Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
2.
Bone Marrow Transplant ; 52(10): 1436-1442, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28650451

RESUMEN

Return to work is critical goal following HSCT. However, late effects may impede return to normal activity after HSCT. In the case of inability to work, patients may need a work disability pension to ensure a reasonable livelihood. This study evaluated inability to work and need for disability pension among long-term survivors and analyzed possible determinants of need for social support. This retrospective, single-center study included all HSCT patients surviving ⩾5 years seen at the outpatient clinic between January 2013 and August 2015. There were 203 patients, median age at HSCT 35 years, and 50 years at time of study; median time between HSCT and study control was 12 years; 178 had allo-HSCT, 187 had a malignant disease. At time of study, 156 (77%) were working full or part-time, 47 (23%) were not working. In total, 76 (37%) survivors were receiving a work disability pension compared to 3.17% of the Swiss working population. Patients with a disability pension were significantly older at HSCT, were more often living alone, had more active physical and mental late effects, and higher score of fatigue compared to patients without. These findings underline the importance of screening for employment and the social consequences of non-employment in long-term survivors after HSCT.


Asunto(s)
Evaluación de la Discapacidad , Personas con Discapacidad , Empleo , Trasplante de Células Madre Hematopoyéticas , Pensiones , Sobrevivientes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Suiza
3.
Bone Marrow Transplant ; 52(4): 506-513, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28067888

RESUMEN

In 2009, the American Society of Parenteral and Enteral Nutrition and its European counterpart (Euopean Society for Parenteral and Enteral Nutrition) published guidelines regarding nutritional support of patients with hematologic stem cell transplantation. Our aim was to do an up-to-date literature review regarding benefit of nutritional interventions and treatment recommendations. We searched MEDLINE, EMBASE and Cochrane Library for interventional and observational clinical studies. We extracted data based on a predefined case report form and assessed bias. Out of 459 potential abstracts, 13 studies of mostly moderate quality with a total of 18 167 patients were included. Two very large trials reported negative associations of malnutrition and survival, transplant-related mortality and relapse risk. Some trials found enteral nutrition (EN) to be as effective as parenteral nutrition (PN) with lower complication rates. In addition, EN was associated with better survival, less acute GvHD and faster neutrophil recovery. A neutropenic diet was not superior regarding overall survival, but in contrast resulted in higher infection risk. Current moderate quality studies show negative associations of malnutrition and clinical outcomes, with EN being superior to PN. There was no benefit of neutropenic diets. Large, randomized controlled studies are needed to better understand optimal nutritional support in this patient population.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Apoyo Nutricional/normas , Nutrición Enteral/normas , Humanos , Desnutrición , Apoyo Nutricional/métodos , Nutrición Parenteral/normas , Resultado del Tratamiento
4.
Bone Marrow Transplant ; 50(11): 1453-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26301968

RESUMEN

The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.


Asunto(s)
Médula Ósea/patología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Nestina/análisis , Nicho de Células Madre , Enfermedad Aguda , Adulto , Anciano , Aloinjertos , Antígenos CD34/análisis , Área Bajo la Curva , Biomarcadores , Médula Ósea/irrigación sanguínea , Médula Ósea/fisiología , Diferenciación Celular , Estudios de Cohortes , Femenino , Factores de Transcripción Forkhead/análisis , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/terapia , Humanos , Masculino , Microvasos/patología , Persona de Mediana Edad , Neovascularización Patológica/etiología , Neovascularización Patológica/patología , Procolágeno/análisis , Curva ROC , Regeneración , Acondicionamiento Pretrasplante/efectos adversos
5.
Ann Hematol ; 94(11): 1899-905, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26233683

RESUMEN

The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13 months (range 1-42); median dose was 600 mg (range 100-1200). Fourteen patients (82 %) achieved a complete remission (CR), while 5 patients (29 %) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95 % CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1 month on/1 month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20 months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Tirosina Quinasa 3 Similar a fms/genética , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Sorafenib , Secuencias Repetidas en Tándem/genética , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
6.
Bone Marrow Transplant ; 50(10): 1331-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26121111

RESUMEN

In vivo T-cell depletion with anti-thymocyte globulin (ATG) can attenuate GvHD but may increase infection and relapse risks. ATG-Fresenius (ATG-F) at a dose of 60 mg/kg was standard GvHD prophylaxis in unrelated donor hematopoietic stem cell transplantation (HSCT) at our institution. We changed to an incremental reduced dose regimen of 35 mg/kg and extended ATG prophylaxis to include older matched-related donor transplants considered to be at higher risk of GvHD. A total of 265 adults with hematological malignancies receiving a first allogeneic HSCT after myeloablative conditioning between 2009 and 2014 were analyzed in this cohort study. Patients had either received higher dose (n=32) or lower dose ATG-F (n=88) or no ATG (n=145). ATG-F was associated with slower engraftment and less chronic GvHD, whereas no effect was noted on acute grade II-IV GvHD and relapse incidence. Transplant-related mortality (TRM) was lower and survival higher with lower dose, but not with higher dose ATG-F. Both ATG-F groups were associated with more viral reactivation, viral disease and bacterial blood stream infection, but not invasive fungal infection, and with slower immune reconstitution. The recently adopted strategy of using lower doses of ATG-F in unrelated and older age-related donor HSCT appears to reduce TRM without increasing disease relapse, leading to slightly enhanced survival.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo/mortalidad , Adulto Joven
7.
Bone Marrow Transplant ; 50(9): 1201-5, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26052916

RESUMEN

Unrelated donor searches in Switzerland require high-resolution HLA typing for HLA-A/B/C/DRB1/DRB3,4/DQB1 loci. We evaluated this strategy accepting donors with ⩾9/10 match. Of 802 unrelated donor transplants in 2000-2013, 570 were 10/10 matched, 31 were DRB3/4 mismatched, 261 were single-allele mismatched and 13 had 2 allele mismatches. Of the 261 single-allele disparities, 60 concerned HLA-A/-B, 55 HLA-C and 73 HLA-DRB1/-DQB1 loci. Transplants were reduced intensity conditioning (289, 36%), marrow (187, 23%), EBMT risk score was low in 39, intermediate I in 331, intermediate II in 333 and high in 99 patients. Five-year survival was 48±4%. HLA affected survival in the multivariate model adjusted for risk score. HLA-A/-B and HLA-C mismatches had twice the mortality risks, whereas HLA-DRB1/-DQB1 mismatches were similar to matched transplants. HLA-DRB3/4 mismatches were associated with a nonsignificant increased mortality risk. HLA-DRB3/4 mismatches had higher graft-versus-host disease and transplant-related mortality risks and lower relapse rates compared with matched transplants. We show significant effects of HLA class I, but not HLA class II, mismatches. The lack of impact of DRB1 disparities may be related to the lower immunogenicity of the DRB1*11:01/11:04 and DRB1*14:01/14:54 mismatches, representing 46% of DRB1 incompatibilities. These results support a matching algorithm that prioritizes mismatches considered as more permissive.


Asunto(s)
Cadenas beta de HLA-DQ/inmunología , Cadenas HLA-DRB1/inmunología , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Antígenos de Histocompatibilidad Clase I/inmunología , Prueba de Histocompatibilidad , Donante no Emparentado , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Selección de Donante , Femenino , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Suiza
8.
Int J Lab Hematol ; 36(3): 382-7, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24750685

RESUMEN

Aplastic anemia (AA) may precede, co-occur, or follow a lymphoproliferative neoplasm. The best molecularly clarified scenario is that of concurrent AA and unsuspected (occult) T-cell large granular lymphocyte leukemia. Several reported cases of AA and concurrent small B-cell lymphomas/leukemias and Hodgkin lymphomas suggest also a possible link to simultaneous or preceding AA that might be sought in an antineoplastic immunological attempt to 'eradicate' the underlying malignant clone. The 'immuno-deregulatory' potential and the direct cytotoxicity of regimens used for lymphoma therapy might be able to trigger AA in cases evolving after lymphoma treatment too. Alternative explanations of AA associated with lymphoproliferative disorders might be particular (immuno-)genetic patient backgrounds predisposing to both AA and lymphoid neoplasms or exposures to environmental factors, increasing the risk for both diseases. Finally, the most common causal relationship of AA and lymphoma is that of immunosuppression- or allogeneous hematopoietic stem cell transplantation-associated posttransplantational lymphoproliferative disorders in AA patients, who are treated in the respective manner. As all above scenarios are differently (specifically) therapeutically approachable and accompanied by diverse outcomes, they should be actively sought for and diagnosed as precisely as possible. This review summarizes the current knowledge on associations between AA and lymphoproliferative neoplasms.


Asunto(s)
Anemia Aplásica/etiología , Trastornos Linfoproliferativos/complicaciones , Anemia Aplásica/diagnóstico , Humanos , Trastornos Linfoproliferativos/diagnóstico
9.
Bone Marrow Transplant ; 48(5): 715-21, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23085826

RESUMEN

There is increasing evidence suggesting that both angiogenesis and endothelial injury are involved in GVHD. To study the dynamics of angiogenesis, we examined 26 patients with AML who had undergone allogeneic haematopoietic SCT. All were in CR and had either acute GVHD (aGVHD) or chronic GVHD (cGVHD). We performed immunohistochemical studies of BM microvessel density (MVD) using Abs against vascular-endothelial (VE)-cadherin, CD34 and CD105, and expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2. At the time of diagnosis, the MVD in AML patients was higher than that in the normal controls, and the MVD decreased after induction chemotherapy. Patients with aGVHD had a significantly higher MVD than patients without aGVHD. Conversely, patients with cGVHD did not have a significantly different MVD. In previous aGVHD, we also found more VEGF+ megakaryocytes. XY FISH in sex-mismatched patients showed that the BM blood vessels consisted mainly of recipient endothelial cells. Taken together, these results suggest that new vessel formation and the VEGF/VEGFR system are involved in aGVHD.


Asunto(s)
Médula Ósea/metabolismo , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/cirugía , Receptores de Factores de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunohistoquímica , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
10.
Praxis (Bern 1994) ; 101(24): 1573-6, 2012 Nov 28.
Artículo en Alemán | MEDLINE | ID: mdl-23184550
11.
Int J Oncol ; 38(2): 455-64, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21152862

RESUMEN

ZD6126 is a vascular-disrupting agent that affects the endothelial tubulin cytoskeleton causing selective occlusion of tumor vasculature and extensive tumor cell necrosis. The present study evaluated the antitumor and antivascular activities of ZD6126 in the clinically relevant murine renal cell carcinoma (RENCA) model and also evaluated biological response to therapy using color Doppler imaging as biomarker. Mice were implanted with RENCA tumor cells (day 0) and established tumors were treated with ZD6126 (100 mg/kg i.p.) or vehicle with repeated intermittent doses on day 10, 14 and 18. ZD6126 treatment led to a significant reduction in tumor size and was associated with extensive tumor necrosis and a reduction in tumor blood flow versus controls. MVD increased with intermittent treatment (day 10, 14 and 18). In an additional study, animals were treated at day 19 and quantitative three-dimensional microvascular corrosion casting was performed to enable detailed assessment of the tumor vascular architecture. Corrosion casting showed that tumor vessel architecture is affected by treatment, whereas pre-existing vessels in control tissues are practically not affected. Inter-vessel and inter-branch distances as well as vessel diameters are influenced by treatment. In conclusion, ZD6126 showed potent antitumor efficacy in the RENCA model and our data suggest that decrease in tumor blood flow may be a useful surrogate marker of treatment effect.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Carcinoma de Células Renales/tratamiento farmacológico , Modelos Animales de Enfermedad , Neoplasias Renales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Compuestos Organofosforados/farmacología , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/patología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Técnicas para Inmunoenzimas , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/patología , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos
12.
Bone Marrow Transplant ; 42(7): 483-7, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18695668

RESUMEN

Allogeneic hematopoietic SCT (HSCT) is increasingly considered an option in refractory or relapsing lymphoma. Today, most patients with B-cell lymphoma are treated with the monoclonal anti-CD20 antibody rituximab before HSCT. We hypothesized that prior therapy with rituximab might alter immune reconstitution after allogeneic transplantation due to in vivo depletion of B cells at the time of graft infusion. We studied B-cell immune reconstitution in 12 patients with lymphoma receiving rituximab 1-12 months before HSCT. Compared to an age- and sex-matched population of patients transplanted for myeloid malignancies, lymphoma patients with rituximab pretreatment showed significantly reduced B-cell counts at time of HSCT at +3, +6 and +12 months; B-cell counts reached values comparable to controls only 24 months after HSCT. In parallel, levels of immunoglobulins were markedly reduced for up to 2 years post transplant in patients with prior rituximab treatment. Two patients suffered from severe late bacterial infections to which the impaired humoral immunity may have contributed. In contrast, T- and NK-cell reconstitution was not different compared to control patients.In conclusion, B-cell reconstitution can be significantly delayed in allogeneic HSCT recipients with prior rituximab treatment. Rituximab appears to have clinical consequences beyond the immediate early post-transplant period.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfocitos B/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma/inmunología , Adolescente , Adulto , Anticuerpos Monoclonales de Origen Murino , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos B/efectos de los fármacos , Linfocitos B/patología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Esquema de Medicación , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Linfoma/patología , Linfoma/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Trasplante Homólogo
13.
Ann Oncol ; 16(4): 558-65, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15705616

RESUMEN

BACKGROUND: Plasma and serum biomarkers of angiogenesis and activated endothelial cells were evaluated to assess biological activity of PTK787/ZK 222584 (PTK/ZK), a novel oral angiogenesis inhibitor targeting all known vascular endothelial growth factor (VEGF) receptor tyrosine kinases. PATIENTS AND METHODS: Patients with colorectal cancer (CRC) (n=63) were enrolled into two phase I/II dose escalation trials of PTK/ZK in 28-day cycles until discontinuation. Patients with stable disease for > or =2 months were categorized as 'non-progressors'. Plasma markers of angiogenesis, VEGF-A and basic fibroblast growth factor (bFGF), and the serum markers of activated endothelial cells, sTIE-2 and sE-Selectin, were assessed at baseline, and pre-dose on days 1, 8, 15, 22 and 28 of every cycle, with additional assessments 10 h post-dose on days 1 and 15. The percentage change from baseline was subsequently correlated with AUC and C(max) of PTK/ZK on day 1, cycle 1 and clinical outcome. RESULTS: A dose-dependent increase in plasma VEGF-A and bFGF was observed in the first cycle of PTK/ZK treatment. The correlation of change in plasma VEGF-A with AUC and C(max) was characterized by an E(max) model, suggesting that a change of > or =150% from baseline VEGF-A correlated with non-progressive disease. Change from baseline plasma VEGF-A within the first cycle of treatment was significantly correlated with clinical outcome by logistic regression analysis (P=0.027). CONCLUSIONS: In patients with CRC treated with PTK/ZK, changes in plasma VEGF-A and bFGF demonstrate biological activity of PTK/ZK, may help to establish optimal dose and correlate with outcome.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Ftalazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Biomarcadores/sangre , Ensayos Clínicos Fase II como Asunto/métodos , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/enzimología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ftalazinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/sangre
14.
Praxis (Bern 1994) ; 93(40): 1633-44, 2004 Sep 29.
Artículo en Alemán | MEDLINE | ID: mdl-15495753

RESUMEN

This article reviews the available data regarding the acticity of postoperative adjuvant systemic therapy for colorectal cancer as first and second-line treatment in metastatic disease. The efficacy of adjuvant treatment of patients with stage III colorectal cancer is well established. 5-fluorouracil (5-FU) and folic acid over 6 months (still) represent todays standard and should serve as comparison in randomized studies. The risk of relapse is low in stage II colon carcinoma and consequently the efficacy is relatively small compared to stage III. New investigation indicate, Capecitabene has the potential to replace 5-FU/FS as standard treatment for patients with colon cancer. Efficacy results are expected to be available in 2004. In metastatic disease combination of 5-FU/folic acid plus CPT-11 or OXA are treatment of choice for the first-line therapy of metastatic colorectal carcinoma. FOLFOX is high-dose intensity oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second- line therapy for metastatic colorectal cancer. It resulted in prolongation of the median progress free survival from 6,8 to 8,8 months and increased the survival for 4,5 months. New perspectives are novel chemotherapeutic and targeted agents in metastatic colorectal cancer: For the first time, there has been a targeted therapy shown convincingly to prolong survival for patients with unresectable metastatic colorectal cancer in a well-performed Phase III trial. This agent is bevacizumab, a humanised monoclonal antibody targeting the circulating proangiogenic growth factor vascular endothelial growth factor. Results with bevacizumab should lead to rapid expansion of the number of strategies targeting tumour neovasculature. Additionally, an antibody against the epidermal growth factor, cetuximab, has been shown to have both single-agent activity and the potential ability to partially reverse resistance to a chemotherapy drug. These advancements, as well as data on other novel treatment agents that have been studied specifically in patients with colorectal neoplasms, are discussed in detail.


Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab , Cetuximab , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Colon/patología , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Neoplasias del Colon/secundario , Neoplasias del Colon/cirugía , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Terapia Combinada , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Ácido Fólico/administración & dosificación , Ácido Fólico/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Compuestos Organoplatinos , Cuidados Paliativos , Cuidados Posoperatorios , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo
15.
Angiogenesis ; 6(3): 225-31, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-15041798

RESUMEN

Angiogenesis is necessary for the growth of primary tumors and the formation of metastases. It is well known that vascular endothelial growth factor (VEGF) and its receptors play a major role in this process. To date, the formation of bone metastases has been poorly understood. Tumor cells must interact with the microenvironment of the bone and new blood vessels must spread. The ET/ET(A) (endothelin) receptor system seems to play an important role in this process. Specimens from metastatic bone lesions and non-malignant bone tissue were analyzed by histological and immunohistochemical staining. Sections were stained with antibodies against CD31, Flt-1, KDR, endothelin-1 (ET-1) and endothelin receptor A (ET(A)). Our studies show that there is an increased microvessel density (MVD) in metastatic bone lesions from different primary tumors in contrast to normal bone tissue. In nearly all tumor formations of the bone, ET-1 and its receptor ET(A) was found by immunohistochemistry. We also performed immunohistochemical staining for the VEGF-receptors Flt-1 and KDR. In conclusion, there is an increased vessel density in metastatic bone lesions in contrast to normal bone tissue. The ET/ET(A) system can be detected in nearly all bone specimens and is upregulated in metastatic bone lesions in contrast to healthy bone tissue.


Asunto(s)
Neoplasias Óseas/química , Neoplasias Óseas/secundario , Endotelina-1/análisis , Neovascularización Patológica/etiología , Receptor de Endotelina A/análisis , Neoplasias Óseas/irrigación sanguínea , Neoplasias Óseas/etiología , Estudios de Casos y Controles , Endotelina-1/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias/química , Neoplasias/patología , Neovascularización Patológica/patología , Receptor de Endotelina A/genética , Regulación hacia Arriba , Receptor 1 de Factores de Crecimiento Endotelial Vascular/análisis , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética
16.
Onkologie ; 25(6): 520-7, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12566896

RESUMEN

Neovascularization is a prerequisite for progressive growth of solid tumors and their metastases. This process is tightly regulated by a large number of proangiogenic and antiangiogenic factors such as VEGF, bFGF and matrix-metalloproteinases. The inhibition of angiogenesis is an innovative therapeutic approach and could represent a powerful adjunct to traditional therapy of malignant tumors. Preclinical trials have been very successful but in clinical studies meaningful response rates could only be shown in some cases. This might indicate the existence of different angiogenic phenotypes in humans. It seems that at present only a part of the interactions between the angiogenic cytokines are known. In addition, new receptor/ligand systems which regulate the neovascularization are being described. This article presents an overview of the most important angiogenically active substances, preclinical and clinical data, surrogate markers as well as future perspectives.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Inhibidores de la Angiogénesis/fisiología , Animales , Ensayos Clínicos como Asunto , Evaluación de Medicamentos , Factores de Crecimiento Endotelial/antagonistas & inhibidores , Humanos , Péptidos y Proteínas de Señalización Intercelular , Linfocinas/antagonistas & inhibidores , Inhibidores de la Metaloproteinasa de la Matriz , Metaloproteinasas de la Matriz/fisiología , Neoplasias/irrigación sanguínea , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA