Tailoring linear and nonlinear plasmons of metal/MoS2/metal nanostructures.

We investigated the linear and nonlinear response of the localized surface plasmons (LSPs) and surface plasmon polaritons (SPPs) in metal and MoS2 nanostructures. The results show that the response of LSPs and SPPs has an important influence on the energy exchange. SPPs with unique non-radiative characteristics can be used as energy recovery tanks to reuse the radiated energy of LSPs and promote the production of hot carriers. The energy exchange through plasmon modes can promote the transfer of hot electrons in the Au grating, the MoS2 layer, and the metal film. The fundamental field induces the increase of the second harmonic wave by introducing the second-order nonlinear source. In addition, the evolution of the lifetime of linear and nonlinear plasmonic modes is also investigated to study the underlying mechanism of the micro process in the plasmonic-photonic interaction. The plasmonic energy exchanging configuration overcomes the challenge by utilizing hot carriers. It is instructive in terms of improving the linear and nonlinear performance of plasmonic opto-electronic devices.

Peroxisomal ERK mediates Akh/glucagon action and glycemic control.

The enhanced response of glucagon and its Drosophila homolog, adipokinetic hormone (Akh), leads to high-caloric-diet-induced hyperglycemia across species. While previous studies have characterized regulatory components transducing linear Akh signaling promoting carbohydrate production, the spatial elucidation of Akh action at the organelle level still remains largely unclear. In this study, we find that Akh phosphorylates extracellular signal-regulated kinase (ERK) and translocates it to peroxisome via calcium/calmodulin-dependent protein kinase II (CaMKII) cascade to increase carbohydrate production in the fat body, leading to hyperglycemia. The mechanisms include that ERK mediates fat body peroxisomal conversion of amino acids into carbohydrates for gluconeogenesis in response to Akh. Importantly, Akh receptor (AkhR) or ERK deficiency, importin-associated ERK retention from peroxisome, or peroxisome inactivation in the fat body sufficiently alleviates high-sugar-diet-induced hyperglycemia. We also observe mammalian glucagon-induced hepatic ERK peroxisomal translocation in diabetic subjects. Therefore, our results conclude that the Akh/glucagon-peroxisomal-ERK axis is a key spatial regulator of glycemic control.

CD40LG and GZMB were correlated with adipose tissue macrophage infiltration and involved in obstructive sleep apnea related metabolic dysregulation: Evidence from bioinformatics analysis.

Both obesity and obstructive sleep apnea (OSA) can lead to metabolic dysregulation and systemic inflammation. Similar to obesity, increasing evidence has revealed that immune infiltration in the visceral adipose tissue (VAT) is associated with obstructive sleep apnea-related morbidity. However, the pathological changes and potential molecular mechanisms in visceral adipose tissue of obstructive sleep apnea patients need to be further studied. Herein, by bioinformatics analysis and clinical validation methods, including the immune-related differentially expressed genes (IRDEGs) analysis, protein-protein interaction network (PPI), functional enrichment analysis, a devolution algorithm (CIBERSORT), spearman's correlation analysis, polymerase chain reaction (PCR), Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), we identified and validated 10 hub IRDEGs, the relative mRNA expression of four hub genes (CRP, CD40LG, CCL20, and GZMB), and the protein expression level of two hub genes (CD40LG and GZMB) were consistent with the bioinformatics analysis results. Immune infiltration results further revealed that obstructive sleep apnea patients contained a higher proportion of pro-inflammatory M1 macrophages and a lower proportion of M2 macrophages. Spearman's correlation analysis showed that CD40LG was positively correlated with M1 macrophages and GZMB was negatively correlated with M2 macrophages. CD40LG and GZMB might play a vital role in the visceral adipose tissue homeostasis of obstructive sleep apnea patients. Their interaction with macrophages and involved pathways not only provides new insights for understanding molecular mechanisms but also be of great significance in discovering novel small molecules or other promising candidates as immunotherapies of OSA-associated metabolic complications.

Serum Transferrin Level Is Associated with the Severity of Obstructive Sleep Apnea Independently of Obesity: A Propensity Score-Match Observational Study.

INTRODUCTION: Dysregulation of iron metabolism is closely associated with the development of obesity and obstructive sleep apnea (OSA), but little is known about the relationship between serum transferrin (TF) level and OSA severity. We aimed to verify this relationship and fit into account for obesity-related confounders among bariatric candidates. METHODS: We compared data retrospectively collected in 270 bariatric candidates. A propensity score-matched (PSM) analysis was used to determine the impact of iron metabolism on OSA severity independently of obesity. Univariate analysis was used to evaluate the relationship between serum TF level and the severity of OSA reflected by hypoxia and night awakenings parameters. Serum TF level to predict the severity of OSA was assessed by using univariate and multiple logistic regression model. RESULTS: The preliminary analysis showed that serum ferritin (113 ng/mL [50-203] vs. 79 ng/mL [40-130], p = 0.009) and TF (2.72 g/L [2.46-3.09] vs. 2.65 g/L [2.34-2.93], p = 0.039) level was significantly higher in the moderate/severe OSA group than the no/mild OSA group. After PSM analysis, there were 75 patients in each group and only serum TF level remained significant (p = 0.014). The proportion of patients with combined T2D and hyperlipidemia also remained higher in moderate/severe OSA groups. Univariate analysis showed that the group with higher degree of hypoxia had higher serum TF levels no matter the severity of OSA was grouped by oxygen desaturation index (ODI; 2.79 g/L [2.56-3.06] vs. 2.55 g/L [2.22-2.84], p < 0.001) or minimum oxygen saturation (SpO2nadir; 2.75 g/L [2.50-3.03] vs. 2.56 g/L [2.24-2.92], p = 0.009). Univariate and multiple logistic regression analysis further showed that serum TF level emerged as a significant and independent factor associated with OSA severity especially grouped by ODI (odds ratio: 2.91, 95% CI: 1.36-6.23, p = 0.006). CONCLUSION: The existence of OSA exacerbates obesity comorbidities, particularly type 2 diabetes and hyperlipidemia. Serum TF level is associated with the severity of OSA independently of obesity and might be a potential identification and therapeutic targets.

Acetylation of lactate dehydrogenase B drives NAFLD progression by impairing lactate clearance.

BACKGROUND & AIMS: Lactate has recently been reported to accumulate in the livers of patients progressing from simple steatosis to non-alcoholic steatohepatitis (NASH). However, the underlying mechanism(s) of lactate accumulation and the role of lactate in the progression of non-alcoholic fatty liver disease (NAFLD) are essentially unknown. METHODS: We compared the acetylome in liver samples taken from healthy individuals, patients with simple steatosis and patients with NASH to identify potential targets of acetylation with a role in lactate metabolism. Interactions between the acetylated target and acetyltransferases were measured in multiple cell lines. An acetyltransferase inhibitor was injected into high-fat diet (HFD)-fed mice to determine the role of lactate on NAFLD progression in vivo. RESULTS: Hyperacetylation of lactate dehydrogenase B (LDHB) was found to be associated with lactate accumulation in NAFL and NASH livers in humans and mice. P300/CBP-associated factor (PCAF)-mediated acetylation of LDHB K82 was found to significantly decrease LDHB activity and impair hepatic lactate clearance, resulting in lactate accumulation. Acetylated LDHB induced lactate accumulation which exacerbated lipid deposition and inflammatory responses by activating histone hyperacetylation in HFD-induced NASH. The administration of embelin, a PCAF inhibitor, and the generation of an acetylation-deficient mutant of LDHB ameliorated NASH. CONCLUSION: PCAF-dependent LDHB acetylation plays a key role in hepatic lipid accumulation and inflammatory responses by impairing lactate clearance; this process might be a potential therapeutic target for the treatment of NASH. LAY SUMMARY: Lactate is known to accumulate in the livers of patients during the progression of non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism(s) of this accumulation and its importance in disease progression are unknown. Herein, we show that the acetylation of an enzyme involved in lactate metabolism leads to impaired lactate clearance and exacerbates NAFLD progression.

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis.

Casein kinase 2 (CK2) has become a potential therapeutic target in gastric cancer; however, the underlying mechanism remains incompletely understood. TAp73, a structural homolog of the tumor suppressor p53, acts as a critical regulator of the Warburg effect. Recent study reveals that aberrant CK2 signaling is able to inhibit TAp73 function. Here we determine that TAp73 is overexpressed in AGS-1 but not in SNU-5 gastric cancer cell line as compared with normal gastric cells. In addition, we show that TAp73 expression is required for the maintenance of glucose uptake and lactate release in AGS-1 but not in SNU-5 gastric cancer cells. Importantly, the use of CX-4945, a selective inhibitor of protein kinase CK2, inhibits cell growth and invasion, and promotes cell apoptosis in AGS-1 with decreased TAp73 expression as well as downregulated glucose uptake and lactate release. Although TAp73 knockdown resulted in significant decreases in TAp73 expressions in SNU-5 cell line, no differences in glucose uptake and lactate release were observed between SNU-5 and normal gastric cells. Moreover, TAp73 gene overexpression promotes glucose uptake and lactate release and abolishes the anti-cancer effects of CX-4945 in gastric cancer cell line AGS-1. The impacts of CX-4945 on glycolysis and tumorigenesis were strongly limited in SNU-5 gastric cancer cell line. These findings suggest that CX-4945 elicits an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibits gastric tumorigenesis.

Tumoricidal activities of pterostilbene depend upon destabilizing the MTA1-NuRD complex and enhancing P53 acetylation in hepatocellular carcinoma.

The present study aimed to assess the tumoricidal effect of metastasis-associated protein 1 (MTA1) induced by pterostilbene (PTER) in hepatocellular carcinoma (HCC). The SMMC-7721 hepatoma cell line was treated with PTER. Following treatment, the mRNA transcript abundance of MTA1 was measured using quantitative polymerase chain reaction. Additionally, cell viability was determined using an MTT assay, and protein expression was measured through western blotting. Cell invasion, motility and apoptosis, as well as the cell cycle, were also investigated. Following PTER treatment, MTA1, histone deacetylase (HDAC) 1 and HDAC2 were downregulated, whereas the ratio of acetyl-p53 to total p53 was increased in HCC cells. Cell viability decreased as the PTER dose increased. MTA1 may be associated with proliferation, motility, invasion and metastasis in HCC cells. PTER appeared to repress cell proliferation, trigger apoptosis, induce cell cycle arrest, and inhibit motility and invasion via MTA1 in human liver cancer cells. The results of the present study demonstrated that PTER can downregulate the MTA1-nucleosome remodeling and deacetylase complex, and enhance p53 acetylation to inhibit the growth of tumor cells in HCC.

Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in a male Chinese Han population.

As a multifunctional cytokine, interleukin-6 (IL-6) plays a key role in chronic inflammation as well as tumor growth and progression of hepatitis B virus (HBV) infection. Recent studies have implicated that single nucleotide polymorphism (SNP) -572C>G (rs1800796) located within the promoter region of IL-6 gene was associated with susceptibility to several diseases. Here, a case-control study was undertaken to investigate the association between this polymorphism and HBV-related hepatocellular carcinoma (HCC) susceptibility in a Chinese Han population. A total of 900 patients with chronic HBV infection, including 505 HBV-related HCC patients and 395 HBV infected patients without HCC were enrolled, and rs1800796 polymorphism was genotyped by the TaqMan method and DNA sequencing technology. The results indicated no significant association between rs1800796 polymorphism and the risk of HBV-related HCC in all subjects; however, a significant difference was identified in male subjects. Under the dominant model, male subjects with the G allele (CG/GG) have higher susceptibility to HBV-related HCC than those with CC genotype after adjusting confounding factors (P=0.012, odds ratio [OR] 1.68, 95% confidence interval [95% CI] 1.15-2.42). Our results suggested that rs1800796 polymorphism of IL-6 gene was associated with susceptibility to HBV-related HCC in a male Chinese Han population.

Rather than Rs1800796 polymorphism, expression of interleukin-6 is associated with disease progression of chronic HBV infection in a Chinese Han population.

Interleukin-6 plays an important role in chronic inflammation as well as tumor growth and progression. Here, a case-control study was undertaken to investigate the association of rs1800796 polymorphism of IL-6 gene and serum levels with disease progression of chronic HBV infection. Rs1800796 polymorphism was genotyped in 641 Chinese Han patients with chronic HBV infection, including 23 IT, 25 IC, 292 CHB, 153 LC, and 148 HCC patients and 265 healthy controls. Serum IL-6 levels were measured in 23 IT, 25 IC, 47 CHB, 41 LC, and 49 HCC patients and 45 healthy controls, and the classifications of HCC were accorded to BCLC staging system. We found no significant association between rs1800796 polymorphism and disease progression of chronic HBV infection; however, serum IL-6 levels showed significant statistical differences between patients with CHB, LC, and HCC. Moreover, statistical differences can be observed in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. Our findings suggest that rs1800796 polymorphism unlikely contribute significantly to affect the progression of chronic HBV infection, and serum IL-6 levels can act as a useful indicator for disease progression and severity of chronic HBV infection.

Inhibition of hepatocelluar carcinoma MAT2A and MAT2beta gene expressions by single and dual small interfering RNA.

RNA interference (RNAi) has been successfully applied in suppression of hepatic cancer genes. In hepatocelluar carcinoma cell, one methionine adenosyltransferase (MAT) isozyme, MATII was found to have two catalytic subunits which were encoded by MAT2A and MAT2beta respectively. During tumorigeness of hepatocelluar carcinoma, expressions of the two genes were discovered to be increased combining with a switch of MAT (form MATI to MATII), To figure out the role played by MATII in hepatic cancer, In this study, for the first time we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules specifically targeting two genes. To test the effectiveness of this system, we applied this approach to express simultaneously two different siRNA duplexes that specifically target MAT2A and MAT2beta genes of hepatocelluar carcinoma respectively in HepG2 cell. Results indicated that dual siRNA could simultaneously inhibit the expression of MAT2A and MAT2beta gene by 89.5% and 97.8% respectively, In addition, dual siRNA molecules were able to significantly suppress growth of hepatocelluar carcinoma cell in vitro as well as induce apoptosis which was involved in arrest cell cycle at the G1/S checkpoint and the expressions of p21, p27 and Bax.

Treatment of upper gastrointestinal fistula and leakage with personal stage nutrition support.

AIM: To investigate the feasibility of treatment for upper gastrointestinal fistula and leakage with personal stage nutrition support. METHODS: Forty-three patients with upper gastrointestinal fistula and leakage were randomly divided into two groups. Patients in group A were treated with personal stage nutrition support and patients in group B were treated with total parental nutrition (TPN) in combination with operation. Nutritional states of the candidates were evaluated by detecting albumin (Alb) and pre-Alb. The balance between nutrition and hepatic function was evaluated by measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (Tbill) before and after operation. At the same time their complications and hospitalized time were surveyed. RESULTS: Personal stage nutrition support improved upper gastrointestinal fistula and leakage. The nutrition state and hepatic function were better in patients who received personal stage nutrition support than in those who did not receive TPN. There was no significant difference in the complication and hospitalized time in the two groups of patients. CONCLUSION: Upper gastrointestinal fistula and leakage can be treated with personal stage nutrition support which is more beneficial for the post-operation recovery and more economic than surgical operation.

Lentivirus mediated shRNA interference targeting MAT2B induces growth-inhibition and apoptosis in hepatocelluar carcinoma.

AIM: To investigate the effects of lentivirus vector mediated short hairpin RNA interference targeting methionine adenosyltransferase 2beta gene (LV-shMAT2B) on hepatocelluar carcinoma (HCC) cells. METHODS: We constructed four plasmids of RNA interference targeting the MAT2B gene. After LV-shMAT2B was transfected with L-02 cells and two kinds of HCC cells, cell viability and proliferation were measured with MTT and [3H]thymidine assays respectively. Flow cytometry was used to assess cell apoptosis. The level of S-adenosyl methionine (SAMe) in HepG2 cells was evaluated. The expressions of cyclin D1, cyclin D2, bcl-x(L) and bcl-x(S) were detected with western blot. RESULTS: We constructed LV-shMAT2B successfully. LV-shMAT2B was safe for human normal liver cells. LV-shMAT2B caused dramatic reduction in proliferation compared with controls in HCC cells Bel-7402 (P = 0.054) and HepG2 (P = 0.031). Flow cytometry analysis showed that cell apoptosis caused by LV-shMAT2B was greater in HCC cells Bel-7402 and HepG2 than in control induced by scrambled siRNA (P = 0.047), but apoptosis rates in L-02 induced by LV-shMAT2B and scrambled siRNA respectively had no significant difference. Moreover, LV-shMAT2B significantly suppressed expression of MAT2B leading to growth-inhibition effect on HCC cells by down-regulating cyclin D1. Apoptosis induced by LV-shMAT2B was involved in down-regulating bcl-x(L) and up- regulating bcl-x(S). CONCLUSION: LV-shMAT2B can induce cell apoptosis and growth-inhibition in HCC cells. MAT2B may be a therapy target in HCC in the future.

Expression of angiopoietin-2 is correlated with vascularization and tumor size in human colorectal adenocarcinoma.

Angiopoietins are endothelial growth factors, which play crucial roles in normal vascular development and tumor angiogenesis. We examined the expression profiles of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and Tie-2, a receptor for Ang-1 and Ang-2, in both colorectal adenocarcinoma and adjacent normal tissues, as judged by histology, in order to elucidate their relationships with microvascular density (MVD) and clinicopathologic properties. Higher MVD was associated with a lower degree of differentiation of colorectal adenocarcinoma. Immunohistochemical analysis revealed that the expression of Ang-2 and VEGF was significantly increased in colorectal adenocarcinoma compared to adjacent normal tissues (p < 0.01), and the expression of Ang-2 positively correlated with that of VEGF (r = 0.997, p < 0.01). In contrast, the expression of Ang-1 was lower in adenocarcinoma tissues than in adjacent normal tissues (p < 0.01), while there was no significant difference in Tie-2 expression in both tissues. Moreover, MVD was increased in Ang-2- and VEGF-expressing adenocarcinoma tissues compared to the Ang-2- and VEGF-negative tissues, respectively (p < 0.01). Importantly, MVD was lower in Ang-1-expressing adenocarcinoma tissues relative to Ang-1-negative tissues (p < 0.01). Furthermore, expression of Ang-2 as well as VEGF was significantly up-regulated in colorectal adenocarcinoma with diameters > or = 5 cm or with lymph-node metastases (p < 0.01). In conclusion, the increased expression of Ang-2 and the decreased expression of Ang-1 may be responsible for blood vessel formation and rapid growth of the colorectal adenocarcinoma.

Effect of complex amino acid imbalance on growth of tumor in tumor-bearing rats.

AIM: To investigate the effect of complex amino acid imbalance on the growth of tumor in tumor-bearing (TB) rats. METHODS: Sprague-Dawley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker-256 carcinosarcoma cells was subcutaneously inoculated. TB rats were randomly divided into groups A, B, C and D according to the formula of amino acids in enteral nutritional solutions, respectively. TB rats received jejunal feedings supplemented with balanced amino acids (group A), methionine-depleted amino acids (group B), valine-depleted amino acids (group C) and methionine- and valine-depleted complex amino acid imbalance (group D) for 10 days. Tumor volume, inhibitory rates of tumor, cell cycle and life span of TB rats were investigated. RESULTS: The G0/G1 ratio of tumor cells in group D (80.5 +/- 9.0)% was higher than that in groups A, B and C which was 67.0 +/- 5.1%, 78.9 +/- 8.5%, 69.2 +/- 6.2%, respectively (P<0.05). The ratio of S/G2M and PI in group D were lower than those in groups A, B and C. The inhibitory rate of tumor in groups B, C and D was 37.2%, 33.3% and 43.9%, respectively (P<0.05). The life span of TB rats in group D was significantly longer than that in groups B, C, and A. CONCLUSION: Methionine/valine-depleted amino acid imbalance can inhibit tumor growth. Complex amino acids of methionine and valine depleted imbalance have stronger inhibitory effects on tumor growth.

Tamoxifen combined with octreotide or regular chemotherapeutic agents in treatment of primary liver cancer: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of tamoxifen (TAM) combined with a somatostatin analogue, octretide (OCT) on advanced liver cancer and whether tamoxifen combined with OCT is superior to regular chemotherapeutic agents 5-Fu and mitomycin C (MMC). METHODS: Thirty-nine patients with inoperable liver cancer were randomly subdivided into TAM+OCT group (n=24) and regular chemotherapeutic group (n=15). They received treatment for three months respectively. Blood cell count, liver function, immunologic function, blood alpha-FP was regularly measured. Liver lump and extrahepatic metastasis were examined by CT. The patients were followed up after treatment and conducted survival analysis. RESULTS: In the TAM+OCT group, complete response is 4 patients, partial response is 7 patients, no change is 9 patients and progressive disease is 4 patients; blood level of ALT and AST had no noticeable change, IgE and IgG increased (P<0.01), and alpha-FP lowered (P<0.05). In regular chemotherapeutic group, no change is 4 patients and progressive disease is 11 patients. There was conspicuous statistical difference in the two groups. The accumulative survival rates of 6 months, 1 year and 2 years were 95.7% vs 41.2% (P<0.01), 63.7% vs 21.1% (P<0.01), 25.4% vs 0 (P<0.01), respectively. Medium survival time was 12.8 months in TAM+OCT group and 5.5 months in chemotherapeutic group. CONCLUSIONS: TAM+OCT excerts reliable therapeutic effect on patients with inoperable ER(+) hepatocellular cancer. It is superior to 5-Fu and MMC in increasing the survival rate, prolonging survival time, and reducing side-effects.

Toxicities and therapeutic effect of 5-fluorouracil controlled release implant on tumor-bearing rats.

AIM: To investigate the toxicities, biodistribution and anticancer effect of 5-fluorouracil controlled release implant (5-FUCI) on Walker 256 carcinosarcoma cells in Wistar rats. METHODS: Experiment 1: Wistar rats were randomly divided into three groups (27 rats per group). Blank implant was implanted in left lobe of the liver, and rats were treated with saline solution (in group A) or 5-fluorouracil (subcutaneous injection, group B). 5-FUCI was inserted in left lobe of the liver (group C). The gastrointestinal and hematological toxicities were observed and contents of element F in group C were assayed. Experiment 2: on day 6 after Walker-256 carcinosarcoma transplantation in left lobe of the liver, 5-FUCI was implanted in right lobe of the liver (group E) or left lobe (group F), and rats in control group (group D) were inserted blank implant. Tumor inhibition rate and survival time were investigated. RESULTS: 5-FUCI showed no obvious toxic effect, extraction of Evan's blue from gastrointestinal tissue was normal, the peripheral white blood cells and bone marrow nucleated cells were not reduced, compared with control group (P>0.05). Histological examination revealed that there were no visible changes in small intestinal mucosa, The concentration of 5-fluorouracil in left lobe of the liver was 9.84, 28, 34 times as much as those of right lobe of the liver, heart and kidney respectively after the implantation in group C. They kept a high level of fluorouracil in left lobe of the liver, ranging from (4.414+/-0.482) % to (7.800+/-0.804) %, for eight weeks. Survival days were 28.0+/-2.2, 30.0+/-3.2 and 38.7+/-6.7 d in group D, E and F, respectively. CONCLUSION: 5-FUCI shows no obvious toxicities to gastrointestinal tract and myelotoxicity. After implantation, it kept a high level of 5- fluorouracil in surrounding tissues of the implant for eight weeks. Its antitumor effect on Walker-256 carcinosarcoma is demonstrated.

Influence of methionine/valine-depleted enteral nutrition on nucleic acid and protein metabolism in tumor-bearing rats.

AIM: To investigate the effects of methionine/valine-depleted enteral nutrition (EN) on RNA, DNA and protein metabolism in tumor-bearing (TB) rats. METHODS: Sprague-Dawlley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker-256 carcinosarcoma cells was subcutaneously inoculated. 48 TB rats were randomly divided in 4 groups: A, B, C and D. The TB rats had respectively received jejunal feedings supplemented with balanced amino acids, methionine-depleted, balanced amino acids and valine-depleted for 6 days before injection of 740 KBq (3)H- methionine/valine via jejunum. The (3)H incorporation rate of the radioactivity into RNA, DNA and proteins in tumor tissues at 0.5, 1, 2, 4 h postinjection of tracers was assessed with liquid scintillation counter. RESULTS: Incorporation of (3)H into proteins in groups B and D was (0.500+/-0.020) % to (3.670+/-0.110) % and (0.708+/-0.019) % to (3.813+/-0.076) % respectively, lower than in groups A ((0.659+/-0.055) % to (4.492+/-0.108) %) and C ((0.805+/-0.098) % to (4.180+/-0.018) %). Incorporation of (3)H into RNA, DNA in group B was (0.237+/-0.075) % and (0.231+/-0.052) % respectively, lower than in group A (P<0.01). There was no significant difference in uptake of (3)H by RNA and DNA between group C and D (P>0.05). CONCLUSION: Protein synthesis was inhibited by methionine/valine starvation in TB rats and nucleic acid synthesis was reduced after methionine depletion, thus resulting in suppression of tumor growth.