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KCNH4  -  potassium channel, voltage gated eag...

Homo sapiens

Synonyms: BEC2, Brain-specific eag-like channel 2, ELK channel 1, ELK1, Ether-a-go-go-like potassium channel 1, ...
 
 
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Disease relevance of KCNH4

  • CONCLUSION: Vaccination with Bec2/BCG has no impact on outcome of patients with limited-disease SCLC responding to combined-modality treatment [1].
  • Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study) [1].
  • Immunization of melanoma patients with BEC2 anti-idiotypic monoclonal antibody that mimics GD3 ganglioside: enhanced immunogenicity when combined with adjuvant [2].
  • Biologic agents such as the anti-idiotypic antibody BEC2 when combined with BCG may offer some hope to those with minimal residual disease after standard chemotherapy and radiation [3].
 

High impact information on KCNH4

  • Twenty-four melanoma patients were randomized to be immunized with either BEC2 followed by GD3-L-KLH or in the opposite order [4].
  • Although GD3 has proven to be one of the least immunogenic gangliosides, our recent studies showed that anti-GD3 antibodies can be induced in patients immunized either with GD3-lactone-KLH (GD3-L-KLH) plus QS-21 adjuvant or with BEC2 anti-idiotypic monoclonal antibody vaccine, which mimics GD3, plus Bacillus Calmette-Guérin [4].
  • We are encouraged by the results with BEC2/BCG, which suggest that further enhancement of the immune response to BEC2 will result in more frequent anti-GD3 antibody responses among immunized patients [2].
  • RESULTS: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice [5].
  • Quantitative RT-PCR analysis of mRNA expression patterns showed that KCNH8, along with the other Elk family genes, KCNH3 and KCNH4, are primarily expressed in the human nervous system [6].
 

Chemical compound and disease context of KCNH4

 

Anatomical context of KCNH4

 

Analytical, diagnostic and therapeutic context of KCNH4

  • PATIENTS AND METHODS: Patients were randomly assigned to receive five vaccinations of Bec2 (2.5 mg)/BCG vaccine or follow-up [1].
  • A Phase III trial is being conducted to evaluate BEC2 plus BCG as adjuvant therapy after chemotherapy and irradiation [7].
  • Booster immunizations of 10 mg of unconjugated BEC2 were administered i.v. on weeks 24, 37, and 50 [9].
  • In this clinical trial, 18 melanoma patients who were free of disease after complete surgical resection within 1-6 months received intradermal immunizations on weeks 0, 2, 4, 6, and 10 with 2.5 mg of BEC2 conjugated to KLH and mixed with BCG (BEC2-KLH/BCG) [9].
  • Previous clinical trials demonstrated that intradermal immunization using 2.5 mg of BEC2 with BCG or i.v. immunization with 10 mg of BEC2 can induce anti-GD3 antibodies in a subset of patients [9].

References

  1. Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study). Giaccone, G., Debruyne, C., Felip, E., Chapman, P.B., Grant, S.C., Millward, M., Thiberville, L., D'addario, G., Coens, C., Rome, L.S., Zatloukal, P., Masso, O., Legrand, C. J. Clin. Oncol. (2005) [Pubmed]
  2. Immunization of melanoma patients with BEC2 anti-idiotypic monoclonal antibody that mimics GD3 ganglioside: enhanced immunogenicity when combined with adjuvant. McCaffery, M., Yao, T.J., Williams, L., Livingston, P.O., Houghton, A.N., Chapman, P.B. Clin. Cancer Res. (1996) [Pubmed]
  3. An overview of lung cancer. Sachs, S., Fiore, J.J. Respiratory care clinics of North America. (2003) [Pubmed]
  4. Sequential immunization of melanoma patients with GD3 ganglioside vaccine and anti-idiotypic monoclonal antibody that mimics GD3 ganglioside. Chapman, P.B., Wu, D., Ragupathi, G., Lu, S., Williams, L., Hwu, W.J., Johnson, D., Livingston, P.O. Clin. Cancer Res. (2004) [Pubmed]
  5. Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. de Nigris, F., Williams-Ignarro, S., Sica, V., Lerman, L.O., D'Armiento, F.P., Byrns, R.E., Casamassimi, A., Carpentiero, D., Schiano, C., Sumi, D., Fiorito, C., Ignarro, L.J., Napoli, C. Cardiovasc. Res. (2007) [Pubmed]
  6. Distribution and functional properties of human KCNH8 (Elk1) potassium channels. Zou, A., Lin, Z., Humble, M., Creech, C.D., Wagoner, P.K., Krafte, D., Jegla, T.J., Wickenden, A.D. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  7. Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus Bacillus Calmette-Guérin. Grant, S.C., Kris, M.G., Houghton, A.N., Chapman, P.B. Clin. Cancer Res. (1999) [Pubmed]
  8. Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination. Krug, L.M., Grant, S.C., Miller, V.A., Ng, K.K., Kris, M.G. Semin. Oncol. (1999) [Pubmed]
  9. Immunization of melanoma patients with BEC2-keyhole limpet hemocyanin plus BCG intradermally followed by intravenous booster immunizations with BEC2 to induce anti-GD3 ganglioside antibodies. Yao, T.J., Meyers, M., Livingston, P.O., Houghton, A.N., Chapman, P.B. Clin. Cancer Res. (1999) [Pubmed]
 
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