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)

On June 20, 2006, the U.S. Food and Drug Administration (FDA) approved bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), administered in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin) for the second-line treatment of metastatic carcinoma of the colon or rectum. Efficacy and safety were demonstrated in one Eastern Cooperative Oncology Group (ECOG) open-label, multicenter, randomized, three-arm, active-controlled trial enrolling 829 adult patients. Patients had received a fluoropyrimidine- and irinotecan-based regimen as initial therapy for metastatic disease; or they had received prior adjuvant irinotecan-based chemotherapy and had recurred within 6 months of completing therapy. Treatments included bevacizumab, 10 mg/kg, as a 90-minute i.v. infusion on day 1, every 2 weeks, either alone or in combination with FOLFOX4, or FOLFOX4 alone. The bevacizumab monotherapy arm was closed to accrual after an interim efficacy analysis suggested a possibly shorter survival in that arm. Overall survival (OS), the primary study endpoint, was significantly longer for patients receiving bevacizumab in combination with FOLFOX4 than for those receiving FOLFOX4 alone. The objective response rate was significantly higher in the FOLFOX4 plus bevacizumab arm than in the FOLFOX4 alone arm. The duration of response was approximately 6 months for both treatment arms. Patients treated with the bevacizumab combination were also reported, based on investigator assessment, to have significantly longer progression-free survival. There were no new bevacizumab safety signals. The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound-healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, and congestive heart failure.
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PMID:FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. 1740 1

This study explored medical conditions associated with mortality among veterans following transfemoral amputation, transtibial amputation, or hip disarticulation. We applied logistic regression models to identify clinical factors associated with mortality postoperatively. The participants included patients with lower-limb amputations (n = 2,375) who were discharged from Veterans Health Administration hospitals between October 1, 2002, and September 30, 2003. Most (98.9%) were male. We measured cumulative in-hospital, 3-month, and 1-year mortality. The results were 180 in-hospital deaths, 368 by 3 months, and 634 by the 1-year postsurgical amputation date. Those who had perioperative systemic sepsis (odds ratio = 4.28, 95% confidence interval = 2.87-6.39) had more than a fourfold increased likelihood of in-hospital mortality. Congestive heart failure, renal failure, and liver disease were significantly associated with mortality at all time periods. Metastatic cancer was associated only at 3 months and 1 year. We concluded that high medical complexity and mortality rates attest to the need for careful medical oversight during the postacute rehabilitation period.
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PMID:Risk factors associated with mortality in veteran population following transtibial or transfemoral amputation. 1743 77

A primary cardiac malignant tumor is very rare; its prevalence is only 0.002-0.28%. Among most malignant tumors, angiosarcoma, leiomyosarcoma, and mesothelioma occupy the majority. A cardiac osteosarcoma is extremely rare: to our knowledge, only 36 cases have been reported worldwide. We present a 22-year-old case featuring severe congestive heart failure. Hemodynamically the tumor led to significant obstruction of the mitral valve. The patient underwent an emergency resection operation, but multiple metastases occurred. Though the characteristics still remain unclear because of the low prevalence, it is very important that these tumors be distinguished from benign tumors because of early resection operation.
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PMID:Primary cardiac osteosarcoma in a young man with severe congestive heart failure. 1752 37

Cachexia is a common finding in various diseases such as chronic renal failure, HIV infection, malignancies, chronic obstructive pulmonary disease, congestive heart failure and rheumatoid arthritis. It is estimated that 30% of patients with malignancies will appear with cachexia, and up to 80% of patients with progressive metastatic disease will be affected. Cachexia is associated with decreased overall survival rates, and decreased beneficial effects of chemotherapy treatment. The underlying pathological processes in cachexia are not completely understood. It is believed that tumor necrosis factor alpha (TNFalpha) plays an essential rule in cachexia induction and propagation. This article reviews and discusses current anti-cachexia treatments, with special emphasis on anti-TNF-alpha treatment in malignancies and various other diseases.
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PMID:[Cachexia, malignancy and tumor necrosis factor alpha (TNF-alpha)]. 1767 50

Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell migration, adhesion and proliferation and possible influences of the activity of integrins and focal adhesion kinase (FAK) were analyzed in RCC cells. The experiments were performed in the RCC cell line CCF-RC1 after pre-incubation of the cells with the PKC inhibitors GF109203X, GO6976, RO31-8220 and rottlerin. Cell migration and adhesion were assessed through chemotaxis analysis and adhesion to an endothelial monolayer, respectively. Cell proliferation was analysed by a BrdU incorporation assay. The expression and activity of beta1 integrins and FAK were analysed by Western blot analysis. GF109203X reduced cell migration to 69%, the activity of beta1 integrins to 63% and FAK expression to 82% compared to untreated cells. Rottlerin reduced cell migration in a concentration-dependent manner to 36%, cell proliferation to 81%, expression and activity of beta1 integrins to 72 and 79%, and expression and activity of FAK to 56 and 76% of untreated cells, respectively. RO31-8220 also reduced the expression and activity of beta1 integrins as well as the expression of FAK to 84, 66 and 66% of untreated cells, respectively. GO6976 reduced the expression of FAK to 60% of untreated cells. Cell migration was only slightly reduced by GO6976 to 84% of untreated cells, and cell adhesion remained uninfluenced. These findings show a critical role of PKCdelta in the regulation of tumor cell migration, which seems to be caused by affecting the expression and activity of beta1 integrins and FAK. These results can provide a basis for new strategies in preventing metastases of renal cell carcinoma.
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PMID:Migration of renal carcinoma cells is dependent on protein kinase Cdelta via beta1 integrin and focal adhesion kinase. 1842 41

Venous thromboembolism is one of the main causes of morbidity and mortality in many diseases, either in medical or in surgical wards. The aim of this study is to determine its frequency in a medical ward and to find all the patients who need a prophylaxys. We examined all the inpatients admitted in our Department during a period of three years, selecting all subjects affected by venous thromboembolism. Patients affected by metastatic cancer, namely pancreatic one, or congestive heart failure showed higher risk to develope venous thromboembolism. A prompt heparinic prophylaxys could reduce thromboembolic events. Male gender could be a further risk factor.
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PMID:[Venous thromboembolism risk in medical inpatients]. 1920 43

The potential for cardiac toxicity in association with targeted biologic agents was first observed with trastuzumab, a monoclonal antibody that targets the ErbB2/HER2 receptor. In the pivotal trial of trastuzumab in ErbB2-positive metastatic cancer, an increased incidence of serious cardiac events was observed, particularly when trastuzumab was administered in combination with anthracyclines. The ErbB2 receptor is expressed on cardiomyocytes, in addition to tumor tissue, where it exerts a protective effect on cardiac function; thus, interference with ErbB2-signaling may block this protective effect. However, in contrast to anthracycline-induced cardiac toxicity, trastuzumab-related cardiac dysfunction does not appear to increase with cumulative dose or to be associated with ultrastructural changes in the myocardium and is generally reversible. When used in adjuvant regimens for the treatment of ErbB2-positive early-stage breast cancer, trastuzumab has been shown to significantly improve disease-free and overall survival. The incidence of class III/IV congestive heart failure (CHF) ranged from 0.4%-3.8% in the major adjuvant trastuzumab trials. More recently, small-molecule tyrosine kinase inhibitors such as lapatinib have been investigated for the treatment of ErbB2-positive metastatic breast cancer. In a comprehensive analysis of cardiac safety data from all lapatinib trials completed to date, which included 3558 healthy volunteers and patients with a variety of solid cancers on 43 trials, the overall incidence of left ventricular ejection fraction declines was 1.6%, with 0.2% of patients experiencing symptomatic CHF. Risk factors that might predict for cardiac dysfunction with ErbB2-targeted therapy are actively under investigation and will aid in the identification of at-risk populations and in the development of strategies for risk minimization in the future. It is important to note that, while careful cardiac monitoring is required for all patients receiving ErbB2-targeted therapy in any disease setting, the overall impact of these agents on the outcomes of patients with ErbB2-positive breast cancer has been dramatic and positive.
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PMID:Cardiac toxicity of ErbB2-targeted therapies: what do we know? 1877 50

The study population comprised 14 patients, operated on account of colon cancer (n=2), sigmoid cancer (n=1), rectal cancer (n=6), synchronous rectal and prostatic cancer (n=1) and lung (n=1) and liver (n=2) colon cancer metastases. The diagnosed concurrent cardiovascular pathology was: coronary heart disease (n=8), valve disease (n=2), aortic aneurism (n=2), coronary heart disease combined with aortic aneurism (n=2). Simultaneous operations were performed in 3 patients, 11 patients were operated on consecutively. No deaths were registered after simultaneous operations. In the group of consecutive operations 2 patients had died of myocardial infarction and cardiac decompensation. 3 (21,4%) patients died of tumor relapse during the follow-up period. The rest 9 patients are under observation for 3 months to 10 years, 2 patients achieved a 5-year cancer-free survival time.
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PMID:[Surgical treatment of patients with colorectal cancer and severe concurrent cardio-vascular diseases]. 1883 43

Primary cardiac tumors are a rare entity compared to tumors that metastasize to the heart. Patients with such tumors may be asymptomatic. Many cases are found incidentally during evaluation of an unrelated medical condition. It is important for the clinician to have a high index of suspicion when evaluating a patient presenting with signs and systemic symptoms concerning possible malignancy, plus cardiac specific symptoms or complications. These can include new onset dyspnea, congestive heart failure, arrhythmias or murmurs varying with body positions. Imaging, particularly the use of echocardiography, remains the cornerstone of diagnosis, and may be combined with new imaging modalities of cardiac CT and MRI. The aim of this paper is to describe the epidemiology and pathophysiology of the various benign and malignant primary cardiac tumors.
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PMID:Primary cardiac tumors. 2093 28

Hypercalcemic crisis, a life-threatening emergency, is defined as decompensated hypercalcemia presented with characteristic symptoms such as oliguria, cardiac arrhythmia, or coma. We report the case of a 63-year-old man diagnosed with mucosa-associated lymphoid tissue lymphoma and multiple bony metastases, who presented to the emergency department (ED) with coma and severe hypercalcemia (4.15 mmol/L). Prompt hydration with normal saline and intravenous pamidronate failed to correct his hypercalcemic coma. Calcium-free hemodialysis rapidly decreased the level of serum total calcium to 2.15 mmol/L after a 2-hour session, and the patient dramatically regained consciousness shortly after hemodialysis. Calcium- free hemodialysis has proved favorable for rapidly correcting hypercalcemia in the presence of severe hypercalcemic symptoms, congestive heart failure, renal failure, or other conditions that contraindicate adequate hydration. This case highlights the fact that for all patients with comas of questionable cause in the ED, hypercalcemia- induced coma must be considered, especially in patients with malignancies. Early diagnosis and prompt treatment with calcium-free hemodialysis not only rapidly improve patient consciousness but also prevent the fatal complication of hypercalcemia.
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PMID:Hypercalcemic crisis successfully treated with prompt calcium-free hemodialysis. 1993 89


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