Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer / 中国中药杂志

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.

Dihydropyrimidine dehydrogenase deficiency as a cause of fatal 5-Fluorouracil toxicity

5-Fluorouracil (5-FU), in combination with other cytotoxic drugs, is commonly used to treat a variety of cancers. Dihydropyrimidine dehydrogenase (DPD) catalyzes the first catabolic step of the 5-FU degradation pathway, converting 80% of 5-FU to its inactive metabolite. Approximately 0.3% of the population demonstrate complete DPD deficiency, translating to extreme toxicity of 5-FU. Here we present a case of a patient who had a fatal outcome after treatment with 5-FU who was found to have an unknown DPD deficiency discovered at autopsy.

Addition of citral controls ROS and reduces toxicity in 5-fluo rouracil treated Schizosaccharomyces pombe cells.

In systemic therapy, chemotherapeutic drugs, often, cause considerable side effects; and combination of natural compounds lessen the extent of such effects. In the present study, combined effect of citral and 5-fluorouracil was studied in Schizosaccharomyces pombe cells. The antagonistic combination index found was at 0.01 and 0.025 mM of citral with 40 µg or higher concentration of 5-fluorouracil. The combined treatment was so effective that higher number of cells underwent apoptosis compared to individual treatment of 5-fluorouracil. Citral controlled ROS levels and increased survival of normal cells. Several differentially expressed proteins observed in the citral treatment could further help understanding its mechanism of action.

Technique of Framework Cemented on Prepared Abutments to Obtain Passive Fit at Fixed Complete Denture: A 2-Year Follow-Up Report

The passive fit of implant-supported dentures is fundamental to the rehabilitation success due the absence of the periodontal ligament in osseointegrated implants. Many techniques to obtain passive fit have been reported in the literature, some inaccessible for the clinicians and dental laboratories. This case report presents a technique to fabricate fixed complete dentures aiming at obtain passive fit with reduced time and cost, but without demerit for the aesthetics, function and longevity. A 40-year-old woman was referred for treatment presenting some teeth in the maxilla and an edentulous mandible, reporting eating problems related to instability and little retention of the mandibular complete denture. Treatment based on the reverse planning was performed to guide the rehabilitation with a complete mandibular fixed complete denture and maxillary occlusal plane adjustment. The framework of the fixed complete denture was manufactured luting a cast metal bar above the prepared titanium cylinder abutments using resin cement. The aim of this technique was to obtain a fixed complete denture with passive fit presenting positive esthetic and functional outcomes after 2 years of follow-up.

A adaptação passiva de próteses implantossuportadas é fundamental para o sucesso da reabilitação devido à inexistência de ligamento periodontal em implantes osseointegrados. Inúmeras técnicas de confecção da infraestrutura destas próteses tem sido relatadas na literatura, algumas inacessíveis para os clínicos e laboratórios de prótese. Este relato de caso apresenta uma técnica para confecção de próteses totais fixas visando obtenção de adaptação passiva com tempo e custo reduzido, porém sem demérito à estética, função e longevidade. Uma paciente de 40 anos se apresentou para tratamento apresentando alguns dentes na maxila e mandíbula edêntula, relatando dificuldades na mastigação relacionados a instabilidade e falta de retenção da prótese total inferior. Foi realizado um planejamento reverso para orientar a reabilitação com prótese total mandibular fixa e adequação do plano oclusal da maxila. A infraestrutura da prótese total fixa foi confeccionada pela cimentação de uma barra metálica em cilindros de titânio preparados com cimento resinoso. O objetivo desta técnica foi obter uma prótese total fixa com adaptação passiva apresentando resultados positivos em termos de estética e função após 2 anos de acompanhamento.

Adenosina trifosfato bioluminescência para avaliação da limpeza de superfícies: uma revisão integrativa / Adenosine triphosphate bioluminescence to evaluate the effectiveness of surface cleaning: an integrative review / Bioluminiscencia adenosina trifosfato para evaluar la eficacia de la limpieza de superficies: una revisión integrativa

Objetivo: Identificar na literatura indicações e controvérsias do ATP bioluminescência para avaliação da efetividade da limpeza de superfícies em estabelecimentos de saúde. Método: Revisão integrativa da literatura, entre 2000 e 2012, nas bases de dados MEDLINE, LILACS, Science Direct, SCOPUS e Isi Web of Knowledge. Resultados: Selecionou-se para esta revisão 15 artigos. O ATP bioluminescência foi apontado como importante recurso educacional e método complementar à inspeção visual e às análises microbiológicas na avaliação da efetividade da limpeza. A impossibilidade de indicar a contaminação da superfície por micro-organismos viáveis, a interferência por substâncias químicas e a dificuldade de interpretação dos resultados constituem as principais controvérsias para o uso deste nos serviços de saúde. Conclusão: Apesar de constituir importante recurso na avaliação da limpeza de superfícies, mais estudos são necessários para incorporação efetiva do método nos serviços de saúde. .

Objective: To identify indications and controversies in the literature of the use of ATP bioluminescence to evaluate the effectiveness of surface cleaning in healthcare facilities. Method: Integrative literature review between 2000 and 2012 in the following databases: MEDLINE, LILACS, Science Direct, SCOPUS and Isi Web of Knowledge. Results: were selected for this review 15 articles. The ATP bioluminescence was considered an important educational resource and complementary method to visual inspection and microbiological evaluation of the effectiveness of cleaning. The impossibility to indicate surface contamination by microorganisms, interference by chemicals and the difficulty of interpreting the results constitute the main controversies in the use of ATP in health services. Conclusion: Although this is an important resource in the evaluation of surface cleaning, more studies are necessary for effective incorporation of the method in health services. .

Objetivo: Identificar en la literatura las indicaciones y controversias sobre el uso de la bioluminiscencia ATP para evaluar la eficacia de la limpieza de superficies en los servicios de salud. Método: Revisión integrativa de la literatura, entre 2000 y 2012, en las siguientes bases de datos: MEDLINE, LILACS, Science Direct, SCOPUS e ISI Web of Knowledge. Resultados: Se seleccionaron para esta revisión 15 artículos. La bioluminiscencia del ATP se considera un importante recurso educativo y método complementario a la inspección visual y la análisis microbiológica de la evaluación de la efectividad de la limpieza. La imposibilidad de indicar contaminación de la superficie por los microorganismos, la interferencia por los productos químicos y la dificultad de interpretar los resultados constituyen las principales controversias en la utilización de ATP en los servicios de salud. Conclusión: Aunque esto es un elemento importante en la evaluación de limpieza de superficies, se necesitan más estudios para incorporación eficaz del método en los servicios de salud. .

Quimioterápicos y cardiotoxicidad: un enfoque actual y práctico para el clínico de una disciplina en pleno desarrollo / Chemotherapy agents and cardiotoxicity: a current and user-friendly approach for the clinician, a developing discipline

La cardiotoxicidad por fármacos quimioterápicos es un efecto adverso frecuente y esperado. En este sentido se ha creado una especialización, la cardiooncología, que tiene como principal objetivo la prevención de estos efectos. La forma de expresión de este fenómeno es muy variada, pudiendo manifestarse como: insuficiencia cardíaca, hipertensión arterial, eventos coronarios agudos y/o trastornos del ritmo. La clave en la prevención está en la idividualización del riesgo cardiotóxico de cada paciente (en base a factores reconocidos como edad, sexo, irradiación mediastinal previa, tipo de fármaco, dosis acumulada, cardiopatía asociada previamente) y el riesgo potencial cardiotóxico de cada quimioterápico. En este sentido se han creado algoritmos de actuación fundamentados en la monitorización y el inicio de tratamiento precoz y oportuno de cada efecto, previniendo el mal mayor en cada paciente.

study comparing two different combination chemotherapy protocol in metastatic breast cancer patients previously treated with anthracycline chemotherapy regimen

Treatment for systemic disease is palliative in intent. Goals of treatment include improving quality of life and prolongation of life. Although median survival has been reported to be 18 to 24 months, some patients experience long-term survival. Several combination chemotherapy has been used with comparable results. Quality of life and cost of treatment are an important factor to determine the best combined chemotherapy. In this study. To compare a Taxane based regimen versus If osphamide fluorouracil and mitomycin combined regimen [FILM]. This study was designed to recruit a total of 52 patients with metastatic breast cancer who has received anthracycline chemotherapy in their initial treatment and were randomized between 4 cycles of FILM chemotherapy [Group A] or Taxane based chemotherapy [Group B] to be given every 3 weeks. Patients were assessed for response and toxicity, statistical analysis was used to estimate survival and disease control. Between January 2006 and January 2007, a 52 female patients with metastatic breast cancer have been randomized to either Taxane based or FILM [26 patients in each arm]. Patients were evenly distributed as regards age, staging at first diagnosis, chemotherapy that was previously used, hormonal receptors status and Her-2, and sites of metastases. All patients received the planned treatment. As regards response rate, overall response rate was 73% for group A and 92% for group B P= .047. Progression free survival was better in taxan based regimen 7.3 +/- 3.4 than FILM based 5.6 +/- 2.8 the difference was statistical significant with P= .02. On the other hand, cost of treatment was extremely higher for group B than group A. The cost of treatment was significantly higher in taxan group than FILM P 0.00002. There was no significant difference in quality of life in both groups. Taxan based chemotherapy is significantly better than FILM in terms of PFS. However, there was no significant difference as regards quality of life or overall survival. On the other hand, cost of treatment is significantly higher in Taxane based chemotherapy

Docetaxel and cisplatin [DC] versus epirubicin, cisplatin and 5 fluorouracil [ECF] as systemic chemotherapy treatment for advanced gastric carcinoma [AGC]

Docetaxel and Cisplatin [DC] versus Epirubicin, Cisplatin and 5 fluorouracil [ECF] as Systemic Chemotherapy Treatment for Advanced Gastric Carcinoma [AGC]. Our study was performed to compare between DC and ECF combination chemotherapy as regard the clinical activity in terms of toxicity and response [primary objective] and the survival [secondary objective] trying to reach to a new effective and well tolerated regimen to improve the poor treatment results for palliative chemotherapy in advanced gastric cancer. Forty patients [pts] with AGC [unresectable and/or metastatic], bi-dimentionally measurable disease, performance status is >/= 70%, normal blood counts, hepatic and renal functions and no prior chemotherapy were randomized to receive DC [Docetaxel 75mg/m[2] dl and Cisplatin 75mg/m[2] dl] every 3w or ECF [Epirubicin 50mg/m[2] dl/3w and Cisplatin 60mg/m[2] dl/3w and 5 fluorouracil 200mg/m[2]/d continuous intravenous infusion for a total of 6 cycles for each regimen. The overall response was 45% for DC [n=9] [8 partial response + 1 complete response] and 30% for ECF [n=6] [all are partial responses]. Median time to progression was 7.0 months for DC and 5 months for ECF p=0.03. Median overall survival time was 10.5 months for DC and 8.5 months for ECF p=0.67. The most frequent G3 and 4 events per patient was neutropenia [DC=85%, ECF=30%]. Febrile neutropenia was recorded in 20% with DC versus 5% with ECF. Grade >/= 3 for other events with DC were anemia 15%, thrombocytopenia 10%, vomiting 10%, Diarrhea 10%, Stomatitis 0%, peripheral neuropathy 10% and lethargy 20% versus 5%, 5%, 20%, 20%, 10%, 0% and 5%, with ECF, respectively. There was no treatment related deaths. DC tends to be more effective in AGC with a higher response rate and better median time to progression and overall survival than ECF but with significantly higher neutropenia which was manageable. Use of primary prophylaxis with G-CSF is reasonably recommended

Avaliação da qualidade de vida e toxicidades em pacientes com câncer colorretal tratados com quimioterapia adjuvante baseada em fluoropirimidinas / Evaluation of the toxicity and quality of life in patients with colorectal cancer treated with chemotherapy

RACIONAL: O câncer colorretal é a quarta causa de câncer no Brasil e o 5-fluourouracil uma das principais drogas usadas no tratamento adjuvante e paliativo dessa doença. A toxicidade da quimioterapia e as alterações de qualidade de vida, causadas pela própria doença e pelo tratamento, são motivo de muitos estudos. OBJETIVO: Avaliar nos doentes com câncer colorretal em tratamento quimioterápico, a toxicidade e possíveis alterações da qualidade de vida. MÉTODOS: Durante o período de março de 2001 a maio de 2003 no Ambulatório de Oncologia da Disciplina de Gastroenterologia Clínica da Universidade Federal de São Paulo, foram acompanhados 45 pacientes com câncer colorretal em tratamento quimioterápico adjuvante ou paliativo com 5-fluourouracil e ácido folínico durante seis ciclos. A toxicidade gastrointestinal e hematológica foi analisada utilizando-se as Recomendações para a Graduação da Toxicidade Aguda e Subaguda. Após o término de cada ciclo quimioterápico, os resultados foram anotados de acordo com os respectivos graus que variaram entre 0 e 4. A qualidade de vida foi pesquisada pelo questionário WHOQOL bref (World Health Organization Quality of Life) que consta de 26 questões e é composto por 4 domínios: físico, psicológico, relações sociais e meio ambiente, no início, no 3° e no 6° ciclo de tratamento. RESULTADOS: Entre os 45 pacientes, 28 eram do sexo masculino, a média de idade foi de 58,4 anos (34 a 79 anos). Segundo a classificação da União Internacional Contra o Câncer, 34 (75,6 por cento) eram estádio II ou III e 11 estádio IV (24,4 por cento). Quanto à localização, 64,4 por cento eram de cólon. Em 57,7 por cento a quimioterapia foi adjuvante e nos demais paliativa. As toxicidades mais comumente encontradas foram náuseas (42 por cento), diarréia (38 por cento) e neutropenia (15,7 por cento). Não houve diferença significante entre os graus de toxicidade nos diferentes ciclos, assim como entre os doentes em tratamento adjuvante ou paliativo. Quanto à qualidade de vida foram observadas alterações significantes nos domínios físico e psicológico quando comparadas a primeira com a segunda ou a primeira com a terceira aplicação do questionário. Não foi encontrada alteração da qualidade de vida entre os doentes em quimioterapia adjuvante quando comparada aos em tratamento paliativo. Independente da indicação terapêutica, a média dos escores de qualidade de vida diminuiu em relação aos domínios físico e social na terceira aplicação do teste. CONCLUSÃO: As toxicidades gastrointestinais foram mais freqüentes que as hematológicas com o esquema utilizado. A qualidade de vida diminuiu após o início da quimioterapia em relação à atividade física e psicológica. No estudo da média dos escores observou-se queda dos mesmos nos domínios físico e social. A análise do questionário não mostrou alteração de qualidade vida quando comparados os doentes em tratamento paliativo com os em adjuvância.

BACKGROUND: The colorectal cancer is the fourth cause of cancer in Brazil and 5-fluorouracil is the drug most commonly used in the adjuvant or palliative treatment of this disease. AIM - Evaluating in patients with colorectal cancer and chemotherapy, the toxicity and the quality of life. PATIENTS AND METHODS: From March 2001 and May 2003, 45 patients treated with colorectal cancer treated with 5-fluourouracil and folinic acid were followed closely during six cycles. The gastrointestinal and hematologic toxicity was analysed making use of the chart "Recommendations for the Graduation of Acute and Subacute Toxicity". After the end of each cycle of chemotherapy, the results were registered according to the respectives degrees that vary from 0 to 4. The quality of life was researched through the WHOQOL bref (World Health Organization Quality of Life) questionary that consists of 26 questions and 4 domains: physical, psychological, social relations and environmental, in the beginning, on the 3rd and 6th cycles of treatment. RESULTS: Among the 45 patients, 28 were male, the average age was 58.4 years old (from 34 to 79 years old). According to the International Union Against Cancer classification, 34 patients (75.6 percent) had tumors stage II or III and 11 had tumors stage IV (24.4 percent), 64.4 percent were in the colon. In 57.7 percent the chemotherapy was adjuvant and in the others palliative. The toxicities more commonly found were nauseas (42 percent), diarrhea (38 percent), and neutropenia (15.7 percent). There was no significant difference among the degrees of toxicity in the different cycles as well as among the patients in adjuvant or palliative treatment. Significant alterations was found among the quality of life in the physical and psychological domains when the 1st and the 2nd or the 1st and the 3rd application of the test were done. Alterations of the quality of life were also found in the social domain when the first evaluation was compared with the last one. There was no difference between the quality of life and the treatment.

CMF with or without medical castration in pre-menopausal women with node positive breast cancer

The prognosis of breast cancer in young women is generally considered to be unfavorable. Thus adjuvant therapy post surgical intervention is essential in many patients especially those with high risk [e.g large tumors or positive nodes]. However the presence of steroid hormone receptors in the primary tumors of young ladies may represent a suitable target for therapy in this group of patients. In the current study 100 premenopausal women with positive axillary lymph nodes and have estrogen and/or progestrone receptor positive tumors were randomized after local therapy of the breast cancer into two groups; Group I received adjuvant chemotherapy CMF for a total of six cycles then medical castration with LHRH agonist for two years and Group II received the same chemotherapy as in group I for six cycles. Adjuvant radiotherapy was given in the majority of patients in both treatment groups. After median follow up of six years, there was no statistical significance difference between both groups as regard the disease free or overall survival P=0.537 and 0.526 respectively. The toxicity reported in both groups was quite mild with only increase in the rate of hot flashes in the medical castration group. This study confirm the safety and tolerability of addition of medical castration to adjuvant chemotherapy which can be easily accepted by young women because of its reversible action, however it didn't answer many important questions about the optimum duration of ovarian suppression and the need for combined hormonal therapy like addition of tamoxifen to ovarian castration and sequence of different therapy

Vinorelbine, 5 fluorouracil and folinic acid [fufol-nav] versus paclitaxel [p] as first line treatment in metastatic breast cancer patients pre-treated with anthracycline

The aim of this study was to investigate the efficacy and safety of Vinorelbine, 5 Fluorouracil and Folinic acid [Fu Fol-Nav] versus Paclitaxel [P] in patients with metastatic breast cancer [MBC] previously treated with Anthracycline. Between January 2001 and September 2003, 50 eligible patients with MBC were randomized to either Folinic acid 3Omg/m2 followed by 5Fu 600 mg/m2 given as intravenous holus injection then Vinorelbine 25 mglm2 [10 minute-infusion] q3 weeks [group A], or Paclitaxel 175 mg/m2 [3 hour infusion] q3 weeks [group B]. Eligibility criteri included: measurable MBC previous treatment with Anthracycline in [neo] adjuvant setting. The two randomized arms were well balanced for FuFol-Nav vs. P, median age [44 vs. 51], nearly three quarter of patients in each group had ECOG performance status 0,1. Hormonal receptor positivity for group A was 60% vs. 72% for group B, about half the patients had one metastatic site [56% vs. 47%] with predominant visceral sites in 68% vs. 60% in groups A and B respectively. Overall, both regimens were relatively well tolerated, grade 314 toxicities for group A vs. B: neutropenia and alopecia were significantly higher in group B: [28% vs. 8, 24% vs. 0] hut neurosensory [4% vs. 8%] and mucositis [8% vs. 4%] were not significantly different between the 2 groups. Other toxicities were mild and manageable and no treatment related mortality has been reported in both arms. Overall response rate was 44% [95% CI 42.1 to 45.9] for group A versus 48% [95% CI 46.9 to 50.1] in group B [P> 0.05]. Median time to progression TTP was 7.5 ms vs. 8ms in groups A and B respectively, median duration of response was comparable in both groups [8.5 vs 9ms]. Notably the median OS was similar in both arms [l3ms]. The present study failed to demonstrate a significant difference in response rate, median time to progression and overall survival between the two regimens, so FuFol-Nav is a well tolerated regimen with comparable efficiency as Paclitaxel hut with less cost burden in the treatment of MBC patients

5-fluorouracil (5-FU) induces the formation of giant cells and sloughing of seminiferous epithelium in the rat testis.

The chemotherapeutic agent, 5-fluorouracil (5-FU) has been widely used in the treatment of a variety of cancers. Its effect on the testis has not been substantially studied. Present study was conducted to evaluate the gonadotoxicity of 5-FU in male albino rats. Animals were injected with single dose of 5-FU (10, 50 and 100 mg/kg, i.p.) and sampled on 1, 3, 15 and 30 day post exposure. Animals were anaesthetised, testes were perfusion fixed by Bouin's fluid. Five micron thick paraffin sections were stained with haematoxylin and eosin. Slides were screened for the incidence of partially and extensively sloughed tubules. Data were analysed by Mann Whitney 'U' test. Only 100 mg/kg induced multinucleated cells on 3rd day. All doses of 5-FU induced sloughing of the seminiferous epithelium. Maximum number of partially sloughed tubules were seen on third day. Partial sloughing was not dose dependent except on 15th day. The extensive sloughing was dose dependent except on 30th day. The result indicates that all the doses of 5-FU tested in this study cause sloughing of epithelium and only 100 mg/kg induces the formation of giant cells on third day.

Adjuvant chemotherapy in surgicallyresect able locally advanced colorectal carcinoma: fluoro-uracilbiomodulationby folinicacid versus interferon

Surgical curative resection of locally advanced colorectal cancer [stage B2 and C] is unfortunately followed by high risk of recurrent malignancies. Ultimate control requires effective adjuvant therapy. The aim of this study was to evaluate efficiency of two regimens of modulation of adjuvant 5 fluorouracil [5 FU] by folinic acid versus interferon after surgical resection of locally advanced colorectal carcinoma. 105 patients with histologically proven colorectal carcinoma [stage B2 and C only] were included in this study. Patients were subjected to surgical treatment with operative resection followed by randomization into 3 groups, each of 35 patients. Group A received 5 FU alone, group B received in addition calcium leucovarin [L V], while group C received interferon in addition to 5 FU. Patients were followed up for a median of three years. All groups were comparable as regard age, sex, histological type, stage and clinical presentation. Three years overall and disease- free survival were relatively higher in patients of group B and C, that received 5 FU modulators. Also recurrence rate was less in group B and C than in group A, but not reaching a significant level. The clinical stage of the disease was the most important prognostic factor followed by the histopathological differentiation of the tumour. Most of patients tolerated chemotherapy with transient mild to moderate degree toxicities. Hematological and gastro intestinal toxicities were comparable in the 3 groups in group C there was mild toxicities related to interferon

Evaluación in vitro de la viabilidad y proliferación de fibroblastos de la Cápsula de Tenon humana: expuestos a 5-fluorouracilo y mitomicina C / Evaluation in vitro of the viability and proliferation of fibroblasts of Human Tenon capsule: expose to 5-fluororacil and mitomicyn C

En este trabajo reportamos los resultados de un estudio prospectivo acerca del efecto del 5-Fluorouracilo (5-Fu) y la Mitomicina C (MMC) sobre los fibroblastos provenientes de la cápsula de Tenon humana. El estudio fue realizado en pacientes del Servicio de Oftalmología del Hospital "F.A. Rísquez", Caracas, Venezuela. Los fibroblastos cultivados y expuestos a 5-FU y MMC en diferentes concentraciones y con diferentes tiempos de exposición. La viabilidad celular fue evaluada por el método del MTT y la proliferación de fibroblastos fue estudiada por cintaje celular con la cámara de Newbauer. Encontramos que la toxicidad celular fue mayor con el uso de la MMC que con el 5-FU, pero nunca mayor del 30 por ciento. La citotoxicidad relacionada con la concentración del 5-FU fue 12,7 por ciento a 14,3 por ciento en comparación con una citotoxicidad de 8.8 a 20.5 por ciento de la MMC. La citotoxicidad del 5-FU y la MMC fue directamente proporcional al tiempo de exposición. La inhibición de la proliferación de fibroblastos de la Cápsula de Tenon Humana fue mayor con la MMC que con el 5-FU. La toxicidad celular puede ser modulada más por la concentración de la droga que por el tiempo de exposición

Evaluation of the efficacy and toxicity of epirubicin and cisplatin with cyclic continuous infusion of 5-fluorouracil in advanced breast cancer

Nineteen evaluable patients with advanced breast cancer were included in this study. Fourteen patients received no previous chemotherapy and five patients received previous chemotherapy [CMF] and two of them received [CAF] as well. Age of patients ranged between 25 and 55 years, the median was 38 years. There were five postmenopausal and fourteen permenopause. The most common site of metastasis was the lymph nodes [supraclavicular or contralateral axillary] which was reported in 12 patients. All patients received the cyclic continuous infusion 5- FU for seven days plus epirubicin in day one and cisplatin in day three only. There were four complete responders, partial response was recorded in eleven patients with an overall response rate 79.1%. The failure free survival for untreated patients was 71.4% after a median follow up of 19 months. In previously treated patients, the failure free survival was 20% after a median follow up period of 13 months with median response period of 9.7 months

Alternância intensiva de drogas sem resistência cruzada presumível com methotrexate, adriamicina, ciclofosfamida, vincristina e fluorouracil (MACOM-F) no câncer da mama avançado locorregional / A

E apresentada uma nova estratégia de tratamento do câncer de mama avançado locorregional, fundamentada no uso de drogas sem resistência cruzada pressumível ou toxidade cumulativa, em 12 ciclos semanais. A finalidade foi a de obter citorreduçäo rápida, visando a operabilidade e tratamento das micrometástases. As drogas empregadas foram a ciclofosfamida 300 mg/m e adriamicina 50 mg/m nas semanas 1, 3, 5, 7, 9 e 11; methotrexate 100mg/m e, 24 horas após, resgate pelo leucovorin 15 mg/m de 6/6 horas, por oito vezes, nas semanas 2, 4, 6, 8, 10 e 12; fluouroracil 600 mg/m nas semanas 2, 6 e 10 e vincristina 1,4 mg/m (máximo 2 mg) nas semanas 4, 8 e 12 (MACOM-F). Neste estudo fase II foram incluidas 24 pacientes considerados avaliáveis e em bom estado geral (PS 0 e 2). Dessas 24 pacientes, 22 (91 porcento) obtiveram respostas positivas, sendo nove 937 porcento) resposta completa (RC), 13 (54 porcento) resposta parcial maior do que 50 porcento (RP) e duas (9 porcento) com doença estável (DE), reduçäo do tumor menor do que 50 porcento. A toxidade foi considerada aceitável e 18 foram submetidas a mastectomia radical. Decorridos 53 meses do ínicio do protocolo, das 18 operadas, sete recidivaram e cinco faleceram. Neste período de 34 semanas de seguimento médio, 59 porcento estäo vivas e 44 porcento sem evidência de doença. Os objetivos deste estudo foram: 1) testar o fundamento da teoria de Goldie-Coldman no tratamento de câncer de mama avançado locorregional; 2) verificar a eficácia e toxidade da administraçäo sequêncial intensiva das drogas mais ativas na atualidade para o câncer de mama; 3) determinar a açäo do MACOM-F, seguido de cirurgia, na qualidade e aumento do intervalo livre da doença (ILD) e sobrevida (SV) dessas doentes. O MACOM-F foi muito eficaz como tratamento neoadjuvante desses casos de câncer de mama avançado locorregional, podendo se tornar a primeira opçäo nessas circunstâncias. Todavia, é necessário maior número de doentes tratados para sua definitiva recomendaçäo.

5 flourouracilo en altas dosis: fundamentos y toxicidad / 5 fluorouracil in high doses: basis and toxicity

El 5 fluorouracilo es el quimioterápico fundamental en el tratamiento del cáncer digestivo. Para obtener un mejor índice terapéutico, se puede emplear este fármaco en altas dosis (3 gr./m2), asociado a allopurinol, que previene la toxicidad en tejidos normales. En este trabajo se evalúan fundamentalmente los efectos colaterales en 20 pacientes portadores de neplasias avanzadas. Se demuestra la aparición de efectos tóxicos en un nivel aceptable que permite el uso de esta forma de suministrar el fármaco mencionado