RESUMO
We report the results of a first experimental search for lepton number violation by four units in the neutrinoless quadruple-ß decay of ^{150}Nd using a total exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane Underground Laboratory. We find no evidence of this decay and set lower limits on the half-life in the range T_{1/2}>(1.1-3.2)×10^{21} yr at the 90% C.L., depending on the model used for the kinematic distributions of the emitted electrons.
RESUMO
The BiPo-3 detector is a low radioactive detector dedicated to measuring ultra-low natural contaminations of 208Tl and 214Bi in thin materials, initially developed to measure the radiopurity of the double ß decay source foils of the SuperNEMO experiment at the µBq/kg level. The BiPo-3 technique consists in installing the foil of interest between two thin ultra-radiopure scintillators coupled to low radioactive photomultipliers. The design and performances of the detector are presented. In this paper, the final results of the 208Tl and 214Bi activity measurements of the first enriched 82Se foils are reported for the first time, showing the capability of the detector to reach sensitivities in the range of some µBq/kg.
RESUMO
PURPOSE: This study was performed to evaluate the activity of the multitargeted antifolate (MTA or LY231514) against a broad range of human tumors taken directly from patients. MATERIALS AND METHODS: Human tumor colony-forming units were treated with MTA at concentrations of 0.1, 1.0, and 10 microg/ml in 1-h exposure studies. The responses of a limited number of specimens were also evaluated concurrently in 1-h exposures to cisplatin, fluorouracil, irinotecan, and/or paclitaxel. RESULTS: Of 358 specimens plated in the 1-h exposure studies, 148 (41%) were evaluable. Overall, responses were observed in 3% of specimens (4/144) at 0.1 microg/ml, 11% (17/148) at 1.0 microg/ml, and 23% (33/141) at 10 microg/ml. In this range of concentrations achievable clinically, there was a significant concentration-response relationship. At 10 microg/ml in the 1-h exposure studies, the response rate in colorectal cancer specimens was 32% (9/28), and the response rate in non-small-cell lung cancer was 25% (6/24). Responses were also observed in several chemoresistant tumors, including renal cell carcinoma, hepatocellular carcinoma, mesothelioma, and pancreatic carcinoma. The activity of MTA was not completely cross-resistant with that of cisplatin, fluorouracil, irinotecan, and paclitaxel. CONCLUSIONS: MTA demonstrated in vitro activity against a spectrum of tumors, including several tumors generally considered chemoresistant.
Assuntos
Antineoplásicos/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Glutamatos/farmacologia , Guanina/análogos & derivados , Ensaio Tumoral de Célula-Tronco , Relação Dose-Resposta a Droga , Guanina/farmacologia , Humanos , PemetrexedeRESUMO
Twenty-one Pelibuey ewes were used from December 21, 1996 to December 21, 1998. Fourteen of them had never been exposed to artificial photoperiod, and they were maintained on natural photoperiod until March 21, 1997, when they were assigned to natural photoperiod (control group, n=8) or to inverse photoperiod (n=6). The other seven animals had been kept on a long photoperiod (16L:8D) from October 21, 1996 to December 21, 1996, when they entered the present study and were subjected to a gradual decrease in photoperiod, so that they reached an equinox photoperiod (12L:12 D) on March 21, 1997. At that time, they were assigned to natural photoperiod (n=3) or to inverse photoperiod (n=4). Blood samples for progesterone determination were taken twice a week from all the animals. During the second year of the study, prolactin was measured in the samples from five animals in inverse photoperiod and from five control ewes. Hourly samples were obtained to determine the 24-h melatonin profile of five animals from each group on September 21, 1997, December 21, 1997, March 21, 1997, and June 21, 1997. Exposure to inverse photoperiod resulted in a gradual shift on the annual reproductive cycle, so that the second ovulatory season was advanced by 5 months in the ewes kept on inverse photoperiod as compared to the control ewes (P<0.05). There were wide variations in the dates for the onset and the end of the ovulatory season within the inverse photoperiod groups, and three animals in this groups maintained ovulatory activity for at least 18 consecutive months. The duration of melatonin secretion was directly related to the length of the dark period (P<0.05), and this response was not affected by the calendar date. Prolactin concentrations were directly related to daylength, however, they were also affected by calendar date, being lower in the inverse group as compared to the corresponding time of the annual photoperiodic cycle of ewes on natural photoperiod. It is concluded that reproductive activity, melatonin secretion and prolactin secretion of Pelibuey ewes respond to the small variations in photoperiod that are present at 19 degrees 13'N, and that under natural conditions, photoperiod appears to be the main regulator of ovarian activity at this latitude. However, other factors such as temperature or humidity may act as modulators, and their relative importance could increase at more equatorial latitudes.
Assuntos
Melatonina/metabolismo , Ovário/fisiologia , Fotoperíodo , Prolactina/metabolismo , Ovinos/fisiologia , Animais , Feminino , Melatonina/sangue , Ovulação , Prolactina/sangueRESUMO
Abstract One of the most used bacteria in the Quorum Sensing (QS) experimental works is the Vibrio harveyi, which is used as reporter bacteria to detect the Autoinducers-2 (AI-2) activity of other bacteria. Nevertheless, the description of its QS mechanism by the mathematical modeling is an approach still unexploited. For biological systems, it is necessary to consider the high variability of the experimental data, thus identifiability and parametric reliability analyses must be performed before a model could be used. The following work describes a methodology for parameter fitting and parametric identifiability analysis in a model that describes the dynamics of AI-2 in V. harveyi bacteria. Identifiability analyses showed that all parameters are identifiable, but parametric dependency analyses showed two linearly dependent parameters. According to our results, the model is adequate to describe the AI-2 dynamics in V. harveyi.
Resumen Una de las bacterias más utilizadas en los trabajos experimentales de detección de quorum (QS) es la Vibrio harveyi, que se utiliza como bacteria reportera para detectar la actividad de Autoinductores-2 (AI-2) de otras bacterias. Sin embargo, la descripción de su mecanismo de QS por medio del modelado matemático es un enfoque aún no explotado. En el caso de los sistemas biológicos, es necesario considerar la alta variabilidad de los datos experimentales, por lo que deben realizarse análisis de identificabilidad y fiabilidad paramétrica antes de que un modelo pueda ser usado. El siguiente trabajo describe una metodología para el ajuste de parámetros y el análisis de la identificabilidad paramétrica en un modelo que describe la dinámica de la AI-2 en las bacterias V. harveyi. Los análisis de identificabilidad mostraron que todos los parámetros son identificables, pero los análisis de dependencia paramétrica mostraron dos parámetros linealmente dependientes. De acuerdo con los resultados, el modelo es adecuado para describir la dinámica AI-2 en V. harveyi.
RESUMO
Fasciolosis caused by Fasciola hepatica, is the most prevalent parasitic disease in dairy cattle from the northern region of Cajamarca, Peru. The control of this parasite is based on the use of Triclabendazole (TCBZ), a drug that has been used for more than fifteen years in this area. Recent studies, however, have reported a lack of clinical efficacy after treating dairy cattle. This research was aimed to determine the efficacy of TCBZ in a clinical trial. Eleven dairy cows all positive to F. hepatica identified by presence of eggs in feces, were treated with TCBZ (Fasinex(®) 10%) at 12 mg/kg body weight. Fourteen and thirty days after treatment, the animals were analyzed for F. hepatica eggs in their feces by the fecal egg count reduction test. The results found show an overall efficacy of 31.05% and 13. 63% (14 and 30 days post treatment, respectively). Furthermore, an in vivo efficacy test was conducted in sheep with metacercariae obtained from eggs isolated from a cow clinically resistant to TCBZ. Eleven sheep divided in two groups, a control group with no treatment (n=5) and a treated group (n=6) were all infected with two hundred metacercariae. One hundred and six days after infection all the animals demonstrated F. hepatica eggs in their feces, confirming the presence of adult parasites in their livers. The animals were then treated with TCBZ (Fasinex(®) 10%) at 10mg/kg body weight. Fifteen days later, the animals were sacrificed and the number of F. hepatica in their livers counted. The results of this experiment showed an efficacy of the flukicide of 25.2% confirming the resistance to TCBZ of the F. hepatica isolated from dairy cattle in Cajamarca, Peru.
Assuntos
Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Doenças dos Bovinos/tratamento farmacológico , Fasciola hepatica/efeitos dos fármacos , Fasciolíase/veterinária , Doenças dos Ovinos/tratamento farmacológico , Animais , Anti-Helmínticos/uso terapêutico , Benzimidazóis/uso terapêutico , Bovinos , Doenças dos Bovinos/parasitologia , Indústria de Laticínios , Resistência a Medicamentos , Fasciolíase/tratamento farmacológico , Fasciolíase/parasitologia , Fezes/parasitologia , Feminino , Metacercárias , Contagem de Ovos de Parasitas/veterinária , Peru , Ovinos , Doenças dos Ovinos/parasitologia , Carneiro Doméstico , Resultado do Tratamento , TriclabendazolRESUMO
Due to growing evidence suggesting that phytoestrogens might protect against various cancers, particularly against breast and prostate cancer, it is important to measure the exposure of populations to these compounds by determining levels in food and in human tissue or body fluids to assess the possible cancer protective properties of these agents. Therefore, we developed a simple and fast procedure to extract and simultaneously hydrolyze phytoestrogens and their conjugates from food items, and present a fast and selective high-performance liquid chromatography (HPLC) method for precise determinations of the most common dietary phytoestrogens genistein, biochanin-A, daidzein, formononetin, and coumestrol using flavone as internal standard. For the first time HPLC was applied to measure these phytoestrogens and their most abundant metabolites equol and O-desmethyl-angolensin from human urine. The proposed methodology has been evaluated for losses due to thermal degradation during extraction and hydrolysis and due to sample handling during the entire work-up including solid phase extraction, and values are given for inter- and intra-assay variability. We present isoflavonoid levels of most common peas and beans used in "western" and "eastern" diets and compare isoflavonoid and coumestrol levels of raw, canned, and cooked foods which can be used in future epidemiological studies. We also determined human urinary levels with our methodology comparing values before and after soybean intake.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dieta , Estrogênios não Esteroides/análise , Estrogênios não Esteroides/urina , Fabaceae/química , Plantas Medicinais , Cromanos/análise , Cumestrol/análise , Equol , Feminino , Humanos , Isoflavonas/análise , Masculino , Fitoestrógenos , Preparações de PlantasRESUMO
Glutathione S-transferase (GST) isozymes have been shown to be elevated in many human cancer types as compared to normal tissues. TER286, one in a class of glutathione-based GST-activated cytotoxins, was tested in a soft agar cloning assay to determine its in vitro activity against primary human tumor colony-forming units. Breast and lung specimens from patients who had received prior therapy and those who were previously untreated were exposed to TER286 at concentrations of 1, 10 and 50 microM using both 1 h and continuous exposures. Overall in vitro responses (50% or less survival compared to untreated controls) were observed in 0% (0/14), 14% (2/14) and 29% (4/14), respectively, in specimens exposed to TER286 for 1 h, and in 5% (2/41), 10% (4/41) and 61% (25/41), respectively, in specimens exposed to TER286 continuously. TER286 has cytotoxic activity against both breast and lung cancer colony-forming units, and demonstrates a concentration-response effect. At 50 microM, there is a significant difference between 1 h and continuous exposures in head-to-head comparisons. These data suggest that TER286 can be activated in human tumor colony-forming units and should be pursued as a treatment candidate for patients whose tumors are resistant to drug treatment based on up-regulation of GST.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Citotoxinas/farmacologia , Glutationa/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Neoplasias do Colo/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/farmacologia , Humanos , Cinética , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/efeitos dos fármacosRESUMO
Adozelesin, bizelesin and carzelesin are synthetic cyclopropylpyrroloindole (CPI) analogs, a class of potent antineoplastic agents modeled on the antitumor antibiotic CC-1065, that specifically bind to the minor groove of DNA and preferentially alkylate AT-rich regions. These compounds were evaluated against fresh human tumors in a human tumor colony-forming assay (HTCFA) to assess and to compare their relative antitumor spectra, concentration-response relationships and schedule-dependence. Human tumor colony-forming units were treated with adozelesin and bizelesin at concentrations of 0.02, 0.1 and 0.5 ng/ml as a continuous exposure for 14 days, and to 0.2, 1.0 and 5.0 ng/ml as a 1 h exposure. Carzelesin concentrations were 0.04, 0.2 and 1 ng/ml as a continuous exposure, and 0.6, 3.0 and 15.0 ng/ml as a 1 h exposure. A response was scored if there was 50% or less colony survival. The three analogs had similar antitumor activity against colon carcinoma, kidney carcinoma and melanoma colony-forming units. Adozelesin also displayed activity against both breast and non-small cell lung carcinoma colony-forming units, and carzelesin was active against ovarian carcinoma colony-forming units. Significantly positive concentration-response relationships were apparent with all three agents. Responses increased from below 15% at the lowest concentration to above 45% at the highest concentration for the three drugs on all schedules (p < 0.01). At the highest concentration, the overall response rate was significantly higher (p < 0.01) with carzelesin on the continuous schedule (71%) compared to the 1 h schedule (46%). However, overall response rates for adozelesin and bizelesin were similar on both schedules (1 h/continuous: adozelesin, 67/58%; bizelesin, 49/44%), indicating that adozelesin and bizelesin are less schedule dependent than carzelesin in the HTCFA. These results demonstrate that the CPIs have broad-spectrum activity against human tumor colony-forming units in the HTCFA at very low concentrations, as well as differences with regard to schedule dependence which may help guide the optimal clinical development of these agents.
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Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Indóis/farmacologia , Ureia/análogos & derivados , Cicloexenos , Ensaios de Seleção de Medicamentos Antitumorais , Duocarmicinas , Humanos , Células Tumorais Cultivadas , Ureia/farmacologiaRESUMO
The anti-proliferative effects of pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) derivative with potent tumor-differentiating properties both in vitro and in vivo, was evaluated against colorectal, breast, lung, ovarian, renal cell, bladder, and other types of tumor colony-forming units in a human tumor cloning assay. A total of 76 evaluable specimens were exposed to AN-9 continuously, 48 of these were also exposed to BA continuously for direct comparison of the two agents, and 20 specimens were exposed to AN-9 for two hours. An in vitro inhibitory response was defined as a > or = 50% decrease in tumor colony formation in treated cells compared to untreated controls. Superior anti-tumor activity was observed with the continuous exposure to AN-9 (39% in vitro response at 100 microM and 70% at 200 microM) than with the two-hour exposure (20% at 100 microM and 25% at 200 microM). At a continuous concentration of 200 microM, AN-9 demonstrated greater tumor-specific activity than BA against melanoma (100% vs. 67%), ovarian (67% vs. 40%), breast (63% vs. 0%), non-small cell lung (60% vs. 10%), and colorectal tumor colony-forming units (62% vs. 20%). AN-9 is a novel differentiating agent with activity against colony-forming units derived from a variety of primary human tumors, including those that are considered relatively chemoresistant, and may thus provide a therapeutic alternative or addition to standard cytotoxic agents, if appropriate drug concentrations can be achieved in patients.
Assuntos
Antineoplásicos/farmacologia , Butiratos/farmacologia , Drogas em Investigação/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Butiratos/administração & dosagem , Clonagem Molecular , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Humanos , Fatores de Tempo , Células Tumorais CultivadasRESUMO
The ONYX-015 virus is a mutated adenovirus that in theory selectively replicates and induces cytolysis in tumor cells lacking functional p53. The present study investigated whether ONYX-015 viral infection alone or in combination with conventional chemotherapeutic agents could significantly increase apoptosis in human colon cancer cell lines, regardless of p53 status, compared to untreated cells. A pair of colon cancer cell lines that differ only in their p53 status (RKO with wild-type p53 and RKOp53 with deficient p53) was tested. Two chemotherapeutic agents, 5-fluorouracil (5-FU) and CPT-11, were tested in combination with ONYX-015. Final concentrations of these agents corresponded to peak plasma levels achievable in patients. ONYX-015 concentration was 10 p.f.u./cell. In RKO and RKOp53 cell lines, ONYX-015 viral infection alone or in combination with 5-FU or CPT-11 induced a significant increase in apoptosis compared to chemotherapeutic agents alone, regardless of p53 status. Moreover, the combination of ONYX-015 and chemotherapeutics induced more apoptosis than chemotherapeutics alone in the two colon cancer cell lines independently of their p53 status. We conclude that ONYX-015 virus infection alone or in combination with 5-FU or CPT-11 induced apoptosis in human colon cancer cell lines, independently of p53 status.
Assuntos
Adenoviridae/fisiologia , Antineoplásicos/farmacologia , Apoptose , Neoplasias do Colo/virologia , Proteína Supressora de Tumor p53/metabolismo , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Terapia Combinada , Fluoruracila/farmacologia , Humanos , Irinotecano , Mutação , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/virologiaRESUMO
Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal osteoblasts. BMP-2 is structurally related to transforming growth factor-beta which inhibits cell proliferation and enhances apoptosis. A recent study has shown the presence of BMP-2 receptors on several cancer cell lines. In this study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can modulate the proliferation of human tumor colony-forming units taken from 113 patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the capillary cloning system. There were 65 evaluable specimens, including 17 breast cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A significant inhibition (50% or less survival of tumor colony-forming units) was seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A concentration-response relationship was observed (p<0.001 by Mantel-extension test). The results of this study encourage further evaluation of the antiproliferative effects of rhBMP-2 against human cancers.
Assuntos
Proteínas Morfogenéticas Ósseas/toxicidade , Fator de Crescimento Transformador beta , Proteína Morfogenética Óssea 2 , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Proteínas Recombinantes/toxicidade , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-TroncoRESUMO
Recombinant human interleukin-11 (rhIL-11) has been shown to enhance recovery from thrombocytopenia and mucosal injury after cancer chemotherapy. Since RNA for the receptor and signal transducer for IL-11 is detected in many cell types including some cancer cells, it was theoretically possible that rhIL-11 could affect the growth of tumor cells. This study was intended to determine whether rhIL-11 stimulates the proliferation of human tumor colony-forming units (TCFUs) taken directly from patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhIL-11 (1.0, 10.0 and 100.0 U/ml) for 14 days in the capillary cloning system. Growth stimulation was noted in two of 66 (3%) of evaluable specimens, including one of 14 evaluable non-small cell lung cancer and one of five evaluable colon cancer specimens. In these two specimens, there was no increased stimulation of TCFUs with escalating concentrations of rhIL-11. Interestingly, the highest concentration of rhIL-11 tested inhibited the growth of 16 specimens (24.2%; 95% confidence interval 13.9-34.5%). Growth inhibition demonstrated a concentration-response relationship (p < 0.001). These results suggest that rhIL-11 appears unlikely to stimulate the growth of the most common solid tumors.
Assuntos
Interleucina-11/farmacologia , Neoplasias/patologia , Proteínas Recombinantes/farmacologia , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Divisão Celular/efeitos dos fármacos , Células Clonais/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controleRESUMO
MGI 114 (6-hydroxymethylacylfulvene, HMAF) is a novel semisynthetic antitumor compound derived from the sesquiterpene mushroom toxin illudin S. Although illudins did not demonstrate significant activity as antiproliferative agents in tumor-bearing animals, several properties including its potent inhibition of DNA synthesis and a unique interaction with DNA led to a structure-activity-based synthetic effort to obtain analogs with improved therapeutic potential. MGI 114 was selected for further development based on its antitumor activity in numerous preclinical tests. MGI 114 was evaluated against adult and pediatric human tumors taken directly from cancer patients and cultured in a human tumor colony-forming assay (HTCFA) to assess the antitumor spectra, concentration-response relationship, schedule dependence and activity of this agent against tumors considered resistant to conventional anticancer drugs. Human tumor colony-forming units were treated with HMAF at concentrations of 0.001, 0.01, 0.1 and 1 microg/ml, both as a 1 h exposure and as a continuous 14 day exposure. A response was scored if there was 50% or less colony survival. In vitro response rates in the range of 50-80% were observed against tumor colony-forming units originating from carcinomas of the colon, kidney, breast, lung cancer, ovary and melanoma. MGI 114 also demonstrated antitumor activity against neuroblastoma colony-forming units. Antitumor activity was not influenced by exposure time as demonstrated by the similar responses rates obtained with the 1 h and continuous exposure at all concentrations tested. However, there was a significant positive concentration-response relationship to both exposure duration with responses increasing from below 10% at the lowest concentration to over 70% at the highest concentration, except for the pediatric tumors on the 1 h exposure for which this relationship was less apparent. At the higher concentration tested, MGI 114 displayed substantial antiproliferative effects in the range of 70% against tumor specimens resistant to classic cytotoxic agents including irinotecan, paclitaxel, 5-fluorouracil, cisplatin, doxorubicin and cyclophosphamide. These results demonstrate that MGI 114 exhibits a broad spectrum of antitumor activity against both adult and pediatric primary tumor colony-forming units in a concentration-dependent manner both at short and prolonged exposure duration. The substantial in vitro activity of MGI 114 at concentrations achievable in clinical trials, together with its activity against tumors resistant to classic standard cytotoxic drugs, justifies the further clinical evaluation of this unique agent.
Assuntos
Antineoplásicos/uso terapêutico , Divisão Celular/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Adolescente , Adulto , Criança , Ensaio de Unidades Formadoras de Colônias , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/fisiologia , Humanos , Fatores de Tempo , Células Tumorais CultivadasRESUMO
BACKGROUND: BCH-4556 ((-)-2'-deoxy-3'-oxacytidine) is an L-nucleoside analogue shown to have broad preclinical anti-cancer activity, particularly against solid neoplasms such as prostate, renal, and hepatoma in vitro and in vivo, in contrast to cytosine arabinoside (ara-C) which is preferentially active against leukemia. MATERIALS AND METHODS: The antitumor activity of BCH-4556 was evaluated using human tumor colony-forming unit (HTCFU) assay, in which fresh tumor specimens were taken directly from patients with and without prior chemotherapy. RESULTS: Overall, in vitro responses (50% or less survival compared to untreated controls) were observed in 11% (two of 18), 29% (five of 17) and 50% (nine of 18) of specimens treated for one hour with BCH-4556 at 1, 10 and 100 micrograms/ml, respectively; and 16% (nine of 55), 32% (24 of 74), 48% (35 of 73) and 65% (11 of 17) of specimens treated continuously with BCH-4556 at 0.1, 1, 10 and 100 micrograms/ml, respectively. With the one-hour schedule, a significant difference in response rates was noted between 100 micrograms/ml and 1 microgram/ml (P = 0.02). With the continuous schedule, significant differences in response rates were observed between 1 microgram/ml and 0.1 microgram/ml (P = 0.02), between 10 micrograms/ml and 0.1 microgram/ml (P = 0.0001), as well as between 10 micrograms/ml and 1 microgram/ml (P = 0.01). A trend suggesting the superiority of continuous exposure was observed in paired specimens (n = 18) at comparable drug concentrations. Activity was noted against ovarian (nine of 16 = 56%), renal (three of four = 75%), and melanoma (two of two = 100%) HTCFU at 10 micrograms/ml using the continuous schedule. Comparisons between BCH-4556 and paclitaxel were made in 32 specimens at 10 micrograms/ml using the continuous exposure. Twenty-three specimens showed similar responses with both drugs; seven showed better responses with BCH-4556; and two showed better responses with paclitaxel (P = 0.18). CONCLUSIONS: Promising activity was observed with BCH-4556 against ovarian, renal, and melanoma HTCFU. There appeared to be a positive relationship between BCH-4556 concentration and response using both one-hour and continuous exposures. Continuous exposure to BCH-4556 provided high response rates especially at concentrations above 10 micrograms/ml. For both one-hour and continuous exposures, BCH-4556 had similar, and at times, greater potency than paclitaxel against the same tumor specimens in the present study.
Assuntos
Antineoplásicos/farmacologia , Citosina/análogos & derivados , Dioxolanos/farmacologia , Citosina/farmacologia , Feminino , Humanos , Neoplasias Renais/patologia , Melanoma/patologia , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas/efeitos dos fármacos , Ensaio Tumoral de Célula-TroncoRESUMO
Camu-camu, es un árbol frutal, oriundo de la amazonía sudamericana que crece en las orillas anegables de ríos amazónicos. Pertenece al género Myrciaria, especie dubia. Presenta gran importancia nutritiva. Su alto contenido en ácido ascórbico (2780 mg/100 g de pulpa) le confieren propiedades antioxidantes. Objetivo: Evaluar la toxicidad subaguda (30 días) del Camu-camu. Material y método: Utilizamos 33 ratas albinas, macho, Holtzman, distribuidas en 3 grupos equitativos: Grupo I (grupo control), se le administró agua destilada, Grupo II y Grupo III, se les administró por vía oral el extracto seco de Camu-camu a las dosis de 100 y 200mg/Kg, respectivamente. Al inicio del experimento (basal), a las 15 y a los 30 días, se determinó: hemoglobina, WBC, urea, albúmina, creatinina, proteínas GGT, TGP, TGO, en sangre, y peso corporal; además, se realizó el examen histológico de hígado, riñones, bazo y estómago al finalizar el estudio (30 días). Resultados: Los valores de hemoglobina, albúmina y proteínas, fueron mayores que las del grupo control (p<0.05); a su vez, los valores de GGT fueron menores que los del grupo control (p<0.05). No encontramos evidencias de toxicidad sub-aguda, en ninguno de los 2 grupos expuestos, en el examen histopatológico. Conclusión: El Camu-camu, a las dosis y formas de administración, del presente trabajo, carece de efectos tóxicos para las ratas.
Camu-camu, is a native fruit tree of the South American jungle and grows at the borders of amazonian rivers. It belongs to Myrciaria generous and dubia specie and has a great nutritional importance. Contains a high amounts of ascorbic acid, (2780mg/100g of pulp), that is why it is good antioxidant. Objective: To evaluate the subacute toxicity of the atomized Camu-camu. Material and method: We used 33 Holtzman albino male rats, distributed in 3 equitable groups: Group I, the control group, only received distilled water, Groups II and III received 100 and 200 mg/Kg of Camu-camu, respectively. Blood samples were taken for biochemical analysis at the beginning, 15th and 30th days (at the end), to determinate Hb, WBC, urea, albumin, total proteins, creatinine, GGT, TGP, TGO and the weight of the animals; we also do the histological examination of liver, kidneys, spleen and stomach at the end of the experiments (day 30th). Results: The values of albumin, total proteins and hemoglobin were higher than the control group (p<0.05) while the values of GGT were lower that control group (p<0.05). We didnÆt find evidences of subacute toxicity in any of the 2 groups exposed to Camu-camu in the histopathological examination. Conclusion: Camu camu hadn´t toxic effect, in rats, with oral administration during 30 days.
Assuntos
Animais , Ratos , Administração Oral , Antioxidantes , Citrus , Técnicas In Vitro , Myrtaceae , Myrtaceae/toxicidade , Ácido AscórbicoRESUMO
Este estudio examinó la relación existente en adolescentes entre el reporte de problemas de salud y diversos factores psicosociales. además de las diferencias de género en las diversas variables. Los participantes fueron 497 estudiantes de ambos sexos de Concepción (Chile) con edades entre 14 y 18 años. Los problemas de salud informados mostraron relaciones significativas con los eventos estresantes, con el estrés percibido y con el ánimo depresivo, una relación baja con el afrontamiento evitativo y una ausencia de relación con el apoyo social percibido. Las mujeres reportaron mayores niveles de problemas de salud, de eventos estresantes, de estrés percibido, de estrategias de afrontamiento y de ánimo depresivo. Se proponen diversos factores para explicar los resultados obtenidos.