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)

A 49-year-old woman had a right adrenalectomy for pheochromocytoma in April 1989. In May 1990 she underwent an operation to remove paraaortic lymph nodes, and the lymph nodes showed pheochromocytoma. Twenty-two months after the first operation, metastases to the left cervical nodes, lung, and liver occurred. Her blood pressure was 172/104 mmHg; fasting plasma glucose (FPG), 342 mg/dl; urinary noradrenaline (NA), more than 2000 micrograms/day; and plasma NA, 17.28 ng/ml. Treatment with the CVD regimen (cyclophosphamide, 750 mg/m2 on day 1; vincristine, 1.4 mg/m2 on day 1; dacarbazine, 600 mg/m2 on days 1 and 2, every 21 days) was begun on February 14, 1991. After 3 cycles of the CVD regimen her blood pressure was 140/82 mmHg; FPG, 157 mg/dl; urinary NA, 917 micrograms/day 1; and plasma NA, 4.54 ng/ml. The size of the metastatic lesions in the liver had decreased. Treatment with the CVD regimen was continued until May 1992. After that she did not go to the hospital for about 2 months. Metastatic lesions progressed gradually and treatment with the CVD regimen was repeated again. She was admitted to the hospital on February 17, 1993 because of appetite loss and nausea. Her blood pressure was 188/94 mmHg; FPG, 197 mg/dl; HbA1c, 9.5%; urinary NA, 18265.3 micrograms/day; and plasma NA, 47.20 ng/ml. She was treated with the CVD regimen in 2 repeated cycles (28th cycle of treatment with the CVD regimen) but there was no effect. She died following hemoptysis on March 15, 1993.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of malignant pheochromocytoma treated with a combination of cyclophosphamide, vincristine, and dacarbazine (CVD). A review of the Japanese literature of malignant pheochromocytoma treated with a combination of CVD]. 785 22

The postoperative course of 159 patients with early gastric cancer operated on between 1974 and 1987 was followed for a median of 7.3 years. The cumulative 10-year survival rate(s.e.) calculated using follow-up data to the end of 1989 was 90.6(2.7) per cent excluding operative death and that from causes other than gastric cancer, or 86.3(3.0) per cent when operative mortality was included. The overall 10-year survival rate(s.e.) was 77.3(3.7) per cent. Univariate analysis showed a significant difference in survival rates between cancers confined to the mucosa and those with submucosal invasion (P = 0.02), between patients with and without lymph node metastases (P = 0.05) and between those < or = 50 and > 50 years of age (P = 0.02). Using Cox multivariate analysis and a stepwise procedure for eight variables (sex, age, depth of invasion, lymph node metastases, presence of ulceration, location, histological type, type of surgery), age and histological type had the most significant effect on survival. Seven operative deaths were recorded. Eleven patients died from recurrent cancer and one is still alive with a gastric remnant recurrence. Other causes of death were metachronous primary cancer (six patients), cardiovascular disease (two), pneumonia (three), sepsis (one) and car accident (one). Although the prognosis of early gastric cancer is relatively good in western countries, patients should be carefully followed over a long period for late recurrence and for metachronous cancer, which has a high incidence.
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PMID:Early gastric cancer: follow-up after gastrectomy in 159 patients. 847 41

The postoperative course of 172 patients with early gastric cancer (EGC) was followed for a median 7 years to evaluate the causes of death, incidence and patterns of recurrence, and characteristic findings in the recurrent cases. The cumulative 10-year mortality rate (+/- SE) was 22 +/- 3.7%. Seven patients (4.1%) died of operative mortality, 11 (6.4%) died of a recurrence of the gastric cancer and 13 (7.6%) died of unrelated causes. Unrelated causes of death were metachronous primary cancer (n = 6), cardiovascular disease (n = 2), pneumonia (n = 3), sepsis (n = 1), and car accident (n = 1). Four patients died from gastric stump recurrence, three from liver metastases, two from lymph node metastases, and two from peritoneal dissemination. Using Cox multivariate analysis, histologic type had the most significant effect on recurrence. Although influenced by the tumor nature, the EGC prognosis is relatively good. Based on the results of this study, particularly in Western institutions, histologic examination of resection margins and lymphadenectomy should be improved. Moreover, patients must be carefully followed for late recurrence and metachronous cancer.
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PMID:Causes of death and recurrence after surgery for early gastric cancer. 914 77

Angiogenesis is the proliferation of endothelial and smooth muscle cells to form new blood vessels. Largely muted after adolescence, angiogenesis may be reignited by cancerous cells. Neoangiogenesis plays a primary role in tumor growth and metastases. Antiangiogenic therapy to limit and even reverse the growth of tumors are under investigation and showing promise. A derivative of fumagillin, TNP 470, is the first angiogenesis inhibitor to be given to humans. Surprisingly, several potent inhibitors are derived from tumors themselves. Researchers nowc recognize that stimulation of angiogenesis may have a place in the treatment of cardiovascular disease. Reestablishing blood flow to ischemic tissue through angiogenesis may provide a biologic "bypass" for patients with ischemic heart disease. The same applies to the treatment of peripheral vascular disease.
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PMID:Regulating angiogenesis: a new therapeutic strategy. 980 69

Microorganisms have evolved a variety of mechanisms designed to evade detection and/or destruction by the host. Many pathogens evade host defenses by invading cells, thus providing the bacterium with an environment free of competing microorganisms. Adherence and invasion are active processes in which microorganisms often use host proteins and enzymes to gain entry into the cell, thus stimulating their own uptake. The investigation of invasion by the periopathogen Porphyromonas gingivalis is in its infancy in comparison with that of the enteric pathogens. However, recent studies with P. gingivalis have revealed that these organisms have developed invasion strategies and mechanisms similar to those of the enteric pathogens for both epithelial and endothelial cells. The study and elucidation of the mechanisms by which microorganisms such as P. gingivalis persist in chronic infection will provide valuable insight into the pathogenesis of P. gingivalis-mediated periodontal disease. The ability to multiply in and to activate endothelial cells may be one of the pathogenic mechanisms exerted by P. gingivalis that may explain the recently described association between this organism and cardiovascular disease.
Invasion Metastasis
PMID:Invasion strategies of the oral pathogen porphyromonas gingivalis: implications for cardiovascular disease. 1036 86

For melanoma, in-transit metastases (ITMs) are a harbinger of systemic disease in over 70% of patients and thus warrant a systemic approach to management. In this study, previously untreated patients with ITMs (n=15) received a systemic regimen of 'CVD' in 21 day cycles (median, three cycles) as follows: dacarbazine 800 mg/m2 intravenously (i.v.) on day 1, vinblastine 1.6 mg/m2 i.v. on days 1-5, and cisplatin (CDDP) 100 mg/m2 by 24 h intra-arterial (i.a.) infusion in 1l of heparinized saline via the iliac or subclavian artery on day 3. There were three clinical complete responses (CRs) in patients with a modest burden of ITMs (< 3 cm in size) and seven partial responses (PRs), yielding a 67% response rate (95% confidence interval, 38-88%). One of the clinical CRs had microscopic residual disease at surgery (a pathological PR). The times to progression (TTP) for the CRs were 5, 21 and 38+ months; the median TTP for the PRs was 4.5 months (range, 2-10 months). Overall median survival was 31 months. Systemic toxicities were similar to those induced by i.v. CVD. However, patients noted more pronounced paraesthesia in the infused extremity. Also, two patients experienced severe CDDP-induced burns, one patient developed brachial plexopathy, and one patient had a haemorrhage in an occult brain metastasis. The high clinical activity of this regimen will have to be confirmed in more patients before a first-pass i.a. advantage can be claimed. Furthermore, the dose, schedule and technique of i.a. CDDP delivery must be further refined before it can be routinely incorporated in regimens as an alternative to isolated regional hyperthermic perfusion, which is technically more difficult and is not readily available in community-based hospitals.
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PMID:Pilot study of intra-arterial cisplatin and intravenous vinblastine and dacarbazine in patients with melanoma in-transit metastases. 1059 15

A 38 year-old man presented with upper abdominal mass and hypertension pointed out at a medical examination. Blood pressure was 170/90 under medication of an alpha-blocker. Abdominal CT scan showed an 8 x 8 cm inter-aortocaval mass displacing pancreas head ventrally, and further a 4 x 4 cm mass at the aortic bifurcation, but there was no tumorous lesion in bilateral adrenal glands. Plasma nor-epinephrine level and urinary VMA excretion were excessive but plasma adrenaline level was within normal limits. MIBG scintigram showed hot spots in the 4th and 9th thoracic vertebrae. The destructive change of the 9th vertebra on magnetic resonance imaging strongly suggested metastasis of the tumor. Histologic and immunohistochemical findings of the biopsy specimen taken from the lower abdominal tumor in addition to the above clinical data led to the diagnosis of extra-adrenal malignant pheochromocytoma with spinal metastases. Since 2 cycles of full dose CYVADIC chemotherapy had no effects on lowering the high blood pressure and reducing the tumor size, low dose (60% of the full dose) CVD (cyclophosphamide, vincristine and dacarbazine) was given as a palliative chemotherapy on an out-patient clinic approximately every 4 weeks. After 4 cycles of the chemotherapy, his backache due to spinal metastasis markedly improved, hypertension as well as the plasma dopamine level was normalized and nor-epinephrine level was markedly decreased, though the tumor size was not reduced. Thereafter, no medication for hypertension was necessary. During 3 years and 6 months until now, 36 cycles of the chemotherapy has been repeated with no significant side effects. He has been at full-time work with quality of life being well preserved. Low dose CVD regimen appears to be an effective tumor dormancy therapy for advanced extra-adrenal pheochromocytoma.
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PMID:[Low dose CVD chemotherapy as a tumor dormancy therapy for extra-adrenal malignant pheochromocytoma: a case report]. 1151 73

The effectiveness and side-effects of various chemotherapy (CT) regimens were compared in 157 patients (74 males and 80 females, aged 23-79) with disseminated skin melanoma (DSM). Most cases had multiple metastases to the skin and subcutaneous fat tissue, regional lymph nodes (59-69%), lung (14-38%) and liver (13-36%); to other sites--82 (52%). Total response in the dacarbazine (DTIC) group was 18% (complete--5, partial--13 and stabilization--29%). DTIC was employed as first-line treatment in 71%. DBDT (cisplatin, DTIC, BCNU, tamoxifen) was used in 42 patients: as first-line--13 (31%), second-line--21 (50%) and third-line (following the first two regimens in cases refractory to treatment or those with response-based evidence of tumor progression)--8 (19%). In DBDT-treated patients, total response was 29% (complete--7, partial 22 and stabilization--38%). Similar results were recorded in the group where 69% were given CT as second- and third-line treatment. The effect of CVD (cisplatin, vinblastin, DTIC) was much the same as that of DTIC alone but was followed by a higher incidence of myelodepression and anemia. Combined treatment with prospidin+ CCNU + BCNU seems to offer more advantage.
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PMID:[Clinical evaluation of the efficacy of modern first, second, and third line regimes of chemotherapy in patients with disseminated cutaneous melanoma]. 1171 Feb 84

The role of endocrine therapy in early as well as advanced breast cancer cannot be overrated. Long-term tamoxifen exposure (5 years) in the adjuvant setting has been shown to be effective not only in improving relapse-free and overall survival but also in reducing the incidence of contralateral cancers. Promising results have been achieved in breast cancer prevention with use of antiestrogens. Novel aromatase inhibitors and inactivators have been found superior to conventional treatment in metastatic disease and are currently being evaluated in the adjuvant setting to improve relapse-free and overall survival. If potential health hazards from estrogen deprivation with regard to cardiovascular disease as well as bone metabolism can be addressed, adjuvant endocrine therapy may include such drugs in the future. However, while endocrine therapy of breast cancer has become more and more important in the clinic, the major problems in hormonal therapy are primary and acquired resistance to endocrine manipulations. The causes for endocrine resistance and possible ways to delay or avoid this phenomenon are only allusively understood. Elucidation of the mechanisms underlying endocrine resistance in vivo represents the key to improve our treatment strategies. Due to intense use of in vitro models and animal systems, many potential mechanisms of endocrine resistance have been described; however, our understanding of the problem of drug resistance in vivo remains limited. Hopefully, ongoing programs on translational research in the neoadjuvant, adjuvant, and palliative settings will provide information that will improve our understanding of the biology of endocrine resistance in vivo and, thus, provide us with a better rationale to improve early as well as late endocrine therapy in breast cancer patients. The present publication summarizes the state of the art with respect to endocrine resistance.
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PMID:Resistance to endocrine therapy of breast cancer: recent advances and tomorrow's challenges. 1189 52

Adenocarcinoma of the mammary gland is the leading type of cancer in women. Among these breast cancers those that are estrogen-responsive respond well to existing therapeutic regimens while estrogen non-responsive cancers metastasize widely, demonstrate a high relapse rate, and respond poorly to therapy. Over-expression of the arachidonic acid-metabolizing enzymes cyclooxygenase-2 and lypoxygenases is frequently observed in breast cancer, particularly the non-estrogen-responsive type, suggesting a role of the arachidonic acid (AA) cascade in the growth regulation of these malignancies. Adenocarcinomas of the lungs, pancreas and colon also frequently over-express AA-metabolizing enzymes, and recent evidence suggests that the growth-regulating AA-cascade in these malignancies is under beta-adrenergic control. Our current experiments have therefore tested the hypothesis that in analogy to these findings adenocarcinomas of the breast are also regulated by beta-adrenergic receptors via stimulation of the AA-cascade. Analysis of DNA synthesis by [3H]-thymidine incorporation assays in three estrogen-responsive and three estrogen non-responsive cell lines derived from human breast cancers demonstrated a significant reduction in DNA synthesis by beta-blockers and inhibitors of cyclooxygenase or lipoxygenases in all cell lines. Analysis of AA-release in one of the most responsive cell lines demonstrated a time-dependent increase in AA-release in response to the beta-adrenergic agonist isoproterenol. Analysis by RT-PCR revealed expression of beta2-adrenergic receptors in all cell lines whereas beta1-adrenergic receptors were not found in two of the estrogen non-responsive cell lines. Our data suggest that a significant subset of human breast cancers is under control of beta-adrenergic receptors via stimulation of the AA-cascade. These findings open up novel avenues for the prevention and clinical management of breast cancer, particularly the non-estrogen-responsive types. Moreover, our findings suggest that cardiovascular disease and adenocarcinomas in a variety of organ systems, including the breast may share common risk factors and benefit from similar preventive and treatment strategies.
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PMID:Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines. 1206 62


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