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1.
Photochem Photobiol Sci ; 15(2): 196-203, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26700693

RESUMO

Bright, long-lasting and non-phototoxic organic fluorophores are essential to the continued advancement of biological imaging. Traditional approaches towards achieving photostability, such as the removal of molecular oxygen and the use of small-molecule additives in solution, suffer from potentially toxic side effects, particularly in the context of living cells. The direct conjugation of small-molecule triplet state quenchers, such as cyclooctatetraene (COT), to organic fluorophores has the potential to bypass these issues by restoring reactive fluorophore triplet states to the ground state through intra-molecular triplet energy transfer. Such methods have enabled marked improvement in cyanine fluorophore photostability spanning the visible spectrum. However, the generality of this strategy to chemically and structurally diverse fluorophore species has yet to be examined. Here, we show that the proximal linkage of COT increases the photon yield of a diverse range of organic fluorophores widely used in biological imaging applications, demonstrating that the intra-molecular triplet energy transfer mechanism is a potentially general approach for improving organic fluorophore performance and photostability.


Assuntos
Corantes Fluorescentes/química , Polienos/química , Carbazilquinona/química , Carbocianinas/química , Ciclização , Transferência de Energia , Oxazinas/química , Fotólise , Fótons , Rodaminas/química
2.
Photochem Photobiol ; 87(2): 275-83, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21138440

RESUMO

Changes in the emission fluorescence intensity of pheophorbide-a (PHEO) in the presence of carboquone (CARBOQ) were used to obtain the association constant, the number of CARBOQ molecules interacting with PHEO, and the fluorescence quantum yield of the complex. Excitation spectra of mixtures of PHEO and CARBOQ in ethanol (EtOH) show an unresolved doublet in the red-most excitation band of PHEO, indicating the formation of a loose ground-state complex. The 1:1 CARBOQ-PHEO complex shows a higher fluorescence quantum yield in EtOH (0.41 ± 0.02) than in buffer solution (0.089 ± 0.002), which is also higher than that of the PHEO monomer (0.28). Quenching of the PHEO fluorescence by DNA nucleosides and double-stranded oligonucleotides was also observed and the bimolecular quenching rate constants were determined. The quenching rate constant increase as the oxidation potential of the DNA nucleoside increases. Larger quenching constants were obtained in the presence of CARBOQ suggesting that CARBOQ enhances DNA photo-oxidation, presumably by inhibiting the back-electron-transfer reaction from the photoreduced PHEO to the oxidized base. Thus, the enhanced DNA-base photosensitized oxidation by PHEO in the presence of CARBOQ may be related to the large extent by which this quinone covalently binds to DNA, as previously reported.


Assuntos
Carbazilquinona/química , Clorofila/análogos & derivados , DNA/química , Luz , Antineoplásicos Alquilantes/química , Clorofila/química , Etanol/química , Fotoquímica , Radiossensibilizantes/química , Espectrometria de Fluorescência
3.
ScientificWorldJournal ; 9: 1148-66, 2009 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-19838601

RESUMO

Quantitative structure-activity relationship (qSAR) models are used to understand how the structure and activity of chemical compounds relate. In the present study, 37 carboquinone derivatives were evaluated and two different qSAR models were developed using members of the Molecular Descriptors Family (MDF) and the Molecular Descriptors Family on Vertices (MDFV). The usual parameters of regression models and the following estimators were defined and calculated in order to analyze the validity and to compare the models: Akaike's information criteria (three parameters), Schwarz (or Bayesian) information criterion, Amemiya prediction criterion, Hannan-Quinn criterion, Kubinyi function, Steiger's Z test, and Akaike's weights. The MDF and MDFV models proved to have the same estimation ability of the goodness-of-fit according to Steiger's Z test. The MDFV model proved to be the best model for the considered carboquinone derivatives according to the defined information and prediction criteria, Kubinyi function, and Akaike's weights.


Assuntos
Carbazilquinona/administração & dosagem , Carbazilquinona/química , Longevidade/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Animais , Carbazilquinona/análogos & derivados , Camundongos , Estrutura Molecular
4.
Chem Pharm Bull (Tokyo) ; 52(6): 751-5, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15187400

RESUMO

Self-organizing map (SOM) of Kohonen seems to be a promising approach beyond the standard one to regression for some classification problems encountered in the field of pharmacy. We apply them, therefore, to the quantitative structure-activity relationship (QSAR) in carboquinones and benzodiazepines, and show their usefulness. Most QSAR analysis using neural networks has been made by adopting neural networks with supervised learning. On the contrary, SOM obeys unsupervised learning and originally does not involve the use of desired target data. If we note that an appreciable fraction of data may be missing without making the similarity comparison impossible in SOM if the number of attributes considered is appreciable, QSAR analysis using SOM is found to be possible as if supervised learning. Similar to target data in supervised learning, we can take into account target data (=observed activity) as one of attributes in addition to other attributes (=structural descriptors). Choice of optimal descriptors as input parameters was found to be essential to generate valuable SOM.


Assuntos
Benzodiazepinas/química , Carbazilquinona/química , Relação Quantitativa Estrutura-Atividade , Benzodiazepinas/análise , Carbazilquinona/análise
5.
Osaka City Med J ; 49(2): 77-83, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15179836

RESUMO

OBJECTIVE: The efficacy of oral fluoropyrimidine carmofur was evaluated for adjuvant use for breast cancer. METHODS: 150 patients with breast cancer of T0N1, T1, N1, T2N0, and T2N1 were randomized to 100 for carmofur and 50 for carboquone. Both drugs were administered continuously for 28 days cyclically for 5 years with a cessation period of 28 days for carmofur and 56 days for carboquone. RESULTS: Overall survival excluding non-breast cancer death was 90% for the carmofur group and 88% for the carboquone group, adjusted by Cox's regression analysis. Difference in drug never affected survival. Leukocyte count was decreased in the carboquone group, but no change in serum transaminase was found in either group. Ten patients, 5 for carmofur and 5 for carboquone, suffered from second malignancy, more than expected in the normal population, but difference in the cumulative rate of each group was not significant. CONCLUSION: Adjuvant use of carmofur as well as carboquone is beneficial for early breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carbazilquinona/uso terapêutico , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
6.
Front Biosci ; 5: E172-80, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11056081

RESUMO

Aziridinyl quinones can be activated by cellular reductases eg. DT-diaphorase and cytochrome P450 reductase to form highly reactive DNA alkylating agents. The mechanisms by which this activation and alkylation take place are many and varied. Using clinically relevant and experimental agents this review will describe many of these mechanisms. The agents discussed are Mitomycin C, EO9 and analogues, diaziridinylbenzoquinones and the pyrrolo[1, 2-alpha]benzimidazolequinones.


Assuntos
Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacologia , Aziridinas/química , DNA/química , Indolquinonas , Quinonas/química , Alquilação , Benzimidazóis/química , Benzoquinonas/química , Carbazilquinona/química , Doxorrubicina/química , Humanos , Indóis/química , Mitomicina/química , Estrutura Molecular , Oxirredução , Relação Estrutura-Atividade
7.
Jpn J Clin Oncol ; 30(7): 310-2, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11007164

RESUMO

In 1991, a 52-year-old woman was diagnosed as having essential thrombocythemia (ET). She was doing well with continuous medication with carboquone (CQ) and subsequently hydroxyurea (HU). However, substantial leukocytosis with leukemic blast cells, anemia and thrombocytopenia developed in 1996. Analysis of peripheral blood showed 4.4 x 10(3)/microl white blood cells with 82% of leukemic blast cells. These blasts showed negative staining with myeloperoxidase by immunostaining, but the myeloperoxidase was positive by electron microscopic analysis. Cytogenetic analysis of bone marrow cells revealed a t(3;17)(p24; q12), del(5)(q13q34). On the basis of these findings, the leukemic blast cells were classified as acute myelogenous leukemia (AML:M0) in the FAB classification. The causative agent, CQ and HU in secondary leukemia from ET and chromosomal abnormality related to ET blastic crisis (BC) are discussed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Crise Blástica/patologia , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 3 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Trombocitemia Essencial/patologia , Carbazilquinona/administração & dosagem , Feminino , Humanos , Hidroxiureia/administração & dosagem , Pessoa de Meia-Idade , Trombocitemia Essencial/tratamento farmacológico
8.
J Chem Inf Comput Sci ; 39(2): 356-61, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10192947

RESUMO

The antileukemic activity (medium effective dose, MED) of a set of 37 carboquinones was modeled using a combination of the electrotopological state (E-state) and molecular connectivity indices with multiple linear regression. A four-variable model gave good statistics: r2 = 0.90, s = 0.21. Using the leave-one-out method, the cross-validation statistics indicate a model useful for prediction: r2press = 0.85, spress = 0.26. The same variables were used to model the optimum effective dose (OD): r2 = 0.88, s = 0.19. The cross-validation statistics indicate a model useful for prediction: r2press = 0.83, spress = 0.23. The descriptor variables are interpreted in terms of the molecular structure.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Carbazilquinona/análogos & derivados , Leucemia Experimental/tratamento farmacológico , Modelos Químicos , Animais , Carbazilquinona/química , Carbazilquinona/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Eletroquímica , Relação Estrutura-Atividade
9.
Anticancer Drugs ; 8(8): 778-83, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9396622

RESUMO

Flavone acetic acid (FAA) has shown the effectiveness of vasoactive drugs in the selective reduction of tumor blood flow. A FAA-mediated decrease in tumor blood flow may produce sufficient hypoxic conditions within the tumor. Carboquone (CQ), a naturally occurring prototype bioreductive alkylating agent like mitomycin C (MMC), has been shown to be selectively more cytotoxic toward hypoxic tumor cells. We have reported enhancement of the combined antitumor effects of MMC plus FAA and hyperthermia (HT). In this study, we examined the combined effects of FAA, CQ and HT. In vitro, although HT (43 degrees C, 60 min) reduced the colonogenicity to 0.58 in CQ (0.01 microg/ml) alone, the combined cytotoxicity of CQ and HT was not enhanced with exposure to FAA at a concentration of 100 microg/ml. In vivo, the tumor growth time, calculated as the time required to reach twice the initial tumor volume, for CQ (2 mg/kg) alone, FAA (150 mg/kg) alone, CQ+FAA, CQ+HT (43 degrees C, 15 min), FAA+HT and FAA+CQ+HT was 6.1, 5.1, 7.1, 8.0, 7.6 and 13.4 days, respectively. A significant enhancement of antitumor effects by trimodality therapy with CQ, FAA and HT was observed, when compared to the treatment with CQ and FAA (p < 0.05). The possible mechanisms of an increased antitumor response achieved with the combination of CQ, FAA and HT may be explained in the following way: the FAA-mediated decrease in tumor blood flow produced sufficient hypoxic conditions within the tumor, and these resulted in a significant increase of the antitumor effects of CQ and HT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipertermia Induzida , Melanoma Experimental/terapia , Animais , Carbazilquinona/administração & dosagem , Hipóxia Celular , Terapia Combinada , Sinergismo Farmacológico , Flavonoides/administração & dosagem , Masculino , Camundongos , Células Tumorais Cultivadas/efeitos dos fármacos
10.
Br J Cancer ; 76(11): 1484-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9400946

RESUMO

The standard management of primary gastric lymphoma (PGL) (stage II) has not been established despite the use of various treatment modalities. The present prospective trial of combined surgery and chemotherapy for the treatment of PGL (stage II) included 25 consecutive patients treated between July 1978 and December 1993. Twenty-one patients were treated with total gastrectomy and four with partial gastrectomy; this was followed by post-operative chemotherapy with m-VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin), followed by consolidation chemotherapy with VEMP (vindesine, cyclophosphamide, methotrexate and prednisolone) or VQEP (vindesine, carbazilquinone, cyclophosphamide and prednisolone). Twenty-one of the 25 patients who completed post-operative chemotherapy were free of relapse 26-203 (median 94) months after the gastrectomy. Of the four patients who did not complete the projected chemotherapy, two relapsed and died of lymphoma. Another patient with recurrent lymphoma died in an accident, and the fourth patient was in remission at 54 months after surgery. The post-operative overall and disease-free survival rates at 10 years for the 25 evaluable patients were 81.6% and 92.0% respectively. Major surgical complications and treatment-related death after chemotherapy were not observed. PGL (stage II) appears to be curable when treated with gastrectomy and adjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carbazilquinona/administração & dosagem , Quimioterapia Adjuvante , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Linfoma não Hodgkin/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisolona/administração & dosagem , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/patologia , Vincristina/administração & dosagem , Vindesina/administração & dosagem
11.
Nihon Ika Daigaku Zasshi ; 62(5): 456-68, 1995 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-7499463

RESUMO

In vitro chemosensitivity of established cell lines from human prostate cancer (8 PC 93, 19 PC 93, DU 145 and PC 3) to various anticancer drugs was examined by clonogenic assay. The drugs used were aclarubicin (ACR), adriamycin (ADM), carboquone (CQ), vincristine (VCR), ifosfamide (IFM), peplomycin (PEP) and cis-platinum (CDDP). To compare antitumor activity of different drugs, the predicted anticancer activity (PAA) was calculated from the 50% inhibition doses and the peak plasma concentration of the clinically used dose. High antitumor activity of drug was considered if PAA > or = 1 was observed. The chemosensitivities were: CQ > ADM > CDDP > VCR > PEP > IFM > ACR in the clonogenic assay. 19 PC 93 and DU 145 were sensitive to CQ, ADM and CDDP, but 8 PC 93 and PC 3 were sensitive to CQ, ADM, CDDP and VCR. Thus, a new combination chemotherapy with CDDP, ADM and CQ (PAQ therapy) was used clinically. PAQ therapy was given to sixteen patients with stage D advanced prostate cancer. Of these patients, 14 were undergoing relapse from antiandrogen therapy and 2 had hormone-resistant prostate cancer. The mean interval from the start of the prior treatment to relapse of the cancer was 18 months. The effectiveness of the new therapy was judged according to the response criteria for prostate cancer treatment of Japan. Three patients showed partial response (PR), 9 were stable disease (Stable) and 4 showed progressive disease (PD). The mean response duration in the patients with PR and with Stable was 11.6 months. The survival length of the responders (PR + Stable) was significantly longer than that of the nonresponders (PD) (p < 0.001). The side effect of PAQ therapy was lower than the moderate degree. Therefore, we considered PAQ therapy to be one of the clinical trials for the treatment of advanced prostate cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carbazilquinona/administração & dosagem , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Células Tumorais Cultivadas/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
12.
Gynecol Oncol ; 57(3): 294-8, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7774832

RESUMO

In order to find out whether the response rate and survival in epithelial ovarian cancer can be improved by aid of sensitivity testing with the subrenal capsule assay (SRCA), 196 patients with FIGO Stage II-IV epithelial ovarian cancer were randomized to be treated with either cyclophosphamide-doxorubicin-cisplatin (CAP) or SRCA-guided chemotherapy. The drug combinations tested with the SRCA were (1) cyclophosphamide-doxorubicin-carboplatin (CACAR), (2) CAP, (3) carboquone-methotrexate-tegafur (CQ-MTX-TEG), (4) cisplatin-etoposide-hexamethyl-melamine (P-VP-HXM), and (5) bleomycin-epirubicin-cisplatin (BEP). A total of 132 patients (CAP, 69; SRCA, 63) were eligible for efficacy analysis based on relaparotomy findings. The overall response rate was 59% in the CAP arm and 62% in the SRCA arm. In the SRCA arm, 16 patients were treated with CACAR, 24 with CAP, 10 with CQ-MTX-TEG, 11 with P-VP-HXM, and 2 with BEP. The response rate to CACAR was 63% and to SRCA-CAP was 75%. The number of complete responses was higher when CAP was given as guided by the assay than when given at random (14/24 vs 23/69; P = 0.03, Pearson chi 2). Survival curves as estimated by Kaplan-Meier method gave a median survival of 24 (SE = 4) months to the SRCA arm and 28 (SE = 5) for the CAP arm (P = 0.7; log-rank test). Because no survival benefit was achieved, the SRCA obviously needs further development before it can be routinely recommended in the choice of first-line chemotherapy for patients with ovarian cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Ensaio de Cápsula Sub-Renal , Idoso , Altretamine/administração & dosagem , Animais , Carbazilquinona/administração & dosagem , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Humanos , Metotrexato/administração & dosagem , Camundongos , Camundongos Endogâmicos , Pessoa de Meia-Idade , Estudos Prospectivos , Tegafur/administração & dosagem
13.
Cancer ; 75(2): 471-7, 1995 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-7812918

RESUMO

BACKGROUND: Leukemic transformation of polycythemia vera (PV) and essential thrombocythemia (ET) is influenced by the therapeutic modalities used. A high incidence of leukemic transformation was found among patients with PV or ET treated with an alkylating agent, carboquone (CQ). The study was conducted to assess the causal relationship between CQ and leukemic transformation of PV and ET. METHOD: Twenty-seven patients with PV and 29 with ET diagnosed from January 1975 to August 1993 and whose clinical course could be followed comprised the members of this retrospective study. The patients were examined for the treatment administered, hematologic data, vascular complications, malignancies including leukemia, and eventual outcome. RESULTS: Eighteen patients with PV and 16 with ET were treated with CQ. The follow-up was 51-209 months for patients with PV and 28-176 months for those with ET. Three patients with PV (17% of those treated with CQ) and 5 with ET (31% of those treated with CQ) had subsequent transformation to acute leukemia. The median period until transformation of patients with PV was 94 months, whereas the median follow-up of patients without transformation was 146 months (P < 0.01). The median total days of CQ administration and the median total dose of CQ were 2022 days and 1226 mg, respectively, for the patients with transformation and 1051 days (P < 0.05) and 435 mg (P < 0.01), respectively, for those without transformation. Likewise, the median follow-ups for patients with ET with or without transformation were 130 and 90 months, respectively; the difference was insignificant. The median total days of CQ administration and the median total dose of CQ were 2075 days and 1019 mg, respectively, for patients with transformation and 571 days (P < 0.05) and 231 mg (P < 0.01), respectively, for those without transformation. These observations suggest that CQ may be involved in the leukemic transformation of PV and ET. The subtypes of leukemia transformed from PV corresponded to M2 in two patients and to M4 in one. All five patients with ET were found to have megakaryoblastic features at transformation, and three were diagnosed as having leukemic subtype M7. Chromosomal abnormalities were found in all five patients (two PV and three ET) examined after leukemic transformation, showing multiple and complex abnormalities in four. CONCLUSION: Showing that both the total days of CQ administration and the total dose of CQ were larger for patients with PV or ET whose disease subsequently transformed to leukemia, with this study, a possible causal role of CQ in leukemic transformation of PV and ET is suggested.


Assuntos
Carbazilquinona/efeitos adversos , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide/induzido quimicamente , Policitemia Vera/complicações , Trombocitemia Essencial/complicações , Adulto , Idoso , Aberrações Cromossômicas , Feminino , Seguimentos , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Policitemia Vera/tratamento farmacológico , Estudos Retrospectivos , Trombocitemia Essencial/tratamento farmacológico
14.
Nihon Jibiinkoka Gakkai Kaiho ; 97(12): 2247-58, 1994 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-7861297

RESUMO

Cellular DNA content and succinate dehydrogenase activity of 92 human head and neck (34 laryngeal, 24 pharyngeal, 21 oral cavity, 13 maxillary) squamous cell carcinomas were examined, and DNA ploidy status and chemosensitivity were analyzed and compared. DNA aneuploidy was observed in 54 tumors (58.7%). The aneuploid pattern was most common in tumors of the maxillary sinus (84%), and least common in tumors of the larynx (41.3%). Histologically, aneuploidy was detected in 71.4% of poorly-differentiated, 63.8% of moderately-differentiated and 37.5% of well-differentiated squamous cell carcinomas. There was a statistically significant difference between the survival rates of patients with diploid and aneuploid patterns. Chemosensitivity was determined by exposing fresh tumor material to five antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5-fluorouracil (5-FU) and mitomycin C (MMC). The average decrease in succinate dehydrogenase (SD) activity was 49.8% with ADM, 33.6% with CDDP, 39.9% with CQ, 68.4% with 5-FU and 45.5% with MMC. Histologically, poorly-differentiated squamous cell carcinomas were most sensitive to these five antitumor drugs. We also compared average SD activity in tumors from different organs and found that pharyngeal tumors tend to be most sensitive to these drugs, except for MMC. The chemosensitivity of a tumor with DNA diploidy tended to be higher among well- and moderately-differentiated squamous cell carcinomas. In contrast, tumors with DNA aneuploidy tended to have higher chemosensitivity in the poorly-differentiated type. The results of this study indicate that simultaneous analysis of DNA ploidy and chemosensitivity will be helpful in understanding the characteristics of tumors as well as in predicting the most effective chemotherapy agents for head and neck cancer patients.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/análise , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Carbazilquinona/farmacologia , Cisplatino/farmacologia , DNA de Neoplasias/genética , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Citometria de Fluxo , Fluoruracila/farmacologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia
15.
Cancer ; 74(4): 1230-6, 1994 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-8055443

RESUMO

BACKGROUND: The authors examined the correlation between the expression of glutathione S-transferase-pi (GST pi) and the sensitivity of gastric cancer to anticancer agents. METHODS: In 62 human gastric carcinomas, the expression of GST pi was immunohistochemically evaluated, and sensitivity to the anticancer drugs, cisplatin (CDDP), doxorubicin (DXR) aclacinomycin A (aclarubicin), (ACR), 5-fluorouracil (5-FU), mitomycin C (MMC) and carboquone (carbazilquinon) (CQ) was examined using the in vitro succinate dehydrogenase inhibition test. The authors used the Chinese hamster ovary (CHO) cell line and its variant CDDP-resistant cell line C/CDP-2, and they analyzed the relationship among CDDP-sensitivity, mRNA expression, and immunohistochemical staining. RESULTS: Immunohistochemically detected GST-pi-positive tumors were noted in 35 of 62 excised tumors. There was no significant correlation between GST-pi expression and clinicopathologic features or prognosis. The succinate dehydrogenase activity of each drug for tumors, with regard to negative or positive GST-pi, was 34.9 plus or minus 13.7% and 46.0 plus or minus 22.0% for CDDP, with a significant statistical difference (P < 0.05). However, there was no statistical difference for the other drugs tested. C/CDP-2 cells showed a lower sensitivity to CDDP, a higher expression of mRNA for GST pi and a stronger immunohistochemical staining than CHO cells. CONCLUSIONS: The overexpression of GST-pi is significantly related to the sensitivity of gastric cancer to CDDP.


Assuntos
Carcinoma/enzimologia , Carcinoma/patologia , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica , Glutationa Transferase/genética , Isoenzimas/genética , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Aclarubicina/farmacologia , Animais , Células CHO , Carbazilquinona/farmacologia , Carcinoma/genética , Carcinoma/fisiopatologia , Núcleo Celular/enzimologia , Núcleo Celular/ultraestrutura , Cricetinae , Citoplasma/enzimologia , Citoplasma/ultraestrutura , Doxorrubicina/farmacologia , Resistência a Medicamentos , Feminino , Fluoruracila/farmacologia , Glutationa Transferase/análise , Humanos , Isoenzimas/análise , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia , Prognóstico , RNA Mensageiro/análise , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/fisiopatologia , Succinato Desidrogenase/antagonistas & inibidores , Taxa de Sobrevida
16.
Oncology ; 51(4): 339-43, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8208517

RESUMO

Carboquone (CQ) and hyperthermia (HT) are capable of preferentially killing oxygen-deficient cells, both in vitro and in vivo. We examined effects of the combination of CQ and HT on an in vitro hypoxic system and on murine solid tumors using hydralazine (HYD), a vasoactive agent. Under in vitro hypoxic conditions, the combined cytotoxicity of CQ and HT (43 degrees C, for 1 h) was enhanced and the enhancement ratio (ER) for the IC90 of CQ was 21.4-, 9.4-, and 2.6-fold compared to that for CQ alone, CQ under hypoxic condition, and CQ plus HT under aerated cells, respectively. Five mg/kg i.p. HYD reduced the level of tumor blood flow in mice to about 20% of constant level and this reduction persisted for 1 h. In mice bearing B16 melanoma tumors, HYD enhanced tumor susceptibility of the combined therapy of CQ and HT. The ER which was a comparison of tumor growth time in the control group, was 2.3, 3.6 for the two combination groups of 1, 2 mg/kg i.p. CQ, HT (43 degrees C for 20 min), and 5 mg/kg i.p. HYD, respectively. Thus, hyperthermochemotherapy using CQ combined with HYD, seems to selectively attack a solid tumor.


Assuntos
Carbazilquinona/uso terapêutico , Hidralazina/uso terapêutico , Hipertermia Induzida , Melanoma Experimental/terapia , Animais , Terapia Combinada , Sinergismo Farmacológico , Hipóxia , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fluxo Sanguíneo Regional/efeitos dos fármacos , Células Tumorais Cultivadas
17.
Semin Surg Oncol ; 10(2): 140-4, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8052784

RESUMO

We retrospectively evaluated the clinical usefulness of the succinate dehydrogenase inhibition (SDI) test as a chemosensitivity test, using 168 resected specimens of gastric cancer, with special reference to the correlation between the results of the SDI test and clinical effects of the corresponding chemotherapy. The rate of sensitivity of these tissues to DDP, CQ, ACR, MMC, ADM, and 5-FU were 63.5%, 54.2%, 47.4%, 42.9%, 31.4%, and 10.8%, respectively. Survival rates for patients with a positive chemosensitivity to MMC and postoperatively prescribed more than 20 mg of MMC were significantly better than those without sensitivity to MMC, even when treated with MMC, although no statistical differences existed in clinicopathologic factors between the two groups. We conclude that the SDI test for human gastric cancer is a rapid, reliable, and useful assay to determine the compatibility between the results of assay and the clinical effects of corresponding chemotherapy. We propose that the regimen of postoperative adjuvant chemotherapy be tailored according to results of the SDI test, using tissues resected from individual patients.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Succinato Desidrogenase/antagonistas & inibidores , Aclarubicina/análogos & derivados , Aclarubicina/farmacologia , Aclarubicina/uso terapêutico , Antineoplásicos/uso terapêutico , Carbazilquinona/farmacologia , Carbazilquinona/uso terapêutico , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/farmacologia , Mitomicina/uso terapêutico , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
18.
Gan To Kagaku Ryoho ; 20(11): 1682-5, 1993 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-8373248

RESUMO

Twenty-nine patients with high grade malignant musculoskeletal sarcoma were treated with chemotherapy. Intra-arterial chemotherapy was performed post-operatively for patients with local recurrence, patients with poor response to pre-operative chemotherapy or patients with intra-lesional or marginal surgical margin. The local recurrence rate in patients with intra-arterial chemotherapy (8.8%) was lower than in those with intravenous chemotherapy (37.5%). Patients with post-operative intra-arterial chemotherapy showed no local recurrence. Of the 29 patients except stage 3 with intra-arterial chemotherapy, the metastatic rate in patients with intra-arterial chemotherapy (41.4%) was lower than in chemotherapy patients with intravenous chemotherapy (83.3%). The rate in the post-operative group (28.6%) was lower than in the pre-operative group (42.9%) or pre- and post-operative group (50.0%). The ten-year survival curve of patients given intra-arterial chemotherapy (51.0%) was higher than in patients on intravenous chemotherapy (17.9%). Among the 34 patients who underwent intra-arterial chemotherapy, the survival rate in the other pre- and post-operative groups and the post-operative group (55.6%) was higher than in the pre-operative group and pre- and post-operative group (49.8%).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Carbazilquinona/administração & dosagem , Quimioterapia Adjuvante , Doxorrubicina/administração & dosagem , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Cuidados Pós-Operatórios , Prognóstico , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Vincristina/administração & dosagem
20.
J Med Chem ; 36(7): 811-4, 1993 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-8464034

RESUMO

We investigated the applications of back propagation artificial neural networks (ANN) for a small dataset analysis in the field of structure-activity relationships. The derivatives of carboquinone were used as an example. It's been found that in this case the use of the same neural network results in unambiguous classification of new molecules. Predictions can be improved with statistical analysis of independent prognosis sets. We suggest that the sign criterion be used as a classification rule. We also compared neural networks with FALS and ALS in leave-one-out prediction. ANN applied to the same dataset has shown the same predictive ability as ALS but poorer than FALS.


Assuntos
Carbazilquinona/análogos & derivados , Mitomicinas/farmacologia , Redes Neurais de Computação , Relação Estrutura-Atividade
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