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1.
Int J Cancer ; 141(5): 1042-1051, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28524247

RESUMO

This was a nation-wide retrospective study in Japan examining women who underwent radical hysterectomy for clinical stage IB-IIB cervical cancer with pelvic and/or para-aortic lymph node metastasis between 2004 and 2008. Time to recurrence or death and patterns of disease recurrence were compared based upon the adjuvant treatment pattern: whole pelvic radiotherapy alone (n = 253), concurrent chemoradiotherapy (CCRT, n = 502) and chemotherapy alone (n = 319). Women who received chemotherapy alone had similar recurrence (5-year rates, 36.6% vs. 34.1%, adjusted-hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.70-1.28, P = 0.72) and cervical cancer mortality (24.7% vs. 21.8%, adjusted-HR 0.96, 95% CI 0.67-1.38, P = 0.83) rates compared to those who received CCRT on multivariate analysis. However, when recurrence patterns were stratified, chemotherapy treatment was independently associated with decreased risk of distant recurrence (5-year cumulative rates, 19.2% vs. 24.6%, adjusted-HR 0.47, 95% CI 0.31-0.71, P < 0.001) but increased risk of local recurrence (23.9% vs. 14.3%, adjusted-HR 2.03, 95% CI 1.34-3.08, P = 0.001) compared to CCRT. Non-squamous histology, parametrial involvement and high lymph node ratio were independent predictors for local recurrence, and presence of multiple risk factors was associated with high 5-year cumulative local recurrence rate in the chemotherapy group: no risk factor 3.9%, single factor 14.2-22.1%, and multiple risk factors 27.8-71.9% (P < 0.001). In conclusion, while exhibiting different recurrence patterns, systemic chemotherapy may be as effective a postoperative treatment as radiation-based therapy in node-positive high-risk stage IB-IIB cervical cancer. When tumor exhibits certain risk factors, chemotherapy alone is likely insufficient for local control and adding pelvic irradiation to systemic chemotherapy is recommended in this subgroup.


Assuntos
Quimiorradioterapia/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Japão , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/mortalidade
2.
Int J Gynecol Cancer ; 24(7): 1333-40, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25078340

RESUMO

OBJECTIVE: The aim of this study was to determine the current operative management of International Federation of Gynecology and Obstetrics (FIGO) stage IB2, IIA2, and IIB uterine cervical cancer (bulky tumors) in Japan by surveying the member institutions of the Japanese Gynecologic Oncology Group. METHODS: We conducted a survey to assess current operative management, including indications and treatment, at all 199 active member institutions of the Japanese Gynecologic Oncology Group. RESULTS: A total of 166 institutions (83.4%) responded to the survey. For patients with stage IIB squamous cell carcinoma, 35.5% (59/166) of the institutions performed surgery. For stage IIB nonsquamous cell carcinoma, surgery was performed at 88 (53.7%) of 164 institutions. Neoadjuvant chemotherapy was provided by 75 (45.5%) of 165 institutions (actively in 44 and reluctantly in 31). At 101 (61.2%) of 165 institutions, para-aortic node dissection was performed as part of radical surgery in patients with any indications. At 96 (57.9%) of 166 institutions, high-risk patients underwent chemoradiotherapy after surgery. On the other hand, adjuvant chemotherapy was given to high-risk and intermediate-risk patients at 19.9% and 33.1% institutions, respectively. More than half of the 166 institutions considered the number of metastatic nodes (91/166, 54.8%) and tumor histology (116/166, 69.9%) when selecting adjuvant therapy. CONCLUSIONS: This survey provided information regarding the current surgical management of uterine cervical cancer (stages IB2, IIA2, and IIA) in Japan.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/cirurgia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia/estatística & dados numéricos , Quimioterapia Adjuvante/estatística & dados numéricos , Comportamento de Escolha , Terapia Combinada/estatística & dados numéricos , Coleta de Dados , Feminino , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Histerectomia/estatística & dados numéricos , Consentimento Livre e Esclarecido/estatística & dados numéricos , Japão/epidemiologia , Excisão de Linfonodo/estatística & dados numéricos , Estadiamento de Neoplasias , Recidiva , Carga Tumoral , Neoplasias do Colo do Útero/patologia
3.
Int J Gynecol Cancer ; 23(9): 1655-60; quiz 1661-2, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24172100

RESUMO

OBJECTIVE: The objective of this study was to determine the current operative principle of uterine cervical cancer of stages Ia2, Ib1, and IIa1 (International Federation of Gynecology and Obstetrics) in Japan by surveying member institutions of the Japanese Gynecologic Oncology Group (JGOG). METHODS: We conducted a survey to assess the current operative principle, including indications and treatment, at all 199 active member institutions of the JGOG. RESULTS: A total of 166 institutions (83.4%) responded to the survey. For Ia2 squamous cell carcinoma without the need to preserve fertility, modified radical hysterectomy was performed, and lymph node dissection was done in about 85%. At 60% of JGOG institutions, it was considered that less invasive procedures might be suitable. At the majority of JGOG institutions, radical surgery and lymph node dissection were considered necessary for stages Ib1 and IIa1 squamous cell carcinoma, with 70% considering that less invasive procedures might not be suitable. CONCLUSIONS: This survey provides information regarding the current status of surgical principle for uterine cervical cancer (stages Ia2, Ib1, and IIa1) in Japan.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Procedimentos Cirúrgicos em Ginecologia/métodos , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Coleta de Dados/estatística & dados numéricos , Feminino , Preservação da Fertilidade/estatística & dados numéricos , Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Gravidez , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Adulto Jovem
4.
J Obstet Gynaecol Res ; 37(1): 13-23, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21040201

RESUMO

AIM: The connective tissue located between the uterine cervix and sacrospinous ligament (the uterospinous connective tissue; USCT) has recently been noted as the level 1 supportive tissue instead of the classical uterosacral ligament. We examined whether or not the USCT changes its histological architecture by vaginal delivery in correlation with the levels 2 and 3 supportive tissues. METHODS: In the pelvic floors of 17 female cadavers (9 nuliparous and 8 multiparous), we compared histological architectures among the USCT, arcus tendineus fasciae pelvis (ATFP) and perineal membrane (PM). RESULTS: The USCT was evident as a string-like tissue structure in multiparous women or a thick mesh in nuliparous women. It consistently contained fewer elastic and smooth muscle fibers than other levels. In contrast, the ATFP usually contained abundant elastic fibers and smooth muscle. Likewise, the PM also displayed a constant morphology. CONCLUSION: Although all three sites were likely to be injured by delivery, the USCT seemed to be more severely damaged and/or more difficult to be recovered than the ATFP and PM.


Assuntos
Envelhecimento/patologia , Paridade , Diafragma da Pelve/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Anatomia Transversal , Tecido Elástico/anatomia & histologia , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Liso/anatomia & histologia , Diafragma da Pelve/patologia , Diafragma da Pelve/fisiologia
5.
Clin Anat ; 24(4): 469-77, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20830792

RESUMO

The fascia pelvis parietalis (FPP) or endopelvic fascia is a well-known structure, but few studies described the detailed histological architecture, including the composite fiber directions. We hypothesized a gender-specific fiber architecture corresponding to the functional demand. For the first step to examine this hypothesis, we investigated specimens from 27 adult cadavers (10 males and 17 females) and 11 midterm fetuses (five males and six females) using immunohistochemistry and aldehyde-fuchsin staining. The adult female FPP was a solid, thick monolayered structure that was reinforced by abundant elastic fibers running across the striated muscle fibers, but it contained little or no smooth muscles (SM). In contrast, the male FPP was multilayered with abundant SM. In midterm fetuses, SM originated from the inferior part of the bladder and extended inferiorly along the gender-specific courses. Thus, we found a clear intergender difference in FPP architecture. However, the functional significance remained unknown because the basic architecture was common between nulliparous and multiparous women. Rather than for meeting the likely mechanical demands of pregnancy and vaginal delivery, the intergender difference of the FPP seemed to result from differences in the amount and migration course of bladder-derived SM as well as in hormonal background.


Assuntos
Ligamento Largo/anatomia & histologia , Fáscia/anatomia & histologia , Diafragma da Pelve/anatomia & histologia , Ligamento Redondo do Útero/anatomia & histologia , Actinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Ligamento Largo/metabolismo , Cadáver , Tecido Elástico/anatomia & histologia , Tecido Elástico/metabolismo , Fáscia/metabolismo , Feminino , Feto/anatomia & histologia , Idade Gestacional , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/anatomia & histologia , Músculo Liso/metabolismo , Ligamento Redondo do Útero/metabolismo , Fatores Sexuais
6.
J Radiat Res ; 62(2): 269-284, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33415337

RESUMO

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20-70 years old with Stages IB1-IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians' questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients' questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4-5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients' questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.


Assuntos
Qualidade de Vida , Inquéritos e Questionários , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Disuria/etiologia , Edema/etiologia , Feminino , Humanos , Japão , Perna (Membro)/patologia , Pessoa de Meia-Idade , Análise Multivariada , Médicos , Autorrelato , Adulto Jovem
7.
Cancer Sci ; 100(8): 1421-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19486012

RESUMO

To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from 43 ovarian cancer tissues comprising eight early stage and 35 advanced stage tissues were carried out using oligonucleotide microarrays of 18,716 genes. By non-negative matrix factorization analysis using 178 genes, which were extracted as stage-specific genes, 35 advanced stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression-free survival (log rank test, P = 0.03). Of the 178 stage-specific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by gene ontology analysis or Ingenuity Pathway Analysis, five genes (ZEB2, CDH1, LTBP2, COL16A1, and ACTA2) were extracted as candidates for prognostic factors associated with progression-free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression-free survival was validated by real-time RT-PCR experiments of 37 independent advanced stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E-cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced stage cancer samples set (n = 74). These findings suggest that the expression of epithelial-mesenchymal transition-related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced stage serous ovarian cancer.


Assuntos
Cistadenoma Seroso/classificação , Perfilação da Expressão Gênica , Proteínas de Homeodomínio/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Repressoras/genética , Cistadenoma Seroso/genética , Cistadenoma Seroso/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/metabolismo , Prognóstico , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homeobox 2 de Ligação a E-box com Dedos de Zinco
8.
J Contemp Brachytherapy ; 11(2): 180-188, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31139228

RESUMO

In November 2011, a 61-year-old woman was diagnosed with squamous cell carcinoma (SCC) of the cervix in a uterus didelphys with vaginal septum. The patient was diagnosed with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIB because of infiltration to the left parametrium without infiltration to the pelvic wall. The patient was treated with external-beam radiotherapy (EBRT) and brachytherapy (BT), using concomitant chemotherapy with cisplatin. A total of 50 Gy were delivered (2 Gy/fraction/day) to the pelvis, with a central shield after 40 Gy. The patient was treated four times with BT (6 Gy × 4 fractions), with tandem and ovoid applicators inserted once to the left side; tandem to the left side and ovoid bilaterally were inserted twice; and tandem to the right side and ovoid bilaterally were inserted once. Six years and 8 months after the start of treatment, the patient had had no relapse or severe late adverse effects. For accurate diagnosis and optimal treatment of the uterus didelphys, careful interview and pelvic examination at initial diagnosis of a patient are very important.

9.
Int Cancer Conf J ; 7(2): 71-75, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31149518

RESUMO

The incidence of endometrial serous carcinoma (ESC) has been increasing, and ESC is resistant to treatment. We report a patient with ESC who responded to radiotherapy for multiple recurrences. The first recurrence was detected in the vaginal wall and left internal iliac lymph node 5 months after the initial treatment. Concurrent chemoradiotherapy (CCRT) was administered. Radiation was delivered using the intensity modulated radiation therapy technique. The second recurrent tumor was detected in the right internal iliac lymph node after 4 months, and CCRT was conducted. After 4 months, the third recurrence was detected in the right common iliac node, and CCRT was performed. After 8 months, the fourth recurrence was detected in the horizontal portion of the duodenum, and radiotherapy was administered. After 9 months, the fifth recurrence was detected in the vaginal wall. Interstitial brachytherapy was conducted. Grade 2 gastrointestinal injury, nausea and radiodermatitis were observed. During the subsequent 13-month follow-up, there has been no recurrence. Although ESC is resistant to treatment, radiotherapy could be effective in some cases. Even when multiple recurrences occur, radiotherapy may be considered a treatment option if the irradiation level is permissible.

10.
Gan To Kagaku Ryoho ; 30(5): 721-9, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12795110

RESUMO

This paper introduces the Japanese translation of the Multidimensional Affect and Pain Survey (MAPS), a 101 item questionnaire which has been demonstrated to possess a number of advantages over the McGill Pain Questionnaire (MPQ). We also review validation and other studies which used translations of MAPS into Chinese, Czech, Italian and Russian to study cancer related and chronic pain.


Assuntos
Comparação Transcultural , Medição da Dor/normas , Dor/psicologia , Afeto , Humanos , Idioma , Medição da Dor/métodos , Limiar da Dor , Inventário de Personalidade , Inquéritos e Questionários
11.
Gan To Kagaku Ryoho ; 31(3): 449-51, 2004 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-15045960

RESUMO

We treated a patient with recurrent ovarian cancer with cancerous peritonitis by weekly paclitaxel (w-TXL) therapy (65 mg/m2). Abdominocentesis was not performed to eliminate ascites, in order to maintain higher quality of life (QOL), and critical adverse reaction was not seen for 12 months. We measured the TXL concentration in blood plasma and ascites after TXL infusion by HPLC method. The TXL titer in plasma was 427 ng/ml after infusion, 23 ng/ml after 24 hours and under 10 ng/ml after 48 hours. The TXL titer in ascites was 41 ng/ml after infusion, 37 ng/ml after 6 hours, 18 ng/ml after 12 hours, 10 ng/ml after 24 hours and under 10 ng/ml after 48 hours. TXL transportation from blood to ascites was good. This result suggested that intravenous infusion of TXL was effective for cancerous peritonitis treatment.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Peritonite/tratamento farmacológico , Adenocarcinoma/metabolismo , Antineoplásicos Fitogênicos/farmacocinética , Líquido Ascítico/química , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacocinética , Qualidade de Vida
12.
Gan To Kagaku Ryoho ; 30(13): 2129-32, 2003 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-14712777

RESUMO

It is well known that neuropathy, myelopathy, and arthropathy are specific adverse effects induced by paclitaxel administration. Parkinson's disease is neural degenerative disease, and the influence of paclitaxel administration on patients with Parkinson's disease is unknown. We have successfully treated an ovarian cancer patient with Parkinson's disease by paclitaxel/CBDCA combined chemotherapy after surgery. The patient was a 57-year-old woman with solid and cystic ovarian tumor. Among the tumor markers CA125, CA19-9, and SLX, only SLX was elevated. We operated and made a pathological diagnosis of the ovarian tumor as clear cell adenocarcinoma (FIGO stage Ic). After surgery, the patient was treated with paclitaxel (260 mg [175 mg/m2]) and CBDCA (600 mg [AUC = 5]) combined chemotherapy for 5 courses. Her status is complete remission. During chemotherapy, she had felt the decreased efficacy of her Parkinson's disease medication. We could continue chemotherapy by increasing the dose of the Parkinson's drug. There is only one case report on the influence of paclitaxel on Parkinson's disease, in which the course was similar to the present case.


Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Doença de Parkinson/complicações , Adenocarcinoma de Células Claras/complicações , Adenocarcinoma de Células Claras/cirurgia , Antiparkinsonianos/administração & dosagem , Área Sob a Curva , Carboplatina/administração & dosagem , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Ovariectomia , Paclitaxel/administração & dosagem , Doença de Parkinson/tratamento farmacológico
13.
Clin Cancer Res ; 18(5): 1374-85, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22241791

RESUMO

PURPOSE: High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients. EXPERIMENTAL DESIGN: In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high- and low-risk ovarian cancer groups. RESULTS: An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 × 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 × 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients. CONCLUSIONS: This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients.


Assuntos
Apresentação de Antígeno/genética , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Neoplasias Ovarianas/genética , Idoso , Análise por Conglomerados , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Transdução de Sinais , Análise de Sobrevida
14.
Int J Dev Neurosci ; 28(7): 581-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20673797

RESUMO

To evaluate the effect of CD133(+) cells (endothelial progenitor cells) on the hypoxia-induced suppression of axonal growth of cortical neurons and the destruction of blood vessels (endothelial cells), we used anterograde axonal tracing and immunofluorescence in organ co-cultures of the cortex and the spinal cord from 3-day-old neonatal rats. CD133(+) cells prepared from human umbilical cord blood were added to the organ co-cultures after hypoxic insult, and axonal growth, vascular damage and apoptosis were evaluated. Anterograde axonal tracing with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was used to analyze axonal projections from the cortex to the spinal cord. Immunolabeling co-cultured tissues of the cortex and the spinal cord were used to investigate the effect of CD133(+) cells on the survival of blood vessels and apoptosis in the brain cortex. Hypoxia remarkably suppressed axonal growth in organ co-cultures of the cortex and the spinal cord, and this suppression was significantly restored by the addition of CD133(+) cells. CD133(+) cells also reduced the hypoxia-induced destruction of the cortical blood vessels and apoptosis. CD133(+) cells had protective effects on hypoxia-induced injury of neurons and blood vessels of the brain cortex in vitro. These results suggest that CD133(+) cell transplantation may be a possible therapeutic intervention for perinatal hypoxia-induced brain injury.


Assuntos
Antígenos CD/imunologia , Axônios/fisiologia , Córtex Cerebral/patologia , Sangue Fetal/citologia , Glicoproteínas/imunologia , Hipóxia , Peptídeos/imunologia , Células-Tronco/fisiologia , Antígeno AC133 , Animais , Animais Recém-Nascidos , Apoptose , Células Cultivadas , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Circulação Cerebrovascular , Técnicas de Cocultura , Humanos , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Técnicas de Cultura de Tecidos
15.
PLoS One ; 5(3): e9615, 2010 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-20300634

RESUMO

BACKGROUND: Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. METHODOLOGY/PRINCIPAL FINDINGS: Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66-5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). CONCLUSIONS/SIGNIFICANCE: The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Platina/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Taxoides/administração & dosagem , Resultado do Tratamento
16.
Menopause ; 16(3): 555-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19169165

RESUMO

OBJECTIVE: The climacteric disturbance seen among perimenopausal women often includes symptoms related to poor microcirculation. This hemorheological condition plays an important role in the hemodynamism of microcirculation. Specifically, erythrocyte deformability is considered to be one of the most significant factors in determining this hemorheological condition. METHODS: The present study investigated the level of erythrocyte deformability in four groups of women: namely, 10 healthy premenopausal women (PRE group), 25 postmenopausal women (POST group), 20 postmenopausal women on estrogen therapy (ET group) who received conjugated equine estrogens 0.625 mg/day, and 20 postmenopausal women on estrogen plus progestogen therapy (EPT group) who received conjugated equine estrogens 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day. The erythrocyte deformability score (EDS), measured by the Micro Channel Array Flow Analyzer, was determined as an index of erythrocyte deformability. RESULTS: The mean EDS for the POST group was significantly higher (mean +/- SE, 1.02 +/- 0.04) (P < 0.01) than that for the PRE group (0.78 +/- 0.05). The mean EDS for the ET group (0.88 +/- 0.03) was significantly lower than that for the POST group and close to that of the PRE group. There was no difference in the EDS values between the ET group and the EPT group (0.87 +/- 0.03). CONCLUSIONS: These results indicate that erythrocyte deformability may worsen with the decrease in the estrogen level because of the onset of menopause, and also suggest that ET and EPT may allow it to recover.


Assuntos
Deformação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica/fisiologia , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Menopausa/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade
17.
Reprod Sci ; 16(12): 1186-92, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19767540

RESUMO

The expression levels of P2X purinergic receptors were determined in the myometrium of pregnant rats using the quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). The messenger RNAs (mRNAs) of P2X4 and P2X7 were expressed most strongly. The expression levels of these receptors increased during the late stages of pregnancy; at the time of delivery, the mRNA levels of P2X4 and P2X7 had increased to 1.9 and 3.2 times the day 19 values, respectively. We also explored the roles of P2X receptors in hormone-induced and inflammation-induced preterm delivery models. In the former, mifepristone caused the P2X4 and P2X7 mRNA levels to increase to 2.1 and 4.1 times the control values, respectively. In the latter, lipopolysaccharide (LPS) caused the mRNA levels of P2X4 and P2X7 to increase dramatically to 7.4 and 18.6 times the control values, respectively. These findings suggest that increased P2X4 and P2X7 receptor expression in pregnant rats is related to uterine contraction leading to term and preterm delivery.


Assuntos
Miométrio/metabolismo , Nascimento Prematuro/metabolismo , Receptores Purinérgicos P2/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Eletroforese em Gel de Poliacrilamida , Feminino , Idade Gestacional , Lipopolissacarídeos , Mifepristona , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2X4 , Receptores Purinérgicos P2X7 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
18.
Int J Radiat Oncol Biol Phys ; 75(2): 369-77, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19735865

RESUMO

PURPOSE: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. MATERIALS AND METHODS: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with (192)Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. RESULTS: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade > or =3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade > or =3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade > or =3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. CONCLUSION: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Braquiterapia/métodos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Feminino , Humanos , Infusões Intra-Arteriais/métodos , Radioisótopos de Irídio/uso terapêutico , Japão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Dosagem Radioterapêutica , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
19.
J Obstet Gynaecol Res ; 33(3): 397-401, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17578376

RESUMO

Epithelioid trophoblastic tumor (ETT) is a rare type of gestational trophoblastic disease and only 25 cases have been reported so far. It was first proposed by Mazur and Kurman in 1994 as an unusual type of trophoblastic tumor that is distinct from placental site trophoblastic tumor and choriocarcinoma and has features resembling carcinoma. A case of ETT of the lung in a 38-year-old Japanese woman is reported. The patient had suffered from a hydatidiform mole at the age of 27 years, and had four normal deliveries at the ages of 24, 31, 35 and 37 years. Because no tumor lesions were detected in the uterus, the patient was suspected of having metastatic choriocarcinoma with multiple lesions in the lung accompanied by an elevated level of human chorionic gonadotropin (hCG). In order to make an exact diagnosis, a partial resection of metastatic foci in the lung was performed. Microscopically, the tumor showed hemorrhagic necrotic foci and was composed of mainly mononuclear tumor cells and some giant tumor cells resembling trophoblastic cells. Immunohistochemical examination showed that a few large cells were stained positively for hCG, and that other cells were positive for human placental lactogen, pregnancy-specific beta1-glycoprotein, cytokeratin 7 and inhibin-alpha. In the ultrastructure, the tumor cells contained large nuclei and rich organella with desmosomes and well-formed filaments. The diagnosis of ETT was confirmed from the findings as described above.


Assuntos
Neoplasias Pulmonares/secundário , Pulmão/patologia , História Reprodutiva , Neoplasias Trofoblásticas/patologia , Neoplasias Uterinas/patologia , Adulto , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/ultraestrutura , Neoplasias Trofoblásticas/diagnóstico , Neoplasias Trofoblásticas/ultraestrutura , Neoplasias Uterinas/diagnóstico
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