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)

This retrospective study in 79 surgically treated patients with a proximal bile duct carcinoma revealed 12 patients with a median age of 59.5 years (range 21-73 years) who survived more than 5 years. These 12 patients were analyzed to identify specific patient characteristics for long-term survival. Fifteen patients died from postoperative complications and were excluded from this survival analysis. In relation with preoperative Bismuth classification, there were 3 (20%) long-term survivors of 15 patients with type I tumors and 9 (35%) long-term survivors of 26 patients with type II tumors. In the group of type III and IV tumors, there were no long-term survivors. Concerning the type of resection, 9 of 51 (18%) patients had long-term survival after local resection and 3 of 13 (23%) patients after local resection combined with hemihepatectomy. Complete tumor-free surgical specimen margins were found in only 4 of 64 cases (6%), among which only one patient survived more than 5 years. Negative proximal bile duct margins, absence of multifocality, and diploid tumors showed a significant correlation with long-term survival. There was no significant correlation between long-term survival and postoperative radiotherapy. Of the 12 long-term survivors, 5 died after 5 years: 2 had developed metastases and 1 a local recurrence; the other 2 died of a metastasis of an ovarian adenocarcinoma and cachexia, respectively. The remaining seven patients were still alive at the completion of this study. The mean survival of the 64 patients analyzed in this study (in which hospital mortality was excluded) was 33.7 months, with a median survival of 18.8 months. In conclusion, the preoperative Bismuth classification of the tumor, absence of multifocality, diploid-type tumors, and negative proximal bile duct margins at histopathologic examination were the only significant prognostic factors for long-term survival.
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PMID:Long-term survival after resection of proximal bile duct carcinoma (Klatskin tumors). 984 70

Dogs and cats with cancer have significant alterations in carbohydrate, protein, and fat metabolism, which can result in cancer cachexia and subsequently can decrease quality of life, reduce response to therapy, and shorten survival time. Nutritional modulation may be beneficial in the treatment of cancer patients to reverse these metabolic alterations. There is evidence that foods relatively low in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat (especially fats of the omega-3 fatty acid series) are beneficial for pets with cancer. In addition, certain supplemental nutrients may have potential to reduce the risk of developing cancer, or the growth and metastases of established malignant disease. Nutritional intervention can be a powerful tool for controlling malignant disease and for reducing toxicity associated with chemotherapy and radiation therapy.
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PMID:Interventional nutrition for the cancer patient. 984 15

The steroid hormone 1,25-dihydroxyvitamin D [1,25(OH)2D, also known as calcitriol] is known to inhibit the proliferation and to promote the differentiation of human prostate cancer cells. Additionally, we showed that 1,25(OH)2D markedly inhibits the invasiveness of human prostate cancer cells in vitro (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997). These properties support the use of 1,25(OH)2D as differentiation therapy in prostate cancer. However, the use of 1,25(OH)2D in vivo is limited by the risk of hypercalcemia. We therefore compared the effects of 1,25(OH)2D and of EB1089, an analogue of 1,25(OH)2D with reduced calcemic effects, in an in vivo model of androgen-insensitive metastatic prostate cancer, the rat Dunning MAT LyLu prostate cancer model. Tumor growth and metastasis were studied using Copenhagen rats given s.c. injections of MAT LyLu cells. Fifty male rats were divided into five groups of 10 rats each. Four experimental groups received i.p. injections of low and high doses of 1,25(OH)2D and EB1089 (0.5 and 1.0 microg/kg, low and high, respectively). A control group received injections of vehicle only. Tumor volumes were measured three times per week. Rats were weighed weekly. The number of metastases to the lungs and the extent of hypercalcemia were evaluated. Compared with controls, tumor volumes were significantly smaller in all experimental groups. Similarly, the number of lung metastases (number of foci/lung) was reduced markedly by both 1,25(OH)2D and EB1089. Control rats developed 22.7 (+/- 1.98 SE) tumor foci per lung. Rats treated with 1,25(OH)2D and with EB1089 (1.0 microg/kg) developed 10.4 (+/- 2.81) and 7.70 (+/- 1.29) tumor foci, respectively (P < 0.001 and P < 0.0001, respectively; drug versus control). Compared with controls (10.79 +/- 0.1 mg/dl), serum calcium levels were significantly elevated in both 1,25(OH)2D and EB1089-treated rats (P < 0.01). However, EB1089 was significantly less calcemic than 1,25(OH)2D (12.59 +/- 0.21 mg/dl versus 14.47 +/- 0.46 mg/dl; 1.0 microg/kg; P < 0.001). Rats treated with 1,25(OH)2D showed marked weight loss: 20.0 +/- 1.9% and 26.3 +/- 1.7% of their initial weight (low and high doses, respectively, P < 0.001). Weight loss was significantly lower in rats treated with EB1089 at the high dose 8.4 (+/- 2.9) %. Moreover, rats treated with low-dose EB1089 gained 5.2 (+/- 3.7) % of their initial weight. In conclusion, 1,25(OH)2D and EB1089 showed marked and equivalent inhibition of prostate cancer metastasis in vivo. EB1089 was significantly less calcemic than 1,25(OH)2D and did not induce severe weight loss. This is the first report of a vitamin D analogue that significantly inhibits prostate cancer metastasis in vivo and that does so without producing cachexia or unacceptable hypercalcemia.
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PMID:Inhibition of prostate cancer metastasis in vivo: a comparison of 1,23-dihydroxyvitamin D (calcitriol) and EB1089. 1009 Mar 2

Paraneoplastic syndromes including leukocytosis, thrombocytosis and hypercalcemia are occasionally seen in patients suffering from progressive malignant disorders. Recent studies have revealed the production of several humoral factors by tumor cells and normal splenic cells of tumor-bearing patients to be the major cause of these reactions. Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), parathyroid hormone-related peptide, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) have been implicated. We describe a 58-year-old Japanese man with squamous cell carcinoma (SCC) on the left sole, which developed in a deep linear scar after a train crash. He developed pulmonary and lymph node metastases, then leukocytosis (57,110/mm3 with 95% neutrophilia), thrombocytosis (86.3 x 10(4)/mm3), and hypercalcemia (7.0 mEq/1), and finally cachexia, followed by death. Serum G-CSF, IL-1 alpha, IL-1 beta, and TNF-beta were determined; revealing G-CSF and IL-1 beta levels were above the upper limits of their normal ranges at 39.2 pg/ml and 4.63 pg/ml, respectively. It is probable that these humoral factors were partially responsible for the paraneoplastic syndromes induced by the cutaneous SCC with metastasis in the present case.
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PMID:Paraneoplastic syndromes of leukocytosis, thrombocytosis, and hypercalcemia associated with squamous cell carcinoma. 1040 79

The prevailing subcutaneous nude rodent tumor xenograft models used for biological and preclinical studies do not optimally reflect some important biological properties of cancer, especially invasion and metastasis. Orthotopic models have been developed to address this need. However, for lung cancer none of the available models are optimal, in that none originate from an orthotopic (bronchial) primary site and exhibit extensive extrathoracic metastasis. Our goal was to develop a consistent rodent model of non-small cell lung cancer with both of these properties. Groups of male Rowett nude rats were given 500 rads of gamma radiation and then endobronchially implanted in the right caudal lobe airway with 50 mg of small NCI-H460 tumor fragments taken from an orthotopic donor tumor. They were then sacrificed at selected post-implantation times and evaluated grossly and histologically for animal weight, primary tumor take and size, and metastatic tumor incidence at multiple sites. At a late time point (32-35 days), consistency of primary tumor size and metastasis was estimated by comparing results from four groups of rats implanted on different occasions. The results showed that the primary tumors grew steadily, reaching four grams by days 32-35. Rats gained weight until days 14 to 21, but then began to show cachexia. High metastatic rates (>60%) were seen for mediastinal lymph nodes (by 21 days), and kidney, bone and brain (by 28 days). Mean primary tumor size and the incidences of both regional and systemic metastasis were consistent at 32-35 days in four different groups of six animals. In conclusion, this orthotopic lung cancer model is highly metastatic and consistent in terms of both primary tumor growth and metastatic behavior. It is the only available rodent model of human lung cancer emanating from an endobronchial site and metastasizing to multiple extrapulmonary sites, and should be very useful for both biological and preclinical studies of lung cancer, particularly where studies of antimetastatic activity are of interest, and/or where survival studies are desired.
Clin Exp Metastasis 1999 Mar
PMID:Characterization of a highly metastatic, orthotopic lung cancer model in the nude rat. 1041 Nov 8

We report three cases of postoperative recurrent cholangitis due to a defective hepaticojejunal anastomosis. Causal diseases were alveolar echinococcosis of the liver, alcoholic chronic pancreatitis, liver colorectal metastases. Clinical presentation included major cholestasis and cachexia. Imaging explorations showed that cholangitis was due to an inversion of the Roux-en-Y jejunal loop which had been disposed in a wrong position. Clinical improvement was remarkable after reoperation and replacement of the defective loop in the right position. This exceptional cause of postoperative cholangitis after Roux-en-Y hepaticojejunal anastomosis must be identified and treated by prompt restorative surgery.
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PMID:[Reoperation for recurrent cholangitis due to a defect in the hepatico-jejunal anastomosis]. 1041 16

The morbidity and mortality associated with prostate cancer can almost universally be attributed to the consequences of metastases to the bone. While clinically there have been descriptive reports of these lesions and their detection by bone scan, there is an embrrassing paucity of reports as to the mechanisms of prostate cancer cell trafficking to the bone, adaptation to the bone environment, pertubation of the normal bone reformation process and the events leading to cachexia and death. In recent years, there have been numerous in vitro studies suggesting that PSA and hK2 may play a significant biological role in these events. Also, recent data generated form reverse transcription polymerase chain reaction assays reveal that metastasis to the bone may be an early event which further underscores the need to better understand this complex and critically important process. This commentary highlights several general concepts and a few specific issues related to CaP bone metastasis with the intent of revealing numerous opportunities for further investigation and inquiry.
Cancer Metastasis Rev
PMID:Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone. 1045 76

Metastatic disease is a major concern of dermal leishmaniasis caused by Leishmania of the Viannia subgenus. The golden hamster provides an experimental model of systemic dissemination and cutaneous metastasis of Leishmania Viannia. We have exploited this model to examine the expression of parasite virulence in cloned populations derived from a strain of L. guyanensis previously shown to be highly metastatic in the hamster. Metastatic capacity manifested as dissemination throughout the lymphoid organs; cachexia and secondary cutaneous lesions were found to differ among clones, yielding a spectrum of virulence. The metastatic phenotype of clonal populations was stable over 5 sequential passages in hamsters. In addition, the low or high propensity to disseminate and produce cutaneous metastatic lesions was reproduced. Capacity to disseminate from the inoculation site was conserved following subcloning of metastatic clones that had been passaged in culture for several generations; clinical manifestations, cachexia, and cutaneous metastatic lesions were variably expressed. Dissemination of parasites and cachexia were significantly related (P = 0.004). Overall, cachexia was an earlier manifestation of dissemination than cutaneous metastases (P < 0.001). The reproducible expression of virulence phenotypes by discrete populations of Leishmania in the golden hamster provides an experimental model for clinically relevant expression of virulence in human leishmaniasis.
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PMID:Clonal diversity in the expression and stability of the metastatic capability of Leishmania guyanensis in the golden hamster. 1095 58

Cachexia often causes deterioration in the quality of life in cancer patients; however, its mechanism remains poorly understood. Cachexia has often been observed in experimental animals with bone metastases, and parathyroid hormone-related protein (PTHrP) plays an important role in the formation of such metastases. We therefore investigated the possible involvement of PTHrP in an experimental cachexia model using human lung-cancer cells (HARA-B). HARA-B cells produce a high amount of PTHrP but no TNF-alpha, IL-6 or leukemia inhibitory factor. The s.c. inoculation of HARA-B cells into nude mice caused reductions in body weight, adipose tissue weight, muscle weight and serum glucose levels. Serum levels of calcium and PTHrP increased. Neutralization of PTHrP with antibody caused rapid weight gain along with a rapid decrease in serum calcium levels. Our findings suggest that PTHrP plays an important role in the development of cancer cachexia. PTHrP therefore is a possible target molecule for the treatment of cancer cachexia.
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PMID:Involvement of parathyroid hormone-related protein in experimental cachexia induced by a human lung cancer-derived cell line established from a bone metastasis specimen. 1166 74

The significant benefit of performing hepatic resection for hepatic metastases from colorectal primary cancers is well established; however, the effectiveness of dissection of the lymph nodes draining the liver remains uncertain. Herein, we report the case of a 52-year-old man who was found to have obstructive jaundice caused by lymphatic remetastasis from the hepatic metastasis of primary rectosigmoid cancer. He had previously undergone a high anterior resection for the rectosigmoid cancer, in April 1990, and a hepatic resection for metastasis was done in March 1994. When the hepatic resection was carried out, dissection of the regional lymph nodes of the liver (i.e., the nodes in the hepatoduodenal ligament) was not performed because no obvious metastatic nodes were identified. Three years after the hepatic resection, enlarged lymph nodes compressing the extrahepatic bile duct from outside were identified by cholangiography and computed tomography (CT). Because radiological studies were unable to determine the lesion capable of metastasizing to these nodes, they were diagnosed as remetastasized lymph nodes from the hepatic metastasis that had been resected 3 years earlier. The lymphatic remetastases were intractable to treatment, and the patient finally died of hepatic failure and malignant cachexia. This case serves to demonstrate that lymphatic dissection of the regional lymph nodes may need to be taken into consideration when resection of hepatic metastases from colorectal cancers is performed.
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PMID:Obstructive jaundice caused by lymphatic remetastasis from the hepatic metastasis of rectosigmoid cancer. 1170 58


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