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)

Only 5% to 10% of metastatic and primary liver tumors are amenable to surgical resection. Hepatic cryoablation has increased the number of patients who are suitable for curative treatment. The aim of this study was to evaluate survival and intrahepatic recurrence in patients treated with cryoablation and resection. From June 1994 to July 1999, thirty-eight surgically unresectable patients underwent a total of 42 cryoablative procedures for 65 malignant hepatic lesions. Twenty patients underwent cryoablation alone, and 18 patients were treated with a combination of resection and cryoablation, with a minimum of 18 months' follow-up. The 38 patients had the following malignancies: primary hepatocellular carcinoma (n = 8) and metastases from colorectal cancer (n = 21), neuroendocrine tumors (n = 3), ovarian cancer (n = 3), leiomyosarcoma (n = 1), testicular cancer (n = 1), and endometrial cancer (n = 1). Patients were evaluated preoperatively with spiral CT scans and intraoperatively with ultrasound examinations for lesion location and cryoprobe guidance. Local recurrence was detected by CT. Major complications included bleeding in three patients and acute renal failure, transient liver insufficiency, and postoperative pneumonia in one patient each. Two patients (5%) died during the early postoperative interval; mean hospital stay was 7.1 days. Median follow-up was 28 months (range 18 to 51 months). Overall survival according to Kaplan-Meier analysis was 82%, 65%, and 54% at 12, 24, and 48 months, respectively. Forty-eight-month survival was not significantly different between those patients undergoing cryoablation alone (64%) and those treated with a combination of resection and cryoablation (42%). Disease-free survival at 45 months was 36% for patients undergoing cryoablation plus resection compared to 25% for those undergoing cryoablation alone. Local recurrences were detected at five cryosurgical sites, for a rate of 12% overall (5 of 42), 11% (2 of 18) for patients in the cryoablation plus resection group, and 12% (3 of 24) for those in the cryoablation alone group. For patients with colorectal metastases, survival was 70% at 30 months compared to 33% for hepatocellular cancer and 66% for other types of tumors. Patients with tumors larger than 5 cm or numbering more than three did not have significantly decreased survival. Cryoablation of hepatic tumors is a safe and effective treatment for some patients not amenable to resection. The combination of cryoablation and resection results in survival comparable to that achieved with cryoablation alone.
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PMID:Rationale for the combination of cryoablation with surgical resection of hepatic tumors. 1133 84

The paper presents a retrospective evaluation of 47 patients with bone metastases treated surgically during the last 10 years at our ward. The mean age of the patients was 62.5 years. There were 31 females (mean age: 62.8 years) and 16 males (mean age: 62.3 years). In 37 cases (78.8%) it as possible to establish the primary localization of the tumour: breast carcinoma--16 cases, ovary cancer 5 cases, lung cancer--5 cases, prostate cancer--5 cases, kidney cancer--2 cases, stomach cancer--1 case, vagina cancer--1 case, hepatocarcinoma--1 cases and plasmocytoma--1 cases. In 10 cases (21.1%) we were unable to establish the primary focus of the tumour. The localization of the metastases was as follows: femur--32 cases, humerus--6 cases, tibia--3 cases, lumbar spine--1 case. Patients treated very briefly after qualification for surgery, in some cases during emergency service. In 2 cases of metastases to the tibia amputations at the femur were performed. The remaining patients were treated by local excisions of the metastatic tumours, followed by: in 33 cases internal osteosynthesis and bone cement application; in 7 cases osteosynthesis, in 4 cases hip arthroplasties and posterior spine instrumentation in 1 case. In 6.4% we had poor results because of the death of 3 patients. The mean follow-up was three months. In 93.6% we had good and very good results--no pain, good function and independence during daily activities. Mean survival time was 13.5 month (range 5-28 months).
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PMID:[Efficacy of operative treatment for pathological fractures in bone metastases in relation to length and comfort of survival]. 1138 15

Most up-to-date information on oral contraceptives (OCs) and breast cancer risk comes from a collaborative re-analysis of individual data on 53297 cases and 100239 controls. It is now established that there is a moderately increased breast cancer risk among current OC users, which tends to level off in the few years after stopping use. With regard to cervical cancer, OC use has been found to be associated with increased risk in human papilloma virus-positive women. With reference to the well known protective effects of OCs against endometrial carcinogenesis, additional information has suggested a consistent protection across types of OCs used. Further data on ovarian cancer confirm that the protection of OCs is long lasting, and may well be observed 15 to 20 years after stopping use. Several studies have suggested an inverse relationship between use of OCs and risk of colorectal cancer, and in a meta-analysis of published data the pooled relative risk of colorectal cancer for DC ever-use was 0.82 (95% confidence interval 0.74 to 0.97). There was no association with duration of use. The increased risk for hepatocellular carcinoma in the absence of hepatitis B viruses is the only established evidence of a direct association between OC use and cancer risk, which led an International Agency for Research on Cancer Working Group to classify OCs as carcinogenic to humans in 1998.
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PMID:Oral contraceptives and cancer: an update. 1167 2

Autoantibodies are often detected in hepatocellular carcinoma (HCC), and these responses may represent recognition of tumor Ags that are associated with transformation events. The identities of these Ags, however, are less well known. Using serological analysis of recombinant cDNA expression libraries (SEREX) from four HCC patients, we identified 55 independent cDNA sequences potentially encoding HCC tumor Ags. Of these genes, 15 are novel. Two such proteins, HCA587 and HCA661, were predominantly detected in testis, but not in other normal tissues, except for a weak expression in normal pancreas. In addition to HCC, these two Ags can be found in cancers of other histological types. Therefore, they can be categorized as cancer-testis (CT) Ags. Two other Ags (HCA519 and HCA90) were highly overexpressed in HCC and also expressed in cancer cell lines of lung, prostate, and pancreas, but not in the respective normal tissues. Four other Ags were identified to be expressed in particular types of cancer cell lines (HCA520 in an ovarian cancer cell line, HCA59 and HCA67 in a colon cancer cell line, HCA58 in colon and ovarian cancer cell lines), but not in the normal tissue counterpart(s). In addition, abundant expression of complement inactivation factors was found in HCC. These results indicate a broad range expression of autoantigens in HCC patients. Our findings open an avenue for the study of autoantigens in the transformation, metastasis, and immune evasion in HCC.
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PMID:Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies. 1209 19

Familial risks for histopathology-specific cancers have not been determined. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 1 million tumors to calculate standardized incidence ratios (SIRs) for familial cancers of specific histology and morphology among 0- to 66-year-old offspring. We used histology codes for both offspring and parents, but because of the limited number of cases, the morphology-specific classification could be used only for offspring by all site-specific cancers in parents, resulting in inflated risk estimates. A number of novel findings emerged in the histopathology-specific analysis of familial risks, in addition to some known associations. Overall, specific histology showed an SIR of 2.07 for all cancers compared to an SIR of 2.00 for any histology. However, the small effect was due to breast and prostate cancers, which showed a negligible effect of specific histology. Familial risks of over 4.0 were found for serous papillary cystadenocarcinoma of the ovary, papillary thyroid cancer and low-grade astrocytoma. Familial risks of over 3.0 were found for signet-ring gastric cancer, various forms of ovarian cancer and squamous cell skin cancer. Also noteworthy were familial risks of hepatocellular carcinoma (2.48), pancreatic adenocarcinoma (1.92), large cell carcinoma and adenocarcinoma of the lung (2.29 and 2.18, respectively) and clear cell carcinoma of the kidney (2.73). Many of the findings were novel and could be revealed only by applying codes for specific histopathology. These data call for a closer description of familial aggregations and probing for the underlying genetic mechanisms.
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PMID:Familial risk of cancer by site and histopathology. 1245 61

Human SNAIL1 (SNAI1) protein encoded by SNAI1/SNA gene represses transcription of E-cadherin/CDH1 gene. Human SNAIL2 (SNAI2) protein encoded by SNAI2/SLUG gene induces the first phase of epithelial-mesenchymal transition (EMT), including desmosome dissociation, cell spreading, and initiation of cell separation. Here, we have identified human SNAIL3 (SNAI3) gene using bioinformatics. Human SNAI3 gene, consisting of at least three exons, spans around the nucleotide position 320214-328221 of human reference genomic contig NT_010404.8 in the reverse orientation. SNAI3 gene, was located between KIAA0233 gene and CBFA2T3 gene in human chromosome 16q24.3, a region affected in breast cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, and therapy-related myeloid leukemia with t(16;21)(q24;q22) translocation. Human SNAI3 gene was found to encode 292-amino-acid polypeptide with the N-terminal SNAG domain and five zinc finger domains. N-terminal SNAG domain was identified in zinc finger proteins SNAI1, SNAI2, SNAI3, SCRATCH (SCRT1), GFI1, and GFI1B. ATP/GTP binding site was identified in SCRT1, GFI1 and GFI1B, but not in SNAI1, SNAI2 and SNAI3. Phylogenetic analysis of human zinc finger proteins with SNAG domain revealed that SNAI1, SNAI2 and SNAI3 were more closely related. These results clearly indicate that SNAI1, SNAI2 and SNAI3 constitute a subfamily among SNAG zinc-finger proteins. Human SNAI3 mRNA was expressed in skin melanotic melanoma, lung epidermoid carcinoma, and germ cell tumor. Because SNAG zinc-finger proteins are transcriptional repressors implicated in carcinogenesis and embryogenesis, SNAI3 gene might be a potent target of pharmacogenomics in the field of oncology and regenerative medicine.
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PMID:Identification and characterization of human SNAIL3 (SNAI3) gene in silico. 1257 45

Emerging data suggest that signaling by heparin-binding growth factors is influenced by the sulfation state of N-acetylglucosamine residues of heparan sulfate proteoglycans (HSPGs). Here we report that the recently identified protein HSulf-1, a heparin-degrading endosulfatase, encodes a cell surface-associated enzyme that diminishes sulfation of cell surface HSPGs. The message encoding this enzyme is readily detectable in a variety of normal tissues, including normal ovarian surface epithelial cells, but is undetectable in 5 of 7 ovarian carcinoma cell lines and markedly diminished or undetectable in approximately 75% of ovarian cancers. Similar down-regulation is also observed in breast, pancreatic, renal cells, and hepatocellular carcinoma lines. Re-expression of HSulf-1 in ovarian cancer cell lines resulted in diminished HSPG sulfation, diminished phosphorylation of receptor tyrosine kinases that require sulfated HSPGs as co-receptors for their cognate ligands, and diminished downstream signaling through the extracellular signal-regulated kinase pathway after treatment with fibroblast growth factor-2 or heparin-binding epidermal growth factor. Consistent with these changes, HSulf-1 re-expression resulted in reduced proliferation as well as sensitivity to induction of apoptosis by the broad spectrum kinase inhibitor staurosporine and the chemotherapeutic agent cisplatin. Collectively, these observations provide evidence that HSulf-1 modulates signaling by heparin-binding growth factors, and HSulf-1 down-regulation represents a novel mechanism by which cancer cells can enhance growth factor signaling.
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PMID:Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer. 1268 63

We have previously reported that direct transfer of the TNF-related apoptosis-inducing ligand (TRAIL) gene resulted in an apoptotic bystander effect, and that this bystander effect was not transferable with cell culture media. To further characterize its mechanism we tested the bystander effect of TRAIL in the human ovarian cancer cell line DOV13, human lung cancer cell line A549, human hepatoma cell line Hepa G2, human breast cancer cell line MDA-MB231 and human colon cancer cell lines Lovo and DLD1. The bystander target cells were transduced with an adenovector expressing the lacZ gene (Ad/CMV-LacZ), while the effector cells were transduced with an adenovector expressing the green fluorescent protein (GFP)/TRAIL fusion gene. Effector and target cells were then cocultured in the same well with or without effector and target cell contact. In all the cell lines tested, target cells were killed if effector and target cell contact was permitted. However, no bystander effect occurred if effector and target cell contact was prevented. Furthermore, the bystander effect and apoptosis induction of TRAIL was dramatically reduced if cells were seeded at a very low density. Moreover, in all the cell lines tested, no detectable soluble TRAIL was found in media from the TRAIL-expressing cell cultures. Together, our results demonstrated that release of soluble TRAIL from transfer of the wild-type TRAIL gene is minimal, and that the bystander effect of the TRAIL gene is mainly mediated by membrane-bound TRAIL on the surface of transduced cells.
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PMID:Cell to cell contact required for bystander effect of the TNF-related apoptosis-inducing ligand (TRAIL) gene. 1273 89

EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene 'hyperplastic discs' and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse tissue sites were analysed for allelic gain or loss (allelic imbalance, AI) at the EDD locus using an EDD-specific microsatellite, CEDD, and other polymorphic microsatellites mapped in the vicinity of the 8q22.3 locus. Of 143 cancers studied, 38 had AI at CEDD (42% of 90 informative cases). In 14 of these cases, discrete regions of imbalance encompassing 8q22.3 were present, while the remainder had more extensive 8q aberrations. AI of CEDD was most frequent in ovarian cancer (22/47 informative cases, 47%), particularly in the serous subtype (16/22, 73%), but was rare in benign and borderline ovarian tumours. AI was also common in breast cancer (31%), hepatocellular carcinoma (46%), squamous cell carcinoma of the tongue (50%) and metastatic melanoma (18%). AI is likely to represent amplification of the EDD gene locus rather than loss of heterozygosity, as quantitative RT-PCR and immunohistochemistry showed that EDD mRNA and protein are frequently overexpressed in breast and ovarian cancers, while among breast cancer cell lines EDD overexpression and increased gene copy number were correlated. These results demonstrate that AI at the EDD locus is common in a diversity of carcinomas and that the EDD gene is frequently overexpressed in breast and ovarian cancer, implying a potential role in cancer progression.
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PMID:EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. 1290 90

Glypican-3 (GPC3) encodes a cell-surface heparan- sulfate proteoglycan and its expression is frequently silenced in ovarian cancer, mesotheliomas, and breast cancer cell lines and ectopic expression of GPC3 inhibited the growth of these cells, suggesting that GPC3 plays a negative role in cell proliferation. In contrast, up-regulation of GPC3 is often observed in hepatoma, neuroblastoma, and Wilms' tumor. Whether GPC3 plays the same growth inhibitory role in these tumors remains to be studied. Here we report that antisense-mediated knockdown of GPC3 in the HepG2 hepatoma cells significantly promotes the growth of hepatoma cells. In addition, we show that this growth promotion is independent of insulin-like growth factor 2 (IGF2) signaling. Our data suggest that GPC3 plays a growth-suppressing role in hepatoma and provide cell biological evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by downregulating IGF2.
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PMID:Growth promotion of HepG2 hepatoma cells by antisense-mediated knockdown of glypican-3 is independent of insulin-like growth factor 2 signaling. 1450 64


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