Publications by authors named "Masaki Fujioka"

119 Publications

Fournier's Gangrene With Subcutaneous Emphysema of the Thigh Caused by Air Inflow Associated With a Rectovaginal Fistula: A Case Report of Pseudo-gas Gangrene.

Wounds 2021 Jan;33(1):E10-E13

Shimane University, Shimane, Japan.

Introduction: Rectovaginal fistulas (RVFs) are abnormal connections between the rectum and vagina.

Case Report: A 61-year-old female patient was admitted to the authors' hospital with swelling, extending from the left thigh to the left lower abdomen and crepitus. An axial computed tomography scan showed air in the soft tissue of the left thigh, left buttock, perineal region, and left lower abdomen. Gas gangrene was suspected. Accordingly, the patient was administered meropenem, clindamycin, and vancomycin and underwent emergency debridement. An intraoperative examination revealed necrotizing fasciitis in the left buttock but no inflammatory signs in the thigh. On postoperative day 8, fecal matter was discharged from the patient's vagina, and an RVF was detected by colon fiberscopy. The patient underwent resurfacing surgery with a free skin graft, and a colon stoma was fashioned 15 days after the primary surgery. The patient was discharged on day 14 following surgery with wound healing.

Conclusion: The existence of free air in subcutaneous tissue combined with an infection, particularly in the extremities, is generally suggestive of gas gangrene. In the present case, subcutaneous gas was not caused by gas gangrene but rather by air inflow from an RVF. Appropriate treatment of the RVF was necessary to avoid the exacerbation of Fournier's gangrene and prevent necrosis spreading to the thigh.
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January 2021

Cache Domain Containing 1 Is a Novel Marker of Non-Alcoholic Steatohepatitis-Associated Hepatocarcinogenesis.

Cancers (Basel) 2021 Mar 10;13(6). Epub 2021 Mar 10.

Department of Molecular Pathology, Graduate School of Medicine, Osaka City University, Abeno-ku 1-4-3 Asahi-machi, Osaka 545-8585, Japan.

In the present study, potential molecular biomarkers of NASH hepatocarcinogenesis were investigated using the STAM mice NASH model, characterized by impaired insulin secretion and development of insulin resistance. In this model, 2-days-old C57BL/6N mice were subjected to a single subcutaneous (s.c.) injection of 200 μg streptozotocin (STZ) to induce diabetes mellitus (DM). Four weeks later, mice were administered high-fat diet (HFD) HFD-60 for 14 weeks (STAM group), or fed control diet (STZ group). Eighteen-week-old mice were euthanized to allow macroscopic, microscopic, histopathological, immunohistochemical and proteome analyses. The administration of HFD to STZ-treated mice induced significant fat accumulation and fibrosis development in the liver, which progressed to NASH, and rise of hepatocellular adenomas (HCAs) and carcinomas (HCCs). In 18-week-old animals, a significant increase in the incidence and multiplicity of HCAs and HCCs was found. On the basis of results of proteome analysis of STAM mice HCCs, a novel highly elevated protein in HCCs, cache domain-containing 1 (CACHD1), was chosen as a potential NASH-HCC biomarker candidate. Immunohistochemical assessment demonstrated that STAM mice liver basophilic, eosinophilic and mixed-type altered foci, HCAs and HCCs were strongly positive for CACHD1. The number and area of CACHD1-positive foci, and cell proliferation index in the area of foci in mice of the STAM group were significantly increased compared to that of STZ group. In vitro siRNA knockdown of CACHD1 in human Huh7 and HepG2 liver cancer cell lines resulted in significant inhibition of cell survival and proliferation. Analysis of the proteome of knockdown cells indicated that apoptosis and autophagy processes could be activated. From these results, CACHD1 is an early NASH-associated biomarker of liver preneoplastic and neoplastic lesions, and a potential target protein in DM/NASH-associated hepatocarcinogenesis.
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http://dx.doi.org/10.3390/cancers13061216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001421PMC
March 2021

Effects of Hand Hygiene Using 4% Chlorhexidine Gluconate or Natural Soap During Hand Rubbing Followed by Alcohol-Based 1% Chlorhexidine Gluconate Sanitizer Lotion in the Operating Room.

Adv Wound Care (New Rochelle) 2021 Mar 30. Epub 2021 Mar 30.

Shabondama Soap Co., Ltd., Fukuoka, Japan.

Hand hygiene using either 4% chlorhexidine gluconate (CHG) or natural soap during hand rubbing, followed by alcohol-based 1% CHG sanitizer lotion in the operating room was compared to assess bacterial reduction, skin moisture, skin texture, and hand hygiene using qualitative questionnaires. A crossover study with 36 professional scrub nurses at two medical centers was performed to compare 4% CHG followed by alcohol-based 1% CHG sanitizer lotion, the Two-stage method with handwashing using natural soap followed by alcohol-based 1% CHG sanitizer lotion, and the Waterless method, after a period of 10 days of use. The study completely followed CONSORT, www.consort-statement.org. There was no significant difference in bacterial reduction based on the bacterial colony-forming units between the two methods. The skin moisture and skin roughness scores were not significantly different between the two methods. The Waterless method was significantly better than the Two-stage method regarding "foaming," "quality," "longevity" ( < 0.0001,  < 0.0001, and  < 0.0001, respectively), but "disappearance" was significantly better by the Two-stage method ( = 0.0095) during washing and rubbing. Immediately after washing and rubbing, the Waterless method was significantly better regarding "tightness" and "moisture," whereas the Two-stage method was significantly better regarding "stickiness" ( = 0.0114,  = <0.0001, and 0.0059, respectively) The Waterless method using natural soap during handwashing followed by alcohol-based 1% CHG sanitizer lotion was as effective as the Two-stage method of 4% CHG followed by alcohol-based 1% CHG sanitizer lotion. Handwashing using natural soap is simple and superior to hand scrubbing in several aspects.
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http://dx.doi.org/10.1089/wound.2020.1352DOI Listing
March 2021

Accumulation of 8-hydroxydeoxyguanosine, L-arginine and Glucose Metabolites by Liver Tumor Cells Are the Important Characteristic Features of Metabolic Syndrome and Non-Alcoholic Steatohepatitis-Associated Hepatocarcinogenesis.

Int J Mol Sci 2020 Oct 20;21(20). Epub 2020 Oct 20.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Abeno-ku, 1-4-3 Asahi-machi, Osaka 545-8585, Japan.

To uncover mechanisms and explore novel biomarkers of obesity, type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH)-associated hepatocarcinogenesis, cellular and molecular alterations in the liver, and hepatocellular carcinomas (HCCs) were investigated in NASH model 60-week-old Tsumura, Suzuki, Obese Diabetic (TSOD) mice and NASH HCC patients. Markedly elevated lipid deposition, inflammation, fibrosis, and peroxisome proliferation in the liver, preneoplastic lesions, and HCCs of TSOD mice were accompanied by accumulation of polysaccharides in the cellular cytoplasm and nuclei and increase of oxidative DNA damage marker, 8-hydroxydeoxyguanosine (8-OHdG) formation in the liver and altered foci. Metabolomics of TSOD mice HCCs demonstrated significant elevation of the concentration of amino acid L-arginine, phosphocreatine, -adenosylmethionine/-adenosylhomocysteine ratio, adenylate, and guanylate energy charges in coordination with tremendous rise of glucose metabolites, mostly fructose 1,6-diphosphate. L-arginine accumulation in HCCs was associated with significant under-expression of arginase 1 (ARG1), suppression of the urea cycle, methionine and putrescine degradation pathways, activation of Ser and Thr kinase Akt AKT, phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinase 1/2 (ERK1/2) kinases, β-catenin, mammalian target of rapamycin (mTOR), and cell proliferation. Furthermore, clinicopathological analysis in 20 metabolic syndrome/NASH and 80 HCV-positive HCC patients demonstrated significant correlation of negative ARG1 expression with poor tumor differentiation, higher pathological stage, and significant decrease of survival in metabolic syndrome/NASH-associated HCC patients, thus indicating that ARG1 could become a potential marker for NASH HCC. From these results, formation of oxidative stress and 8-OHdG in the DNA and elevation of glucose metabolites and L-arginine due to ARG1 suppression in mice liver cells are the important characteristics of T2DM/NASH-associated hepatocarcinogenesis, which may take part in activating oxidative stress resistance, synthesis of phosphocreatine, cell signaling, methylation, and proliferation.
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http://dx.doi.org/10.3390/ijms21207746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594076PMC
October 2020

Dimethylarsinic acid (DMA) enhanced lung carcinogenesis via histone H3K9 modification in a transplacental mouse model.

Arch Toxicol 2020 03 12;94(3):927-937. Epub 2020 Feb 12.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Pregnant CD-1 mice received 200 ppm dimethylarsinic acid (DMA) in the drinking water from gestation day 8-18, and tumor formation was assessed in offspring at the age of 84 weeks. DMA elevated the incidence of lung adenocarcinoma (10.0%) and total tumors (33.3%) in male offspring compared to male control offspring (1.9 and 15.1%, respectively). DMA also elevated the incidence of hepatocellular carcinoma (10.0%) in male offspring compared to male control offspring (0.0%). DMA and its metabolites were detected in the lungs of transplacental DMA-treated neonatal mice. Transplacental DMA exposure increased cell proliferation in the epithelium in the lungs of both neonatal and 6-week-old male mice. Microarray and real-time PCR analyses detected high expression of keratin 8 (Krt8) in the lungs of both neonatal and 6-week-old DMA-treated mice. Western blot analysis indicated that DMA elevated methylation of histone H3K9, but not H3K27, in the lungs of male mice. Importantly, chromatin immunoprecipitation sequencing (ChIP-seq) analysis using an H3K9me3 antibody found differences in heterochromatin formation between mice exposed to DMA and the controls. Notably, ChIP-seq analysis also found regions of lower heterochromatin formation in DMA-treated mice, and one of these regions contained the Krt8 gene, agreeing with the results obtained by microarray analysis. High expression of Krt8 was also detected in adenoma and adenocarcinoma of the lung in male offspring. Overall, these data indicate that transplacental DMA treatment enhanced lung and liver carcinogenesis in male mice. In the lung, DMA caused aberrant methylation of histone H3K9, increased Krt8 expression, and enhanced cell proliferation.
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http://dx.doi.org/10.1007/s00204-020-02665-xDOI Listing
March 2020

Cardiopulmonary resuscitation of a cardiac arrest patient with left ventricular assist device in an out-of-hospital setting: A case report.

Medicine (Baltimore) 2020 Jan;99(2):e18658

Emergency and Critical Care Center, Mie University Hospital.

Rationale: Despite increasing number of left ventricular assist device (LVAD) implantation, standardized cardiopulmonary resuscitation (CPR) protocol for patients with LVAD, especially in out-of-hospital settings are not well known.

Patient Concerns: A 41-year-old LVAD implanted man became cardiac arrest in an out-of-hospital setting. Bystander CPR was started and the patient was brought to our hospital without noticing LVAD. Upon arrival, the medical staff noted the LVAD and that the battery of the LVAD was exhausted.

Diagnosis: Cardiac arrest on LVAD.

Interventions: It took 50 minutes to change the battery, then the patient has become ventricular fibrillation; hence, we introduced extracorporeal membranous oxygenation and defibrillated the patient. After the sinus rhythm was restored, the LVAD started working uneventfully.

Outcomes: The patient became brain dead.

Lessons: There are several difficulties in treating these patients. First, hemodynamic collapse is difficult to diagnose. Second, chest compression for LVAD implanted patients remains controversial. Third, education to first responders who are not familiar with LVAD are not enough. Appropriate education for those issues is needed.
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http://dx.doi.org/10.1097/MD.0000000000018658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959936PMC
January 2020

Promotion effects of acetoaceto-o-toluidide on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats.

Arch Toxicol 2019 12 31;93(12):3617-3631. Epub 2019 Oct 31.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Abeno-ku, 1-4-3 Asahi-machi, Osaka, Japan.

Recent epidemiological studies have indicated that occupational exposure to the aromatic amine acetoaceto-o-toluidide (AAOT) was associated with a marked increase in urinary bladder cancers in Japan. However, little is known about the carcinogenicity of AAOT. To evaluate the urinary bladder carcinogenicity of AAOT, male and female F344 rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks followed by dietary administration of 0, 0.167, 0.5, or 1.5% AAOT for 31 weeks. The incidences and multiplicities of bladder tumors were significantly increased in the 0.5 and 1.5% groups of male and female rats in a dose-response manner. AAOT and seven downstream metabolites were detected in the urine of the male and female rats administered AAOT with levels increasing in a dose-dependent manner. The most abundant urinary metabolite of AAOT was the human bladder carcinogen o-toluidine (OTD), which was at least one order of magnitude higher than AAOT and the other AAOT metabolites. In a second experiment, male F344 rats were administered 0, 0.167, or 1.5% AAOT for 4 weeks. Gene expression analyses revealed that the expression of JUN and its downstream target genes was increased in the urothelium of male rats treated with 1.5% AAOT. These results demonstrate that AAOT promotes BBN-induced urinary bladder carcinogenesis in rats and suggest that overexpressed of JUN and its downstream target genes may be involved the bladder carcinogenicity of AAOT. In conclusion, AAOT, like other carcinogenic aromatic amines, is likely to be a carcinogen to the urinary bladder, and OTD metabolized from AAOT is the ultimate carcinogen.
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http://dx.doi.org/10.1007/s00204-019-02605-4DOI Listing
December 2019

Long-term administration of excess zinc impairs learning and memory in aged mice.

J Toxicol Sci 2019 ;44(10):681-691

Department of Molecular Pathology, Osaka City University Graduate School of Medicine.

Zinc (Zn) is an essential element, but excess amounts are known to cause neurotoxic effects. The risk of excessive Zn intake is increased by supplementing food intake with dietary supplements. Ageing affects many cellular processes that predispose individuals to neurodegeneration. Indeed, the prevalence of senile dementia such as Alzheimer's disease, Parkinson's disease, and vascular-type dementia increases with age. As such, we investigated the effects of long-term exposure to excess Zn on learning and memory in aged mice. ICR-JCL female mice (aged 26 weeks) were administered 0, 200, or 500 ppm Zn as zinc chloride in drinking water for 30 weeks. After 30-week administration, aged female animals were subjected to Y-maze, novel object recognition, and step-through passive avoidance tests. Chronic exposure to Zn did not inhibit learning and memory in the Y-maze test, but dose-dependently inhibited learning and memory in novel object recognition and step-through passive avoidance tests. These results indicate the potential for chronic Zn exposure to dose-dependently inhibit both long-term and novel object recognition memory. Results of microarray analysis revealed significant changes in gene expression of transthyretin and many olfactory receptors in the hippocampus of Zn-treated mice.
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http://dx.doi.org/10.2131/jts.44.681DOI Listing
February 2020

Eccrine Porocarcinoma on the Lateral Nose Wall: A Rare Case Report.

Case Rep Dermatol 2019 May-Aug;11(2):215-219. Epub 2019 Jul 16.

Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.

Eccrine porocarcinoma (EPC) is an uncommon malignant tumor derived from the eccrine sweat glands. We present a case of EPC on the lateral nose wall, in which the tumor was excised, and the resultant defect was reconstructed using a nasolabial flap. A 66-year-old female was referred to the Department of Plastic and Reconstructive Surgery to receive treatment for a cutaneous tumor on her right lateral nose wall, which had been growing rapidly for 3 months. Histological analysis of a biopsy specimen of the tumor suggested that it was a squamous cell carcinoma. Surgical excision was performed with a 3-mm margin. The tumor was histologically diagnosed as an EPC. EPC exhibits various pathological features; therefore, it is often confused with other malignant cutaneous tumors. We consider that histologically examining surgical specimens obtained via total resection, rather than incisional biopsy specimens, is important for correctly diagnosing EPC.
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http://dx.doi.org/10.1159/000501444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696782PMC
July 2019

A chronic toxicity study of diphenylarsinic acid in the drinking water of C57BL/6J mice for 52 weeks.

J Toxicol Pathol 2019 Jul 21;32(3):127-134. Epub 2019 Mar 21.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to mice in their drinking water for 52 weeks. DPAA was administered to mice at concentrations of 0, 6.25, 12.5, and 25 ppm in their drinking water for 52 weeks. There were no significant differences in final body weights between the control groups and the DPAA treatment groups in male or female mice. Relative liver weights were significantly increased in males treated with 25 ppm DPAA, and absolute liver weights were significantly decreased in female mice treated with 25 ppm DPAA. In female mice, cholangitis and simple bile duct hyperplasia were observed in the 12.5 and 25 ppm DPAA groups, and focal necrosis of hepatocytes was observed in the 25 ppm DPAA group. Proteomic analysis and Ingenuity Pathway Analysis identified 18 proteins related to hepatotoxicity that were overexpressed in the female 25 ppm group. The phase I metabolic enzyme CYP2E1 was one of these overexpressed proteins. Immunostaining confirmed high expression of CYP2E1 in the livers of females in the 25 ppm group. These results suggest that DPAA is toxic to the intrahepatic bile duct epithelium and hepatocytes in female mice and that CYP2E1 might be involved in DPAA-associated toxicity. The no-observed-adverse-effect levels of DPAA were 12.5 ppm (1.6 mg/kg bw/day) for males and 6.25 ppm (1.1 mg/kg bw/day) for females under the conditions of this study.
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http://dx.doi.org/10.1293/tox.2018-0067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682552PMC
July 2019

Quantitative analysis of mutagenicity and carcinogenicity of 2-amino-3-methylimidazo[4,5-f]quinoline in F344 gpt delta transgenic rats.

Mutagenesis 2019 09;34(3):279-287

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.

Quantitative analysis of the mutagenicity and carcinogenicity of the low doses of genotoxic carcinogens present in food is of pressing concern. The purpose of the present study was to determine the mutagenicity and carcinogenicity of low doses of the dietary genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 gpt delta transgenic rats were fed diets supplemented with 0, 0.1, 1, 10 or 100 ppm IQ for 4 weeks. The frequencies of gpt transgene mutations in the liver were significantly increased in the 10 and 100 ppm groups. In addition, the mutation spectra was altered in the 1, 10 and 100 ppm groups: frequencies of G:C to T:A transversion were significantly increased in groups administered 1, 10 and 100 ppm IQ in a dose-dependent manner, and the frequencies of G:C to A:T transitions, A:T to T:A transversions and A:T to C:G transversions were significantly increased in the 100 ppm group. Increased frequencies of single base pair deletions and Spi- mutants in the liver, and an increase in glutathione S-transferase placental form (GST-P)-positive foci, a preneoplastic lesion of the liver in rats, was also observed in the 100 ppm group. In contrast, neither mutations nor mutation spectra or GST-P-positive foci were statistically altered by administration of IQ at 0.1 ppm. We estimated the point of departure for the mutagenicity and carcinogenicity of IQ using the no-observed-effect level approach and the Benchmark dose approach to characterise the dose-response relationship of low doses of IQ. Our findings demonstrate the existence of no effect levels of IQ for both in vivo mutagenicity and hepatocarcinogenicity. The findings of the present study will facilitate an understanding of the carcinogenic effects of low doses of IQ and help to determine a margin of exposure that may be useful for practical human risk assessment.
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http://dx.doi.org/10.1093/mutage/gez015DOI Listing
September 2019

Influence of Skull Base or Frontal Bone Fracture on the Result of Treatment for Le Fort Type Maxillofacial Fractures: Outcomes of Le Fort IV Fractures.

Authors:
Masaki Fujioka

J Emerg Trauma Shock 2019 Jan-Mar;12(1):71-72

Department of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, Ohmura City, Nagasaki, Japan. E-mail:

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http://dx.doi.org/10.4103/JETS.JETS_105_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6496990PMC
May 2019

Influenza-associated septic shock accompanied by septic cardiomyopathy that developed in summer and mimicked fulminant myocarditis.

Acute Med Surg 2019 Apr 10;6(2):192-196. Epub 2019 Feb 10.

The Emergency and Critical Care Center Mie University Hospital Tsu Mie Japan.

Case: Fulminant myocarditis (FM) and septic cardiomyopathy (SC) are two different disease entities, and distinction between them is important. A 34-year-old man had refractory shock, multiple organ failure, and elevation of cardiogenic markers. Echocardiogram showed tachycardia with extended ST elevation, and a rapid test for influenza A virus was positive. He was admitted with suspected FM induced by influenza.

Outcome: Echocardiography showed severe left ventricular dysfunction and dilatation, but no myocardial edema. Inconsistent with FM, a right heart catheter examination showed preserved cardiac output. Therefore, SC was considered and standard therapy for septic shock was initiated. He was stabilized in the first 72 h without mechanical circulatory support.

Conclusion: Influenza A infection can cause septic shock accompanied by SC. This condition is confusing in the clinical appearance of FM. However, SC shows critically different features of FM, and it might not occur in the epidemic period.
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http://dx.doi.org/10.1002/ams2.394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442530PMC
April 2019

Acetoaceto-o-Toluidide Enhances Cellular Proliferative Activity in the Urinary Bladder of Rats.

Toxicol Sci 2019 06;169(2):456-464

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Acetoaceto-o-toluidide (AAOT) is made from ortho-toluidine (OTD) and is used for the synthesis of pigments. A report of occupational urinary bladder carcinomas in Japanese workers chronically exposed to OTD and AAOT has recently been published. OTD is a well-known human urinary bladder carcinogen; however, little is known about the toxicity and the carcinogenicity of AAOT. The aim of the present study is to evaluate the toxic effects of AAOT on urinary bladder epithelium. In vitro, the cytotoxicities of AAOT and OTD were evaluated in rat (MYP3) and human (1T1) urothelial cells. The LC50 of AAOT was higher than that of OTD in both MYP cells and 1T1 cells. In vivo, 6-week-old male and female F344 rats were fed diets supplemented with 0%, 1.5%, or 3% AAOT for 4 weeks. Incidences of simple hyperplasia, cell proliferative activity, and γ-H2AX expression, which is a novel marker for the prediction of carcinogenicity, were significantly increased in a dose-dependent manner in the bladder urothelium of male and female rats administered AAOT. Furthermore, in male and female rats administered AAOT, the major urine metabolite of AAOT was OTD. These results demonstrate that AAOT has proliferation-enhancing activity and suggest that OTD metabolized from AAOT may play a pivotal role in the deleterious effects of AAOT in rats. The results of the present study also indicate that AAOT, like other carcinogenic aromatic amines, is likely to be a human bladder carcinogen.
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http://dx.doi.org/10.1093/toxsci/kfz051DOI Listing
June 2019

Clinicopathological features of TAFRO syndrome complicated by acquired hemophilia A and development of cardiopulmonary arrest that were successfully treated with VA-ECMO and tocilizumab.

Int J Hematol 2019 Jun 24;109(6):737-743. Epub 2019 Jan 24.

The Emergency and Critical Care Center, Mie University Hospital, 2-174, Edobashi, Tsu, Mie, 514-8507, Japan.

TAFRO syndrome and acquired hemophilia A (AHA) are rare, life-threatening diseases; however, the relationship between these two diseases is unknown. A 25-year-old man was transferred to our hospital because of bleeding tendency accompanied by multiple organ failure with generalized edema, massive pleural effusion, and ascites. He was diagnosed with AHA. Bypass therapy for hemostasis and cyclophosphamide with prednisolone to eradicate possible inhibitors were provided. However, he suffered from cardiopulmonary arrest. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated as rescue therapy. His hemodynamic status stabilized and he was weaned from VA-ECMO in 1 week. We confirmed normal FVIII activity and disappearance of the inhibitor, and bypass therapy was discontinued. However, generalized edema with massive ascites, pleural effusion, and renal insufficiency persisted. Bone marrow biopsy showed reticulin fibrosis. These symptoms fulfilled the diagnostic criteria of TAFRO syndrome. He received tocilizumab (TCZ) and steroid was tapered off. After four cycles of TCZ, symptoms of TAFRO syndrome gradually improved. To the best of our knowledge, this is the first report of TAFRO syndrome accompanied by AHA with rescue by VA-ECMO. Additionally, AHA and TAFRO syndrome were well controlled by TCZ.
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http://dx.doi.org/10.1007/s12185-019-02604-2DOI Listing
June 2019

Foot reconstruction with the superficial circumflex iliac artery perforator flap under local anesthesia: Two case reports.

Medicine (Baltimore) 2019 Jan;98(2):e13888

Division of Plastic and Reconstructive Surgery, National Nagasaki Medical Center, Japan.

Rationale: The superficial circumflex iliac artery perforator (SCIP) free flap is a popular method used in foot reconstruction. Although the SCIP flap has a relatively short pedicle and does not require intramuscular dissection, general anesthesia is largely preferred for SCIP flap reconstruction. We report 2 cases with the free SCIP flap for skin and soft tissue reconstruction of the foot under local anesthesia.

Patient Concerns: Case 1 was a 34-year-old man sustained a crush injury to the dorsal foot, resulting in a soft tissue defect with bone and tendon exposure. Case 2 was a 41-year-old man with type 2 diabetes was referred to our division for an intractable ankle wound after surgery for a calcaneal bone fracture.

Diagnosis: The diagnosis was intractable wounds on feet caused by trauma and surgery. Patients were unable to receive general anesthesia because of asthma or elevated liver enzymes.

Interventions: Two patients with tissue defects on their feet were treated with SCIP flaps under local anesthesia. Fifteen milliliter of 0.5% bupivacaine was injected for ankle block. SCIP flaps were harvested after injecting 10 to 15 mL of 1% lidocaine combined with epinephrine around the flap incisions.

Outcomes: No complications related to the use of local anesthesia developed during the operation or postoperatively. Two flaps survived and fully took without complications.

Lessons: With proper local anesthesia, successful foot reconstruction with a free SCIP flap was possible. This method can be considered a sufficient option for foot reconstruction for patients unable to receive general anesthesia.
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http://dx.doi.org/10.1097/MD.0000000000013888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336647PMC
January 2019

Steroid sulfatase promotes invasion through epithelial-mesenchymal transition and predicts the progression of bladder cancer.

Exp Ther Med 2018 Dec 21;16(6):4463-4470. Epub 2018 Sep 21.

Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.

Androgen signal has been recently suggested to be associated with the progression of bladder cancer. Steroid sulfatase (STS) is a steroid sulfate activation enzyme, considered to be one of the key enzymes in the androgen signaling pathway. However, the role of STS in bladder cancer has not been elucidated. The purpose of the present study was to determine the clinical and functional significance of STS in bladder cancer. Immunohistochemical analysis of surgical specimens obtained by radical cystectomy (n=114) demonstrated that overexpression of STS was associated with the invasion of bladder cancer, as evidenced by the incidence of STS-positive cancers (11.5 and 37.1% in non-muscle invasive and muscle invasive bladder cancers, respectively; P=0.003). STS-positive cancer demonstrated shorter recurrence-free survival and cancer-specific survival (P=0.0027 and 0.0030, respectively). Furthermore, knockdown of STS significantly reduced cell migration and invasion capacities of bladder cancer cells (P<0.001 and P=0.005, respectively), accompanied by the upregulation of E-cadherin and downregulation of vimentin. In summary, the present study demonstrated that STS promotes the invasion capability of bladder cancer via regulation of the epithelial-mesenchymal transition, and may be a useful marker for predicting the progression of bladder cancers.
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http://dx.doi.org/10.3892/etm.2018.6787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257456PMC
December 2018

mTOR Activation in Liver Tumors Is Associated with Metabolic Syndrome and Non-Alcoholic Steatohepatitis in Both Mouse Models and Humans.

Cancers (Basel) 2018 Nov 22;10(12). Epub 2018 Nov 22.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan.

Non-alcoholic steatohepatitis (NASH) can cause liver fibrosis and cirrhosis, with final progression to hepatocellular carcinoma (HCC) in some cases. Various factors have been suggested to be involved in the development of NASH. Considering the many possible contributing factors, we postulated that mechanisms of progression from NASH to HCC could differ depending on the risk factors. In the present study, we applied two mouse models of NASH⁻HCC and performed histopathological and proteome analyses of mouse liver tumors. Furthermore, to compare the mechanisms of NASH⁻HCC progression in mice and humans, we investigated HCCs in humans with a background of metabolic syndrome and NASH, as well as HCCs associated with hepatitis virus infection by immunohistochemistry. It was demonstrated that upstream regulators associated with the mammalian target of rapamycin (mTOR) pathway were altered in liver tumors of mice with metabolic syndrome characteristics (TSOD mice) using proteome analysis. Immunohistochemical analysis showed that mTOR was characteristically phosphorylated in liver tumors of TSOD mice and HCCs from metabolic syndrome cases in humans. These results indicated that the mTOR pathway is characteristically activated in liver tumors with metabolic syndrome and NASH, unlike liver tumors with other etiologies.
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http://dx.doi.org/10.3390/cancers10120465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315895PMC
November 2018

Quantitative Approaches to Assess Key Carcinogenic Events of Genotoxic Carcinogens.

Toxicol Res 2018 Oct 15;34(4):291-296. Epub 2018 Oct 15.

Japan Bioassay Research Center, Hadano, Kanagawa, Japan.

Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at transgene, and induction of preneoplastic glutathione -transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts < Mutations < GST-positive foci (preneoplasia) < Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.
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http://dx.doi.org/10.5487/TR.2018.34.4.291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195881PMC
October 2018

AST-120 Reduces Neuroinflammation Induced by Indoxyl Sulfate in Glial Cells.

J Clin Med 2018 Oct 17;7(10). Epub 2018 Oct 17.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano, I-84084 Salerno, Italy.

Chronic kidney disease (CKD) involves multiple organ dysfunction, and the neurological complications that are often present in CKD patients support the idea of a crosstalk between the kidneys and the brain. Evidence suggests a possible role for products accumulating in these patients as uremic toxins in various CKD complications, including neurodegeneration. Indoxyl sulfate (IS), derived from tryptophan metabolism, is well-known as a uremic nephron-vascular toxin, and recent evidence suggests it also has a role in the immune response and in neurodegeneration. Inflammation has been associated with neurodegenerative diseases, as well as with CKD. In this study, we demonstrated that sera of CKD patients induced a significant inflammation in astrocyte cells which was proportional to IS sera concentrations, and that the IS adsorbent, AST-120, reduced this inflammatory response. These results indicated that, among the uremic toxins accumulating in serum of CKD patients, IS significantly contributed to astrocyte inflammation. Moreover, being also chronic inflammation associated with CKD, here we reported that IS further increased inflammation and oxidative stress in primary central nervous system (CNS) cells, via Nuclear Factor-κB (NF-κB) and Aryl hydrocarbon Receptor (AhR) activation, and induced neuron death. This study is a step towards elucidating IS as a potential pharmacological target in CKD patients.
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http://dx.doi.org/10.3390/jcm7100365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210605PMC
October 2018

Chronic dietary toxicity and carcinogenicity studies of dammar resin in F344 rats.

Arch Toxicol 2018 12 24;92(12):3565-3583. Epub 2018 Sep 24.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Dammar resin is a natural food additive and flavoring substance present in many foods and drinks. The present study evaluates the chronic toxicity and carcinogenicity of dietary dammar resin in F344 rats. Dietary concentrations in the 52-week chronic toxicity study were 0, 0.03, 0.125, 0.5, or 2%. The major treatment-related deleterious effects were body weight suppression, increased relative liver weight, and low hemoglobin levels in males and females. Foci of cellular alteration in the liver were observed in the male 2% group, but not in any other group. The no-observed-adverse-effect level for chronic toxicity was 0.125% for males (200.4 mg/kg b.w./day) and females (241.9 mg/kg b.w./day). Dietary concentrations in the 104-week carcinogenicity study were 0, 0.03, 0.5, or 2%. Dammar resin induced hemorrhagic diathesis in males and females, possibly via the inhibition of extrinsic and intrinsic coagulation pathways. Incidences of hepatocellular adenomas and carcinomas were significantly increased in the male 2% group, but not in any other group. In the 4-week subacute toxicity study, the livers of male rat-fed diet-containing 2% dammar resin had increased levels of protein oxidation and increased the expression of two anti-apoptotic and seven cytochrome P450 (CYP) genes. There was also an increased tendency of oxidative DNA damage. These findings demonstrate that dammar resin is hepatocarcinogenic in male F344 rats and underlines the roles of inhibition of apoptosis, induction of CYP enzymes, and oxidative stress in dammar resin-induced hepatocarcinogenesis.
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http://dx.doi.org/10.1007/s00204-018-2316-7DOI Listing
December 2018

In vivo positive mutagenicity of 1,4-dioxane and quantitative analysis of its mutagenicity and carcinogenicity in rats.

Arch Toxicol 2018 10 27;92(10):3207-3221. Epub 2018 Aug 27.

Japan Bioassay Research Center, Japan Organization of Occupational Health and Safety, Hadano, Kanagawa, 257-0015, Japan.

1,4-Dioxane is a widely used synthetic industrial chemical and its contamination of drinking water and food is a potential health concern. It induces liver tumors when administered in the drinking water to rats and mice. However, the mode of action (MOA) of the hepatocarcinogenicity of 1,4-dioxane remains unclear. Importantly, it is unknown if 1,4-dioxane is genotoxic, a key consideration for risk assessment. To determine the in vivo mutagenicity of 1,4-dioxane, gpt delta transgenic F344 rats were administered 1,4-dioxane at various doses in the drinking water for 16 weeks. The overall mutation frequency (MF) and A:T- to -G:C transitions and A:T- to -T:A transversions in the gpt transgene were significantly increased by administration of 5000 ppm 1,4-dioxane. A:T- to -T:A transversions were also significantly increased by administration of 1000 ppm 1,4-dioxane. Furthermore, the DNA repair enzyme MGMT was significantly induced at 5000 ppm 1,4-dioxane, implying that extensive genetic damage exceeded the repair capacity of the cells in the liver and consequently led to liver carcinogenesis. No evidence supporting other MOAs, including induction of oxidative stress, cytotoxicity, or nuclear receptor activation, that could contribute to the carcinogenic effects of 1,4-dioxane were found. These findings demonstrate that 1,4-dioxane is a genotoxic hepatocarcinogen and induces hepatocarcinogenesis through a mutagenic MOA in rats. Because our data indicate that 1,4-dioxane is a genotoxic carcinogen, we estimated the point of departure of the mutagenicity and carcinogenicity of 1,4-dioxane using the no-observed effect-level approach and the Benchmark dose approach to characterize its dose-response relationship at low doses.
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http://dx.doi.org/10.1007/s00204-018-2282-0DOI Listing
October 2018

Risk Factors for Postoperative Complications among the Elderly after Plastic Surgery Procedures Performed under General Anesthesia.

Plast Surg Int 2018 8;2018:7053839. Epub 2018 Jul 8.

Department of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.

Background: The frequency of surgery involving elderly patients has been increasing. The use of free tissue transfers in the elderly has been examined previously (Howard et al., 2005, Hwang et al., 2016, Grammatica et al., 2015, Serletti et al., 2000, and Sierakowski et al., 2017), whereas there have not been any such studies of plastic surgery procedures. We evaluated the risk factors for complications after plastic surgery procedures performed under general anesthesia in patients aged ≥75 years.

Methods: The cases of patients aged ≥75 years who underwent plastic surgery procedures under general anesthesia at the Department of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, between 2009 and 2016 were reviewed retrospectively. Multiple logistic regression analysis was used to identify the risk factors for postoperative complications.

Results: Two hundred and sixty-three cases were reviewed. Complications were seen in 137 patients. Age was not predictive of complications. The risk factors included a serum albumin level of <2.8 g/dl (odds ratio (OR): 2.96), an operative time of ≥120 min (OR: 6.22), and an American Society of Anesthesiologists performance status of ≥3 (OR: 2.39).

Conclusions: Age is not contraindication for surgery in the elderly. It is important to assess comorbidities and perform surgical procedures as soon as possible to shorten the surgical period.
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http://dx.doi.org/10.1155/2018/7053839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077609PMC
July 2018

Hypoxia-inducible factor-2 alpha up-regulates CD70 under hypoxia and enhances anchorage-independent growth and aggressiveness in cancer cells.

Oncotarget 2018 Apr 10;9(27):19123-19135. Epub 2018 Apr 10.

Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Hypoxia-inducible factors (HIFs) facilitate cellular adaptation to environmental stress such as low oxygen conditions (hypoxia) and consequently promote tumor growth. While HIF-1α functions in cancer progression have been increasingly recognized, the contribution of HIF-2α remains widely unclear despite accumulating reports showing its overexpression in cancer cells. Here, we report that HIF-2α up-regulates the expression of CD70, a cancer-related surface antigen that improves anchorage-independent growth in cancer cells and is associated with poor clinical prognosis, which can be induced via epigenetic modifications mediated by DNMT1. The ablation of CD70 by RNAi led to decreased colony forming efficiency in soft agar. Most strikingly, we identified the emergence of CD70-expressing cells derived from CD70-negative cell lines upon prolonged hypoxia exposure or DNMT1 inhibition, both of which significantly reduced CpG-nucleotide methylations within CD70 promoter region. Interestingly, DNMT1 expression was decreased under hypoxia, which was rescued by HIF-2α knockdown. In addition, the expression of CD70 and colony forming efficiency in soft agar were decreased by knockdown of HIF-2α. These findings indicate that CD70 expression and an aggressive phenotype of cancer cells is driven under hypoxic conditions and mediated by HIF-2α functions and epigenetic modifications. This provides additional insights into the role of HIF-2α in coordinated regulation of stem-like functions and epigenetics that are important for cancer progression and may present additional targets for the development of novel combinatorial therapeutics.
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http://dx.doi.org/10.18632/oncotarget.24919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922382PMC
April 2018

Successful reconstruction of congenital perineal skin defect using gluteal-fold bilobed perforator flap.

Afr J Paediatr Surg 2017 Jan-Mar;14(1):15-17

Department of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.

Perineovaginorectal defect usually requires surgical repair; however, direct closure often leads to dehiscence. We present two patients with a congenital perineal skin defect who were successfully treated using a gluteal-fold bilobed perforator flap. This flap facilitates esthetic restoration and a more natural perineovaginorectal appearance, using only a one-stage procedure. This technique may be a favorable option for perineal and genital repair.
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http://dx.doi.org/10.4103/ajps.AJPS_29_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853016PMC
June 2018

Sacral Pressure Ulcer-induced Fournier's Gangrene Extending to the Retroperitoneum: A Case Report.

Wounds 2018 Jan;30(1):E5-E8

National Hospital Organization Nagasaki Medical Center, Ohmura City, Japan.

Introduction: Fournier's gangrene (FG) is a type of necrotizing fasciitis of the perineum and scrotum that is characterized by very rapid progression. Sacral pressure ulcers are one of the causes of FG.

Case Report: An 85-year-old man was referred to the National Hospital Organization Nagasaki Medical Center (Ohmura City, Japan) with a diagnosis of FG extending to the retroperitoneum caused by a sacral pressure ulcer. Immediate debridement was performed; however, it was not possible to remove all necrotic tissue from the pelvis. The wound was cleansed with continuous irrigation combined with negative pressure wound therapy, which brought the infection under control. The exposed rectum was resurfaced with a gracilis musculocutaneous flap, and the remaining wound in the sacral region was covered with a gluteal artery perforator flap.

Conclusions: The authors consider continuous irrigation combined with negative pressure wound therapy as extremely useful for patients with FG in whom sufficient debridement cannot be performed.
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January 2018

Novel Application of Cultured Epithelial Autografts (CEA) with Expanded Mesh Skin Grafting Over an Artificial Dermis or Dermal Wound Bed Preparation.

Int J Mol Sci 2017 Dec 25;19(1). Epub 2017 Dec 25.

Department of Plastic Surgery, Wound Repair and Regeneration, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.

Cultured epithelial autografts (CEA) with highly expanded mesh skin grafts were used for extensive adult burns covering more than 30% of the total body surface area. A prospective study on eight patients assessed subjective and objective findings up to a 12-month follow-up. The results of wound healing for over 1:6 mesh plus CEA, gap 1:6 mesh plus CEA, and 1:3 mesh were compared at 3, 6, and 12 months using extensibility, viscoelasticity, color, and transepidermal water loss by a generalized estimating equation (GEE) or generalized linear mixed model (GLMM). No significant differences were observed among the paired treatments at any time point. At 6 and 12 months, over 1:6 mesh plus CEA achieved significantly better expert evaluation scores by the Vancouver and Manchester Scar Scales ( < 0.01). Extended skin grafting plus CEA minimizes donor resources and the quality of scars is equal or similar to that with conventional low extended mesh slit-thickness skin grafting such as 1:3 mesh. A longitudinal analysis of scars may further clarify the molecular changes of scar formation and pathogenesis.
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http://dx.doi.org/10.3390/ijms19010057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796007PMC
December 2017

Enhanced Susceptibility of Ogg1 Mutant Mice to Multiorgan Carcinogenesis.

Int J Mol Sci 2017 Aug 18;18(8). Epub 2017 Aug 18.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan.

The role of deficiency of oxoguanine glycosylase 1 () homolog, a repair enzyme of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) residue in DNA, was investigated using the multiorgan carcinogenesis bioassay in mice. A total of 80 male and female six-week-old mice of C57BL/6J background carrying a mutant allele of the gene () and wild type (Ogg1) mice were administered N-diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), N-bis (2-hydroxypropyl) nitrosamine (DHPN) and 1,2-dimethylhydrazine dihydrochloride (DMH) (DMBDD) to induce carcinogenesis in multiple organs, and observed up to 34 weeks. Significant increase of lung adenocarcinomas incidence was observed in DMBDD-treated male mice, but not in DMBDD-administered animals. Furthermore, incidences of lung adenomas were significantly elevated in both males and females as compared with respective control and DMBDD-treated groups. Incidence of total liver tumors (hepatocellular adenomas, hemangiomas and hemangiosarcomas) was significantly higher in the DMBDD-administered males and females. In addition, in DMBDD-treated male mice, incidences of colon adenomas and total colon tumors showed a trend and a significant increase, respectively, along with significant rise in incidence of simple hyperplasia of the urinary bladder, and a trend to increase for renal tubules hyperplasia in the kidney. Furthermore, incidence of squamous cell hyperplasia in the forestomach of DMBDD-treated male mice was significantly higher than that of males. Incidence of small intestine adenomas in DMBDD groups showed a trend for increase, as compared to the wild type mice. The current results demonstrated increased susceptibility of mutant mice to the multiorgan carcinogenesis induced by DMBDD. The present bioassay could become a useful tool to examine the influence of various targets on mouse carcinogenesis.
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http://dx.doi.org/10.3390/ijms18081801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578188PMC
August 2017

Progression of Hepatic Adenoma to Carcinoma in Mutant Mice Induced by Phenobarbital.

Oxid Med Cell Longev 2017 13;2017:8541064. Epub 2017 Jul 13.

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Abeno-Ku, Asahi-Machi 1-4-3, Osaka 545-8585, Japan.

The carcinogenic potential of phenobarbital (PB) was assessed in a mouse line carrying a mutant allele of the gene encoding the enzyme oxoguanine DNA glycosylase (Ogg1) responsible for the repair of 8-hydroxy-2'-deoxyguanosine (8-OHdG). homozygous mutant () and wild-type () male and female, 10-week-old, mice were treated with 500 ppm PB in diet for 78 weeks. Hepatocellular carcinomas (HCCs) were found in PB-treated mice, while animals developed only hepatocellular adenomas (HCAs) at the same rate. This was coordinated with PB-induced significant elevation of 8-OHdG formation in DNA and cell proliferation in adjacent liver of mice. Proteome analysis predicted activation of transcriptional factor Nrf2 in the livers and HCAs of PB-administered mice; however, its activation was insufficient or absent in the livers and HCCs of mice, respectively. Significant elevation of phase I and II metabolizing enzymes was demonstrated in both and animals. Treatment of mice with PB resulted in significant elevation of cell proliferation in the liver. These results indicate that PB induced progression from HCA to HCC in mice, due to persistent accumulation of DNA oxidative base modifications and suppression of Nrf2-mediated oxidative stress response, resulting in significant elevation of cell proliferation.
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http://dx.doi.org/10.1155/2017/8541064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530452PMC
April 2018

Correlation Between NKG2DL Expression and Antitumor Effect of Protein-bound Polysaccharide-K in Tumor-bearing Mouse Models.

Anticancer Res 2017 08;37(8):4093-4101

Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

Background/aim: We investigated the relationship between the expression of natural killer group 2, member D ligands (NKG2DLs) and the antitumor effects of protein-bound polysaccharide-K (PSK).

Materials And Methods: PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in multiple cell lines.

Results: PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60. PSK had little antitumor effect in mice implanted with cells expressing both Rae-1 and H60. A correlation between the expression of NKG2DLs and the antitumor effect of PSK was observed. After PSK administration, INF-γ production in CD8 T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60.

Conclusion: We demonstrated that the expression of NKG2DLs affects tumor immunity and the efficacy of immuno therapy in tumor-bearing mouse model.
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http://dx.doi.org/10.21873/anticanres.11796DOI Listing
August 2017