In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

Context: Animal models for hepatic metastases can facilitate the investigation of lymphokine-activated killer (LAK) cell-based immunotherapy. The aim of this study was to investigate the efficacy of ccM4 antibody-targeted LAK cells in inhibiting hepatic micrometastases.', 'Hepatic micrometastases were generated after the intrasplenic injection of HM7 colon carcinoma cells. TAG72 expression was detected in these hepatic micrometastases using ccM4 antibody. The ccM4 antibody was conjugated onto LAK cells by treatment with 17.5% polyethylene glycol 8000. After the intrasplenic injection of HM7 cells, severe combined immunodeficient mice were randomized into five groups (i-v) and received either 10(7) ccM4-LAK cells plus 1000 U interleukin 2 (IL-2; group i), LAK cells plus 50 micrograms ccM4 and IL-2 (group ii), LAK cells plus IL-2 (group iii), IL-2 alone (group iv), or only phosphate-buffered saline (group v).', 'The ccM4-LAK cells retained cytolytic activity and acquired TAG72-binding reactivity. The results showed that group i had significantly fewer hepatic metastases compared with group ii or group iii (P < 0.05) and even fewer hepatic metastases compared with group iv or group v (P < 0.001).\Question: Do antibody-targeted lymphokine-activated killer cells inhibit liver micrometastases in severe combined immunodeficient mice?
These results show that ccM4 antibody-targeted LAK cells significantly inhibited tumor growth in vivo; thus, they can be potentially useful in treatment of hepatic micrometastases.

Context: The goal of this study was to identify genetic determinants of plasma N-terminal proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in vitro cell studies and on disease susceptibility.', 'Genotyping was performed across 16 000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single-nucleotide polymorphisms were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess the significance, in vitro functional genomic studies and clinical outcomes for carriers of a single-nucleotide polymorphism rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 558% of wild-type protein (P=0.01) as assessed by quantitative western blots. Carriers of rs5063 had lower NT-proANP levels (1427 versus 2291 pmol/L; P<0.001) and higher diastolic blood pressures (75 versus 73 mm Hg; P=0.009) and were at an increased risk of stroke when compared with wild-type subjects independent of age, sex, diabetes mellitus, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio, 1.6; P=0.004).\Question: Does circulating atrial natriuretic peptide genetic association study identify a novel gene cluster associated with stroke in whites?
This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation is related to lower NT-proANP levels, higher blood pressures, and an increased risk of stroke in the general community.

Context: Obesity-associated insulin resistance (IR) is highly correlated with soluble tumor necrosis factor- (sTNF-), which is released from transmembranous TNF- by TNF- converting enzyme (TACE). In vivo, TACE activity is suppressed by tissue inhibitor of metalloproteinase 3 (TIMP3). Agents that can interact with TACE/TIMP3 to improve obesity-related IR would be highly valuable. In the current study, we assessed whether (2S,3R,4S)-4-hydroxyisoleucine (4-HIL) could modulate TACE/TIMP3 and ameliorate an obesity-induced IR-like state in 3T3-L1 adipocytes.', '3T3-L1 adipocytes were incubated in the presence of 25 mM glucose and 0.6 nM insulin to induce an IR-like state, and were then treated with different concentrations of 4-HIL or 10 M pioglitazone (positive control). The glucose uptake rate was determined using the 2-deoxy-[(3)H]-D-glucose method, and the levels of sTNF- in the cell supernatant were determined using ELISA. The protein expression of TACE, TIMP3, and insulin signaling-related molecules was measured using western blotting.', 'Exposure to high glucose and insulin for 18 hours increased the levels of sTNF- in the cell supernatant. The phosphorylation of insulin receptor substrate-1 (IRS-1) Ser(307) and Akt Ser(473) was increased, whereas the protein expression of IRS-1, Akt, and glucose transporter-4 was decreased. The insulin-induced glucose uptake was reduced by 67% in 3T3-L1 adipocytes, which indicated the presence of an IR-like state. The above indexes, which demonstrated the successful induction of an IR-like state, were reversed by 4-HIL in a dose-dependent manner by downregulating and upregulating the protein expression of TACE and TIMP3 proteins, respectively.\Question: Does 4-Hydroxyisoleucine ameliorate an insulin resistant-like state in 3T3-L1 adipocytes by regulating TACE/TIMP3 expression?
4-HIL improved an obesity-associated IR-like state in 3T3-L1 adipocytes by targeting TACE/TIMP3 and the insulin signaling pathway.