Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neocarzinostatin is a protein antitumor antibiotic isolated from cultures of Streptomyces carzinostaticus var.F41. The drug has undergone extensive clinical trial in Japan, and has been reported active against a variety of human tumors. A phase I and preliminary phase II evaluation of the drug has been performed, using an iv bolus daily x 5 schedule. Ninety-six patients have been treated at doses from 500 to 2250 units/m2/day. Courses were repeated at 4-week intervals if allowed by bone marrow recovery. Dose-limiting toxicity was myelosupppression, which occurred late (median nadir, Day 27). Myelosuppression was more pronounced in patients who had received previous chemotherapy. In nine patients (9%) thrombocytopenia was prolonged (greater than or equal to 45 days) or irreversible. Acute administration of the drug was associated with rigors in approximately half the patients. Gastrointestinal side effects were mild. Three patients had a severe acute reaction resembling anaphylaxis. The maximally tolerated dose for this dose schedule is approximately 2250 units/m2/day. Antitumor activity has been seen in hepatoma and hematologic malignancies. Activity in lung and colorectal carcinoma appears limited with this dose schedule.
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PMID:Phase I and preliminary phase II study of neocarzinostatin. 22 Nov 12

Cholesterol, ubiquinone and dolichol biosynthesis from mevalonic acid was measured in non-malignant and malignant cultured human lymphocytes, freshly isolated human mononuclear leucocytes and in cultured human hepatoma cells. The relative flux of mevalonate into ubiquinone, dilichol and cholesterol was not significantly different between malignant and non-malignant cells, although the extent of labelling of each product was an order of magnitude greater in the malignant cultured cells. The most prominent dolichol isolated from total cellular lipid and synthesized in short-term labelling of cultured leukaemic cells had a chain length one isoprene unit shorter than that observed in normal human cells. Cultured human hepatoma cells and mononuclear leucocytes isolated from the peripheral blood of individuals with lymphoblastic and myelogenic leukaemia similarly synthesized shorter-chain dolichols. The dolichols made in cultured non-tumorigenic cells, freshly isolated mononuclear leucocytes from a normal individual or a patient with non-haematological malignancy had normal chain length.
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PMID:Dolichol biosynthesis in human malignant cells. 165 90

Seven patients of hematological malignancy with second primary cancer had been found at Veteran General Hospital from 1983 to 1988. The second primary cancers either developed subsequently or concurrently with the hematological malignancies. Four patients were diagnosed to be non-Hodgkin's lymphoma and three of them developed squamous cell carcinoma of lung(2) and hepatocellular carcinoma (1) at 44, 20 and 45 months after the initial diagnosis of on-Hodgkin's lymphoma. All three had received chemotherapy and/or radiotherapy. Another one was found to have liposarcoma in the retroperitoneum concurrently. Three patients had chronic lymphocytic leukemia (CLL). Two of them were found to have skin squamous cell carcinoma at the same time. Another one developed cervical squamous cell cancer ten months after treatment with oral leukeran and prednisolone. Literature about synchronous and metachronous neoplasms was reviewed.
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PMID:[Second primary cancer in hematological malignancy experience in VGH-Taipei]. 263 73

Carcinoembryonic antigen (CEA), a oncofetal glicoprotein, has been regarded as specific marker for colorectal cancer initially and restricted to the significance of tumor-associated antigen afterwards. Circulating CEA levels were determined in 47 patients with hematologic malignancies, resulting elevated in 10 (21%). The highest values had been discovered in a chronic lymphocitic leukemia complicated by primary hepatoma, causing the problem of the role played by the second tumor, likewise to another CEA-positive patient with the association "Hodgkin's disease-pancreatic carcinoma". The CEA employment had not been particularly satisfactory in the therapeutic monitoring and in the early detection of the relapses, in opposition to the results referred in the colorectal, mammary and bronchogenic carcinoma.
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PMID:[Evaluation of carcinoembryonic antigen (CEA) in patients with neoplasms and hematologic diseases]. 734 Jul 29

To investigate the roles of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTH-rP) in hypercalcemic patients with various malignancies, we measured the plasma levels of intact PTH and intact PTH-rP in five hypercalcemic patients with hematologic malignancies and 29 hypercalcemic patients with solid cancers. Ten eucalcemic cancer patients with either hepatocellular carcinoma or squamous cancer of the lung served as controls. The results showed a suppressed PTH level in all of the 34 hypercalcemic cancer patients. The PTH-rP levels were within normal limits (< 2.5 pg/mL) for all of the eucalcemic cancer controls, all of the five hematologic cancer patients with hypercalcemia, and only two out of the 29 hypercalcemic patients with solid cancers. The PTH-rP level was elevated in nearly all (27/29) hypercalcemic patients with or without bony metastasis. There was a good correlation between the corrected total serum calcium level and the natural log of PTH-rP level in 39 patients (10 eucalcemic and 29 hypercalcemic) with solid cancers (r = 0.75, p < 0.001). These results suggest that PTH-rP plays an important role in the hypercalcemia of patients with solid cancers, but this was not the case in our patients with hematologic malignancies. True ectopic secretion of PTH is unlikely in most of these patients. The mean serum total calcium levels of 17 hypercalcemic patients (13 solid cancers, four hematologic malignancies) dropped significantly after the third day of treatment with a new-generation bisphosphonate-clodronate product. This treatment consisted of 300 mg daily intravenous infusion for seven days, followed by oral administration (800 mg, bid) for the following three weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma PTH and PTH-rP levels and clodronate therapy in cancer patients with hypercalcemia. 791 69

Members of the DEAD/H box-containing helicase superfamily include proteins essential to genome replication, repair, and expression. We report here the cloning and initial characterization of a novel human member of this protein family, designated hHel1 (human helicase 1), now designated SMARCAD1 by HUGO. This DEAD/H box-containing molecule has seven highly conserved sequence regions that allow us to place it in the SNF2 family of the helicase superfamily. Uniquely, though, hHel1 contains two DEAD/H box motifs, a property not reported to be shared by any other SNF2 family members. This defines a new subfamily consisting of hHel1 and its homologues. In addition to these DEAD/H box/ATP-binding motifs, hHel1 has a putative nuclear localization signal and several regions that may mediate protein-protein interactions. Expression analysis indicates that hHel1 transcripts are ubiquitous, with particularly high levels in endocrine tissue. We have mapped the gene for hHel1 to human chromosome 4q22-q23; this region is rich in breakpoints and deletion mutants of genes involved in several human diseases, notably soft tissue leiomyosarcoma, hepatocellular carcinoma, and hematologic malignancies. Our observation that human Hel1 gene overexpression is present in an E1A-expressing cell line with increased capacity for gene reactivation events by genomic rearrangement suggests that human Hel1 may play a role in genetic instability development.
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PMID:SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases. 1103 Oct 99

The Ras gene product is a monomeric membrane-localized G protein of 21 kd that functions as a molecular switch linking receptor and nonreceptor tyrosine kinase activation to downstream cytoplasmic or nuclear events. Each mammalian cell contains at least three distinct ras proto-oncogenes encoding closely related, but distinct proteins. Activating mutations in these Ras proteins result in constitutive signaling, thereby stimulating cell proliferation and inhibiting apoptosis. Oncogenic mutations in the ras gene are present in approximately 30% of all human cancers. K-ras mutations occur frequently in non-small-cell lung, colorectal, and pancreatic carcinomas; H-ras mutations are common in bladder, kidney, and thyroid carcinomas; N-ras mutations are found in melanoma, hepatocellular carcinoma, and hematologic malignancies. The ras-signaling pathway has attracted considerable attention as a target for anticancer therapy because of its important role in carcinogenesis. In this review, the physiologic and biochemical properties of the Ras proteins, their mechanism of cell signaling, and their relation to human cancer will be discussed. Novel cancer therapeutic approaches based on the inhibition of Ras-mediated signaling, including inhibition of Ras processing, inhibition of Ras protein synthesis, and blockage of downstream Ras effectors, will be discussed.
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PMID:Blocking oncogenic Ras signaling for cancer therapy. 1209 90

Treatment with arsenic trioxide (As(2)O(3)) by inducing apoptosis and partial differentiation of acute promyelocytic leukemia (APL) cells results in clinical remission in APL patients resistant to chemotherapy and all-trans-retinoic acid. As(2)O(3) (iAs(III)) is methylated in the liver to mono- and dimethylated metabolites, including methylarsonic acid, methylarsonous acid, dimethylarsinic acid, and dimethylarsinous acid. Methylated trivalent metabolites that are potent cytotoxins, genotoxins, and enzyme inhibitors may contribute to the in vivo therapeutic effect of iAs(III). Therefore, we compared the potency of iAs(III) and trivalent metabolites using chemical precursors of methylarsonous acid and dimethylarsinous acid to induce differentiation, growth inhibition, and apoptosis. Methylarsine oxide (MAs(III)O) and to a lesser extent iododimethylarsine were more potent growth inhibitors and apoptotic inducers than iAs(III) in NB4 cells, an APL cell line. This was also observed in K562 human leukemia, lymphoma cell lines, and in primary culture of chronic lymphocytic leukemia cells, but not human bone marrow progenitor cells. Apoptosis was associated with greater hydrogen peroxide accumulation and inhibition of glutathione peroxidase activity. MAs(III)O, in contrast to iAs(III), did not induce PML-retinoic acid receptor alpha degradation, or restore PML nuclear bodies or differentiation in NB4 cells. In a cocultivation experiment, hepatoma-derived HepG2 cells, but not NB4 cells, methylate radiolabeled iAs(III). Methylated metabolites released from HepG2 cells are preferentially accumulated by NB4 cells. This experimental model suggests that in vivo hepatic methylation of iAs(III) may contribute to As(2)O(3)-induced apoptosis but not differentiation of APL cells. MAs(III)O as an apoptotic inducer should be considered in the treatment of other hematologic malignancies like lymphoma.
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PMID:Methylated metabolites of arsenic trioxide are more potent than arsenic trioxide as apoptotic but not differentiation inducers in leukemia and lymphoma cells. 1270 73

We review the therapeutic and preventive applications of a retinoid analog (vitamin A and its derivatives) for human cancers. Chemoprevention of cancer is an intervention in the carcinogenic process by chemical agents that block or reverse the malignant transformation of cells. Retinoids are prime candidates for cancer chemoprevention since cancer is characterized by abnormal growth with a lack of differentiation, which could be modified by retinoids. Retinoids exert their biological functions through nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR). A number of experimental and clinical studies have been performed in the past two decades with retinoids showing that they inhibit or reverse the carcinogenic process in some organs, including hematological malignancy as well as premalignant and malignant lesions in the oral cavity, head and neck, breast, skin and liver. We particularly focus upon the therapeutic application of all-trans RA (atRA) to acute promyelocytic leukemia (APL) and on the preventive approach to hepatocellular carcinoma (HCC) by a synthetic retinoid analog, acyclic retinoid. In both malignancies, malfunction of retinoid nuclear receptors is closely related to their carcinogenic process. In APL, a chromosomal translocation produces a chimeric protein between RAR alpha and a protein called promyelocyte leukemia protein (PML). PML-RAR alpha works as a dominant negative receptor in the leukemic cells, interfering with the normal function of RAR alpha and/or PML, which in turn results in the arrest of cell maturation at the stage of promyelocytes. Oral administration of atRA induces differentiation of promyelocytic leukemic cells to mature neutrophils, and leads to a high rates (over 90%) of complete remission. AtRA therapy has become standard in the treatment of APL. In the case of HCC, post-translational modification of RXR by phosphorylation impairs its function, which leads to uncontrolled cell growth. Acyclic retinoid suppresses the phosphorylation of RXR alpha, restores its function in the presence of its endogenous ligand, 9-cis RA, and thereby induces apoptosis of the cancer cells. Acyclic retinoid given orally successfully suppresses the development of second primary tumors in cirrhotic patients who undergo curative removal of preceding HCC. Eradication of (pre)malignant clones ('clonal deletion') from the liver is suggested as a mechanism of the chemopreventive effect. Further development of more effective retinoids as well as their use in combination with other classes of anticancer agents including immunopreventive drugs like interferons may provide strategies for cancer prevention.
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PMID:Retinoids in cancer chemoprevention. 1513 35

Secondary malignant tumors of the kidney are uncommon. These secondary tumors are usually the result of hematogenous spread from solid or hematologic malignancies. These tumors are almost always discovered at autopsy, with only 40 cases diagnosed prior to death reported in the literature. Primary tumors of the lung, breast and gastrointestinal tract are the most common sources of renal metastases. The occurrence of a renal secondary from a primary hepatocellular carcinoma is the subject of this presentation. To the best of our knowledge, such an occurrence has not been reported previously.
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PMID:Renal metastasis from primary hepatocellular carcinoma. A case report and review of the literature. 1526 1


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