Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer

Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several types of cancer. The present study investigated the biological role for PAI-1 in ovarian cancer and potential of targeted pharmacotherapeutics. In patients with ovarian cancer, PAI-1 mRNA expression in tumor tissues was positively correlated with poor prognosis. To determine the role of PAI-1 in cell proliferation in ovarian cancer, the effects of PAI-1 inhibition were examined in PAI-1-expressing ovarian cancer cells. PAI-1 knockdown by small interfering RNA resulted in significant suppression of cell growth accompanied with G2/M cell cycle arrest and intrinsic apoptosis. Similarly, treatment with the small molecule PAI-1 inhibitor TM5275 effectively blocked cell proliferation of ovarian cancer cells that highly express PAI-1. Together these results suggest that PAI-1 promotes cell growth in ovarian cancer. Interestingly, expression of PAI-1 was increased in ovarian clear cell carcinoma compared with that in serous tumors. Our results suggest that PAI-1 inhibition promotes cell cycle arrest and apoptosis in ovarian cancer and that PAI-1 inhibitors potentially represent a novel class of anti-tumor agents.     

Chondrosarcoma of the mandible. Report of case and a survey of 23 cases in the Japanese literature

A huge chondrosarcoma of the mandible (80 X 95 X 100 mm in size) with extension into the infratemporal fossa is described. The tumour was successfully treated by surgical removal and postoperative irradiation. A survey of the Japanese literature revealed 23 cases of chondrosarcoma with involvement of the mandible. The tumours occurred equally in males and females whose mean age was 38 years. The molar region was the site of predilection. The most common symptom was swelling and it was accompanied by pain in 7 cases and paraesthesia in 5 cases. Radiographically, the lesions were quite variable and with the exception of 3 cases in which information was not available, they consisted of a combination of irregular radiopacity and radiolucency in 9 cases, whereas the predominant feature was radiopacity in 6 cases and radiolucency in 4 cases. There was no radiographical abnormality in 2 cases. Root resorption of adjacent teeth was noted in 3 of 6 cases where information existed. Computed tomography was thought to be quite valuable in determining the nature and extent of the tumour. Although an elevation of serum alkaline phosphatase was observed in our case, results of laboratory tests were mostly of no diagnostic significance. Surgical removal was employed in 22 cases alone or in conjunction with irradiation and/or chemotherapy. Of 14 cases on whom information was available, local recurrence occurred in 6 cases in which radiotherapy was not given and distant metastasis in 2 of 10 cases on whom information was available. Of 20 patients on whom information was available on the postoperative course, 7 patients died 5 months to 6 years after the primary treatment.     

Crouzon syndrome with acanthosis nigricans: case report and mutational analysis.

OBJECTIVE: To describe the 22nd case of Crouzan syndrome with acanthosis nigricans, a hyperkeratotic skin disorder with hyperpigmentation. METHODS: DNA analysis and sequencing of the FGFR3 gene were performed. RESULTS: The 13-year-old Japanese boy described here also had dyspnea, facial palsy, sensorineural hearing loss, and skeletal and mental retardation. Examination of a skin biopsy specimen revealed the typical findings of acanthosis nigricans. Genetic analysis revealed the Ala391Glu mutation in one FGFR3 gene. CONCLUSIONS: Crouzon syndrome with acanthosis nigricans is a distinct clinical entity different from classic Crouzon syndrome.     

Excised human larynx in N-vinyl-2-pyrrolidone-embalmed cadavers can produce voiced sound by pliable vocal fold vibration

Anatomical Science International - Tissue-hardening effect and health-hazard issue of formaldehyde (FA) have long been a great disadvantage of this conventional fixative in anatomical research. We...     

Serum binding and biliary excretion of bilirubin after bilirubin loading in Nagase analbuminemic rats and heterozygous (Jj) Gunn rats

To elucidate the effects of albumin on the handling of serum bilirubin, hepatic metabolism and biliary excretion of bilirubin were examined during intravenous bilirubin infusion in Sprague-Dawley (SD) rats, Gunn (heterozygous, Jj) rats, and Nagase analbuminemic rats (NARs). Serum bilirubin was primarily bound to a protein fraction with a molecular weight of about 600 x 10(3) or more in NARs. About 39.2% +/- 12.5% of the serum bilirubin during infusion of bilirubin was bound to the same fraction in Gunn rats. Bilirubin was substantially taken up into the liver and excreted into the bile in NARs, suggesting the role of a high molecular protein, probably a lipoprotein, in its blood transport and the hepatic uptake process. In NARs, biliary bilirubin secretion reached the peak between 20 and 40 minutes after the initiation of bilirubin loading and decreased thereafter, whereas it continued to increase in SD rats and in NARs to which albumin was administered 20 minutes after the start of bilirubin loading. Biliary bilirubin fractions before bilirubin loading were similar in SD rats and NARs, whereas an increase in bilirubin monoglucuronide (BMG) and a decrease in bilirubin diglucuronide (BDG) were observed in Gunn rats. After the initiation of bilirubin loading, a decrease in biliary BDG and an increase in BMG and unconjugated bilirubin were observed in all groups of rats.     

Novel models for bacterial colonization and infection of full‐thickness wounds in rats

An animal model is needed to study the pathophysiology of wound infections; however, an animal model that is reproducible and clinically relevant has not previously been available. In addition, an animal model of wound colonization generated in a manner similar to the wound infection model would be useful. Here, we describe new animal models of the wound infection continuum for the characterization of essential host–pathogen relationships. We determined the conditions needed to establish rat models of stable wound colonization and infection, without the use of disturbing factors (e.g., foreign bodies or induction of diabetes mellitus). We found that the age of the rats, bacterial inoculum size, and wound location were important elements in generating reproducible, obvious, spreading wound infections. We inoculated approximately 6‐month‐old rats with 2.06 × 10⁹ or 4.12 × 10⁹ colony‐forming units of Pseudomonas aeruginosa to generate the wound colonization and wound infection models, respectively. Wounds were made 2 cm cranial to the greater trochanter. These clinically relevant and highly reproducible animal models can be used to investigate the mechanisms of wound infection and monitor the effect of therapeutic agents in vivo.     

Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function

We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.