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1.
Strahlenther Onkol ; 188(9): 777-81, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22878547

RESUMEN

BACKGROUND: An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. PATIENTS AND METHODS: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or-in case of breast conservation-a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. RESULTS: The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). CONCLUSION: pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX.


Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Quimioradioterapia Adyuvante/mortalidad , Terapia Neoadyuvante/mortalidad , Adulto , Anciano , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Alemania/epidemiología , Humanos , Mastitis/mortalidad , Mastitis/terapia , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Inducción de Remisión , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
2.
Eur J Med Res ; 16(10): 437-44, 2011 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-22024422

RESUMEN

Patients with ESCC (squamous cell carcinoma of the esophagus) are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Neoadyuvante , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Terapia Combinada , Neoplasias Esofágicas/patología , Humanos , Metaanálisis como Asunto , Estadificación de Neoplasias , Radioterapia Adyuvante , Nivel de Atención , Tasa de Supervivencia , Resultado del Tratamiento
3.
Eur J Med Res ; 16(10): 451-6, 2011 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-22024424

RESUMEN

OBJECTIVE: Insulin-like growth factor (IGF)-1, -2 and Insulin like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated, if the IGF-system can serve as a tumor marker in neoplasms. METHODS: In our prospective study 163 patients with colorectal cancer (22), prostate cancer (21), head and neck tumors (17), lymphomas (20), lung cancer (34) and other entities (49) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared to 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared. RESULTS: The serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected. CONCLUSION: The IGF-system cannot serve as a new tumor marker. The detected differences are very small, sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.


Asunto(s)
Biomarcadores de Tumor/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neoplasias/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto Joven
4.
Dtsch Med Wochenschr ; 136(43): 2205-11, 2011 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-22009175

RESUMEN

Locally advanced gastric cancers are characterized by poor prognosis. Clinical outcome can be improved if surgery becomes part of a multimodal treatment approach. The purpose of neoadjuvant treatment includes downsizing of the primary tumor, improvement of the T- and N- categories, and early therapy of micrometastasis. Several controlled clinical trials showed that neoadjuvant chemotherapy as well as neoadjuvant combined radio-chemotherapy, especially for tumors of the gastroesophageal junction, can improve the rate of primary R0 resections, relapse-free survival, and overall survival. While patients with locally advanced tumors clearly benefit from this strategy, the approach is still controversial in patients with early stage disease. Nonresponders do not benefit from neoadjuvant therapy. Therefore, response evaluation and response prediction are of great importance. After successful neoadjuvant chemotherapy, patients should undergo gastrectomy with D(2)-lymphadenectomy because of a high probability of lymph node metastasis. This article summarizes current developments in this field.


Asunto(s)
Micrometástasis de Neoplasia/terapia , Neoplasias Gástricas/terapia , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Terapia Combinada , Humanos , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Micrometástasis de Neoplasia/prevención & control , Estadificación de Neoplasias , Pronóstico , Radioterapia Adyuvante , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
5.
Eur J Med Res ; 16(6): 265-74, 2011 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-21810561

RESUMEN

Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemo?radiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection.


Asunto(s)
Adenocarcinoma/terapia , Neoplasias Gastrointestinales/terapia , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Quimioterapia Adyuvante , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Unión Esofagogástrica , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/patología , Humanos , Metaanálisis como Asunto , Terapia Neoadyuvante , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Resultado del Tratamiento
6.
Eur J Med Res ; 16(1): 20-8, 2011 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-21345766

RESUMEN

BACKGROUND: Classic wound drainage is still common in hip replacement but its benefit is doubtful. The role of systemic administration of proteinase inhibitors like aprotinin to avoid perioperative blood loss is still unclear. PATIENTS AND METHODS: In a prospective randomized trial, the perioperative blood loss in alloplastic hip replacement under the influence of proteinase inhibitor (aprotinin, Trasylol®) using wound drainage as well as compression treatment alone were compared. 80 patients were prospectively randomized in 4 arms. Patients received either aprotinin or placebo during surgery as well as drainage or targeted external wound compression. RESULTS: Observing the "drug therapy" aprotinin had no effect on the intra- or postoperative blood loss (p>0.05), a trend to lower postoperative hemoglobin decline was found, but without significance. Thrombosis occurred in neither the aprotinin nor in the placebo group. Two patients had a severe allergic drug reaction and were excluded from the study. Under "non drug therapy" with compression therapy and wound drainage a significant difference in blood loss was found (p<0.001). The blood loss was higher under the wound drainage. There was no influence on the infection rate. Yet we could observe increased bruising under the sole external compression treatment. CONCLUSION: The administration of aprotinin did not achieve the desired reduction of perioperative blood loss. Hence, costs and two severe allergic drug reactions in our study represent arguments against its use in regular treatment. Furthermore, it seems that wound drainage is neglectable in hip replacement and can be substituted by a sole compression treatment.


Asunto(s)
Aprotinina/uso terapéutico , Artroplastia de Reemplazo de Cadera/métodos , Succión , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Transfusión Sanguínea , Vendajes de Compresión , Método Doble Ciego , Recuento de Eritrocitos , Femenino , Hematoma/etiología , Hematoma/prevención & control , Hemostáticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/prevención & control , Estudios Prospectivos
7.
Eur J Med Res ; 16(1): 29-33, 2011 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-21345767

RESUMEN

OBJECTIVE: Treatment options for patients with diffuse type gastric cancer (linitis plastica) are discussed controversial. It is sometimes discussed that these patients should be treated primarily in palliative intention conservative without resection. METHODS: In a single-center analysis, we investigated 120 patients with diffuse type gastric cancer. All patients underwent a total gastrectomy, 45 patients even a multivisceral resection because of infiltrating growth, or metastases. Serum tumor marker CEA, CA 72-4, and CA 19-9 were recorded in all patients before surgery. An immunocytochemical detection of free peritoneal tumor cells (FPTC) using Ber-EP4 antibody was correlated with tumor stage and survival. Median follow-up time was 38 months. RESULTS: Complete resection rate was 31% (n = 37). 61% (n = 73) of all patients had already distant metastases at the time of surgery, 80% of them peritoneal carcinomatosis. Median survival for the whole group was 8 months, after complete resection 17 months. Lavage cytology, distant metastases, resection rate, and CA19-9 levels had significant influence on survival. CONCLUSION: A significant survival advantage for patients with diffuse type gastric cancer can only be achived after complete resection. We could define a subset of patients with an extremely poor prognosis even after surgical resection. Meticulous preoperative staging, including a diagnostic laparoscopy to exclude peritoneal carcinomatosis and free peritoneal tumor cells before resection should be mandatory in these patients.


Asunto(s)
Linitis Plástica/cirugía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Líquido Ascítico/patología , Antígeno CA-19-9/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Linitis Plástica/inmunología , Linitis Plástica/mortalidad , Linitis Plástica/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología
9.
Eur J Med Res ; 15(9): 383-9, 2010 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-20952347

RESUMEN

BACKGROUND: the constantly growing amount of different kinds of colloid fluids necessitates comparative investigations with regards to the safety and effectivity in clinical use of these preparations. Hence we compared three colloid fluids in an observational study. The objective was the exploration of the influence of these three colloids on blood coagulation, hemodynamics and renal function of the cardiac surgical patient. METHODS: we included 90 patients undergoing an elective open-heart surgery with the use of the heart-lung machine and observed them consecutively. Group 1 [gelatin 4% (n = 30)], Group 2 [HES 200/0,5 (n = 30)] and Group 3 [HES 130/0,42 (n = 30)]. We measured the perioperative volume replacement, the administration of blood- and coagulation-products, the application of catecholamines, the renal function, blood gas and the platelet aggregation using multiplate electrode analyzer (Multiplate, Dynabyte medical, Munich, Germany). RESULTS: the gelatin-group needed significantly more norepinephrine than the HES 130/0.42 group. The responsible surgeon considered the blood coagulation in the HES 200/0.5 group most frequently as impaired. Furthermore we saw a significant decrease in platelet function in the HES 200/0.5 group when performing the multiplate-analysis (ADP-and COL-test). HES 130/0.4 as well as gelatin 4% showed no significant change in platelet function. The gelatin-group and the HES 200/0.5 needed significantly more aprotinine than the HES 130/0.4 group. We saw no significant difference with regards to administration of blood and coagulation products between the three groups. The urinary excretion during the intervention was significantly higher in the HES 200/0.5 group and in the gelatin group than in the HES 130/0.4 group. CONCLUSIONS: our results confirm the lower stabilizing effect of gelatin on circulation during fluid resuscitation. The blood coagulation was mostly impaired due to HES 200/0.5 confirmed by the multiplate®-analysis as well as by different clinical findings.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Gelatina/uso terapéutico , Derivados de Hidroxietil Almidón/uso terapéutico , Fenoxiacetatos/uso terapéutico , Anciano , Anciano de 80 o más Años , Coagulación Sanguínea/efectos de los fármacos , Volumen Sanguíneo/efectos de los fármacos , Peso Corporal , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Sustitutos del Plasma/uso terapéutico , Estudios Prospectivos
10.
Eur J Med Res ; 15(9): 410-4, 2010 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-20952351

RESUMEN

INTRODUCTION: the deadly threat of systemic infections with coagulase negative Staphylococcus lugdunensis despite an appropriate antibiotic therapy has only recently been recognized. The predominant infectious focus observed so far is left-sided native heart valve endocarditis, but bone and soft tissue infections, septicaemia and vascular catheter-related bloodstream infections have also been reported. We present a patient with a fatal Staphylococcus lugdunensis septicaemia following zoster bacterial superinfection of the pelvic region. case presentation: a 71-year old male diagnosed with IgG kappa plasmocytoma presented with a conspicuous weight loss, a hypercalcaemic crisis and acute renal failure. After initiation of haemodialysis treatment his condition improved rapidly. However, he developed a varicella-zoster virus infection of the twelfth thoracic dermatome requiring intravenous acyclovir treatment. Four days later the patient presented with a fulminant septicaemia. Despite an early intravenous antibiotic therapy with ciprofloxacin, piperacillin/combactam and vancomycin the patient died within 48 hours, shortly before the infective isolate was identified as Staphylococcus lugdunensis by polymerase chain reaction. CONCLUSION: despite S. lugdunensis belonging to the family of coagulase-negative staphylococci with an usually low virulence, infections with S. lugdunensis may be associated with an aggressive course and high mortality. This is the first report on a Staphylococcus lugdunensis septicaemia following a zoster bacterial superinfection of the pelvic region.


Asunto(s)
Herpes Zóster/complicaciones , Herpesvirus Humano 3 , Sepsis/microbiología , Infecciones Estafilocócicas/complicaciones , Staphylococcus lugdunensis , Anciano , Resultado Fatal , Humanos , Masculino , Pelvis/virología , Sepsis/virología , Sobreinfección/microbiología , Sobreinfección/virología
11.
Eur J Med Res ; 15(8): 367-8, 2010 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-20947475

RESUMEN

Diffuse large B-cell lymphoma usually starts as a rapidly growing mass in an internal lymph node and can grow in other areas such as the bone or intestines. About 1/3 of these lymphomas are confined to one part of the body when they are localized. In the case of a 78-year-old man, an extensive tumour was located on the right thigh. Biopsies of the tumour revealed diffuse proliferation of large lymphoid cells which have totally affected the normal architecture of striated muscle. The patient received multimodality treatment including chemotherapy of the CHOP regimen and adjuvant radiotherapy. Despite this being a fast growing lymphoma, about 3 out of 4 people will have no signs of disease after initial treatment, and about half of all people with this lymphoma are cured with therapy.


Asunto(s)
Linfoma no Hodgkin/patología , Muslo , Anciano , Humanos , Masculino
12.
Eur J Med Res ; 15: 277-86, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20696638

RESUMEN

BACKGROUND: Tumor-related methylated DNA and circulating tumor cells (CTC) in the peripheral blood might be of prognostic importance in breast cancer. Thus, the aim of our study was to examine free methylated DNA and CTC in the blood from breast cancer patients and to correlate it with clinicopathological features known to influence prognosis. MATERIALS AND METHODS: We prospectively obtained serum samples from 85 patients with breast cancer and 22 healthy volunteers. Sera were analysed by methylation specific PCR (MethyLight PCR) for five genes: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A), estrogen receptor 1 (ESR1), CDKN2A (p16) and glutathione s-transferase pi 1 (GSTP1). Beta actin (ACTB) served as control. In parallel matched peripheral blood of 63 patients was used to assay for circulating tumor cells in the peripheral blood by a modified immunomagnetic AdnaTest BreastCancerSelect with PCR detection for EPCAM, MUC1, MGB1 and SPDEF. RESULTS: A hypermethylation in the APC gene in 29% (25/85), in RASSF1A in 26% (22/85), in GSTP1 in 18% (14/76) and in ESR1 in 38% (32/85) of all breast cancer patients was detected. No hypermethylation of CDKN2A was found (0/25). Blood samples of patients were defined CTC positive by detecting the EPCAM 13% (8/63), MUC1 16% (10/63), MGB 9% (5/55), SPDEF 12% (7/58) and in 27% detecting one or more genes (15/55). A significant difference was seen in methylated APC DNA between cancer patients and healthy volunteers. Moreover, methylated APC, RASSF1 and CTC were significantly different in metastatic versus non-metastatic disease. In addition, the presence of methylated APC, RASSF1A and CTC correlated significantly with AJCC-staging (p = 0.001, p = 0.031 and 0.002, respectively). High incidences of methylations were found for the genes RASSF1 and ESR1 in healthy individuals (both 23% 5/22). Methylated GSTP1 was predominantly found in the serum of patients with large primaries (p = 0.023) and was highly significantly correlated with positive Her2/neu status (p = 0.003). Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters. The presence of CTC in peripheral blood was significantly associated with methylated APC (p = 0.012) and methylated GSTP1 (p = 0.001). CONCLUSION: The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients. Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Metilación de ADN , Genes APC , Gutatión-S-Transferasa pi/genética , Células Neoplásicas Circulantes , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , ADN/sangre , Femenino , Sitios Genéticos , Humanos , Persona de Mediana Edad , Pronóstico
13.
Eur J Med Res ; 15(5): 204-9, 2010 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-20562059

RESUMEN

BACKGROUND: Antiseptics are frequently used for the prophylaxis and treatment of local infections of chronic wounds. Whereas local antiseptics in general have a positive effect on wound healing an uncritical use may impair wound healing due to toxic side effects. OBJECTIVE: We sought to assess the vascular irritation potential of different antiseptic solutions and ointments commonly used for short and long term application as a measure of tissue toxicity. METHOD: The vascular irritation was evaluated by the hen's egg test (HET) on the chorioallantoic membrane (CAM). The effects on the vessels of a mucous membrane were directly assessed by stereomicroscopic observation in vivo. RESULTS: Severe CAM irritation was observed after short-term applications of 1% octenidin-2HCl (Octenisept), 72% isopropanol (Cutasept), 0.35% chloroxylenol (Dettol) and 10% PVP-I ointment (Betaisodona). Medium irritations were observed for 10% PVP-I solution (Betaisodona), 3% lysosomal PVP-I ointment (Repithel), 1.8% cadexomer-iodine ointment (Iodosorb) and 1% cadexomer-iodine pellets (Iodosorb). Finally, slight irritations were observed for 1% PVP-I solution (Betaisodona), 0.1% polyhexanid plus betain (Prontosan) and 1% silver-sulfadiazine ointment (Flammazine), whereas 0.04% polyhexanid solution (Lavanid), washings from sterile maggots of Lucilia sericata and filtrated enzymes from Clostridium histolyticum (Iruxol-N) showed no effects of irritation. In the long-term approaches, no vascular irritations were found for polyhexanid, washings from Lucilia sericata and enzyme filtrations from Clostridium histolyticum. CONCLUSION: The vascular injuries caused by the studied antiseptics are an indirect indicator of their tissue toxicity. Strikingly, even therapeutic substances, which have been regarded as safe in their application for the treatment of chronic wounds in clinical studies, showed severe irritations on the CAM. We suggest that agents with no or low irritation potential on the CAM should be preferred in the clinical practice in order to obtain optimal results.


Asunto(s)
Antiinfecciosos Locales/toxicidad , Membrana Corioalantoides/efectos de los fármacos , Irritantes/toxicidad , Pruebas de Toxicidad/métodos , Heridas y Lesiones/tratamiento farmacológico , Animales , Embrión de Pollo , Enfermedad Crónica , Heridas y Lesiones/complicaciones
14.
Eur J Med Res ; 15(4): 162-8, 2010 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-20564833

RESUMEN

The sequences of many genomes are available; therefore, relevant methods are needed for rapid and efficient identification of functional genes. The ability of tumour cells to resist apoptosis induced by anticancer agents may decide about the success or failure of tumour elimination. Although the CD95-signaling pathway is functional in tumour cells, the increased resistance of tumour cells to CD95-mediated apoptosis has been widely reported. In order to identify genes that might determine the response of tumour cells to CD95-mediated apoptosis, we modified the conventional technical knock out (TKO) strategy for isolation of genes that function in CD95-mediated apoptosis. Due to the fact that multiple different plasmids are usually introduced into the same cells, the effectiveness of the conventional TKO strategies is low. To overcome this obstacle, we replaced the conventional TKO strategy (based on stably expressed randomly fragmented cDNA libraries) with a multi-cycle selection procedure (based on transiently expressed randomly fragmented cDNA libraries with multi-cycle selection). Using this approach we could rapidly and significantly identify small numbers of antisense mRNA molecules, whose re-introduction into different tumour types confirmed their ability to block the pro-apoptotic function of their cognate genes. Thus, our modified TKO strategy provides a generally applicable procedure for the identification of functional genes with pro-apoptotic properties that may be clinically relevant to tumour therapy.


Asunto(s)
Apoptosis/genética , Fragmentación del ADN , Biblioteca de Genes , Proyecto Genoma Humano , Receptor fas/genética , Línea Celular Tumoral , Supervivencia Celular , Bases de Datos Genéticas , Técnicas de Inactivación de Genes/métodos , Humanos , Neoplasias/genética , Neoplasias/patología
15.
Eur J Med Res ; 14(11): 480-6, 2009 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-19948443

RESUMEN

Today, the biomechanical fundamentals of skin expansion are based on viscoelastic models of the skin. Although many studies have been conducted in vitro, analyses performed in vivo are rare. Here, we present in vivo measurements of the expansion at the skin surface as well as measurement of the corresponding intracutaneous oxygen partial pressure. In our study the average skin stretching was 24%, with a standard deviation of 11%, excluding age or gender dependency. The measurement of intracutaneous oxygen partial pressure produced strong inter-individual fluctuations, including initial values at the beginning of the measurement, as well as varying individual patient reactions to expansion of the skin. Taken together, we propose that even large defect wounds can be closed successfully using the mass displacement caused by expansion especially in areas where soft, voluminous tissue layers are present.


Asunto(s)
Oxígeno/metabolismo , Fenómenos Fisiológicos de la Piel , Expansión de Tejido , Adulto , Anciano , Fenómenos Biomecánicos , Técnicas Biosensibles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión Parcial , Piel/irrigación sanguínea , Piel/metabolismo
16.
World J Surg ; 33(12): 2599-605, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19838751

RESUMEN

BACKGROUND: Assuming a benign tumor, soft tissue sarcomas are often treated by inadequate resection. The concept of reexcision in these patients is still under debate. Therefore, it was our goal to evaluate the results of this treatment with particular respect to residual tumor. METHODS: During a 14-year period, a total of 143 patients were referred to Heinrich-Heine-University Düsseldorf and the University of Hamburg [corrected] after unplanned excision. Reexcision was performed in 139 patients. The assessed endpoints were local recurrence-free survival, distant metastasis-free survival, and tumor-related mortality. Univariate and multivariate analyses were performed using a log-rank test and Cox's proportional-hazard models. RESULTS: Over a median observation period of 109 months, local recurrence appeared in 18 patients (12%) and distant metastasis in 46 patients (33%). Residual tumor was detected in 43 patients (31%) and was significantly associated with reduced relapse-free and overall survival. Local recurrence, however, was not affected. CONCLUSIONS: Despite an incomplete initial resection, reexcision enables local control similar to that in patients without residual tumor. Still, these patients have a worse prognosis owing to an increased rate of distant metastasis; therefore, patients with soft tissue masses of unknown identity should be transferred to centers that specialize in treating sarcomas for adequate initial resection.


Asunto(s)
Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/cirugía , Sarcoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Neoplasia Residual/patología , Reoperación , Sarcoma/patología , Análisis de Supervivencia , Adulto Joven
17.
Eur J Med Res ; 14(10): 426-32, 2009 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-19748849

RESUMEN

BACKGROUND: The diagnostic tools to predict the prognosis in patients suffering from breast cancer (BC) need further improvements. New technological achievements like the gene profiling of circulating tumour cells (CTC) could help identify new prognostic markers in the clinical setting. Furthermore, gene expression patterns of CTC might provide important informations on the mechanisms of tumour cell metastasation. MATERIALS AND METHODS: We performed realtime-PCR and multiplex-PCR analyses following immunomagnetic separation of CTC. Peripheral blood (PB) samples of 63 patients with breast cancer of various stages were analyzed and compared to a control group of 14 healthy individuals. After reverse-transcription, we performed multiplex PCR using primers for the genes ga733.3, muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying realtime-PCR. RESULTS: ga733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2 did not show any significant correlation to BC, possibly due to a highly ambient expression. Besides single gene analyses, gene profiles were additionally evaluated. Highly significant correlations to BC were found in single gene analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3*muc-1 and GA7 ga733.3*muc-1*mgb1*spdef. CONCLUSION: Our study reveals that the single genes ga733.3, muc-1 and the gene profiles ga733.3*muc-1 and ga733.3*3muc-1*mgb1*spdef can serve as markers for the detection of CTC in BC. The multigene analyses found highly positive levels in BC patients. Our study indicates that not single gene analyses but subtle patterns of multiple genes lead to rising accuracy and low loss of specificity in detection of breast cancer cases.


Asunto(s)
Neoplasias de la Mama/patología , Perfilación de la Expresión Génica , Células Neoplásicas Circulantes/metabolismo , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Inmunohistoquímica , Mamoglobina A , Persona de Mediana Edad , Mucina-1/genética , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , Receptor ErbB-2/análisis , Receptor ErbB-2/genética , Uteroglobina/genética
18.
Eur J Med Res ; 14(9): 393-405, 2009 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-19748858

RESUMEN

BACKGROUND: The aim of the present study was to determine whether regular exercise training (ET) is effective at promoting the mobilization of CPCs and improving their functional activity in patients with recently acquired myocardial infarction (STEMI). Regular physical training has been shown to improve myocardial perfusion and cardiovascular function. This may be related in part to a mobilization of bone marrow-derived circulating progenitor cells (CPCs) as well as an enhanced vascularisation. METHODS: 37 patients with STEMI were randomly assigned to an ET group or a non-ET group (controls). Two weeks after STEMI, three weeks after regular ET and three months after ET, BNP levels, exercise echocardiography and exercise spiroergometry were evaluated. The number of CD34+/CD45+ and CD133+/CD45+ CPCs was measured by flow cytometry analysis. The migration capacity of the CPCs was determined with a boyden chamber and the clonogenic capacity by CFU-assay. RESULTS: In the ET-group the number and migration capacity of CPCs increased significantly after regular exercise training. The BNP level decreased significantly from 121 +/- 94 to 75 +/- 47 pg/ml (p<0.001) after the ET period, the left ventricular ejection fraction raised in parallel at peak exercise, and the cardiorespiratory condition improved as demonstrated by an increase of VO2max (from 1641 +/- 522 to 1842 +/- 724 ml/min, p<0.02). These three effects persist till three months after the ET period. CONCLUSIONS: Regular physical activity appears to predispose the mobilization and enhanced functional activity of CPCs, a phenomenon which might lead to an improved cardiac function in patients with recently acquired acute myocardial infarction.


Asunto(s)
Células de la Médula Ósea/metabolismo , Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Movilización de Célula Madre Hematopoyética/métodos , Infarto del Miocardio/rehabilitación , Antígeno AC133 , Anciano , Antígenos CD/sangre , Antígenos CD34/sangre , Células de la Médula Ósea/citología , Movimiento Celular/fisiología , Terapia Combinada , Ecocardiografía de Estrés , Femenino , Citometría de Flujo , Glicoproteínas/sangre , Células Madre Hematopoyéticas , Humanos , Antígenos Comunes de Leucocito/sangre , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Péptido Natriurético Encefálico/sangre , Péptidos/sangre , Estudios Prospectivos , Espirometría
19.
Eur J Med Res ; 14(8): 359-63, 2009 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-19666396

RESUMEN

BACKGROUND: Breast cancer (BC) represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting. MATERIALS AND METHODS: Circulating tumour cells (CTC) of 63 BC patients were isolated from peripheral blood (PB) through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls. RESULTS: Significant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/ spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed. CONCLUSION: Herein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Regulación Neoplásica de la Expresión Génica/genética , Células Neoplásicas Circulantes/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
20.
Eur J Med Res ; 14(6): 240-3, 2009 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-19541583

RESUMEN

Desmoid tumors are fibroblastic/myofibroblastic neoplasms, which originate from musculo-aponeurotic structures and are classified as deep fibromatoses. Despite their benign histologic appearance and lack of metastatic potential, desmoid tumors may cause aggres?sive local infiltrations and compression of surrounding structures. They are often associated with female gender, familial adenomatous polyposis (FAP) and sporadically may occur at sites of previous trauma, scars or irradiation. Molecular studies have demonstrated that these patients are associated with a bi-allelic APC mutation in the affected tissue. Radical tumor resection with free margins remains the first therapy of choice. In cases with anatomical or technical limitations for a wide excision, radiation therapy represents a proven and effective alternative or supplementary treatment.


Asunto(s)
Fibromatosis Abdominal/patología , Fibromatosis Agresiva/patología , Neoplasias Torácicas/patología , Pared Torácica/patología , Adolescente , Femenino , Fibromatosis Abdominal/diagnóstico por imagen , Fibromatosis Abdominal/terapia , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/terapia , Humanos , Masculino , Radiografía Torácica/métodos , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/terapia , Pared Torácica/diagnóstico por imagen , Pared Torácica/cirugía , Tomografía Computarizada por Rayos X
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