RESUMO
Housing nursery pigs according to body weight is an observed common practice in production systems and, supposedly, improves growth performance and reduces body weight (BW) variation. This 42-day study evaluated the effects of housing nursery pigs according to BW on performance, onset of feed intake, and aggressive behavior. A total of 504 pigs were ranked by BW at weaning and categorized into three groups of 168 pigs each: light, medium, and heavy. Pigs were randomly distributed to unsorted pens (Unsorted) containing 6 pigs of each weight group and sorted pens with 18 pigs from just one group per pen (Sorted). From weaning to day 3, pigs were fed a diet containing 1% iron oxide dye and rectal swabs presenting red coloration were evaluated to assess feed intake onset. Eight pens were video recorded to evaluate aggressive behavior. Sorted-Heavy pigs delayed the onset of feed intake (P ≤ 0.011) and presented more aggressive behaviors than Sorted-Light and Sorted-Medium pigs (P ≤ 0.036). In Unsorted, onset of feed intake showed no differences between weight categories. Also, no differences were observed for aggressive behavior between Sorted and Unsorted. Final BW showed no differences between Sorted and Unsorted pigs. The within-pen weight coefficient variation (CV) was slightly different (P = 0.042) between Sorted and Unsorted pigs (13.3 and 15.6%, respectively), at the end of the study. Thus, sorting nursery pigs by BW did not improve growth performance and also, induce a lag of post-weaning feed intake onset and increased fights in Heavy pigs.
Assuntos
Agressão , Comportamento Animal , Comportamento Alimentar/fisiologia , Abrigo para Animais , Suínos/fisiologia , Ração Animal/análise , Animais , Feminino , Masculino , Suínos/crescimento & desenvolvimentoRESUMO
The microorganisms are the best source of extracellular enzymes since they allow an economical technology with low-resource consumption compared to animals and plants. The amylases are among the most important enzymes being the genus Bacillus one of the most investigated due to its ability to produce this enzyme. The objective of this study was to isolate and analyze the genetic diversity among bacteria of the genus Bacillus sp producer of amylase originated from the soil. To this end, soil samples were collected and submitted to the condition of extreme temperature. The serial dilution procedure followed by seeding on solid medium containing starch was used for isolation of strains that produce amylase. The microorganisms isolated were subjected to standard morphological methods for presumptive identification of the genus Bacillus. The PCR assay with the universal genetic marker 16S rDNA was used for confirmation of bacterial strain. All the 10 isolates presumptively identified as bacteria amplified a fragment of 370 bp corresponding to the 16S rDNA gene. The enzymatic activity was expressed as an enzymatic index (EI), after 24 h of incubation. All isolate producers of amylase exhibited EI ≥ 2.0. The determination of the genetic profile and the clonal relationship among the isolates were performed by the method of ERIC-PCR polymorphism. The isolates of Bacillus spp were divided into 2 groups (I and II). Through this method, the discriminatory capacity of this analysis of polymorphisms was verified in differing producer strains from those not producing amylase.
Assuntos
Amilases/metabolismo , Bacillus/enzimologia , Proteínas de Bactérias/metabolismo , Polimorfismo Genético , Microbiologia do Solo , Amilases/genética , Bacillus/genética , Bacillus/metabolismo , Proteínas de Bactérias/genética , Microbiologia Industrial/métodos , RNA Ribossômico 16S/genéticaRESUMO
This study evaluated the efficiency of prostaglandin F2α (PGF) to hasten ovulation in weaned sows. In experiment I, weaned sows detected in estrus (0 h) received: no hormone (Control; n = 56); 0.5 mg PGF IM at 0 h and 2 h (PGF0; n = 56); or 0.5 mg PGF IM at 24 h and 26 h (PGF24; n = 55). In experiment II, weaned sows that did not express estrus signs until 72 h after weaning (0 h) were assigned to: no hormone (Control; n = 45); 10 µg buserelin acetate IM at 0 h (Buserelin; n = 43); 0.5 mg PGF IM at 34 h and 36 h (PGF; n = 44); or 10 µg buserelin acetate IM at 0 h plus 0.5 mg PGF IM at 34 h and 36 h (Buserelin + PGF; n = 45). In experiment I, no effect of PGF on the interval treatment onset to ovulation was observed (P > 0.05), and no treatment effect was observed on the relative or cumulative proportion of females that ovulated post-treatment onset (P > 0.05). In experiment II, treatment onset to ovulation interval was shorter for Buserelin group than for PGF group (P < 0.05), and a higher cumulative percentage of Buserelin treated sows ovulated up to 48 h compared to PGF and Control groups (P < 0.01), with no differences from Buserelin + PGF. Treatments did not affect total number of piglets born in both experiments (P > 0.05). In conclusion, PGF did not hasten ovulation timing or affect litter size in weaned sows.
Assuntos
Busserrelina , Dinoprosta , Ovulação , Animais , Feminino , Dinoprosta/farmacologia , Dinoprosta/administração & dosagem , Suínos/fisiologia , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Busserrelina/farmacologia , Busserrelina/administração & dosagem , Desmame , Indução da Ovulação/veterinária , Indução da Ovulação/métodosRESUMO
In this paper, we use geometric algebra to describe the polarization ellipse and Stokes parameters. We show that a solution to Maxwell's equation is a product of a complex basis vector in Jackson and a linear combination of plane wave functions. We convert both the amplitudes and the wave function arguments from complex scalars to complex vectors. This conversion allows us to separate the electric field vector and the imaginary magnetic field vector, because exponentials of imaginary scalars convert vectors to imaginary vectors and vice versa, while exponentials of imaginary vectors only rotate the vector or imaginary vector they are multiplied to. We convert this expression for polarized light into two other representations: the Cartesian representation and the rotated ellipse representation. We compute the conversion relations among the representation parameters and their corresponding Stokes parameters. And finally, we propose a set of geometric relations between the electric and magnetic fields that satisfy an equation similar to the Poincaré sphere equation.
RESUMO
In this paper, we use Clifford (geometric) algebra Cl(3,0) to verify if electromagnetic energy-momentum density is still conserved for oblique superposition of two elliptically polarized plane waves with the same frequency. We show that energy-momentum conservation is valid at any time only for the superposition of two counter-propagating elliptically polarized plane waves. We show that the time-average energy-momentum of the superposition of two circularly polarized waves with opposite handedness is conserved regardless of the propagation directions of the waves. And, we show that the resulting momentum density of the superposed waves generally has a vector component perpendicular to the momentum densities of the individual waves.
RESUMO
Traumatic neuroma is a rare disorder that represents a reactive proliferation of neural tissue following damage to an adjacent nerve. Clinically, oral lesions usually appear as a nodule of normal or grayish white smooth surface colouration, and patients may complain of pain as a frequent symptom. We report a case of a painless lower lip traumatic neuroma, clinically misdiagnosed as lipoma, in a 24-year-old Caucasian woman. On intraoral examination, a yellowish and smooth sessile, well-delimited, painless, nodular lesion measuring 10 mm x 7 mm x 4 mm in size was observed on the mucosal lower lip. An excisional biopsy was performed and the final diagnosis was traumatic neuroma. After 18 months of follow-up, the patient is asymptomatic and there are no signs of recurrence.
Assuntos
Lábio/patologia , Neoplasias Bucais/patologia , Neoplasias Pós-Traumáticas/patologia , Neuroma/patologia , Feminino , Humanos , Neoplasias Pós-Traumáticas/diagnóstico , Neuroma/diagnóstico , População Branca , Adulto JovemRESUMO
The authors studied the oral manifestations of a sample of 70 diabetic patients, divided into controlled and uncontrolled patients. Medical history and stomatological data were analyzed and diabetic controlled patients were matched to uncontrolled patients. The main symptoms observed were hyposalivation, taste alterations and burning mouth, with the main sign being parotid enlargement. The lesions observed were candidosis of the erythematous type and proliferative lesions both associated to the use of total prosthesis. No pathognomic lesions or alterations could be observed in relation to the disease. The frequency of carriers of Candida albicans and also the lesions observed could be compared to normal patients also using total dentures.
Assuntos
Assistência Odontológica para Doentes Crônicos , Prótese Total/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Doenças da Boca/etiologia , Doenças Parotídeas/etiologia , Candidíase Bucal/etiologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sialorreia/etiologia , Distúrbios do Paladar/etiologia , Xerostomia/etiologiaRESUMO
OBJECTIVES: Although emerging data suggest that zoledronic acid (Zol) may have different anti-tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti-tumoural and anti-angiogenetic effect of zoledronic acid in non-small-cell lung cancer (NSCLC) cells. MATERIAL AND METHODS: We treated A549 NSCLC cells with zoledronic acid to investigate survival, cell cycle activity, anti-angiogenic activity and apoptotic responses to it. RESULTS: We observed that highest Zol concentration (100µm) caused arrest in G1 phase of the cell cycle and also induced different percentages of apoptosis in presence (0.9% versus 4.4%) or absence (2.4% versus 28.5%) of serum (P=0.0001). Zol concentration from 5 to 100µm for 2 days induced significant concentration-dependent cell death in adherent cells. Furthermore, Zol (10-100µm) induced dose-dependent reduction both of mRNA and protein expression of VEGF associated with parallel decrease in VEGF secretion in the culture medium. CONCLUSION: Taken together, these results support a possible anti-cancer and anti-angiogenetic activity of Zol. Our data may not only provide a basis for the clinical use of this drug as preventive agent of bone metastases but also suggest that Zol deserves attention as an anti-cancer agent in non-small-cell lung cancer.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Apoptose , Linhagem Celular Tumoral , Ciclinas/genética , Ciclinas/metabolismo , Fase G1 , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Survivina , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ácido ZoledrônicoRESUMO
Este estudo objetivou caracterizar qualitativamente grupos de metabólitos secundários e alguns constituintes de 9 espécies de plantas medicinais nativas do cerrado utilizadas pela comunidade rural do Assentamento Vale Verde, identificando potencialidades biológicas e farmacológicas. As informações referentes às plantas de uso medicinal foram obtidas por meio de estudos etnobotânicos e etnofarmacológicos, realizados no período de 2010 a 2012. O material botânico coletado foi identificado e depositado no Herbário da Universidade Federal do Tocantins, Porto Nacional (TO). O extrato etanólico e metanólico foi obtido a partir do material seco em estufa, filtrado e concentrado em evaporador rotatório sob pressão reduzida, pesados e novamente colocados em estufa por 24h a 50ºC, obtendo o rendimento (m/m) resultante da relação entre a massa de extrato concentrado e após seco. A análise fitoquímica das plantas selecionadas foi feita usando a metodologia da Prospecção Preliminar, realizando testes para detecção de alguns constituintes importantes e dos principais grupos de metabólitos: saponinas, fenóis e taninos, catequinas, esteróides e triterpenóides, cumarinas, antraquinonas e flavonóides. Os testes foram considerados positivos através de reações de precipitados com colorações, formações de espumas e manchas coloridas. Os testes fitoquímicos realizados nos extratos revelarem a presença de constituintes do metabolismo secundário das plantas que podem contribuir para a identificação de marcadores químicos para as espécies estudadas, sendo estes indispensáveis para os testes de qualidade e integridade de fitoterápicos e uso popular mais seguro das plantas medicinais, possibilitando melhor controle farmacognóstico dessas espécies e direcionamento dos seus usos e aplicações na pesquisa pela bioatividade preliminarmente conhecida. Neste caso, especialmente devido às atividades antimicrobianas, antioxidantes e contra insetos, sugerindo relação com a presença de compostos fenólicos e flavonoídicos, positivos nos extratos da maioria das espécies. Estas informações são inéditas no Tocantins e estratégicas para fortalecimento das políticas de conservação de Áreas de Reserva Legal no âmbito do Cerrado, bioma prioritário para conservação da biodiversidade, melhorando a caracterização dos recursos medicinais ainda disponíveis na flora nativa regional bem como vislumbrando suas aplicações biológicas e farmacológicas.
This qualitative study aimed to characterize the groups of secondary metabolites and some constituents of 9 species of native medicinal plants of the Cerrado region used by the rural community of Vale Verde Settlement, identifying their biological and pharmacological potential. The information on medicinal plants were obtained through ethnobotanical and ethnopharmacological studies performed during the period 2010-2012. The botanical material collected was identified and deposited in the Herbarium of the Federal University of Tocantins, Porto Nacional (TO). The ethanolic and methanolic extracts were obtained from the oven dried material, filtered and concentrated in a rotary evaporator under reduced pressure, then weighed and placed again in an oven for 24h at 50 ° C, obtaining the yield (m / m), resulting from the ratio between the mass of concentrated extract and the mass after drying. Phytochemical analysis of selected plants was done using the methodology of Preliminary Prospecting, with tests for the detection of some important constituents and of the main groups of metabolites: saponins, phenols and tannins, catechins, steroids and triterpenoids, coumarins, anthraquinones and flavonoids. The tests were considered positive by the reactions of precipitates with colorations, the formation of foams and colored stains. Phytochemical tests performed on the extracts revealed the presence of constituents of secondary metabolism of plants, which can help to identify chemical markers of species. These markers are indispensable for testing quality and integrity of phytochemicals and a safer popular use of medicinal plants, enabling a better pharmacognostic control of these species and guidance for their use and applications in research by the preliminarily known bioactivity. In this case, it is especially due to the antimicrobial, antioxidant and anti insect activities, suggesting an association with the presence of phenolic compounds and flavonoids, positive in extracts of most species. These data are novel in Tocantins and strategic for the strengthening of conservation policies of Legal Reserve Areas within the Cerrado, priority biome for the conservation of biodiversity, improving the characterization of medicinal resources still available in the regional native flora, also foreseeing their biological and pharmacological applications.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pradaria , Mineração de Dados , Plantas Medicinais/efeitos adversos , Biodiversidade , Compostos Fitoquímicos/análiseRESUMO
Several schedules of 5-fluorouracil (FU) and irinotecan (IRI) have been shown to improve overall survival in advanced colorectal cancer (CRC). Preclinical evidence suggests that the sequential administration of IRI and FU produces synergistic activity, although their clinical use has not been fully optimised. We investigated the interaction between short-term exposure to SN-38, the active metabolite of IRI, and prolonged exposure to FU in human CRC HT-29 cells and observed that the synergism of action between the two agents can be increased by extending the time of cell exposure to FU and reducing the interval between administration of the two agents. Based on these findings, we performed a phase I trial in 25 advanced CRC patients using a modified IRI/FU regimen as first-line therapy and evaluated three dose levels of IRI (150-300 mg/m(2)) and two of continuous infusion of FU (800-1000 mg/m(2)) in a 3-weekly schedule. The most severe grade III-IV toxicities were neutropoenia in four cycles and diarrhoea in three. One patient achieved complete response (4%), 12 a partial response (48%), the overall response rate was 52% (+/-20, 95% CI); seven of 25 patients had stable disease (28%), the overall disease control was 80% (+/-16, 95% CI). This modified IRI/FU schedule is feasible and exhibits potentially interesting clinical activity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Apoptose/efeitos dos fármacos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimioterapia Adjuvante , Estudos de Coortes , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Estudos de Viabilidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/farmacologia , Células HT29 , Humanos , Infusões Intravenosas , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
S100 proteins are Ca(2+)-binding polypeptides involved in the tumourigenesis of several human neoplasms. S100A13 is a key regulator of the stress-dependent release of FGF1, the prototype of the FGF protein family involved in angiogenesis. Indeed, S100A13 is a copper binding protein able to enhance the export of FGF1 in response to stress in vitro and to induce the formation of a multiprotein aggregate responsible for FGF1 release. We investigated the expression of S100A13 in human astrocytic gliomas in relation to tumour grading and vascularization. A series of 26 astrocytic gliomas was studied to evaluate microvessel density and to assess FGF1, S100A13 and VEGF-A expression. FGF1 was equally expressed in the vast majority of tumours, whereas S100A13 and VEGF-A were significantly up-regulated in high-grade vascularized gliomas. Moreover, both S100A13 and VEGF-A expression significantly correlated with microvessel density and tumour grading. These data suggest that the up-regulation of S100A13 and VEGF-A expression correlates with the activation of angiogenesis in high-grade human astrocytic gliomas.
Assuntos
Astrocitoma/irrigação sanguínea , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/irrigação sanguínea , Neovascularização Patológica/metabolismo , Proteínas S100/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Regulação para CimaRESUMO
OBJECTIVE: The combined assessment of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) gene expressions in metastatic colorectal cancer has been reported to be able to predict the efficacy of fluoropyrimidine-based chemotherapy. In order to evaluate the prognostic role in the adjuvant setting, we investigated the TS, DPD and TP expression in primary tumors of colorectal cancer patients treated with 5-fluorouracil (5-FU). METHODS: TS, DPD and TP expression levels were determined by immunohistochemistry in paraffin-embedded primary tumor tissues from 62 patients with Dukes' stage B and C colorectal cancers who underwent surgery and received adjuvant systemic chemotherapy with 5-FU. The median follow-up was 90 months (range 17-127). RESULTS: Dukes' stage C cancer and high TS expression were independent markers of poor prognosis for disease-free survival (DFS; p = 0.0009 and p = 0.007, respectively) and overall survival (OS; p = 0.0005 and p = 0.011, respectively). By multivariate analysis, patients with high DPD expression had significantly shorter DFS (p = 0.007) and OS (p = 0.005) compared to patients with low DPD expression. In the combined analysis of 2 markers, patients with low TS and low DPD had the best outcome in terms of DFS (p = 0.007) and OS (p = 0.03). The analysis of all 3 proteins showed that the patients with low expression of all 3 markers had significantly longer DFS (p = 0.04) and OS (p = 0.01) than patients with a high value of any one of the protein expressions. However, the joint analysis of 3 markers (group with TS-/DPD-/TP-) could not identify a subgroup of patients with a better prognosis compared to the analysis of 2 markers (group with TS-/DPD-). The analysis of Dukes' stage C cancer patients confirmed a significant benefit in terms of DFS and OS (p = 0.001 and p = 0.006, respectively) when all 3 markers had low expression. We also found a positive significant correlation between TS and TP protein expression (p = 0.033). CONCLUSIONS: This retrospective investigation suggests that the combined assessment of TS and DPD may be useful to evaluate the prognosis of patients with Dukes' B and C colon carcinoma receiving 5-FU adjuvant chemotherapy. The role of TP as a predictor for 5-FU-based therapy needs further investigations.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Fluoruracila/uso terapêutico , Timidina Fosforilase/metabolismo , Timidilato Sintase/metabolismo , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
The site of reduced electrolyte transport in Bartter's syndrome (BS) was studied with a new technique whereby resorption can be separately measured as equivalent volumes of free water generated along the ascending limb of Henle's loop (CH2O-HL) and cortical distal tubule (CH2O-DT): the fractional proximal resorption (FPR) and the volume of free water dissipated along collecting ducts (CD) by back diffusion (CH2O-BD) in the absence of ADH are also measured during maximal water diuresis. Data are expressed as ml . min-1 GFR-1 . 100. The studies were performed on 2 brothers with all clinical and laboratory features of BS. They achieved external Na balance within 3 days when placed on either 10, 100, or 230 mEq Na daily. With the 100-mEq-Na diet indomethacin caused a stable 1.5 kg weight gain. FPR was 0.69 in normal controls (NC), 0.77 in BS; CH2O-HL 16.7 vs. 16.4; CH2O-DT 9.7 vs. 3.9; CH2O-BD 13.8 vs. 13.8; CH2O (free water excretion) 12.5 vs. 6.1; urine flow rate (V) 17.6 vs. 9.9. Thus, BS is characterized by a slight fall in proximal delivery, normal HLNa transport, a striking impairment of DTNa transport and preserved interstitial hypertonicity which drives a normal osmotic flow of CH2O-BD. Aspirin injected intravenously during water load affected CH2O and V in proportion to the change in GFR, which fell from 145 +/- 19 to 114 +/- 12 ml . min-1, p less than 0.01). Thus, the primary abnormality of BS is impaired Na transport along the early portion of the distal tubule. This is compensated by volume contraction attended by reduced proximal delivery and full activation of renin-angiotensin-aldosterone system. Consequently, more distal cation exchange sites reclaim Na+ at the expenses of excessive K+ and H+ losses, trapping NH4Cl within tubular lumen and generating hypokalemic metabolic alkalosis. The excess angiotensin is counterbalanced by increased prostaglandin (PG) secretion, which brings renal vascular resistances toward normal and causes tachyphylaxis to angiotensin. Inhibition of PG synthesis leads to a fall in GFR and proximal delivery: this causes distal delivery to fall below reabsorptive capacity for Na: therefore both Na and K retention ensues causing partial volume reexpansion till a new balance is established. PGs do not affect either Na or Cl resorption in BS except by a purely hemodynamic action.
Assuntos
Síndrome de Bartter/fisiopatologia , Hiperaldosteronismo/fisiopatologia , Túbulos Renais/fisiopatologia , Sódio/fisiologia , Adulto , Aspirina/farmacologia , Síndrome de Bartter/urina , Dieta , Taxa de Filtração Glomerular , Humanos , Indometacina/farmacologia , Capacidade de Concentração Renal , Alça do Néfron/fisiopatologia , Masculino , Potássio/urina , Sódio/administração & dosagem , Sódio/urinaRESUMO
OBJECTIVE: In this phase I-II study we explored the potential of the combination of weekly gemcitabine (GEM) and 24-hour continuous infusion of 5-fluorouracil (5-FU) in order to determine the toxicity profile in pancreatic cancer. The efficacy of this drug combination was studied as a secondary endpoint. METHODS: Twenty-one patients with histologically or cytologically proven unresectable or metastatic previously untreated pancreatic adenocarcinoma were included in this study. Two dose levels of GEM and two dose levels of 5-FU were evaluated in three cohorts of patients who received GEM 1,000 mg/m(2) and 5-FU 2,000 mg/m(2), GEM 1,200 mg/m(2) and 5-FU 2,000 mg/m(2), or GEM 1,200 mg/m(2) and 5-FU 2,250 mg/m(2), on days 1, 8, and 15, every 4 weeks, respectively. RESULTS: Grade 3-4 neutropenia was observed in 10% of the cycles. Non-myelosuppressive toxicities included fatigue (22%), grade 1-2 diarrhea (12%) and grade 1 liver toxicity. There was no limiting toxicity and the maximum tolerated dose has not been reached. Two patients experienced a partial response (9.5 +/- 12.6%) and 12 patients had stable disease (57.1 +/- 21.2%). Seven of the 14 symptomatic patients improved their disease-related symptoms and 4 of the 8 patients evaluable for clinical benefit had a clinically beneficial response (50 +/- 34.6%). The median progression-free survival was 6 months (range 2-28), median survival was 11 months (range 3-32+), and the actuarial 1-year survival rate 33%. CONCLUSION: The weekly administration of GEM combined with 24-hour continuous infusion of 5-FU shows a good safety profile at the dose levels evaluated. Some partial responses had also been achieved, disregarding the dose level of the two drugs. Survival confirms the activity of this drug combination.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: The aim of this study was to observe the effects of neoadjuvant therapy with irinotecan and 5-fluorouracil (5-FU)/folinic acid (FA) on the resection rate and survival of colorectal cancer patients with initially unresectable hepatic metastases. PATIENTS AND METHODS: Forty patients received neoadjuvant chemotherapy comprising irinotecan 180 mg/m(2) administered intravenously (i.v.) on day 1, FA 200 mg/m(2) i.v. on days 1 and 2, 5-FU 400 mg/m(2) i.v. bolus on days 1 and 2, and 5-FU 1200 mg/m(2) as a continuous 48-h i.v. infusion on day 1. The treatment was repeated every 2 weeks and response was assessed every 12 weeks (six cycles). RESULTS: The objective response rate to chemotherapy was 47.5% (n = 19), with two complete responses and disease stabilization in 11 (27.5.%) patients. Responses were unconfirmed for 11 patients undergoing surgery within 2 weeks. Treatment was well tolerated and adverse events were typical of the chemotherapy agents used. Twenty-seven (67.5%) patients reported hematological toxicity (35.0% grade 3/4) and 14 (35.0%) reported gastrointestinal toxicity (12.5% grade 3/4). Thirteen patients (32.5%) underwent potentially curative liver resection following chemotherapy. Chemotherapy was particularly effective in patients with large metastases on entry to the study. The median time to progression is 14.3 months and, at a median follow-up of 19 months, all patients are alive. CONCLUSIONS: Neoadjuvant therapy with irinotecan combined with 5-FU/FA enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. The effects of treatment on survival have yet to be determined.