RESUMO
Previously, we found out that in ovariectomized female rats, estrogen and progesterone produce a memory deficit which is reverted by the intrahippocampal administration of allopregnanolone. Here, we study the possible interplay between allopregnanolone and hippocampal serotonergic activity. Ovariectomized rats injected subcutaneously with estrogen and progesterone were subsequently injected in the dorsal hippocampus with vehicle, allopregnanolone alone or allopregnanolone shortly after 8OH-DPAT, a predominantly 5HT1A-7 receptor agonist. Then, the subjects were sequentially tested in: (1) an inhibitory avoidance task and (2) K+-evoked [3H]-serotonin ex vivo release through superfusion experiments. Allopregnanolone increased the K+-evoked [3H]-serotonin release compared to control. 8OH-DPAT infusions reversed the effects of allopregnanolone on memory and K+-evoked [3H]-serotonin release. These results suggest that allopregnanolone memory improvement could be mediated, at least in part, through modulation of the hippocampal serotonergic system reactivity.
Assuntos
Estrogênios/farmacologia , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , Pregnanolona/uso terapêutico , Progesterona/farmacologia , Serotonina/metabolismo , Animais , Feminino , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Transtornos da Memória/induzido quimicamente , Ovariectomia/efeitos adversos , Pregnanolona/farmacologia , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
In the framework of the Italian TOP-IMPLART project (Regione Lazio), ENEA-Frascati, ISS and IFO are developing and constructing the first proton linear accelerator based on an actively scanned beam for tumor radiotherapy with final energy of 150 MeV. An important feature of this accelerator is modularity: an exploitable beam can be delivered at any stage of its construction, which allows for immediate characterization and virtually continuous improvement of its performance. Currently, a sequence of 3 GHz accelerating modules combined with a commercial injector operating at 425 MHz delivers protons up to 35 MeV. Several dosimetry systems were used to obtain preliminary characteristics of the 35-MeV beam in terms of stability and homogeneity. Short-term stability and homogeneity better than 3% and 2.6%, respectively, were demonstrated; for stability an improvement with respect to the respective value obtained for the previous 27 MeV beam.
Assuntos
Aceleradores de Partículas/instrumentação , Prótons , Radiometria/instrumentação , Radiometria/métodos , Desenho de Equipamento , Doses de RadiaçãoRESUMO
Background: Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. Patients and methods: In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. Results: A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. Conclusion: This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Biópsia Líquida/métodos , Proteínas Proto-Oncogênicas p21(ras)/genética , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Mutação , Metástase Neoplásica , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
BACKGROUND: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. PATIENTS AND METHODS: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. RESULTS: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. CONCLUSIONS: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab/efeitos adversos , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Itália , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Resultado do TratamentoRESUMO
BACKGROUND: In the cetuximab after progression in KRAS wild-type colorectal cancer patients (CAPRI) trial patients with metastatic colorectal cancer (mCRC) received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) and cetuximab in first line followed by 5-Fluorouracil, folinic acid, oxaliplatin (FOLFOX) with or without cetuximab until progression. Limited data are available on the efficacy and safety of anti-epidermal growth factor receptor (anti-EGFR) agents on elderly patients with mCRC. In the current study we evaluated the efficacy and safety of FOLFIRI plus cetuximab in age-defined subgroups. METHODS: A post-hoc analysis was performed in CAPRI trial patients; outcomes (progression-free survival (PFS), overall response rate (ORR), safety) were analysed by age-groups and stratified according to molecular characterisation. 3 age cut-offs were used to define the elderly population (≥65; ≥70 and ≥75â years). RESULTS: 340 patients with mCRC were treated in first line with FOLFIRI plus cetuximab. Among those, 154 patients were >65â years, 86 >70â years and 35 >75â years. Next-generation sequencing (NGS) was performed in 182 patients. Among them, 87 patients were >65â years, 46 >70 and 17 >75. 104 of 182 patients were wild type (WT) for KRAS, NRAS, BRAF, PIK3CA genes. In the quadruple WT group, 51 patients were ≥65â years; 29 were ≥70; 9 were ≥75. Median PFS was similar within the age-subgroups in the intention-to-treat population, NGS cohort and quadruple WT patients, respectively. Likewise, ORR was not significantly different among age-subgroups in the 3 populations. Safety profile was acceptable and similarly reported among all age-groups, with the exception of grade ≥3 diarrhoea (55% vs 25%, p=0.04) and neutropaenia (75% vs 37%, p=0.03) in patients ≥75â years and grade ≥3 fatigue (31% vs 20%, p=0.01) in patients <75â years. CONCLUSIONS: Tolerability of cetuximab plus FOLFIRI was acceptable in elderly patients. Similar ORR and PFS were observed according to age-groups. No differences in adverse events were reported among the defined subgroups with the exception of higher incidence of grade ≥3 diarrhoea and neutropaenia in patients ≥75â years and grade ≥3 fatigue in patients <75â years. TRIAL REGISTRATION NUMBER: 2009-014041-81.
RESUMO
BACKGROUND: Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information. PATIENTS AND METHODS: In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer. RESULTS: Objective responses in the NGS cohort were observed in 104/182 patients [overall response rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4%] with a median progression-free survival (mPFS) of 9.8 (95% CI 8.7-11.5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons 9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of 62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2-12.8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI 39.9-57.5%) with mPFS of 8.9 (95% CI 7.4-9.6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect. CONCLUSIONS: This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Mutação , Antineoplásicos/uso terapêutico , Sequência de Bases , Camptotecina/uso terapêutico , Cetuximab , Classe I de Fosfatidilinositol 3-Quinases , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Fluoruracila/uso terapêutico , GTP Fosfo-Hidrolases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucovorina/uso terapêutico , Proteínas de Membrana/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , Proteínas ras/genéticaRESUMO
Turin, Italy, was one of the two European sites for the INTERGROWTH-21(st) Project. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two obstetric hospitals that together account for 79% of the city's approximately 12,000 births per year. Women were recruited for the Fetal Growth Longitudinal Study (FGLS) from ten antenatal clinics serving the city's largest obstetric hospital, Azienda Ospedaliera OIRM-S. Anna. Special activities to encourage participation and raise awareness of the project in this population included obtaining an endorsement from the coordinator of the city's antenatal care service, and disseminating information about the project to women through posters and leaflets in antenatal clinics. One of the major challenges at this site was the low recruitment rate in the early phase of FGLS because of the high prevalence of smoking and of women >35 years old in the population. The addition of six extra recruiting clinics served to increase the pool of potentially eligible women who could be screened and led to a marked improvement in the recruitment rate.
Assuntos
Desenvolvimento Infantil , Desenvolvimento Fetal , Gráficos de Crescimento , Recém-Nascido/crescimento & desenvolvimento , Estudos Multicêntricos como Assunto/métodos , Projetos de Pesquisa , Pesos e Medidas Corporais , Protocolos Clínicos , Estudos Transversais/métodos , Feminino , Humanos , Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Itália , Estudos Longitudinais/métodos , Seleção de Pacientes , Gravidez , Ultrassonografia Pré-NatalRESUMO
There are approximately 10,000 births per year in the county of Oxfordshire in the UK, which is one of the two European sites for the International Fetal and Newborn Growth Consortium for the 21(st) Century (INTERGROWTH-21(st) ) Project. The samples for both components of the project--the Fetal Growth Longitudinal Study (FGLS) and Newborn Cross-Sectional Study (NCSS)--were drawn from the John Radcliffe Hospital, a major university hospital with a large regional role that covers more than 75% of deliveries in the county. Special activities to encourage participation in this population included the formation of a research coalition to streamline recruitment in the Maternity Unit and the distribution of study information leaflets to women using the hospital's antenatal care service. This was a demanding project and several challenges were overcome to reach recruitment targets and to maintain high standards of data quality. Amongst the major challenges for FGLS at this study site was the level of ineligibility because of maternal age, smoking and body mass index (BMI) ≥ 30. The major challenge for the NCSS field teams was to ensure that all anthropometric data were collected before the early discharge of uncomplicated deliveries, often within 6 hours of birth. It is evident from our experience in implementing this project that, when large-scale clinical studies are meticulously planned and avoid major disruption to routine clinical care, they are well received by hospital staff and can contribute to the improvement of the overall standard of clinical care.
Assuntos
Desenvolvimento Infantil , Desenvolvimento Fetal , Gráficos de Crescimento , Recém-Nascido/crescimento & desenvolvimento , Estudos Multicêntricos como Assunto/métodos , Projetos de Pesquisa , Pesos e Medidas Corporais , Protocolos Clínicos , Estudos Transversais/métodos , Estudos Transversais/normas , Feminino , Humanos , Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Estudos Longitudinais/métodos , Estudos Longitudinais/normas , Estudos Multicêntricos como Assunto/normas , Seleção de Pacientes , Gravidez , Controle de Qualidade , Ultrassonografia Pré-Natal , Reino UnidoRESUMO
Alterations in hormone secretion and cytokine levels have been evidenced in many neoplastic diseases. In this study we have evaluated the circadian profile of growth hormone (GH), insulin-like growth factor-1 (IGF-1), interleukin-2 (IL2), melatonin (MEL) and cortisol (COR) serum levels in non-small cell lung cancer patients. Blood was sampled every 4 h for 24 h in 11 healthy (H) men (ages 35-53 years) and 9 men with stage 2, 3 or 4 non-small cell lung cancer (C) (ages 43-63 years). Serum GH, total IGF1, IL2, MEL and COR were measured and examined for group differences, trends, and rhythm characteristics. 24-h means were significantly higher in C234 vs H for GH, GH/IGF1, IL2 and COR, and lower for IGF1, but IL2 and COR were not different for C23 vs H. A linear regression across 4 groups (H, C2, C3, C4) found a positive trend for COR, GH, GH/IGF1 and IL2, and a negative trend for IGF1. A linear regression run between the 24-h mean levels of GH, IGF1, COR, MEL and IL2 in healthy subjects evidenced a statistically significant positive trend between MEL and GH (R = 0.281, p = 0.022) and in cancer patients showed a statistically significant negative trend between GH and IGF1 (R = 0.332, p = 0.01), COR and IGF1 (R=0.430, p=0.001), and a statistically significant positive trend between the 24-h mean of COR and GH (R = 0.304, p = 0.02). Rhythms in MEL and COR (peaks near 01:00h and 08:00h, respectively) indicated identical synchronization to the light-dark cycle for both groups. A circadian rhythm was detected in GH and GH/IGF1 for C23 and H, with IGF1 and IL2 non-rhythmic in any group. In conclusion, an increasing trend and progressive loss of circadian rhythmicity in GH and GH/IGF1, an increasing trend in cortisol and IL2, and a decreasing trend in IGF1 in C, reflect a complex chain of events that could be involved in progression of neoplastic disease. A therapeutic strategy needs to take into account circadian patterns and complex interactions of the multiple functions that characterize the hormone and cytokine levels in the frame cancer progression.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Ritmo Circadiano , Hormônios/sangue , Interleucina-2/sangue , Neoplasias Pulmonares/sangue , Adulto , Análise de Variância , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Progressão da Doença , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Análise dos Mínimos Quadrados , Modelos Lineares , Neoplasias Pulmonares/patologia , Masculino , Melatonina/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de TempoRESUMO
BACKGROUND: The role of nutritional counselling (NC) with or without oral nutritional supplements (ONS) in patients receiving chemoradiotherapy (CRT) for head and neck cancer (HNC) still remains to be clearly defined, particularly with regard to CRT-related toxicity. METHODS: Patients undergoing CRT for HNC received NC by the dietitian within the first 4 days of radiotherapy and weekly for the course of radiotherapy (approximately 6 weeks). A weekly supply of oral nutrition supplements [1560 kJ (373 kcal) per 100 g] for up to 3 months was provided to all patients. RESULTS: Twenty-one patients completed CRT. Mucositis G3 developed in seven (33.3%) patients, whereas mucositis G4 was absent. Dysphagia was present before the start of treatment in four patients. In the remaining 17 patients, dysphagia G3 developed during/at the end of treatment in five cases. The percentage of patients interrupting anti-neoplastic treatment for was 28% for ≥6 days, 28% for 3-5 days and 44% for 0-2 days. Mucositis G3 frequency was lower in patients with a baseline body mass index (BMI, kg m(-2) ) ≥25 (two out of 12; 16.6%) than in patients with BMI <25 (five out of nine; 55.5%) (P = 0.161) and in patients with a baseline mid arm circumference >30 cm than in those with a mid arm circumference in the range 28.1-30 cm and <28 cm, and higher in patients with a greater weight loss and a greater reduction of serum albumin and mid arm circumference. CONCLUSIONS: Nutritional counselling and ONS are associated with relatively low CRT-related toxicity and with mild deterioration of nutritional parameters.
Assuntos
Quimiorradioterapia/efeitos adversos , Aconselhamento , Dietética/métodos , Nutrição Enteral , Neoplasias de Cabeça e Pescoço/terapia , Desnutrição/terapia , Terapia Combinada , Suplementos Nutricionais , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Masculino , Desnutrição/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Specific lymphocyte cell surface molecules involved in antigen recognition and cell activation present different circadian patterns, with peaks and troughs reflecting a specific time-related compartment of immune cell function. In order to study the dynamics of variation in expression of cytotoxic lymphocyte cell surface molecules that trigger immune responses, several lymphocyte cell surface clusters of differentiation (CD) and antigen receptors, analyses were performed on blood samples collected every 4 h for 24 h from eleven clinically-healthy men. Assays for serum melatonin (peaking at night) and cortisol (peaking near awakening) confirmed 24-h synchronization of the subjects to the light-dark schedule. A significant (p≤0.05) circadian rhythm could be demonstrated for six of the 10 lymphocyte subpopulations, with midday peaks for CD8+dim (T cytotoxic cells, 11:15 h), gammadeltaTCR (gamma-delta T cell receptor-expressing cells, 11:33 h), CD8+ (T suppressor/cytotoxic cells, 12:08 h), and for CD16+ (natural killer cells, 12:59 h), and peaks during the night for CD4+ (T helper/inducer cells, 01:23 h) and CD3+ (total T cells, 02:58 h). A borderline significant rhythm (p = 0.056) was also observed for CD20+ (total B cells), with a peak late in the evening (23:06 h). Acrophases for 3 subsets, CD8+bright (T suppressor cells, 15:22 h), HLA-DR+ (B cells and activated T cells, 23:06 h) and CD25+ (activated T lymphocytes with expression of the alpha chain of IL2 receptor, 23:35 h), where a 24-h rhythm could not be definitively determined, nevertheless provide information on the location of their highest values and possible physiological significance. Thus, specific lymphocyte surface molecules present distinctly-timed profiles of nyctohemeral changes that indicate a temporal (i.e., circadian) organization of cellular immune function, which is most likely of physiological significance in triggering and regulating immune responses. Such a molecular cytotoxic timetable can potentially serve as a guide to sampling during experimental, diagnostic, therapeutic and/or other medical procedures.
Assuntos
Antígenos de Diferenciação/metabolismo , Ritmo Circadiano/fisiologia , Linfócitos/citologia , Linfócitos/metabolismo , Fotoperíodo , Adulto , Humanos , Masculino , Melatonina/sangue , Pessoa de Meia-IdadeRESUMO
La intervención comunitaria (IC), desde la perspectiva de la psicología social comunitaria (PSC), se ha caracterizado por el trabajo con comunidades pobres, para contribuir a transformar las condiciones de exclusión de sus integrantes, redistribuir el poder, fomentar la equidad entre diversos actores y promover la justicia social, entre otros. La promoción de procesos comunitarios (organización, participación, sentido de comunidad, fortalecimiento), clave en la IC, ha sido fundamental para las metas de la PSC y para su desarrollo y consolidación como disciplina a mediados de los ochenta, lo que llamamos su segundo momento. En Venezuela, desde fines de los noventa se vienen generando cambios políticos con incidencia en todas las esferas de la vida. Uno de ellos es el impulso a la participación comunitaria desde las instituciones públicas, lo que repercutió en las condiciones de inserción y trabajo de profesionales de la PSC. Esta situación nos coloca, como académicos y practicantes de la PSC ante retos y dilemas de impostergable debate. En este trabajo analizamos algunos de estos retos y aportamos algunas reflexiones, que a nuestro juicio pueden servir para guiar una nueva agenda de la disciplina, dentro de lo que denominamos tercer momento, que vivimos en el contexto comunitario venezolano.
Assuntos
Humanos , Psicologia Social , Participação da Comunidade , Mudança Social , VenezuelaRESUMO
Surgery is the only curative therapy for gastric cancer. In the metastatic setting the objective of treatment is to manage symptoms, improve quality of life and prolong survival, but current treatment options have limited efficacy and some of them exhibit unfavourable toxicity profiles. Fluoropyrimidine, taxanes and platinum-based regimens are used most frequently and offer a response rate of 30-50% with a median overall survival of =1 year. These discouraging data support the need for new therapeutic strategies based on targeted drugs. Trastuzumab, a monoclonal antibody against HER2, has shown survival benefits when given with chemotherapy in all setting of HER2-positive breast cancer patients. The ToGA trial, the first study evaluating the efficacy and safety of adding trastuzumab to chemotherapy in HER-2 positive advanced gastric cancer, showed a significant superiority of combination over chemotherapy alone. Based on these results trastuzumab combined with a cisplatin and fluoropyrimidine regimen appear the new reference treatment for HER-2 positive metastatic gastric cancer.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Anticorpos Monoclonais Humanizados , Cisplatino/administração & dosagem , Humanos , Lapatinib , Quinazolinas/administração & dosagem , Receptor ErbB-2/metabolismo , TrastuzumabRESUMO
In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic "treatment until progression".
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Neoplasias do Colo/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Humanos , Irinotecano , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Taxa de SobrevidaRESUMO
In this case-report a case of severe fetal anemia of unknown origin is presented. Diagnosis of fetal anemia was made at 24 weeks of gestational age, when fetal ascites was identified. Doppler sonography of medium cerebral artery showed a high systolic speed velocity (ACM-PSV), of 65 cm/s (>1.55 MoM). This value predicts a severe fetal anemia. Funicolocentesis confirmed hyporegenerative anemia, low reticulocytosis and low erythroblastosis. A fetal transfusion was performed. At birth anemia was still present and the baby presented blueberry muffin and liver erythropoietic foci. The blueberry muffin morphology presents as non-blanching, blue-red macules or firm, dome-shaped papules (2-8 mm in diameter). The eruption is often generalized but favors the trunk, head, and neck. Infectious (Toxoplasmosis, Cytomegalovirus, Rubella, Herpes, Parvo, Coxackievirus, Ebstein Barr, Syphilis), hematologic (sferocytosis, alloimmunization, foeto-maternal transfusion), metabolic, neoplastic (congenital leukemia, neuroblastome, congenital rhabdomyosarcome) and systemic (histiocytosis, lupus) pathologies indicated until now as possible disease causes were excluded. In the first day of life the neonate received a RBC transfusion for anemia (Hb=5.1 g/dL; Hct 15,7% at birth), followed within 48-72 hours by rapid disappearance of the rash, that wasn't then histologically examined. During two weeks of hospitalization reticulocytes raised spontaneously from 0.8% to 3.17%. Until two years of age the auxologic and clinical course was regular and the child is now in good health conditions. Due to the absence of systematic disease and the complete regression, no exact diagnosis and prognosis could be established in this case.
Assuntos
Anemia , Dermatopatias Vesiculobolhosas , Anemia/complicações , Anemia/diagnóstico , Feminino , Humanos , Recém-Nascido , Remissão Espontânea , Dermatopatias Vesiculobolhosas/complicações , Dermatopatias Vesiculobolhosas/diagnósticoRESUMO
As a result of progresses in surveillance programs and improvements in diagnosis, an increased number of hepatocellular carcinomas are diagnosed in early stage, when effective treatment options are available. Surgical resection, liver transplantation and radiofrequency ablation are considered potentially curative treatments and may be successfully applied when the disease is limited. In intermediate and advanced stages only palliative therapies can be employed and chemoembolization and the oral dual inhibitor sorafenib are considered the treatments of choice. Future directions will explore the role of sorafenib in the adjuvant setting, the addition of sorafenib to chemoembolization procedures and the combination of sorafenib with chemotherapeutic agents or other biological drugs in advanced stages of disease.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Terapia Combinada , Humanos , Neoplasias Hepáticas/patologia , Transplante de Fígado , Estadiamento de Neoplasias , Prognóstico , Resultado do TratamentoRESUMO
El Grupo de Investigación Historia , Enseñanza y Profesionalización de la Psicología en los países del Cono Sur de la UNMP desarrolla actualmente el proyecto Antecedentes de los estudios psicológicos en Mar del Plata y prospectiva en el marco de la psicología como profesión regulada, representando este trabajo un avance del mismo. En una primera etapa se atendió, especialmente, a indagar el período preuniversitario en el que se impartió en Mar del Plata, Argentina, formación psicológica en estudios sistemáticos. En tal sentido, se reconocen como antecedentes al Instituto de Pedagogía [ISP], uno de los cinco creados en 1949 en la Provincia de Buenos Aires bajo el gobierno peronista, y al Instituto Superior de Ciencias de la Educación [ISCE] que funcionó desde 1960 y hasta la creación del grado académico en la UPMP, en 1966. Estos Institutos formaban recursos humanos destinados al ámbito educativo, siendo el ISCE la institución otorgante de las primeras titulaciones específicas en Psicología. El presente trabajo se centra en esta última institución, e intenta indagar las razones que propiciaron el viraje del énfasis educativo al clínico en la formación de sus alumnos y posterior inserción laboral de sus egresados, incluyendo el análisis de testimonios orales de sus protagonistas.
Assuntos
Humanos , Universidades , Psicologia/história , ArgentinaRESUMO
Gastric cancer is still a major health problem and a leading cause of cancer mortality despite a worldwide decline in incidence. Surgery is the primary curative treatment of locoregional gastric cancer. In Western countries, however, at the time of resection, most patients are expected to have regional lymph node involvement with poor prognostic implications. To improve these results, different trials have been carried out in the adjuvant or neo-adjuvant setting. Many phase III trials of adjuvant therapy have been conducted; however, postoperative treatment modalities have not proven to be superior to postsurgical observation alone. Therefore, at present the routine use of adjuvant therapy should be regarded as an investigational approach. Improved clinical trial designs with standardized surgical techniques and the incorporation of newer active drugs are needed. On the contrary, neo-adjuvant chemotherapy has shown promising results as suggested by the final results of UK Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial.
Assuntos
Adjuvantes Farmacêuticos/farmacologia , Antineoplásicos/farmacologia , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/tendências , Ensaios Clínicos Fase III como Assunto , Humanos , Metanálise como Assunto , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/tendências , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: In daily clinical practice second-line chemotherapy (SLCT) is frequently given to patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy without solid scientific support. PATIENTS AND METHODS: A retrospective survey was carried out including 42 patients. Patients received standard FOLFOX4 regimen biweekly until progression or unacceptable toxicity. RESULTS: Six partial responses (14%) and 16 stabilizations (38%) were recorded for a tumor growth control rate of 57%. The median time to progression (TtP) was 4 months (range 1-7 months), and median overall survival (OS) was 6.7 months (range 2-9 months). A stabilization of performance status (PS) and a subjective improvement of cancer-related symptoms were recorded in 27 patients. CONCLUSIONS: Data presented in this paper support the use of FOLFOX4 regimen in the second-line treatment of adenocarcinoma of the pancreas patients. The use of SLCT, however, should be carefully proposed to patients with good PS or those who had a good response to first-line therapy.