RESUMO
PURPOSE: This study aims to evaluate survival and the objective response to neoadjuvant combination therapy with gemcitabine and radiation therapy in patients with biliary tract cancer. METHODS: The chemoradiation therapy regimen consisted of 3 cycles of full-dose gemcitabine (1000 mg/m2 at days 1, 8, and 15, every 4 weeks) with 50-60 Gy radiation. We compared 27 patients who received neoadjuvant chemoradiation therapy and 79 patients who were treated without neoadjuvant therapy. Hemi-hepatectomy or pancreatoduodenectomy was planned for all of the patients in the study population. CT-based staging was used to adjust for the pre-treatment characteristics of the patients. RESULTS: After confirming the reproducibility of CT-based staging, we analyzed the survival of the patients. The multivariate analysis showed that the absence of arterial invasion on CT, the absence of lymph node swelling, and neoadjuvant therapy were independent prognostic factors. The three-year recurrence-free survival (RFS) rates in patients treated with and without neoadjuvant therapy were 78% and 58%, respectively (P = 0.0263). The adjusted overall survival (OS) (determined by the inverse probability of treatment weighting method using the inverse propensity score) was improved by neoadjuvant therapy (P = 0.00187); the hazard ratio was 0.3505. CONCLUSIONS: Neoadjuvant chemoradiation therapy might have the potential to improve RFS and OS. REGISTRATION: UMIN-CTR UMIN000015450.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/terapia , Quimiorradioterapia , Colangiocarcinoma/terapia , Desoxicitidina/análogos & derivados , Hepatectomia , Terapia Neoadjuvante , Pancreaticoduodenectomia , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Neoplasias do Sistema Biliar/diagnóstico por imagem , Neoplasias do Sistema Biliar/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/patologia , Tumor de Klatskin/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , GencitabinaRESUMO
BACKGROUND: We developed a prediction tool for recurrence and survival in patients with stage IV colorectal cancer (CRC) following surgically curative resection. PATIENTS AND METHODS: From January 1983 to December 2012, 113 patients with CRC and synchronous liver and/or lung metastatic CRC were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. All patients underwent curative resection of primary and metastatic lesions. In the group of patients who underwent surgery from 1983 to 2008, a Cox regression model was used to develop prediction models for 1-year, 3-year and 5-year cancer-specific survival (CSS) and relapse-free survival (RFS). In the other group of patients who underwent surgery from 2009 to 2012, the developed prediction model was validated. RESULTS: Univariate analysis of clinicopathological factors showed that the following factors were significantly correlated with CSS and RFS: preoperative serum carcinoembryonic antigen level, tumour location, pathologically defined tumour invasion and lymph node metastasis, and synchronous metastatic lesions. Using these variables, novel prediction models predicting CSS and RFS were constructed using the Cox regression model with concordance indexes of 0.802 for CSS and 0.631 for RFS. The prediction models were validated by external data sets in an independent patient group. CONCLUSIONS: We developed novel and reliable personalised prognostic models, integrating tumour, node, metastasis (TNM) factors as well as the preoperative serum carcinoembryonic antigen level, tumour location and metastatic lesions, to predict patients' prognosis following surgically curative resection. This individualised prediction model may help clinicians in the treatment of postoperative stage IV CRC following surgically curative resection.
RESUMO
BACKGROUND: The optimal surgical resection method in patients with HCC to minimize the risk of local recurrence has not yet been determined. The aim of this study was to compare the prognosis following anatomical versus non-anatomical hepatic resection for hepatocellular carcinoma (HCC). METHODS: Consecutive patients with HCC without macroscopic vascular invasion, treated by curative resection between 1981 and 2012 at Osaka Medical Centre, were included in this retrospective study. The outcomes of patients selected by propensity score matching were compared. RESULTS: Some 1102 patients were included, 577 in the anatomical and 525 in the non-anatomical resection group. By propensity score matching, 329 patients were selected into each group. Demographic, preoperative and tumour variables were similar between the propensity score-matched groups, including tumour size, tumour multiplicity, α-fetoprotein level and 15-min indocyanine green retention rate at 15 min. The incidence of microvascular invasion was higher in the matched anatomical resection group (P = 0·048). Stratified analysis of recurrence-free and overall survival rates revealed no statistically significant differences between the two propensity score-matched groups (P = 0·704 and P = 0·381 respectively). There was also no significant difference in the early recurrence rate within 2 years after resection between these groups (P = 0·726). Subset analysis of the early recurrence-free survival rate in patients with and without microvascular invasion revealed no significant differences between the groups (P = 0·312 and P = 0·479 respectively). CONCLUSION: The resection method had no impact on the risk of HCC recurrence or survival.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/anatomia & histologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The branches of the LSA are the main causative arteries for lacunar infarction, though the vascular changes are largely unknown. Herein, we examined the correlation of LSA imaging findings in patients with lacunar infarction compared with controls by using FSBB-MRA. MATERIALS AND METHODS: Fifteen patients (9 men, 6 women; mean age, 73 years) with infarction at the basal ganglia and/or its vicinity were prospectively enrolled, and 12 aged-matched control subjects (6 men, 6 women; mean age, 68 years) were examined by using FSBB-MRA on a 1.5T MR imaging system. Total number and length of visualized LSA branches were compared by a 2-tailed 2-sample t test. Stepwise multiple regression analyses were performed, including hypertension, hyperlipidemia, smoking history, and diabetes mellitus after evaluation of their colinearity. P<.05 after correction for multiple comparisons was considered significant. RESULTS: Patients with stroke had significantly fewer LSA branches (average, 6.3; 95% CI, 5.4-7.1) than controls (8.7; 95% CI, 7.8-9.5) (P=.0003). The total LSA lengths were 117 mm (95% CI, 96-138 mm) for patients with stroke and 162 mm (95% CI, 133-91 mm) for control subjects (P=.01). In stepwise multiple regression analysis, only the LSA branch numbers were significantly related to infarction (P=.0003), while only hypertension was significantly related to total LSA length (P=.0085). CONCLUSIONS: Using FSBB-MRA to visualize LSA branches, we found a significant reduction in the numbers of LSA branches in patients with stroke, and hypertension was inversely related to total LSA length. FSBB is a promising method to investigate the LSA by using 1.5T MR imaging.
Assuntos
Doença Cerebrovascular dos Gânglios da Base/patologia , Gânglios da Base/irrigação sanguínea , Gânglios da Base/patologia , Angiografia por Ressonância Magnética/métodos , Acidente Vascular Cerebral Lacunar/patologia , Idoso , Idoso de 80 Anos ou mais , Doença Cerebrovascular dos Gânglios da Base/epidemiologia , Circulação Cerebrovascular , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperlipidemias/epidemiologia , Angiografia por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Fumar/epidemiologia , Acidente Vascular Cerebral Lacunar/epidemiologiaRESUMO
Para-aortic lymph node (PALN) recurrence is often seen in patients with lower thoracic esophageal cancer treated by esophagectomy with extended lymph node dissection. However, the clinicopathological characteristics of patients with PALN metastasis and the significance of PALN dissection are unknown. A total of 283 patients with lower thoracic esophageal cancer underwent esophagectomy with lymphadenectomy at our hospital between April 1984 and March 2007. Among these 283 patients, 60 patients were enrolled in this retrospective study according to following criteria: (i) clinical T2 to T4 tumor, (ii) no clinical PALN metastasis, and (iii) received PALN dissection. PALN dissection was indicated by a tumor depth of at least T2 and no severe complications. The clinicopathological data, recurrence pattern, and overall survival were compared between patients with PALN and without PALN metastasis. The mean length of surgery was 587 min and the mean blood loss was 1383 mL. The morbidity was 33.3% and mortality was 5% in this series. Sixteen patients (26.7%) had PALN metastasis; these showed significantly more lymph node metastases (15.8 ± 13.2 vs. 3.0 ± 3.2, P < 0.0001) and significantly worse survival rates (53.3% vs. 79.9% at 1 year, 6.7% vs. 62.0% at 3 years, P < 0.0001) than patients without PALN metastasis. The incidence of lymph node recurrence (P < 0.0001) and hematogenous recurrence (P= 0.0487) was also higher in patients with PALN metastasis than in patients without PALN metastasis. Among the 16 patients with PALN metastasis, a univariate analysis revealed total number of metastatic nodes < 8 (P= 0.0325) to be a significant prognostic factor. A multivariate logistic regression analysis of the regional lymph nodes identified the invasion of the lower mediastinal nodes (hazard ratio = 6.120) and retroperitoneal nodes (hazard ratio = 15.167) to be significantly correlated with PALN metastasis. PALN metastasis is suggested to be related to the systemic spread of lymphatic metastasis even in lower thoracic esophageal cancer. PALN dissection for pathological PALN(+) patients should not be performed. It remains to be determined in future prospective studies whether patients without pathological PALN metastasis, but showing PALN micrometastasis, could achieve improved survival with PALN dissection.
Assuntos
Neoplasias Abdominais/secundário , Neoplasias Esofágicas/patologia , Excisão de Linfonodo , Linfonodos/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Reflux of gastroduodenal contents and delayed gastric emptying are the most common and serious problems after esophagectomy with gastric reconstruction. However, attempts to reduce the above symptoms, surgically as well as non-surgically, had no or limited effect. To address this issue, we performed retrosternal gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis (RY) in eight patients with thoracic esophageal cancer and compared the outcomes with control patients who underwent standard reconstruction. The procedure is simple, safe, and not associated with any postoperative complications. The pancreatic amylase concentrations in the gastric juice samples on postoperative day 2 were slightly lower in the non-RY group than in the RY group (1884 ± 2152 vs. 25,790 ± 23,542IU/mL, respectively, P= 0.07). Postoperative endoscopic examination showed neither reflux esophagitis nor residual gastric content in the RY group. Quality of life assessed by the Dysfunction After Upper Gastrointestinal Surgery-32 questionnaire postoperatively was significantly better in the RY group than in the non-RY group for 'decreased physical activity,''symptoms of reflux,''nausea and vomiting,' and 'pain.' The results of this pilot study suggest that gastric reconstruction with duodenal diversion plus RY seems effective in improving both the reflux and delayed gastric emptying. The benefits of this procedure need to be further assessed in a large-scale, randomized controlled trial.
Assuntos
Anastomose em-Y de Roux , Carcinoma de Células Escamosas/cirurgia , Refluxo Duodenogástrico/prevenção & controle , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagoplastia/métodos , Esvaziamento Gástrico , Idoso , Amilases/metabolismo , Refluxo Duodenogástrico/etiologia , Duodeno/cirurgia , Feminino , Derivação Gástrica , Suco Gástrico/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Náusea/etiologia , Dor Pós-Operatória/etiologia , Projetos Piloto , Qualidade de Vida , Recuperação de Função Fisiológica , Estudos Retrospectivos , Estômago/cirurgia , Inquéritos e Questionários , Vômito/etiologiaRESUMO
An outbreak of acute keratoconjunctivitis involving 27 patients occurred in the Department of Ophthalmology, Kurume University Hospital. Adenoviral DNA was detected in four inpatients, one outpatient and one healthcare worker. Sequence-based typing of adenoviral DNA indicated serotype 3 from one inpatient, the rest being serotype 37. At a later stage of the outbreak adenoviral DNA types 37 and/or 3 were also detected from almost all environmental instruments and commonly used eye drops, despite thorough disinfection of the environment and enforcement of various infection control measures. The detection rate of adenoviral DNA in environmental swabs was 81%. A further second disinfection of the environment reduced the detection rate of adenoviral DNA to 38%. The outbreak ceased after closing the ophthalmology ward and outpatient consulting room, accompanied by enhanced cleaning of environmental instruments and the introduction of disposable eye drops for individual patients.
Assuntos
Infecções por Adenoviridae/epidemiologia , Infecção Hospitalar/virologia , Surtos de Doenças , Ceratoconjuntivite/virologia , Soluções Oftálmicas/efeitos adversos , Adenoviridae/classificação , Adenoviridae/genética , Adenoviridae/patogenicidade , Infecções por Adenoviridae/genética , Infecção Hospitalar/epidemiologia , Fômites/virologia , Hospitais Universitários , Humanos , Japão/epidemiologia , Ceratoconjuntivite/epidemiologiaRESUMO
The aim of this study was to assess the value of alphafeto protein (AFP) mRNA-expressing cells detected in peripheral blood for predicting tumor recurrence after living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). The test group consisted of 25 patients who underwent LDLT for end-stage liver disease with HCC while the control group consisted of 37 living donors. Quantitative real-time reverse-transcriptase polymerase chain reaction was used for detection of AFP mRNA-expressing cells in peripheral blood. Nine (36%) of 25 patients developed tumor recurrences (four lung; one liver; one peritoneum; two bone; one adrenal gland) during the follow-up period. Perioperatively, AFP mRNA was positive in peripheral blood of eight patients (32.0%) but only in 1 (2.7%) of the control. Preoperative AFP mRNA was positive in three cases. Univariate analyses revealed that preoperative and perioperative AFP mRNA and microscopical vascular invasion were the significant predictors for HCC recurrence (P = .007, .037, and .005, respectively). In the patients with HCC exceeding Milan criteria (n = 15), the presence of AFP mRNA-positive cells in the peripheral blood correlated significantly with HCC recurrence (P = .033). We concluded that the presence of AFP mRNA-expressing cells could be a useful predictor of HCC recurrence in liver transplant patients.
Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/fisiologia , RNA Mensageiro/sangue , RNA Mensageiro/genética , alfa-Fetoproteínas/genética , Adulto , Carcinoma Hepatocelular/genética , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/genética , Período Pós-Operatório , Valor Preditivo dos Testes , Recidiva , Estudos RetrospectivosRESUMO
We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell lines in vitro. The present study further investigated the in vivo anti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cells in vitro dose dependently, with a 50% inhibitory concentration (IC50) value of around 200 microM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water, ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Ácido Gálico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA de Neoplasias/análise , Relação Dose-Resposta a Droga , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Among 11 isoflavones tested, genistein [YS13] produced higher cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) than against normal cells (human gingival fibroblast, HGF), suggesting its tumor-specific action. Electron spin resonance (ESR) spectroscopy showed that YS13 did not produce radical, nor scavenged O2*- generated by hypoxanthine-xanthine oxidase reaction system, suggesting that radical-mediated oxidation mechanism is not be involved in the YS13-induced cytotoxicity. Addition of one prenyl group produced YS18 and YS19 with higher anti-Helicobacter pylori activity. Addition of two prenyl groups produced YS21 with the highest cytotoxic activity but lower tumor-specificity. Since YS21 produced the highest amount of radical and most efficiently scavenged O2*-, this compound may induce cytotoxicity by radical-mediated oxidation mechanism. All isoflavones failed to induce anti-human immunodeficiency virus (HIV) activity. These data suggest the medicinal efficacy of isoflavones.
Assuntos
Fármacos Anti-HIV/farmacologia , Anti-Infecciosos/farmacologia , Antineoplásicos/toxicidade , Isoflavonas/toxicidade , Animais , Antibacterianos , Fármacos Anti-HIV/química , Anti-Infecciosos/química , Antineoplásicos/química , Carcinoma de Células Escamosas/tratamento farmacológico , Bovinos , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Gengiva/citologia , Gengiva/efeitos dos fármacos , HIV/efeitos dos fármacos , Helicobacter pylori/efeitos dos fármacos , Humanos , Isoflavonas/química , Neoplasias Bucais/tratamento farmacológico , Neoplasias das Glândulas Salivares/tratamento farmacológico , Relação Estrutura-Atividade , Superóxidos/metabolismoRESUMO
We have previously found that T140, a 14-amino acid residue peptide, inhibits infection of target cells by T cell-line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. Here, we report synthesis and evaluation of bifunctional anti-HIV compounds, which are composed of T140 analogues and a reverse transcriptase inhibitor, 3'-azido-3'-deoxythymidine (AZT). Novel conjugated analogues have been proved to have the ability for controlled release of AZT in neutral aqueous media as well as mouse and feline sera, and high selectivity indexes (SIs, 50% cytotoxic concentration/50% effective concentration) caused by a synergistic effect of two different regenerating agents. Thus, these bifunctional compounds have several potential advantages. T140 analogues can possibly work as a carrier of AZT targeting T cells due to their specific affinity for CXCR4 on T cells. A synergistic effect by two types of regenerating agents may enable drug dosage to be reduced, and thus it may effectively suppress toxic side effects and the appearance of drug-resistant virus.
Assuntos
Fármacos Anti-HIV/síntese química , Receptores CXCR4/antagonistas & inibidores , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Gatos , Estabilidade de Medicamentos , HIV-1/efeitos dos fármacos , Meia-Vida , Humanos , Soros Imunes/metabolismo , Camundongos , Receptores CXCR4/química , Células Tumorais Cultivadas , Zidovudina/síntese química , Zidovudina/química , Zidovudina/farmacologiaRESUMO
We previously reported a truncated polyphemusin peptide analogue, T140, which efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. We have found that T140 is not stable in feline serum due to the cleavage of the C-terminal Arg,(14) indispensable for anti-HIV activity. On the other hand, a C-terminally amidated analogue of T140, TZ14004, has been found to be completely stable in incubation in the serum for 2 days. The C-terminal amide is thought to be needed for stability in serum. However, TZ14004 does not have fairly strong anti-HIV activity, but has relatively strong cytotoxicity, probably due to an increase by +1 charge from total +7 charges of T140. In our previous study, the number of total +6 charges seemed to be a suitable balance between activity and cytotoxicity. In this study, we have conducted a double-L-citrulline (Cit)-scanning study on TZ14004 based on the C-terminally amidated form in due consideration of the total net charges in the whole molecule to find novel effective CXCR4 inhibitors, TN14003 ([Cit(6)]-T140 with the C-terminal amide) and TC14012 ([Cit(6), D-Cit(8)]-T140 with the C-terminal amide), which possess high selectivity indexes (SIs) and complete stability in feline serum.
Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Citrulina/química , HIV-1/efeitos dos fármacos , Receptores CXCR4/antagonistas & inibidores , Animais , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/toxicidade , Gatos , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Estabilidade de Medicamentos , Humanos , Concentração Inibidora 50 , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Peptídeos/síntese química , Peptídeos/química , Peptídeos/farmacologiaRESUMO
The chemokine receptors CXCR4 and CCR5 are considered to be potential targets for the inhibition of HIV-1 replication. We found that the synthetic peptides T134 and T140 (see text for full names) inhibited X4 HIV-1 infection with selectivity and low toxicity because they acted as CXCR4 antagonists. However, high concentrations of T134, T140, and ALX40-4C (see text for full name) increased the expression of CCR5 and R5 HIV-1 infection, as did stromal cell-derived factor 1 (SDF-1). In contrast to CXCR4 antagonists and SDF-1, viral monocyte inflammatory protein (vMIP) II inhibited not only anti-CXCR4 monoclonal antibody (MAb) but also inhibited anti-CCR5 MAb binding to human peripheral blood mononuclear cells, and inhibited both X4 and R5 HIV-1 strains. T134, T140, ALX40-4C, and SDF-1 increased viral transcription in the treated cells. In addition, ALX40-4C and SDF-1 also increased nuclear transcription factor (NF)-kappaB. However, the mechanisms of action of T134 and T140 are different from those of clinically used anti-HIV drugs. Thus, synergistic activities were observed in the concomitant treatment with T134 and reverse transcriptase inhibitors or protease inhibitors. Our findings, presented here, are noteworthy in regard to the potential clinical use of these agents as drugs for the treatment of AIDS.
Assuntos
Fármacos Anti-HIV/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Quimiocinas CXC/farmacologia , Quimiocinas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , HIV-1/fisiologia , Oligopeptídeos/farmacologia , Receptores CCR5/biossíntese , Receptores CXCR4/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , Animais , Anticorpos Monoclonais/farmacologia , Benzilaminas , Antígenos CD4/biossíntese , Antígenos CD4/genética , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Células COS , Quimiocina CXCL12 , Chlorocebus aethiops , Ciclamos , Sinergismo Farmacológico , Repetição Terminal Longa de HIV , Compostos Heterocíclicos/farmacologia , Humanos , Metionina/análogos & derivados , Metionina/farmacologia , Fragmentos de Peptídeos/farmacologia , Receptores CCR5/genética , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/virologia , Zidovudina/farmacologiaRESUMO
The purpose of this study was to clarify which myocardial histological findings associated with dilated cardiomyopathy (DCM) are reflected in quantitative 201Tl myocardial SPECT. We obtained studied SPECT images from 21 patients with DCM 10 minutes and 2 hours after they received an injection of 111 MBq 201Tl at rest. We calculated the percent coefficient of variation of myocardial 201Tl counts [%CV(TI)], the washout rate (WR), standard deviation of WR [SD(WR)], extent score (ES) and severity score (SS). We used image analysis to measure % fibrosis, % myocytes, the ratio of fibrous tissue to myocyte tissue (F/My), myocyte size and standard deviation of myocyte size [SD(My)] in left ventricular endomyocardial biopsy specimens. The %CV(Tl) was correlated with % fibrosis and F/My. The ES and SS also correlated with F/My. The correlation between SD(WR) and SD(My) was significant. The present findings suggest that %CV(Tl), ES and SS of rest 201Tl SPECT reflect myocardial fibrosis and that the standard deviation of washout reflects the distribution of myocyte size.
Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/patologia , Coração/diagnóstico por imagem , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Biópsia , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Compostos RadiofarmacêuticosRESUMO
Betulinic acid, a triterpenoid isolated from the methyl alcohol extract of the leaves of Syzigium claviflorum, was found to have a potent inhibitory activity against human immunodeficiency virus type 1 (HIV-1). Betulinic acid derivatives were synthesized to enhance the anti-HIV activity. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl) betulinic acid, designated YK-FH312, showed the highest activity against HIV-induced cytopathic effects in HIV-1-infected MT-4 cells. To determine the step(s) of HIV replication affected by YK-FH312, a syncytium formation inhibition assay in MOLT-4/HIV-1(IIIB) and MOLT-4 coculture, a multinuclear-activation-of-galactosidase-indicator (MAGI) assay in MAGI-CCR5 cells, electron microscopic observation, and a time-of-addition assay were performed. In the syncytium formation inhibition assay or in the MAGI assay for de novo infection, the compound did not show inhibitory effects against HIV replication. Conversely, no virions were detected in HIV-1-infected cell cultures treated with YK-FH312 either by electron microscopic observation or by viral yield in the supernatant. In accordance with a p24 enzyme-linked immunosorbent assay of culture supernatant in the time-of-addition assay, YK-FH312 inhibited virus expression in the supernatant when it was added 18 h postinfection. However, Western blot analysis of the cells in the time-of-addition assay revealed that the production of viral proteins in the cells was not inhibited completely by YK-FH312. These results suggest that YK-FH312 might affect the step(s) of virion assembly and/or budding of virions, and this is a novel mechanism of action of an anti-HIV compound.
Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Triterpenos/farmacologia , Fusão Celular , Formazans/metabolismo , Células Gigantes/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , HIV-1/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Triterpenos Pentacíclicos , Sais de Tetrazólio/metabolismo , Fatores de Tempo , Células Tumorais Cultivadas , Proteínas Virais/metabolismo , Vírion/efeitos dos fármacos , Vírion/ultraestrutura , Ácido BetulínicoRESUMO
A 24-year-old male presented with headache. He had been treated with antituberculous drugs for 19 months. MRI revealed 4 intracranial Gd-DTPA enhanced lesions surrounded by massive edema in the right frontal, both occipital and left basal ganglionic regions. Digital subtraction angiography showed no tumor stain. Two procedures for tumor resection were performed for the right frontal and left occipital regions, the latter of which definitively diagnosed by the polymerase chain reaction method. The tumors were well demarcated, showed a rough surface, and were elastically hard. The two residual lesions responded differently to chemotherapy. The lesion in the right occipital region decreased in size, while the other in the left basal ganglionic region continued to grow gradually 26 months after the antituberculous chemotherapy was started. According to previous reports, treatment should be continued for as long as 12-30 months in cases showing paradoxical expansion. In this case, the left basal ganglionic lesion began to decrease in size after 28 months of administration of anti-tuberculous drugs. We report successful treatment of a case of multiple tuberculomas presenting with paradoxical expansion managed by a combination of surgery and continuous chemotherapy.
Assuntos
Tuberculoma Intracraniano/patologia , Adulto , Neoplasias Encefálicas/diagnóstico , Diagnóstico Diferencial , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Masculino , Tuberculoma Intracraniano/diagnóstico , Tuberculoma Intracraniano/cirurgiaRESUMO
In the present paper, we examined a mechanism of the papaverine induced relaxation in the smooth muscle of non-pregnant rat uterus. The hyperosmotic 65 mM KCl (H-65K+)-or oxytocin-induced contraction in the uterus was inhibited by an addition of papaverine in a concentration-dependent manner. Papaverine did not increase both cAMP and cGMP contents in the uterus in the presence of H-65K+ or oxytocin. In fura 2 loaded muscles, papaverine did not affect an increase of [Ca2+]i level by high K+ or oxytocin. In permeabilized muscles, papaverine had no effect on the Ca2+-induced contraction. H-65K+ and oxytocin increased the rate of oxygen consumption 1.8 and 1.5 times higher than that in the resting condition, respectively. The increase of oxygen consumption in the H-65K+ or oxytocin was significantly inhibited by papaverine (1-100 microM). These results suggested that papaverine inhibits smooth muscle contraction mainly by inhibition of mitochondrial respiration in rat uterus as well as guinea pig ileum, which shows a highly spontaneous activity and a highly metabolic dependency of a contraction.
Assuntos
Músculo Liso/efeitos dos fármacos , Papaverina/farmacologia , Útero/efeitos dos fármacos , Animais , Cálcio/análise , AMP Cíclico/análise , GMP Cíclico/análise , Feminino , Cobaias , Técnicas In Vitro , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ocitocina/farmacologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Three major components of human telomerase, RNA component (hTERC), telomerase-associated protein (TEP1), and catalytic subunit (hTERT) have been cloned recently. The aim of this study was to examine the expression of these genes and to search for clinical usefulness. METHODS: Expression of these genes was evaluated by reverse transcription-polymerase chain reaction in 92 human lung cancers and in 32 non-neoplastic lung tissues. In 15 patients, both telomerase activity by telomeric repeat amplification protocol assay and expression were evaluated. RESULTS: hTERT expression was best associated with telomerase activity with a concordance of 77%. In 92 lung cancer tissues, hTERC, TEP1, and hTERT were expressed in 100%, 93%, and 89%, respectively. Whereas most adjacent non-neoplastic lung tissues expressed hTERC and TEP1 (94% and 100%, respectively), hTERT was detected in only 1 of 32 normal lungs. However, there was no relationship between hTERT expression and clinicopathologic features. CONCLUSIONS: hTERT expression can be a surrogate for telomerase activity that may serve as a novel biomarker of lung cancer with high specificity and sensitivity.
Assuntos
Adenocarcinoma/enzimologia , Carcinoma de Células Escamosas/enzimologia , Proteínas de Transporte/metabolismo , Domínio Catalítico , Neoplasias Pulmonares/enzimologia , RNA , Telomerase/genética , Telomerase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Proteínas de Ligação a DNA , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas de Ligação a RNA , DNA Polimerase Dirigida por RNA/genética , DNA Polimerase Dirigida por RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Análise de Sobrevida , Células Tumorais CultivadasRESUMO
There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. Recently, the usefulness of combined cancer agent chemotherapy based on the concept of biochemical modulation has been reported. For example sequential MTX and 5-FU therapy, low-dose CDDP plus 5-FU, and the like. In this paper, we report the usefulness of low-dose CDDP plus 5-FU therapy in combination with pirarubicin (THP) for inoperable scirrhous type gastric cancer. A 32-year-old man who was suffering from scirrhous type gastric cancer with pyloric stenosis was treated with this regimen. Eight weeks after the start of therapy, his gastric capacity and lumen diameter had clearly increased, and he was taking ordinary meals. Ascites had also completely disappeared. CR has now been continued about 7 months. This regimen is considered to be promising for scirrhous type gastric cancers with a poor prognosis.
Assuntos
Adenocarcinoma Esquirroso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Esquema de Medicação , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , MasculinoRESUMO
Damage to the paraspinal muscle after various lumbar back surgery procedures was evaluated by measuring the paraspinal muscle thickness preoperatively and postoperatively in 89 patients, 61 males and 28 females. There were 42 single interlaminar level procedures (SL group), 13 multiple interlaminar level procedures (ML group), and 34 posterolateral fusion procedures (PLF group). Changes in paraspinal muscle thickness were evaluated at more than 10 months after surgery, because muscle swelling continued as long as 10 months after surgery, and then reduced as the edema subsided. Postoperative serum creatine phosphokinase (CPK) level on postoperative day 2 was also measured. The decrease of paraspinal muscle thickness was significantly larger in the PLF group than in the SL group (-12.9% and -2.7%, respectively, p < 0.02). There was no significant correlation between postoperative serum CPK level and decrease of paraspinal muscle thickness. However, the postoperative elevation of serum CPK level was significantly higher in the PLF group than in the SL and ML groups (979 +/- 114 vs. 292 +/- 45 and 410 +/- 44 IU/l, respectively, p < 0.001). In conclusion, posterolateral fusion is the most invasive procedure of the paraspinal muscles in various lumbar back surgery procedures. Paraspinal muscle damage during lumbar back surgery may be one of the most important factors that causes atrophy of the muscles.