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)

Primary choroid plexus (CP) tumors are rare neoplasms that present in childhood or, less frequently, in adult life. The majority are benign and amenable to complete surgical excision, but occasionally more invasive variants are encountered. Although generally pathologically distinct, occasionally primary CP neoplasms may be difficult to distinguish from metastatic papillary carcinomas or papillary ependymomas. Conventional cytologic markers are not sufficiently specific to permit accurate diagnosis of primary CP tumors. The authors have reported that the CP is the unique site of synthesis within the brain of transthyretin (TTR, prealbumin), a transport protein for thyroxine and retinol. They therefore investigated the utility of TTR as a biochemical marker for CP tumors. They detected intense immunoreactivity for TTR at high dilutions of primary antiserum in the neoplastic epithelium of all of nine primary CP tumors (six papillomas and three carcinomas), but not in eight cellular or three papillary intracerebral ependymomas, meningiomas, oligodendrogliomas, astrocytomas, primary extracerebral papillary carcinomas (three thyroid, two breast) or five of six cerebral metastases from systemic papillary carcinomas. In one case of cerebral metastasis from papillary thyroid carcinoma, rare isolated immunoreactive cells were observed. Faint staining of the stromal-ependymal junction was seen in myxopapillary ependymomas of the filum terminale, which were otherwise nonreactive. By in situ hybridization, TTR mRNA was abundant in neoplastic CP epithelium, confirming local TTR synthesis. The authors conclude that TTR is synthesized by neoplastic CP epithelium and is an excellent marker for primary CP neoplasms.
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PMID:A marker for primary choroid plexus neoplasms. 235 63

Serum retinol levels were determined by a fluorometric method in patients with colorectal cancer or polyps and those with inflammatory bowel disease. Serum retinol levels in patients with benign or malignant colorectal polyps and stage B cancer (modified Dukes' classification) were similar to those found in controls. By contrast, serum retinol levels were significantly lower in patients with Dukes' stage C or D. Among cancer patients that were followed after surgical treatment serum retinol levels did not differ significantly from those found in controls. Patients who died of metastases during follow-up possessed very low serum retinol levels. These findings suggest that a decreased serum retinol level in cancer patients is a consequence rather than a precursor of the neoplastic process. Furthermore, this study suggests that the marked decrease in serum retinol level might be an indicator of poor prognosis in colorectal cancer patients after surgery.
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PMID:Serum retinol level in patients with colorectal premalignant and malignant lesions. 381 89

In order to determine whether low plasma levels of retinol and its carrier (retinol binding protein) are related to increased risk of cancer recurrence, these were measured in 103 patients who had had colorectal cancer surgically removed. According to the modification of the Dukes' classification, 66 had B2 tumours (with no nodal involvement' and 37 had C tumours (with lymph-node metastases). These patients were part of the Cross Cancer Institute Adjuvant GI Cohorts who were on the control arms receiving no further treatment. At the time of blood sample collection, they were believed to be free of neoplastic disease. The post-operative patients were found to be associated with subnormal circulatory levels of retinol (43.3 micrograms dl-1 vs 65.3 micrograms dl-1) and its carrier protein (4.6 mg dl-1 vs 5.7 mg dl-1), when compared with apparently healthy subjects. The latter being more markedly depressed in patients with "C" type tumour (3.8 mg dl-1) than that in those with "B2" type tumour (5.0 mg dl-1). These findings appeared to be persistent during the follow-up study when a second blood sample was collected, one to four months later from 40 patients. Furthermore, the initial plasma retinol level in conjunction with RBP was found to be even lower in 12 patients (35.1 micrograms dl-1, 3.7 mg dl-1) who subsequently had cancer recurrence than in those who remained free of apparent cancer (44.5 micrograms dl-1, 4.6 mg dl-1). The lowest initial values of retinol (19.3 micrograms; 18.8 micrograms dl-1) and RBP (2.4; 1.6 mg dl-1) recorded in the study were seen in the only two patients who died of the disease at the time of follow-up.
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PMID:Retinol and postoperative colorectal cancer patients. 403 54

Vitamin A is attracting increasing attention as a potential cancer chemopreventative agent. To investigate the effect of vitamin A on tumor establishment, growth and metastasis, rats were fed diets containing zero, adequate or excess (100X adequate) amounts of vitamin A prior to subcutaneous injection with transplantable hepatocellular carcinomas derived from solid tumors induced by N-2-fluorenylacetamide. When rats were injected at the same time the dietary regimen was begun, tumor growth was similar in both the deficient and adequate vitamin A groups with 20% less in the excess vitamin A group. However, when rats were injected 2 weeks post-initiation of the dietary regimen, tumors were fewer and appeared later under conditions of either vitamin A deficiency or excess. When rats were injected with a metastatic line 2 weeks following initiation of the dietary regimen, no metastases were observed in the animals fed excess vitamin A, but 60% had metastases in the deficient group and 75% in the adequate group. Results suggest that dietary extremes of vitamin A affect tumor establishment and growth and excess amounts prevent metastasis of transplantable hepatomas in the rat.
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PMID:Chemoprevention of tumor development and metastasis of transplantable hepatocellular carcinomas in rats by vitamin A. 624 1

In vitro and in vivo investigations have shown that nontoxic treatment with vitamin A (retinol) has an inhibitory effect on the growth of malignant cells. The tumorigenic CaMa -15 cell line responds to both retinol and retinoic acid under both anchorage-dependent and anchorage-independent conditions, reducing growth or colony formation by at least 50%. To date, there have been few studies on the effects of vitamin A on xenotransplanted neoplastic cells. Twenty-five adult female nude rats (rnu/rnu) were inoculated in the inguinal fat pad with 10(6) CaMa -15 cells, a tumorigenic epithelial cell line. The rats were divided into three groups: ten high dose (3 mg retinol/day i.p.); five low dose (30 micrograms retinol/day i.p.); and ten controls (corn oil i.p.). All animals were housed in specific-pathogen-free conditions and permitted access to sterile laboratory chow (5.4 micrograms retinol/g chow) and water ad libitum. Rats were sacrificed at 21 days after inoculation. Onset of tumor development occurred between Days 9 and 13 in all groups. Tumors grew progressively and were reduced in mean diameter by 26% (p = less than 0.05) with high-dose retinol and 44% (p = less than 0.02) by low-dose treatment. No clinical signs of vitamin A toxicity were apparent. Necropsy and radiological examination revealed no evidence of toxic effects or metastases. These results indicate that vitamin A can reduce the growth of xenotransplanted tumorigenic cells at nontoxic levels in T-cell-deficient hosts. The nude rat offers a potential model to study the inhibitory effects of retinoids on xenotransplanted cancers.
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PMID:Antiproliferative effect of vitamin A on xenotransplanted CaMa-15 cells. 672 79

Swainsonine, an alpha-mannosidase inhibitor which blocks Golgi oligosaccharide processing, represents a new class of compounds that inhibit both rate of tumor growth, and metastasis, in murine experimental tumor models. In this first phase I study, the quantitative and qualitative toxicities of swainsonine have been studied in patients given a continuous i.v. infusion over 5 days, repeated at 28-day intervals. Dose levels were escalated in increments of 100 micrograms/kg/day from 50-550 micrograms/kg/day. Nineteen patients with both solid tumor and hematological malignancies were given a total of 31 courses. Hepatotoxicity, particularly in patients with liver metastases, was the dose-limiting toxicity. The maximum tolerated dose (MTD) and the recommended starting dose (MTD -1 level) were 550 and 450 micrograms/kg/day, respectively. Common side effects included edema, mild liver dysfunction, a rise in serum amylase, and decreased serum retinol. Acute respiratory distress syndrome possibly precipitated by swainsonine resulted in a treatment-related death in a patient with significant pretreatment hepatic dysfunction. One patient with head and neck cancer showed > 50% shrinkage of tumor mass for 6 weeks after treatment. Two patients with lymphangitis carcinomatosis on chest X-ray noted improvement in cough and shortness of breath during the infusion of swainsonine and for 1 week thereafter. Clearance and serum half-life for swainsonine were determined to be approximately 2 ml/h/kg, and 0.5 day, respectively. Golgi oligosaccharide processing, a putative anticancer target for swainsonine was inhibited in peripheral blood lymphocytes as evidenced by a marked decrease in leukoagglutinin binding after 5 days of treatment. Oligomannosides in patient urine increased 5-to 10-fold over the 5 days of treatment, indicating that tissue lysosomal alpha-mannosidases were also blocked by swainsonine. Urine oligomannoside accumulation reached steady state at 3 days, approximately 1 day after serum drug levels reached steady state. The fraction of HLA-DR-positive cells in peripheral blood lymphocytes increased following 5 days of swainsonine treatment, an effect similar to that observed for peripheral blood lymphocytes from normal subjects cultured with swainsonine. No significant changes in CD3, CD4, CD8, CD16, and CD25 were observed. Swainsonine produces minimal toxicity when administered i.v. to cancer patients at dosages that inhibit both Golgi alpha-mannosidase II and lysosomal alpha-mannosidases. Detection of hepatic metastases or liver enzyme abnormalities prior to treatment predict for more significant toxicity.
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PMID:A phase I study of swainsonine in patients with advanced malignancies. 813 47

The pharmacokinetics of 13-cis-retinoic acid (13cisRA) and its effects on retinol plasma levels were investigated after the first and the last doses in melanoma patients, who participated in a study run to assess tolerance over a long period of a treatment schedule of 13cisRA associated with recombinant interferon alpha2a (rIFN-alpha2a). Melanoma patients with regional node metastases after radical surgery were randomized to be treated for 3 months with rIFN-alpha2a, 3 x 10(6) IU s.c. every other day, associated with oral 13cisRA at doses of 20 mg day(-1) (five patients) or 40 mg every other day (seven patients). Maximum 13cisRA blood concentrations usually occurred 4 h after drug administration, with average values of 406 and 633 ng ml(-1) (i.e. 1.3 and 2.1 microM) after the 20 and 40 mg dose respectively. The average half-life (t(1/2)) was approximately 30 h. The maximum concentration, the t(1/2) and the area under the concentration-time curves from 0 to 48 h (AUC(0-48)) of 13cisRA did not change after multiple dosing, whereas the AUC(0-48) of its major blood metabolite, 4-oxo-13-cis-retinoic acid, increased. Immediately after 13cisRA treatment, retinol plasma levels started to decline and they reached the lowest values (approximately 20% reduction) shortly after the time of maximum 13cisRA concentrations (i.e. 4-12 h after drug intake). Afterwards, values returned to baseline. The amount of retinol reduction in time was correlated with 13cisRA maximum concentrations.
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PMID:Pharmacokinetics and effects on plasma retinol concentrations of 13-cis-retinoic acid in melanoma patients. 941 58

Because of the poor response of pancreatic cancer to conventional therapy, the authors performed a phase II pilot study to evaluate whether beta-interferon and retinoids, added to active chemotherapeutic agents, could increase response rate and survival in a group of patients who had metastatic disease. Twenty-three chemotherapy-naive patients were treated as follows: epirubicin, 60 mg/m2, and mitomycin C, 10 mg/m2, intravenously on day 1; folinic acid, 200 mg/m2, and 5-fluorouracil (5-FU), 370 mg/m2, intravenously for 5 consecutive days. beta-Interferon, 1 x 10(6) IU/m2, subcutaneously three times a week, and retinol palmitate, 50,000 IU orally twice a day, were given between chemotherapy cycles. Patients having responses and disease stabilization were maintained with the same dose of beta-interferon and retinol palmitate. Treatment was given every 4 weeks for four courses or until onset of progression. A median of three courses of chemotherapy was delivered to each patient. All patients were evaluable. Eight patients responded (35%) and 8 (35%) had stable disease. Median time to progression and survival for all patients were, respectively, 6.1 months and 11 months. Toxicity was severe: 60% of patients had hematologic toxicity, 40% had gastrointestinal toxicity, 13% had cardiac toxicity, and 1 patient had a hemolitic-uremic syndrome. The combination of chemotherapy, beta-interferon, and retinoids shows activity in metastatic pancreatic carcinoma. Toxicity was high but patients who had responses and disease stabilization had prolonged symptom palliation.
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PMID:Advanced carcinoma of the pancreas: phase II study of combined chemotherapy, beta-interferon, and retinoids. 962 97

Oral cancer is often preceded by precancerous lesions, the most common of which is leukoplakia. Several treatment modalities are available: elimination of the possible cause, cold knife, laser, or cryosurgery, and topical application of bleomycin and 5-fluorouracil. In research, oral leukoplakia is used as a model to study the value of chemoprevention as a strategy to prevent cancer, because its effect is directly visible and material for analysis is easily obtainable from the mouth. In several studies and chemoprevention trials the efficacy of retinoids, retinol and/or beta-carotene on oral leukoplakia has been demonstrated. Second primary tumors occur in 10-30% of head and neck cancer patients and 10% of lung cancer patients. Chemoprevention offers an attractive approach to combat this threat to such patients, which is bound to cast a shadow over their lives. In the last 10-15 years several chemoprevention studies with vitamin A, retinoids or agents working through other mechanisms (antioxidants) have been launched. The largest chemoprevention study in curatively treated early-stage oral cancer, laryngeal cancer and lung cancer (N = 2595) is EUROSCAN, an EORTC study initiated in 1988. End-points are second tumors, local/regional recurrence and distant metastases, and long-term survival rates. Preminary results will be available in 1998.
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PMID:Chemoprevention of head and neck and lung (pre)cancer. 1033 16

Vitamin A possesses both wound-healing and antitumor actions. Vitamin A-induced fibroplasia results in subsequent increased collagen production and deposition. This effect of vitamin A has been shown to result in the production of collagenous capsules around several murine breast and lung tumor systems. This tumor encapsulation process can potentially convert a systemic disease to a local one that can be easily treated by tumor excision. The goal of the present study was to determine whether supplemental vitamin A could promote the encapsulation of a murine melanoma. Sixty DBA/2J male mice were inoculated intracutaneously with 1 x 106 Cloudman S91 melanoma cells using a 30-gauge needle. The mice were divided into three groups: a control group, a pre-vitamin A group, and a post-vitamin A group. The control mice were fed a commercial chow containing 15,000 IU of vitamin A and 6.4 mg of beta-carotene per kilogram diet, considerably more than the National Research Council's recommended daily allowance of vitamin A for normal mice. The control diet was, therefore, not vitamin A-deficient. The pre-vitamin A mice were fed the basal chow supplemented with 150,000 IU of vitamin A per kilogram diet for 10 days before inoculation and for the remainder of the study. The post-vitamin A mice were fed the vitamin A-supplemented diet beginning on the day of inoculation and continuing for the remainder of the study. Sixty days after inoculation, tumor growth was assessed and the five mice remaining in each group were euthanized. Ventral skin at the site of inoculation was harvested for histologic assessment of local tumor growth and invasiveness. The liver and lungs of each of these mice were also harvested for histologic assessment of tumor metastasis. Sixty days after tumor inoculation, a 60 percent survival rate was observed in the control group as opposed to the vitamin A-supplemented animals, which demonstrated a 100 percent survival rate in both groups (n = 5 in each group). Decreased mean tumor size and gross tumor in most vitamin A-supplemented animals were statistically significant when compared with the control animals. The control animals had a mean tumor size of 26.1 mm, whereas the post-vitamin A group had a mean tumor size of 5.7 mm. One hundred percent of the control group exhibited tumor; one animal had distant metastases. The pre-vitamin A group did not exhibit any tumor growth, and the post-vitamin A group exhibited tumor growth in 40 percent of animals. Neither vitamin A-supplemented group showed any evidence of distant metastases. The animals supplemented with vitamin A demonstrated decreased tumor growth and metastasis. This in vivo model may indicate a potential prophylactic and therapeutic role for supplemental vitamin A in the treatment of malignant melanoma.
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PMID:Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A. 1283 88


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