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Alpk1  -  alpha-kinase 1

Mus musculus

 
 
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Disease relevance of Alpk1

  • In the case of colorectal tumors, some cells are highly sensitive, whereas others are resistant to NK and can even be quite resistant to LAK-mediated lysis [1].
  • We showed in previous work that LAK cell supernatants contain a large molecular weight factor with toxic activity for A375 melanoma and other cell lines [2].
  • Compared with the LAK activity induced by rhuIL-2, the cytotoxicity of the killer cells induced by rhuIL-4 to K562 and Raji cells was lower, but that to TBL-E, a human lymphoid leukemia cell line established in our laboratory, and PHA-activated blast cells (PHA-blasts) was of similar magnitude [3].
 

High impact information on Alpk1

  • Although IL-2-FuP induced a T helper type 1 response with recruitment of LAK and CTL, TNF-FuP efficiently recruited and activated monocytes and, in a less pronounced manner, CTLS:[4]
  • In the present paper, we tried to correlate the stage of differentiation of 17 human colorectal tumor cell lines with their NK- or LAK-cell susceptibility [1].
  • In contrast, HT29 MTX10(-5), a highly differentiated mucus-secreting variant of HT29 obtained by methotrexate selection, was much more resistant to LAK cells than parental HT29 cells [1].
  • Furthermore, we evaluated the effects on IL-2-induced GVHD protection of depleting NK cells and LAK precursor cells in vivo with mAb against NK1.1 or antiserum against asialo GM1 [5].
  • Because several groups of investigators have demonstrated that lymphokine-activated killer cells can mediate GVHD protection, we hypothesized that the mechanism of protection by IL-2 administration might involve the in vivo activation of natural killer and/or LAK cells [5].
 

Biological context of Alpk1

  • Groups of five male and five female C57BL/6J/Alpk mice were exposed, by gavage, to doses of 4000, 2500 and 1250 mg/kg MC in corn oil, the highest dose-level being selected to be the maximum tolerated dose [6].
  • Tissue distribution of adoptively transferred adherent LAK cells: role of the route of administration [7].
  • The results suggest that Lyophyllum restrains blood cell-count falling after irradiation, which is probably mediated at least in part by hemopoietic function, and NK and LAK activities seems to play a role in preventing secondary infections associated with irradiation [8].
  • From the therapeutic point of view, the cytolytic activity of MAb 9C4-targeted ADCC/LAK killing against GD2-positive tumor cells to be more effective than that of LAK alone and a possibility for dendritic cells to effectively acquire antigen through pulsing with MAb-induced apoptotic cells are both of great clinical importance [9].
 

Anatomical context of Alpk1

  • These findings suggest that ProT alpha may provide an overall protective effect against tumor growth in vivo through induction of NK and LAK activities possibly indirectly via the production of IL-2 and TNF alpha in the spleen, peritoneal cavity and probably other lymphoid organs [10].
  • All three prostate tumor cell lines were sensitive to killing by TIL and LAK and cell killing was primarily mediated through the Ca(2+)-dependent perforin pathway because it was blocked by the addition of EGTA/MgCl2 [11].
  • Morphological studies revealed that LAK activity occurred at the time when macrophage precursors with NK like activity containing few cytoplasmic granules had further differentiated into cells with abundant azurophilic granules in their cytoplasma [12].
  • It has been reported that NCTD is an immunological stimulator to NK, LAK, neutrophil and lymphocyte [13].
  • Two sets of studies were done with one involving the known NK- and K-cell deficient Be mouse and another in which a normal mouse was induced with high levels (3 to 5 times normal) of LAK cell killing by a constant Osmolar Mini-Pump infusion of rIL-2 [14].
 

Associations of Alpk1 with chemical compounds

  • In splenocytes of nude mice, 5-FU increased and CY diminished LAK activation in bulk cultures, starting 3 days after chemotherapy [15].
  • In bulk cultures containing IL-2 (1000 CU/ml, 3-4 days), both 5-FU and CY reduced LAK activity of euthymic mice splenocytes for up to 6 days after chemotherapy, which was followed on day 9 by full recovery [15].
  • We analyzed the temporal effect of 5-fluorouracil (5-FU, 100-120 mg/kg), cyclophosphamide (CY, 100 mg/kg), Adriamycin (8 mg/kg) and dacarbazine (100 mg/kg) on the activation of natural killer/lymphokine-activated killer (NK/LAK) cells by IL-2 in several strains of euthymic mice and in athymic nude mice [15].
  • Hexachloro-1,3-butadiene (HCBD) produced a time- and dose-related increase in hepatic water content following i.p. administration to male Alderley Park (Alpk/AP) mice [16].
 

Analytical, diagnostic and therapeutic context of Alpk1

  • Various natural and induced immunodeficiency states (immunotherapy, irradiation, immunosuppressive drugs, cytoreductive drugs) have been examined for the ability of in vivo treatment with rIL-2 to enhance NK/LAK activity [17].
  • Based on preclinical models, one would also predict that LAK cell-mediated tumor killing against nonimmunogenic tumors would be most effective in low tumor burden states and could only be demonstrated clinically in large-scale, randomized, adjuvant trials [18].
  • The effect of chemotherapy on LAK and NK activity was essentially similar [15].
  • However, blastogenesis and elevated levels of LAK-type killing were observed following incubation of higher numbers of scid/scid.bg/bg splenocytes in hrIL-2 [19].
  • The ability of LAK and adherent LAK (A-LAK) cells to migrate to and localize into tumors might be a limiting factor for the efficacy of adoptive immunotherapy [7].

References

  1. Analysis of the relationship between stage of differentiation and NK/LAK susceptibility of colon carcinoma cells. Blottière, H.M., Zennadi, R., Grégoire, M., Aillet, G., Denis, M.G., Meflah, K., Le Pendu, J. Int. J. Cancer (1993) [Pubmed]
  2. LAK cells release a novel form of directly acting TGF beta, tightly bound to a high molecular weight carrier(s). Larisch-Bloch, S., Sulitzeanu, D. Growth Factors (1993) [Pubmed]
  3. Evaluation of the antitumor activity of human IL-4 by in vitro and in vivo assays. Wang, T., Chen, W. Chin. Med. Sci. J. (1994) [Pubmed]
  4. Interleukin 2-antibody and tumor necrosis factor-antibody fusion proteins induce different antitumor immune responses in vivo. Christ, O., Matzku, S., Burger, C., Zöller, M. Clin. Cancer Res. (2001) [Pubmed]
  5. The mechanism of IL-2-mediated protection against GVHD in mice. II. Protection occurs independently of NK/LAK cells. Sykes, M., Abraham, V.S. Transplantation (1992) [Pubmed]
  6. Inactivity of methylene chloride in the mouse bone marrow micronucleus assay. Sheldon, T., Richardson, C.R., Elliott, B.M. Mutagenesis (1987) [Pubmed]
  7. Tissue distribution of adoptively transferred adherent LAK cells: role of the route of administration. Basse, P.H., Herberman, R.B., Hokland, M.E., Goldfarb, R.H. Nat. Immun. (1992) [Pubmed]
  8. Radioprotective effect of lyophyllum decastes and the effect on immunological functions in irradiated mice. Nakamura, T., Itokawa, Y., Tajima, M., Ukawa, Y., Cho, K.H., Choi, J.S., Ishid, T., Gu, Y. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan / sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine (2007) [Pubmed]
  9. Analysis of a murine anti-ganglioside GD2 monoclonal antibody expressing both IgG2a and IgG3 isotypes: monoclonality, apoptosis triggering, and activation of cellular cytotoxicity on human melanoma cells. Lin, C.C., Shen, Y.C., Chuang, C.K., Liao, S.K. Adv. Exp. Med. Biol. (2001) [Pubmed]
  10. Induction of lymphokine-activated killer activity in mice by prothymosin alpha. Baxevanis, C.N., Gritzapis, A.D., Dedoussis, G.V., Papadopoulos, N.G., Tsolas, O., Papamichail, M. Cancer Immunol. Immunother. (1994) [Pubmed]
  11. Immunosensitization of prostate carcinoma cell lines for lymphocytes (CTL, TIL, LAK)-mediated apoptosis via the Fas-Fas-ligand pathway of cytotoxicity. Frost, P., Ng, C.P., Belldegrun, A., Bonavida, B. Cell. Immunol. (1997) [Pubmed]
  12. Differentiation of macrophage precursors to cells with LAK activity under the influence of CSF-1 and high dose IL-2. Li, H., Kniep, E., Emmendörffer, A., Lohmann-Matthes, M.L. Scand. J. Immunol. (1991) [Pubmed]
  13. The preliminary observation on immunosuppressive effect of norcantharidin in mice. Yan, M.S., Xiue, S., Wei, L.X., Piao, X.H. Immunopharmacology and immunotoxicology. (1993) [Pubmed]
  14. Role of natural killer and killer cells in concordant xenograft rejection. Patselas, T., Thomas, F., Araneda, D., Marchman, W. Transplant. Proc. (1995) [Pubmed]
  15. Chemotherapy-induced modulation of natural killer and lymphokine-activated killer cell activity in euthymic and athymic mice. Gazit, Z., Kedar, E. Cancer Immunol. Immunother. (1994) [Pubmed]
  16. Hexachloro-1,3-butadiene-induced hydropic change in mouse liver. Lock, E.A., Pratt, I.S., Ishmael, J. Journal of applied toxicology : JAT. (1985) [Pubmed]
  17. In vivo effects of recombinant human interleukin 2 on antitumor and antiviral natural immunity in induced or natural murine immunodeficiency states. Butler, L.D., Browne, C.P., Layman, N.K., Riedl, P., Tang, J., Marder, P., DeLong, D., Manetta, J., Bobbitt, L., Strnad, J. Cancer Res. (1988) [Pubmed]
  18. Interleukin-2 antitumor and effector cell responses. Hawkins, M.J. Semin. Oncol. (1993) [Pubmed]
  19. Demonstration of a splenic cytotoxic effector cell in mice of genotype SCID/SCID.BG/BG. MacDougall, J.R., Croy, B.A., Chapeau, C., Clark, D.A. Cell. Immunol. (1990) [Pubmed]
 
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