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)

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

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

The content of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (Ca 19-9), carbohydrate antigen 15-3 (Ca 15-3) and the expression of LewisY related carbohydrate antigens in benign and malignant pleural effusion were determined. These included 35 malignant pleural effusions: 13 breast cancers, 12 lung cancers (6 squamous cell carcinomas, 5 adenocarcinomas and 1 microcytoma), 2 mesotheliomas, 1 epithelioma, 1 kidney cancer, 1 hepatocarcinoma, 1 colon carcinoma, 3 lymphomas, 1 osteosarcoma and 9 benign pleural effusions. We showed that pleural fluid content of CEA, Ca 19-9 and Ca 15-3 were higher in malignant than in benign effusions. However CEA levels in squamous lung cancers were very high in both serum and pleural fluids whereas its levels were only slightly above the cut-off in breast cancers and in lung adenocarcinomas. Serum and pleural fluid Ca 15-3 values were higher in breast and in lung cancers with the highest values in the patients with breast cancer. Furthermore, the LewisY related carbohydrate antigens, evaluated by the reactivity of the cell extracts to MAb B3, were expressed only in breast cancers. These data suggest that pleural fluid content of CEA, and Ca 15-3 associated with the immunoblotting of cell extracts with MAb B3 appear to be very useful to improve the diagnosis of malignant pleural effusions.
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PMID:New approaches in the diagnostic procedure of malignant pleural effusions. 1520 63

Novel approaches are needed to improve the antitumor potency and to increase the cancer specificity of oncolytic adenoviruses (Ad). We hypothesized that the combination of interferon-alpha (IFN-alpha) expression with a specific mutation in the e1a gene of Ad could target vector replication to genetic defects in the IFN-alpha pathway resulting in both improved antitumor efficacy and reduced toxicity. The conditionally replicative Ad vector KD3-IFN carries the dl1101/1107 mutation in the e1a gene that eliminates binding of E1A proteins to p300/CBP and pRb. KD3-IFN expresses human IFN-alpha in concurrence with vector replication and overexpresses the adenovirus death protein (ADP; E3-11.6K). The antitumor activity of KD3-IFN was significantly higher than that of a control vector in established human hepatocellular carcinoma tumors in immunodeficient mice and in hamster kidney cancer tumors in immunocompetent Syrian hamsters. The dl1101/1107 mutation rendered Ad replication sensitive to the antiviral effect of IFN-alpha in normal as opposed to cancer cells. These results translated to reduced vector toxicity upon systemic administration to C57BL/6 mice. The combination of Ad oncolysis, ADP overexpression, and IFN-alpha-mediated immunotherapy represents a three-pronged approach for increasing the anticancer efficacy of replicative Ads. Exploiting the dl1101/1107 mutation provides a mechanism for additional selectivity of IFN-alpha-expressing replication-competent Ads.
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PMID:Targeting interferon-alpha increases antitumor efficacy and reduces hepatotoxicity of E1A-mutated spread-enhanced oncolytic adenovirus. 1719 Oct 72

Cancer cells may often support their own growth, survival, and drug resistance by autocrine/paracrine loops based on the production of different factors; results from us and others have shown that similar interleukin-6 (IL-6)-related loops are operative in multiple myeloma and prostate or renal cancer. Because this aspect has not been investigated in detail for hepatocellular carcinoma (HCC), we have examined it in HA22T/VGH cells. These differ from other primary liver cancer cell lines (that is, HepG2, HuH-6, and HuH-7) in that enzyme-linked immunosorbent assay (ELISA) showed the HA22T/VGH cells to secrete remarkable amounts of IL-6 (16.8 ng/10(6) cells/24 h); this production, due to constitutive activation of NF-kappaB, is inhibited by agents like curcumin and dehydroxymethylepoxyquinomicin (DHMEQ), which interfere with the transcription factor. Flow cytometry, ELISA, mRNA, and Western blotting analyses were performed to characterize the status of the IL-6 receptor in HA22T/VGH cells. Two transmembrane glycoproteins that form the functional IL-6 receptor have been identified: the ligand-binding gp80 and the signal-transducer gp130. Soluble forms of gp80 also trigger membrane gp130 signaling when complexed with IL-6, while soluble forms of gp130 inhibit the same process. Our results showed that HA22T/VGH cells express gp130 at their surface, but release only traces of its soluble form. For gp80, the cells produced the mRNAs of both its membrane and soluble form. However, in immunoblotting they exhibited a very faint content of the same subunit, which, in addition, was neither expressed at the cell surface nor secreted. In MTT assays, incubation with a neutralizing anti-IL-6 antibody for up to 7 days did not affect the growth of HA22T/VGH cells. Also, other specific anti-IL-6 approaches (siRNA or AODN) failed to produce this result. In conclusion, autostimulatory loops mediated by IL-6 are less likely to occur in HCC than in other kinds of cancer. However, since release of IL-6 is frequent in HCC, especially in its more advanced stages, the use of agents like curcumin or DHMEQ might be beneficial to counteract its adverse systemic effects (e.g., cachexia).
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PMID:Significance of autologous interleukin-6 production in the HA22T/VGH cell model of hepatocellular carcinoma. 1726 74

A series of 11 bis-indolylthiophenes of type 8-10 were obtained by cyclization of diketones 4 and 7 using Lawesson's reagent. Derivatives 8c, 9c, 9d, and 10c were selected to be evaluated in the full panel of about 60 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity generally in the micromolar range. The most sensitive cell lines were: CCRF-CEM, MOLT-4, HL60 (TB), and RPMI-8226 of the leukemia subpanel, HT29 and HCC-2998 cell lines of the colon sub-panel, NCI-H522 of the non-small cell lung cancer sub-panel, LOX IMVI of the melanoma sub-panel, and UO-31 of the renal cancer sub-panel.
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PMID:Synthesis and antitumor properties of 2,5-bis(3'-indolyl)thiophenes: analogues of marine alkaloid nortopsentin. 1730 31

Sorafenib is an orally available multikinase inhibitor active on vascular endothelial growth factor receptor-2 and -3, platelet-derived growth factor receptor-beta, B-RAF, C-RAF, flt3 and C-Kit. Phase I studies showed its activity on renal cell carcinoma (RCC) and other neoplasms and identified the schedule of 400 mg (two tablets) b.i.d. as better tolerated and potentially active. The original design selected for the principal phase II trial, randomization discontinuation trial, showed the particular activity profile of this drug: low objective response rates but significant increases in progression-free survival [PFS, which frequently translate in increased overall survival (OS)]. A pattern of response completely agrees with an antiangiogenic (cytostatic) agent. The potential efficacy of sorafenib was confirmed in immunotherapy-refractory advanced RCC cases by 'TARGETs', the largest randomized double-blind study ever carried out in kidney cancer. With a doubled PFS, a trend in OS and a modest toxicity profile, mainly grade 1-2 skin toxicity and diarrhea, sorafenib has been recently approved from the Food and Drug Administration and European Agency for the Evaluation of Medicinal Products for the second-line treatment of advanced RCC. Numerous trials are ongoing to test new schedules and drug combinations, while promising results were recently achieved also in hepatocellular carcinoma. With drugs such as sorafenib, angiogenesis could become an Achilles's heel for RCC.
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PMID:Protein kinase inhibitors in the treatment of renal cell carcinoma: sorafenib. 1759 26

We newly cloned the gene encoding the human aspartyl (asparaginyl) beta-hydroxylase (HAAH) from the surgical tissue of a patient with hepatocellular carcinoma. This study was designed to generate HAAH-specific monoclonal antibody (MAb) for further exploration of its structure and function. Mice were co-immunized with naked plasmid DNA containing N-terminal domain of encoding HAAH gene and recombinant HAAH polypeptide. Hybridomas were developed by the electrofusion of the splenocytes from mice immunized with plasmid DNA to Sp2/0 myeloma cells in vitro. Three hybridoma cell lines (designated G3, G9, and F11, respectively) stably secreting HAAH-specific MAbs were obtained. The specificity and sensitivity of MAbs were assessed by indirect enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results showed that the three MAbs belong to IgG1 kappa isotype, the titer of MAbs reached was 5 x 10(4) - 1 x 10(5), and the affinity constant (k(aff)) of MAbs ranged between 2.5 x 10(8) - 1.1 x 10(9). MAb G3 was preliminarily applied to detection expression of HAAH for seven tumor tissues, including hepatocellular carcinoma, lung cancer, kidney cancer, cholangiocarcinoma, prostate cancer, breast cancer, and glioblastoma by immunohistochemical stain. Our studies demonstrated that co-immunization of naked DNA containing encoding gene of target antigen and recombinant target protein, and combined with in vitro electrofusion, is an effective and simple method to raise MAbs.
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PMID:Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization. 1966 97

Aim of this paper is to review and describe Health-Related Quality of Life (HRQoL) measures applied in kidney cancer, hepatocellular carcinoma, and leukemia patients under drug therapy. A comprehensive search in PubMed was conducted to identify studies assessing quality of life (QoL) in these indications. In total 32 studies, including four studies through reference list checking and 21 different HRQoL instruments, were identified. Six generic, five disease-specific, and 10 domain-specific instruments were identified. In conclusion no overall standards in HRQoL measurement could be observed in the respective indications.
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PMID:A structured review and guide through studies on health-related quality of life in kidney cancer, hepatocellular carcinoma, and leukemia. 1986 45

Targeted therapies against cancer have become more and more important. In particular, the inhibition of tumor angiogenesis and vascular targeting have been the focus of new treatment strategies. Numerous new substances were developed as angiogenesis inhibitors and evaluated in clinical trials for safety, tolerance, and efficacy. With positive study results, some of these molecules have already been approved for clinical use. For example, this is true for the vascular endothelial growth factor neutralizing antibody bevacizumab (BEV) in metastatic colorectal cancer, nonsmall cell lung cancer, renal cancer, and breast cancer. The tyrosine kinase (TK) inhibitors sorafenib and sunitinib have been approved for metastatic renal cancer as well as for hepatocellular carcinoma, and sunitinib has also been approved for gastrointestinal stroma tumors. In this chapter we try to give an overview of the substances currently investigated in Phase III studies and beyond with regard to antiangiogenesis in cancer therapy.
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PMID:Compounds in clinical Phase III and beyond. 2003 82


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