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

The level of serum alpha-fetoprotein (AFP) was estimated by radioimmunoassay in 153 normal healthy Malysians of different ethnic groups. The mean level was 7.5 In1/ml (SD 2.28InU/ml). Among 330 patients with malignant tumors, 11 had increased levels of AFP. The only patient who had hepatoma had a very high level of serum AFP. High levels were also found in three of four patients with dysgerminoma of the ovary, in the only two patients with carcinoma of the testis, and in one patient with secondary carcinoma of the humerus of unknown origin. Lower, but significantly increased levels were observed in one patient (of 48) with breast carcinoma, one patient (of 8) with basal cell carcinoma of the nose, one patient (0f 27) with carcinoma of the lung, and one patient (of 59) with nasopharynegeal carcinoma.
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PMID:Radioimmunoassay of serum alpha-fetoprotein in patients with different maliganant tumors. 5 26

Soluble proteoglycans (SPG) were extracted from bovine (BCC) and human (HCC) costal cartilages by the dissociative method using 4 M guanidinium chloride (GuHCl). Proteoglycans which are resistant to extraction (RPG) were obtained following collagenase digestion or hydroxylamine treatment of the cartilage residues. Similarly, SPG were extracted from bovine metaphyseal and cortical bone using EDTA. The RPG were extracted from the bones using hydroxylamine. Density gradient fractionation under dissociative conditions of cartilage SPG and RPG followed by chromatography on Sepharose 2B revealed that A1D1 RPG are smaller than the SPG. SPG reacted with either collagenase or hydroxylamine are also smaller than the parent SPG. A1D1 fractions obtained from BCC-SPG and RPG or from mixtures of SPG and acid-soluble collagen are free of hydroxyproline. Hydroxyproline is not completely separated from HCC-RPG. Density gradient fractionation of bone proteoglycans and Sepharose chromatography of the A1 and A1D1 fractions showed that those obtained from metaphysis are larger than those from cortical bone. This was attributed to the presence of calcified cartilage in metaphyseal bone. The A1D1 fractions of the metaphyseal proteoglycans seemed to undergo self-association since this fraction is larger than the A1 fraction from which it is derived. Cortical bone proteoglycans do not behave similarly. Density gradient purification under dissociative conditions failed to separate hydroxyproline from the proteoglycans obtained from bone. It is hypothesized that in bone proteoglycans and collagen might be linked.
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PMID:Studies on extractable and resistant proteoglycans from metaphyseal and cortical bone and cartilage. 626 Mar 14

We developed transgenic rabbits with a DNA construct containing the proto-oncogene c-myc conjugated to the Ig kappa-chain enhancer gene, E kappa. One of four transgenic rabbits was mated to a normal rabbit and we used the offspring to develop a colony of rabbits carrying the E kappa-myc transgene in their germline. Of a total of 19 E kappa-myc transgenic rabbits, eight developed tumors. The tumors were characterized histologically and four were diagnosed as lymphoma, and one each was diagnosed as embryonic carcinoma, hepatoma, ovarian carcinoma and basal cell carcinoma. By Southern analysis, we showed the four lymphomas were of B-lymphoid lineage and by nucleotide sequence analysis we found three of them most likely used VH1 in their VDJ gene rearrangements. Cells from the embryonic carcinoma, the hepatoma and two of the B-lymphomas were adapted to tissue culture. We discuss the possibility that tumors of non-lymphoid origin develop in the E kappa-myc transgenic rabbits because of the potential for NF-kappa B to activate the kappa-enhancer in cells other than B-lymphoid lineage cells.
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PMID:Lymphoid and non-lymphoid tumors in E kappa-myc transgenic rabbits. 780 3

We are giving an overview over the clinical features and different therapeutic options of HIV associated malignancies. There are three AIDS-defining malignancies: - Kaposi's sarcoma - Non-Hodgkin's lymphoma (NHL) - cervical cancer. In Kaposi sarcoma there is a broad therapeutic spectrum from cryotherapy to systemic chemotherapy depending on the site and stage of the Kaposi sarcoma. In NHL early therapeutic intervention is necessary because of the fast progress of the tumor. The cervical cancer in HIV-infected women seems to be more aggressive than in non-infected and also needs early therapeutic intervention. Many other tumors seem to occur more frequently in patients with HIV infection: anorectal cancer, malignant testicular tumors, lung cancer, Hodgkin's lymphoma, basal cell carcinoma, squamous cell carcinoma, and even malignant melanoma. The cancer incidence in HIV-patients seems to be higher among nonblacks. Most of the immunodeficiency associated tumors are virus induced and they are accompanied by a persistent viral infection, including HHV-8 in Kaposi's sarcoma; Epstein Barr virus (EBV) in NHL; and human papillomavirus (HPV) in cervical cancer. But there are also types of virus induced tumors which are not frequently associated with HIV-infection like the primary hepatocellular carcinoma in patients with hepatitis B virus infection.
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PMID:Clinical manifestations and therapies of AIDS associated tumors. 950 54

Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.
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PMID:Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. 976 49

Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water.
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PMID:Pathology related to chronic arsenic exposure. 1242 52

3,3'-Dimethylbenzidine dihydrochloride is one of five chemicals being evaluated in 2-year carcinogenicity and toxicity studies as part of the NTP's Benzidine Dye Initiative. This Initiative was designed to evaluate representative benzidine congeners, benzidine congener-derived dyes, and benzidine-derived dyes. 3,3'-Dimethylbenzidine dihydrochloride was nominated for study because of the potential for human exposure during production of bisazobiphenyl dyes and because benzidine, a structurally related chemical, is a known human carcinogen. Toxicology and carcinogenesis studies were conducted by administering 3,3'-dimethylbenzidine dihydrochloride (approximately 99% pure) in drinking water to groups of F344/N rats of each sex for 14 days, 13 weeks, or 9 or 14 months. The 14-month exposures were planned as 24-month exposures but were terminated early because of rapidly declining animal survival, due primarily to neoplasia. These studies were performed only in rats because similar studies were being performed in mice at the National Center for Toxicological Research (NCTR). Hematologic and serum chemical analyses and thyroid hormone determinations were conducted in conjunction with the 13-week and 9-month studies. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary (CHO) cells, and Drosophila melanogaster. 14-Day Studies: Rats were exposed to 3,3'-dimethylbenzidine dihydrochloride in drinking water at doses ranging from 600 to 7,500 ppm. All five males and one female in the 7,500 ppm group and 1/5 males in the 5,000 ppm group died. Final mean body weights were decreased in males receiving 1,250 ppm or more and in all exposed females, and final mean body weights of animals receiving 2,500 ppm or more were lower than initial weights. Water consumption decreased with increasing chemical concentration. Compound-related effects observed in rats receiving 5,000 ppm or more included minimal to slight hepatocellular necrosis, accumulation of brown pigment (presumably bile) in individual hepatocytes, increased severity of nephropathy relative to controls, and severe lymphocytic atrophy of the thymus. Treated animals also showed an increased severity of atrophy of the bone marrow relative to controls, varying degrees of lymphocytic atrophy of the mandibular and mesenteric lymph nodes and spleen, increased vacuolization and necrosis of cells of the adrenal cortex, focal acinar cell degeneration in the pancreas, and, in males, increased immature sperm forms in the testis and epididymis. 13-Week Studies: 3,3'-Dimethylbenzidine dihydrochloride was administered in drinking water at doses of 300, 500, 1,000, 2,000, and 4,000 ppm. All rats receiving 4,000 ppm and 4/10 males and 1/10 females receiving 2,000 ppm died before the end of the studies. Depressions in final mean body weight relative to controls ranged from 12% to 48% for males and from 9% to 42% for females. Water consumption decreased with increasing dose. At compound concentrations of 300 to 2,000 ppm, mean water consumption was 29% to 83% of control values. Compound-related effects included an increase in the severity of nephropathy relative to controls; hepatocellular necrosis and accumulation of brown pigment (presumably bile) in sinusoidal lining cells; lymphocytic atrophy of the thymus, spleen, and mandibular and mesenteric lymph nodes; atrophy of the bone marrow in the higher-dose groups; degeneration of pancreatic acinar cells; and, in males, immature sperm forms in the testis and epididymis. Decreases in serum triiodothyronine (T3) values were observed in exposed females, and decreases in mean thyroxin (T4) concentrations in exposed males and females; no significant changes were observed in thyroid stimulating hormone (TSH) levels in exposed rats. Based on the decreased survival, reductions in water consumption and body weight gain, and chemical-induced hepatocellular and renal lesions observed in the 13-week studies, the doses selected for the 9- and 14-month drinking water studies of 3,3'-dimethylbenzidine dihydrochloride were 0, 3 3,3'-dimethylbenzidine dihydrochloride were 0, 30, 70, and 150 ppm. Seventy rats of each sex were used in the control group, 45 in the low-dose group, 75 in the mid-dose group, and 70 in the high-dose group. 9-Month Studies: Ten rats of each sex in the control and 150 ppm dose groups were evaluated after 9 months. Chemical-related effects observed in exposed animals included alveolar/bronchiolar carcinoma in one male, basal cell carcinoma of the skin in one male, a squamous cell carcinoma of the oral cavity in one female, preputial gland carcinoma in two males, clitoral gland carcinoma in three females, adenocarcinoma of the small intestine in two males, Zymbal's gland carcinoma in two males and three females, hepatocellular carcinoma in two males, and adenomatous polyps of the large intestine in three males. Other effects seen in dosed rats included focal cellular alteration in the liver, lymphoid atrophy in the spleen, and increased severity of nephropathy relative to controls. An increase in serum T3 values was observed in exposed males, and a decrease in mean T4 concentrations in exposed males and females. TSH concentrations were increased in exposed male and female rats. Body Weights and Survival in the 14-Month Studies: The average amount of 3,3'-dimethylbenzidine dihydrochloride consumed per day was approximately 1.8, 4.0, or 11.2, mg/kg for low-, mid-, or high-dose male rats and 3.0, 6.9, or 12.9 mg/kg for low-, mid-, or high-dose female rats. The mean body weight of high-dose males was about 85% of the control value by week 28. By the end of the study, mean body weights of low-, mid-, and high-dose males were 97%, 92%, and 70% of the control values, respectively. Mean body weights of high- and mid-dose females were about 85% of the control values at week 32 and week 44, respectively. At the end of the study, mean body weights of exposed females were about 94%, 81%, and 74% of the control values for low-, mid-, and high-dose groups, respectively. Because of extensive neoplasia, many exposed males and females were dying or were sacrificed moribund in the first year, and all high-dose males died by week 55. The studies were terminated at weeks 60 to 61, at which time the group survivals were male: control, 60/60, low dose, 41/45; mid dose, 50/75; high dose, 0/60; female: 59/60; 39/45; 32/75; 10/60. Nonneoplastic Effects in the 14-Month Studies: Increases in nonneoplastic lesions in dosed rats included cystic degeneration and foci of cellular alteration in the liver; exacerbation of nephropathy; and focal or multifocal hyperplasia of the Zymbal's gland, preputial and clitoral glands, and alveolar epithelium. Neoplastic Effects in the 14-Month Studies: Neoplasms were observed in exposed rats at many sites: skin, Zymbal's gland, preputial and clitoral glands, liver, oral cavity, small and large intestine, mammary gland, lung, brain, and mesothelium. The incidence of these neoplastic effects in male and female rats is summarized in the table at the end of this section (see page 8 of the Technical Report). Genetic Toxicology: 3,3'-Dimethylbenzidine dihydrochloride was mutagenic in Salmonella typhimurium strain TA98 with exogenous metabolic activation; it was not mutagenic in strains TA100, TA1535, or TA97 with or without activation. 3,3'-Dimethylbenzidine dihydrochloride induced sister-chromatid exchanges (CHO) and chromosomal aberrations in CHO cells in the absence of exogenous metabolic activation; these effects were not evident in test with S9 activation. Sex-linked recessive lethal mutations were induced in germ cells of adult male Drosophila melanogaster administered 3,3'-dimethylbenzidine dihydrochloride in feed or by injection. No reciprocal translocations occurred in D. melanogaster germ cells following exposure to 3,3'-dimethylbenzidine dihydrochloride. Conclusions: Under the conditions of these 14-month drinking water studies, there was clear evidence of carcinogenic activity of 3,3'-dimethylbenzidine dihydrochloride for male F344/N rats, as indicated by benign and malignant neoplasms of the skin, Zymbal's gland, preputial gland, liver, oral cavity, small and large intestine, lung, and mesothelium. Increased incidences of neoplasms of the brain may have been related to chemical administration. There was clear evidence of carcinogenic activity for female F344/N rats, as indicated by benign and malignant neoplasms of the skin, Zymbal's gland, clitoral gland, liver, oral cavity, small and large intestine, mammary gland, and lung. Increased incidences of neoplasms of the brain and mononuclear cell leukemia may have been related to chemical administration. Synonyms: o-tolidine dihydrochloride; 3,3'-dimethylbiphenyl-4,4'-diamine dihydrochloride; 3,3'-dimethylbiphenyl-4,4'-biphenyldiamine dihydrochloride; 4,4'-diamino-3,3'-dimethylbiphenyl dihydrochloride
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PMID:NTP Toxicology and Carcinogenesis Studies of 3,3'-Dimethylbenzidine Dihydrochloride (CAS No. 612-82-8) in F344/N Rats (Drinking Water Studies). 1263 69

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
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PMID:Noncalcemic actions of vitamin D receptor ligands. 1579 98

Expression of the forkhead transcription factor FoxM1 correlates with proliferative status in a variety of normal and transformed cell types. Elevated expression of FoxM1 has been noted in both hepatocellular carcinoma and basal cell carcinoma. However, whether FoxM1 expression is essential for the viability of transformed cells is unknown. We report here that the expression of FoxM1 is significantly elevated in primary breast cancer. Microarray analysis shows that FoxM1 regulates genes that are essential for faithful chromosome segregation and mitosis, including Nek2, KIF20A, and CENP-A. Loss of FoxM1 expression generates mitotic spindle defects, delays cells in mitosis, and induces mitotic catastrophe. Time-lapse microscopy indicates that depletion of FoxM1 generates cells that enter mitosis but are unable to complete cell division, resulting in either mitotic catastrophe or endoreduplication. These findings indicate that FoxM1 depletion causes cell death due to mitotic catastrophe and that inhibiting FoxM1 represents a therapeutic strategy to target breast cancer.
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PMID:Loss of the forkhead transcription factor FoxM1 causes centrosome amplification and mitotic catastrophe. 1595 62

A58-year-old man with upper abdominal pain had a duodenal perforation and a huge hepatocellular carcinoma (BCC). Atumor embolism in the main portal vein was also seen. Extended right lobectomy against a huge tumor in right lobe and ethanol injection to a tumor in the lateral segment were performed. In addition, fluorouracil arterial infusion and interferon therapy(FAIT)were carried out. He has been for 4 years and 6 months without recurrence. Although prognosis of patients with a huge BCC is miserable even if curative hepatic resection is performed, it may be possible for adjuvant FAIT to suppress the recurrence after hepatic resection for huge BCC.
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PMID:[A resected case of huge advanced hepatocellular carcinoma(BCC)treated with intra-arterial infusion chemotherapy combined with interferon-alpha]. 1893 83


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