Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis

Objective

In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases.

Basal cell adenoma and lymphoepithelial cyst as recurrent tumors of pleomorphic adenoma of the parotid gland

Basal cell adenoma of the parotid gland is a rare benign tumor. Lymphoepithelial cyst of the parotid gland is also a rare benign tumor-like lesion. We report an elderly woman, who previously underwent a removal of pleomorphic adenoma, with multiple masses in the left parotid gland. Physical, MR and intra-operative examination suggested the masses as multiple recurrences of the previous pleomorphic adenoma. A total parotidectomy with facial nerve preservation was performed. The histological examination revealed that the masses were two basal cell adenomas and one lymphoepithelial cyst. These rare tumors should be considered in the differential diagnosis of recurrent masses after a removal of pleomorphic adenoma of the parotid gland.     

Heterogeneity of the effects of monensin on two types of contractions evoked by inhibition of Na+-K+ ATPase in the guinea-pig vas deferens

The interactions between ouabain or K+-free medium and monensin on noradrenaline (NA) release and Ca2+-evoked contractions were assessed in guinea-pig vas deferens. Ouabain (10 microM) produced large, sustained contractions and monensin (1 microM) small, transient contractions. The ouabain-evoked contraction tended to be potentiated in the presence of monensin. The marked contraction induced by ouabain plus monensin was nearly abolished by phentolamine or by treatment with 6-hydroxydopamine. Ouabain caused the release of NA from the tissue, as determined in an HPCL-ECD study. This ouabain-evoked release of NA was enhanced by the simultaneous administration of monensin. High Ca2+ (10 mM) per se, ouabain, monensin or K+-free medium did not elicit contraction of the tissue in the presence of phentolamine. However, 10 mM Ca2+ caused a large contraction 45-65 min after exposure to ouabain or K+-free medium and this contraction was suppressed by monensin. The contraction evoked by Ca2+ in the presence of ouabain was further inhibited by amiloride, an inhibitor of Na+-Ca2+ or Na+-H+ exchange transport, but not by nifedipine, a voltage-dependent Ca2+ antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperreactivity of alpha 1-adrenoceptors, but not of P2X-purinoceptors, in vas deferens of spontaneously hypertensive rats.

We evaluated the contractile reactivity to various stimuli, and the content and release of noradrenaline (NA) from a non-vascular tissue, the vas deferens, isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The concentration-contraction curves for NA in tissue from animals of two ages (10-25 weeks and 30-45 weeks) were shifted to the left in SHR as compared with in age-matched WKY, with significant differences at 1.0 and/or 10 microM of NA. Similarly, the amplitude of contraction produced by electrical stimulation at 4, 8 and 16 Hz in the tissue was much larger in SHR than in WKY. However, ATP (10-100 microM) evoked contractions of the tissue to a similar extent in both SHR and WKY. The electrically evoked contractions of vas deferens from both strains were inhibited by isoprenaline in an approximate dose-dependent and equipotent manner. The tissue NA content, determined by HPLC-ECD, was nearly same in both SHR and WKY. In addition, the same amount of NA was released from the vas deferens of both strains by electrical stimulation in the presence of 4-aminopyridine. The present findings indicate that the contractile response of vas deferens to stimulation of alpha 1-adrenoceptors, but not of beta-adrenoceptors or P2X-purinoceptors, is more pronounced in SHR than in WKY and that a response indicative of hypertension may also occur in non-vascular tissue as it does in vascular tissue.     

Immunohistochemical expression of Mina53 and Ki67 proteins in human primary gingival squamous cell carcinoma

Studies have reported the presence of relationships between the Myc target gene Mina53 and poor prognostic factors in several cancers including esophageal cancer. In this study, we investigated the relationships between Mina53 expression in gingival squamous cell carcinoma and clinicopathological factors. Seven samples of normal and dysplastic gingival tissues and 15 samples of gingival squamous cell carcinoma were immunostained for Mina53 and Ki67, and examined for the relationships between their expression and differentiation degree, lymph node metastasis, stage, tumor diameter, and prognosis. In normal and dysplastic gingival tissues, the localization of the expression of Mina53 and Ki67 was similar, but that in gingival squamous cell carcinoma tissue varied depending on the degree of differentiation. In well-differentiated GSCC with pearl formation, Mina53 was negative at the center of the clearly keratinized cancer nest, but positive in the nuclei of cells in the periphery and adjacent area of the cancer nest. In diffusely proliferating undifferentiated and moderately-differentiated GSCC showing no pearl formation, both Mina53 tended to be positive in the nuclei of cancer cells in the entire cancer nest. A significant correlation was found between the expression of Mina53 and that of Ki67 in patients with gingival squamous cell carcinoma or dysplastic gingiva. No significant correlation was noted between the expression of Mina53 or Ki67 and prognostic factors such as the degree of differentiation, lymph node metastasis, stage, and tumor diameter. In gingival squamous cell carcinoma, Mina53 expression was correlated with the proliferation of tumor cells, but unlike esophageal and other squamous cell carcinomas, not with the prognosis. The absence of correlations with prognostic factors suggests that may differ gingival squamous cell carcinoma differs biologically from esophageal squamous cell carcinoma which is correlated with Mina53 in terms of the biological expression of Mina53.     

Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice

The matrix metalloproteinase (MMP) family (approximately 25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP (membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.     

Phase I study of concurrent radiotherapy with TS-1 and vitamin A (TAR Therapy) for head and neck cancer

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been effectively used to treat head and neck cancer. The biological anti-tumor effect of 5-FU depends on the activity of its metabolizing enzyme, dihydropyrimidine dehydrogenase (DPD). TS-1 is a novel oral DPD inhibitory fluoropyrimidine (DIF). To improve the anti-tumor effect of FAR therapy, we have applied TS-1 in place of 5-FU injection in the combination of Vitamin A and radiation (TAR therapy). In this study, we have examined the appropriate duration of TS-1 medication and the clinical efficacy and safety of TAR therapy. TS-1 was administered orally at a dose of 65 mg/m2 twice a day. Vitamin A (Retinol Palmitate: 50,000 U/day) was administered intra-musculary on each day of radiation. Radiation was given (1.5-2 Gy/day: 5 days/week) for 30-40 Gy. The levels were divided according to the length of TS-1 application as follows: level 1, 2 weeks; level 2, 3 weeks; level 4, 4 weeks. Grade 4 toxicity of anorexia was observed in one case of level 3. We decided that level 2 (3 weeks of TS-1 administration) was the appropriate length of TS-1 application. TAR therapy is a useful concurrent chemo-radiotherapy which might improve the response rate and QOL of patients with HNSCC.     

Role of individual ionic current systems in ventricular cells hypothesized by a model study

Individual ion channels or exchangers are described with a common set of equations for both the sinoatrial node pacemaker and ventricular cells. New experimental data are included, such as the new kinetics of the inward rectifier K+ channel, delayed rectifier K+ channel, and sustained inward current. The gating model of Shirokov et al. (J Gen Physiol 102: 1005-1030, 1993) is used for both the fast Na+ and L-type Ca2+ channels. When combined with a contraction model (Negroni and Lascano: J Mol Cell Cardiol 28: 915-929, 1996), the experimental staircase phenomenon of contraction is reconstructed. The modulation of the action potential by varying the external Ca2+ and K+ concentrations is well simulated. The conductance of I(CaL) dominates membrane conductance during the action potential so that an artificial increase of I(to), I(Kr), I(Ks), or I(KATP) magnifies I(CaL) amplitude. Repolarizing current is provided sequentially by I(Ks), I(Kr), and I(K1). Depression of ATP production results in the shortening of action potential through the activation of I(KATP). The ratio of Ca2+ released from SR over Ca2+ entering via I(CaL) (Ca2+ gain = approximately 15) in excitation-contraction coupling well agrees with the experimental data. The model serves as a predictive tool in generating testable hypotheses.     

Next‐generation sequencing of endoscopically obtained tissues from patients with all stages of pancreatic cancer

Routinely available clinical samples of all stages of pancreatic cancer are used in the present study to elucidate its molecular mechanisms and identify novel therapeutic targets. We evaluated the use of next‐generation sequencing (NGS) of endoscopically obtained pancreatic cancer tissues. We enrolled 147 patients who underwent endoscopic ultrasound‐guided fine‐needle aspiration or endoscopic biopsy. The quantity and quality of the extracted DNA was assessed. Tissue samples were used for NGS of 78 cancer‐related genes, from which gene alterations and microsatellite instability (MSI) were extracted. NGS was successful in 141 out of 147 (96%) cases. Gene alterations were detected in 134 out of 141 (91%) samples, among which eight out of 10 samples with a DNA concentration below the detection limit had some type of gene alteration. Targetable genes were detected in 28 (19.9%) cases. MSI and germline mutations in homologous recombination repair associated genes were detected in 5% and 3% of cases, respectively. Cox regression analysis revealed that metastasis (P < .005; hazard ratio [HR], 3.30) was associated with poor prognosis in all pancreatic cancer patients. In addition, fewer than three mutations (P = .03; HR, 2.48) and serum carcinoembryonic antigen levels >5 ng/mL (P < .005; HR, 3.94) were associated with worse prognosis in cases without and with metastasis, respectively. Targeted sequencing of all stages of pancreatic cancer using available samples from real clinical practice could be used to determine the relationship between gene alterations and prognosis to help determine treatment choices.