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1.
Asia Pac J Clin Oncol ; 14(2): e95-e102, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29052960

RESUMO

BACKGROUND: Acral melanoma (AM) and mucosal melanoma (MM) make up more than half of melanomas in Asia but comprise only 5% of cases in Caucasians, where cutaneous melanoma (CM) predominates. AM and MM are thought to be genetically and biologically distinct from CM. We report the characteristics and outcomes of melanoma patients from the National Cancer Centre Singapore. METHODS: Case records of 210 patients treated between 2002 and 2014 were reviewed. RESULTS: Median follow-up was 2.5 years. CM, AM and MM made up of 37.6%, 33.8% and 16.2% of cases, respectively, with 6.2% each having ocular melanoma and unknown primary. Caucasians made up 16.2% of patients, accounting for 36.7% of CM but only 2.8 of AM and 2.9% of MM. Patients with MM (2.9% stage I, 14.7% stage IV) presented with higher American Joint Committee on Cancer (AJCC) stage than those with AM (16.9% stage I, 5.6% stage IV) or CM (24.1% stage I, 8.9% stage IV) (P = 0.01). Median overall survival (OS) was 5.7 years for all patients, and 1.0 year for metastatic disease. Considering stage I-III disease, multivariable Cox regression analysis demonstrated age ≥60 years and higher stage to be independent adverse prognostic factors for RFS and OS. Sentinel lymph node biopsy, undertaken for 56 stage I-III patients (25 AM, 31 CM) did not influence outcome. CONCLUSION: Our study reinforces the known unique clinicopathologic features of melanomas in Asians where AM and MM predominate. Age and stage remain the most critical prognostic factors across all subtypes.


Assuntos
Melanoma/terapia , Ásia , Feminino , Humanos , Masculino , Melanoma/etnologia , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Singapura , Resultado do Tratamento
2.
Bioorg Med Chem Lett ; 22(1): 431-5, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22123322

RESUMO

Boswellic acid acylates including their epimers were synthesized and screened against a panel of human cancer cell lines. They exhibited a range of cytotoxicity against various human cancer cell lines thereby leading to the development of a possible SAR. One of the identified lead compounds was found to be an inhibitor of the NF-κB and STAT proteins, warranting further investigations to be developed into a potential anticancer lead.


Assuntos
NF-kappa B/metabolismo , Fatores de Transcrição STAT/metabolismo , Triterpenos/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Citometria de Fluxo/métodos , Células HL-60 , Humanos , Modelos Químicos , Fosforilação , Triterpenos/química
4.
Int J Gynecol Cancer ; 20(3): 428-33, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20375809

RESUMO

BACKGROUND: This is a retrospective study evaluating the survival outcomes, patterns of failure, and prognostic factors of chemoradiotherapy incorporating high-dose rate brachytherapy in the treatment of locally advanced cervical cancer. METHODS: A review of 120 consecutive patients with Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stages IB2 to IVA cervical cancer treated with concurrent cisplatin-based chemoradiotherapy between April 1999 and January 2005. Overall (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. RESULTS: The 5-year OS and DFS rates were, respectively, 65.0% (35.0% IB2, 65.7% IIA-B, 71.0% IIIA-B, and 40.0% IVA) and 57.3% (30.0% IB2, 58.2% IIA-B, 64.0% IIIA-B, and 40.0% IVA). Most patients had squamous cell carcinoma (89.2%) and belonged to FIGO stages IIB (40.8%) and IIIB (30.8%). All but 4 patients completed the planned radiotherapy regimen. There were 48 documented recurrences, of which 13 were locoregional only, 26 were distant only, and 9 were both sites. Five patients (4.2%) experienced late grade 3 to 4 gastrointestinal toxicity. On multivariate analysis, a preradiotherapy hemoglobin level of less than 10 g/dL and tumor size of 4 cm or greater or bulky on computed tomography were independently significant variables for OS, whereas a nadir hemoglobin level of less than 10 g/dL and presence of radiologically enlarged pelvic or paraaortic lymph nodes were independently significant variables for DFS. CONCLUSIONS: We conclude that this regimen is efficacious and feasible, but the safety profile about concurrent administration of high-dose rate brachytherapy and chemotherapy should be studied further. Finally, for cervical cancer patients selected for nonsurgical treatment, radiological assessment of tumor size and lymph node status can provide valuable prognostic information over and above FIGO staging alone.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Carcinoma de Células Escamosas/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
5.
Org Biomol Chem ; 7(16): 3230-5, 2009 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-19641779

RESUMO

Two novel saponins and a 13-nor-pseudoguaianolide designated as hysterolactone were isolated from Parthenium hysterophorus. The two saponins were found to be potent inhibitors of TNF-alpha. Their mode of inhibition was studied through molecular modeling. The wet lab results were in concordance with the data obtained from docking experiments.


Assuntos
Asteraceae/química , Extratos Vegetais/química , Saponinas/isolamento & purificação , Sesquiterpenos de Guaiano/isolamento & purificação , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Bioorg Med Chem Lett ; 19(15): 4394-8, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19501509

RESUMO

Analogues of parthenin were synthesized by substitutions at different reaction centres to establish a structure-activity relationship (SAR). Some of the molecules have displayed significant cytotoxicity in human cervical carcinoma (HeLa) and human myeloid leukemia (HL-60) cells. A few of the compounds also induced apoptosis in HL-60 cells measured in terms of sub-Go/G1 DNA fraction. Also one of the lead molecules has been shown to be the inhibitor of both telomerase and topoisomerase-II.


Assuntos
Antineoplásicos/síntese química , Apoptose , Química Farmacêutica/métodos , Neoplasias/tratamento farmacológico , Sesquiterpenos/síntese química , Antineoplásicos/farmacologia , Desenho de Fármacos , Células HL-60 , Células HeLa , Humanos , Concentração Inibidora 50 , Modelos Químicos , Plasmídeos/metabolismo , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade , Telomerase/antagonistas & inibidores , Inibidores da Topoisomerase II
7.
J Clin Epidemiol ; 62(2): 206-13, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18619790

RESUMO

OBJECTIVE: To assess measurement equivalence of the Singaporean English and Chinese versions of the EuroQol Group's 5-domain questionnaire (EQ-5D) in cancer patients. STUDY DESIGN AND SETTING: Seven hundred and seventy-one ethnic Chinese patients in Singapore were recruited, and they answered either an English or a Chinese version of the EQ-5D. Seven days later, a similar questionnaire in the same language was mailed to the patients. Regression analysis was used to assess equivalence of the mean values obtained by using the two language versions. The validity, responsiveness to change, and reliability of the two versions of the EQ-5D were assessed and compared. RESULTS: Based on the prespecified equivalence margin of +/-10% for binary outcome, +/-0.05 for utility index, and +/-5 points in the visual analog scale, the two language versions of the EQ-5D gave equivalent mean values at item and scale levels. They also showed similar characteristics in validity, responsiveness, and reliability. For example, the test-retest reliability values for the EQ-5D utility index in the two language samples were identical in two significant digits: 0.79. CONCLUSION: The Singaporean English and Chinese versions of the EQ-5D were validated in cancer patients and were shown to achieve measurement equivalence.


Assuntos
Barreiras de Comunicação , Idioma , Neoplasias/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Adulto , Povo Asiático/etnologia , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/métodos , Reprodutibilidade dos Testes , Singapura
8.
Value Health ; 12(2): 371-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18783392

RESUMO

OBJECTIVE: This study aims to develop a function for mapping the English and Chinese versions of the Functional Assessment of Cancer Therapy-General (FACT-G) scores to the EuroQoL Group's EQ-5D utility index and to test whether a single function is sufficient for the two language versions. METHODS: A baseline survey of 558 cancer patients in Singapore using the FACT-G and EQ-5D was conducted (308 English and 250 Chinese questionnaires). Regression models were used to predict the EQ-5D utility index values based on the FACT-G scores and thus derive a mapping equation. Data from a follow-up survey of the patients were used to validate the results. RESULTS: The FACT-G Social/Family scale was not associated with the EQ-5D utility index (P = 0.701). There was no interaction between language version and the predictors (each P > 0.1). An equation that maps the FACT-G Physical, Emotional, and Functional well-being scales to the EQ-5D utility index was derived. In the validation sample, the mean observed utility values was larger than the mapped by only 0.005 (95% confidence interval [CI]-0.006 to 0.016), but the mean absolute difference was 0.083 (95% CI 0.076 to 0.090). CONCLUSIONS: At the group level, but not individual level, the equation developed can accurately map the English and Chinese versions of the FACT-G scores to the EQ-5D utility index.


Assuntos
Idioma , Neoplasias/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários/normas , Adaptação Psicológica , Algoritmos , Coleta de Dados , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Neoplasias/terapia , Psicometria , Análise de Regressão , Singapura
9.
Chem Biol Interact ; 171(3): 332-47, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18070620

RESUMO

An essential oil from a lemon grass variety of Cymbopogon flexuosus (CFO) and its major chemical constituent sesquiterpene isointermedeol (ISO) were investigated for their ability to induce apoptosis in human leukaemia HL-60 cells because dysregulation of apoptosis is the hallmark of cancer cells. CFO and ISO inhibited cell proliferation with 48 h IC50 of approximately 30 and 20 microg/ml, respectively. Both induced concentration dependent strong and early apoptosis as measured by various end-points, e.g. annexinV binding, DNA laddering, apoptotic bodies formation and an increase in hypo diploid sub-G0 DNA content during the early 6h period of study. This could be because of early surge in ROS formation with concurrent loss of mitochondrial membrane potential observed. Both CFO and ISO activated apical death receptors TNFR1, DR4 and caspase-8 activity. Simultaneously, both increased the expression of mitochondrial cytochrome c protein with its concomitant release to cytosol leading to caspase-9 activation, suggesting thereby the involvement of both the intrinsic and extrinsic pathways of apoptosis. Further, Bax translocation, and decrease in nuclear NF-kappaB expression predict multi-target effects of the essential oil and ISO while both appeared to follow similar signaling apoptosis pathways. The easy and abundant availability of the oil combined with its suggested mechanism of cytotoxicity make CFO highly useful in the development of anti-cancer therapeutics.


Assuntos
Apoptose/efeitos dos fármacos , Citocromos c/biossíntese , Leucemia Promielocítica Aguda/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Óleos Voláteis/farmacologia , Receptores Tipo I de Fatores de Necrose Tumoral/biossíntese , Receptores do Fator de Necrose Tumoral/biossíntese , Sesquiterpenos/farmacologia , Caspase 8/biossíntese , Caspase 8/efeitos dos fármacos , Caspase 8/metabolismo , Caspase 9/efeitos dos fármacos , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cymbopogon/química , Citocromos c/efeitos dos fármacos , DNA/efeitos dos fármacos , DNA/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/patologia , Mitocôndrias/metabolismo , Conformação Molecular , NF-kappa B/biossíntese , NF-kappa B/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Receptores do Fator de Necrose Tumoral/efeitos dos fármacos , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/efeitos dos fármacos , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
10.
Bioorg Med Chem Lett ; 17(23): 6411-6, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17950603

RESUMO

4-Amino analogues prepared from beta-boswellic acid and 11-keto-beta-boswellic acid, wherein the carboxyl group in ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules. The same molecules also exhibited apoptotic activity by inducing DNA fragmentation.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Boswellia , Inibidores do Crescimento/toxicidade , Triterpenos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/genética , Boswellia/química , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Humanos , Triterpenos/química
11.
Apoptosis ; 12(10): 1911-26, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17636381

RESUMO

A triterpenediol (TPD) comprising of isomeric mixture of 3alpha, 24-dihydroxyurs-12-ene and 3alpha, 24-dihydroxyolean-12-ene from Boswellia serrata induces apoptosis in cancer cells. An attempt was made in this study to investigate the mechanism of cell death by TPD in human leukemia HL-60 cells. It inhibited cell proliferation with IC50 approximately 12 microg/ml and produced apoptosis as measured by various biological end points e.g. increased sub-G0 DNA fraction, DNA ladder formation, enhanced AnnexinV-FITC binding of the cells. Further, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation, which were significantly inhibited by their respective inhibitors. Persistent high levels of NO and ROS caused Bcl-2 cleavage and translocation of Bax to mitochondria, which lead to loss of mitochondrial membrane potential (Deltapsim) and release of cytochrome c, AIF, Smac/DIABLO to the cytosol. These events were associated with decreased expression of survivin and ICAD with attendant activation of caspases leading to PARP cleavage. Furthermore, TPD up regulated the expression of cell death receptors DR4 and TNF-R1 level, leading to caspase-8 activation. These studies thus demonstrate that TPD produces oxidative stress in cancer cells that triggers self-demise by ROS and NO regulated activation of both the intrinsic and extrinsic signaling cascades.


Assuntos
Antineoplásicos , Apoptose , Boswellia/química , Células HL-60/efeitos dos fármacos , Extratos Vegetais/química , Triterpenos , Acetilcisteína/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/metabolismo , Caspases/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fragmentação do DNA , Inibidores Enzimáticos/metabolismo , Sequestradores de Radicais Livres/metabolismo , Humanos , Proteínas Inibidoras de Apoptose , Isotiurônio/análogos & derivados , Isotiurônio/metabolismo , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/metabolismo , Potenciais da Membrana/fisiologia , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Estrutura Molecular , Óxido Nítrico/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras , Survivina , Triterpenos/química , Triterpenos/farmacologia
12.
Clin Dysmorphol ; 15(4): 221-223, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16957477

RESUMO

We report a mother and son with an interstitial deletion of chromosome 2: del(2)(p21p22.2). Both have mildly dysmorphic facial features and learning difficulties. This phenotype contrasts with two previously described cases with a similar deletion that presented with cyclopia and alobar holoprosencephaly.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 2/genética , Anormalidades Craniofaciais/genética , Deficiências da Aprendizagem/genética , Adulto , Pré-Escolar , Bandeamento Cromossômico , Feminino , Holoprosencefalia/genética , Humanos , Masculino , Fenótipo
13.
J Clin Oncol ; 23(27): 6730-8, 2005 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-16170180

RESUMO

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Endêmicas , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Probabilidade , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Radioterapia Adjuvante , Valores de Referência , Medição de Risco , Singapura/epidemiologia , Análise de Sobrevida , Resultado do Tratamento
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