1,046 research outputs found
Activity and side effects of imatinib in patients with gastrointestinal stromal tumors: data from a german multicenter trial
Gastrointestinal stromal tumors (GIST) are mesenchymal tumors that in the past were classified as leiomyosarcomas or leiomyomas not responding to standard sarcoma chemotherapy. In several phase I and II trials the efficacy and safety of imatinib was shown before the largest trial ever performed in a single sarcoma entity revealed response rates (CR/PR) of 52%. This multicenter phase II trial presented here was performed to open access to imatinib for patients with unresectable or metastastatic GIST when the EORTC 62005 trial had been closed before imatinib was approved in Germany. It was designed to follow the best clinical response and to assess the efficacy, safety and tolerability of imatinib 400 mg/d in patients with unresectable or metastatic gastrointestinal stromal tumor
Treatment strategies and prognostic factors of patients with primary germ cell tumors in the mediastinum
Se presenta una paciente que fue intervenida quirúrgicamente por presentar una lesión tumoral a nivel del mediastino anterior, totalmente asintomática y descubierta, de forma incidental (incidentaloma), en el estudio preoperatorio por padecer litiasis vesicular. La tumoración resultó ser, histológicamente, un teratoma quÃstico maduro. La paciente evolucionó satisfactoriamente.It presents a patient who was surgery because of a tumor at the level of the anterior mediastinum, totally asymptomatic and uncovered, incidentally (incidentaloma), in the preoperative study due to vesicular lithiasis. The tumor turned out to be, histologically, a mature cystic teratoma. The patient evolved satisfactorily
Molecular determinants of treatment response in human germ cell tumors
PURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based
chemotherapy. This feature is unexplained, as is the intrinsic
chemotherapy resistance of mature teratomas and the resistant phenotype of
a minority of refractory GCTs. Various cellular pathways may influence the
efficacy of chemotherapy. Their impact has not been investigated in a
comprehensive study of tumor samples from clinically defined subgroups of
GCT patients. EXPERIMENTAL DESIGN: We investigated proteins involved in
regulation of apoptosis (p53, BAX, BCL-2, and BCL-X(L)), cell cycle
control [p21 and retinoblastoma protein (RB)], and drug export and
inactivation [P-glycoprotein, multidrug resistance-associated protein
(MRP) 1, MRP2, breast cancer resistance protein, lung resistance protein,
metallothionein, and glutathione S-transferase pi] immunohistochemically
in samples of unselected GCT patients (n = 20), patients with advanced
metastatic disease in continuous remission after first-line chemotherapy
(n = 12), and chemotherapy-refractory patients (n = 24). Mature teratoma
components (n = 10) within tumor samples from all groups were analyzed
separately. The apoptotic index was studied by terminal deoxynucleotidyl
transferase-mediated nick end labeling assay. RESULTS: Invasive GCTs of
all groups showed a correlation between wild-type p53 and apoptotic index
(r(s) = 0.66; P < 0.001). The levels of the antiapoptotic proteins BCL-2
and BCL-X(L) were generally low. p21 was hardly detectable and did not
correlate with p53 (r(s) = 0.29; P = 0.07). No significant differences
among the three patient groups were identified regarding any of the
investigated parameters (all Ps were >0.08), even though only individual
samples from chemotherapy-resistant cases showed a strong staining for
MRP2 and GSTpi. In contrast to other components, mature teratomas showed
an intense p21 and RB staining and were mostly positive for MRP2, lung
resistance protein, and GSTpi. CONCLUSIONS: Our results indicate a
multifactorial basis for the chemosensitivity of GCTs with lack of
transporters for cisplatin, of antiapoptotic BCL-2 family members, of p21
induction by p53, and of RB and an intact apoptotic cascade downstream of
p53. These findings suggest a preference for apoptosis over cell cycle
arrest after up-regulation of p53. None of the examined parameters offers
a general explanation for the chemotherapy-resistant phenotype of
refractory tumors. The up-regulation of various factors interfering with
chemotherapy efficacy and ability for a p21-induced cell cycle arrest may
explain the intrinsic chemotherapy resistance of mature teratomas
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