RESUMO
Caloric restriction (CR) is a dietetic intervention based on the reduction of daily calorie intake by 10-30 %. When subjected to CR, the organism adjusts its metabolism to the changing availability of key nutrients. However, fatty acids' content in organisms subjected to long-term CR has not been evaluated. The aim of the research was to analyze the influence of long-term CR on the contents of medium- and long-chain fatty acids, as well as on the contents of fatty acid derivatives in liver. The study was performed on C57BL female (n = 12) and male (n = 12) mice subjected to lifelong 30 % calorie restriction. Fatty acids were analyzed using gas chromatography, while fatty acid derivatives were analyzed with liquid chromatography. The dynamics of change of the lipid profile of the labeled fatty acids observed in the liver tissue confirms that lipolysis actively takes place in this organ when hungry. Moreover, it is highly possible that de novo synthesis of acids takes place, with the aim to ensure energy substrates to the body. Moreover, an increase of concentration was observed for fatty acid derivatives, those with anti-inflammatory properties (resolvin, LTX A4). However, there was no increase in the concentration of pro-inflammatory eicosanoids. The results suggest that it is important to take into consideration the introduction of appropriate supplements when using CR.
Assuntos
Restrição Calórica , Ácidos Graxos , Masculino , Feminino , Camundongos , Animais , Ácidos Graxos/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismoRESUMO
Stevens-Johnson's Syndrome (SJS) and Toxic Epidermal Necrolysis are rare, life-threatening dermatologic conditions with acute onset and not clearly established treatment protocol. A plethora of observational studies are present with lack of up-to-date consensus based on evaluation of objective endpoints, among others mortality. Thorough analysis of available databases (Pubmed, EMBASE, Cinahl, Web of Science, Clinical Trials) was conducted according to PRISMA guidelines. Authors initially identified 700 papers, with 82 of them potentially eligible according to adopted criteria. A total of 42 studies were included into pooled synthesis. For continuous outcomes we analyzed the pooled means for endpoint scores using observed cases data. Categorical outcomes were analyzed by calculating the pooled event rates. We conducted subgroup and exploratory maximum likelihood random effects meta-regression analyses regarding SCORTEN of all outcomes. Using random-effects model, the overall pooled Mortality Rate was 0.191 (95%CI, 0.132-0.269). The lowest mortality rate was found to be linked with Etanercept and highest in Total Plasma Exchange (TPE) and Intravenous Immunoglobulin (IVIG). Overall reepithelization was 13.278 days (95%CI, 8.773-17.784),The highest was found in cyclosporine treatment; 14.739 whilst the lowest for steroids. Length of hospital stay in overall analysis was 19.99 days (95%CI, 16.53-23.44),the highest was linked with TPE/TPE+IvIg treatment, the lowest with steroids. Risk of bias of assessed studies was estimated to be high (for observational studies mean STROBE score 12.44). High quality TEN and SJS studies are lacking. Almost all papers report observational data without randomization and double-blind control. Therefore, the pooled analysis cannot be presented with initial bias. In our meta-analysis the most successful regimen was Etanercept treatment. It was linked with the lowest mortality. The most negative treatment outcome was observed in studies reporting TPE and IVIG. Randomized trials of high quality are needed in SJS and TEN.
Assuntos
Queimaduras , Síndrome de Stevens-Johnson , Queimaduras/tratamento farmacológico , Etanercepte/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Esteroides/uso terapêuticoAssuntos
Distrofia Miotônica/diagnóstico , Pilomatrixoma/etiologia , Pilomatrixoma/genética , Adulto , Eletromiografia , Humanos , Masculino , Mutação , Distrofia Miotônica/fisiopatologia , Miotonina Proteína Quinase , Neoplasias Primárias Múltiplas/patologia , Pilomatrixoma/diagnóstico , Pilomatrixoma/patologia , Neoplasias Cutâneas/patologia , beta CateninaRESUMO
Concern regarding the occurrence of chemicals that disrupt endocrine system functions in aquatic species has heightened over the last 15 years. However, little attention has been given to monitoring for estrogenic endocrine disrupting chemicals (EEDCs) in California's freshwater ecosystems. The objective was to screen surface water samples for estrogenic activity using vitellogenin (Vtg) mRNA quantification in livers of juvenile rainbow trout by real-time reverse transcriptase polymerase chain reaction (Q-RT PCR). Vtg mRNA analysis of livers from fish exposed to 113 ambient water samples collected from surface waters in California's Central Valley and northern area indicated that six samples (5% of total) may have contained EEDCs. The six samples induced marginal, but statistically significant, increases of Vtg mRNA. No ambient water sample evoked Vtg mRNA responses equivalent to those in positive controls (all responses were less than 2% of the positive control response). Thus, EEDC concentrations in these samples were low (at or near the threshold for the procedure) or results may have included false positives. To establish a more definitive assessment of EEDC occurrence, follow-up screening at sites where statistically significant, but weak, estrogenic activity was observed is recommended. Overall, results reveal that a majority of the California surface waters tested were below EEDC detection threshold concentration for the screening procedure utilized.
Assuntos
Disruptores Endócrinos , Estrogênios não Esteroides , Fígado/efeitos dos fármacos , Oncorhynchus mykiss , Vitelogeninas/biossíntese , Poluentes Químicos da Água , Animais , California , Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Monitoramento Ambiental , Estrogênios não Esteroides/análise , Estrogênios não Esteroides/toxicidade , Água Doce/química , Fígado/metabolismo , Oncorhynchus mykiss/crescimento & desenvolvimento , Oncorhynchus mykiss/metabolismo , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Dominance status is associated with individual differences in reproductive capacity in many animal societies, but the mechanisms that link social dominance to reproductive physiology are poorly understood. We propose a model for social dynamics that incorporates the nutritional costs and benefits of behavior: dominant individuals avoid energy-expensive behavior and build their nutritional reserves, thereby increasing their potential for reproduction. Greater reproductive capacity, once achieved, favors increased social dominance. To test the model, we measured relationships of females' nutrient storage and reproductive capacities with dominance status and task performance in the eusocial wasp Mischocyttarus mastigophorus. Ovary development was positively related with high levels of nutrient storage and with high rates of dominance behavior, but was not correlated with task performance. In contrast, high levels of nutrient storage were positively related with the performance of nutrient garnering and conserving tasks, but not with dominance behavior. These data support a model which places the nutritional costs of task performance as an intermediate causal link that connects dominance status with the accumulation of nutrient stores. Nutrient flow may be a general causal mechanism linking dominance status to reproductive capacity in animal societies.
Assuntos
Comportamento Alimentar/fisiologia , Predomínio Social , Vespas/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Tamanho Celular , Feminino , Modelos Lineares , Oócitos/citologia , Ovário/fisiologia , Reprodução/fisiologia , Comportamento Sexual Animal/fisiologiaRESUMO
Adolescents' friendship quality and observed emotional expression with their best friends were predicted from reports of their mother's interpersonal relationships-specifically the quality of her marriage and social network. Two models explaining these relationships received support. Consistent with an Attachment Theory model, adolescents' perceptions of marital quality predicted attachment security with mother, father and friends. Security of attachment to friends in turn predicted best friendship quality, but not affective behavior with the friend. A Social Learning Theory model was also supported, in which perceptions of both marital quality and mother's social network quality predicted adolescents' prosocial behavior. Prosocial behavior in turn predicted both best friendship quality and affective behavior with the friend.
Assuntos
Relações Interpessoais , Modelos Psicológicos , Relações Mãe-Filho , Apego ao Objeto , Psicologia do Adolescente , Adolescente , Feminino , Humanos , Funções Verossimilhança , Masculino , Casamento/psicologia , Poder Familiar , Grupo Associado , Quebeque , Análise de Regressão , Percepção Social , Gravação de VideoteipeRESUMO
Using a new longitudinal clustering technique, this study aimed to (a) empirically identify groups of children with distinct longitudinal profiles of peer social preference during elementary school; (b) compare these groups regarding their longitudinal pattern of classification into J. D. Coie, K. A. Dodge, and H. Coppotelli's (CDC; 1982) sociometric categories; and (c) compare these groups regarding their longitudinal trajectories of antisocial, hyperactive, and anxious behavior. Based on 299 children, 3 groups were identified: a stable popular group, a stable average group, and an unpopular group whose social preference decreased over time. Each of the groups showed considerable overlap over time with their closest corresponding CDC category (popular, average, rejected). Growth curve analyses showed that externalizing and internalizing behavior generally decreased over time, but overall means and the rates of decrease differed in the 3 groups.
Assuntos
Transtornos do Comportamento Infantil/epidemiologia , Desenvolvimento Infantil , Comportamento de Escolha , Grupo Associado , Percepção Social , Transtorno da Personalidade Antissocial/epidemiologia , Transtorno da Personalidade Antissocial/psicologia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Criança , Transtornos do Comportamento Infantil/psicologia , Análise por Conglomerados , Feminino , Seguimentos , Humanos , Masculino , Semântica , Inquéritos e QuestionáriosRESUMO
The goal of this study was the prognostic evaluation of histology, mitotic rate, S-phase fraction (SPF) and expression of proliferative antigen Ki67 and p53 protein in phyllodes tumor of the breast. The study was performed in the group of 118 patients with phyllodes tumor treated by surgery from 1952 to 1998. Mitotic rate was assessed on the representative histological specimens. Expressions of Ki67 and p53 were evaluated by immunohistochemistry on a section from the corresponding paraffin blocks which were also used for flow cytometric DNA evaluation. Histologically, 52 tumors were benign (LGM), 24 borderline malignancies (BM) while among 42 malignant tumors, 20 were monomorphous (HGM) and the remaining 22 revealed heterologic elements (HGH). Tumor recurrencies occurred in 17 patients, predominantly during the first three years after surgery, and 13 patients died of the tumor (1 BM, 12 both malignant variants). Multivariate analysis demonstrated mitotic rate, SPF and p53 expression as independent prognostic parameters for the disease-free survival. Histological tumor type and expression of Ki67 influenced independently the overall survival. In conclusion, the histological type of tumor phyllodes forms the basis for the prognosis of clinical outcome, but the indicators of the proliferative activity, especially Ki67 index, are valuable prognostic factors among patients with malignant variant of phyllodes tumor of the breast. Expression of the p53 protein in tumor cells could be also useful when the percentage of cells and intensity of expression are considered.
Assuntos
Neoplasias da Mama/genética , Divisão Celular , DNA de Neoplasias/análise , Regulação Neoplásica da Expressão Gênica , Tumor Filoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Ciclo Celular , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Antígeno Ki-67/biossíntese , Pessoa de Meia-Idade , Índice Mitótico , Recidiva Local de Neoplasia , Tumor Filoide/patologia , Prognóstico , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossínteseRESUMO
PURPOSE: Radiation therapy has a high success rate in the treatment of early glottic carcinoma. Excellent outcomes have been reported from centers using cobalt-60 or relatively low-energy (< or = 4 MV) radiation therapy to achieve these results. Whether similar outcomes can be achieved with a 6 MV linear accelerator has been less rigorously evaluated. This study assesses the efficacy of 6 MV radiation therapy for early stage glottic cancer and identifies prognostic factors for local control and overall survival in this common disease. MATERIALS AND METHODS: One hundred twenty-eight consecutive cases of Tis, T1, and T2 squamous cell carcinomas of the glottis from 1982 to 1996 were retrospectively analyzed with regard to local control and survival. All patients were treated with definitive radiation therapy with a 6-MV linear accelerator. Potential prognostic factors for local control and survival were evaluated with univariate and multivariate models. Median follow-up of locally controlled patients was 65 months. RESULTS: The overall 3-year actuarial local control rates for T1 and T2 carcinomas were 86% and 68%, respectively. Patients with lesions involving the posterior third of the vocal cord had significantly worse 3-year local control (76% vs. 86%, P =.038). Radiation therapy technique and overall treatment time did not significantly affect local control. For patients with Tis and T1 lesions, factors associated with significantly worse local control included cordectomy-ineligible disease (P =.024), dose less than 6,600 cGy (P =.024), and lesions limited to the posterior third of the vocal cord (P =.004). Three-year local control was 76%, with doses less than 6,600 cGy and 90% with higher doses. High rates of second primary malignancies were observed and represented the major cause of death. Five-year overall survival was 84%. CONCLUSIONS: The use of 6-MV photons for treatment of early glottic cancer seems to achieve local control similar to that reported with lower-energy photons. However, patients with posterior third involvement had a poorer local control rate with standard radiation therapy, thereby suggesting that alternative approaches be considered.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Glote/efeitos da radiação , Neoplasias Laríngeas/radioterapia , Radioterapia de Alta Energia/métodos , Prega Vocal/efeitos da radiação , Idoso , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Glote/cirurgia , Humanos , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Prega Vocal/cirurgiaRESUMO
Cystic fibrosis (CF) is caused by mutations in the CFTR gene. The spectrum of CFTR mutations varies between populations and depends on different factors, such as ethnic background and geographical location. The extensive CFTR mutation screening of 129 patients with classical or atypical CF from the south-western region of Sweden revealed the presence of 37 CFTR mutations, including 12 novel alleles. The overall mutation detection rate in this study population was 92%, the highest among all tested regions in Sweden. Eight mutations with a frequency above 1% (DeltaF508, 394delTT, R117C, 3659delC, E60X, 1112delT, R764X, and 621 + 1G --> T) accounted for 78% of CF chromosomes and have been recommended for inclusion in the CFTR mutation screening panel for molecular diagnosis of CF in this region. The multiple occurrence of specific CFTR alleles less common than the predominant DeltaF508 mutation (394delTT, R117C, 3659delC) allowed for genotype-phenotype comparisons and revealed consistent relationships between these mutations and disease severity.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação , Adulto , Pré-Escolar , Códon sem Sentido , Fibrose Cística/fisiopatologia , DNA/sangue , Análise Mutacional de DNA , Mutação da Fase de Leitura , Heterogeneidade Genética , Genótipo , Humanos , Lactente , Mutação de Sentido Incorreto , Fenótipo , SuéciaAssuntos
Cromossomos Humanos Par 19 , Fibrose Cística/genética , Obstrução Intestinal/genética , Mecônio , Criança , Mapeamento Cromossômico , Fibrose Cística/fisiopatologia , Volume Expiratório Forçado , Marcadores Genéticos , Humanos , Repetições de Microssatélites , Núcleo Familiar , Polimorfismo GenéticoRESUMO
This study examined developmental differences in two dimensions of attachment security (parental availability and child dependency on parents) in late childhood (N = 274) and early adolescence (N = 267) and their association with peer relations. Children's perceptions of mother's availability and boys' perceptions of father's availability did not differ as a function of age. Dependency on parents, however, decreased with age. Findings highlight the importance of distinguishing between parental availability and reliance on parental help when measuring attachment developmentally. Children's reports of positive friendship qualities and lack of conflict in their best friendships were related to attachment to both mother and father, whereas the presence of a reciprocated friendship and popularity were not. Father availability was a particularly important predictor of lower conflict with best friends. Findings indicate that the quality of parent-child attachment generalizes primarily to the quality of children's close peer relations.
Assuntos
Desenvolvimento Infantil/fisiologia , Relações Interpessoais , Apego ao Objeto , Relações Pais-Filho , Grupo Associado , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
DNA content according to six various ploidy classes was analysed by flow cytometry on fresh tumor tissue in 701 unselected, consecutive breast cancers. Age, menopausal status, tumor size, histology and in particular nodal status were also taken into consideration. Diploid and nondiploid mammary carcinomas differed significantly in values of proliferative indicators. In node positive patients nondiploid tumors were more frequent. In node negative and node positive breast cancer patients tumor grade strongly influenced disease free survival and in the last group hypertriploidy (1.6 < DI < or = 1.8) was also an independent prognostic factor. The combination of tumor grade and hypertriploidy permitted differentiation of three groups of node positive patients, differing in the risk of relapses.
Assuntos
Adenocarcinoma/genética , Neoplasias da Mama/genética , DNA de Neoplasias/análise , Recidiva Local de Neoplasia/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Divisão Celular , Feminino , Citometria de Fluxo , Fase G2 , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Fase S , Análise de SobrevidaRESUMO
PURPOSE: The optimal sequencing of chemotherapy and radiation therapy in patients with early-stage breast cancer undergoing breast-conservation treatment remains controversial. The purpose of this study is to evaluate the outcome of patients treated with one specific sequence of concurrent chemoradiation followed by additional chemotherapy. METHODS: Between 1977 and 1992, 210 patients with stage I and II breast cancer underwent lumpectomy and axillary lymph node dissection followed by treatment with concurrent chemotherapy and radiation therapy, followed by further chemotherapy. Chemotherapy consisted of two 28-day cycles of CF (oral cyclophosphamide, 100 mg/m2 day 1 to 14, and intravenous 5-fluorouracil, 600 mg/m2 days 1 and 8) during radiation therapy, followed in general by six cycles of CMF (CF doses as above plus intravenous methotrexate 40 mg/m2 days 1 and 8) after the completion of radiation therapy. Fifty patients also received hormonal therapy, predominantly tamoxifen. One hundred ten patients had clinical T1 lesions, and 100 had T2 lesions. Fifty-three patients were pathologic N0, and 157 patients were pathologic N1 (123 patients had one to three positive nodes, and 34 patients had four or more positive nodes). Median follow-up for node-negative patients (5.2 years) is shorter than for node-positive patients (7.6 years). Therefore, outcome is reported at 5 and 10 years for node-positive patients but only at 5 years for node-negative patients. RESULTS: For node-positive patients, outcomes at 5 and 10 years, respectively, were 86% and 70% for overall survival, 78% and 67% for no evidence of disease survival, and 82% and 69% for freedom from distant metastases. For node-negative patients, outcomes at 5 years were 94% for overall survival, 94% for no evidence of disease survival, and 94% for freedom from distant metastases. Pathologic nodal status was predictive of outcome after treatment. Local failure in the treated breast was 5% at 5 years and 13% at 10 years for all patients. CONCLUSIONS: Concurrent CF with radiation therapy followed by six cycles of CMF after radiation therapy results in excellent survival, freedom from distant metastases, and local control for both node-negative and node-positive patients. This regimen of concurrent chemotherapy and radiation therapy is one option for sequencing, and it avoids the delays in administration of either modality that are associated with other sequencing regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Adulto , Neoplasias da Mama/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamoxifeno/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Choice of treatment for base of tongue carcinoma is controversial, with options including surgery alone, radiotherapy alone, or multimodality treatment. Given the highly aggressive nature of these tumors, it has been our institutional policy to manage this disease with combined partial glossectomy (with attempt to avoid laryngectomy if possible) with planned postoperative radiotherapy (RT). We reported on our institutional experience with this approach. METHODS: A retrospective review of the charts of 17 patients with primary base of tongue squamous cell carcinoma treated with surgery and postoperative RT was performed. Patients treated with chemotherapy as part of their management were excluded. All patients underwent partial, hemi-, or subtotal glossectomy; 15/17 patients underwent ipsilateral radical or modified radical neck dissection. All patients received comprehensive postoperative RT (median dose 6000 cGy; range 5040-6920 cGy). Stage distribution was as follows: stage I, 2; stage II, 3; stage III, 2; stage IV, 10. Positive margins for invasive carcinoma were found in 9/17 patients. Median follow-up of surviving patients is 46 months; median follow-up for all patients is 31 months. RESULTS: For the entire group of patients, the actuarial 3-year local-regional control rate was 68%. The actuarial 3-year overall survival rate was 46%. The local-regional control rate was 83% for patients with stage I-III disease versus 50% for stage IV disease. There were no local failures among eight patients with negative margins (local control 100%) compared with an actuarial local control rate of 36% among patients with positive margins (p = .03). Survival, disease-specific survival, and locoregional control were also highly correlated with margin status (p = .003). Late major complications included 5/17 patients requiring permanent G-tubes and/or tracheostomy to prevent aspiration. CONCLUSIONS: Surgery plus postoperative RT is an intensive treatment for carcinoma of the base of tongue which offers high locoregional control in patients in whom negative margins are achieved. Positive margins indicate a high risk of locoregional and systemic failure, and these patients should be considered for innovative clinical trials after surgery.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias da Língua/cirurgia , Análise Atuarial , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Terapia Combinada , Intervalo Livre de Doença , Nutrição Enteral/instrumentação , Seguimentos , Gastrostomia/instrumentação , Glossectomia/efeitos adversos , Glossectomia/métodos , Humanos , Esvaziamento Cervical , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Deiscência da Ferida Operatória/etiologia , Taxa de Sobrevida , Neoplasias da Língua/patologia , Neoplasias da Língua/radioterapia , Traqueostomia , Falha de Tratamento , Resultado do TratamentoAssuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Ducto Deferente/anormalidades , Anormalidades Congênitas/genética , Fibrose Cística/complicações , Fibrose Cística/genética , Análise Mutacional de DNA , Mutação da Fase de Leitura/genética , Humanos , Masculino , Mutação/genéticaRESUMO
The present study examined the influence of caregivers' Attachment Styles (Anxious-ambivalent and Avoidant factors) and personality traits (Neuroticism, Extraversion, Agreeableness, and Conscientiousness) on their experiences of caring for dementia dependents. A total of 126 caregiver-dependent pairs participated in the study. Support was found for the contribution of the attachment style factors in explaining aspects of caregiver experiences. Those who chose to institutionalize dependents were higher on the Avoidance factor than those choosing to maintain them in the community. Less Anxious-ambivalent caregivers reported larger social support networks, and more satisfaction with the support received than those lower on this factor. The caregiver Anxious/ambivalence and Neuroticism dimensions seemed to function as generalized responses reflected in perceptions and appraisals of the stressful situation.
Assuntos
Cuidadores/psicologia , Demência , Apego ao Objeto , Personalidade , Adaptação Psicológica , Idoso , Tomada de Decisões , Emoções , Feminino , Humanos , Institucionalização , Masculino , Autoimagem , Apoio Social , Estresse Psicológico , Inquéritos e QuestionáriosRESUMO
PURPOSE: Chemotherapy plays an increasingly important role in the treatment of both node-negative and node-positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established. The purpose of this study is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of Stage I and II breast cancer patients treated with breast-conserving therapy. METHODS AND MATERIALS: The records of 1053 Stage I and II breast cancer patients treated with curative intent with breast-conserving surgery, axillary dissection, and radiation therapy between 1977-1991 were reviewed. Median follow-up after treatment was 6.7 years. Two hundred fourteen patients received chemotherapy alone, 141 patients received hormonal therapy alone, 86 patients received both, and 612 patients received no adjuvant therapy. Patients who received chemotherapy +/- hormonal therapy were grouped according to sequence of chemotherapy: (a) concurrent = concurrent chemotherapy with radiation therapy followed by chemotherapy; (b) sequential = radiation followed by chemotherapy or chemotherapy followed by radiation; and (c) sandwich = chemotherapy followed by concurrent chemotherapy and radiation followed by chemotherapy. Compared to node negative patients, node-positive patients more commonly received chemotherapy (77 vs. 9%, p < 0.0001) and/or hormonal therapy (40 vs. 14%, p < 0.0001). Among patients who received chemotherapy, the majority (243 patients) received concurrent chemotherapy and radiation therapy with two cycles of cytoxan and 5-fluorouracil (5-FU) administered during radiation followed by six cycles of chemotherapy with cytoxan, 5-fluorouracil and either methotrexate (CMF) or doxorubicin(CAF). For analysis of cosmesis, patients included were relapse free with 3 years minimum follow-up. RESULTS: The use of chemotherapy had an adverse effect on cosmetic outcome compared to no chemotherapy, which was of borderline significance at 3 years (92% excellent or good cosmetic outcome vs. 96% respectively, p = 0.057); however, cosmesis was not different at 5 years (91 vs. 93% respectively, p = 0.67). Cosmesis was not significantly different between patients treated sequentially and those treated concurrently (3 year: 87 vs. 93% respectively, p = 0.33), nor was it different between patients who received CMF vs. CAF (3 year: 92 vs. 93% respectively, p = 0.89). Hormonal therapy did not influence cosmetic outcome (p = 0.78). The incidence of Grade 4 or 5 arm edema (> or = 2 cm difference in arm circumference) was 2% without chemotherapy vs. 8% with chemotherapy (p = 0.00002). However, the incidence of arm edema was not affected by sequencing or type of chemotherapy (all p > or = 0.52). Patients treated sequentially had a 10% incidence of Grade 4 or 5 arm edema vs. 7% in the patients treated concurrently (p = 0.52). The incidence was 7 vs. 9% in patients treated with CMF vs. CAF (p = 0.73). The incidence of clinical pneumonitis and rib fracture was not influenced by use of chemotherapy, sequence of chemotherapy or use of hormonal therapy (all p > or = 0.06). CONCLUSIONS: Chemotherapy can be given concurrently with radiation therapy in the treatment of Stage I and II breast cancer with breast-conserving therapy without seriously compromising cosmetic outcome or incidence of complications compared to patients receiving other sequences of chemotherapy. Hormonal therapy did not affect cosmesis or complications. The chemotherapeutic regimen of cytoxan and 5-FU concurrent with radiation therapy followed by more chemotherapy is one reasonable option for breast conservation therapy in patients requiring chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Radioterapia/efeitos adversosRESUMO
Primary fibroblasts, after serum withdrawal or after irradiation, do not undergo apoptosis. Myc-transfected fibroblasts, in contrast, undergo apoptosis upon serum withdrawal and after irradiation. We have studied the relationship of apoptosis induction to effects on the G2 phase cell cycle in a series of rat embryo cells transformed by rasH plus myc or immortalized by myc alone. In this system, while the presence of rasH had little effect on the extent of apoptosis induction by serum withdrawal, rasH greatly suppressed the apoptotic response of myc-transfected cells to X-rays. The cells into which rasH had been introduced showed a profound G2 arrest associated with suppression of cyclin B1 mRNA expression. In contrast, cells with myc alone had a minimal G2 delay after irradiation and no suppression of cyclin B1 mRNA expression. We hypothesize that rasH, by influencing the G2 response of cells to X-rays, exerts an anti-apoptotic effect. In support of this hypothesis; we found that treatment of cells with caffeine, an agent that relieves the G2 delay after irradiation resulted in increased apoptosis in the irradiated cells, but not in control cells.