24,248 research outputs found
Phase Ii Trial of the Efficacy and Safety of Sunitinib Malate Monotherapy in Unresectable Hepatocellular Carcinoma
No full textNuclear Extracellular Signal-Regulated Kinase 2 Phosphorylates P53 at Thr 55 in Response to Doxorubicin
No full textIn this study, we showed that nuclear ERK2 phosphorylates p 53 at Thr55 in response to doxorubicin. p53 was found to physically interact with ERK2 as evidenced by Western blotting of ERK2 coimmunoprecipitated complex. The gene fragment encoded for N-terminal 68 amino acids was subcloned and fused with 6-His. Each serine or threonine site in this fragment, the possible phosyphorylation site, was mutated to alanine. The recombinant proteins were used as substrates in ERK2 kinase assay. The results show that ERK2 phosphorylated p53 at Thr55. Further, electromobility shift assay showed that the phosphorylation of p53 by nuclear ERK2 was closely related to the transactivating activity of p53. These findings suggest that ERK2 may play a role in response to DNA damage via interaction with p 53. (C) 2001 Academic Press
Impact of Lung and Lymph Node Metastasis on Efficacy and Safety Following Treatment with Sorafenib in Patients with Hepatocellular Carcinoma from the Asia-Pacific Region
No full textEfficacy and Safety of Sorafenib in Patients with Advanced Hepatocellular Carcinoma (Hcc): Collective Results from the Phase Iii Sorafenib Hcc Assessment Randomized Protocol (Sharp) and Asia-Pacific (Ap) Trials
No full textImpact of Prior Tace/Tae on the Efficacy and Safety of Sorafenib in Patients with Advanced Hepatocellular Carcinoma (Hcc) from the Asia- Pacific Region
No full textIncrease of the Resistance of Human Cervical Carcinoma Cells to Cisplatin by Inhibition of the Mek to Erk Signaling Pathway Partly Via Enhancement of Anticancer Drug-Induced Nf Kappa B Activation
No full textIn this study, we showed that suppression of the MEK-ERK transduction pathway by a selective inhibitor, 2-amino-3'- methoxyflavone (PD98059), increased drug resistance of SiHa cells to cisplatin, but not to another common anticancer drug, doxorubicin. The downstream mechanism of this discrepant cellular response was investigated. Both cisplatin and doxorubicin activated nuclear ERK2 and nuclear transcription factor kappaB (NFkappaB) of SiHa cells. However, suppression of the MEK-ERK2 pathway by PD98059 resulted in a further enhancement of cisplatin-induced NFkappaB activation, while no further regulation of NFkappaB was noted in doxorubicin-treated cells. The activation of NFkappaB by cisplatin or doxorubicin was not due to the degradation of cytoplasmic IkappaBalpha, as demonstrated by western blotting. Transfection of a dominant negative IkappaBalpha resulted in a markedly diminished PD98059- induced cisplatin resistance in SiHa cells. Our results suggest that the MEK-ERK signaling pathway plays a role in the chemosensitivity of SiHa cells, and suppression of this pathway increases cisplatin resistance partly via an increase of NFkappaB activation. The mechanism responsible for the discrepant effect of PD98059 on NFkappaB activation and hence the chemo sensitivity of SiHa cells towards cisplatin and doxorubicin remains to be investigated. (C) 2002 Elsevier Science Inc, All rights reserved
Comparison of Malt and Non-Malt Primary Large Cell Lymphoma of the Stomach - Does Histologic Evidence of Malt Affect Chemotherapy Response?
No full textBACKGROUND. Although the clinicopathologic features of low grade gastric MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have been well delineated, the significance of identifying histologic evidence of MALT origin in a primary high grade gastric lymphoma is less clear. The authors sought to address this issue and, in particular, to clarify if MALT and non-MALT primary large cell gastric lymphoma might have a different response to systemic chemotherapy.METHODS. The authors reviewed the pathologic specimens of all patients who had a diagnosis of primary large cell lymphoma of the stomach and who had been treated primarily by systemic chemotherapy in our institutions January 1, 1988-December 31, 1998. The patients were divided into two groups by experienced hematopathologists, based on the presence or absence of histologic features suggestive of MALToma, including typical lymphoepithelial lesions and infiltration of characteristic centrocyte-like cells. Disease staging was done according to the AJCC/UICC system with Musshoff modification. The median number of gastric biopsies for each patient was 7 ( range, 1-21 ).RESULTS. Seventeen patients with and 26 patients without histologic evidence of MALToma were identified. Clinical features were similar between the two groups except that a greater proportion of patients without evidence of MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%, P = 0.01). The median duration of follow-up for the 43 patients was 46.5 months (range, 17- 124 mos). All patients received standard systemic chemotherapy including anthracyclines or anthracenedione. The response rate was 88.2% for patients with evidence of MALToma and 57.7% for those without (P = 0.03). The 5-year overall survival rate was 80.5% for patients with evidence of MALToma and 48.9% for those without (P = 0.02). Multivariate analysis indicated that response to chemotherapy, disease stage (Stage I and II-1 vs. Stage II-2 , III, and IV), and the presence of MALToma features were independent prognostic factors for overall survival. CONCLUSION. The results of this relatively small study series suggested that the presence of histologic features of MALToma in patients with primary large cell gastric lymphoma might have been associated with a better response to systemic chemotherapy and a better prognosis. Further studies to consolidate this conclusion are necessary
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