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1.
Ann Oncol ; 32(12): 1496-1510, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34411693

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.


Assuntos
Neoplasias do Colo , Oncologia , Ásia/epidemiologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/terapia , Seguimentos , Humanos , República da Coreia
2.
Ann Oncol ; 31(7): 861-872, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272210

RESUMO

A Japan Society of Clinical Oncology (JSCO)-hosted expert meeting was held in Japan on 27 October 2019, which comprised experts from the JSCO, the Japanese Society of Medical Oncology (JSMO), the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the Taiwan Oncology Society (TOS). The purpose of the meeting was to focus on what we have learnt from both microsatellite instability (MSI)/deficient mismatch repair (dMMR) biomarkers in predicting the efficacy of anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) immunotherapy, and the neurotrophic tyrosine receptor kinase (NTRK) gene fusions in predicting the efficacy of inhibitors of the tropomyosin receptor kinase (TRK) proteins across a range of solid tumour types. The recent regulatory approvals of the anti-PD-1 antibody pembrolizumab and the TRK inhibitors larotrectinib and entrectinib, based on specific tumour biomarkers rather than specific tumour type, have heralded a paradigm shift in cancer treatment approaches. The purpose of the meeting was to develop international expert consensus recommendations on the use of such tumour-agnostic treatments in patients with solid tumours. The aim was to generate a reference document for clinical practice, for pharmaceutical companies in the design of clinical trials, for ethics committees in the approval of clinical trial protocols and for regulatory authorities in relation to drug approvals, with a particular emphasis on diagnostic testing and patient selection.


Assuntos
Ensaios Clínicos como Assunto , Instabilidade de Microssatélites , Neoplasias , Humanos , Consenso , Japão , Oncologia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Taiwan
3.
Ann Oncol ; 30(1): 34-43, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475943

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.


Assuntos
Neoplasias Esofágicas , Humanos , Ásia , Consenso , Gerenciamento Clínico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/secundário , Neoplasias Esofágicas/terapia , Sociedades Médicas
4.
Ann Oncol ; 30(1): 19-33, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475956

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.


Assuntos
Neoplasias Gástricas , Humanos , Ásia , Consenso , Gerenciamento Clínico , Sociedades Médicas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/secundário , Neoplasias Gástricas/terapia
5.
Ann Oncol ; 29(1): 44-70, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29155929

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Povo Asiático , China , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , Humanos , Malásia , Metástase Neoplásica , República da Coreia , Taiwan
6.
Br J Cancer ; 110(10): 2434-40, 2014 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-24755882

RESUMO

BACKGROUND: Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours. METHODS: Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course. RESULTS: Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ∼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile. CONCLUSIONS: These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pteridinas/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Terapia Combinada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Meia-Vida , Doenças Hematológicas/induzido quimicamente , Humanos , Infusões Intravenosas , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/enzimologia , Neoplasias/patologia , Neoplasias/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Pteridinas/administração & dosagem , Pteridinas/efeitos adversos , Pteridinas/farmacocinética , Taiwan , Resultado do Tratamento , Quinase 1 Polo-Like
7.
ESMO Open ; 9(2): 102226, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458658

RESUMO

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Seguimentos , Ásia , Oncologia , Sociedades Médicas
8.
Ann Oncol ; 24(2): 463-468, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23059959

RESUMO

BACKGROUND: The purpose of this study is to characterize the risk factors of bloodstream infection (BSI) associated with the use of permanent implantable venous ports (Port-A) in solid cancer patients. METHODS: Solid cancer patients implanted with a Port-A were prospectively observed for the occurrence of Port-A-associated BSI (PABSI), defined as BSI without other identifiable infection foci. A PABSI risk score was developed using the Cox proportional hazards model. RESULTS: A total of 415 patients were registered; 88 PABSI episodes occurred in 58 patients (incidence1.05 per 1000 catheter-days). All but one patient had stage IV cancer. Independent predictors of PABSI occurrence included neutropenia, total parenteral nutrition (TPN), chronic steroid use, invasive procedures, postoperative antibiotics, and preoperative antibiotics. A PABSI risk score with a cut-off value of 0 (sensitivity 88.5%, specificity 64.3%) was defined for stage IV cancer patients as follows: neutropenia, +1.350; TPN, +1.256; chronic steroid use, +1.947; preoperative antibiotics, -0.970; postoperative antibiotics, +0.959; and invasive procedures, +1.098. The median PABSI-free survival was 4.47 months for patients with scores ≥ 0 but not reached for patients with scores <0 (P < 0.0001). CONCLUSION: The PABSI risk score can assist in identifying high-risk solid cancer patients and may assist in designing future preventive strategies.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Nutrição Parenteral Total/efeitos adversos , Sepse/mortalidade , Dispositivos de Acesso Vascular/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neutropenia , Modelos de Riscos Proporcionais , Risco , Sepse/epidemiologia , Sepse/microbiologia , Sobrevida , Adulto Jovem
9.
West Indian Med J ; 62(7): 651-3, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24831906

RESUMO

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas of the breast.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Antraciclinas/administração & dosagem , Evolução Fatal , Feminino , Humanos , Ifosfamida/administração & dosagem , Tamoxifeno/administração & dosagem , Adulto Jovem
10.
ESMO Open ; 8(3): 101558, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37236086

RESUMO

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.


Assuntos
Neoplasias do Colo , Humanos , Seguimentos , Ásia , Sociedades Médicas , Oncologia
11.
Curr Biol ; 9(12): 661-4, 1999 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-10375532

RESUMO

Many tumorigenic processes affect cell-cycle progression by their effects on the levels of the cyclin-dependent kinase inhibitor p27(Kip1) [1,2]. The phosphorylation- and ubiquitination-dependent proteolysis of p27 is implicated in control of the G1-S transition in the cell cycle [3-6]. To determine the factors that control p27 stability, we established a cell-free extract assay that recapitulates the degradation of p27. Phosphorylation of p27 at Thr187 was essential for its degradation. Degradation was also dependent on SCF(Skp2), a protein complex implicated in targeting phosphorylated proteins for ubiquitination [7-10]. Immunodepletion of components of the complex - Cul-1, Skp1, or Skp2 - from the extract abolished p27 degradation, while addition of purified SCF(Skp2) to Skp2- depleted extract restored the capacity to degrade p27. A specific association was observed between Skp2 and a p27 carboxy-terminal peptide containing phosphorylated Thr187, but not between Skp2 and the non-phosphorylated peptide. Skp2-dependent associations between Skp1 or Cul-1 and the p27 phosphopeptide were also detected. Isolated SCF(Skp2) contained an E3 ubiquitin ligase activity towards p27. Our data thus suggest that SCF(Skp2) specifically targets p27 for degradation during cell-cycle progression.


Assuntos
Proteínas de Ciclo Celular , Proteínas Associadas aos Microtúbulos/metabolismo , Peptídeo Sintases/metabolismo , Proteínas Supressoras de Tumor , Ubiquitinas/metabolismo , Ciclo Celular , Sistema Livre de Células , Inibidor de Quinase Dependente de Ciclina p27 , Células HeLa , Humanos , Proteínas Associadas aos Microtúbulos/química , Peptídeo Sintases/genética , Fosforilação , Recombinação Genética , Proteínas Ligases SKP Culina F-Box , Treonina/química , Treonina/metabolismo
12.
Cancer Chemother Pharmacol ; 75(3): 579-86, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25577133

RESUMO

PURPOSE: To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02, a novel liposome-encapsulated irinotecan, in patients with advanced refractory solid tumors. METHODS: Patients were enrolled in cohorts of one to three to receive escalating dose of PEP02 in a phase I trial. PEP02, from 60 to 180 mg/m(2), was given as a 90-min intravenous infusion, every 3 weeks. RESULTS: A total of 11 patients were enrolled into three dose levels: 60 (one patient), 120 (six patients) and 180 mg/m(2) (four patients). DLT was observed in three patients, one at 120 mg/m(2) (grade 3 catheter-related infection) and two at 180 mg/m(2) (grade 4 neutropenia lasting for >3 days in one, grade 4 hematological toxicities and grade 4 diarrhea in the other). MTD was determined as 120 mg/m(2). Comparing with those after free-form irinotecan in the literature, the dose-normalized PK of SN-38 (the active metabolite) after PEP02 was characterized by lower C max, prolonged terminal half-life and higher AUC but with significant inter-individual variation. One patient who died of treatment-related toxicity had significantly higher C max and AUC levels of SN-38 than those of the other three patients at 180 mg/m(2). Post hoc pharmacogenetic study showed that the patient had a combined heterozygosity genotype of UGT1A1*6/*28. Two patients had objective tumor response. CONCLUSIONS: PEP02 apparently modified the PK parameters of irinotecan and SN-38 by liposome encapsulation. The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m(2), which will be the recommended dose for future studies.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/análogos & derivados , Glucuronosiltransferase/genética , Nanopartículas , Neoplasias/tratamento farmacológico , Adulto , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Área Sob a Curva , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Genótipo , Meia-Vida , Humanos , Infusões Intravenosas , Irinotecano , Lipossomos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/patologia , Farmacogenética , Resultado do Tratamento
13.
Am J Cardiol ; 67(9): 854-62, 1991 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-2011985

RESUMO

Percutaneous transvenous mitral commissurotomy (PTMC) was performed in 219 patients with symptomatic, severe rheumatic mitral stenosis. There were 59 men and 160 women, aged 19 to 76 years (mean 43). Pliable, noncalcified valves were present in 139 (group 1), and calcified valves or severe mitral subvalvular lesions, or both, in 80 patients (group 2). Atrial fibrillation was present in 133 patients (61%) and 1+ or 2+ mitral regurgitation in 59 (27%). Technical failure occurred with 3 patients in our early experience. There was no cardiac tamponade or emergency surgery. The only in-hospital death occurred 3 days after the procedure in a group 2 premoribund patient in whom last-resort PTMC created 3+ mitral regurgitation. Mitral regurgitation appeared or increased in 72 patients (33%); 3+ mitral regurgitation resulted in 12 patients (6%). There were 3 systemic embolisms. Atrial left-to-right shunts measured by oximetry developed in 33 patients (15%). Immediately after PTMC, there were significantly reduced (p = 0.0001) left atrial pressure (24.2 +/- 5.6 to 15.1 +/- 5.1 mm Hg), mean pulmonary artery pressure (39.7 +/- 13.0 to 30.6 +/- 10.9 mm Hg) and mitral valve gradient (13.0 +/- 5.1 to 5.7 +/- 2.6 mm Hg). Mitral valve area increased from 1.0 +/- 0.3 to 2.0 +/- 0.7 cm2 (p = 0.0001) and cardiac output from 4.4 +/- 1.4 to 4.7 +/- 1.2 liters/min (p less than 0.01). The results mirrored clinical improvements in 209 patients (97%). Multivariate analysis showed an echo score greater than 8, and valvular calcification and severe subvalvular lesions as independent predictors for suboptimal hemodynamic results.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Oclusão com Balão , Cateterismo , Estenose da Valva Mitral/terapia , Cardiopatia Reumática/terapia , Adulto , Idoso , Função Atrial/fisiologia , Pressão Sanguínea/fisiologia , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Calcinose/terapia , Débito Cardíaco/fisiologia , Cateterismo/instrumentação , Ecocardiografia , Ecocardiografia Doppler , Desenho de Equipamento , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/fisiopatologia , Prognóstico , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/fisiopatologia , Função Ventricular/fisiologia
14.
Biochem Pharmacol ; 55(4): 523-31, 1998 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9514088

RESUMO

Hepatocellular carcinoma (HCC) is characterized by high drug resistance to currently available chemotherapeutic agents. In a prospective clinical study, we have demonstrated that high-dose tamoxifen significantly enhanced the therapeutic efficacy of doxorubicin in patients with far-advanced HCC. In a search for a possible mechanism, we found that tamoxifen at a clinically achievable concentration (2.5 microM) significantly enhanced doxorubicin-induced cytotoxicity and apoptosis of Hep-3B cells, a multidrug resistance (MDR)-1 expressing HCC cell line. This synergistic cytotoxic effect of tamoxifen, at this concentration, however, was not mediated by MDR inhibition. Instead, as evidenced by both western blot and immunofluorescence studies, tamoxifen inhibited the cytoplasmic-membrane translocation of protein kinase C (PKC)-alpha. 12-O-Tetradecanoylphorbol-13-acetate (TPA) restored the membrane translocation of PKC-alpha and abrogated the synergistic cytotoxicity of tamoxifen. We also showed that tamoxifen, at this concentration, did not directly affect the enzyme activity of PKC. Further, membrane translocation of other membrane-bound proteins, such as Ras protein, was similarly inhibited by tamoxifen, but could not be restored by the addition of TPA. Together, these data suggested that tamoxifen may act on the cytoplasmic membrane, and thereby inhibit PKC-alpha translocation to the membrane where it is activated. We hypothesize that high-dose tamoxifen may be an effective modulator of doxorubicin in the treatment of HCC, and suggest that biochemical modulation of PKC as a measure to improve systemic chemotherapy for HCC deserves further investigation.


Assuntos
Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Proteína Quinase C/metabolismo , Tamoxifeno/farmacologia , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Hormonais/agonistas , Antineoplásicos Hormonais/farmacologia , Transporte Biológico Ativo/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Resistência a Medicamentos , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Corantes Fluorescentes , Humanos , Isoenzimas/metabolismo , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/enzimologia , Rodamina 123 , Rodaminas , Tamoxifeno/administração & dosagem , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais Cultivadas , Proteínas ras/metabolismo
15.
Mayo Clin Proc ; 71(2): 134-40, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8577187

RESUMO

OBJECTIVE: To examine the utility of intracardiac echocardiography in guiding complex transseptal catheterization of patients undergoing percutaneous transvenous mitral commissurotomy. DESIGN: We assessed this procedure in high-risk patients in whom transseptal catheterization is technically complex and more demanding. MATERIAL AND METHODS: Fifteen patients with mitral stenosis were studied. Twelve patients had giant left atria (70 mm or more), two had atrial septal aneurysms, and one had severe kyphoscoliosis. A newly developed 8-F 10-MHz intracardiac transducer catheter was placed in the right atrium through an 8-F Mullins sheath inserted from the left femoral vein. Echocardiographic images were used to confirm the septal position of the Brockenbrough needle tip before septal punctures. RESULTS: Transseptal puncture was successful and uncomplicated in all 15 patients. Use of intracardiac echocardiography eliminated the need for atrial angiography. Before transseptal puncture, the needle tip was identified to be in contact with the atrial septum, as an echogenic point with its acoustic shadow and septal indentation. In addition, in the two patients with aneurysms, puncture of the thin-walled aneurysms was avoided. CONCLUSION: Intracardiac echocardiography facilitates safe complex transseptal catheterization in patients with mitral stenosis and giant left atria, atrial septal aneurysms, or severe kyphoscoliosis.


Assuntos
Cateterismo Cardíaco/métodos , Ecocardiografia/métodos , Valva Mitral/cirurgia , Cateterismo Cardíaco/instrumentação , Feminino , Aneurisma Cardíaco/complicações , Átrios do Coração , Humanos , Cifose/complicações , Masculino , Pessoa de Meia-Idade , Estenose da Valva Mitral/cirurgia , Escoliose/complicações
16.
Chest ; 119(2): 493-501, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11171728

RESUMO

BACKGROUND: While coronary dissection, which is one of the most frequently occurring complications during interventional procedures, has various forms, extensive coronary dissection retrograde to the coronary sinus of Valsalva (CSV) is very rarely observed. METHODS AND RESULTS: Within the last 5 years, we retrospectively reviewed our experience with 4,700 consecutive patients who underwent angioplasty procedures, 7 of whom (0.15%) developed extensive coronary dissection retrograde to the CSV. Six of the seven patients developed retrograde dissection of the right CSV during angioplasty to the right coronary artery. One of the seven patents developed retrograde dissection of the left CSV during angioplasty to the left anterior descending artery. Retrograde dissection, which extended to the ascending aorta in two patients, was observed by transthoracic echocardiography and surgical findings, respectively. Five patients were successfully treated by coronary stenting. However, this complication caused four patients to have acute myocardial infarctions, resulting in emergency surgery for one patient and in-hospital death for another. CONCLUSIONS: Our experience increased our understanding of this very rare complication. However, this complication may be life threatening, and patients in this clinical setting may have a potential risk for acute myocardial infarction, emergency surgery, or even sudden cardiac death. Therefore, it is important to learn how to promptly diagnose and manage this complication.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Aneurisma Aórtico/etiologia , Dissecção Aórtica/etiologia , Seio Aórtico , Cateterismo Cardíaco/efeitos adversos , Angiografia Coronária , Feminino , Humanos , Masculino , Estudos Retrospectivos , Stents
17.
Chest ; 105(3): 951-3, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8131575

RESUMO

Clinical panhypopituitarism caused by cancer with parasellar metastasis and hypothalamic invasion is very rare. This report concerns a lung cancer patient who had solitary parasellar metastasis with diabetes insipidus and panhypopituitarism as an initial manifestation, which was documented by contrast-enhanced computed tomographic scan, Gd-DTPA-enhanced magnetic resonance imaging, and endocrinologic studies.


Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/secundário , Hipopituitarismo/etiologia , Neoplasias Pulmonares/patologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/secundário , Adenocarcinoma/diagnóstico , Idoso , Diabetes Insípido/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Testes de Função Hipofisária , Adeno-Hipófise , Neoplasias Hipofisárias/diagnóstico , Tomografia Computadorizada por Raios X
18.
Bone Marrow Transplant ; 14(2): 319-21, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7994249

RESUMO

A 28-year-old man with chronic myelogenous leukaemia in blastic transformation underwent allogeneic bone marrow transplantation from his HLA-identical brother. Severe, progressive cholestatic jaundice developed from day 25 and did not respond to repeated therapy with high-dose methylprednisolone. In addition to marked cholestasis, both liver biopsy (day 69) and autopsy (day 134) findings revealed total disappearance of interlobular bile ducts in all of the portal areas, although extrahepatic manifestations of GVHD were minimal. Isolated acute vanishing bile duct syndrome can occur as the most severe form of acute hepatic GVHD.


Assuntos
Doenças dos Ductos Biliares/etiologia , Transplante de Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Hepatopatias/etiologia , Doença Aguda , Adulto , Humanos , Masculino , Transplante Homólogo
19.
Ann Thorac Surg ; 65(6): 1666-72, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9647078

RESUMO

BACKGROUND: Previous studies have shown that the maze operation can restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation. The purpose of this study was to test the feasibility of the application of radiofrequency and cryoablation as an alternative to the classic maze operation. METHODS: Twelve patients undergoing mitral valve procedures were included in this study. Radiofrequency and cryoablation were applied to create lesions in both atria to simulate the classic maze operation. RESULTS: There were two surgical deaths. At the mean follow-up of 10.25 months for the remaining 10 patients; 6 were in sinus rhythm, 2 in atrial rhythm, 1 in paroxysmal atrial tachycardia, and 1 in atrial fibrillation. Doppler echocardiography at 6-month follow-up showed emergence of biatrial transport function in 3 patients and right atrial contractility in 8. At 12-month follow-up of 5 patients, Doppler echocardiography showed biatrial transport function in 3 and right atrial contractility in 4. CONCLUSIONS: Our modified maze procedure during valvular operation is effective for achieving an acceptable success rate to restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation.


Assuntos
Valva Aórtica/cirurgia , Fibrilação Atrial/cirurgia , Ablação por Cateter , Criocirurgia , Valva Mitral/cirurgia , Adulto , Idoso , Fibrilação Atrial/diagnóstico por imagem , Flutter Atrial/etiologia , Ablação por Cateter/efeitos adversos , Causas de Morte , Doença Crônica , Criocirurgia/efeitos adversos , Ecocardiografia Doppler , Eletrocardiografia , Estudos de Viabilidade , Feminino , Seguimentos , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Complicações Pós-Operatórias , Recidiva , Taxa de Sobrevida , Taquicardia Paroxística/etiologia , Resultado do Tratamento
20.
Am J Ophthalmol ; 125(5): 717-9, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9625564

RESUMO

PURPOSE: To report a rare case of T-cell malignant lymphoma involving the conjunctiva. METHODS: A 63-year-old woman had rapid onset of bilateral perilimbal congestion and chemosis. Perilimbal thickening with corneal infiltration developed 20 days later. Computed tomography incidentally disclosed a right maxillary sinus mass. Biopsy specimens from the maxillary sinus mass and the left limbus were subjected to histopathologic examination and immunohistochemical study. RESULTS: T-cell malignant lymphoma of diffuse large cell type, stage IV, was diagnosed. The patient was treated with combination chemotherapy plus 13-cis-retinoic acid and remained in remission 1 1/2 years after diagnosis. CONCLUSION: Conjunctival involvement with T-cell lymphoma may present as episcleritis and chemosis.


Assuntos
Neoplasias da Túnica Conjuntiva/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Células T/patologia , Neoplasias do Seio Maxilar/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Túnica Conjuntiva/química , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Isotretinoína/uso terapêutico , Antígenos Comuns de Leucócito/análise , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Células T/química , Linfoma de Células T/tratamento farmacológico , Neoplasias do Seio Maxilar/química , Neoplasias do Seio Maxilar/tratamento farmacológico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
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