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Monday, March 17, 2008

Fwd: Mutations in the epidermal growth factor receptor gene and effects of EGFR-tyrosine kinase inhibitors on lung cancers.



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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Mar 16, 2008 at 1:55 AM
Subject: Mutations in the epidermal growth factor receptor gene and effects of EGFR-tyrosine kinase inhibitors on lung cancers.
To: mesothelioma77@gmail.com


[1]Gen Thorac Cardiovasc Surg. 2008 Mar; 56(3): 97-103
Fukui T, Mitsudomi T

Epidermal growth factor receptor (EGFR) gene mutations are frequent in lung cancer arising in patients of Asian ethnicity, female sex, nonsmokers, and adenocarcinoma histology. About 70% of the patients with EGFR mutations respond to EGFR tyrosine kinase inhibitors (TKIs) including gefitinib and erlotinib, whereas only 10% of those without the mutations do so. Therefore, EGFR mutation is being recognized as one of the most reliable predictive factors for treatment using EGFR-TKIs. Another important issue in clinical practice is the fatal interstitial lung disease (ILD) that can develop in patients with gefitinib treatment, especially Asian patients. A nested case-control study recently conducted in Japan identified some risk factors that cause ILD, including age >/= 55 years, a history of smoking, preexisting ILD, poor performance status, short duration since diagnosis of lung cancer, reduced extent of normal lung on computed tomography, and concurrent cardiac disease. About half of the acquired resistance to EGFR-TKIs that almost always occurs during the course of treatment is caused by a secondary mutation at codon 790 (T790M). EGFR-TKIs are not universally effective for treating lung cancers but are effective in patients with particular genotypes. Therefore, patients who would benefit from EGFR-TKIs therapy should be concentrated in clinical trials. Based on this concept, Phase III clinical trials comparing gefitinib monotherapy with standard platinum-based chemotherapy are currently ongoing for patients with EGFR mutations and lung cancer.



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Fwd: Results of video-assisted thoracoscopic surgery for esophageal cancer during the induction period.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Mar 16, 2008 at 1:55 AM
Subject: Results of video-assisted thoracoscopic surgery for esophageal cancer during the induction period.
To: mesothelioma77@gmail.com


[1]Gen Thorac Cardiovasc Surg. 2008 Mar; 56(3): 119-25
Ninomiya I, Osugi H, Fujimura T, Kayahara M, Takamura H, Takemura M, Lee S, Nakagawara H, Nishimura G, Ohta T

OBJECTIVE: The attainment of proficiency in thoracoscopic radical esophagectomy for thoracic esophageal cancer requires much experience. We aimed to master this procedure safely with our regular surgical team members under the direction of an experienced surgeon. We evaluated the efficacy of instruction during the induction period and the significance of our results. METHODS: We compared the results of 12 thoracic esophageal cancer patients who underwent thoracoscopic radical esophagectomy in our institution (group A) to those of the initial 17 patients who underwent the same operation at the director's institution (group B). RESULTS: We were able to perform complete thoracoscopic radical esophagectomies without any direction after experiencing 10 cases that were performed under adequate direction. The number of dissected lymph nodes and the duration of the procedure were similar in the two groups: 34 (22-53) vs. 26 (9-55) nodes, P = 0.23; and 327.5 (230-455) vs. 315 (190-515) min, P = 0.947, respectively. The amount of thoracic blood loss was significantly less in group A than in group B: 185 (110-380) g vs. 440 (110-2360) g, P = 0.0035. Postoperative pneumonia and atelectasis were observed in 25.0% of group A patients and in 17.6% of group B patients. The incidence of recurrent nerve palsy was 30.7% in group A and 11.7% in group B, but there was no statistically significant difference (P = 0.19). The morbidity rates in group A and group B were 41.6% and 29.4%, respectively (P = 0.694). CONCLUSION: Thoracoscopic radical esophagectomy can be mastered relatively quickly and safely under the direction of an experienced surgeon and a regular surgical team.



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Fwd: Role for epithelial dysregulation in early-onset colitis-associated colon cancer in Gi2-alpha-/- mice.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Mar 16, 2008 at 1:55 AM
Subject: Role for epithelial dysregulation in early-onset colitis-associated colon cancer in Gi2-alpha-/- mice.
To: mesothelioma77@gmail.com


[1]Inflamm Bowel Dis. 2008 Mar 13;
Edwards RA, Wang K, Davis JS, Birnbaumer L

Background: Inflammatory bowel disease (IBD) is a risk factor for developing colorectal cancer but the mechanisms are poorly characterized. Mice lacking the G-protein alpha subunit Gi2-alpha spontaneously develop colitis and colon cancer with high penetrance. Compared to canonical Wnt/APC signaling-based animal models of colon cancer, the tumors in Gi2-alpha-/- mice more closely recapitulate the features of IBD-associated cancers seen in humans. They are predominantly right-sided, multifocal, mucinous, and arise from areas of flat dysplasia.Methods: In evaluating the potential contribution of epithelial Gi2-alpha signaling to this phenotype, we found that Gi2-alpha-/- colonic epithelium is hyperproliferative even before the onset of colitis, and resistant to the induction of apoptosis. We generated colon cancer cell lines overexpressing dominant-negative Gi2-alpha.Results: Like other cells lacking Gi2-alpha, these cells release less arachidonic acid, an important antiinflammatory and epithelial growth regulator. They are also hyperproliferative and resistant to camptothecin-induced apoptosis and caspase-3 activation.Conclusions: The colitis-associated cancers in Gi2-alpha-/- mice appear very similar to those seen in human IBD patients, and Gi2-alpha is a direct negative regulator of colonic epithelial cell growth.(Inflamm Bowel Dis 2008).



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Fwd: TP53 mutations in head and neck cancer.



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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Mar 16, 2008 at 1:55 AM
Subject: TP53 mutations in head and neck cancer.
To: mesothelioma77@gmail.com


[1]N Engl J Med. 2008 Mar 13; 358(11): 1194-5; author reply 1195
Perrone F, Bossi P, Licitra L





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