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)

One hundred and thirty-nine patients with non-hematologic malignancy were studied to define the incidence of vitamin B12-related abnormalities and correlate them with clinical findings. Based on vitamin B12-binding patterns, the following relatively distinct groups were defined: (A) 50% had normal results; (B) 6% had very high transcobalamin (TC) I and vitamin B12 levels as reported in isolated instances previously: most had hepatic metastases and early death, and all had definite metastatic disease; (C) 11% had high vitamin B12 levels with little or no unsaturated TC I elevation: most also had hepatic and other metastases and early death; (D) 23% had high vitamin B12-binding capacity with normal TC I and vitamin B12 levels: there were no distinguishing features for this group other than an increased proportion of black patients; and (E) 10% had low vitamin B12 levels, in many cases not associated with vitamin B12 deficiency or other known causes of low serum levels. Thus, high serum vitamin B12 level, with or without unsaturated TC I elevation, usually implies a poor prognosis in a patient with cancer. However, while most such patients have hepatic and other metastases, hepatic involvement was not universal nor did most patients with hepatic disease have high vitamin B12 levels. High serum TC I thus is not always due to increased granulocytic proliferation or to hepatic tumor, and alternative mechanisms for TC I accumulation should be sought.
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PMID:Serum vitamin B12 and transcobalamin abnormalities in patients with cancer. 90 43

Elevation of transcobalamin I and serum vitamin B12 levels has usually been associated with increased granulocytic proliferation, such as occurs in chronic myelogenous leukemia. Two patients with metastatic cancer had extremely high serum vitamin B12 and transcobalamin I levels--greater than those seen in even the most intense granulocytic proliferation--that were not explainable by leukocytosis. The subjects' serum vitamin B12 levels were 18,750 and 21,221 pg per milliliter (normal, 471 plus or minus 174 pg per milliliter, mean plus or minus S.D.) and unsaturated vitamin B12 binding capacity 158,750 and 5,400 pg per milliliter (normal, 1153 plus or minus 313 pg per milliliter) respectively. The abnormally elevated serum binder was shown to be identical with transcobalamin balamin I in every respect. Levels of transcobalamin II and serum third binder were normal. The cause of the binder abnormality is unknown, but factors other than granulocyte proliferation may control or contribute to the production or accumulation of transcobalamin I.
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PMID:Extreme elevation of serum transcobalamin I in patients with metastatic cancer. 105 6

The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease progression remains to be established. In monitoring the response of hepatic metastases, CEA remains the least unsatisfactory marker but should always be used in conjunction with serial ultrasound scans. Tumour markers now play an important role in the diagnosis and monitoring of PLC but a role is also emerging in tumour imaging and drug targeting. The next 20 years should see the introduction of tumour markers of high sensitivity and specificity which make a fundamental contribution not only to detection and monitoring, but also to the effective treatment of liver cancer.
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PMID:Tumour markers in diagnosis and management. 243 83

This work includes results from studies on oesophageal cytopathology, dietary studies and the correlation of oesophageal cytological abnormalities and micronutrient blood levels in populations at risk for oesophageal carcinoma (OC) in remote rural areas of Southern Africa. The incidence of malignant lesions was 1.6 - 2.8%, and moderate to severe dysplastic lesions 0.5 - 1.8% in subjects aged over 35 years. Subjects 25-34 years of age showed malignant and dysplastic lesions in 0.8 and 1.3% respectively. Subjects younger than 24 years of age showed mild cytological lesions only. Early stages of OC were diagnosed in 8 patients. Three of them successfully underwent surgical intervention and are free from recurrence or metastases over a 3 year follow-up period. The incidence of mild oesophageal cytological lesions was inversely related to the frequency of the intake of green vegetables, fruit and animal proteins, and directly related to alcohol intake or tobacco smoking. A lower plasma concentration of vitamins A, E, B12 and folic acid was detected in individuals with cytological abnormalities. Of the mineral elements, only selenium, but not zinc, copper or magnesium was significantly related to the risk for OC on a regional or individual basis. An exceptionally low whole blood selenium level (58-72 ng/ml) and a relationship between its concentration and degree of cytological abnormalities were found.
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PMID:Oesophageal carcinoma: cytopathology and nutritional aspects in aetiology. 262 30

A 12 year old girl with a localised fibrolamellar hepatoma had a raised serum unsaturated vitamin B12 binding capacity (UBBC) and transcobalamin I (TCI) prior to complete resection and chemotherapy. Regular clinical and radiological follow-up detected no recurrence of her disease, but the UBBC and TCI slowly rose. Local recurrence and pulmonary metastases became detectable 2 1/2 years after diagnosis, 18 months after the UBBC and TCI level became elevated. Measurement of UBBC and TCI can help in the early detection of recurrence long before there is clinical or radiological evidence of recurrent fibrolamellar hepatoma.
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PMID:Transcobalamin I as a "marker" for fibrolamellar hepatoma. 301 64

Peritoneal carcinomatosis, a common spreading of human colon carcinoma, can be obtained by intraperitoneal injection of colon tumor cells in rats. When BDIX rats are injected with 10(6) syngeneic tumor cells, isolated and cloned from a chemically induced colon carcinoma, they die within 2-3 months with solid peritoneal tumors and hemorrhagic ascites. Repeated intraperitoneal injections of 20 micrograms endotoxins (Escherichia coli W0128:B12) from day 3 after tumor cell challenge inhibited tumor growth. This effect was long-lasting since 7 out of 10 treated rats were still alive and tumor-free 6 months after tumor cell challenge. When the endotoxins were administered from day 15 after the tumor cell challenge, in rats with established tumors visible with the naked eye, the survival times were significantly increased, and 6 out of 30 treated rats were still alive and tumor-free 6 months after tumor cell challenge. The optimum effect was obtained with 5 repeated injections. The different frequencies of injection tested, i.e. 1, 3 or 5 days apart were equally effective. Endotoxins were ineffective when administered intravenously. No side effect was observed.
Invasion Metastasis 1987
PMID:Treatment with endotoxins of peritoneal carcinomatosis induced by colon tumor cells in the rat. 358 23

A homogeneous group of 53 Caucasian subjects with high-grade osteosarcoma (OS) was typed for HLA-A and B locus antigens. Although no significant differences in the distribution of these antigens were found in comparison with 425 local controls, a trend towards an increase of HLA-B18 and decrease of HLA-B12 was observed. All the patients underwent amputation plus adjuvant chemotherapy and among the 29 patients with a follow-up longer than one year, 9 out of 10 subjects with HLA-A3 antigens developed metastases within a few months. None of the OS patients had the HLA-A3, B7 haplotype which is present in linkage-disequilibrium in the control population.
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PMID:Frequency and prognostic value of HLA antigens in osteosarcoma patients. 698 58

The possibility that anticoagulation with warfarin might inhibit the development of spontaneous metastases from intestinal carcinomas induced by azoxymethane (AOM) was tested in Sprague-Dawley rats with and without 60% distal small-bowel resection (DSBR). Warfarin (0.5 mg/l) was added to the drinking water from 1 week or 12 weeks postoperatively, and thromboplastin times were measured thereafter. AOM was given by 12 weekly s.c. injections (10 mg/kg/week), starting 1 week after DSBR. Besides increasing the sensitivity of rats to warfarin, DSBR itself caused partial anticoagulation, probably because of vitamin K malabsorption: at 30 weeks faecal fat was 59-93% higher, while serum B12 was 40% lower (> 0.05 P > 0.005). Adaptive growth of the jejunum and caecum after DSBR was manifested by 22-76% increases in segmental weight and surface area (P < 0.001). DSBR produced a 4-fold increase in duodenojejunal tumours at 15-25 weeks (P = 0.025) and a 76% increase in colorectal tumours at 25-35 weeks (P < 0.005). Eight of 20 control rats dying after 15 weeks had lymphatic metastases, compared with 0 of 15 rats with DSBR plus warfarin from week 1 (P = 0.005). The overall prevalence of metastases was reduced by both DSBR and warfarin, when assessed independently. Intestinal carcinogenesis induced by AOM is enhanced by the adaptive response to DSBR, but anticoagulation inhibits spontaneous metastases in this model.
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PMID:Effects of anticoagulation and ileal resection on the development and spread of experimental intestinal carcinomas. 742 32

A cloned cell line (IP-B12) derived from a transplantable rat pulmonary carcinoma (IP), of which neoplastic cells produce parathyroid hormone-related protein (PTHrP), was established. Tumors induced in syngeneic F344 rats by intraperitoneal injection of IP-B12 cells had features of pulmonary adenocarcinomas, consisting of neoplastic cells immunopositive to PTHrP. The IP-B12 tumor-bearing rats developed severe emaciation and hypercalcemia, with a marked elevation of plasma PTHrP level; there was an increase in osteoclastic areas of the femur and calcium depositions in systemic organs, indicating progression to humoral hypercalcemia of malignancy (HHM) in the tumor-bearing rats. In addition, the injection of IP-B12 cells into the left cardiac ventricle of syngeneic rats resulted in osteolytic skeletal metastases in the long bones and vertebrae. In the metastatic lesions, histologically, neoplastic cells showed an immunopositive reaction to PTHrP, and a prominent osteoclastic activity was seen; bone lesions, including osteolysis, fracture, and nerve compression as well as replacement of bone marrow cells by proliferated tumor cells were similar to those reported in human cancer patients with bone metastases. IP-B12 is a new animal model for HHM and osteolytic bone metastases, and will become a useful tool for studies on the pathogenesis and therapeutic strategies for such conditions.
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PMID:Establishment of a transplantable rat pulmonary carcinoma-derived cell line (IP-B12) as a new model of humoral hypercalcemia of malignancy and bone metastasis. 1285 1

An 11-year-old, male castrated, Labrador Retriever was evaluated for the presence of rapidly growing concurrent leg and intraocular masses. Metastasis was noted in the chest at time of initial presentation. Indium-111 labeled vitamin B12 imaging was performed, and there was significant uptake by both primary tumors and the lung metastases. Enucleation and amputation were performed for palliative relief. The leg mass was a grade 2 soft tissue sarcoma and the ocular mass a ciliary adenoma. The dog remained symptom-free for approximately 10 weeks before developing signs of respiratory distress. He was euthanized 12 weeks after initial presentation, and there was diffuse infiltration of the lungs with metastatic sarcoma. Indium-111 labeled vitamin B12 imaging identified a ciliary adenoma in this case and may provide a useful differentiation technique for evaluation of intraocular and retrobulbar masses if it can be demonstrated that there is differential uptake between inflammatory or infectious conditions and neoplasia.
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PMID:Indium-111 labeled vitamin B12 imaging of a ciliary adenoma with concurrent grade 2 soft tissue sarcoma of the leg in a Labrador Retriever. 1509 31


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