Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical response to Gefitinib (Iressa, ZD1839) has been found to be associated with somatic mutations, primarily of exons 18-21, of the epidermal growth factor receptor gene (EGFR) in non-small cell lung cancer (NSCLC). Evidence of a positive response was also reported recently on a patient with brain metastasis from NSCLC. On the other hand, amplification of EGFR appears to be associated with a poor prognosis. To determine whether EGFR mutations and amplification are involved in the tumorigenesis of brain metastases, we performed polymerase chain reaction/single-strand conformation polymorphism to examine exons 1, 2, and 7-26 of EGFR in a series of 18 brain metastases. The metastases derived from malignant melanoma (three cases), lung carcinoma (six cases), breast carcinoma (three cases), ovarian carcinoma (two cases), and one each from colon, kidney, bladder, and undifferentiated carcinoma. In addition to several sequence polymorphisms, we identified two mutations on E19 consisting of 18-base pair (bp) deletions: 2423-24440del and 2426-2443del. These mutations presented in lesions derived from kidney carcinoma and lung adenocarcinoma. By real-time quantitaive polymerase chain reaction technique, we determined the amplification/overdose status of EGFR by analyzing exons 11 and 25. Amplification (5- to 100-fold) was identified in three tumors, and overdose (low-level gene amplification corresponding to increases of 1- to 5-fold) presented in four additional metastases. These findings suggest that EGFR mutations and polymorphisms are not exclusively present in metastases derived from lung carcinoma. Accordingly, targeting of EGFR to determine molecular alterations of this gene may be useful in the management of patients with brain metastases.
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PMID:EGFR sequence variations and real-time quantitative polymerase chain reaction analysis of gene dosage in brain metastases of solid tumors. 1728 72

The expression of EGFR, HER2 and HER3 receptors were analyzed in immunohistochemical preparations from primary esophageal tumours and corresponding lymph node metastases. The goal was to evaluate whether any of these receptors are suitable as targets for radionuclide based imaging and therapy. The receptor expressions were evaluated in parallel samples, primary tumour and metastasis, from each patient (n=51). The majority of the cases were esophageal squamous cell carcinomas, ESCC (n=40). The HercepTest scoring was used for the analysis of both HER2 and EGFR expression (0, 1+, 2+ or 3+). HER3 was only evaluated as negative, weak or strong staining. EGFR overexpression (2+/3+) was found in 67.5% (27/40) of both the ESCC primary tumours and the corresponding lymph node metastases. There were only a few changes in these EGFR-scores: two cases from 2+/3+ to 0/1+ when the primary tumours were compared to the corresponding metastases and 2 changes the other way around. HER2 overexpression (2+/3+) was found in only 3 of the primary ESCC tumours and 2 of the lymph node metastases. EGFR and HER2 stainings were found mainly in the cell membranes. The HER3 staining (weak or strong) was mainly cytoplasmic and granular and was observed in about half (20/39) of the cases, for both the ESCC primary tumours and the corresponding lymph node metastases. It was concluded that ESCC lymph node metastases generally have a strong expression of EGFR in their cell membranes and to the same extent as in the primary tumours. The stability in EGFR expression is encouraging for efforts to develop radionuclide based EGFR imaging agents. It is also possible that EGFR targeting agents (e.g. Iressa, Tarceva, Erbitux or radiolabelled antibodies) can be applied for therapy of ESCC.
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PMID:EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases. 1767 74

The expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) was analyzed in immunohistochemical preparations from 46 primary parotid mucoepidermoid carcinomas (MEC). For the cases with lymph node metastases, the receptor expressions were investigated in parallel samples, primary tumour and metastasis, from each patient (n=11). The goal was to evaluate whether any of these receptors are suitable as a target for radionuclide-based imaging and therapy. The HercepTest scoring was used for the analysis of both HER2 and EGFR expression (0, 1+, 2+ or 3+). EGFR overexpression (2+/3+) was found in 67.4% (31/46) of the primary tumours. Out of the 11 cases with evaluated paired samples, EGFR overexpression was observed in 81.8% (9/11) of the primary tumours and 72.7% (8/11) of the corresponding lymph node metastases. There was only one patient who had EGFR overexpression in the primary tumours which changed to negative in the lymph node metastases but no changes occurred reciprocally. The HER2 overexpression was only found in 4.3% (2/46) of the primary mucoepidermoid carcinoma and none of the lymph node metastases (0/11). EGFR and HER2 stainings were mainly found in the cell membranes. It was concluded that the majority of parotid mucoepidermoid carcinomas express EGFR strongly in their cell membranes and that lymph node metastases generally express EGFR to approximately the same extent as in the primary tumours. The stability in the EGFR expression is encouraging in the effort to develop radionuclide-based EGFR imaging agents. It is also possible that EGFR targeting agents (e.g. Iressa, Tarceva, Erbitux or radiolabelled antibodies) can be applied for the therapy of mucoepidermoid carcinoma.
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PMID:Epidermal growth factor receptor and human epidermal growth receptor 2 expression in parotid mucoepidermoid carcinoma: possible implications for targeted therapy. 1820 92

Lung cancer is the most common cancer and a highly lethal disease, with improvements in survival rates being dependent on advances in early detection and improved systemic therapies applied to surgery and/or irradiation in early-stage disease. Non-small cell lung cancer (NSCLC) represents around 80% of all lung cancers, and unfortunately at diagnosis most patients have advanced unresectable disease with a very poor prognosis. Indeed, 30%-40% of patients treated with first-line therapy will subsequently be candidates for second-line treatment. Current U.S. Food and Drug Administration-approved second-line treatments are docetaxel (a taxane), pemetrexed (a folate antimetabolite), and erlotinib (an epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]). Gefitinib, another EGFR TKI, currently has only limited use in North America and is not available in Europe. These and other new molecular-target-specific agents may have the potential to maximize therapeutic benefit while minimizing toxicity to normal cells. Overexpression of EGFR is reported to occur in 40%-80% of NSCLC cases, and EGFR mutations are associated with a significantly higher response rate and longer duration of response following treatment with EGFR TKIs. Another option is antiangiogenesis: the growth and persistence of solid tumors and their metastases are angiogenesis dependent, and so antiangiogenic therapies have been developed, such as the use of TKIs that block the vascular endothelial growth factor receptor. In fact, many commonly used chemotherapeutic drugs have antiangiogenic activity. Ongoing studies are focusing on patient selection and targeted therapies, and there are many new agents undergoing clinical trials.
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PMID:Systemic treatment for advanced (stage IIIb/IV) non-small cell lung cancer: more treatment options; more things to consider. Introduction. 1826 68

A 61-year-old woman who had never smoked was given a diagnosis of adenocarcinoma of the lung with multiple pulmonary metastases. Systemic chemotherapy consisting of carboplatin and paclitaxel was not effective, thereafter daily oral administration of gefitinib was initiated. Six days later, bilateral pneumothorax was found. The extent of the pneumothorax was slight and she recovered without drainage within about one month although treatment of gefitinib was restarted. Gefitinib was effective for lung cancer in this case. Bilateral pneumothorax is a rare complication of chemotherapy for lung cancer. Only 3 such cases under treatment with gefitinib were reported in Japan.
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PMID:[Case of bilateral pneumothorax observed during the administration of gefitinib for lung adenocarcinoma with multiple pulmonary metastases]. 1859 95

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib improves survival of lung cancer as second- or third-line therapy. However, after an initial response, most patients will recur, particularly within the central nervous system. The present study reports the case of a 27-yr-old nonsmoking male presenting with a metastatic lung adenocarcinoma with EGFR exon 19 deletion, associated with sensitivity to EGFR-TKI. Gefitinib, followed by chemotherapy and finally erlotinib resulted in prolonged disease control, until multiple liver metastases were detected. After stopping EGFR-TKI, brain metastases with carcinomatous meningitis were diagnosed. A secondary T790M mutation, associated with resistance to EGFR-TKI, was found on the liver biopsy but not in the cerebrospinal fluid. Erlotinib was reintroduced and allowed a quick neurological improvement, even though the extra-cranial disease remained resistant to erlotinib. The present report underscores the interest of molecular monitoring in lung cancer. Persistent cerebral tyrosine kinase inhibitor sensitivity should be considered in patients presenting with an early central nervous system relapse after stopping epidermal growth factor receptor tyrosine kinase inhibitor, even with a T790M-resistant mutation in noncerebral metastases. Questions remain concerning the selection of sub-clones during epidermal growth factor receptor tyrosine kinase inhibitor therapy, which could differ according to metastatic sites, especially in the central nervous system.
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PMID:EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up. 1918 17

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is effective in treating patients with non-small cell lung cancer (NSCLC) after unsuccessful chemotherapy. However, survival outcomes and predictors for its effectiveness in chemotherapy-naive NSCLC patients are still not clear. The goal of this study was to investigate the response and survival rates and identify the predictive factors for patients with advanced or metastatic disease receiving gefitinib as first-line therapy. We retrospectively analyzed the response and survival rates of patients with advanced or metastatic NSCLC who had received gefitinib as first-line therapy across six medical institutes in Southern Taiwan between May 2004 and April 2006. The relationship between the response and survival rates to the known predictive factors for gefitinib response and survival was also investigated. A total of 97 patients (65 females and 32 males) were enrolled in this study. Seventy-four patients (76%) had never smoked. Eighty-eight patients (91%) had adenocarcinoma or bronchioloalveolar cell carcinoma. The objective response rate was 56% and the disease control rate (partial response plus stable disease) was 76%. Only poor performance status (Eastern Cooperative Oncology Group score, 3-4) was statistically significantly associated with overall response in this study. The 1-year survival rate was 77%. We suggest that first-line gefitinib monotherapy is promising in some subgroups of Asian patients with NSCLC. Further randomized controlled studies are needed to validate the effectiveness of first-line gefitinib therapy.
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PMID:Gefitinib as first-line therapy for advanced or metastatic non-small cell lung cancer patients in southern Taiwan. 2004 Apr 66

Non-small-cell lung cancer (NSCLC) is a heterogeneous illness associated with a high mortality rate. Personalized therapy may improve treatment outcomes by identification of a specific genotypic anomaly and target-specific therapy. The most significant development in recent years was the discovery of activated EGF receptor (EGFR) mutations at exons 19 and 21. Patients with EGFR mutations respond dramatically to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib, resulting in longer progression-free survival. Multiple randomized studies, including the Iressa Pan-Asia Study and WJTOG3405, have confirmed the role of EGFR tyrosine kinase inhibitors as standard first-line therapy for patients with the EGFR mutation. In this article, we summarize the current nonpersonalized therapies and examine the available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, or metastatic disease.
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PMID:Personalized medicine for non-small-cell lung cancer. 2094 31

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including the lung malignancy. Genetic modifications such as deletions, insertions and Single Nucleotide Polymorphisms in the tyrosine kinase (TK) domain of EGFR is a common feature observed in most lung cancers. Gefitinib and erlotinib are commonly available therapeutic drugs which act as specific inhibitors for the tyrosine kinase domain of EGFR and associated with EGFR mutations in exons 18-21. However the prevalence of mutation varies among ethnicity, grade, age and gender. This is the first report on the prevalence of EGFR mutation in non-small cell lung cancer patients using DNA obtained from samples such as biopsy/cytology/pleural fluid and Fine Needle Aspiration (FNA), across India. We have screened for 29 somatic mutations which span exons 18, 19, 20 and 21 of EGFR gene using Scorpion probe based ARMS-PCR technique. DNA from 220 NSCLC tissue samples were analyzed for EGFR mutations and mutations were detected in 51.8% of the study population. Among the mutant positive cases, the deletions in exon 19 (52%) and a missense mutation L858R in exon 21 (26%) were most predominant. There was a significant increase in overall mutations (p=0.01) as a function of age, mutation in exons 19 and 21 together (p=0.003), mutations in exons 18, 19 and 21 (p=0.04) and mutations in exons 18 and 19 (p=0.03) in females. Mutations did not seem to significantly correlate metastases or disease progression. Mutations in exons [19] and 21 together were significant in non-smokers compared to smokers (p=0.01) using Mann-Whitney tests. The study suggests high prevalence of EGFR positivity in NSCLC in Indian sub-population and provides opportunities for targeted therapies for this group.
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PMID:Screening for EGFR mutations in lung cancer, a report from India. 2199 90

Enteritis is one of the side effects of radiotherapy to the abdominal cavity. Radiation enteritis involves damage to mucous membranes in the acute phase and to stromal tissues in the late phase. Perforation of the intestine tends to occur in the late phase, and rarely in the acute phase. However, we describe here a case of intestinal perforation occurring in the acute phase after irradiation in a patient who received gefitinib treatment. Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is widely used to treat non-small cell lung cancer (NSCLC) patients, but is simultaneously known to inhibit wound healing. We suspect that gefitinib may affect regeneration of the small intestinal mucosa injured by irradiation. A 76-year-old woman had NSCLC with metastases to the 5th lumbar, sacral, and right iliac bones. To control the pain from bone metastasis, anterior-posterior opposing portal irradiation (total 35 Gy) was started, and was completed over 22 days. On day 25 after starting radiotherapy, the patient began to take gefitinib. On day 35, she presented with acute peritonitis, and an emergency laparotomy was performed. The terminal ileum was affected by radiation enteritis and there were two pin-hole perforations. In the surgical specimen, no cancerous lesions were detected, and immunohistochemical staining of phosphorylated EGFR (pEGFR) was negative. pEGFR has an important role in mucous membrane repair after irradiation. Intestinal perforation in the acute phase of radiation enteritis may be associated with impaired mucosal repair mechanisms due to the use of an EGFR-TKI such as gefitinib, as evidenced by the absence of pEGFR.
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PMID:Ileal perforation induced by acute radiation injury under gefitinib treatment. 2170 25


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