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1.
Integr Cancer Ther ; 23: 15347354241239930, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680047

RESUMO

BACKGROUND: Integrative nursing (IN) is an essential component of integrative medicine and integrative oncology. IN includes a range of external naturopathic, integrative nursing interventions, such as compresses, embrocation, and foot/hand baths, aimed at alleviating symptoms and side effects of conventional treatment. The project IMPLEMENT-UKU ("Implementation of IN at the University Hospital Ulm") was accompanied by a descriptive pilot study on the use of IN interventions on cancer-related symptoms in oncology inpatients, the characterization of these patients and the evaluation of the impact. METHODS: A single-arm study was conducted using a paper-based questionnaire administered before the IN interventions (t0) and 24 hours after the IN interventions (t1). Topics included sociodemographic data, symptoms, quality of life, health status, psychological burden, attitudes, and experience and satisfaction with the IN interventions. Analyses were descriptive using absolute and relative frequencies. RESULTS: During the 6-month study period out of 66 patients recommended for IN consultation by medical and nursing staff on 2 wards, 62 (93.9%) accepted the offer. Of those patients who received IN, 21 patients (33.9%) participated in the study. The number of IN interventions received per patient ranged from 1 to 3 during the 24-hour survey period. And a total of 36 IN interventions were performed: The most treated body region was the feet/legs (50.0%), followed by the back (25.0%), using oils such as solum oil (41.7%) and lavender oil (13.9%). Embrocation (77.8%) was the predominant type of IN intervention. For patients, the mean FACIT-F score was 29.2 ± 12.5. The mean PHQ-4 score was 3.0 ± 1.9. Regarding sleep quality in the last 4 weeks, 13 participants (61.9%) described it as rather or very poor. Satisfaction with the IN was high, with a large proportion of participants evaluating the IN interventions very positively. CONCLUSION: The study's findings suggest that there is a great need for IN among oncology inpatients. These patients are open to and interested in IN interventions and evaluate them positively. IN provides a promising opportunity to provide non-pharmacological support to inpatients. The integration of IN in conventional oncology care settings may enhance patient-centered care and contribute to improved patient wellbeing.


Assuntos
Pacientes Internados , Neoplasias , Qualidade de Vida , Humanos , Projetos Piloto , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/enfermagem , Neoplasias/psicologia , Idoso , Inquéritos e Questionários , Pacientes Internados/psicologia , Adulto , Oncologia Integrativa/métodos , Terapias Complementares/métodos , Satisfação do Paciente , Medicina Integrativa/métodos , Idoso de 80 Anos ou mais
2.
JMIR Res Protoc ; 12: e46765, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37851493

RESUMO

BACKGROUND: Patients with cancer receiving neoadjuvant treatment prior to surgery are in a very stressful situation. Chemotherapy and radiation therapy put a strain on the quality of life and the pending surgery poses a relevant burden for many patients. Preparation of these patients for the intervention in terms of prehabilitation has great potential to reduce the burden of postoperative complications and may improve the clinical outcome. A prehabilitation approach also yields the possibility to address unmet patients' needs and to help them modify their lifestyle in a maintainable way. Therefore, a multimodal approach is mandatory during this critical period. OBJECTIVE: The aim of this study is to assess the feasibility of prehabilitation in an integrative medicine day clinic (PRIME-DC) prior to cancer surgery at a major university clinic. PRIME-DC is considered feasible if 80% of enrolled patients are willing and able to complete at least 6 out of the 8 weekly meetings, each lasting 6.5 hours, at such a clinic. Secondary end points aim to evaluate this multimodal program. METHODS: The PRIME-DC intervention combines mind-body medicine, exercise therapy, nutrition therapy, naturopathic counseling, and the application of a yarrow liver compress. Adult patients with cancer, with a primary tumor in the abdomen (including intraperitoneal cancer, stomach cancer, and extraperitoneal cancers such as pancreatic, bladder, rectal, esophageal, endometrial, ovarian, and cervical cancer) or the breast requiring a neoadjuvant oncological treatment setting are eligible to participate. The addressed cancer entities imply either an extensive surgical intervention with an expected need for prehabilitation (eg, abdominal surgery) or a neoadjuvant treatment of several months with a high burden of treatment-associated side effects (breast cancer). Adherence to the day clinic program is the primary end point being defined as presence during the day clinic session. Secondary end points are physical assessment and quality of life, together with a structured assessment of neoadjuvant treatment-associated side effects. Furthermore, to collect qualitative data voluntary participants of the day clinic will be interviewed in a semistructured way after completion of the day clinic program on each component of the study (mind-body intervention, exercise, nutrition, naturopathic counseling, and a yarrow liver compress). RESULTS: The procedures used in this study adhere to the tenets of the Declaration of Helsinki. As of February 2023, we enrolled 23 patients; the dominant cancer entity is breast cancer (18 enrolled patients). CONCLUSIONS: The presented protocol combines prehabilitation, lifestyle modification, naturopathic counseling, dietary assistance, and naturopathic treatment in an innovative and integrative way. TRIAL REGISTRATION: Deutsches Register Klinischer Studien German Clinical Trials Register DRKS00028126; https://drks.de/search/de/trial/DRKS00028126. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46765.

3.
BMJ Open ; 12(2): e055076, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35149568

RESUMO

INTRODUCTION: According to international literature, patients with cancer wish to have information on complementary and integrative healthcare (CIH). Medical guidelines recommend actively approaching patients with cancer discussing potential benefits and risks of individual CIH methods. While some CIH methods, for example, acupuncture and yoga, have been proven effective in high-quality studies, other CIH methods lack studies or bear the risk of interactions with chemotherapeutics, for example, herbal drugs. Therefore, an evidence-based interprofessional counselling programme on CIH will be implemented at four Comprehensive Cancer Centres in the federal state of Baden-Wuerttemberg, Germany. METHODS AND ANALYSIS: A complex intervention consisting of elements on patient, provider and system levels will be developed and evaluated within a multilayer evaluation design with confirmatory evaluation on patient level. Patients with a cancer diagnosis within the last 6 months will receive three individual counselling sessions on CIH within 3 months (=intervention on patient level). The counselling will be provided by an interprofessional team of medical and nursing staff. For this purpose, an intensive online training programme, a CIH knowledge database and an interprofessional team-building process were developed and implemented (=intervention on provider level). Moreover, training events on the basics of CIH are offered in the outpatient setting (=intervention on system level). Primary outcome of the evaluation at the patient level is patient activation measured (PAM) with the PAM-13 after 3 months. Secondary outcomes, for example, quality of life, self-efficacy and clinical parameters, will be assessed at baseline, after 3 months and at 6 months follow-up. The intervention group (n=1000) will be compared with a control group (n=500, treatment as usual, no CIH counselling. The outcomes and follow-up times in the control group are the same as in the intervention group. Moreover, the use of health services will be analysed in both groups using routine data. A qualitative-quantitative process evaluation as well as a health economic evaluation will identify relevant barriers and enabling factors for later roll-out. ETHICS AND DISSEMINATION: The study has been approved by the appropriate Institutional Ethical Committee of the University of Tuebingen, No. 658/2019BO1. The results of these studies will be disseminated to academic audiences and in the community. TRIAL REGISTRATION NUMBER: DRKS00021779; Pre-results.


Assuntos
Neoplasias , Qualidade de Vida , Aconselhamento/métodos , Atenção à Saúde , Alemanha , Humanos , Neoplasias/terapia , Pesquisa Qualitativa
4.
Skin Res Technol ; 26(2): 234-240, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31549768

RESUMO

BACKGROUND: The early detection of skin cancer is still challenging and calls for objective, fast diagnostic, and ideally non-invasive methods in order to leave the potentially malignant tumor cells unaltered. In this paper, the parelectric spectroscopy was applied to evaluate the potential of a non-invasive detection of basal cell carcinoma (BCC) and malignant melanoma. MATERIALS AND METHODS: A prototype of parelectric spectroscopy was used to investigate non-invasively dipole density and mobility of suspicious skin lesions. The differences in investigated tissue were analyzed compared to pathohistological findings in a clinical study on 51 patients with suspected BCC and malignant melanoma. RESULTS: The non-invasive parelectric spectroscopy could differentiate between normal skin, BCC, and melanoma but failed to distinguish between different types of skin cancer. The data were normalized to unsuspected nearby skin because the different skin locations influence dipole density and mobility. CONCLUSION: The results of the pilot study indicate that the parelectric spectroscopy might be an additional, useful non-invasive diagnostic procedure to distinguish between normal skin and skin cancer.


Assuntos
Processamento de Sinais Assistido por Computador , Neoplasias Cutâneas/diagnóstico , Análise Espectral/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/química , Carcinoma Basocelular/diagnóstico , Feminino , Humanos , Masculino , Melanoma/química , Melanoma/diagnóstico , Pessoa de Meia-Idade , Fotografação , Projetos Piloto , Pele/química , Neoplasias Cutâneas/química , Adulto Jovem , Melanoma Maligno Cutâneo
5.
Tumour Biol ; 37(7): 8731-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26738869

RESUMO

Cancers arising from the large intestine or rectum are called colorectal cancer (CRC) and represent the fourth leading cause of cancer-related death worldwide. Since casein kinase 1 (CK1) isoforms are involved in many cellular processes and have been reported to be deregulated in various tumor entities, CK1 has become an interesting drug target. In this study, we examined the potential of CK1δ expression levels in tumor tissue of CRC patients as a prognostic biomarker. We show by quantitative RNA expression analyses that decreased CK1δ expression levels in tumor tissue predict prolonged survival rates. Random sampling of CK1δ stained tumor tissue indicates that CK1δ gene expression corresponds with CK1δ protein expression. Especially in low grade (grade 1, grade 2) and in UICC II/III classified tumors decreased CK1δ RNA levels correlate with significantly improved survival rates when the tumor was located in the right colon. We furthermore found gender-specific differences within these subgroups, revealing most significant increase in overall survival rates in male patients with tumors in right colon expressing low levels of CK1δ RNA. Results become even clearer, when only male patients over 50 years were considered. Together, these findings support the assumption that CK1δ might be a prognostic biomarker for CRC thereby providing an interesting drug target for the development of new therapy concepts.


Assuntos
Caseína Quinase Idelta/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA/genética , Taxa de Sobrevida
6.
Front Pharmacol ; 7: 504, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28082898

RESUMO

Background: Due to adjuvant treatment concepts for patients with R0-resected gastrointestinal stromal tumors (GIST), a reproducible and reliable risk classification system proved of utmost importance for optimal treatment of patients and prediction of prognosis. The aim of this study was to reevaluate the impact of five widely-applied and well-established GIST risk classification systems (i.e., scores by Fletcher, Miettinen, Huang, Joensuu, and TNM classification) on a series of 558 GIST patients with long-term follow-up after R0 resection. Methods: Tumor size, mitotic count and site were used in variable combination to predict high- and low risk patients by the use of the five risk classification models. For survival analyses disease-specific survival, disease-free survival and overall-survival were investigated. Patients with initial metastatic disease or incompletely resectable tumors were excluded. Results: All GIST classification models distinguished well between patients with high-risk and low-risk tumors and none of the five risk systems was superior to predict patient outcome. The models showed significant heterogeneity. There was no significant difference between the different risk-groups regarding overall-survival. Subdivision of GIST patients with very low- and low-risk appeared to be negligible. Conclusions: Currently applied GIST risk classification systems are comparable to predict high- or low-risk patients with initial non-metastatic and completely resected GIST. However, the heterogeneity of the high-risk group and the absence of differences in overall survival indicate the need for more precise tumor- and patient-related criteria for better stratification of GIST and identification of patients who would benefit best from adjuvant tyrosine kinase inhibitor therapy.

7.
BMC Cancer ; 15: 57, 2015 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-25886494

RESUMO

BACKGROUND: Risk classification and prediction of prognosis in GIST is still a matter of debate. Data on the impact of age and gender as potential confounding factors are limited. Therefore we comprehensively investigated age and gender as independent risk factors for GIST. METHODS: Two independent patient cohorts (cohort I, n = 87 [<50 years]; cohort II, n = 125 [≥50 years]) were extracted from the multicentre Ulmer GIST registry including a total of 659 GIST patients retrospectively collected in 18 collaborative German oncological centers. Based on demographic and clinicopathological parameters and a median follow-up time of 4.3 years (range 0.56; 21.33) disease-specific-survival (DSS), disease-free-survival (DFS) and overall survival (OS) were calculated. RESULTS: GIST patients older than fifty years showed significantly worse DSS compared to younger patients (p = 0.021; HR = 0.307, 95% CI [0.113; 0.834]). DSS was significantly more favorable in younger female GIST patients compared with elderly females (p = 0.008). Female gender resulted again in better prognosis in younger patients (p = 0.033). CONCLUSIONS: Patient age (<50 years) and female gender were significantly associated with a more favourable prognosis in GIST. Extended studies are warranted to confirm our clinical results and to elucidate underlying pathophysiological mechanisms.


Assuntos
Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/mortalidade , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Análise de Sobrevida , Adulto Jovem
8.
Am J Cancer Res ; 5(1): 333-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25628942

RESUMO

BACKGROUND AND OBJECTIVES: To elucidate diagnostic criteria, clinicopathological features and clinical outcome in patients with esophageal gastrointestinal stromal tumors (GIST), representing an extremely rare subform of GIST with an estimated incidence of about 0.1 to 0.3 per million people. PATIENTS AND METHODS: Esophageal GIST cases from the Ulmer GIST registry consisting of 1077 cases were pooled with case reports and case series of esophageal GIST extracted from MEDLINE. Data were compared with those from 683 cases with gastric GIST from the Ulmer GIST registry. RESULTS: In comparison to gastric GIST, esophageal GIST (n = 55) occurred significantly more frequent in men (p = 0.035) as well as in patients younger than 60 at diagnosis (p < 0.001). Primary tumor sizes were significantly larger (p < 0.001), thereby resulting more frequently in a high-risk classification (OR = 4.53, CI 95% 2.41-8.52, p < 0.001). The 5-year rates of disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) were 50.9%, 65.3% and 48.3%, respectively. The prognosis of esophageal GIST was less favorable compared with gastric GIST (DSS: p < 0.001, HR = 0.158, 95% CI: 0.087-0.288; DFS: p = 0.023, HR 0.466, 95% CI: 0.241-0.901; OS p = 0.003, HR = 0.481, 95% CI: 0.294-0.785; univariate Cox model) after a median follow-up time of 28 months (range 1.9 to 202). Mutational analysis for KIT showed more frequently wild-type status in esophageal GIST (OR = 10.13, CI 95% 3.02-33.96, p < 0.001). CONCLUSIONS: Esophageal GIST differ significantly from gastric GIST in respect to clinicopathological features and clinical outcome. To optimize treatment options further prospective data on patients with esophageal GIST are urgently warranted.

9.
Obes Surg ; 23(12): 1957-65, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23856991

RESUMO

BACKGROUND: Optimal obesity therapy is a matter of debate. Besides weight reduction, other criteria such as safety and nutritional status are of relevance. Therefore, we compared a favored surgical intervention with the most effective conservative treatment regarding anthropometry and nutritional status. METHODS: Fifty-four obese patients were included who underwent laparoscopic sleeve gastrectomy (LSG, n = 27) or a 52-week multidisciplinary intervention program (MIP, n = 27) for weight loss. Body weight, body composition assessed by bioelectrical impedance analysis, and serum protein levels were measured before and within 12 months after intervention. RESULTS: After 1 year of observation, excess weight loss was more pronounced following LSG (65 %) compared to MIP (38 %, p < 0.001). In both groups, body fat was clearly reduced, but a higher reduction occurred in the LSG group. However, protein status deteriorated particularly in the LSG group. Within 1 year, body cell mass declined from 37.1 to 26.9 kg in the LSG group, but only from 35.7 to 32.2 kg in the MIP group. This resulted in an increased mean extracellular mass/body cell mass ratio (1.42 versus 1.00, p < 0.001), in a decreased mean phase angle (4.4° versus 6.6°, p < 0.001), and in a lower prealbumin level in serum (p < 0.02) in the LSG group compared to the MIP group. CONCLUSIONS: LSG, compared to MIP, was more effective regarding excess weight loss and body fat loss within 1 year, however, induced more pronounced muscle mass and protein loss, possibly requiring particular interventions such as exercise or protein supplements.


Assuntos
Composição Corporal , Gastrectomia , Laparoscopia , Obesidade/terapia , Equipe de Assistência ao Paciente , Desnutrição Proteico-Calórica/etiologia , Redução de Peso , Programas de Redução de Peso , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal , Suplementos Nutricionais , Terapia por Exercício , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Obesidade/metabolismo , Avaliação de Programas e Projetos de Saúde , Desnutrição Proteico-Calórica/prevenção & controle , Resultado do Tratamento , Programas de Redução de Peso/métodos
10.
Pharmacol Res ; 67(1): 68-78, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23103594

RESUMO

Cardiopulmonary bypass still often is a necessary tool in cardiac surgery in particular in the correction of congenital heart defects in small infants. Nevertheless, among the complications linked to extracorporeal circulation (ECC) with cardiopulmonary bypass (CPB) in both infants and adults one of the most serious problems is renal impairment. Since this might be caused by ischemia/reperfusion injury and accumulation of free radicals, we used (-)-epigallocatechin-3-gallate (EGCG), a derivate from green tea, which is known to possess antioxidant, antiapoptotic and NO-scavenging properties in order to find out whether EGCG may protect the kidney. 23 four-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into three groups: control-group (n=7), ECC-group (n=10), EGCG-group (n=6). The ECC- and EGCG-group were thoracotomized and underwent CPB for 120 min followed by a 90-min recovery-time. The EGCG-group received 10 mg/kg EGCG before and after CPB. Histology revealed that CPB led to widening of Bowman's capsule, and to vacuolization of proximal tubular cells (p<0.05) which could be prevented by EGCG (p<0.05). Using immunohistology, we found significant nuclear translocation of hypoxia-inducible-factor-1-alpha (HIF-1-alpha) and increased nitrotyrosine formation in the ECC-group. Both were significantly (p<0.05) inhibited by EGCG. ECC-induced loss of energy-rich phosphates was prevented by EGCG. In blood samples we found that CPB resulted in increases in creatinine and urea (in serum) and led to loss of total protein (p<0.05), which all was not present in EGCG-treated animals. We conclude that CPB causes damage in the kidney which can be attenuated by EGCG.


Assuntos
Ponte Cardiopulmonar , Catequina/análogos & derivados , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Fator de Indução de Apoptose/metabolismo , Pressão Sanguínea , Catequina/farmacologia , Creatinina/sangue , Frequência Cardíaca , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Poli Adenosina Difosfato Ribose/metabolismo , Suínos , Tirosina/análogos & derivados , Tirosina/metabolismo , Ureia/sangue
11.
Obes Surg ; 22(6): 881-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22403000

RESUMO

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been identified as an innovative surgical approach for the treatment of obesity and is increasingly applied worldwide. However, data on outcome of LSG regarding nutrient deficiencies, protein status, and body composition are scarce. METHODS: Obese subjects (54; f:m = 4:1) scheduled for LSG were included in this study. Micronutrient analysis, protein status assessment, and bioimpedance measures were performed before and 1, 3, 6, and 12 months after LSG. RESULTS: In 51% of the subjects, at least one micronutrient deficiency was found prior to surgery. Baseline concentrations were below normal for 25-OH vitamin D (27%), iron (29%), vitamin B6 (11%), vitamin B12 (9%), folate (6%), and potassium (7%). Frequencies of deficiencies for vitamin B12, folate, iron, and vitamin B6 tended to increase following LSG within the first year after intervention. Also, parameters of protein status (albumin, transferrin, cholinesterase, and total protein) decreased. After surgery, bioimpedance measures indicated a reduction of total body fat, but also of body cell mass. CONCLUSIONS: Preoperative micronutrient deficiencies were common in morbid obese individuals scheduled for LSG. LSG had a modest effect on micronutrient status by further reducing iron, vitamin B12, vitamin B6, and folate within the first year after intervention. Our data suggest that especially obese patients with preoperative deficits require control and supplementation of micronutrients and protein in the postoperative period.


Assuntos
Deficiência de Vitaminas/etiologia , Suplementos Nutricionais , Gastroplastia/efeitos adversos , Laparoscopia/efeitos adversos , Desnutrição/complicações , Desnutrição/etiologia , Micronutrientes/deficiência , Obesidade Mórbida/complicações , Adulto , Deficiência de Vitaminas/dietoterapia , Composição Corporal , Índice de Massa Corporal , Feminino , Seguimentos , Gastroplastia/métodos , Humanos , Laparoscopia/métodos , Masculino , Desnutrição/dietoterapia , Obesidade Mórbida/dietoterapia , Obesidade Mórbida/cirurgia , Período Pós-Operatório , Período Pré-Operatório , Resultado do Tratamento
12.
BMC Cancer ; 10: 350, 2010 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-20598140

RESUMO

BACKGROUND: Risk estimation of gastrointestinal stromal tumours (GIST) is based on tumour size and mitotic rate according to the National Institutes of Health consensus classification. The indication for adjuvant treatment of patients with high risk GIST after R0 resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. Therefore, additional prognostic indicators are needed. Here, we evaluated the prognostic value of cyclin H expression in GIST. METHODS: In order to identify prognostic factors of GIST we evaluated a single centre cohort of ninety-five GIST patients. First, GISTs were classified with regard to tumour size, mitotic rate and localisation according to the NIH consensus and to three additional suggested risk classifications. Second, Cyclin H expression was analysed. RESULTS: Of ninety-five patients with GIST (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42% high risk, 20% intermediate risk, 23% low risk and 15% very low risk GIST. In patients with high risk GIST, the expression of cyclin H was highly predictive for reduced disease-specific survival (p = 0.038). A combination of cyclin H expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p < or = 0.001). Moreover, in patients with tumour recurrence and/or metastases, cyclin H positivity was significantly associated with reduced disease-specific survival (p = 0.016) regardless of risk-classification. CONCLUSION: Our data suggest that, in addition to high risk classification, cyclin H expression might be an indicator for "very-high risk" GIST.


Assuntos
Ciclina H/genética , Tumores do Estroma Gastrointestinal/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclina H/metabolismo , Feminino , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
13.
Cell Signal ; 22(7): 984-1002, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20096351

RESUMO

The protein kinase family, one of the largest gene families in eukaryotes, plays an important role in regulating various cellular processes such as cell proliferation, cell death, cell cycle progression, differentiation and cell survival. Therefore, it is not surprising that the deregulation of many kinases is usually directly linked to cancer development. In all solid tumors, changes in protein kinase expression levels and activities, as well as alterations in the degree of posttranslational modifications can contribute to cancer development. Consequently, the identification of molecular targets and signaling pathways specific to cancer cells is becoming more and more important for cancer drug development and cancer therapies. Inhibition of various protein kinases has already been investigated in many pre-clinical and clinical trials targeting all stages of signal transduction, demonstrating promising results in cancer therapy. Conventional chemotherapeutics are often ineffective as well as harmful; hence a combination of both chemotherapeutics and protein kinase inhibitors may result in new and more successful therapeutic approaches. In this review we focus on protein kinases involved in different signaling pathways and their alterations in solid tumors.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
14.
PLoS One ; 4(1): e4174, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19137063

RESUMO

BACKGROUND: Casein kinase 1 delta (CK1delta) phosphorylates many key proteins playing important roles in such biological processes as cell growth, differentiation, apoptosis, circadian rhythm and vesicle transport. Furthermore, deregulation of CK1delta has been linked to neurodegenerative diseases and cancer. In this study, the cell specific distribution of CK1delta in various tissues and organs of young adult BALB/c mice was analysed by immunohistochemistry. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical staining of CK1delta was performed using three different antibodies against CK1delta. A high expression of CK1delta was found in a variety of tissues and organ systems and in several cell types of endodermal, mesodermal and ectodermal origin. CONCLUSIONS: These results give an overview of the cell-type specific expression of CK1delta in different organs under normal conditions. Thus, they provide evidence for possible cell-type specific functions of CK1delta, where CK1delta can interact with and modulate the activity of key regulator proteins by site directed phosphorylation. Furthermore, they provide the basis for future analyses of CK1delta in these tissues.


Assuntos
Caseína Quinase Idelta/metabolismo , Camundongos Endogâmicos BALB C/metabolismo , Animais , Anticorpos Monoclonais , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C/anatomia & histologia , Coelhos , Distribuição Tecidual
15.
Neoplasia ; 10(10): 1154-62, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18813351

RESUMO

Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. One hundred one patients (54 women and 47 men) with a mean age of 64.1 years (range, 17-94 years) were surgically treated for a GIST within a 10-year period. Of these patients, 28 (28%) were affected by metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97 GIST patients (96%). In patients with high-risk GIST, the expression of p16 expression was highly predictive for poor prognosis, i.e., the development of recurrence or metastases (P = .006) and poor survival (P = .004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041). The disease-specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85% and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high-risk classification were confirmed as relevant predictors for unfavorable prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases, the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for "very high risk GIST."


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/genética , Genes p16 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Metástase Neoplásica , Valor Preditivo dos Testes , Prognóstico , Recidiva , Fatores de Risco , Adulto Jovem
16.
World J Surg ; 32(7): 1462-5, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18368447

RESUMO

BACKGROUND: The aim of this study was to define a standardized technique for laparoscopic sleeve gastrectomy in the morbidly obese patient. METHODS: There are several surgical options for the morbidy obese patient. In general, there are the restrictive procedures [e.g., laparoscopic adjustable gastric banding (LAGB)] and the malabsorptive procedures [e.g. laparoscopic Roux-en-Y gastric bypass (LRYGBP)]. Those techniques are already standardized. The laparoscopic sleeve gastrectomy (LSG) seems to have some advantages over both procedures, but it is not standardized yet, and so there can be no comparison between the different techniques. In our center we have standardized the LSG technique with respect to abdominal access and narrowness of the gastric sleeve. After dissection of the greater omentum and the short gastric vessels, the greater curvature is resected along a 34-Fr gastric tube using the Endo-GIA. The remaining gastric sleeve has a volume of about 100 ml. RESULTS: The standardized LSG procedure is presented step by step. A comparison of operative data and early outcome with a matched group of patients with adjustable gastric banding showed no difference between the two techniques with respect to operating time, surgical complications, and weight loss 6 months after surgery. CONCLUSION: With our standardized LSG technique it is possible to evaluate the positive aspects of the LSG compared with other standardized bariatric procedures like LAGB or LRYGBP.


Assuntos
Cirurgia Bariátrica/métodos , Gastrectomia/normas , Obesidade Mórbida/cirurgia , Adulto , Idoso , Feminino , Gastrectomia/métodos , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade
17.
World J Gastroenterol ; 13(24): 3384-7, 2007 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-17659681

RESUMO

The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Primárias Múltiplas/patologia , Neurofibromatose 1/patologia , Feocromocitoma/patologia , Feminino , Tumores do Estroma Gastrointestinal/etiologia , Humanos , Pessoa de Meia-Idade , Neurofibromatose 1/complicações
18.
J Nutr ; 136(5): 1287-93, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16614418

RESUMO

Epidemiologic studies have repeatedly associated a high intake of lycopene and vitamin E with reduced prostate cancer risk. The present study examined the ability of the 2 compounds to reduce tumor growth and prostate-specific antigen (PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight (BW)], vitamin E in the form of alpha-tocopheryl acetate (5 or 50 mg/kg BW), a mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic tumor volume and plasma PSA concentrations were measured at regular intervals. Mice were killed when the tumor load exceeded 1000 mm(3) or on d 95 when the study was terminated. Prostate and liver were analyzed by HPLC for lycopene isomers and alpha- and gamma, delta-tocopherol concentrations. None of the single treatments significantly reduced tumor volume. In contrast, combined treatment with lycopene and vitamin E, at 5 mg/kg BW each, suppressed orthotopic growth of PC-346C prostate tumors by 73% at d 42 (P < 0.05) and increased median survival time by 40% from 47 to 66 d (P = 0.02). The PSA index (PSA:tumor volume ratio) did not differ between experimental groups, indicating that PSA levels were not selectively affected. Lycopene was detected only in mice supplemented with lycopene. As in humans, most tissue lycopene was in the cis-isomer conformation, whereas 77% trans-lycopene was used in the dosing material. Liver alpha-tocopherol concentrations were increased in mice supplemented with both 50 mg/kg (226%, P < 0.05) and 5 mg/kg vitamin E (41%, P < 0.05), whereas prostate alpha-tocopherol concentrations were increased only by the higher dose (83%, P < 0.05). Our data provide evidence that lycopene combined with vitamin E may inhibit the growth of prostate cancer and that PSA can serve as a biomarker of tumor response for this treatment regimen.


Assuntos
Anticarcinógenos/farmacologia , Carotenoides/farmacologia , Neoplasias da Próstata/patologia , Vitamina E/farmacologia , Animais , Carotenoides/administração & dosagem , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Suplementos Nutricionais , Humanos , Licopeno , Masculino , Camundongos , Camundongos Nus , Transplante Heterólogo , Vitamina E/administração & dosagem
20.
Ann Thorac Surg ; 77(1): 151-7; discussion 157, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14726052

RESUMO

BACKGROUND: Postcardiotomy cardiogenic shock occurs in approximately 1% of patients. We prospectively evaluated the early and long-term outcome as well as predictors of survival when using temporary extracorporeal membrane oxygenation (ECMO) support. METHODS: During 5 years 219 of 18150 patients (1.2%) undergoing cardiac surgery (coronary artery bypass grafting, n = 119; aortic valve replacement, n = 24; coronary artery bypass grafting and aortic valve replacement, n = 21; coronary artery bypass grafting and mitral valve replacement, n = 11; other procedures, n = 44) required temporary postoperative ECMO support. The ECMO implantation was performed through the femoral vessels or through the right atrium and ascending aorta. Additional intraaortic balloon counterpulsation was employed in 144 patients to improve coronary blood flow. RESULTS: Mean duration of ECMO support was 2.8 +/- 2.2 days. One hundred thirty-four patients (60%) were successfully weaned from ECMO. Of these, 52 patients (24%) were discharged from the hospital after 29.9 +/- 24 days. The main cause of death was myocardial failure. Five-year follow-up is 96% complete; 37 patients (74%) were alive with reasonable exercise capacity. CONCLUSIONS: Extracorporeal membrane oxygenation is an acceptable technique for short-term treatment of refractory postoperative low cardiac output. It can save the lives of a group of very high risk patients.


Assuntos
Oxigenação por Membrana Extracorpórea , Complicações Pós-Operatórias/cirurgia , Choque Cardiogênico/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Prognóstico , Estudos Prospectivos , Choque Cardiogênico/mortalidade , Taxa de Sobrevida , Fatores de Tempo
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