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Objective: Immune checkpoint inhibitors (ICI) are recommended as the first‐line therapy for platinum‐refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features‐associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. Methods: A total of 31 platinum‐refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI‐based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. Results: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey‐level co‐occurrence matrix‐associated texture features were the most important in identifying the patients with or without 9‐month R/M death. A radiomic risk‐stratification model was established and equally separated the patients into high‐, intermittent‐ and lower‐risk groups (1‐year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short‐run high grey‐level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD‐L1) expression in selecting whether patients received ICI‐based therapy. Conclusions: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates. Case Presentation: A 14‐year‐old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow‐up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis. Conclusion: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway. [ABSTRACT FROM AUTHOR]

In recent years, during the ravages of COVID-19, a variety of vaccines have been developed and are now on the market. However, although these new vaccines have undergone various trials, there are still many unknown side effects. We report a case of a 30-year-old woman who presented with general weakness, sore throat, generalized skin rashes, symmetrical arthralgia, and persistent fever of up to 40 °C with onset 16 days after receiving the Moderna COVID-19 vaccine. Adult-onset Still's disease (AOSD) was diagnosed according to Yamaguchi's criteria after excluding the feasibility of infectious diseases, autoimmune diseases, and malignancies. In particular, her responses to glucocorticoids and naproxen were significant and inversely proportional to her use of empirical antibiotics in the initial stage of treatment. We studied some similar cases of AOSD, which also considered the adverse effects of COVID-19 vaccination and suggested the immunogenicity and possibility of inflammatory responses related to COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Purpose: Pemetrexed-based chemotherapy (Pem-C) is the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, limited tumor-associated proteins in blood are available to predict pemetrexed response and/or survival. Patients and Methods: Plasma samples from three responders and three nonresponders with stage IIIB–IV NSCLC were collected prior to Pem-C and analyzed using Proteome ProfilerTM Human XL Oncology Array to detect 84 oncology-related proteins. The plasma concentrations of cathepsin S, endoglin (ENG), and matrix metalloproteinases 3 and 9 in 71 patients with advanced NSCLC treated with Pem-C were further measured using enzyme-linked immunosorbent assay based on the remarkable differences in the four proteins between responders and nonresponders in the array results. Results: Pem-C responders had significantly higher ENG levels but not the other three markers than nonresponders (mean ENG level: 27.1 ± 7.4 vs 22.3 ± 6.9, p < 0.01). High ENG concentration was correlated with improved progression-free survival (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.31– 0.86, p < 0.01) and overall survival (HR: 0.55, 95% CI: 0.32– 0.94, p < 0.05) in patients treated with Pem-C, and the ENG level was an independent factor in our cohort (HR: 0.54, 95% CI: 0.33– 0.89, p < 0.05). ENG concentration in Pem-C responders also significantly increased at the time of best response (p < 0.05). Conclusion: Cumulatively, this study reveals that ENG is correlated with Pem-C responsiveness in patients, which indicates the potential use of plasma ENG levels as a non-invasive biomarker for pemetrexed-based treatment in patients with non-squamous NSCLC. [ABSTRACT FROM AUTHOR]

Background/Aims: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. Methods: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl4-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Results: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl4-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl4-induced hepatic iNOS and COX-2 expression, as well as CCl4-induced hepatic inflammation and necrosis in mice. Conclusion: MRE exhibited antiinflammatory and hepatic protective activity. [ABSTRACT FROM AUTHOR]

This is the first study to investigate the relationships among fibroblast growth factor receptor 4 (FGFR4) genetic polymorphisms, development of uterine cervical cancer, clinicopathological variables, and patient prognosis in Taiwanese women. Real-time polymerase chain reaction and genotyping were used to detect the genotype frequencies of 4 FGFR4 single-nucleotide polymorphisms (SNPs), rs351855 (C/T, Gly388Arg), rs2011077 (G/A), rs7708357 (G/A), and rs1966265 (Ile10Val), in 138 patients with invasive cancer, 89 with precancerous lesions of uterine cervix, and 335 normal controls. The results showed that there is no significant difference in the frequencies of FGFR4 SNPs rs351855, rs2011077, rs7708357, and 1966265 between women with cervical invasive cancer and normal controls even after controlling for age. However, significant differences existed in the distributions of the FGFR4 genetic polymorphism rs2011077, when mutant homozygotes (AA) were compared using other genotypes (GG/GA) as a reference, as well as rs1966265, when mutant homozygotes (AA) were compared using GG/GA as a reference, between women with cervical precancerous lesions and normal women even after controlling for age. In multivariate analysis, lymph node metastasis was associated with cancer recurrence, and lymph node metastasis and FGFR4 rs351855 were associated with patient survival. In conclusion, our study demonstrated that FGFR4 rs2011077 and rs1966265 are associated with the progression of cervical normal tissues to precancerous lesions in Taiwanese women. Moreover, rs351855 (Gly388Arg) is the only FGFR4 genetic polymorphism that is associated with patient survival. [ABSTRACT FROM AUTHOR]

ABSTRACT Apigenin (4′,5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21WAF1/CIP1 and increased the interaction of p21WAF1/CIP1 with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21WAF1/CIP1 promoter region, resulting in the increase of p21WAF1/CIP1 transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21WAF1/CIP1 and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017. [ABSTRACT FROM AUTHOR]

To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12-3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24-3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22-3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22-3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer. [ABSTRACT FROM AUTHOR]

Background: Moniliformediquinone (MFD), a phenanthradiquinone in Dendrobium moniliforme, was synthesized in our laboratory. Beyond its in vitro inhibitory effects on cancer cells, other biological activity of MFD is unknown. The purpose of the present study was to investigate the effects of MFD on hepatic fibrogenesis in vitro and in vivo.Methods: Hepatic stellate HSC-T6 was cultured. Cell viability assay and western blot analyses were performed. Male ICR mice were evaluated on CCl4-induced hepatotoxicity using both histological examination and immunohistochemical staining.Results: First, in vitro study showed that the synthesized MFD effectively attenuated the expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and type I collagen (COL-1), which modulated the hepatic fibrogenesis. Furthermore, MFD reduced the phosphorylation of p65 NFκB in HSC-T6 cells. In vivo, liver fibrosis was induced by CCl4 twice a week for 10 weeks in mice. The administration of the MFD was started after 1 week of CCl4 thrice-weekly; the MFD significantly reduced plasma aspartate transaminase (AST) and lactose dehydrogenase (LDH) as well as hepatic hydroxy-proline, α-SMA, and COL-1 expression in CCl4-treated mice. Pathological analysis showed that the MFD alleviated CCl4-induced hepatic inflammation, necrosis and fibrosis. These results suggest that MFD possesses therapeutic potential for liver fibrosis.Conclusions: The synthesized MFD exhibits anti-fibrotic potential by inactivation of HSCs in vitro and decreases mouse hepatic fibrosis in vivo. Further investigation into their clinical therapeutic potential is required. [ABSTRACT FROM AUTHOR]

Background: To investigate the implication of ribonucleotide reductase M2 (RRM2) in the carcinogenesis of uterine cervix and its relationship with clinicopathological characteristics and prognosis of cancer patients. Methodology and Principal Findings: The impact of RRM2 on cell viability was investigated in SiHa cervical cancer cells after RRM2 knockdown and the addition of cisplatin, which induces inter- and intra-strand DNA crosslinks. RRM2 immunoreactivity was evaluated by semi-quantitative H score among 29 normal, 30 low-grade dysplasia, 30 high-grade dysplasia and 103 invasive cancer tissue specimens of the uterine cervix, using tissue microarrays. RRM2 was then correlated with the clinicopathological variables of cervical cancer and patient survival. A greater toxic effect on cell viability using cisplatin was reflected by the greater reduction in RRM2 protein expression in SiHa cells. The RRM2 expression in cancer tissues was higher than that in high-grade dysplasia, low-grade dysplasia or normal cervical tissues. RRM2 upregulation was correlated with deep stromal invasion, large tumors and parametrial invasion and predicted poor survival. Conclusions: RRM2 is a new molecular marker for the diagnosis and clinical outcomes of cervical cancer. It is involved in cervical carcinogenesis and predicts poor survival, and may be a potential therapeutic target including in cisplatin treatment. [ABSTRACT FROM AUTHOR]

Carcinogenic agents such as N-methyl- N-nitrosourea can cause tumors. The aims of the present study were to evaluate and classify a subtype of AML (acute myeloid leukemia) that was induced by NMU. According to previous publications, NMU induces not only mammary cancer but also leukemia in Sprague-Dawley (S-D) rats. However, the subtype of leukemia involved in NMU-treated rats is unknown. We found that both organ weight and relative organ weights were significantly higher in NMU-exposed rats than in controls. Morphological changes of rat livers and spleens were assessed by histological evaluation (H&E staining), which found that these tissues were abnormal in appearance. Also, cytological examination of the blood showed immature white blood cells in a smear using Liu's and Papanicolaou stains, indicating that gross abnormalities and histopathological changes were pathologically observed. NMU leukemia incidence was 97.1%. In this study, immunohistochemical (IHC) analysis was valuable in classifying the leukemia of poorly differentiated blasts induced by NMU. Paraffin blocks were stained for MPO, CD3, CD15, CD20, and CD34 markers. The NMU-induced group was positive for MPO, but negative for CD3, CD15, CD20, and CD34. These CD markers suggest that they are useful in helping diagnose APL (M3) leukemia. The model of NMU-induced leukemogenesis in an S-D rat suggests a more definite way to classify APL. This APL will provide an important tool for chemical carcinogenesis and leukemia studies. [ABSTRACT FROM AUTHOR]

Background: HER2 gene amplification and HER2 protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast cancer patients. The purpose of this study is to evaluate the correlation between HER2 protein expressions and the HER2 gene copies per tumor cell either before or after chromosome-17 correction in epithelial ovarian cancer (EOC). Methods: Adopting 2007 ASCO/CAP guideline recommendations for HER2 testing, 27 tissue microarray (TMA) samples from EOC patients were analyzed by immunohistochemistry (IHC) using Dako, c-erb-B2 antibody and subsequently examined by fluorescence in situ hybridization (FISH) using Abbott/Vysis, PathVysion HER2 DNA Probe Kit. Results: The overall concordance revealed 81.5% between HER2 IHC and HER2 FISH results. Additionally, HER2 gene copies prior to chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories ( P = 0.026), as did the HER2 gene copies after chromosome-17 correction ( P = 0.028). On the other hand, HER2 IHC results correlated significantly with both chromosome-17 uncorrected HER2 gene copy numbers ( ρ = 0.430, P = 0.025) and chromosome-17 corrected HER2 gene copy numbers ( ρ = 0.524, P = 0.027). Conclusion: We demonstrated that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC result categories; and tests for the HER2 gene copies per tumor cell either before or after correction for chromosome-17 can be applied as a potentially valuable tool in analyzing the HER2 status in EOC. [ABSTRACT FROM AUTHOR]

Background: Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC). Methods: Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing. Results: The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases. Conclusions: HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC ( P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy. [ABSTRACT FROM AUTHOR]

Actinomycosis is an uncommon disease, which is usually manifested as cervicofacial infection and related to poor oral hygiene or compromised immune function. Pulmonary actinomycosis is rare, but its diagnosis is changing due to its variable presentation and the similarity in appearance to other intrapulmonary diseases. Here we report an 80-year-old man with a solitary pulmonary nodule over the left upper lobe. Pulmonary neoplasm was highly suspected in this patient and thus resection of the mass was undertaken through video-assisted thoracic surgery (VATS). Histopathological examination demonstrated this patient had an Actinomyeces infection. While the application of VATS in patients with pulmonary actinomycosis has rarely been reported in literature, we conclude that VATS is valuable for the diagnosis and treatment of patients with undetermined pulmonary nodule(s). [ABSTRACT FROM AUTHOR]

Berberine, a main protoberberine component of Coptidis Rhizoma, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver. In the preliminary study, berberine expressed an antioxidant property by its capacity for quenching the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further investigations were conducted using t-BHP-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats to evaluate the antioxidative bioactivity of berberine. The results in rat primary hepatocytes demonstrated that berberine, at the concentrations of 0.01–1.0 mM, significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and the formation of malondialdehyde (MDA) induced by 30 min treatment of t-BHP (1.5 mM). Berberine also attenuated the t-BHP-induced depletion of glutathione (GSH) and induced a high level of DNA repair synthesis. The in vivo study showed that the intraperitoneal pretreatment with berberine (0.5 and 5 mg/kg) for 5 days before a single dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of hepatic enzyme markers (ALT and aspartate aminotransferase) and reduced oxidative stress in the liver. The histopathological evaluation of the livers revealed that berberine reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltrations, and necrosis induced by t-BHP. These results lead us to speculate that berberine may play a chemopreventive role via reducing oxidative stress in living systems. [ABSTRACT FROM AUTHOR]

The modulation of cytochrome P-450 2B1 expression by α-tocopheryl succinate and whether prostaglandin E[sub 2] is involved in this modulation in primary rat hepatocytes in the presence of phenobarbital were investigated. A primary rat hepatocyte culture model that faithfully reproduces the phenobarbital response observed in vivo was used. Intracellular α-tocopherol content was dose dependently increased by α-tocopheryl succinate incubation. Hepatocytes were demonstrated to have prostaglandin E[sub 2]-synthesizing capability. α-Tocopheryl succinate inhibited prostaglandin E[sub 2] synthesis by hepatocytes and increased cytochrome P-450 2B1 expression in the presence of phenobarbital; however, it had little effect on intracellular cAMP level. To mimic the exogenous source of prostaglandin E[sub 2] from nonparenchymal cells, various concentrations of prostaglandin E[sub 2] were added to the cell culture. High doses of exogenous prostaglandin E[sub 2] (100 and 1,000 nM) inhibited the cytochrome P-450 2B1 expression in the presence of phenobarbital compared with low doses (1 and 10 nM); however, the presence of high doses of prostaglandin E[sub 2] had no effect on intracellular cAMP level. Forskolin significantly increased intracellular cAMP level and inhibited cytochrome P-450 2B1 expression in the presence of phenobarbital. The results of this study indicate that α-tocopheryl succinate increases cytochrome P-450 2B1 expression via its inhibition of prostaglandin E[sub 2] synthesis in the presence of phenobarbital; however, changes in intracellular cAMP level are not related to cytochrome P-450 2B1 expression. [ABSTRACT FROM AUTHOR]

Increasing evidence regarding free radical-generating agents and inflammatory processes suggests that accumulation of reactive oxygen species can cause hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydroperoxide (t-BHP), can be metabolized to free radical intermediates by cytochrome P-450 in hepatocytes, which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. In this study, we used t-BHP to induce hepatotoxicity in vitro and in vivo and determined the antioxidative bioactivity of esculetin, a coumarin compound. Our investigations showed that pretreatment with esculetin (5–20 µg/ml) significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT), and also decreased the formation of malondialdehyde (MDA) in primary cultured rat hepatocytes induced by a 30-min treatment with t-BHP. An in vivo study in rats showed that pretreatment with esculetin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that esculetin reduced the incidence of liver lesions induced by t-BHP, including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that esculetin may play a chemopreventive role via reducing oxidative stress in living systems. [ABSTRACT FROM AUTHOR]

Effects of low corn oil, high corn oil, and high fish oil diets on altered hepatic foci development in female Sprague-Dawley rats were investigated. Rats assigned to Groups 1‐4 were initiated with saline as the control and those assigned to Groups 5‐7 were initiated with diethylnitrosamine (DEN 15 mg/kg) at 24 hours of age. After weaning, all rats, except those in Group 1, received 500 ppm phenobarbital (PB) in their diet as tumor promoter for three months. Altered hepatic foci development was significantly lower in DEN-initiated rats fed the high fish oil + PB diet than in DEN-initiated rats fed the high corn oil + PB diets. Liver weight and relative liver weight were significantly greater in rats fed the high fish oil + PB diet than in rats fed the other diets, and hepatic biotransformation/detoxification enzyme activities were greater in rats fed the fish oil + PB diets than in rats fed the other diets. These results suggest that the effect of a high fish oil diet on altered hepatic foci may occur through regulation of hepatic biotransformation/detoxification enzyme activities, leading to alteration in the tumor-promoting action of PB. Dietary lipid significantly affected the hepatic phospholipid fatty acid composition of rats. n-3 polyunsaturated fatty acids were incorporated into membrane phospholipid at the expense of n-6 polyunsaturated fatty acids. A high fish oil diet caused greater oxidative stress in rats, as measured by plasma vitamin E level, red blood cell glutathione status, liver lipid peroxidation, and hepatic glutathione reductase activity. Pearson's correlation analysis indicated that the foci number was negatively correlated to the liver thiobarbituric acid-reactive substance and 7-pentoxyresorufin O-dealkylase activity, and the foci area was negatively correlated to the liver thiobarbituric acid-reactive substance activity (p <> . [ABSTRACT FROM AUTHOR]

Abstract: The effects of topical application of baicalein on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors, hyperplasia, ornithine decarboxylase activity, and inflammation were evaluated in female CD-1 mice. Topical application of baicalein (0.08, 0.16, or 0.2 mumol) with TPA (5 nmol) twice weekly for 24 weeks to mice previously initiated with benzo[a]pyrene inhibited the number of TPA-induced tumors per mouse significantly. Preapplication of the same amount of baicalein also afforded significant protection against TPA-induced hyperplasia in the ear skin. Topical application of baicalein inhibited tumor promoter-caused induction of epidermal ornithine decarboxylase activity by TPA (5 nmol). The topical application of baicalein (0.008, 0.016, or 0.02 mumol) inhibited TPA-induced edema of mouse ears by 88%, 96%, or 97%, respectively. Pretreatment of mouse skin with various amounts of baicalein caused inhibition of H[sub 2]O[sub 2] and myeloperoxidase formation by TPA. These results indicate that baicalein can be a potential cancer-chemopreventive agent against tumor promotion. [ABSTRACT FROM AUTHOR]

Background:Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. Methodology/Principle Findings:Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of invivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice. Conclusion:The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection. [ABSTRACT FROM AUTHOR]