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1.
Artigo em Inglês | MEDLINE | ID: mdl-30148213

RESUMO

BACKGROUND: Since the introduction of recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke, rt-PA rate and number of stroke centers have increased. Despite this, studies have shown racial and ethnic disparities in stroke care especially in Black and Hispanic populations. What factors are related to the administration of rt-PA within the Hispanic population has to date been unclear. METHODS: We performed a retrospective review of IRB approved, prospectively collected data from the UC San Diego Stroke Registry from 7/2004-7/2016. Patients were included based on the primary diagnosis of Transient Ischemic Attack or Ischemic Stroke. Hispanic vs non-Hispanic patients were compared to assess for overall rt-PA treatment rates and process of care intervals. For the Hispanic cohort itself, demographics and NIHSS scores were assessed to determine why some Hispanics received rt-PA while others were not. RESULTS: Overall, 1489 patients (300 Hispanic vs. 1189 non-Hispanic) were included. Comparing Hispanics to non-Hispanics, there was no difference in rt-PA rate (35.3% vs. 33.1%; p=0.49). In rt-PA treated patients, "onset to arrival" interval was higher in Hispanics (1.03 vs. 0.88 hours; p=0.04), while the "arrival to treatment" interval was not different (1.13 vs. 1.02 hours; p=0.07). When looking at Hispanic patients only, there was no difference in baseline characteristics except for initial NIHSS in treated vs. non-treated patients (13.27 vs. 7.24; p<.001). CONCLUSION: Our analyses sought to determine the factors important to administration of rt-PA to Hispanic patients. These findings highlight the need for strategies to improve recognition and presentation pathways for Hispanics.

2.
Cancer Gene Ther ; 21(9): 389-96, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25124811

RESUMO

Thymosin beta-4 (Tß4) is known to be involved in tumorigenesis. Overexpression of this polypeptide has been observed in a wide variety of cancers, including colorectal carcinoma (CRC). Accordingly, Tß4 has been proposed to be a novel therapeutic target for CRC, especially in its metastatic form. Although in vitro tumor-suppressive effects of Tß4 gene silencing mediated by small hairpin RNA (shRNA) have already been demonstrated, the in vivo efficacy of such an approach has not yet been reported. Herein, we demonstrated that infection with recombinant adenovirus expressing an shRNA targeting Tß4 markedly reduced the growth of and robustly induced apoptosis in CT-26 mouse CRC cells in culture. Additionally, tumors grown in nude mice from the CT-26 cells whose Tß4 expression already been downregulated by virus infection were also drastically reduced. Most importantly, significant growth arrest of tumors derived from the parental CT-26 cells was observed after multiple intratumoral injections of these viruses. Together, our results show for the first time that in vivo silencing of Tß4 expression by its shRNA generated after adenoviral infection can suppress CRC growth. These results further demonstrate the feasibility of treating CRC by a Tß4 knockdown gene therapeutic approach.


Assuntos
Adenoviridae/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Vetores Genéticos/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Timosina/genética , Actinas/genética , Actinas/metabolismo , Animais , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Humanos , Camundongos , Interferência de RNA , Transdução Genética , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Oncogene ; 33(29): 3851-60, 2014 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-23995788

RESUMO

LKB1 loss is a frequent homozygous deletion and/or gene mutation found in lung adenocarcinomas. However, few cases of LKB1 loss by either deletion or mutation are seen in Asian patients. Our preliminary data showed that LKB1 loss was associated with p53 mutation in lung tumors from Taiwanese adenocarcinoma patients and p53 transcription is directly regulated by NKX2-1. Therefore, we hypothesized that LKB1 loss could occur due to aberration of p53 regulation mediated by NKX2-1. In the present study, 16 lung adenocarcinoma cell lines were investigated to determine if LKB1 transcription could be deregulated by NKX2-1-mediated p53 aberration. Mechanistic studies indicated that LKB1 was directly upregulated by p53 and that NKX2-1-mediated p53 expression may positively regulate LKB1 expression in p53 wild-type cells. However, in p53-mutated cells, LKB1 transcription was deregulated by NKX2-1 via suppression of SP1 binding onto the LKB1 promoter. Therefore, the action of the NKX2-1/p53 pathway on LKB1 loss differed in p53 wild-type versus p53-mutated cells. As expected, soft-agar growth and invasion capability was significantly reduced by ectopic expression of NKX2-1 in p53 wild-type cells, but it was markedly elevated by silencing NKX2-1 in p53-mutated cells. Similar reciprocal observations were also seen in lung tumors from lung adenocarcinoma patients with either wild-type or mutated p53 tumors. Cox regression analysis showed that patients with low-LKB1 tumors had poorer overall survival (OS) and relapse-free survival (RFS) when compared with patients with high-LKB1 tumors. In p53 wild-type patients, shorter OS and RFS periods were predicted for low-NKX2-1/low-LKB1 tumors than for high-NKX2-1/high-LKB1 tumors. In patients with p53-mutated tumors, poorer OS and RFS were predicted for high-NKX2-1/low-LKB1 tumors than for low-NKX2-1/high-LKB1 tumors. In summary, losses of LKB1 at the transcriptional level by altered activity of the NKX2-1/p53 pathway may promote tumor malignancy and poor patient outcome.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/deficiência , Transdução de Sinais , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator Nuclear 1 de Tireoide , Transcrição Gênica , Carga Tumoral , Proteína Supressora de Tumor p53/genética
4.
Blood Cancer J ; 2: e93, 2012 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-23064741

RESUMO

To select an appropriate prognostic model in the treatment of mature T- and natural killer (NK) -cell lymphoma (peripheral T-cell lymphoma (PTCL) and NK-/T-cell lymphoma (NKTCL)) is crucial. This study investigated the usefulness of Ann Arbor staging classification International prognostic index (IPI), prognostic index for T-cell lymphoma (PIT) and International peripheral T-cell lymphoma Project score (IPTCLP). Between 2000 and 2009, 176 patients (122 males) with PTCL and NKTCL were diagnosed and treated from a single institute in Taiwan. The correlation between complete response (CR) rate, 3-year overall survival (OS), early mortality rate and four prognostic models was analyzed. Thirty-one patients received hematopoietic stem cell transplantation (HSCT) and were analyzed separately. Three-year OS rate was 34.7%, and anaplastic large-cell lymphoma harbored better outcome than others. IPI score had the lowest Akaike information criterion value (1081.197) and was the best score in predicting OS and early mortality (P=0.009). Ann Arbor stage classification can predict CR rate more precisely (P=0.006). OS was significantly better in patients who received HSCT, even in patients with unfavorable features compared with chemotherapy alone. All prognostic models were useful to evaluate the outcome of patients with PTCL and NKTCL but IPI score did best in predicting OS in PTCL and PIT score in NKTCL. This study also supported the role of HSCT in patients with high-risk or refractory PTCL or NKTCL.

5.
Bone Marrow Transplant ; 46(9): 1231-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21113186

RESUMO

This study aimed to determine the impact of blood stream infections (BSIs) on outcome of allogeneic hematopoietic SCT (HSCT), and to examine the influence of old (non-levofloxacin-containing) and new (levofloxacin-based) prophylactic antibiotic protocols on the pattern of BSIs. We retrospectively enrolled 246 allogeneic HSCT recipients between January 1999 and June 2006, dividing patients into BSI (within 6 months post-HSCT, n=61) and non-BSI groups (n=185). We found that Gram-negative bacteria (GNB) predominated BSI pathogens (54%). Multivariate analyses showed that patients with a BSI, compared with those without, had a significantly greater 6-month mortality (hazard ratio, 1.75; 95% confidence interval, 1.09-2.82; P=0.021) and a significantly increased length of hospital (LOH) stay (70.8 vs 55.2 days, P=0.014). Moreover, recipients of old and new protocols did not have a significantly different 6-month mortality and time-to-occurrence of BSIs. However, there were significantly more resistant GNB to third-generation cephalosporins and carbapenem in recipients of levofloxacin-based prophylaxis. Our data suggest that BSIs occur substantially and impact negatively on the outcome and LOH stay after allogeneic HSCT despite antibiotic prophylaxis. Levofloxacin-based prophylaxis, albeit providing similar efficacy to non-levofloxacin-containing regimens, may be associated with increased antimicrobial resistance.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Administração Oral , Adulto , Antibioticoprofilaxia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Levofloxacino , Masculino , Ofloxacino/uso terapêutico , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
6.
Pharmacogenomics J ; 11(3): 227-36, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20531372

RESUMO

The -460T → C polymorphism of vascular endothelial growth factor (VEGF) gene significantly increases its promoter activity. A pilot study was conducted to assess the influence of this polymorphism on clinicopathological features of patients with colorectal carcinoma. In total, 228 patients were enrolled, including 100 with stage II/III colorectal carcinoma receiving curative surgery and 128 with metastatic disease. An excellent correlation in VEGF -460 genotypes based on white blood cells and tumor tissues existed, but there was no between-group difference in patients with or without colorectal carcinoma. A marked increase in intratumor and circulating VEGF levels were observed in patients with the T/C or C/C genotypes (P < 0.01), which was associated with increased extent of invasion, nodal involvement, poor histological differentiation, subsequent metastasis and shorter survival in stage II/III patients treated with curative surgery (P < 0.01). For patients with metastatic disease, this polymorphism was associated with a lower response rate to FOLFOX-4 (P = 0.03) and shorter survival (P < 0.001). By multivariate analysis, this polymorphism was identified as an independent prognostic factor (P = 0.01). These data suggest that -460T → C polymorphism of VEGF gene, by increasing VEGF expression and subsequent angiogenesis, could be a key determinant for increased tumor recurrence and a poor prognosis of patients with colorectal carcinoma. However, this study is exploratory and is not adjusted for multiple comparisons, requiring independent replication.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Carcinoma/patologia , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/uso terapêutico , Expressão Gênica , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Polimorfismo Genético , Resultado do Tratamento
7.
Bone Marrow Transplant ; 46(4): 567-72, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20622906

RESUMO

Hematopoietic SCT (HSCT) is a well-recognized therapeutic procedure to prolong life and cure patients with life-threatening hematological malignancies; however, the risk of developing secondary carcinoma may increase in long-term survivors. The objective of this study was to determine the incidence and risk factors for secondary squamous carcinoma after HSCT. Between 1984 and 2004, 170 allogeneic HSCT recipients aged >15 years, who had survived for >5 years were enrolled. Demographic data and the characteristics of secondary carcinoma were collected and analyzed for the determination of the incidence and risk of developing secondary carcinoma. Eight patients developed secondary carcinoma, including five oral squamous cell carcinomas, one esophageal, one gastric and one ovarian carcinoma, but no cutaneous carcinomas were detected at a median follow-up of 14.1 years (range, 5.1-23.3 years) after HSCT. The accrual 10-year cumulative incidence of secondary carcinoma was 2.89%. In univariate and multivariate analyses, chronic GVHD and age >40 years at the time of HSCT were both significant risk factors independently associated with the development of secondary carcinoma. Thus, the occurrence of secondary carcinoma is one of the late complications in patients undergoing HSCT. Oral squamous cell carcinoma was more common in our patients after HSCT, indicating the need for lifelong surveillance of the oral cavity. Moreover, because of the relatively long latency in developing secondary carcinoma, extended follow-up is required for a thorough understanding of the incidence and characteristics of secondary carcinoma after HSCT.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Segunda Neoplasia Primária/epidemiologia , Infecções por Papillomavirus , Adolescente , Adulto , Fatores Etários , Carcinoma de Células Escamosas/etiologia , Feminino , Seguimentos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan , Transplante Homólogo , Adulto Jovem
8.
Bone Marrow Transplant ; 45(12): 1682-91, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20190847

RESUMO

The hematopoietic SCT (HSCT) activity in nine Asian countries/regions was surveyed to overview the current situation. Data of 58 113 HSCTs (allogeneic: 63% vs autologous: 37%) performed between 1986 and 2006 by 432 transplant teams were collected. The number of HSCTs has been increasing in the past two decades in most countries/regions. The increase in allogeneic HSCTs is greater than in autologous HSCTs. The proportion of unrelated donors among allogeneic HSCTs in 2006 varied widely from <1% (Iran and Vietnam) to 62% (Japan). The use of each stem cell source, that is, BM, PBSC, cord blood and others (including co-infusion of BM and PBSC), also varied widely (36, 58, 0.1 and 6% in HSCT from related donors, respectively, and 53, 11, 35 and 1% in HSCT from unrelated donors, respectively). HSCTs have been continuously increasing for all indications except for chronic myelogenous leukemia and solid tumors. Hemoglobinopathy is a common indication among non-malignant diseases in many Asian countries/regions except for China, Japan and Korea. This survey clearly shows the recent progress of HSCTs in Asia and also some differences in donor and stem cell selection and disease application among countries/regions.


Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Ásia , Humanos
9.
Eur J Cancer Care (Engl) ; 19(2): 267-72, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19709171

RESUMO

The terminal cancer patients increase needs for hospice care day by day. A new hospice consulting system has been developed in Taiwan to provide options for terminal cancer patients in choosing a suitable post-acute hospice care while a combined hospice care system is also given by the consulting team in the acute wards. Hereinafter is our report. From March 2005 to January 2006, 313 terminal cancer patients were analysed. These patients had signed consent forms for palliative treatment and had received consultations from the new hospice consulting system. Multivariate analysis showed that the home care patients had better performance status (P = 0.012), less shortness of breath (P = 0.006), less limbs swelling (P = 0.043), less flatulency (P = 0.000) and less constipation (P = 0.018). Among the 162 patients with regular follow-up, the symptoms/signs were significantly improved after intervention of consulting team in pain (P = 0.000), shortness of breath (P = 0.000), difficulty in sleeping (P = 0.002), nausea (P = 0.004), constipation (P = 0.008), changes in skin (P = 0.024) and adoption (P = 0.000). This new system had significant improvement in the terminal cancer patients' symptoms/signs control in acute wards and could contribute to the care quality of home care patients.


Assuntos
Atenção à Saúde/métodos , Neoplasias/terapia , Cuidados Paliativos/métodos , Encaminhamento e Consulta , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Serviços de Assistência Domiciliar , Cuidados Paliativos na Terminalidade da Vida/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Cuidados Paliativos/psicologia , Satisfação do Paciente , Taiwan , Doente Terminal/psicologia
10.
Hong Kong Med J ; 15(3 Suppl 3): 13-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19494390

RESUMO

In Taiwan, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with haematological diseases since 1983. Thereafter till 2007, there were 2537 patients who had undergone HSCT in more than 15 hospitals. Their diseases included acute myeloid leukaemia in 27.8% of cases, non-Hodgkin's lymphoma 23.3%, acute lymphoblastic leukaemia 12.8%, chronic myeloid leukaemia 11.9%, severe aplastic anaemia 8.7%, and multiple myeloma 4.1%. Most of the cases received myeloablative conditioning regimens. More than 15% of cases received non-myeloablative regimens, and the mean age of these cases was at least 10 years older than those who received myeloablative regimens. The types of graft included peripheral blood (60.4%) and bone marrow (32.0%). A total of 35% of patients received autologous grafts. Of 1557 allogeneic HSCT patients, 338 (21.7%) received grafts from unrelated donors. Cord blood transplantation has been successfully performed in paediatric patients with thalassaemia major and with a large body size, and adult patients. The incidence of acute graft-versus-host disease was relatively low in Taiwan. On the contrary, a relatively higher proportion of hepatitis B carrier in the recipients had led to a higher incidence of reactivation hepatitis, which was markedly decreased following lamivudine prophylaxis. In conclusion, HSCT has become a routine therapy for major medical centres in Taiwan. Our unique experiences in the past decades also contributed to the progress of HSCT. With the establishment of professional association and patient supportive groups, we hope we can fully improve our daily practice and clinical as well as basic research in HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Adulto , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/tendências , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/etnologia , Humanos , Prevalência , Sistema de Registros/estatística & dados numéricos , Taiwan/epidemiologia , Transplante Homólogo/tendências
11.
Hong Kong Med J ; 15(3 Suppl 3): 42-4, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19494397

RESUMO

Impact of hepatitis B virus (HBV) infection on haematopoietic stem cell transplantation (HSCT) was reported earlier since late 1980s. It was shown that changing patterns of HBV serological markers was accompanied by variable severity of hepatitis after transplantation. Recipient's hepatitis B virus surface antigen (HBsAg) positivity was not considered an absolute contra-indication to allogeneic HSCT. However, HBsAg positivity was an important risk factor of reactivation hepatitis after transplantation, especially in allogeneic setting. Managing HBV reactivation in HSCT recipients was not successful till the availability of lamivudine since mid-1990s. For HBsAg-positive recipients, prophylactic lamivudine has been shown to significantly reduce reactivation hepatitis. As for HBsAg-negative recipients, there have been a small number of patients who develop so-called reverse seroconversion, that is, appearance of HBsAg after transplantation. In addition to chronic graft-versus-host disease, the risk was also high in allogeneic HSCT recipients who received fludarabine-antithymocyte globulin-containing conditioning regimens. The HBV is harboured earlier in the recipients before transplantation rather than transmitted via transfusion. At present, the optimal duration of lamivudine prophylaxis is not well-defined, and there are several fatal cases associated with early withdrawal and resistant HBV mutants. In conclusion, in HBV-endemic areas, the war between HBV and HSCT recipients continued even though several anti-HBV agents and molecular detection techniques are available. It deserves additional effort to overcome and also presents a chance to elucidate underlying mechanisms of HBV immunity, which are not easily studied in non-HSCT setting.


Assuntos
Doenças Endêmicas/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Humanos , Taiwan/epidemiologia , Ativação Viral
12.
J Infect ; 58(2): 154-60, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19162330

RESUMO

OBJECTIVE: To explore the impact of retention of non-tunneled central venous catheters (CVCs) on survival in candidemic cancer patients, where CVCs are commonly used and essential. A second object was to determine whether early CVC removal would benefit a subset of cancer patients. METHODS: We retrospectively evaluated 92 cancer patients who had a single, non-tunneled CVC in place. Patients were grouped according to CVC retention or removal; the later group was subdivided into early (CVC removed

Assuntos
Candidíase/terapia , Cateterismo Venoso Central/efeitos adversos , Fungemia/terapia , Neoplasias/complicações , Idoso , Idoso de 80 Anos ou mais , Candida/isolamento & purificação , Candidíase/mortalidade , Feminino , Fungemia/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
13.
Bone Marrow Transplant ; 42 Suppl 1: S133-S136, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18724286

RESUMO

In Taiwan, hematopoietic SCT (HSCT) has been used to treat patients with hematological diseases since 1983. Since then, more than 2200 patients have undergone HSCT in 15 large hospitals. The disease entities included acute leukemia in 37% of cases, non-Hodgkin's lymphoma in 26%, CML in 10%, multiple myeloma in 7% and severe aplastic anemia in 6%. The conditioning regimens used were mainly myeloablative (84% of cases). Non-myeloablative regimens were fludarabine-based. The average age of allogeneic recipients was at least 10 years older than those in the era before their application. The grafts of all patients were derived from peripheral blood in 85% of cases, BM in 13% and cord blood (CB) in 2%. Forty percent of HSCT patients received autologous grafts, whereas more than 25% of allogeneic HSCT patients received grafts from unrelated donors, and overall, there were more than 200 Taiwan HSCT recipients. Currently, CB has been used successfully in pediatric patients with thalassemia major and also in adult patients with hematological malignancy. After transplantation, there was a relatively lower prevalence of acute GVHD. However, a relatively higher proportion of hepatitis B carriers in the recipients had led to a higher incidence of viral reactivation and clinical hepatitis, which was dramatically decreased following lamivudine prophylaxis. In conclusion, HSCT has been successfully adapted to routine clinical care in Taiwan. Several important findings contributing to the progress of HSCT in the past two decades have also been noticed on this island.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Taiwan , Doadores de Tecidos
14.
Oncogene ; 26(10): 1459-67, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16936774

RESUMO

Major causes of head and neck squamous cell carcinoma (HNSCC)-related deaths are cervical node and distant metastasis. We previously demonstrated that overexpression of the DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) is a prognostic marker of advanced HNSCCs. Epithelial-mesenchymal transition (EMT) was demonstrated to be the major mechanism responsible for mediating invasiveness and metastasis of late-stage cancers. We therefore investigated the role of NBS1 overexpression in mediating EMT and metastasis. NBS1 overexpression was associated with metastasis of HNSCC patients using tissue microarray-immunohistochemistry approach. Induction of EMT was observed in an NBS1-overexpressing HNSCC cell line (FADUNBS), whereas short-interference RNA (siRNA)-mediated repression of endogenous NBS1 reversed the shift of EMT markers. Increased migration/invasiveness of FADUNBS was shown by in vitro and in vivo assays. NBS1 overexpression upregulated the expression of an EMT regulator Snail and its downstream target matrix metalloproteinase-2. EMT phenotypes and increased migration/invasiveness of FADUNBS cells were reversed by siRNA-mediated repression of Snail expression or a phosphatidylinositol 3-kinase-specific inhibitor. In HNSCC samples, co-expression of NBS1/Snail in primary tumors correlated with metastasis and the worst prognosis. These results indicate that NBS1 overexpression induces EMT through the upregulation of Snail expression, and co-expression of NBS1/Snail predicts metastasis in HNSCCs.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Transformação Celular Neoplásica , Quebras de DNA de Cadeia Dupla , Epitélio , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Mesoderma , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/patologia , Prognóstico , RNA Interferente Pequeno/farmacologia , Fatores de Transcrição da Família Snail , Células Tumorais Cultivadas
15.
Oncogene ; 26(19): 2781-90, 2007 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-17072345

RESUMO

The epithelial-mesenchymal transition (EMT) is crucial for the invasion and metastasis of many epithelial tumors including colorectal carcinoma (CRC). In the present study, a scattering and fibroblastic morphology with reduced intercellular contacts was found in the SW480 colon cancer cells overexpressing the gene encoding thymosin beta4 (Tbeta4), which was accompanied by a loss of E-cadherin as well as a cytosolic accumulation of beta-catenin, two most prominent markers of EMT. Whereas E-cadherin downregulation was likely to be accounted by a ZEB1-mediated transcriptional repression, the accumulation of beta-catenin was a result of glycogen synthase kinase-3beta inactivation mediated by integrin-linked kinase (ILK) and/or its downstream effector, Akt. Intriguingly, ILK upregulation in Tbeta4-overexpressing SW480 cells seemed to be attributed mainly to a stabilization of this kinase by complexing with particularly interesting new Cys-His protein (PINCH) more efficiently. In the meantime, a strong correlation between the expression levels of Tbeta4, ILK and E-cadherin in CRC patients was also revealed by immunohistochemical analysis. Taken together, these data suggest a novel role of Tbeta4 in promoting CRC progression by inducing an EMT in tumor cells via upregulating ILK and consequentially its signal transduction.


Assuntos
Neoplasias do Colo/enzimologia , Neoplasias Colorretais/metabolismo , Células Epiteliais/metabolismo , Mesoderma/citologia , Proteínas Serina-Treonina Quinases/metabolismo , Timosina/farmacologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Caderinas/metabolismo , Caseína Quinase I/metabolismo , Neoplasias do Colo/patologia , Neoplasias Colorretais/secundário , Proteínas de Ligação a DNA/metabolismo , Inibidores Enzimáticos/farmacologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Técnicas Imunoenzimáticas , Proteínas com Domínio LIM , Proteínas de Membrana , Mesoderma/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Proteínas Serina-Treonina Quinases/genética , RNA Antissenso/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Timosina/antagonistas & inibidores , Timosina/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Transfecção , Células Tumorais Cultivadas , Regulação para Cima , Homeobox 1 de Ligação a E-box em Dedo de Zinco , beta Catenina/metabolismo
16.
Neuroscience ; 140(4): 1467-79, 2006 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-16650619

RESUMO

In CA1 area and the hilus of the dentate gyrus of the mouse hippocampus, drastic reduction of NeuN, calbindin, calretinin, or parvalbumin immunopositive neurons was shown at 3, 7 and 60 days after pilocarpine-induced status epilepticus. In gliotic CA1 area at 60 days, few dendritic branches of calcium binding protein immunopositive neurons could be found suggesting reorganization of the afferents of surviving calcium binding protein immunopositive neurons. Calbindin, calretinin, or parvalbumin and 5-bromo-2'-deoxyuridine (BrdU) double labeling showed that calcium binding protein immunopositive neurons in gliotic CA1 area at 60 days were surviving instead of newly generated neurons. Iontophoretic injection of Phaseolus vulgaris leucoagglutinin into the medial septum and the nucleus of the diagonal band of Broca or the lateral entorhinal cortex showed contacts between Phaseolus vulgaris leucoagglutinin immunopositive en passant and terminal boutons and surviving calcium binding protein immunopositive neurons in the hippocampus. The presence in the gliotic hippocampus of enlarged and/or aggregated bouton-like structures 60 days after pilocarpine-induced status epilepticus is indicative for the reorganization of connections between the hippocampal afferents and surviving hippocampal neurons. This reconstruction could be a factor in the ongoing epileptic activity in this model of mesial temporal lobe epilepsy.


Assuntos
Proteínas de Ligação ao Cálcio/biossíntese , Córtex Entorrinal/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Núcleos Septais/metabolismo , Vias Aferentes/química , Vias Aferentes/metabolismo , Animais , Proteínas de Ligação ao Cálcio/análise , Córtex Entorrinal/química , Hipocampo/química , Masculino , Camundongos , Neuroglia/química , Neuroglia/metabolismo , Neurônios/química , Núcleos Septais/química
17.
Cell Mol Life Sci ; 63(6): 663-71, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16501890

RESUMO

Colorectal carcinoma (CRC) is a complicated and often fatal genetic disease. Fortunately, owing to rapid expansion of knowledge and technology development in oncology, much progress has been made regarding the diagnosis, understanding of the molecular genetics and malignant progression, as well as the novel regimens of CRC. In this review, we summarize the staging system, the most critical genetic and epigenetic alterations, the pleiotropic effects of MMP-7, the controversial roles of Hedgehog signaling, the intriguing involvement of thymosin beta-4, and the possible contribution of the putative colon (cancer) stem cells in CRC tumorigenesis. Current treatments as well as several potentially applicable therapeutic strategies for CRC are also discussed.


Assuntos
Carcinoma/etiologia , Neoplasias Colorretais/etiologia , Estadiamento de Neoplasias , Animais , Carcinoma/genética , Carcinoma/terapia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Proteínas Hedgehog , Humanos , Metaloproteinase 7 da Matriz/metabolismo , Células-Tronco/fisiologia , Timosina/metabolismo , Transativadores/metabolismo
18.
Surg Endosc ; 19(5): 702-4, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15759183

RESUMO

BACKGROUND: Flexible endoscopy is a vital component of gastrointestinal surgery. It has and will replace many of the surgical procedures now commonly performed. Flexible endoscopy, unfortunately, is not an integral part of surgical residency training based on resident operative experience as reported by the Residency Review Committee. Moreover, general surgeons have deferred the practice of flexible endoscopy to the gastroenterologists because of concerns over turf battles and referral patterns. The purpose of this study was to assess the overall case load and the economic impact of flexible endoscopy on the practice of general surgery in a community hospital setting. METHODS: This retrospective review was performed over a 6-month period. The total cases and the total billings of inpatient and outpatient procedures for a group practice of five general surgeons in a community hospital were evaluated. The billings were the actual charges based on current procedural terminology (CPT) codes for these procedures using the Medicare fee schedule. RESULTS: Of the 2,159 procedures performed, 1,154 involved flexible endoscopy cases accounting for 54% of all cases (1,154 of 2,159) performed from February 1, 2003 to July 31, 2003. Flexible endocopy accounted for 43% of the total charges. A. total of 46 surgical procedures and 216 future endoscopies were generated from the flexible endoscopic procedures. Future endoscopic cases were for surveillance of colonic neoplasia and Barrett's esophagus. CONCLUSIONS: Flexible endoscopy contributed to a major portion of the caseload and revenue generated by the general surgery group studied. The overall impact of flexible endoscopy is even greater than reported because of the future endoscopic surveillance cases or surgical interventions generated on the basis of endoscopic findings.


Assuntos
Endoscopia do Sistema Digestório/economia , Cirurgia Geral/economia , Hospitais Comunitários/economia , Prática Profissional/economia , Procedimentos Cirúrgicos Ambulatórios/economia , Procedimentos Cirúrgicos do Sistema Digestório/economia , Custos Diretos de Serviços , Honorários e Preços , Prática de Grupo/economia , Custos Hospitalares , Humanos , Pacientes Internados , Medicare/economia , Estudos Retrospectivos
19.
Eur J Haematol ; 74(2): 152-7, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15654907

RESUMO

Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen-matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post-transplant function from January 1995 to December 2002. Of 20 patients, eight received non-myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12 months post-transplant. Possible pre-HSCT and post-HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non-myeloablative conditioning therapy. We conclude that non-myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post-transplant pulmonary function changes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Pulmão/fisiopatologia , Testes de Função Respiratória , Condicionamento Pré-Transplante , Adulto , Volume Expiratório Forçado , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Pessoa de Meia-Idade , Transplante Homólogo
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