Disease relevance of ALPK1

• HLA class I-restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent cultures from 3 of 3 EBV- tumors, whereas cultures from 6 of 6 EBV+ tumors were either noncytotoxic or exerted LAK-type cytotoxicity [1].
• Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients [2].
• These data show a reciprocal interaction between DCs and NK/LAK cells, leading to the amplification of NK cell effector functions, and support the implementation of DC/NK cell-based immunotherapy for purging the graft and/or controlling minimal residual disease after autologous stem cell transplantation [2].
• In an effort to stimulate in vivo LAK cell activity at relatively nontoxic doses, 20 patients with advanced metastatic malignancy (13 renal cell carcinoma, 6 melanoma, 1 lymphoma) were treated with recombinant human interleukin-2 (IL-2) by continuous 5-day splenic artery perfusion using the femoral approach [3].
• Their LAK activity against Daudi cells was 66.2 +/- 13.1% and 48.7 +/- 12.7% against self glioma cells, 54.4 +/- 10.1% against K562 cells, 43.1 +/- 7.9% against Raji cells, and 33.5 +/- 16.2% against allogeneic glioma cells [4].

Psychiatry related information on ALPK1

• Crisis intervention after the Tsunami in Phuket and Khao Lak [5].
• Alteration in body image for the patient undergoing RIL-2/LAK cell therapy [6].

High impact information on ALPK1

• Furthermore, anti-beta treatment of the K562 and A549 tumor cell lines inhibited NK (by > 95%) and interleukin 2-activated killer (LAK) cell (by 75%) cytotoxicity, respectively [7].
• This technique not only provides a novel method for the purification of LGL/NK cells for in vitro studies but also provides a means for the rapid expansion of highly purified cells with high levels of broad antitumor (LAK) cytotoxicity [8].
• From the experiments of negative selection with mAbs and complements, these newly developed killer cells after chemotherapy were thought to be LAK-like cells [9].
• These rapidly expanding LGL/NK cells also generated very high levels of LAK activity (including lysis of fresh NK-resistant solid tumor cells), expressed a phenotype characteristic of activated rat NK/LAK cells, and incorporated [3H]TdR into DNA [8].
• Clonogenic assay demonstrated a fivefold to 10-fold reduction in the surviving fraction of tumor cells with doxorubicin but no change with LAK/rIL-2.(ABSTRACT TRUNCATED AT 250 WORDS)[10]

Chemical compound and disease context of ALPK1

• The sensitivity of tumor cells to lysis by natural killer (NK) and interleukin-2 (IL-2)-activated killer (LAK) cells was studied in three ovarian carcinoma cell lines (2780.9S, SKOV-3, and CHOAUXB1), four multidrug-resistant (MDR) variants, and a melphalan-resistant line [11].
• Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells [12].
• A positive correlation between the sensitivity to LAK and the ID50 for doxorubicin (Dx) was found in 44 melanoma clones analyzed, suggesting that spontaneously drug-resistant clones have a higher sensitivity to LAK than the drug-sensitive clones [13].
• Staurosporine and pertussis toxin, which slightly suppressed LAK induction, did not inhibit tyrosine phosphorylation of the 105-110 kDa protein [14].
• We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity [15].

Biological context of ALPK1

• Taken together, our data suggest that the phosphorylation of myosin I by ALPK1 is an essential process in the apical trafficking of raft-associated SI [16].
• A phosphorylation assay on isolated SI-carrying vesicles revealed the phosphorylation of a protein band of about 105 kDa, which could be identified as the motor protein myosin I. Finally, a specific reduction of ALPK1-expression by RNA interference results in a significant decrease in the apical delivery of SI [16].
• Alpha-kinase 1, a new component in apical protein transport [16].
• AM-mediated down-regulation was seen only when AM were added immediately after the start of incubation of lymphocytes with IL 2; AM potentiated LAK activity when added 1 day later [17].
• Cold target inhibition studies showed that IFN-treated and untreated monocytes could effectively compete with each other for binding sites on LAK cells [18].

Anatomical context of ALPK1

• The expression of ALPK1 increases by the time of epithelial cell differentiation, whereas the intracellular localization of ALPK1 on apical transport vesicles was confirmed by confocal analysis [16].
• After incubation for 4 days with IL-2 (1 U/ml), purified lymphocytes showed maximal LAK activity against NK cell-resistant target (Daudi) cells, as assessed by 4-hour 51Cr release assay [19].
• Direct comparison of equal numbers of CML ALAK cells and a CML LAK cell population produced by incubation of peripheral blood mononuclear cells in rIL-2 for 14 days without adherence revealed that the CML LAK population had significantly lower lytic activity against K562 and Raji cell lines [20].
• At a concentration of 4-HC commonly used for BM purging (60 micrograms/mL), there were 4 to 5 logs of T-cell depletion and almost complete elimination of NK- and LAK-cell activity [21].
• The CML ALAK population is relatively homogeneous, not contaminated with viable stem cells, not derived from a malignant lineage, and more cytotoxic than equal numbers of CML LAK cells [20].

Associations of ALPK1 with chemical compounds

• Both AM and monocytes stimulated with lipopolysaccharide markedly suppressed LAK cell induction by IL 2 [17].
• The serologic phenotype of the LAK precursors was asialo GM1 (AsGM1+) cells, but the T3AK precursors could be either AsGM1+ or AsGM1-, depending on the target cell [22].
• Treatment of LoVo sublines with differentiating agents (dimethylformamide and retinoic acid) led to a decreased expression of all adhesion molecules studied, accompanied by increased resistance to LAK-mediated lysis [23].
• Prostaglandin E did not seem to play a regulatory role, since addition of indomethacin did not affect the regulation of LAK cell induction by monocytes [24].
• L-Leucyl-L-leucine methyl ester (LLME) is a lysosomatropic compound that is converted by dipeptidyl peptidase I to metabolites that are membranolytic for cytotoxic T cells, NK cells, and LAK cells [25].

Analytical, diagnostic and therapeutic context of ALPK1

• The combinational use of IFN-gamma and anti-CD3 x anti-tumor BsAb might be a promising way of enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer patients [26].
• Splenic artery perfusion with IL-2 can result in significant in vivo peripheral LAK cell generation as well as enhancement of I-LAK and NK activity that persists at least 16 days after the cessation of treatment [3].
• AMs, obtained by bronchoalveolar lavage from healthy volunteers, or peripheral blood monocytes were added to a standard 4-h chromium release LAK assay at varying concentrations [27].
• Following chronic treatment with intramuscular injections of IL2 at 1 x 10(6) units/m2, we observed augmentation of peripheral blood natural killer activity and induction of peripheral blood LAK activity [28].
• Ten patients were treated with a protocol of 5-day i.v. rIL-2 bolus priming (10(5) units/kg, every 8 h), followed by 5 daily phereses with harvested lymphocytes cultured in vitro to generate LAK, and 5 days of rIL-2 bolus with infusion of LAK cells [29].

References