Yoshihiro Tamura

Influence of methylated p15 INK4b and p16 INK4a genes on clinicopathological features in colorectal cancer

Background and Aim:  Genetic silencing by promoter methylation has attracted attention in the carcinogenesis of colorectal cancer. Methylation of the p16INK4a gene has been found in primary colorectal cancer. Although the p15INK4b gene displays high homology to the p16INK4a gene in the amino acid sequence, methylation of p15INK4b has not been fully studied. We investigated p15INK4b methylation status in patients with colorectal cancer to verify the association between the methylation of p15INK4b and clinicopathological features compared with p16INK4a.

Chemosensitivity Determinants of Irinotecan Hydrochloride in Hepatocellular Carcinoma Cell Lines

Irinotecan hydrochloride (CPT-11) is an effective anticancer drug, and its metabolic pathway has been well studied. Nevertheless, in human hepatocellular carcinoma (HCC), its cytotoxicity is less well studied and the determination of its chemosensitivity is unclear. We, therefore, examined chemosensitivities of HCC cell lines for CPT-11 and SN-38, and mRNA expressions of several molecules in their metabolic pathway. Three markers were found to correlate well with chemosensitivity: breast cancer resistance protein (BCRP), cytochrome P450 (CYP) 3A4 and uridine diphosphate-glucuronosyl transferase (UGT) 1A1. Next, CYP3A4/UGT1A1/BCRP inhibitor naringenin and BCRP inhibitor elacridar were tested for enhancement of their chemosensitivity. Both of naringenin and elacridar separately enhanced the sensitivity for CPT-11 and SN-38 in KYN-2 cells abundantly expressing BCRP, CYP3A4/5 and UGT1A1, but not in KYN-1 cells expressing lower levels. However, naringenin had little effect on the sensitivity in JHH-4 and HLE cells with higher CYP3A4/5 and lower UGT1A1 and BCRP expression. On the other hand, naringenin and elacridar significantly increased the chemosensitivity for CPT-11 and SN-38 in the KYN-1-derived cells artificially overexpressing BCRP. Furthermore, flow cytometric analysis showed that naringenin raised intracellular accumulation of CPT-11 as well as elacridar. Those results suggest that BCRP is one of the chemosensitivity determinants of CPT-11 in HCC cells and its inhibition might be critical for cells expressing abundant BCRP.

Teeth and physical fitness in a community-dwelling 40 to 79-year-old Japanese population

Purpose Decline in the number of teeth and physical fitness begins from 40 years of age; however, several epidemiological studies have identified relationships between oral conditions and physical performance parameters in community-dwelling elderly population. The aim of this study was to validate the relationship between the muscle mass and its function and oral conditions (number of teeth and dental occlusion) after 40 years of age in a community-dwelling population in Japan. Materials and methods The subjects comprised of 552 volunteers (198 males and 354 females, 40–79 years) who participated in the Iwaki Health Promotion Project in 2013. Multiple linear regression analyses were performed with the measures of the muscle mass and its function as objective variables and the measures of the number of teeth, age, body mass index, medical history, serum albumin concentration, smoking status, habitual alcohol intake, marital status, education levels, and exercising habits as explanatory variables. The relationships between the Eichner index and the muscle mass and its function were analyzed using analysis of covariance, with adjustment for confounding factors. Results After adjusting for confounding factors, the number of teeth was shown to be an independent risk factor for the timed 10 m walk test (in females) and the skeletal muscle mass of the whole body (in males). The results also revealed that the timed 10 m walk test was significantly correlated with the Eichner index (Classes A and C in females were correlated). Conclusion This cross-sectional study on a Japanese community-dwelling population revealed relationships between oral conditions and the muscle mass and its function. However, the interpretation of our results was hampered by a lack of data, including those on socioeconomic status and longitudinal observations. Future research exploring teeth loss and the muscle mass and its function is warranted.

Oral conditions and dysphagia in Japanese, community-dwelling middle- and older- aged adults, independent in daily living

Purpose Prevention, early detection and effective rehabilitation of dysphagia are important issues to be considered in an aging society. Previous studies have shown conflicting findings regarding the association between dysphagia and its potential risk factors, including age, malnutrition, oral conditions, lifestyle and medical history. Herein, we assessed the prevalence and association of dysphagia with potential risk factors in 50- to 79-year-old adults dwelling in a community in Japan. Patients and methods In this study, there were 532 participants (185 males and 347 females). Participants who responded positively to the question “Do you sometimes choke on drinks/food such as tea and soup?” or those who presented with abnormal repetitive saliva swallowing test findings were diagnosed with dysphagia. The data collected from these participants included the following: number of teeth, occurrence of oral dryness, age, body mass index, serum albumin concentration, smoking, drinking and exercise habits, presence of diseases, such as diabetes mellitus and hypertension, and questions from the Mini–Mental State Examination. Results Dysphagia was observed in 33 males (17.8%) and 76 females (21.9%). To explore the effect of the potential risk factors on the prevalence of dysphagia, a model was built by multivariate logistic regression analysis. Using the forced entry method, oral dryness (odds ratio [OR] =3.683 and P=0.003 in males; OR =1.797 and P=0.032 in females) and the number of teeth (OR =0.946 and P=0.038 in males) were found to be significantly related to dysphagia. Conclusion This cross-sectional study demonstrated associations between oral conditions and dysphagia. Factors such as oral dryness and number of teeth may contribute to dysphagia more so than aging, lifestyle and comorbidity in community-dwelling adults over the age of 50.

Antitumor effect of combination of murine recombinant interferon β, murine recombinant interferon γ and human recombinant interleukin-2 in methA-bearing mice

SummaryWe have previously reported that the combination of murine recombinant interferon β (Mu-rIFNβ) with murine recombinant interferon γ (Mu-rIFNγ) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFNβ with Mu-rIFNγ on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 × 103 U or 5 × 104 U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 × 105 U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 × 103 U and 5 × 105 U) in addition to the combination of IFNβ and IFNγ showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFNβ and IFNγ had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFNβ and γ was effective for cancer treatment.

Comparison of sialolithiasis in pediatric and adult patients

Abstract Aims To compare the clinical characteristics of sialolithiasis between pediatric and adult patients. Settings and Design Subject characteristics, clinical manifestations, salivary calculi characteristics, and treatment modalities and outcomes from medical records were retrospectively compared between pediatric and adult patients with sialolithiasis visiting the Department of Oral and Maxillofacial Surgery, Hirosaki University Hospital, between 2005 and 2014. Subjects We included 5 pediatric (all boys) and 45 adult (20 men; 25 women) patients. Results Most patients had submandibular swelling. The calculi were located on the right in 100.0% of pediatric patients and 57.8% of adult patients. Moreover, 20.0% of pediatric patients and 35.6% of adult patients exhibited sialoliths in the glands. Calculi were Conclusions A large number of relatively small and distal sialoliths in pediatric patients was removed using intraoral retrieval under local anesthesia. This difference in the choice of treatment between pediatric and adult sialolithiasis may be attributed to the size and palpability of the calculi.

Impalement of an unusual foreign body on the temporomandibular joint causing severe trismus.

A penetrating injury by a foreign body is comparatively common in the oral and maxillofacial region. On the other hand, injury to the temporomandibular joint (TMJ) by a foreign object is very rare. The TMJ is an anatomically narrow space surrounded by hard bony processes. An unusual case of trauma with severe trismus caused by a foreign body that impaled the TMJ is reported. A 55-year-old man presented with a 5 × 1-cm laceration to the right cheek caused by a flying object propelled during the use of a lawn mower. The edge of the foreign body had a metallic wire, which became imbedded in the wound. His jaw opening was severely limited. Computed tomography revealed that the foreign body was 3 mm in diameter and was impaled on the articular capsule. The object was successfully removed, and the wound and interior of the TMJ were irrigated. Rehabilitation of mouth opening was started on postoperative day 3. On day 9, mouth opening had improved to 35 mm, and he was discharged. After 1 year, mouth opening was 45 mm with no sign of any TMJ disorders.

A novel model of solitary hepatic tumor in rats using ascites hepatoma AH13: suitability for chemotherapeutic studies.

A highly reproducible model of a solitary hepatic tumor in rats using ascites hepatoma AH13 has been developed using a two‐step method which was suitable for quantitative chemotherapeutic studies. Diffuse hepatic metastases were induced first by inoculation of three different ascites hepatomas, AH13, AH130 and AH7974 into the portal vein in a dose‐dependent fashion. Second, the induced hepatic tumor (3×107 cells) was minced into 1×1×4 mm fragments and implanted in the liver of normal rats. In this procedure, the AH13 strain proved best suited for the generation of a solitary hepatic tumor. The growth of the solitary liver tumor using AH13 was highly reproducible. To demonstrate the suitability of this solitary hepatic tumor model for the evaluation of chemotherapy, the tumor‐burdened rats were treated with adriamycin (ADR) and mitomycin C (MMC). The reduction in tumor size was proportional to dosage, and the statistical significance of the differences between the treatment group and control group was proportional to dosage. A synergistic effect of ADR and MMC on the tumor also was demonstrated. This model should prove to be a useful tool for the testing of newly developed treatments of hepatic cancer.