THREE CASES OF RHABDOMYOSARCOMA ORIGINATED FROM RELATIVELY UNUSUAL SITES

The present paper is a clinicopathological study of three cases of rhabdomyosarcoma originating from relatively unusual sites, in the neck, heart and peritesticular region. A review on the frequency of the original site for 114 cases of rhabdomyosarcoma reported in recent Japanese literatures revealed 3 originating from the neck (2.6%) 2 from the heart (1.8%), and 2 from the peri-testicular region (1.8%).     

Digital multiplexed analysis of circular RNAs in FFPE and fresh non‐small cell lung cancer specimens

Although many studies highlight the implication of circular RNAs (circRNAs) in carcinogenesis and tumor progression, their potential as cancer biomarkers has not yet been fully explored in the clinic due to the limitations of current quantification methods. Here, we report the use of the nCounter platform as a valid technology for the analysis of circRNA expression patterns in non‐small cell lung cancer (NSCLC) specimens. Under this context, our custom‐made circRNA panel was able to detect circRNA expression both in NSCLC cells and formalin‐fixed paraffin‐embedded (FFPE) tissues. CircFUT8 was overexpressed in NSCLC, contrasting with circEPB41L2, circBNC2, and circSOX13 downregulation even at the early stages of the disease. Machine learning (ML) approaches from different paradigms allowed discrimination of NSCLC from nontumor controls (NTCs) with an 8‐circRNA signature. An additional 4‐circRNA signature was able to classify early‐stage NSCLC samples from NTC, reaching a maximum area under the ROC curve (AUC) of 0.981. Our results not only present two circRNA signatures with diagnosis potential but also introduce nCounter processing following ML as a feasible protocol for the study and development of circRNA signatures for NSCLC.     

Angiotensin type 2 receptor-mediated phosphorylation of eNOS in the aortas of mice with 2-kidney, 1-clip hypertension

To evaluate the role of vascular angiotensin II (Ang II) type 2 (AT2) receptor in renovascular hypertension, we investigated expressions of AT2 receptor and endothelial nitric oxide synthase (eNOS) in thoracic aortas of mice with 2-kidney, 1-clip (2K1C) hypertension. The mRNA levels of AT2 receptor in aortas, but not those of AT1 and bradykinin B2 receptors, increased 14 days but not 42 days after clipping. The contractile response to Ang II (>0.1 micromol/L) was attenuated in aortic rings excised 14 days after clipping and was restored to that of rings from sham mice by antagonists of AT2 receptor (PD123319) and B2 receptor (icatibant). The aortic levels of total eNOS, phosphorylated eNOS at Ser1177 (p-eNOS), total Akt, and phosphorylated Akt at Ser473 (p-Akt) were increased in 2K1C mice on day 14, whereas only eNOS levels were increased on day 42. The aortic cGMP levels were 20-fold greater in 2K1C mice on day 14 compared with sham mice. Administration of nicardipine for 4 days before the excision of aortas 14 days after clipping not only reduced blood pressure but also decreased the aortic levels of eNOS, p-eNOS, Akt, p-Akt, and cGMP to sham levels, whereas the administration of PD123319 or icatibant to 2K1C mice decreased p-eNOS and cGMP to sham levels without affecting blood pressure and the levels of eNOS, Akt and p-Akt. These results suggest that vascular NO production is enhanced by increased eNOS phosphorylation via the activation of AT2 receptors in the course of 2K1C hypertension.     

Rebamipide has the potential to reduce the intensity of NSAID-induced small intestinal injury: a double-blind, randomized, controlled trial evaluated by capsule endoscopy

Background

A study reported that rebamipide was effective at reducing short-term nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. The purpose of this study was to re-evaluate the effect of the co-administration of rebamipide on small intestinal injuries induced by short-term NSAID treatment.

Methods

Eighty healthy male volunteers were randomly assigned to two study groups: a control group (N?=?40), which received NSAID (diclofenac sodium, 75?mg/day) and omeprazole (20?mg/day) treatment along with a placebo; and a rebamipide group, which received NSAID, omeprazole and rebamipide (300?mg/day). Small intestinal injuries (mucosal breaks plus denuded areas) were evaluated by capsule endoscopy before and after 14?days of treatment.

Results

A total of 38 control subjects and 34 rebamipide subjects completed the treatment and were evaluated by capsule endoscopy. NSAID therapy increased the mean number of mucosal injuries per subject from a basal level of 0.1?±?0.3 to 16?±?71 and 4.2?±?7.8 in the control and rebamipide groups, respectively, but the difference was not significant. The difference in the percentage of subjects with at least one mucosal injury post-treatment was also not significant (control 63%; rebamipide 47%). Limiting our analysis to subjects with mucosal injuries, rebamipide co-treatment had the tendency to reduce the mean number of mucosal injuries per subject from 25 in the control group to 8.9 in the rebamipide group (multiple comparisons test; p?=?0.088, Mann?CWhitney U test; p?=?0.038).

Conclusions

Rebamipide co-therapy had the potential to reduce the intensity of small intestinal injury induced by 2-week administration of diclofenac.     

α-Parvin,a pseudopodial constituent,promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma

Invasive lobular carcinoma (ILC) is more frequently lymph node positive than is invasive ductal carcinoma (IDC), and ILC cell infiltration shows distinctive histological characteristics, suggesting the action of ILC-specific invasion molecules. To identify such a molecule, we used a proteomic approach in the pseudopodia of MDA-MB-231 breast cancer cells. A pseudopodial constituent was identified using excimer laser ablation, two-dimensional difference gel electrophoresis, mass spectroscopy, and immunocytofluorescence. MDA-MB-231 cells were modified to express various levels of this constituent by transient transfection and were examined for pseudopodia formation and migratory abilities using wound healing and two-chamber assays. Immunohistochemical positivity of human breast cancer cells (56 ILCs and 21 IDCs) was compared with clinicopathological variables. An actin-binding adaptor protein, α-parvin, was found to localize to pseudopodia and to form focal adhesions in cells not induced to extend pseudopodia. Pseudopodial length and density and migratory abilities correlated with α-parvin expression. Twenty-one (37.5 %) ILCs stained positive for α-parvin, whereas the results were negative for all 21 IDCs (P < 0.001). α-Parvin positivity in ILC was significantly associated with lymphatic invasion (P = 0.038) and lymph node metastasis (P = 0.003) in univariate analyses and to lymph node metastasis (P = 0.020) in multivariate analyses. α-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by ILC, suggesting that α-parvin is an ILC-specific invasion molecule that may have clinical utility as a biomarker for aggressive subsets of ILC.     

A retrospective study of the treatment of locally advanced prostate cancer by six institutions in eastern and north-eastern Japan

OBJECTIVE: To investigate patients with locally advanced prostate cancer treated at six academic institutions in eastern and north-eastern Japan from 1988 to 2000, to facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer. PATIENTS AND METHODS: The study included 391 eligible patients with locally advanced prostate cancer who were treated by radical prostatectomy (RP), radiotherapy and/or primary hormone therapy. Disease-specific survival rates for these patients were assessed in relation to their clinicopathological characteristics and the types of treatment they received. The Mann-Whitney U-test, Kruskal-Wallis, chi-square and log-rank test were used for statistical analysis, as appropriate. RESULTS: In all, 128 patient with lower prostate-specific antigen levels (P = 0.023) and/or better performance status (P = 0.001) had RP. Neoadjuvant hormone therapy before RP was the treatment in 68 (53%) of these 128 patients; 66 (52%) received immediate adjuvant hormone therapy. Of 87 patients treated with radiotherapy, 75 (86%) had external beam radiotherapy (EBRT) as the primary treatment with no brachytherapy, and 12 (14%) had brachytherapy as the primary method. Neoadjuvant hormone therapy was given to 56 of the 87 patients (64%); 48 (55%) received immediate adjuvant hormone therapy. Of the 176 patients treated with primary hormone therapy alone, combined androgen blockade and surgical or medical castration was the treatment in 76 (43%) and 85 (48%), respectively. Disease-specific survival rates at 5 years for patients treated with RP, EBRT and primary hormone therapy were 90%, 98%, and 89%, respectively. CONCLUSION: The treatments provided by the participating institutions did not differ significantly from those set out in European and American guidelines, and short-term disease-specific survival rates for each treatment did not differ significantly from those of historical controls. Further investigation may facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer.