Increased oxidative stress and effects on inflammatory cytokine secretion by heated tobacco products aerosol exposure to mice.

Although the amount of chemicals in heated tobacco products (HTPs) aerosols is reduced compared to conventional combustible cigarette smoke, the association between HTPs and reduced health effects remains unclear. In this study, we hypothesized that exposure to IQOS, an HTP, would increase oxidative stress and affect the secretion of inflammatory cytokines. First, C57BL/6 mice exposed to IQOS aerosols were evaluated to determine the adverse effects of IQOS exposure. IQOS exposure significantly decreased the concentration of GSH in alveolar macrophages in a dose-dependent manner and increased the percentage of GSSG in lung tissues. These results indicate that IQOS exposure increases oxidative stress, and GSH is consumed to remove oxidative stress. In addition, foamy alveolar macrophages were observed in the bronchial alveolar lavage fluid after IQOS exposure. Although the concentration of inflammatory cytokines, IL-6, and GM-CSF, in the plasma increased significantly after IQOS exposure, there were no significant changes in other cytokines. These results indicate that short-term exposure to IQOS aerosols may increase oxidative stress and induce the secretion of inflammatory cytokines. Lastly, the longer-term effects of IQOS aerosols exposure should be evaluated in the future.

A Newly Developed Aerosol Exposure Apparatus for Heated Tobacco Products for In Vivo Experiments Can Deliver Both Particles and Gas Phase With High Recovery and Depicts the Time-Dependent Variation in Nicotine Metabolites in Mouse Urine.

INTRODUCTION: There is no standardized aerosol exposure apparatus to deliver heated tobacco products (HTPs) for in vivo experiments. Therefore, we developed a novel HTPs aerosol exposure apparatus for mice and demonstrated that nicotine and other chemicals in HTPs aerosol generated by the apparatus can be delivered to mice which replicate human smoke. AIMS AND METHODS: The amounts of nicotine, tar, and carbon monoxide (CO) in IQOS (Marlboro Regular HeatSticks) aerosol generated by two types of apparatuses were determined. C57BL/6N mice were exposed to IQOS aerosol, followed by determination of the urinary nicotine metabolites. Further, the skin surface temperature of mice was monitored to confirm the vasoconstriction action of nicotine. RESULTS: The amount of chemicals in IQOS aerosol by the novel air push-in inhalation apparatus for HTPs (APIA) was equivalent to that of the analytical vaping machine (LM4E) (1.60 ± 0.08 [APIA] vs. 1.46 ± 0.07 mg/stick [LM4E] in nicotine and 0.55 ± 0.04 [APIA] vs. 0.45 ± 0.01 mg/stick [LM4E] in CO). After mice were exposed to IQOS aerosol by APIA, the urinary nicotine metabolite levels were determined; peak values in cotinine and 3-hydroxycotinine (3-HC) were 6.82 µg/mg creatinine at 1 hour after exposure and 32.9 µg/mg creatinine at 2 hours after exposure, respectively. The skin surface temperature decreased and was lower (33.5°C ± 0.5°C) at 30 minutes than before exposure (37.6°C ± 0.8°C). CONCLUSIONS: The new apparatus for HTPs aerosol exposure to mice showed good performances in terms of both chemical analysis of collected aerosol and fluctuations in the urinary nicotine metabolites. IMPLICATIONS: The APIA reported in this study can expose small animals to HTPs aerosol, including nicotine and other chemical substances as same amounts as LM4E and replicate actual human smoking process by in vivo experiments. Therefore, the experiments using APIA can provide evidence to assess the health risks of HTPs use.

[A Case of Myeloid Sarcoma in the Small Intestine Presenting with Intussusception].

A sixty-something man presented with lower abdominal pain in early Y month 20XX, and was examined at the hospital's internal medicine outpatient clinic. An abdominal CT showed a soft tissue mass around the left hip joint, and multiple enlarged lymph nodes from inside the pelvis to the mesentery of the abdomen. We noted a small-intestinal intussusception in the lower right abdomen, and suspected malignant lymphoma. We did a CT-guided biopsy on the left hip joint soft tissue mass, and performed surgery on the small-intestinal intussusception. During surgery, we noted an approximately 30 cm ileal intussusception located about 60 cm from the terminal ileum, and enlarged lymph nodes in the nearby mesentery. We removed the ileal intussusception. The pathological diagnosis was myeloid sarcoma, and the soft tissue mass in the left hip joint was also diagnosed as myeloid sarcoma. We performed a bone-marrow biopsy at the hematology department, and diagnosed acute myeloid leukemia M2. We then started remission-induction therapy and consolidation therapy, and the patient was diagnosed as in remission in Y+5 month 20XX. We also need to keep in mind myeloid sarcoma in the intestine as a subtype of acute myeloid leukemia, as malignant tumor in the small intestine presenting with intussusception.

A Case of Primary Colonic Signet Ring Cell Carcinoma in a Young Man which Preoperatively Mimicked Phlebosclerotic Colitis.

A 35-year-old man was referred to our hospital for chronic abdominal pain and diarrhea. Computed tomography showed wall thickening, poor contrast enhancement and calcification of the ascending colon, which were consistent with phlebosclerotic colitis. Malignant character was not detected from a biopsy specimen. Operatively, we observed a scirrhous mass of the ascending colon invading surrounding tissue, which was diagnosed as signet ring cell carcinoma based on analysis of an intraoperative frozen section. Right hemicolectomy with regional lymph node dissection was performed. This case was extremely similar to phlebosclerotic colitis in clinical findings; surgical resection was required for correct diagnosis.

Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity.

Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells.

In vivo genotoxicity of high-intensity intermediate frequency magnetic fields in somatic cells and germ cells.

Intermediate frequency magnetic fields (IF-MFs) at ~85 kHz are one of the components of wireless power transfer (WPT) systems. However, the available data needed for the assessment of the safety of organisms from IF-MF exposure are scarce. Thus, there is an imminent need to accumulate evidence-based assessment data. In particular, if humans are exposed to IF-MF due to an accident or trouble, they are at increased risk of being exposed to high-intensity IF-MF within a short period. The already existing exposure system was improved to a system that could intermittently expose animals at 3 s intervals. This system allows the exposure of a mouse to high-intensity IF-MF (frequency: 82.3 kHz; induced electric field: 87 V/m, which was 3.8 times the basic restriction level for occupational exposure in the ICNIRP guideline), while regulating the heat generated by the coil. In vivo genotoxicity after IF-MF exposure was assessed using micronucleus (MN) test, Pig-a assay, and gpt assay. The results of MN test and Pig-a assay in hematopoietic cells revealed that neither the reticulocytes nor the mature erythrocytes exhibited significant increases in the IF-MF-exposed group compared with that in the sham-exposed group. In germ cells, MN test and gpt assay outcomes showed that IF-MF exposure did not cause any genetic or chromosomal abnormality. Based on these data, there was no genotoxic effect of our set IF-MF exposure on somatic and germ cells. These findings can contribute to the widespread use of WPT systems as effective data of IF-MF safety assessment.

Interferon gamma induces steroid sulfatase expression in human keratinocytes.

Steroid sulfatase (STS) plays an important role in steroid metabolism in which estrogens and dehydroepiandrosterone (DHEA) are produced from their sulfates. However, little is known about the transcriptional regulation of the STS gene in keratinocytes. Since keratinocytes are thought to be a primary target of interferon gamma (IFNγ) in inflammatory and immune responses, we assessed the effects of this cytokine upon STS gene expression in the human keratinocyte cell line SVHK and in normal human keratinocytes (NHEK). Stimulation of SVHK cells with 50 ng/mL of IFNγ for 24 h induced an approximately three-fold increase in STS activity and in its mRNA levels compared to non-treated cells. IFNγ treatment also induced an approximately 1.5-fold increase in STS mRNA levels in NHEK cells. This induction was completely inhibited by treatment with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, and by the nuclear factor-kappa B (NF-κB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). These data suggest that activation of the PI 3-kinase signal transduction pathway mediates induction of STS gene expression by IFNγ through activation of NF-κB. The anti-inflammatory agent dexamethasone inhibited IFNγ induction of STS gene expression, suggesting involvement of a glucocorticoid receptor in the regulation of STS gene expression in keratinocytes. Regulation of STS gene expression in skin as a novel target of drugs for therapy of psoriasis in the skin is discussed.

Exposure to Heated Tobacco Products Aerosol Causes Acute Stress Responses in the Lung of Mouse.

In the present study, we evaluated the acute response of mice exposed to IQOS aerosol, a brand-name heated tobacco product (HTP), in the lung tissue. First, the thiobarbituric acid-reactive substances (TBA-RS) value was measured as an index to assess oxidative stress, and a significant increase was observed after exposure, followed by a significant increase in the total lung GSH concentration. The stress responses induced by IQOS aerosols was then analyzed by focusing on the changes in Nrf2 and ATF4, which are transcription factors that induce the expression of genes involved in GSH biosynthesis or metabolism. Although Nrf2 activation was not observed, significant accumulation of ATF4 in the nuclear fraction was noted three hours after exposure to IQOS aerosols. Upon an examination of changes in factors in the GSH biosynthetic system, a significant increase in cystine concentration in the lung tissue was measured, and an increase in xCT expression level was observed in the cell membrane fraction three-six hours after IQOS exposure. Furthermore, characteristic changes in HO-1, a stress-response protein regulated by ATF4, was discovered six hours after IQOS exposure. Moreover, analysis of the upstream ATF4 regulatory system revealed that phosphorylation of eIF2α was enhanced in the lung cytoplasmic fraction three hours after exposure to IQOS aerosols. These findings suggest that ER stress might be induced as an early response to IQOS aerosol exposure, accompanied by the activation of the eIF2α-ATF4 axis. These intracellular changes have also been reported after exposure to combustible cigarette smoke. Thus, the acute response found in the lungs of mice in the present study demonstrate that the inhalation of aerosols from IQOS elicits a biological response similar to that of combustible cigarette smoke. In conclusion, our results provide evidence that the biological effects of HTPs, such as IQOS, cannot be ignored in the lungs.

Sulfation of estradiol in human epidermal keratinocyte.

Epidermis is one of the well-known estrogen target tissues. Information regarding estrogen metabolism in epidermis is still very limited compared to that of estrogen action. In the breast cancer tissue, 17ß-estradiol (E(2)) is inactivated by sulfation and the expression level of estrogen sulfotransferase (SULT1E1) is inversely correlated with its malignancy. However, there is little datum about inactivation of estradiol in skin. In order to detect and measure E(2) and its metabolites simultaneously, we established an assay method with radio HPLC. A majority of [(3)H] labeled E(2) was converted to E(2) sulfate in normal human epidermal keratinocyte (NHEK) cells. The estimated activity of sulfotransferase toward E(2) at 20 nM was 0.11±0.01 (pmol/min/mg protein). Significant induction of estrogen sulfotransferase activity was observed in calcium-differentiated NHEK cells (0.58±0.07 (pmol/min/mg protein)). The gene expression of SULT1E1 was fifteen-fold higher in differentiated keratinocyte than in proliferating keratinocyte, whereas that of steroid sulfatase was reduced. These results suggest that E(2) inactivation is primarily mediated by SULT1E1 in keratinocyte and E(2) action is likely suppressed in epidermal differentiation.

No evidence for genotoxicity in mice due to exposure to intermediate-frequency magnetic fields used for wireless power-transfer systems.

Time varying magnetic fields (MFs) are used for the wireless power-transfer (WPT) technology. Especially, 85 kHz band MFs, which are included in the intermediate frequency (IF) band (300 Hz - 10 MHz), are commonly used WPT system for charging electric vehicles. Those applications of WPT technology have elicited public concern about health effects of IF-MF. However, existing data from health risk assessments are insufficient and additional data are needed. We assessed the genotoxic effects of IF-MF exposure on erythroid differentiation in mice. A high-intensity IF-MF mouse exposure system was constructed to induce an average whole-body electric field of 54.1 V/m. Blood samples were obtained from male mice before and after a 2-week IF-MF exposure (1 h/day, total: 10 h); X-irradiated mice were used as positive controls. We analyzed the blood samples with the micronucleus (MN) test and the Pig-a mutation assay. No significant differences were seen between IF-MF-exposed and sham-exposed mice in the frequencies of either MN or Pig-a mutations in mature erythrocytes and reticulocytes. IF-MF exposure did not induce genotoxicity in vivo under the study conditions (2.36× the basic restriction for occupational exposure, 22.9 V/m, in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines). The absence of significant biological effects due to IF-MF exposure supports the practical application of this technology.

A Case of Eosinophilic Chronic Rhinosinusitis Associated with Choroidal Folds and Ocular Motility Disorder.

We report a case of eosinophilic chronic rhinosinusitis (ECRS) associated with choroidal folds and ocular motility disorder. A 50-year-old male with rhinosinusitis and bronchial asthma presented with anorthopia of the lower visual field and ocular motility disorder of the left eye. Dilated fundus examination and optical coherence tomography (OCT) revealed wavy choroidal folds in the upper retina. An emergent computed tomography (CT) showed sinusitis, a partial defect of the superior wall of the orbit on the left side, and deformation of the left eye. Based on the clinical findings, the patient was diagnosed with sinusitis complicated by ocular motility disorder. Endoscopic sinus surgery (ESS) was performed. A histopathological examination of the excised polyps showed extensive eosinophil invasion. According to the clinical findings of the nasal polyps, CT images, and peripheral blood tests, he was diagnosed as ECRS. One month after ESS, both ocular movement and anorthopia were improved. The choroidal folds observed using OCT disappeared 2 months after ESS. Although ECRS is rarely associated with ocular complications, bone involvement in sinusitis may result in deformation of the eyeball leading to choroidal folds and ocular motility disorder.

Global Analysis of Transcriptional Expression in Mice Exposed to Intermediate Frequency Magnetic Fields Utilized for Wireless Power Transfer Systems.

BACKGROUND: Intermediate frequency magnetic fields (IF-MFs) at around 85 kHz are a component of wireless power transfer systems used for charging electrical vehicles. However, limited data exist on the potential health effects of IF-MFs. We performed a comprehensive analysis of transcriptional expression in mice after IF-MF exposure. MATERIALS AND METHODS: We developed an IF-MF exposure system to generate a high magnetic flux density (25.3 mT). The system can expose the IF-MF for a mouse whole-body without considering thermal effects. After 10 days (1 h/day) of exposure, a comprehensive expression analysis was performed using microarray data from both the brain and liver. RESULTS: No significant differences in transcriptional expression were detected in the 35,240 probe-sets when controlling the false discovery rate (FDR) under a fold change cutoff >1.5. However, several differential expressions were detected without FDR-adjustment, but these were not confirmed by RT-PCR analysis. CONCLUSIONS: To our knowledge, this is the first in vivo study to evaluate the biological effects of IF-MF exposure with an intense magnetic flux density 253 times higher than the occupational restriction level defined by the International Commission on Non-Ionizing Radiation Protection guidelines. However, our findings indicate that transcriptional responses in the living body are not affected under these conditions.

Pneumonia and Extracorporeal Cardiopulmonary Resuscitation Followed by Targeted Temperature Management in Patients With Out-of-Hospital Cardiac Arrest　- Retrospective Cohort Study.

Background: We examined the association between initiation of extracorporeal cardiopulmonary resuscitation (ECPR) and the incidence of infectious complications, such as pneumonia, sepsis, and bacteremia, after out-of-hospital cardiac arrest (OHCA) in patients who received targeted temperature management (TTM). Methods and Results: This retrospective study used data from hospital medical records of patients with OHCA treated with TTM who had been admitted to St. Luke's International Hospital between April 2006 and December 2018. The primary endpoint was the association between the type of CPR and the incidence of early onset pneumonia in the intensive care unit (ICU; between 48 h and 7 days of hospitalization). Univariate and multivariate logistic regression analyses were performed for the primary endpoints. After applying the inclusion/exclusion criteria, 254 patients were included in the analyses; of these, 52 were enrolled in the ECPR group, and 202 were enrolled in the CCPR group. Median age was 58 years, 88.5% were male, prophylactic antibiotics were used in 80.3%, and favorable neurological outcomes were observed in 51.9%. On multivariate analysis, ECPR (odds ratio [OR], 2.78; 95% CI: 1.16-6.66; P=0.037) was significantly associated with the development of early onset pneumonia. Conclusions: ECPR was an independent predictor of pneumonia after OHCA in patients who received TTM.

Spontaneous deletion of a 209-kilobase-pair fragment from the Escherichia coli genome occurs with acquisition of resistance to an assortment of infectious phages.

To breed resistance to an assortment of infectious phages, continuous cultures of Escherichia coli JM109 grown in a chemostat were exposed to phage mixtures prepared from sewage influent. Four sequential chemostat-grown cultures were each infected with a different phage mixture. At the end of a chemostat run, one phage-resistant colony was isolated and used to inoculate the subsequent culture. This process was repeated, and increased phage resistance of the input bacterial strain resulted from the successive challenges with different phage cocktails. Multiple mutations apparently accumulated progressively. A mutant isolated at the end of the four runs, designated D198, showed resistance to 38 of 40 phages that infect the parent strain, JM109. D198 produced less outer membrane protein C (OmpC) than JM109. However, restoration of the OmpC protein by plasmid-mediated complementation did not completely restore the susceptibility of D198 to the 38 phages. Therefore, alterations beyond the level of OmpC protein production contribute to the phage resistance of D198. PCR-based genetic analysis revealed that D198 has a genome that is 209 kbp (about 200 genes) smaller than JM109. The deletion includes the chromosomal section from ompC to wbbL that encodes the rhamnosyl transferase involved in lipopolysaccharide biosynthesis. Strains D198 and JM109 were comparable in their growth characteristics and their abilities to express a recombinant protein.

Cloning, expression, and characterization of cytosolic sulfotransferase isozymes from Drosophila melanogaster.

We have identified four cytosolic sulfotransferase (SULT) homologs in the genome database of Drosophila melanogaster, and have designated these genes dmST1-4. Each of these four isozymes was subsequently classified into a different and novel gene family, as determined by the low amino acid sequence homology (less than 40%) between them, and also toward their vertebrate homologs. The transcripts for these four SULT homologs were detectable at all developmental stages in D. melanogaster. In addition, three of these isozymes, the exception being dmST2, were successfully expressed and purified in Escherichia coli. These recombinant dmST1, 3, and 4 products showed high sulfating activity toward phenolic compounds such as vanillin and 4-nitrophenol, but showed no activity toward typical endogenous substrates such as tyramine and serotonin. DmST4 and dmST3 showed the lowest and highest K(m) values for 3'-phosphoadenosine-5'-phosphosulfate (PAPS) respectively. DmST4 also showed low but not negligible activity toward 20-hydroxyecdysone.

A novel sulfotransferase abundantly expressed in the dauer larvae of Caenorhabditis elegans.

We have isolated a gene (clone Y113G7A.11) from Caenorhabditis elegans (C. elegans), that we have designated as ceST1, and which is the only member of the cytosolic sulfotransferase (SULT) gene family present in the genome of this organism. We identified the SULT motifs of ceST1 based upon their deduced amino acid sequence, and subsequently expressed the ceST1 cDNA in Escherichia coli and characterized its enzymatic properties. The recombinant protein showed sulfation activity for 4-nitrophenol and 2-naphthol substrates, but did not catalyze the sulfation of either monoamines or hydroxysteroids. Another compound sulfated by ceST1 is bisphenol A, which is known to stimulate germ cell proliferation in C. elegans. SULT activity was not detected in the cytosol of C. elegans, probably due to heat labile inhibitors. The ceST1 protein was detectable in the cytosol of C. elegans using anti-sera raised against recombinant ceST1, and transcripts could also be detected throughout the developmental stages. Moreover, high levels of ceST1 expression were evident at both the embryonic and adult stages and were augmented in dauer larva. These findings suggest that this sulfotransferase either forms part of a defence system against xenobiotics or regulates germ cell proliferation in C. elegans.

New scoring system of an interview for the diagnosis of benign paroxysmal positional vertigo.

Conclusion This study investigated a novel instrument to diagnose benign paroxysmal positional vertigo (BPPV). Objective To develop a new scoring system of an interview for the diagnosis of BPPV. Methods The answers to questions on dizziness and/or vertigo (D/V) (571 patients) were analyzed and the questions for which the answers differed significantly between the patients with and without BPPV were selected. Results This study established an intensive questionnaire with a scoring system. It consists of the following questions: (1) Is rotary vertigo a characteristic of your D/V? (2) Is your D/V triggered when you roll your head over in a supine position? (3) Does your D/V disappear within 5 min? (4) Have you previously experienced hearing loss in one ear, or have you experienced hearing loss, tinnitus, or ear fullness with this D/V? One point each was given to an answer of 'yes' to questions (1) and (2). Two points were given to an answer of 'yes' to question (3). One point was subtracted upon an answer of 'yes' to question (4). When the total score was greater than two points, the patient was diagnosed with BPPV. The sensitivity of the diagnosis of BPPV by this scoring system was 81% and the specificity was 69%.

Exposure time-dependent thermal effects of radiofrequency electromagnetic field exposure on the whole body of rats.

We investigated the thermal effects of radiofrequency electromagnetic fields (RF-EMFs) on the variation in core temperature and gene expression of some stress markers in rats. Sprague-Dawley rats were exposed to 2.14 GHz wideband code division multiple access (W-CDMA) RF signals at a whole-body averaged specific absorption rate (WBA-SAR) of 4 W/kg, which causes behavioral disruption in laboratory animals, and 0.4 W/kg, which is the limit for the occupational exposure set by the International Commission on Non-Ionizing Radiation Protection guideline. It is important to understand the possible in vivo effects derived from RF-EMF exposures at these intensities. Because of inadequate data on real-time core temperature analyses using free-moving animal and the association between stress and thermal effects of RF-EMF exposure, we analyzed the core body temperature under nonanesthetic condition during RF-EMF exposure. The results revealed that the core temperature increased by approximately 1.5°C compared with the baseline and reached a plateau till the end of RF-EMF exposure. Furthermore, we analyzed the gene expression of heat-shock proteins (Hsp) and heat-shock transcription factors (Hsf) family after RF-EMF exposure. At WBA-SAR of 4 W/kg, some Hsp and Hsf gene expression levels were significantly upregulated in the cerebral cortex and cerebellum following exposure for 6 hr/day but were not upregulated after exposure for 3 hr/day. On the other hand, there was no significant change in the core temperature and gene expression at WBA-SAR of 0.4 W/kg. Thus, 2.14-GHz RF-EMF exposure at WBA-SAR of 4 W/kg induced increases in the core temperature and upregulation of some stress markers, particularly in the cerebellum.

In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization.

Circulating endothelial progenitor cell (EPCs) have been reported to contribute to vasculogenesis in adult organisms. To investigate the possible recruitment of EPCs and organization to form tumor vasculature, we investigated the in vivo real-time trafficking of EPCs non-invasively by using positron emission tomography (PET). A conditionally immortalized endothelial cell line derived from rat bone marrow (TR-BME1) was labeled with [2-(18)F] 2-fluoro-2-deoxy-D-glucose (FDG) and chased the accumulation in the rat tumor with PET. TR-BME1 cells were accumulated in the tumor tissues time-dependently. To investigate that the accumulation of the cells is specific or not, rats were previously irradiated with gamma-ray to suppress the influence of non-labeled EPCs derived from its bone marrow and used for PET analysis. The accumulation of TR-BME1 cells in the tumor was enhanced in gamma-ray-irradiated rats compared with that of non-irradiated ones, suggesting that TR-BME1 cells accumulated in the tumor specifically like as EPCs. Then the involvement of matrix metalloproteinases (MMPs) in EPC recruitment was examined. An inhibitor of MMP, MMI270, which suppressed invasion and tube formation abilities of TR-BME1 cells, only slightly suppressed the accumulation of TR-BME1 cells in the tumor of rats. These results suggest that EPCs are recruited in the tumor tissues for formation of tumor vasculature, and demonstrate the usefulness of TR-BME1 cells for studies on EPC related phenomena.

Papillary cystadenocarcinoma arising from minor salivary glands in the anterior portion of the tongue: a case report.

Papillary cystadenocarcinoma is a rare malignant neoplasm of the salivary gland. We report a case of papillary cystadenocarcinoma arising from the minor salivary gland in the anterior portion of the tongue of a 72-year-old male patient with a history of adenocarcinoma of the colon and prostate. Further, we discussed histopathological and clinical features of this lesion, and reviewed the literature.