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)

The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.
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PMID:Common symptoms in advanced cancer. 1583 69

Pancreatic cancer has an abysmal prognosis because of late diagnosis and lack of effective therapeutics. New drugs are desperately needed. The present study determined the effect of the LTB4 receptor antagonist, LY293111, on tumor growth and metastases in a fluorescent orthotopic model of pancreatic cancer. Pancreatic cancer cells (S2-013) with stable expression of enhanced green fluorescent protein were implanted into the duodenal pancreatic lobe of athymic mice. Animals were allocated to four groups (eight mice per group): control (no treatment); LY293111; gemcitabine; and LY293111 + gemcitabine. Monitoring of the surgical procedure and follow-up examinations at 2, 3, and 4 weeks after implantation to monitor tumor growth and metastases were performed using a fluorescence microscope and the reversible skin-flap technique. A staging and scoring system was developed to evaluate tumor progression, based on the TNM classification. Control animals developed end-stage disease with invasive cancer, metastases, and cachexia. Tumor growth and incidence of metastases were significantly reduced in all treated mice. However, combined treatment with LY293111 and gemcitabine was most effective. LY293111 is a novel therapeutic agent for pancreatic cancer, which improves the efficacy of gemcitabine. It is well tolerated and can be administered orally and, therefore, provides a new hope for patients suffering from pancreatic adenocarcinoma.
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PMID:LY293111 improves efficacy of gemcitabine therapy on pancreatic cancer in a fluorescent orthotopic model in athymic mice. 1596 19

Patients harboring cancer and other tumors frequently exhibit such bone morbidity as metabolic bone diseases and bone metastases. Cancers produce and secrete cytokines and growth factors for their growth and survival. Cytokines are also produced by reacting immune systems. Those humoral factors, when produced in a sizable quantity, enter into the general circulation and become a causative principle for paraneoplastic syndrome. An example is parathyroid hormone-related protein (PTHrP) for humoral hypercalcemia of malignancy, and fibroblast growth factor 23 (FGF23) for oncogenic osteomalacia. In animal models, PTHrP appear to produce cancer-associated cachexia as well. Some particular cancers such as those of lung, prostate, breast and thyroid are prone to metastasize into bone resulting in metastatic bone disease. Interactions between these cancers and inhabitant bone cells and bone matrices constitute a favorable condition where particular cancer cells deposit and survive. A variety of principle factors, mostly signal materials, were identified that are responsible for these interactions and these principle factors can be a target for the development of new chemotherapeutic agents.
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PMID:[Bone in malignant disorders: introduction]. 1658 3

Cancer metastases (spread to distant organs from the primary tumor site) signify systemic, progressive, and essentially incurable malignant disease. Anorexia and wasting develop continuously throughout the course of incurable cancer. Overall, in Westernized countries nearly exactly half of current cancer diagnoses end in cure and the other half end in death; thus, cancer-associated cachexia has a high prevalence. The pathophysiology of cancer-associated cachexia has two principal components: a failure of food intake and a systemic hypermetabolism/hypercatabolism syndrome. The superimposed metabolic changes result in a rate of depletion of physiological reserves of energy and protein that is greater than would be expected based on the prevailing level of food intake. These features indicate a need for nutritional support, metabolic management, and a clear appreciation of the context of life-limiting illness.
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PMID:Cancer-associated cachexia and underlying biological mechanisms. 1660 32

Most deaths from urinary bladder cancer are owing to metastatic disease. A reduction in Rho GDP Dissociation Inhibitor 2 (RhoGDI2) protein has been associated with increased risk of metastasis in patients with locally advanced bladder cancer, whereas in animal models, RhoGDI2 reconstitution in cells without expression results in lung metastasis suppression. Recently, we noted an inverse correlation between tumor RhoGDI2 and Neuromedin U (NMU) expression, suggesting that NMU might be a target of the lung metastasis suppressor effect of RhoGDI2. Here we evaluated whether NMU is regulated by RhoGDI2 and is functionally important in tumor progression. We used small interfering RNA knockdown of endogenous RhoGDI2 in poorly tumorigenic and non-metastatic human bladder cancer T24 cells and observed increased NMU RNA expression. Although NMU overexpression did not increase the monolayer growth of T24 or related T24T poorly metastatic human bladder cancer cells, it did augment anchorage-independent growth for the latter. Overexpression of NMU in T24 and T24T cells significantly promoted tumor formation of both cell lines in nude mice, but did not alter the growth rate of established tumors. Furthermore, NMU-overexpressing xenografts were associated with lower animal body weight than control tumors, indicating a possible role of NMU in cancer cachexia. NMU overexpression in T24T cells significantly enhanced their lung metastatic ability. Bioluminescent in vivo imaging revealed that lung metastases in T24T grew faster than the same tumors in the subcutaneous microenvironment. In conclusion, NMU is a RhoGDI2-regulated gene that appears important for tumorigenicity, lung metastasis and cancer cachexia, and thus a promising therapeutic target in cancer.
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PMID:Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia. 1687 52

Renal cell carcinoma is unique among the genitourinary malignancies in that close to one third of affected patients show signs and symptoms of a paraneoplastic syndrome. The paraneoplastic syndromes associated with renal cell carcinoma range from those manifesting in constitutional symptoms (ie, fever, cachexia, and weight loss) to those that result in specific metabolic and biochemical abnormalities (ie, hypercalcemia, nonmetastatic hepatic dysfunction, amyloidosis, etc). The presence of a paraneoplastic syndrome in a patient with renal cell carcinoma is neither a marker of metastatic disease nor necessarily indicative of a poor prognosis. The importance of understanding the pathophysiology and biology behind the many paraneoplastic syndromes associated with renal cell carcinoma lies in the fact that the presence of these protean symptoms may be the initial presentation of either primary or recurrent disease. In this review, we will describe the proposed mechanisms of action of the many paraneoplastic syndromes associated with renal cell carcinoma as well as outline the clinical evaluation and treatment options currently available for these noteworthy disorders.
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PMID:Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma. 1698 75

Here we report an unusual case of mixed Wilms' tumour and angiosarcoma in a 38-year-old female patient who presented with haematuria and right lower back pain. A computed tomographic (CT) scan confirmed a massive renal tumour associated with extensive retroperitoneal lymph node involvement, bony metastases and a right hip fracture. She was initially managed with palliative nephrectomy, which was followed by rapid postoperative deterioration. Histopathology revealed differentiated adult Wilms' tumour with renal angiosarcoma, whereas the pathology of the para-aortic lymph node and bone metastasis revealed angiosarcoma only. In view of her cachexia and cytopaenia, emergency chemotherapy was initiated using a modified regimen of carboplatin, etoposide and vincristine (CEO) in preference to the more traditional but less well-tolerated VAC (vincristine, actinomycin D, cyclophosphamide). Four cycles of this protocol yielded a dramatic response on re-staging CT scan. This case suggests that highly angiogenic tumours such as angiosarcoma may be effectively palliated using agents usually reserved for refractory Wilms' tumour, and supports the view that adult Wilms' tumour is more sensitive to such agents.
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PMID:A case of mixed adult Wilms' tumour and angiosarcoma responsive to carboplatin, etoposide and vincristine (CEO). 1757 Dec 63

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

Previous studies have demonstrated an effect of corticotropin-releasing factor 2 receptor (CRF2R) agonists in the maintenance of skeletal muscle mass. The aim of this study was to evaluate the effects of a CRF2R agonist in preserving skeletal muscle in a mouse cachexia model. Implantation of a fast-growing tumor to mice (Lewis lung carcinoma) resulted in a clear cachectic state characterized by a profound muscle wasting. We found that administration of a CRF2R agonist (PG-873637) at 100 microg/kg/day by means of osmotic minipumps to tumor-bearing mice resulted in beneficial effects on muscle weight loss. Thus, muscle loss was partially reversed by the CRF2R agonist at different stages of tumor growth (at day 14 after tumor inoculation: 12% in tibialis posterior; 9% in gastrocnemius; and 48% in soleus). Moreover, the CRF2R agonist significantly reduced both the number of metastases and their mass (at day 19 after tumor inoculation: 66% and 61%, respectively). These data suggest a potentially beneficial effect of the CRF2R agonist in preserving skeletal muscle during cancer cachexia and open a line of research for the development of new therapeutic approaches for the treatment of muscle wasting associated with cancer.
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PMID:Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells. 1791 49

Ghrelin is a potent orexigenic peptide principally produced in the stomach by a distinct population of neuroendocrine cells in the oxyntic mucosa of the fundus. Exogenous ghrelin given as an intravenous infusion has been shown to increase caloric intake in patients with cancer cachexia. In this study, we hypothesized that elevated endogenous ghrelin, produced by increased neuroendocrine cell tumor burden, also exerts an orexigenic effect helping to maintain body mass index. To evaluate the effect of elevated endogenous ghrelin, 35 patients with neuroendocrine tumors were enrolled, assigning them to one of two groups depending on the presence of hepatic metastases. Following an overnight fast, serum was collected and sent for ghrelin measurement by an outside laboratory. The two groups were well matched for all other relevant clinical variables including subtype of tumor, primary location of tumor and tumor treatment history. Nearly all patients with hepatic metastases had elevated levels of ghrelin compared to the standard reference range given for matched controls. The presence of hepatic metastases was associated with significantly elevated ghrelin levels (p<0.05) and a greater mean body mass index. In addition, we report a positive correlation between serum ghrelin and total tumor surface area and between serum ghrelin and body mass index, suggesting that elevated endogenous ghrelin may be sufficient to overcome any partial ghrelin resistance typically seen in cancer cachexia. These results support the possibility that ghrelin is co-released from neuroendocrine tumors and exerts an orexigenic effect in these patients, helping to maintain their body mass index despite widely disseminated disease.
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PMID:Elevated serum ghrelin exerts an orexigenic effect that may maintain body mass index in patients with metastatic neuroendocrine tumors. 1795 31


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