Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/ or transformed cell lines, e.g. derived from breast and lung tumor, leukemia, lymphoma, osteosarcoma melanoma, cholangiocarcinoma, and hepatoma. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 can accelerate this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In animal models Apoptin-induced apoptosis appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by Bcr-Abl in these cells, imply that Apoptin is a potential anti-tumor therapy.
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PMID:Apoptin-induced apoptosis: a review. 1463 34

The core protein of Hepatitis C virus affects several biological functions of the host cells such as cellular growth and apoptosis. The core was shown to interact with 53BP2/Bbp/ASPP2, a p53-binding protein, in a yeast two-hybrid assay. The core competed with p53 in binding to ASPP2 in vitro. In an apoptosis assay using human osteosarcoma Saos-2 cells or hepatocellular carcinoma HepG2 cells, ectopic expression of p53 induced apoptosis and ASPP2 enhanced this p53-induced apoptosis. However, coexpression of the core with p53 and ASPP2 increased the number of surviving cells. In a reporter assay, neither ASPP2 nor the core with ASPP2 affected the transcriptional activity of p53 on the promoters of Bax and p21, major p53 target genes. These findings suggest that the core inhibits p53-mediated apoptosis by blocking the interaction between p53 and ASPP2, without modulating the transcriptional activity of p53, which plays a role in oncogenesis of hepatocellular carcinoma.
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PMID:Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis. 1498 81

The ideal treatment of localized cancer should directly cause an irreversible and complete death of tumor cells without damage to surrounding normal tissue. High intensity focused ultrasound (HIFU) is such a potential treatment, which induces a complete coagulative necrosis of a tumor at depth through the intact skin. The idea that using an extracorporeal source of therapeutic ultrasound was introduced more than 50 years ago [J. Gen. Physiol. 26 (1942) 179]. However, up to now, most of the studies on HIFU have been dealing with animal experiments because this extracorporeal technique is very complicated in clinical applications. The purpose of this study is to introduce Chinese clinical experience of using extracorporeal HIFU for the treatment of patients with various kinds of solid tumor. From December 1997 to October 2001, a total of 1038 patients with solid tumors underwent HIFU ablation in China. Among them, 313 patients were treated at the Chongqing University of Medical Sciences, China. Pathological examination showed that the target region presented clear evidence of cellular destruction. Small blood vessels less than 2 mm in diameter were severely damaged. Follow-up diagnostic imaging revealed that there was no, or reduced, blood supply, and no uptake of radioisotope in the treated tumor after HIFU, both indicating a positive therapeutic response and an absence of viable tumor. Imaging at 6-12 months showed obvious regression of the lesion. Four-year follow-up data were significantly observed in patients with hepatocellular carcinoma, osteosarcoma, and breast cancer. An extremely low major complication rate was noted. It is concluded that HIFU ablation is a safe, effective, and feasible modality for the ablation of carcinomas.
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PMID:Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. 1508 72

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Here, we provide evidence that the Forkhead Box (Fox) m1b (Foxm1b or Foxm1) transcription factor is essential for the development of HCC. Conditionally deleted Foxm1b mouse hepatocytes fail to proliferate and are highly resistant to developing HCC in response to a Diethylnitrosamine (DEN)/Phenobarbital (PB) liver tumor-induction protocol. The mechanism of resistance to HCC development is associated with nuclear accumulation of the cell cycle inhibitor p27(Kip1) protein and reduced expression of the Cdk1-activator Cdc25B phosphatase. We showed that the Foxm1b transcription factor is a novel inhibitory target of the p19(ARF) tumor suppressor. Furthermore, we demonstrated that conditional overexpression of Foxm1b protein in osteosarcoma U2OS cells greatly enhances anchorage-independent growth of cell colonies on soft agar. A p19(ARF) 26-44 peptide containing nine D-Arg to enhance cellular uptake of the peptide was sufficient to significantly reduce both Foxm1b transcriptional activity and Foxm1b-induced growth of U2OS cell colonies on soft agar. These results suggest that this (D-Arg)(9)-p19(ARF) 26-44 peptide is a potential therapeutic inhibitor of Foxm1b function during cellular transformation. Our studies demonstrate that the Foxm1b transcription factor is required for proliferative expansion during tumor progression and constitutes a potential new target for therapy of human HCC tumors.
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PMID:Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. 1508 32

The theoretical possibility that exposure of a solid malignancy to high-intensity focused ultrasound (US), or HIFU, could lead to an increased rate of metastasis still remains. Using reverse transcriptase polymerase chain reaction (RT-PCR), the potential risk of hematogenous dissemination was assessed in HIFU-treated patients with solid malignancy. RT-PCR can demonstrate the presence or absence of specific RNA fragments. On the day before HIFU ablation, 5-mL peripheral blood samples were collected, and again 5 to 7 days after HIFU, from 26 enrolled patients (hepatocellular carcinoma, HCC: 10; osteosarcoma: 16). Total RNA was isolated and RT-PCR was performed to analyze the mRNA expression of (alpha-fetoprotein (AFP) and bone-specific alkaline phosphatase (BALP) genes. Positive AFP mRNA expression was preoperatively detected in 8 of 10 patients with HCC. In the postoperative specimens, positive expression was also detected in 8 of 10 patients. In 2 patients, circulating tumor cells were found preoperatively, but not postoperatively. Conversely, 2 patients with no circulating tumor cells preoperatively were found to have circulating tumor cells after HIFU. Of 16 osteosarcoma patients, 12 patients had circulating tumor cells and 4 had none. After HIFU treatment, 2 of the 12 patients had converted from presence to absence of circulating cells and the remaining 4 patients remained negative. It is concluded that patients undergoing complete HIFU ablation may demonstrate conversion from presence to absence of circulating tumor-specific marker mRNA, and that HIFU would not enhance the potential risk of metastasis in patients with malignant diseases.
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PMID:Circulating tumor cells in patients with solid malignancy treated by high-intensity focused ultrasound. 1512 Dec 53

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

IFN-alpha combined with ribavirin is used for the treatment of chronic hepatitis C. However, HCV has mechanisms to resist the antiviral actions of IFN-alpha. In order to study the molecular mechanisms of this resistance, the effect of HCV gene expression on IFN-induced nuclear import of STAT transcription factors and the expression of antiviral MxA protein were studied. In transiently transfected hepatoma cells, HCV core and NS5A proteins clearly inhibited the nuclear import of STAT1 and MxA protein expression (core only), whereas other viral proteins had only a marginal effect. To confirm these observations, human osteosarcoma-derived cell lines, which inducibly express HCV core protein, the entire structural region (core-E1-E2-p7), the NS3-4A complex, NS4B, NS5A, or NS5B proteins were also used. IFN-induced nuclear accumulation of STAT1 was almost completely and STAT2 was partially blocked in cell lines expressing high levels of HCV core protein. Subsequently, in these cells, IFN-alpha-induced MxB protein expression was decreased. Tumor necrosis factor-alpha (TNF-alpha)-induced nuclear import of NF-kappaB was only weakly or not at all inhibited, suggesting that the nuclear import machinery in general was not impaired. The results demonstrate a novel mechanism by which HCV gene expression may interfere with IFN-mediated host defence systems.
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PMID:Expression of hepatitis C virus core protein inhibits interferon-induced nuclear import of STATs. 1522 97

T cell-mediated immune responses represent the main cellular antitumor immunity in cancer patients. Recent studies have shown that that both surgical procedure and radiation therapy could cause the functional suppression of lymphocyte-mediated cellular immunity. The purpose of current study is to evaluate whether high intensity focused ultrasound (HIFU) might change a systemic antitumor immunity, particularly T lymphocyte-mediated immunity in cancer patients. A total of 16 patients with solid malignancies were treated with HIFU. Among them, six patients had osteosarcoma (Enneking stage, II(B)4, III(B) 2), five had hepatocellular carcinoma (TNM stage, III 3, IV 2), and five had renal cell carcinoma (TNM stage, III 2, IV 3). Using flow cytometry technique, T lymphocyte and subset, B lymphocyte and natural killer cell (NK) in the peripheral blood were measured in these patients on the day before HIFU and 7 to 10 d after HIFU. The statistical significance of any observed difference is evaluated by Student's t-test. The results showed a significance increase in the population of CD4(+) lymphocytes (p < 0.01) and the ratio of CD4(+) /CD8(+) (p < 0.05) in the circulation of cancer patients after HIFU treatment. The abnormal levels of CD3(+) lymphocytes returned toward the normal range in two patients, CD4(+)/CD8(+) ratio in 3, CD19(+) lymphocytes in one and cytotoxic NK in one, respectively, in comparison to control values. It is concluded that HIFU could enhance a systemic antitumor cellular immunity in addition to local tumor destruction in patients with solid malignancies.
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PMID:Activated anti-tumor immunity in cancer patients after high intensity focused ultrasound ablation. 1555 Mar 25

The fragility of the evidence for SV40 association with human cancer is seen in studies of NHL. A publication in 1999 stated that SV40 is rarely present in NHL. In 2002, two laboratories reported SV40 sequences in 42% to 43% of cases of NHL . One of these laboratories also detected SV40 sequences in small proportions of pediatric tumors (e.g., Wilm's tumor, hepatoblastoma, rhabdomyosarcoma, medulloblastoma, osteosarcoma, and retinoblastoma) and adult carcinomas (e.g., lung, colon, breast, and prostate) These positive results were not confirmed in subsequent studies published in 2003. Capello et al and Mackenzie et al failed to detect SV40 sequences in NHL tissues. Sanjose et al examined sera from patients with NHL and from controls for antibodies reactive to SV40 VLPs, and they detected no significant differences between the two groups. The association of SV40 with NHL is in doubt. An etiologic link between a virus and a cancer becomes plausible when evidence from different lines of enquiry (e.g., epidemiology, pathogenesis, and molecular mechanisms) is mutually reinforcing and together provides a coherent picture that can connect the biology the virus to the characteristics of the disease. The associations of human papillomaviruses with cervical cancer and hepatitis B and C viruses with hepatocellular carcinoma are examples in which the etiologic link is clear. With SV40 and mesothelioma, the data on viral sequences in tumors is inconsistent and disputed, and serologic evidence does not support any association. The epidemiologic data do not show that documented exposures tt SV40 increase the risk of mesothelioma. It seems improbable that a single virus (which cannot be conclusively demonstrated to be present in the community) contributes to the development of such a wide variety of tumors, spanning all age groups and histologic types. The weaknesses in the evidence linking SV40 with mesothelioma are summarized in Box 11 It seems unlikely that infection with SV40 contributes to the development of human mesothelioma or any other human cancer.
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PMID:Causality of mesothelioma: SV40 question. 1555 56

Mice lacking both p18(Ink4c) and p27(Kip1) develop a tumor spectrum similar to pRb(+/-) mice, and loss of p53 function accelerates tumorigenesis in pRb(+/-) mice. We hypothesized that codeletion of either p18 or p27 in conjunction with p53 deletion will also accelerate tumorigenesis. Mice lacking both p18 and p53 develop several tumors not reported in either single null genotype, including hepatocellular carcinoma, testicular choriocarcinoma, hemangiosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. Mice lacking both p27 and p53 exhibit a decreased lifespan and develop unique tumors, including papillary carcinoma of the colon, hemangiosarcoma, and leiomyosarcoma. In both p18/p53 and p27/p53 double null genotypes, the incidence and spectra of tissues that develop lymphoma are also increased, as compared to the single null genotypes. The development of p27/p53 double null colon tumors correlates with secondary changes in cell-cycle protein expression and CDK (cyclin-dependent kinase) activity, perhaps contributing to the progression of colorectal cancer. We concluded that p18 and p27 can, not only functionally collaborate with one another, but also can independently collaborate with p53 to modulate the cell cycle and suppress tumorigenesis in a tissue-specific manner.
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PMID:Tumorigenesis in p27/p53- and p18/p53-double null mice: functional collaboration between the pRb and p53 pathways. 1558 24


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