Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.
 ...
PMID:Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer. 1687 Mar 3

Somatic mutations of the PIK3CA (phosphatidylinostitol 3-kinase catalytic subunit) gene have been found in human cancer patients. Previous reports suggested that about 4% of lung cancers harbored PIK3CA gene mutations. However, the clinico-pathological background for PIK3CA gene mutations has not yet been investigated in lung cancer. We have genotyped the PIK3CA gene in Japanese lung cancer patients. The study included 235 lung cancer cases surgically removed in Nagoya City University Hospital. The two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by real time polymerase chain reaction (PCR)-based assay. The data were confirmed by direct sequencing. In exon 9, somatic mutation was found in eight patients (3.4%). The mutation included three E542K (G1624A), three E545K (G1633A), one E542Q (G1624C), and one Q546K (C1636A). However, in exon 20, there was no mutation in our lung cancer patients. PIK3CA mutations were not correlated with gender (women versus men, p=0.4162), age (< or =60 versus >60, p=0.8027), or smoking status of the lung cancers (never versus smoker, p=0.5666). PIK3CA mutation incidence was significantly lower in adenocarcinoma (2/135, 1.5%) than in squamous cell carcinoma (5/77, 6.5%, p=0.0495). Among eight patients with a PIK3CA mutation, three patients also harbored an EGFR somatic mutation. PIK3CA gene mutations were rare in lung cancer; rarer in adenocarcinoma. Further functional analyses of the PIK3CA mutations are warranted to study if they could be the target of therapy for the lung cancer.
 ...
PMID:PIK3CA mutation status in Japanese lung cancer patients. 1693 Jul 67

Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.
 ...
PMID:Mutational analysis of the HER2 gene in lung tumors from Caucasian patients: mutations are mainly present in adenocarcinomas with bronchioloalveolar features. 1698 31

Epidermal growth factor receptor is over-expressed in several tumors and is the target for the tyrosine kinase inhibitor gefitinib. This receptor is also over-expressed in esophageal adenocarcinomas. In non-small cell lung cancer, specific somatic mutations residing in the epidermal growth factor receptor tyrosine kinase in the activation loop and the glycine-rich P-loop, are responsible for an enhanced sensitivity toward gefitinib. We analyzed exons 19 and 21 coding for the receptor tyrosine kinase of the epidermal growth factor gene in 105 samples of esophageal (Barrett's) adenocarcinoma by denaturing high-pressure liquid chromatography. We found only one silent mutation in exon 19 of adenine to guanine in codon 754 leading to a substitution of K to K, the rest of the sample being wild-type genotype. In conclusion, mutations within the tyrosine kinase domain of EGFR associated with sensitivity of non-small cell lung cancer patients to gefitinib are not present in esophageal (Barrett's) adenocarcinoma.
 ...
PMID:Lack of EGFR gene mutations in exons 19 and 21 in esophageal (Barrett's) adenocarcinomas. 1722 3

The usual primary endpoint in clinical trials for first-line chemotherapy in advanced non-small cell lung cancer is overall survival. Second-line chemotherapy can also prolong overall survival. Non-smoking history has been associated with a treatment effect for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) versus placebo for overall survival. We performed a retrospective analysis to identify prognostic factors for progression-free survival and overall survival in patients with advanced non-small cell lung cancer treated with first-line carboplatin/paclitaxel, and to examine the effect of second-line therapy on progression-free survival and overall survival. Ninety-eight patients (median age 61 years, 35 female, 74 adenocarcinoma, 68 smokers, 56 performance status 0) fulfilled our criteria, of which 75 patients (78%) received more than second-line therapy (docetaxel [54%] gefitinib [48%] erlotinib [4%]). For overall survival, smoking history and histology were significant prognostic factors. The 2-year overall survival rates were as follows: smokers, 17%; non-smokers, 52%, P < 0.0001; adenocarcinoma, 40%; other 15%, P = 0.0017. Multivariate analysis in patients who received second-line therapy showed treatment with EGFR-TKI was an independent predictor of overall survival. Smoking history and adenocarcinoma histology were prognostic factors for an improved outcome with carboplatin/paclitaxel in patients with non-small cell lung cancer. Our study results suggest that the use of EGFR-TKI after first-line treatment may be associated with an improvement in overall survival.
 ...
PMID:Influence of histological type, smoking history and chemotherapy on survival after first-line therapy in patients with advanced non-small cell lung cancer. 1723 40

Erlotinib, a potent inhibitor of the tyrosine-kinase (TK) activity of human epidermal growth factor receptor (HER1/EGFR), produces significant survival and quality of life benefits in patients with previously treated advanced-stage non-small-cell lung cancer. Although the survival benefit from erlotinib was observed in varied subgroups of patients, the radiographic responses were more common in certain patient subgroups, such as women, never-smokers, patients with adenocarcinoma histology, patients of Asian ethnicity, and patients with presence of HER1/EGFR TK domain mutations. Herein, we describe a white male former smoker with advancedstage squamous cell non-small-cell lung cancer, who responded to first-line erlotinib. A molecular analysis of the tumor did not reveal HER1/EGFR TK mutations. This case study, along with subgroup analyses of the BR.21 phase III study, suggests that patients should not be selected for erlotinib treatment based only on characteristics, such as smoking status, tumor histology, HER1/EGFR TK mutation status, sex, or ethnicity.
 ...
PMID:Response to erlotinib in first-line treatment of non-small-cell lung cancer in a white male smoker with squamous-cell histology. 1723 98

Lung cancer is the leading cause of cancer-related death in the United States. Although tobacco smoking accounts for the majority of lung cancer, approximately 10% of patients with lung cancer in the United States are lifelong never smokers. Lung cancer in the never smokers (LCINS) affects women disproportionately more often than men. Only limited data are available on the etiopathogenesis, molecular abnormalities, and prognosis of LCINS. Several etiologic factors have been proposed for the development of LCINS, including exposure to radon, cooking fumes, asbestos, heavy metals, and environmental tobacco smoke, human papillomavirus infection, and inherited genetic susceptibility. However, the relative significance of these individual factors among different ethnic populations in the development of LCINS has not been well-characterized. Adenocarcinoma is the predominant histologic subtype reported with LCINS. Striking differences in response rates and outcomes are seen when patients with advanced non-small-cell lung cancer (NSCLC) who are lifelong never smokers are treated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors such as gefitinib or erlotinib compared with the outcomes with these agents in patients with tobacco-associated lung cancer. Interestingly, the activating mutations in the EGFR-TK inhibitors have been reported significantly more frequently in LCINS than in patients with tobacco-related NSCLC. This review will summarize available data on the epidemiology, risk factors, molecular genetics, management options, and outcomes of LCINS.
 ...
PMID:Lung cancer in never smokers: a review. 1729 53

Malignancies arising from the pancreatic and biliary ductal systems present the gastroenterologist and pathologist with diagnostic challenges. Tumors of the pancreatic and/or biliary ductal system may present as either duct strictures or mass lesions. When lesions present as strictures without associated demonstrable masses, brushing cytology may represent the only reasonable diagnostic technique aside from open biopsy. Diagnostic sensitivities for brushing cytology have ranged from 18 to 90%. Positive diagnoses of malignancy are of great clinical value but a negative result is of relatively little clinical aid when the radiographic or clinical findings are suspicious for a malignancy.A variety of techniques have been used in an attempt to improve diagnostic sensitivity for brushing cytology. These have included immunohistochemistry and various molecular diagnostic techniques. Using the high resolution melting curve technique, we performed mutational analysis on 20 bile duct brushing specimens for mutations in p53, K-ras, BRAF, and EGFR genes. Eleven specimens had corresponding surgical specimens, which were similarly analyzed. Our series included twelve adenocarcinomas, one islet cell tumor, one case of dysplasia, and six benign cases. K-ras mutations were found in cytology specimens of 3 out of 12 malignancies. No EGFR or B-raf mutations were detected and only a single p53 mutation in an adenocarcinoma was detected in the corresponding cytology specimen. No mutations were detected in benign lesions or in the dysplasia. Only 8% of specimens from adenocarcinomas had p53 mutations and only 33% of cases had K-ras mutations. Mutational analysis did not appear to improve the cytologic detection of adenocarcinoma by bile duct brushings.
 ...
PMID:Molecular diagnostic testing as an adjunct to morphologic evaluation of pancreatic ductal system brushings: potential augmentation for diagnostic sensitivity. 1735 44

The patient was a 39-year-old woman admitted with complaints of fever, clubbed fingers and arthralgia. A chest roentgenogram and chest computed tomographic scan revealed a mass in the left lower lobe. Transbronchial lung biopsy was performed, and a diagnosis of moderately differentiated adenocarcinoma was made. Physical examination confirmed finger clubbing in both hands. Bone scintigram showed marked accumulation of 99mTc-MDP in the long bones, bones of the elbows, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in young adult. The patient had fever and disturbance of gait of arthralgia on admission, and was treated with an oral non-steroidal anti-inflammation drug (NSAID). Advanced non small cell lung cancer (clinical stage T2 N3 M1, Stage IV) was then diagnosed. Gefitinib was administered after EGFR mutation was found in the tumor specimen. NSAID therapy alleviated the fever and arthralgia. After starting gefitinib and discontinuing the NSAID, She had kept a remission of rational symptom with cytoreductive effect. The abnormal findings of bone scintigrams subsequently disappeared and the patient's serum ICTP dropped.
 ...
PMID:[A case of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in a young adult successfully treated with gefitinib]. 1735 79

EGFR-TKI has been synthesized as a potential target for cancer therapy because EGFR is overexpressed and associated with poor prognosis of lung cancer. It was reported that EGFR mutations were more sensitive to EGFRTKI than those without the mutations among lung cancer patients. A subgroup of patients of Asian origin, female sex, adenocarcinoma, and no history of smoking were significantly associated with a high rate of EGFR mutations. These patients with EGFR mutations were not only favorable responders but also had a longer survival than without. In this article, we discuss the EGFR-TKI predictive factors by EGFR mutations.
 ...
PMID:[Prediction of effectiveness of EGFR tyrosine kinase inhibitors for the patients with by EGFR mutations]. 1743 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>