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)

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.
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PMID:Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. 223 Aug 77

Tumor-induced neovascularization is essential for invasion, metastases, and exponential growth of solid tumors. The authors studied the differences in macromolecular leakage from the neovasculature of a fast-growing, early-metastasizing tumor, the Walker 256 carcinosarcoma, and a slow-growing, nonmetastasizing tumor, a rat chondrosarcoma. A 1-mm3 piece of the Walker 256 carcinoma or the chondrosarcoma was implanted in the cremaster muscle of rats. Five days after surgery the cremaster muscle with the implanted tumor was placed in a special bath containing Krebs solution such that the circulation and nerves from the animal to the cremaster were intact. Fluorescein isothiocyanate-labeled rat serum albumin (FITC-RSA) was injected (intra-arterially) into each rat to permit visualization of the vasculature by fluorescent microscopy. A closed-circuit television system was used to quantitate macromolecular leakage as a change in interstitial fluorescent intensity. Data are given as a relative fluorescent intensity (mean +/- standard error of the mean) in an area of the cremaster with tumor-induced neovascularization. These studies demonstrated that the vasculature induced by rapidly growing Walker 256 carcinosarcoma leak albumin freely when compared with the vasculature induced by the slow-growing chondrosarcoma. Furthermore, there was a significant increase in fluorescent intensity (albumin leakage) in the Walker tumor from 1 minute (24 +/- 3.0) to 30 minutes (49 +/- 5.6). In the normal cremaster area there was a significantly lower fluorescent intensity in the interstitium and a very slight increase with time (4 +/- 1.5 at 1 minute vs. 7 +/- 1.4 at 30 minutes). One interpretation of these data is that the mechanisms responsible for protein leakage from the vasculature of the Walker tumor may be involved in the fast growth and metastases of this tumor as compared with slower-growing tumors such as the chondrosarcoma.
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PMID:Differential macromolecular leakage from the vasculature of tumors. 241 77

Variation in response rates to chemotherapy and survival in patients with hepatic metastases from colorectal carcinoma may be due to patient selection factors. The prognostic importance of 13 factors were analyzed in 112 patients with only hepatic metastases, who were eligible for hepatic artery infusional chemotherapy. When individually analyzed, six factors were found to significantly (less than 0.001) affect survival: the percentage of tumor involvement of the liver, assessed medically or surgically; initial serum albumin and lactic dehydrogenase; initial Karnofsky performance status; and weight loss. Patients with less than or equal to 30% liver involvement had a median survival of 24 months versus 10 months if they had greater than 30% involvement. There was a highly significant agreement between medical and surgical assessment of liver involvement (P = 0.0001). When the variables affecting survival were studied together by multivariable analyses, the most important factor was the medical assessment of liver involvement accomplished by evaluation of radionuclide liver scan and CTT scans. The next two most important factors in the model were the ability of the patient to obtain a tumor response and the presence or absence of weight loss. Only one factor helped predict response to chemotherapy, the type of perfusion seen on a 99Technetium-macroaggregated albumin (MAA) arterial flow scan. Forty-five percent of patients with good perfusion had a partial response while 13% of patients with poor perfusion had a tumor response (P = 0.006). We recommend that future studies, dealing with patients who have hepatic metastases from colorectal carcinoma and are eligible for hepatic arterial infusion, document and stratify for the following factors: the percentage of liver involvement, the presence or absence of weight loss, and the type of perfusion seen on MAA scans.
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PMID:Prognostic variables in patients with hepatic metastases from colorectal cancer. Importance of medical assessment of liver involvement. 252 70

The discriminative ability of several skeletal and tumour markers was assessed in 102 patients with prostatic disease. These comprised serum acid and alkaline phosphatase, serum albumin and osteocalcin, urinary excretion of calcium, hydroxyproline and 6-oxo prostaglandin F1 alpha. None of the tests was of value in distinguishing patients with benign prostatic disease from those with tumour not involving the skeleton. Values of serum osteocalcin, urinary excretion of calcium and urinary 6-oxo prostaglandin F1 alpha failed to discriminate significantly between patients with or without metastases. The remaining four markers were compared by decision matrix analysis and receiver operating characteristic (ROC) curves. Serum alkaline phosphatase provided the most sensitive marker of skeletal metastases (80.5%), followed by serum acid phosphatase (80%), hydroxyproline (68%) and albumin (30%). ROC analysis suggested that alkaline phosphatase conformed most closely to the "ideal marker" with highest specificity and sensitivity.
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PMID:Biochemical markers and skeletal metabolism in carcinoma of the prostate. Use of decision matrix theory and ROC analysis. 300 34

Fifty-two patients with histologically confirmed small-cell carcinoma of the lung, 15 with disease localized to one hemithorax and 37 with extensive metastases, were studied. Only patients whose general condition was considered good enough to tolerate intensive combination chemotherapy were included in this study. The median survival time of these patients was 33 weeks (range 7-192 weeks) with a mean survival time of 43 weeks. Patients who responded with objective tumour improvement within 6 weeks had a median survival time of 39 weeks. Those showing disease stabilization at 6 weeks had a median survival time of 35 weeks while those having disease progression at this time had a median survival of 22 weeks. Patients without liver involvement and a normal serum albumin level at the start of treatment had statistically superior survival times.
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PMID:Prognostic factors in patients with small-cell carcinoma of the lung. 302 57

One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less than .05) and independent prognostic variables for survival duration. For colorectal cancer, serum albumin, alkaline phosphatase, lactic dehydrogenase (LDH) levels, and percent targeted caloric intake (TCI) were significant independent predictors of survival duration.
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PMID:A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer. 302 67

DNR can be targeted to the liver by linking to galactosylated human serum albumin (AG). The linkage is stable in the blood stream and allows the release of active DNR after endocytosis of the conjugate by the target cells. Receptors for AG are present at the cell membrane of hepatocytes, primary human hepatoma cells and lung metastases. After i.v. administration of AG-DNR more than 70% of the drug is taken up by the liver and in rats 50% of DNR is eliminated in the bile after 16 h. Nude mice bearing human hepatoblastoma cells implanted s.c. were treated twice a week with a dose equivalent to 6.6 mg/kg of DNR either for the free drug or the conjugate AG-DNR. After 7 injections, tumor growth is inhibited in both case, however, the conjugate seems more active and is at least twice less toxic in terms of LD50. A phase I clinical trial of AG-DNR on 11 patients bearing hepatocarcinoma revealed that despite a transitory hyperthermia (37-38 degrees C) during the first day of the 4 day-perfusion, and modifications of hepatic enzymes in 3 cirrhotic patients, no hematologic and cardiac toxicity could be detected. A subjective response has been obtained in half of the patients with a decrease of plasmatic alpha-foetoprotein levels by more than 50% in 4 patients and one complete remission of more than 23 months with disparition of pulmonary metastases.
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PMID:[Targeting of anthracyclines and hepatomas]. 303 67

Between 1975 and 1986, the Manchester Lymphoma Group treated 127 patients with localized (Stages I/II) high and intermediate grade non-Hodgkin's lymphoma (NHL) on one of three protocols of combined involved field radiotherapy and chemotherapy. The study included patients with widespread bulky abdominal disease providing there was no apparent spread outside the abdomen and the liver was not involved with metastatic disease. The median duration of follow-up was 70 months. The complete response rate was 86% and the overall 5-year survival was 70%. The 5-year relapse-free survival of the complete responders was 80%. Cox model multivariate analysis showed that bulk disease (greater than 5 cm), low serum albumin and gut involvement were the pretreatment factors associated with shorter survival. When remission status was included in the model the attainment of a complete response was the major determinant of long-term survival but bulk disease and gut involvement were still significant adverse predictors for survival. These factors need to be assessed when analysing results of therapy in NHL and in the design of future treatment strategies.
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PMID:Prognostic factors in stage I and II high and intermediate grade non-Hodgkin's lymphoma. 320 6

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
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PMID:Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. 349 66

Adoptive immunotherapy with lymphokine-activated killer cells and recombinant interleukin 2 (IL 2) can produce significant reduction of visceral metastases in tumor-bearing mice and, as shown recently, in humans with disseminated cancer. Because further dose escalations of IL 2 have been prevented by the development of a vascular leak syndrome (VLS) in both mice and humans, we investigated this VLS in mice undergoing the systemic administration of high-dose IL 2. A model for quantitating capillary permeability was used in which 125I-bovine serum albumin was injected i.v., and 2 hr later, tissues were counted in a gamma analyzer. A permeability index (PI) was calculated by dividing the mean counts per minute (cpm) of tissues from IL 2-treated mice by those from control animals. The injection of IL 2 produced increases in vascular permeability that were most pronounced in the thymus, spleen, lungs, liver, and kidneys (PI = 18.0, 10.0, 9.7, 6.7, and 6.3, respectively, on day 6). The development of the VLS was highly dependent on the number of days of IL 2 treatment (for example, the lungs contained 638, 1382, 3350, and 6187 cpm after 0, 1, 3, and 6 days of IL 2, respectively). Moreover, the degree of the VLS was directly related to the dose of IL 2 administered. Measurement of the wet and dry weights of lungs from IL 2-treated mice demonstrated that IL 2 produced a dramatic increase in their water weight (from 0.10 g at base line to 0.22 g after 200,000 U of IL 2 for 6 days). The injection of the IL 2 excipient failed to induce capillary leakage in tissues. Immunosuppression of mice by pretreatment irradiation (500 rad) or by injection of cyclophosphamide or by concurrent use of cortisone acetate markedly reduced or eliminated the development of the VLS. Similarly, the VLS was not observed in nude mice receiving IL 2. Thus, the administration of IL 2 produces a dose-limiting VLS that may be mediated, directly or indirectly, by host lymphoid elements.
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PMID:Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. 352 89


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