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)

Six patients with multiple myeloma (MM) and a second non-hematological neoplasm (solid tumor) are documented in this study. Two patients had a previous history of adenocarcinoma of the colon prior to MM diagnosis; in three patients a second neoplasm (lung cancer, adenocarcinoma of the urinary bladder and adenocarcinoma of the colon) appeared at the time of MM diagnosis; one patient, a woman with a six-year history of MM, developed hepatoma. The two patients who had had a neoplasm of the colon ten years before and the patient with bladder carcinoma, responded to MM therapy. The patient with lung cancer and the patient with adenocarcinoma of the colon died; the last patient, with MM and liver cancer, is alive but with aggressive disease. In conclusion we have found that in MM patients a second neoplasm may develop or co-exist, in greater frequency than that of the general population.
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PMID:Patients with multiple myeloma and solid tumors: six case reports. 970 May 87

Angiogenesis is essential for the development of a solid tumor, including hepatocellular carcinoma (HCC). HCC is a well-known hypervascular tumor. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. Its role has not been clarified in vivo in HCC development. We used a self-contained, tetracycline-regulated retroviral vector system to elucidate the effect of VEGF on murine HCC development in a xenograft experimental model. By delivering the VEGF gene within the retroviral vector and under the control of a tetracycline-regulated promoter, we were able to manipulate VEGF expression in vivo tumor by providing tetracycline in the drinking water. Overexpression of VEGF showed a marked increase in tumor development accompanied by augmentation of neovascularization. The degree of tumor enlargement corresponded to the level of VEGF gene expression. Suppression of VEGF led to a decrease in tumor growth at the established tumor size, whether relatively small or large. The level of VEGF expression did not alter the proliferation of HCC cells in vitro. In a double-chamber chemoinvasion assay, the in vitro invasion activity of VEGF-transduced cells was not changed. In the presence of endothelial cells (EC), however, VEGF-transduced cells showed a marked increase in their in vitro invasion activity. These results suggested that VEGF plays a critical role in the development of HCC in cooperation with EC
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PMID:Vascular endothelial growth factor tightly regulates in vivo development of murine hepatocellular carcinoma cells. 982 11

To determine the role of the Wilms' tumor gene WT1 in tumorigenesis of solid tumors, expression of the WT1 gene was examined in 34 solid tumor cell lines (four gastric cancer cell lines, five colon cancer cell lines, 15 lung cancer cell lines, four breast cancer cell lines, one germ cell tumor cell line, two ovarian cancer cell lines, one uterine cancer cell line, one thyroid cancer cell line, and one hepatocellular carcinoma cell line) by means of quantitative reverse transcriptase-polymerase chain reaction. WT1 gene expression was detected in three of the four gastric cancer cell lines, all of the five colon cancer cell lines, 12 of the 15 lung cancer cell lines, two of the four breast cancer cell lines, the germ cell tumor cell line, the two ovarian cancer cell lines, the uterine cancer cell line, the thyroid cancer cell line, and the hepatocellular carcinoma cell line. Therefore, of the 34 solid tumor cell lines examined, 28 (82%) expressed WT1. Three cell lines expressing WT1 (gastric cancer cell line AZ-521, lung cancer cell line OS3, and ovarian cancer cell line TYK-nu) were further analyzed for mutations and/or deletions in the WT1 gene by means of single-strand conformation polymorphism analysis. However, no mutations or deletions were detected in the region of the WT1 gene ranging from the 3' end of exon 1 to exon 10 (the WT1 gene consists of 10 exons) in these three cell lines. Furthermore, when AZ-521, OS3, and TYK-nu cells were treated with WT1 antisense oligomers, the growth of these cells was significantly inhibited in association with a reduction in WT1 protein levels. Furthermore, constitute expression of the transfected WT1 gene in cancer cells inhibited the antisense effect of WT1 antisense oligomer on cell growth. These results indicated that the WT1 gene plays an essential role in the growth of solid tumors and performs an oncogenic rather than a tumor-suppressor gene function.
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PMID:Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. 1018 90

We report here the case of a 17-year-old female with typical fibrolamellar hepatocellular carcinoma, no hepatitis B or C viral infection and a normal, non-cirrhotic liver. Computed tomography and magnetic resonance imaging revealed a solid tumor with a central fibrous scar. A fibrolamellar hepatocellular carcinoma is an uncommon malignancy of unknown etiology, without cirrhosis, usually without an increase in tumor markers, and rarely associated with hepatitis B virus. It occurs mainly in young patients. This tumor presents a high resectability rate (48-100%), a good prognosis and a mean survival of 68 months. This tumor is an important differential diagnosis of space occupying lesions in younger adults.
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PMID:[A fibrolamellar variety of hepatocarcinoma in a young woman 17 years old]. 1020 16

The growth of any solid tumor depends on angiogenesis. Among the known angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to play a pivotal role in tumor angiogenesis. However, to date, the signal transduction pathway initiated by VEGF is still not fully understood. It has been suggested that protein kinase C (PKC) plays an important role in the VEGF-induced signal transduction pathway in vitro, although the role of PKC in tumor angiogenesis in vivo still remains to be elucidated. By delivering the VEGF gene within the self-contained tetracycline-regulated retroviral vector (Retro-Tet) into hepatocellular carcinoma (HCC) cells, we manipulated VEGF expression by providing tetracycline in the drinking water to assess the tumor kinetics mediated exclusively by VEGF. In this study, we combined this Retro-tet system and LY333531, an inhibitor of the PKC-beta isoform, to elucidate the role of PKC-beta in tumor development and angiogenesis. Using a syngenic xenograft model, tumor augmentation induced by VEGF overexpression in HCC was markedly suppressed by oral administration of the PKC-beta inhibitor, with an accompanying reduction of neovascularization and p44/42 mitogen-activated protein kinase activation. This inhibitory effect was achieved even after the tumor was fully established. Immunohistochemical analysis revealed that apoptosis increased markedly in the tumor upon PKC-beta inhibitor treatment, whereas tumor cell proliferation itself did not change. Furthermore, with orthotopical transplantation, PKC-beta inhibition suppressed HCC tumor development in the liver. These results suggest that PKC-beta lies on the signal transduction pathway by which VEGF augments development and angiogenesis not only at the initial stage but also after the tumor is fully established.
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PMID:Protein kinase C lies on the signaling pathway for vascular endothelial growth factor-mediated tumor development and angiogenesis. 1048 91

Metallothionein I can be induced in response to a variety of agents that include heavy metals and oxidative stress. On the contrary, its induction was suppressed in some lymphoid-derived cancer cells. The mechanism of this repression has not been elucidated. Here, we show silencing of MT-I gene in a solid transplanted rat tumor as a result of promoter methylation at all the 21 CpG dinucleotides that span the region from -225 bp to +1 bp. By contrast, none of these CpG dinucleotides were methylated in the livers from the rats bearing the tumor, which was consistent with the efficient induction of the gene in this tissue by zinc sulfate. Genomic footprinting revealed lack of access of the transcriptional activators to the respective cis-acting elements of the methylated MT-I promoter in the hepatoma. The absence of footprinting was not due to inactivation of the metal regulatory transcription factor MTF-1, because it was highly active in the hepatoma. Treatment of the hepatoma bearing rats with 5-azacytidine, a demethylating agent, induced basal as well as heavy metal-activated MT-I gene expression in the hepatoma, implying that methylation was indeed responsible for silencing the gene. Bisulfite genomic sequencing showed significant (>90%) demethylation of CpG dinucleotides spanning MT-I promoter in the hepatoma following treatment with 5-AzaC. The hypermethylation of MT-I promoter was probably caused by significantly higher (as much as 7-fold) level of DNA methyl transferase activity as well as enhanced expression of its gene in the hepatoma relative to the host liver. These data elucidated for the first time the molecular mechanism for the silencing of a highly inducible gene in a solid tumor transplanted in an animal, as compared with the robust induction in the corresponding parental tissue and have discussed the probable reasons for the suppression of this gene in some tumors.
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PMID:Suppression of metallothionein gene expression in a rat hepatoma because of promoter-specific DNA methylation. 1061 49

New data show that perioperative cytostatic therapy is beneficial in the case of liver transplantation for hepatic cancer. However, it has not been established clearly whether chemotherapy interferes with graft rejection. We therefore studied the interactions between tumor growth and graft rejection, especially with regard to chemotherapy, using a combined tumor/transplantation model. As a tumor model, we used the Novikoff hepatoma, a malignant hepatoma that was injected subcutaneously into the backs of rats. Heterotopic heart grafting served as the transplantation model. In a first step (a), we studied the effect of cytostatic therapy on tumor growth: tumor cells were injected, and in four groups epirubicin, cyclosporine, epirubicin + cyclosporine, and placebo were applied, in corresponding groups, transplantation was additionally performed. Tumor growth was measured and the resected tumors were examined by histology and immunohistology. In a second step (b), we studied the effect of chemotherapy on graft rejection: transplantation was performed and the above-mentioned drugs were applied; in corresponding groups, a solid tumor was additionally induced and resected immediately before transplantation. The results of these procedures were as follows: (a) Epirubicin decreased tumor growth and diminished the volume-increasing effect of cyclosporine significantly. After transplantation, tumor growth was similar. (b) Epirubicin prolonged graft survival significantly, and the combination with cyclosporine had an augmenting effect. In the corresponding groups, graft survival was similar. In conclusions. chemotherapy diminishes the tumor-increasing effect of cyclosporine and does not interfere negatively with graft survival. It might therefore be beneficial after transplantation for malignancy.
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PMID:The efficacy of adjuvant cytostatic therapy after organ transplantation for malignancy: an experimental study with a combined transplantation/tumor model. 1083 50

We examined whether patients with both amyotrophic lateral sclerosis (ALS) and cancer differ from classical ALS patients, and whether motor neuron disease responds to oncological therapy. We analyzed clinical and immunological features of 14 patients (9 men, 5 women; mean age 65.3 years) with pure/definite ALS and cancer. Patients with solid tumor cancer and definite ALS were selected according to the E1 Escorial criteria; cases with ALS plus were excluded. Four patients had breast cancer, three lung adenocarcinoma, and three bowel tumor; hepatocarcinoma, kidney cancer, and mesothelioma were observed in one case each, and in one patient the primary tumor was unidentified. Patients' sera were examined for antinervous system antibodies by means of immunohistochemistry and western blot analysis. Of five patients who underwent surgical therapy, two worsened during the procedure, while the other three had no benefit. The remaining two patients did not improve after chemotherapy and radiotherapy. In none of our cases did the oncological disease progress. Death was a consequence of ALS in all eight patients who died. Median survival was 18 months and did not differ from that of 28 ALS patients matched for age, sex, and onset features (bulbar or spinal). Anti-nervous system antibodies were never detected. We conclude that our group of pure ALS patients with cancer do not significantly differ from patients with classical ALS. They usually die as a consequence of the motor neuron syndrome in the absence of cancer progression. To date we have not observed any response of ALS to antitumor therapy.
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PMID:Patients with amyotrophic lateral sclerosis and cancer do not differ clinically from patients with sporadic amyotrophic lateral sclerosis. 1112 33

We describe a combined tumor and simultaneous transplant model in rats in tended to investigate interactions between tumor growth and graft rejection. To study the influence of tumor growth on graft rejection. Novikoff hepatoma cells were injected subcutaneously into the back of Lewis rats. Eight days later, the grown solid tumor was resected, and allogeneic heart transplantation was performed. Four groups were formed, receiving 5-fluorouracil (5-FU), cyclosporin A (CsA), 5-FU + CsA, and placebo, respectively. In the corresponding groups, tumor injection was omitted. Graft survival was significantly prolonged when CsA was given 5-FU did not abrogate or augment CsA efficiency nor influence graft survival when given alone. In the corresponding control groups, graft survival was similar, thus excluding an immunomodulating effect of the prior tumor growth on graft survival. To study the reverse interaction of allogeneic graft on tumor growth, heart grafting and tumor cell injection were performed on the same day. In different groups, 5-FU, CsA, 5-FU + CsA, and placebo was given. For the control, no transplantation was carried out. The tumor was resected on the 8th postoperative day and examined by immunohistology. A slight decrease of tumor growth by 5-FU, but a marked increase by CsA were found, whereas the graft alone showed no immunomodulation.
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PMID:Interactions between malignant tumor growth and allogeneic graft rejection in an experimental rat model. 1127 22

We previously reported that the retroviral vector expressing the herpes simplex virus-thymidine kinase gene under the control of 0.3-kb human alpha-fetoprotein (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir (GCV) in high-AFP-producing human hepatoma cells but not in low-AFP-producing cells. Therefore, specific enhancement of AFP promoter activity is likely to be required to induce enough cytotoxicity in low-AFP-producing hepatoma cells. In this study, we constructed a hybrid promoter, [HRE]AF, in which a 0.4-kb fragment of human vascular endothelial growth factor 5'-flanking sequences containing hypoxia-responsive element (HRE) was fused to AF0.3 promoter. By means of the reporter gene transfection assay, hypoxia-inducible transcriptions that were mediated by [HRE]AF promoter were detected in low- and non-AFP-producing human hepatoma cells, but not in nonhepatoma cells. When the herpes simplex virus-thymidine kinase gene controlled by [HRE]AF promoter was transduced into hepatoma and nonhepatoma cells by a retroviral vector, the exposure to 1% O2 induced GCV cytotoxicity specifically in the hepatoma cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors consisting of the virus-infected hepatoma cells gradually disappeared by GCV administration. These results indicate that the hypoxia-inducible enhancer of the human vascular endothelial growth factor gene, which is directly linked to human AFP promoter, involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.
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PMID:Gene therapy targeting for hepatocellular carcinoma: selective and enhanced suicide gene expression regulated by a hypoxia-inducible enhancer linked to a human alpha-fetoprotein promoter. 1130 81


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