PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms. 相似文献
The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues. 相似文献
Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.
Objectives
The objective of this paper, part of the MAPEC_LIFE project, is to describe the frequency of micronuclei and meta-nuclear alterations in exfoliated buccal cells of 6–8year-old Italian children recruited in five Italian towns (i.e., Brescia, Torino, Pisa, Perugia and Lecce) with different air pollution levels.
Methods
About 200 children per town were recruited from primary schools. Biological samples were collected twice from the same children, in two different seasons (winter 2014-15 and late spring 2015). Cytogenetic damage was evaluated by the buccal micronucleus cytome assay.
Results
Overall,n?=?1046 children represent the final cohort of the MAPEC_LIFE study. On the whole, the results showed a higher mean MN frequency in winter (0.42?±?0.54‰) than late-spring (0.22?±?0.34‰). MN frequency observed among the five Italian towns showed a trend that follows broadly the levels of air pollution in Italy: the highest MN frequency was observed in Brescia during both seasons, the lowest in Lecce (winter) and Perugia (late-spring).
Conclusions
To the best of our knowledge, the number of recruited children included in the analysis (n?=?1046) is the highest compared to previous studies evaluating the frequency of MN in exfoliated buccal cells so far. MN frequency was associated with winter season and living in towns at various levels of air pollution, suggesting an important role of this exposure in determining early cytogenetic effects. 相似文献
The National Institute for Occupational Safety and Health evaluated farm pesticide exposure and glioma risk in a study that included 457 glioma cases and 648 population-based controls, all adult men (18-80 yr old) and nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic regressions were used to control for farm residence, age, age group, education, and exposure to other pesticides. No associations were found between glioma and 12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and found reduced glioma risk for insecticides (OR = 0.53, CI = 0.37-0.77), fumigants (OR = 0.57, CI = 0.34-0.95), and organochlorines (OR = 0.66, CI = 0.47-0.94). In analyses excluding proxy respondents (47% of cases) most CIs included 1.0. No positive association of farm pesticide exposure and glioma was found. Other farm exposures may explain the excess brain cancer risk seen in previous studies. 相似文献
Introduction: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are two effective bariatric surgical procedures with positive outcomes in terms of weight loss, comorbidities remission, and adverse events profiles. OAGB seems to carry a higher risk of malnutrition, but existing data are controversial. The aim of this study is to objectively evaluate and compare malnutrition in patients undergoing RYGB and OAGB. Methods: Retrospective monocentric study of obese patients undergoing RYGB or OAGB between the 15 September 2020 and the 31 May 2021. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score and compared between groups. The primary outcome was the mean CONUT score at 6 months. The secondary outcomes included the incidence of malnutrition, comorbidities, including hypertension, insulin resistance and type II diabetes mellitus, and weight loss. Results: 78 patients were included: 30 underwent RYGB and 48 underwent OAGB. At 6-Month Follow-Up there was no difference between groups in the mean CONUT score nor in incidence of malnutrition. In both groups, the nutritional status significantly worsened 6 months after surgery (preoperative and postoperative score of 0.48 ± 0.9 and 1.38 ± 1.5; p = 0.0066 for RYGB and of 0.86 ± 1.5 and 1.45 ± 1.3; p = 0.0422 for OAGB). Type II Diabetes mellitus (DMII) and hypertension remission were significant in the OAGB group with a 100% relative remission in the DMII-OAGB group (p = 0.0265), and a 67% relative remission in the hypertension-OAGB group (p = 0.0031). Conclusions: No difference in nutritional status has been detected between patients undergoing RYGB or OAGB at the 6-Month Follow-Up. Both procedures may have significant mal-absorptive effects leading to decline in nutritional status. OAGB may be more efficacious in inducing DMII and hypertension remission. Larger prospective studies dedicated specifically to nutritional status after gastric bypass are needed to confirm the impact of different bypass procedures on nutritional status. 相似文献
Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C14) have not yet been reported. In this study an evaluation of the ability of C14 to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C14 was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C14 decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C14 induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C14 has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases. 相似文献
ABSTRACTContext: A limited number of studies have been conducted examining the role of beliefs in the prediction of breast self-examination (BSE) behavior in Australian women, particularly women under 50 years of age for which it is the primary method of early detection of breast cancer. Objective: The present research investigated the differences in behavioral, normative and control beliefs between BSE performers and non-performers, within a theory of planned behavior framework, to assist in the development of specific education programs aimed at increasing BSE amongst this demographic group. Method: Two hundred and fifty-three women enrolled in an undergraduate psychology course completed a questionnaire assessing beliefs regarding BSE. One month later, these women reported their BSE behavior during the previous month. Multivariate analyses were performed to identify belief-based differences between BSE performers and non-performers. Results: Underlying behavioral and control, but not normative, beliefs about BSE distinguished between BSE performers and non-performers. Performers were more likely than non-performers to believe that engaging in BSE would be associated with identifying a lump or breast change sooner and detecting a breast cancer earlier in its course. Non-performers were more likely to perceive factors such as forgetting to perform the behavior, lack of time, lack of knowledge about how to perform the behavior, laziness, and a lack of confidence in their ability to identify lumps and breast changes as factors preventing their control over the performance of BSE. Conclusions: The belief-based differences between BSE performers and non-performers found in this study can be used to inform health promotion strategies aimed at increasing BSE behavior in women less than 50 years of age. 相似文献
Objective: Describe the use of assistive technology to enhance communication opportunities for older adults.
Methods: A systematic review was conducted in two databases, PubMed and Web of Science, by using two different searches in each. The search was limited to original articles, in English language, including people aged 60 years and older that used any type of assistive technology for communication. The articles found in the initial search were filtered by title, abstracts and the remaining articles were fully read.
Results: Eighteen studies were included in this review after the reading of full-texts. Most of the studies included apparently healthy participants with communication limitations due to aging related changes and the others included people with some pathology that prevent them from normal communication.
Conclusion: Four categories of assistive technology were identified: assistive technology for people with speech problems; robot or videoconferencing systems; Information and Communication Technologies and, other types of assistive technology for communication, such as hearing aids and scrapbooks. Assistive technology for communication of older adults is not only used by people with disabilities that prevent them from usual communication. They are mostly for older adults without a pathological communication problem. 相似文献