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 expression of metalloproteinases, such as type IV collagenase/gelatinase, enables tumor cells to degrade type IV collagen present in the basement membrane and correlates with metastatic potential of several tumor types. We found that increased levels of rat serum type IV collagenolytic activity are associated with increased 13762NF mammary adenocarcinoma metastases in lungs and lymph nodes of syngeneic rats. To investigate serum metalloproteinases responsible for type IV collagenolysis, we performed zymography and Western blot analysis of rat sera. A M(r) 92,000 progelatinase (progelatinase B, M(r) 92,000 type IV procollagenase, MMP-9) was detected on zymograms of rat sera within 16 days after intramammary fat pad inoculation of highly metastatic MTLn3 cells. The activated serum M(r) 92,000 progelatinase degraded sodium dodecyl sulfate-denatured type I and IV collagens but was not active on casein, albumin, hemoglobin, and immunoglobulin. Sera from rats with fat pad tumors and lung metastases formed from highly metastatic clones possessed greater than 7 times higher levels of serum M(r) 92,000 progelatinase than control sera or sera from rats bearing similar size fat-pad tumors of low or nonmetastatic clones. The results were confirmed by Western blot analysis of rat sera using rabbit anti-human M(r) 92,000 progelatinase antibodies. Similar results were obtained from the analysis of rat plasma samples. The serum and plasma M(r) 92,000 progelatinase levels correlated with the extent of metastases in the lung and lymph nodes. The results indicate that high levels of serum and plasma M(r) 92,000 progelatinase are associated with the presence of disseminated metastatic adenocarcinoma cells and suggest that this enzyme may facilitate the invasion of blood-borne tumor cells through vascular basement membranes.
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PMID:Serum and plasma M(r) 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. 824 39

Interleukin-2 (IL-2) therapy is dose limited by a severe vascular leak with resulting systemic and pulmonary toxicity. Although recognized as a mediator of septic shock and vascular leak, the relative role of IL-1 in IL-2 toxicity is unclear. We evaluated the effect of IL-1 receptor antagonist (IL-1ra) on IL-2 lethality, pulmonary vascular leak, and treatment of pulmonary metastases in a murine model. In vivo induction of mRNA for IL-1 alpha was evaluated in liver by Northern blots after 0, 5, 8, and 11 doses of IL-2 in C3H/HEN mice. The expression index for the IL-1 alpha gene increased from 0.16 to 0.74 after 5 doses of IL-2, and further increased to 1.04 after 11 doses of IL-2. C3H/HEN mice (n = 56) were randomized to receive phosphate-buffered saline (PBS), IL-1ra high dose (HD), or IL-1ra low dose (LD) by continuous subcutaneous infusion via Alzet mini-pumps. The biologic effectiveness of the dose and administration of IL-1ra was determined by the ability to block IL-1-induced IL-6 production in vivo. Mean serum IL-6 levels 3 hr after intraperitoneal IL-1 alpha (10 micrograms/kg) were: PBS, 3730 +/- 526 (mean +/- SEM pg/ml); IL-1ra (LD), 1156 +/- 398; and IL-1ra (HD), 594 +/- 30 (P < 0.01, IL-1ra HD or LD vs PBS). Pulmonary vascular leak was measured by iv I125 albumin after 8 doses of IL-2 (100,000 U ip q 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-1 receptor antagonist (IL-1ra) augments IL-2-induced pulmonary vascular leak. 833 27

Fibronectins are a family of glycoproteins with modular functional domains. They mediate cell-cell and cell-matrix interactions which are important in embryogenesis, wound healing, metastasis and other processes. We present data on the influence of fibronectin on wound implantation of a murine mammary carcinoma line, TA3Ha. Fibronectin used in these studies was derived from bovine plasma, human serum, human foreskin fibroblasts, and mouse embryo cultures. TA3Ha cells rarely form tumors in the liver of syngeneic mice when injected intravenously but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Wound implantation is markedly reduced when the cells are pre-exposed to 200 micrograms/ml bovine plasma fibronectin (13%, P = 0.007), human serum fibronectin (0%, P = 0.02), human cellular fibronectin (0%, P = 0.02), or mouse cellular fibronectin (0%, P = 0.04). Lung colonization is also reduced by these fibronectins. These effects are not due to a cytotoxic action of fibronectin, since intraperitoneally injected fibronectin-treated cells form ascites tumor as effectively as do control untreated cells. Local application of a solution containing 0.25 mg/ml mouse cellular fibronectin to the hepatic wound reduces the frequency of tumor implantation from 45% to 5% (1/21, P = 0.001). No tumor implantation inhibition is seen when only suspending medium or albumin in suspending medium is used. The mechanism by which topical application of fibronectin reduces hepatic wound implantation of tumor cells is unclear, but this finding raises an exciting possibility of preventing local recurrence of cancer.
Clin Exp Metastasis 1993 Mar
PMID:The role of fibronectin in tumor implantation at surgical sites. 844 8

We performed a retrospective analysis on all head and neck cancers with hypercalcemia seen between January 1988 and June 1993 at the Centre Oscar-Lambret, cancer center of northern France. Hypercalcemia, non albumin-corrected, higher than 2.60 mmol/l was observed in 173 of 3,394 consecutive patients (5%). Median age of patients with hypercalcemia was 53 years and 97% of these patients were males. All patients with hypercalcemia had advanced or recurrent and/or metastatic squamous cell carcinoma of head and neck (SCCHN); 31 of them were not pretreated. There was no significant difference in histology between patients with or without hypercalcemia, but hypercalcemia was most commonly associated with lesions of the oropharynx (p = 0.00001). The median of calcemia was of 2.83 mmol/l (2.61-4.70). Gastrointestinal and neurologic symptoms respectively occurred in 24% and in 14% of patients and bone metastases in 25% of patients. Median survival after the first determination of hypercalcemia was of 7 weeks (0-128) for the overall group of 173 patients and of 12 weeks (1-128) for those 31 patients with hypercalcemia at initial diagnosis. Prognosis associated factors were: efficacy of antitumour treatment, performance status and hypercalcemia superior or not to 3 mmol/l. We concluded that hypercalcemia in head and neck cancer is usually a late manifestation associated with advanced, recurrent and/or metastatic disease and carries a poor prognosis. The prolongation of survival can be obtained in some patients if an effective antitumour treatment is feasible.
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PMID:[Hypercalcemia and squamous cell carcinoma of the upper respiratory-digestive tracts. Incidence and prognosis]. 853 25

In cutaneous melanoma, biopsy of the first tumour-draining lymph node (sentinel node, SN) may replace routine elective lymph node dissection (ELND). Even in experienced hands the original technique using vital dyes fails to localise the SN in 20% of cases. In this study we investigated whether the procedure benefits from lymphoscintigraphy and the use of a gamma probe. In 41 patients technetium-99m-colloidal albumin was injected intracutaneously around the scar of the excised tumour. This was followed by dynamic and late static imaging. The first focal accumulation was assumed to be the SN. In all patients at least one SN was found, in 95% within the first 20 min. By showing multiple or ramifying lymphatic channels, dynamic lymphoscintigraphy differentiated between spill and multiple SNs. In all cases the initial focus retained the highest fraction of radioactivity for at least 18 h. The gamma probe was especially useful in the axilla and neck, where it accurately showed the optimal incision site and facilitated the search for deep-seated nodes. Gamma probe-localised SNs were dye-positive in 93% of cases. The SN contained metastases in 20% of the patients. Only in these patients was ELND performed, which revealed that the SN had been the only metastatic node in four of eight cases. We conclude that dynamic lymphoscintigraphy is essential for SN localisation, that tracer kinetics allow flexible timing of surgery, and that the surgical procedure benefits from use of the gamma probe.
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PMID:The impact of dynamic lymphoscintigraphy and gamma probe guidance on sentinel node biopsy in melanoma. 857 70

To study the regulation of the endothelial barrier, we examined the relationship between the paracellular barrier function and the expression of 7H6 antigen localized at tight junctions of endothelial cells by using transendothelial electrical resistance (TER), fluxes of albumin and dextran, transmigration of rat mammary cancer (SST-2) cells across rat lung endothelial (RLE) cells, and immunocytochemical expression of 7H6 antigen as parameters. RLE cells cultured at a confluent cell density did not express immunohistochemically demonstrable 7H6 antigen and had low paracellular barrier functions. However, treatment of the endothelial cells with 0.5 mM dibutyryl-cAMP or 10(-6) M all-trans-retinoic acid for 4 days induced 7H6 antigen preferentially at the cell border and simultaneously enhanced the barrier function twofold, in terms of TER and fluxes of albumin and dextran. Furthermore, RA-treated RLE cell monolayers with the enhanced barrier function significantly inhibited the transmigration of SST-2 cells. These results together with those of our previous study indicate that 7H6 antigen has a crucial role in the regulation of paracellular barrier function not only in epithelial cells but also in vascular endothelial cells. The present study also suggests that tight junctions of vascular endothelium in vivo function as a barrier between blood and tissues against metastatic cancer cells.
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PMID:Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells. 859 13

Invasion-inhibiting factor 2 (IIF-2) and its albumin conjugate have been reported to inhibit spontaneous metastasis of highly metastatic cancer cells with no effect on primary tumor growth. To confirm the inhibitory effects of the IIF-2 conjugate on tumor invasion and spontaneous metastasis, we administered the conjugate intra-peritoneally (i.p.) to female nude mice bearing transplanted tumors with MKL-4 cells, which are MCF-7 human breast cancer cells cotransfected with fibroblast growth factor 4 and lacZ. Neither 10 nor 20 mg/kg doses of the conjugate caused any inhibition of primary tumor growth, but 20 mg/kg significantly inhibited tumor invasion and spontaneous metastasis. Tumor invasion was measured by a novel computer-assisted image analysis. Spontaneous microscopic metastases into lymph nodes and distant organs were measured by whole organ staining for beta-galactosidase activity and observed with a dissecting microscope. The dose of 10 mg/kg significantly inhibited tumor invasion but not metastasis. Interestingly, the number of factor VIII-positive microvessels in the tumors was not reduced by treatment at either dose level. These findings suggest that the anti-invasive effect of the IIF-2 conjugate may reduce both lymphatic and hematogenous metastases in this MKL-4 metastasis model without affecting angiogenesis.
Clin Exp Metastasis 1996 Mar
PMID:Invasion-inhibiting factor 2-albumin conjugate inhibits invasion and spontaneous metastasis of MKL-4 human breast cancer cells transplanted into female nude mice. 860 32

This prospective, randomized, controlled trial from the University of Hong Kong evaluated the efficacy of perioperative parenteral nutrition (PN) in patients requiring hepatectomy for primary hepatocellular carcinoma. From September 1990 through June 1993, 150 consecutive patients with resectable hepatocellular carcinoma were randomly assigned to receive either perioperative PN (n = 75), in addition to usual oral diet, or to no additional therapy (oral diet alone without PN; n = 75). Excluding patients with metastatic disease, a total of 64 patients in the perioperative PN group (39 with associated cirrhosis, 18 with chronic active hepatitis, and 7 without associated liver disease) were compared to 60 control patients (33 with cirrhosis, 12 with chronic active hepatitis and 15 with no associated liver disease). PN was started 7 days before hepatic resection and continued for 7 days after operation in the experimental patients. The PN consisted of standard micronutrients, dextrose, lipid emulsion (containing 50 percent of lipid as medium-chain triglycerides, MCT) and amino acids enriched in branched-chain amino acids (BCAA, 35 percent of PN protein intake), and provided = 1.5 g protein/kg/day and 30 kcal/kg/day. PN was administered via a superior vena cava Broviac catheter cycled over 12 hours each evening preoperatively, and as a 24 hour infusion during the postoperative week. Control patients received only 5 percent dextrose in normal saline postoperatively, with volume and sodium content similar to the experimental PN-treated patients. All patients studied (experimental and control) received 25 grams of albumin intravenously for 5 days postoperatively, and all were allowed to consume enteral diet as tolerated throughout the entire study period. Preoperative assessment included standard anthropometric indices, serum chemistries and proteins, indocyanine green clearance (an index of hepatic function), hand grip strength, and immune function tests (serum immunoglobulin concentrations and peripheral lymphocyte stimulation by phytohemagglutinin). Postoperative assessment included the same preoperative indices (chemistries measured from days 1 to 8 post-operatively), and overall postoperative mortality and morbidity during the hospitalization. Morbidity indices included both infectious complications and non-infectious complications (eg, pleural effusion, ascites, renal failure, hepatic coma). The two groups of patients were similar in age, sex, total and percent weight loss, hepatic carcinoma stage, incidence of cirrhosis, and other preoperative indices. However, a higher percentage of patients in the PN group had abnormal preoperative hepatic function by indocyanine green clearance (67 vs 47%, p = 0.03). The proportion undergoing major hepatectomy and other important intraoperative factors were similar between groups. No significant difference in postoperative hospital mortality occurred between groups (PN 8% vs control 15%; p = 0.30), and PN use did not change hand-grip strength, skin-fold thickness or midarm circumference. However, a significant beneficial effect of PN on hospital morbidity was observed Perioperative PN use was associated with a significant reduction in the overall postoperative morbidity rate (PN group 34% vs control group 55%; p = 0.02). This difference was mainly due to a significant reduction in infectious complications (PN 17% vs control 37%; p = 0.01), and in the need for diuretic drugs to control ascites (PN 25% vs control 50%; p = 0.004). There were no differences between groups in serum immunoglobulins or lymphocyte response to mitogens. There was less deterioration of liver function with PN as measured by the change in the rate of indocyanine green clearance (PN group -2.8% loss vs control group -4.8% loss; p = 0.05). The attenuation of hepatic function loss with PN occurred despite a significant rise in serum transaminase values from days 5 to 8 postoperatively. PN therapy was also associated with le
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PMID:Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. 878 71

Retrospective analysis of 135 patients who presented with liver metastases at the NCI-Free Cancer Clinic and the Aga Khan University Hospital, Karachi is presented. The mean age was 55 years and there was no significant sexual predilection. Commonly observed primary sites were gall bladder (13%), pancreas (11%), breast (10%), colorectum (8%) and lung (8%). In 41 cases (30%), primary location remained undetermined. Most common histologic type was adenocarcinoma in both sexes. Majority (83%) had multiple metastases. Amongst those with solitary metastatis, 78% had right lobe involvement. Almost half of the patients presented with constitutional symptoms alone, while 31% had signs and symptoms related to hepatic involvement. Overall, the most commonly deranged laboratory tests were LDH (93%), albumin (84%), gamma glutamyl transferase (78%) and alkaline phosphatase (76%). Chemotherapy was offered to most cases. Majority of patients expired, mostly due to hepatic failure. Median survival was 30 days and was shorter in those who presented with multiple metastases. These findings are compatible with previous reports and may assist in the management of these patients.
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PMID:Clinico-pathological features and survival of patients presenting with hepatic metastases: a retrospective analysis. 896 97

Pre-operative levels of the acute phase protein C-reactive protein (CRP), albumin (assessing nutritional status), the tumour marker CEA and three plasma protease inhibitors, i.e. C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III, were prospectively studied in 183 patients with various solid cancers. First, the predictive value of abnormal levels for operability at the primary operation was studied. Secondly, the predictive value of abnormal levels for cancer recurrence and metastases was evaluated during 2 years of follow-up. The results show that malignancy induces increased CRP and C1-esterase inhibitor levels and decreased albumin levels in serum. These changes, as well as raised alkaline phosphatase and lowered haemoglobin levels, also correlate to the 'overall' tumour burden. The most important conclusion is, that increased pre-operative CRP levels (CRP > or = 10 mg/l; sensitivity, 79%; specificity, 71%) and/or low albumin levels (albumin <37 g/l; sensitivity, 94%; specificity, 54%) are seen in inoperable cancer patients compared with patients having operable cancers. The second main important conclusion is, that high pre-operative C1-esterase inhibitor levels (C1-esterase inhibitor >152%; sensitivity, 45%; specificity, 90%), and in some patients a high alkaline phosphatase level, are seen in patients exhibiting early cancer recurrence (within 2 years post-operatively).
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PMID:Pre-operative plasma levels of C-reactive protein, albumin and various plasma protease inhibitors for the pre-operative assessment of operability and recurrence in cancer surgery. 900 49


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