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)

In the present study, we aimed to clarify the potential of oncogene amplifications as markers for the prediction of (i) (relapse-free) survival, (ii) response to first-line endocrine therapy and (iii) subsequent chemotherapy in patients with recurrent breast cancer. To attain this goal, amplification of different oncogenes (HER-2/neu, c-MYC and INT-2) was studied in primary tumors of a series of 259 patients with breast cancer (median follow-up of 72 mo). Of these tumors, 49.8% did not contain an amplification of any of the oncogenes studied, whereas in the amplified subgroup, INT-2 was amplified in 13%, HER-2/neu in 24% and c-MYC in 20% of the tumors. In univariate analysis, INT-2 amplification was associated with an increased risk of relapse (p < 0.03), especially in the subgroups of 85 node-negative (p = 0.05) and 156 ER/PgR-positive patients (p = 0.01). Cox multivariate regression analysis showed that c-MYC was the only oncogene whose amplification was significantly related with the rate of relapse. With respect to amplification in patients developing metastatic disease, who received first-line hormonal therapy (n = 114), HER-2/neu amplification was associated with a less favorable response to endocrine therapy (objective response rate only 17% and a progression-free survival (PFS) of only 4% at 12 mo). Interestingly, distinct INT-2 amplification might predict a better response to endocrine therapy (objective response rate of 56%, and a PFS after relapse of 42% at 12 mo).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oncogene amplification and prognosis in breast cancer: relationship with systemic treatment. 760 64

The records of 3,795 cases of malignant melanoma treated at the INT (Milan) from 1975 to 1992 were reviewed. Histologic confirmation was obtained in all cases. Thirty-one patients (0.82%) with solitary or multiple skeletal metastases were identified. The review of conventional films, tomograms, CT, MR and bone scintigraphy images enabled us to detect 120 single bone lesions. The X-ray features were divided into two groups according to typical and atypical skeletal lesions. Typical bone metastases are osteolytic (87.5%), with medullary origin (91.6%), and they cannot be distinguished from other osteolytic metastases on the basis of imaging criteria alone. Lesion growth causes cortical erosion and destruction (46.6%), pathologic fractures (22.5%) and soft tissue involvement (12.5%). Lytic areas usually have ill-defined margins. Clear-cut outline is an uncommon finding. Atypical skeletal metastases exhibit a mixed osteolytic-osteoblastic pattern (10%), which is hardly ever completely osteoblastic (2.5%). Other unusual metastatic patterns include intense trabecular rarefaction with no detectable single lesion (3.3%), the presence of a well-defined sclerotic rim and periosteal reaction (12.5%). Atypical growth may cause extensive cortical destruction and periosteal production resembling osteogenic osteosarcoma. The various imaging methods show that conventional radiology has relatively poor sensitivity because of anatomical reasons, while MRI is the most sensitive method to detect skeletal localizations. Treatment changes the radiologic patterns of the lesions: recalcification, sclerotic rim, periosteal reaction are common response patterns. Finally, in spite of the above limitations, conventional radiology remains the method of choice to assess lesion evolution during the follow-up.
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PMID:[The radiodiagnosis of bone metastases from melanoma]. 804 25

Between 1964 and 1990 inclusive, 204 consecutive naive patients with penile cancer and 14 patients with recurrence in the inguinal nodes have been referred at INT, Milano. Nodal metastases occurred in 100% of category T3, T4 patients, in 82% T2, in 60% G2-3 T1 and only in 16.5% of G1 T1. Out of the 47 patients who had primary ileoinguinal lymphadenectomy, 16 (34%) had negative nodes, versus 100% metastases in the 25 patients operated during the follow-up. The relapse rate was 45% in the 31 patients treated only surgically in the 1964-77 period, versus 16% in the 25 cases submitted to adjuvant chemotherapy between 1978 and 1990. All 4 relapses in the adjuvant treatment group occurred in the 8 patients with bilateral metastases. Twenty-six patients had fixed inguinal nodes: the first 10 were treated with radiotherapy, with or without methotrexate or bleomycin, and the last 16 have been submitted to neoadjuvant chemotherapy. Only one patient of the first group could be operated and all 10 died of cancer within 3 years. On the contrary, 9 (56%) of the 16 patients treated with neoadjuvant chemotherapy could undergo subsequent surgery and 5 (31%) are alive disease free since over 5 years. Prophylactic lymphadenectomy may be indicated in all T2, T3, T4 patients and in indifferentiated T1 tumors. Adjuvant and neoadjuvant chemotherapy can improve the results of radical surgery, significantly.
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PMID:[Treatment of lymphatic metastasis of squamous cell carcinoma of the penis: experience at the National Tumor Institute of Milan]. 876 5

Oncogene amplification is frequent in many epithelial tumors and often associated with advanced tumor progression. In different epithelial neoplasias it helps to provide prognostic information on individual patients. The present study was performed to evaluate the hitherto unknown prevalence of INT-2 gene amplification and its potential usefulness as prognostic marker in patients with human thyroid cancer. We used differential quantitative polymerase chain reaction and fluorescent DNA technique as a reliable method to detect low copy-number amplification of oncogenes from archival carcinoma specimens. Sequences from the int-2 gene and the single copy gamma-interferon gene were amplified simultaneously by PCR and quantified on a fluorescence activated sequencer. Native tumor tissue from 63 patients with differentiated thyroid cancer (43 papillary, 3 oncocytary, and 17 follicular) and from 12 goiters was analyzed by differential quantitative polymerase chain reaction. The study group contained many far advanced tumors. 40% of tumors were recurrent, 35% were staged T4 tumors and 70% presented with lymph node metastases. The prevalence of INT-2 amplification was 12% for follicular and 7% for papillary carcinomas. In goiter tissue no amplification was found. Amplification was only 2-4fold in positive cases. Low grade amplification is of no apparent importance in differentiated thyroid cancer.
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PMID:INT-2 gene amplification in differentiated human thyroid cancer. 898 Oct 13

The Italian Oncology Group for Clinical Research tested two experimental chemotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-two patients were randomly allocated as follows: (a) to the conventional cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intensification program (SEQ-INT). The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly higher complete response (32% vs. 6%, p = 0.0006) and objective response rate (72% vs. 42%, p = 0.0047) than CMF did. There were no differences in survival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, but the treatments were generally tolerable. Although some caution is required when interpreting a significant advantage found between an entire chemotherapeutic strategy and a single conventional combination, this study documents the potential therapeutic advantage of administering different sequential chemotherapies, and changing each at the time of maximum result without waiting for a progression. The impressive cytoreductive effects achievable with this policy (SEQ-INT) in metastatic disease merit further investigation in the adjuvant setting.
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PMID:Comparison of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) with a rotational crossing and a sequential intensification regimen in advanced breast cancer: a prospective randomized study. 1059 44

Radiation therapy has been used in the treatment of patients with gastric cancer in two clinical settings: definitive therapy for locally advanced, unresectable tumors and adjuvant therapy following surgery for high-risk disease. For patients with locally advanced, unresectable or subtotally resected gastric carcinoma, radiotherapeutic approaches with and without chemotherapy have been employed, because these tumors appear localized, without clinically detectable metastases. Combined treatment with radiation therapy and chemotherapy appears to prolong survival but rarely results in long-term cure. Although only a modest effect was seen on survival, importantly, these studies established the foundation of contemporary combined-modality therapy and have served to stimulate further clinical investigation in gastric cancer as well as other gastrointestinal disease sites. For patients undergoing resection and lymphadenectomy with curative intent, the development of local or regional failure is common, occurring in 40% to 65% of patients. Sites of local and regional failure following resection include the gastric/tumor bed in 20% to 55%, the anastomosis in 25% to 50%, and the regional nodes in 40% to 50% of patients. Intergroup Trial 0116 (INT 0116), a phase III trial, has recently demonstrated that adjuvant radiation therapy with concurrent and maintenance 5-fluorouracil (5-FU) and leucovorin (LV) reduces local failure and improves survival. Adjuvant therapy is now routinely administered to patients undergoing resection of gastric cancer for high-risk disease. Ongoing trials are now investigating new systemic agents with radiation therapy to establish efficacy compared to 5-FU and LV, as well as evaluating neoadjuvant approaches prior to resection.
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PMID:Results of radiation therapy in gastric cancer. 1197 18

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing in association with the epidemiologic rise in distal esophageal adenocarcinoma and gastric cardial (AEG type III) tumors. The overall survival rate is poor in most patients with AEG because lymph node or visceral metastases are frequently present at the time patients become symptomatic. A few patients are identified early in the disease because of screening for gastroesophageal reflux and Barrett's esophagus. Early stage AEG (T1N0 or T2NO, carcinoma in situ, or severe dysplasia ) can in many instances be cured with surgery alone. Ablative treatments for early stage AEG, including endoscopic fulguration by cautery and laser or photodynamic therapy, are investigational at this time. Locoregionally advanced AEG (T3, T4, N1, or M1a ) without distant systemic metastases (M1b) has a poor overall survival rate with surgery alone or definitive chemotherapy and radiation therapy without surgery. Analysis of the use of multimodality treatment strategies for locoregionally advanced AEG types I and II have demonstrated improved survival rates in two small phase III trials with preoperative concurrent chemoradiotherapy followed by surgical resection. In contrast, three small phase III trials with preoperative concurrent or sequential chemoradiotherapy in patients with predominantly squamous cell carcinoma did not demonstrate any clear survival advantage. Additionally, a randomized phase III study evaluating preoperative chemotherapy without radiation therapy in esophageal cancer (predominantly adenocarcinoma) has demonstrated no survival benefit. In light of these results, additional large randomized phase III studies are needed to confirm the potential benefit of preoperative concurrent chemoradiotherapy. At the present time, preoperative chemoradiotherapy remains investigational. For locoregionally advanced gastric adenocarcinoma, including AEG type III, postoperative concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy is associated with improved survival as demonstrated in a recently completed random assignment trial (INT 0116). As a result, surgery with postoperative chemoradiotherapy has recently become the standard of care for patients with AJCC stage II and III gastric adenocarcinoma (including patients with AEG type III). Metastatic AEG (M1b) should be treated with palliative chemotherapy (in good performance patients) or supportive care (poor performance) in asymptomatic patients. Radiation therapy and endoscopic stent placement (expandable wire mesh) can be used to palliate dysphagia in patients with M1b disease. The development of expandable stents and improved radiotherapy has obviated surgical bypass to palliate patients with symptomatic, metastatic AEG.
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PMID:Gastroesophageal junction adenocarcinoma. 1205 46

In the treatment of advanced prostate cancer, androgen ablation has proven to be the cornerstone. Several important questions about its use, however, remain unanswered. The first question is whether androgen ablation should be started at the time of diagnosis, or when symptoms arise. Although previous evidence had suggested no benefit to early therapy, a recent large trial of patients has shown clear benefit. Patients with locally advanced and asymptomatic metastatic disease were randomly assigned to early treatment, or treatment started at signs of progression: the early treatment group showed benefit in time to progression, incidence of severe complications, and time to death. The other major unresolved issue is the type of androgen ablation to be used. Maximal androgen blockade (MAB) has been shown to increase the survival of patients with metastatic disease in a least two large, well-conducted trial, although other trials have contradicted this finding. A recent meta-analysis of 22 MAB trials containing more than 5000 patients has suggested that MAB does not prolong life. A large trial by the National Cancer Institute (NCI) NCI INT-0105, from which preliminary results are now available, has shown that castration and an antiandrogen is no better than castration alone in terms of time to progression and survival. This trial, furthermore, did not find that MAB was superior in low-volume, good-performance status patients. Androgen ablation is not a cure for advanced prostate cancer, but it does provide excellent palliation. New treatment regimens, and new studies, are needed to optimize treatment for these men.
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PMID:A review of hormonal treatment in advanced prostate cancer. 1273 38

The curative management of gastric adenocarcinoma depends on complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared with less extensive operations. Until recently, attempts at preventing recurrence, usually using adjuvant chemotherapy, have been ineffective. A large United States Intergroup study (INT-0116) showed that combined chemoradiation following gastric resection improves median time to relapse (30 months v 19 months, P <.0001) and overall survival (35 months v 28 months, P =.01). This treatment has become a standard of care. Future advances in the therapy for resectable gastric cancer may come from studies of preoperative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and anti-angiogenesis agents.
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PMID:Adjuvant therapy for gastric cancer. 1450

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large US Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 v 19 months, P <.0001) and overall survival (35 months v 28 months, P =.01). The improvements in disease-free and overall survival created by postoperative chemoradiation have defined a new standard of care. Also the publication of a large phase III neoadjuvant chemotherapy clinical trial using epirubicin, cisplatin, and 5-fluorouracil (5-FU) suggested that this technique may downstage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of preoperative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and antiangiogenesis agents.
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PMID:Treatment of localized gastric cancer. 1529 47


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