluation for tumor detection. RESULTS: All 3 of the tracers showed positive correlations with astrocytic tumor (AT) grades (II/IV and III/IV). The MET T/N ratio of oligodendroglial tumors (OTs) was significantly higher than that of ATs of the same grade. The CHO T/N ratio showed a significant positive correlation with histopathologic grade in OTs. Tumor grade and type influenced MET uptake only. MET T/N ratios of more than 2.0 were seen in 87% of all of the gliomas. All of the tracers showed significantly positive correlations with Mib-1 labeling index in ATs but not in OTs and oligoastrocytic tumors. CONCLUSION: MET PET appears to be useful in evaluating grade, type, and proliferative activity of ATs. CHO PET may be useful in evaluating the potential malignancy of OTs. In terms of visual evaluation of tumor localization, MET PET is superior to FDG and CHO PET in all of the gliomas, due to its straightforward detection of "hot lesions".
Assuntos
Neoplasias Encefálicas/metabolismo , Colina/farmacocinética , Fluordesoxiglucose F18/farmacocinética , Glioma/metabolismo , Metionina/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Radioisótopos de Carbono/farmacocinética , Feminino , Perfilação da Expressão Gênica/métodos , Glioma/diagnóstico por imagem , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
Alkylating agents have strong leukemogenic potential. There are a number of recent acute myeloid leukemia (t-AML) cases related to previous paclitaxel exposure. These leukemias tend to be of aggressive subtypes with long-latency periods. Unlike previously reported cases, the present case was of the secondary acute megakaryoblastic myeloid leukemia (AML M7) subtype. Additionally, it did not harbor a translocation in chromosome 19. A 73-year-old woman was diagnosed with t-AML M7 with antecedent myelodysplasia. Leukemia followed a second induction of paclitaxel- and carboplatin-based chemotherapy for recurrent ovarian cancer. Her second induction began 25 months after completion of her first course of chemotherapy. The increased incidence of postpaclitaxel leukemia suggests a probable role for paclitaxel as a leukemogenic agent. It highlights the importance of assessing for leukemia risk factors prior to beginning paclitaxel therapy.
Assuntos
Carboplatina/uso terapêutico , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/complicações , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/complicações , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/patologiaRESUMO
Epithelioid hemangioendothelioma of the liver is a rare vascular neoplasm with intermediate malignant potential. The prognosis is highly unpredictable. We report the case of a 59-year-old woman who had the tumor radically resected, but multiple metastases of the liver developed associated with thrombocytopenia and consumption coagulopathy, as observed in Kasabach-Merritt syndrome. The patient did not respond to any treatment and the behavior of the tumor was very aggressive. The patient died 15 months after radical resection of the tumor.
Assuntos
Coagulação Intravascular Disseminada/complicações , Hemangioendotelioma/complicações , Neoplasias Hepáticas/complicações , Trombocitopenia/complicações , Coagulação Intravascular Disseminada/diagnóstico , Evolução Fatal , Feminino , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Síndrome , Trombocitopenia/diagnósticoRESUMO
Ethanol is known to induce apoptosis in hepatocytes. However, intracellular signaling events of ethanol-induced death are still only partially understood. We studied such processes in ethanol-induced apoptosis in HepG2 cells as a model system for human liver cells. We determined the incidence of apoptosis by DNA fragmentation and tested the effects of various known inhibitors. Ethanol induces apoptosis in HepG2 cells in a dose- and time-dependent manner as well as in rat primary hepatocytes. This effect was not mediated through the death receptor CD95 and the tumor necrosis factor receptors. It was efficiently inhibited by the caspase inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (zVAD-fmk), the Ca(2+) chelator EGTA, and the serine protease inhibitor N-p-tosyl-l-lysine chloromethyl ketone (TLCK). Upon ethanol treatment, the intracellular calcium ion concentration was increased and cytochrome c was released from the mitochondria, and caspases were activated. EGTA and TLCK could inhibit cytochrome c release from the mitochondria. Furthermore, overexpression of Bcl-x(L) saved cells from ethanol-induced apoptosis. These data suggest that ethanol-induced apoptosis in liver cells is initiated by the intracellular Ca(2+) elevation in the cytoplasm and activation of TLCK-sensitive serine proteases. Our data provide new insight into ethanol-induced apoptosis in liver cells and may lead to therapeutic strategies to prevent liver damage.
Assuntos
Apoptose , Cálcio/metabolismo , Carcinoma Hepatocelular/patologia , Grupo dos Citocromos c/metabolismo , Endopeptidases/metabolismo , Etanol/farmacologia , Neoplasias Hepáticas/patologia , Tosilina Clorometil Cetona/metabolismo , Clorometilcetonas de Aminoácidos/metabolismo , Western Blotting , Calmodulina/metabolismo , Calpaína/metabolismo , Caspase 3 , Caspase 9 , Caspases/metabolismo , Separação Celular , Densitometria , Relação Dose-Resposta a Droga , Ácido Egtázico/farmacologia , Ativação Enzimática , Proteína Ligante Fas , Citometria de Fluxo , Humanos , Íons , Glicoproteínas de Membrana/metabolismo , Potenciais da Membrana , Mitocôndrias/metabolismo , Modelos Biológicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transfecção , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/metabolismo , Proteína bcl-X , Receptor fas/metabolismoRESUMO
Ninety-four patients with moyamoya disease (56 in the pediatric age group and 38 adults) were treated by revascularization surgery in the past 21 years (1979--2000). Combined surgery of the superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and indirect revascularization of encaphalo-duro-arterio-myo-synangiosis (EDAMS) was performed. Ischemic attacks disappeared in most patients within 1 year (mean) after surgery in pediatric cases. No morbidity or mortality was experienced in the pediatric group. Some children with cerebral infarction before the surgery, however, had mild mental retardation even after the surgery. Early diagnosis and proper prophylactic surgical treatment is indispensable for pediatric patients with moyamoya. MR angiography is an important diagnostic modality for the screening and longitudinal follow-up of moyamoya disease.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/cirurgia , Revascularização Cerebral/métodos , Doença de Moyamoya/cirurgia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Doença de Moyamoya/diagnóstico , Cuidados Pré-Operatórios , Radiografia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: The purpose of this study was to examine the utility and reliability of arterial flow measurements made with a transit time ultrasonic flowmeter for monitoring blood flow changes during intracranial and carotid surgery. METHOD: A total of 25 patients underwent intra-operative arterial blood flow measurements. The pulsatile flow curve and mean flow values were obtained using 1- to 6-mm transit time probes with a dual channel flowmeter. Four cases underwent aneurysm clipping, 11 cases superficial temporal artery (STA)--middle cerebral artery (MCA) bypass, 2 cases external carotid artery (ECA)--radial artery--MCA bypass for aneurysm trapping, and 8 cases carotid endarterectomy. In aneurysm clipping, blood flow in the branches distal to the aneurysm was measured before and after clipping. Blood flow in the STA was measured before and after STA-MCA anastomosis, and blood flow in the internal carotid artery (ICA) cervical portion was measured during carotid endarterectomy. Blood flow in the MCA and STA was monitored during radial artery grafting. FINDINGS: Blood flow in the STA was elevated after STA-MCA anastomosis. However, post-operative hyperperfusion syndrome was found in some cases whose flow elevation was over 50 ml/min. Also in one case of carotid stenosis, of which blood flow of ICA was elevated to 400 ml/min after carotid endarterectomy, hyperperfusion syndrome was found after surgery. In the cases of MCA aneurysm clipping, decreasing of M2 flow was detected when clipping caused bifurcation stenosis. INTERPRETATION: We found transit time flow measurement useful for management of cerebrovascular surgery: the technique was simple to use and provided stable, reliable results. The method was able to reveal distal branch flow diminution in aneurysm clipping, or residual flow during temporary clipping in aneurysm surgery, and has the potential to predict post-operative complications such as hyperperfusion by signalling over-elevation of donor artery flow in bypass surgery or ICA flow in carotid surgery.