A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.

Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980.

Evaluation of PSF1 as a prognostic biomarker for prostate cancer.

BACKGROUND: Partner of SLD5 1 (PSF1) is an evolutionarily conserved DNA replication factor. Previous studies have suggested that transcriptional activity of the PSF1 gene correlated with malignancy of cancer cells. The objective of the current study was to evaluate the relationship between PSF1 expression and the clinical features of prostate cancer. METHODS: We determined the expression of PSF1 in 120 needle biopsy samples of prostate cancer by immunohistochemistry. We divided patients into PSF1-positive or -negative groups and analyzed the relationships between the expression of PSF1, the Gleason score, PSA level, TNM classification and prognosis. RESULTS: Our results showed that the PSF1 expression correlated significantly with PSA values at diagnosis (P=0.0028), with tumor grade (P<0.0001), and with clinical stage (P=0.0005). Moreover, the PSF1 expression correlated significantly with overall survival (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.17-15.8; P=0.003) and progression-free survival in 99 consecutive patients with prostate cancer. Noteworthy, the prognosis of PSF1-positive cases was also worse in patients with a Gleason score of 8-10 (HR 3.7; 95% CI 1.28-13.43; P=0.0143). Limitations include that this study had a retrospective design, that patients in the study were heterogeneous and included those with early and advanced cancer, and that small tumor fragments may not be representative of the entire carcinoma. CONCLUSIONS: PSF1 is expressed in high-grade prostate cancer and may be a useful biomarker to identify patients with a poor prognosis at the time of diagnosis.

Characterization of highly osteoblast/cementoblast cell clones from a CD105-enriched periodontal ligament progenitor cell population.

BACKGROUND: It is known that periodontal ligament (PDL) harbors a heterogeneous progenitor cell population at different stages of lineage commitment. However, characterization of PDL stem cells committed to osteoblast/cementoblast (O/C) differentiation remains to be elucidated. The present study is carried out to isolate single cell-derived, cluster of differentiation (CD)105-positive PDL clones and to characterize the clones that present high potential to differentiate toward O/C phenotype in vitro. METHODS: Isolation of single cell-derived colonies (clones) from a CD105-enriched PDL progenitor cell population was performed by the ring-cloning technique. Cell clones were evaluated for their O/C differentiation potential, metabolic activity, and expression of STRO-1 protein. Additionally, the clones that showed potential to O/C differentiation were characterized by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for expression of runt-related transcriptor factor 2 (RUNX2), alkaline phosphatase, CD105, and CD166 during osteogenic induction. RESULTS: Six PDL-CD105(+) clones were obtained, three being highly O/C clones (C-O) and three others that did not have the ability to produce mineralized matrix in vitro (C-F). The C-O group showed lower metabolic activity compared with the C-F group, and both cell groups were positively immunostained for STRO-1. qRT-PCR analysis demonstrated an increased expression of transcripts for RUNX2 and CD166 during the maturation of C-O cells toward O/C phenotype. CONCLUSIONS: These results provide evidence that PDL-CD105(+) purified progenitor cells comprise a heterogeneous cell population that presents a cell subset with high O/C potential and, further, that surface antigen CD166 is modulated during the O/C maturation of this cell subset.

Immunoreactivity of glucose transporter 5 is located in epithelial cells of the choroid plexus and ependymal cells.

High fructose intake is associated with increased plasma triglyceride concentration, hepatic steatosis, impaired glucose tolerance, insulin resistance, and high blood pressure. In addition, increased fructose intake has recently been supposed to be a risk factor for dementia. However, direct effects of fructose on the brain function remain to be clarified. The localization of glucose transporter 5 (Glut5), a representative transporter of fructose, was immunohistochemically examined in the brains of humans, rats, and mice to clarify whether fructose was transported from the blood into the brain. Glut5 immunoreactivity was demonstrated to be located in the epithelial cells of the choroid plexus and the ependymal cells in the brains of humans and rats using commercial antibodies for Glut5. In addition, mRNA expression of mouse Glut5 was confirmed in the brains of mice. Immunohistochemical examination using a custom-made antibody against two regions of amino acid sequences of mouse Glut5 revealed that Glut5 immunoreactivity was also seen in the epithelial cells of the choroid plexus and the ependymal cells in the brains of mice. These findings show that Glut5 immunoreactivity is located in the epithelial cells of the choroid plexus and the ependymal cells, suggesting the possibility of the direct transportation of intravascular fructose into the brain parenchyma.

Relationship between vegetable and carotene intake and risk of prostate cancer: the JACC study.

BACKGROUND: We examined the associations of intakes of vegetables and carotenes with risk of prostate cancer in Japanese. METHODS: A total of 15,471 Japanese men participating in the Japan Collaborative Cohort study completed a questionnaire including food intake. Of them, 143 incident prostate cancers were documented. We examined the associations stated above by using Cox proportional hazard model. RESULTS: Vegetable intake was not associated with the risk of prostate cancer, but so was dietary alpha-carotene intake. The multivariable hazard ratio (95%CI) in the secondary highest and highest quintiles of alpha-carotene intake was 0.50 (0.26-0.98) (P=0.043) and 0.46 (0.22-0.97) (P=0.041) (P for trend=0.224), respectively. Beta-carotene intake was not associated with the risk of prostate cancer. CONCLUSION: Alpha-carotene intake was associated with lower risk of prostate cancer among Japanese.

Comparison of haemodynamic responses to tracheal intubation using the Airway Scope(®) and Macintosh laryngoscope in normotensive and hypertensive patients.

We compared the effects of the Airway Scope(®) on haemodynamic responses during tracheal intubation with those of direct laryngoscopy in normotensive and hypertensive patients. The systolic blood pressure, diastolic blood pressures and heart rate were recorded: (a) before anaesthesia; (b) immediately before intubation; (c) at intubation; and (d) 1, 2, 3, 4 and 5 min after intubation. In normotensive patients, the increase in blood pressure and heart rate over time were significantly lower with the Airway Scope than with the Macintosh laryngoscope (p < 0.003). In hypertensive patients, however, there was no difference in the changes over time in any of these haemodynamic measures between the two devices (p > 0.05). We conclude that the Airway Scope attenuates haemodynamic responses to tracheal intubation in comparison with the laryngoscope in normotensive but not in hypertensive patients. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Lack of association of dairy food, calcium, and vitamin D intake with the risk of Parkinson's disease: a case-control study in Japan.

Three previous cohort studies in the USA reported that dairy product consumption was significantly associated with an increased risk of Parkinson's disease (PD) in men, but not in women. We examined the relationship between consumption of dairy products, calcium, and vitamin D and the risk of PD using data from a multicenter hospital-based case-control study in Japan. Included were 249 cases within 6 years of onset of PD based on the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, and dietary factors including cholesterol, dietary glycemic index, vitamin E, ß-carotene, vitamin B(6), caffeine, iron, and alcohol. Total dairy product consumption was not materially associated with the risk of PD (P for trend = 0.62). No evident relationships were observed between intake of milk, yogurt, cheese, or ice cream and the risk of PD (P for trend = 0.75, 0.63, 0.59, and 0.35, respectively). There were no measurable associations between consumption of calcium or vitamin D and PD (P for trend = 0.37 and 0.69, respectively). No significant interactions were observed between the dietary exposures and sex regarding PD. Our results suggest that intake of dairy products, calcium, and vitamin D was not related to PD, regardless of sex. However, such null relationships might be a consequence of PD.

Dietary intake of antioxidant vitamins and risk of Parkinson's disease: a case-control study in Japan.

BACKGROUND: antioxidant vitamins are expected to protect cells from oxidative damage by neutralizing the effects of reactive oxygen species. However, epidemiological evidence regarding the associations between antioxidant vitamin intake and Parkinson's disease (PD) is limited and inconsistent. We investigated the relationship between dietary intake of selected antioxidant vitamins, vegetables and fruit and the risk of PD in Japan using data from a multicenter hospital-based case-control study. METHODS: included were 249 patients within 6 years of onset of PD. Controls were 368 inpatients and outpatients without a neurodegenerative disease. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for sex, age, region of residence, pack-years of smoking, years of education, body mass index, dietary intake of cholesterol, alcohol, total dairy products, and coffee and the dietary glycemic index. RESULTS: higher consumption of vitamin E and ß-carotene was significantly associated with a reduced risk of PD after adjustment for confounders under study: the adjusted odds ratio in the highest quartile was 0.45 (95% confidence interval [CI]: 0.25-0.79, P for trend = 0.009) for vitamin E and 0.56 (95% CI: 0.33-0.97, P for trend = 0.03) for ß-carotene. Stratified by sex, such inverse associations were significant only in women. No material relationships were shown between intake of vitamin C, α-carotene, cryptoxanthin, green and yellow vegetables, other vegetables, or fruit and the risk of PD. CONCLUSIONS: higher intake of vitamin E and ß-carotene may be associated with a decreased risk of PD.

Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling.

The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene had been isolated as an antagonist to RAS signaling; however, the mechanism of its action is not clear. In this study, the effect of loss of RECK function was assessed in various ways and cell systems. Successive cell cultivation of mouse embryonic fibroblasts (MEFs) according to 3T3 protocol revealed that the germline knockout of RECK confers accelerated cell proliferation and early escape from cellular senescence associated with downregulation of p19(Arf), Trp53 and p21(Cdkn1a). In contrast, short hairpin RNA-mediated depletion of RECK induced irreversible growth arrest along with several features of the Arf, Trp53 and Cdkn1a-dependent cellular senescence. Within 2 days of RECK depletion, we observed a transient increase in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation associated with an upregulated expression of cyclin D1, p19(Arf), Trp53, p21(Cdkn1a) and Sprouty 2. On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence. In addition, we observed that epidermal growth factor receptor (EGFR) activity was transiently upregulated by RECK depletion in MEFs, and continuously downregulated by RECK overexpression in colon cancer cells. These findings indicate that RECK is a novel modulator of EGFR signaling.

GST polymorphisms, interaction with smoking and pesticide use, and risk for Parkinson's disease in a Japanese population.

Patients with idiopathic Parkinson's disease (PD) appear to have reduced capacity for detoxification of certain environmental compounds. The glutathione S-transferases (GSTs) are candidate genes for PD because they are involved in the metabolism of pesticides and cigarette smoke. We investigated the relationship of the seven GST polymorphisms (GSTM1 deletion, GSTT1 deletion, GSTP1 rs1695, GSTO1 rs4925, GSTO1 rs11191972, GSTO2 rs156697 and GSTO2 rs2297235) and PD risk with special reference to the interaction with pesticide use or cigarette smoking among 238 patients with PD cases and 370 controls in a Japanese population. None of the GST polymorphisms were associated with PD. GSTO1 rs4925 and GSTO2 rs2297235 were found to be in strong linkage disequilibrium (D' = 0.98). Cigarette smoking was significantly associated with decreased risk of PD. However, no interaction of smoking with any of the GST polymorphisms was observed. Self-reported pesticide use was not associated with increased risk of PD. There was no evidence of interaction between self-reported pesticide use and either GST polymorphism. Our results suggest that the tested GST polymorphisms did not play an important role in PD susceptibility in our Japanese population. Our study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. As for interaction between GSTP polymorphisms and pesticide use, the power of this study to detect an interactive effect was low due to a small number of pesticide users. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the GST polymorphisms in PD development.

Active and passive smoking and risk of Parkinson's disease.

OBJECTIVE: To assess the association between active and passive smoking and the risk of Parkinson's disease (PD), a case-control study with 249 PD patients and 369 controls was carried out in Japan. METHODS: Information on smoking was obtained through a self-administered questionnaire. Adjustment was made for age, sex, region of residence, educational level, and occupational exposure. RESULTS: Ever having smoked cigarettes was associated with a reduced risk of PD [adjusted odds ratio = 0.38; 95% confidence interval (CI): 0.24-0.59]. Risk for former smokers was intermediate between the high risk for never smokers and the low risk for current smokers. Adjusted odds ratios for former and current smokers were 0.51 (95% CI: 0.32-0.82) and 0.12 (95% CI: 0.05-0.26), respectively. There was an inverse dose-response gradient with pack-years smoked. No significant association was detected for passive smoking exposure. CONCLUSION: Our results appear to confirm data from previous epidemiological studies.

Short-term exposure to ethanol causes a differential response between nerve growth factor and brain-derived neurotrophic factor ligand/receptor systems in the mouse cerebellum.

Alcohol ingestion affects both neuropsychological and motor functions. We hypothesized that one of the key factors involved in such functions are neurotrophins and their receptors. We have therefore examined the effects of short-term ethanol exposure on the mRNA expression and protein levels of neurotrophin ligands and receptors in the cerebellum using real-time RT-PCR and Western blotting techniques. Male BALB/C mice were fed a liquid diet containing 5% (v/v) ethanol. The pair-fed control mice were fed an identical liquid diet except that sucrose was substituted isocalorically for ethanol. The cerebellum of mice exhibiting intoxication signs of stage 1 or 2 were used in the present study. We found that exposure to ethanol resulted in elevated levels of nerve growth factor (NGF) and TrkA mRNA expression but a decreased level of brain-derived neurotrophic factor (BDNF) mRNA expression. The expression of TrkB and p73 mRNA was unchanged. Changes in the level of these proteins were found to mirror these mRNA expression levels. We conclude that exposure to ethanol for a short period can cause a differential responsive in the various neurotrophin ligand/receptor systems. The functional consequences of these changes are unknown at present.

Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways.

Prostate cancer (PC) is the most common malignancy in males. Despite high response rates and clinical benefits, androgen-ablation therapy is ineffective for advanced or relapsed PC because of the emergence of aggressive castration-resistant prostate cancer (CRPC). Through our genome-wide gene expression analysis of PC cells purified from clinical CRPC tissues, we here identified a novel molecular target, PKIB (cAMP-dependent protein kinase inhibitor-beta), which was overexpressed specifically in CRPCs and aggressive PCs. Immunohistochemical analysis confirmed its overexpression in CRPCs and its strong correlation with high Gleason scores of PCs. Knockdown of PKIB by siRNA resulted in drastic growth suppression of PC cells, and, concordantly, exogenous introduction of PKIB into PC cells enhanced their growth and mobility. We found the direct interaction between PKIB and cAMP-dependent protein kinase A catalytic subunit (PKA-C), and showed that knockdown of PKIB in PC cells diminished the nuclear translocation of PKA-C. Knockdown of PKIB also decreased the phosphorylation level of Akt at Ser473 in PC cells, and exogenous PKIB introduction enhanced Akt phosphorylation in PC cells by incorporating with endogenous PKA-C kinase. In vitro kinase assay validated the recombinant PKIB enhanced phosphorylation of Akt at Ser473 by PKA-C kinase. These findings show that PKIB and PKA-C kinase can have critical functions of aggressive phenotype of PCs through Akt phosphorylation and that they should be a promising molecular target for PC treatment.

Niflumic acid-sensitive ion channels play an important role in the induction of glucose-stimulated insulin secretion by cyclic AMP in mice.

AIMS/HYPOTHESIS: We have previously reported that glucose-stimulated insulin secretion (GSIS) is induced by glucagon-like peptide-1 (GLP-1) in mice lacking ATP-sensitive K(+) (K(ATP)) channels (Kir6.2(-/-) mice [up-to-date symbol for Kir6.2 gene is Kcnj11]), in which glucose alone does not trigger insulin secretion. This study aimed to clarify the mechanism involved in the induction of GSIS by GLP-1. METHODS: Pancreas perfusion experiments were performed using wild-type (Kir6.2(+/+)) or Kir6.2(-/-) mice. Glucose concentrations were either changed abruptly from 2.8 to 16.7 mmol/l or increased stepwise (1.4 mmol/l per step) from 2.8 to 12.5 mmol/l. Electrophysiological experiments were performed using pancreatic beta cells isolated from Kir6.2(-/-) mice or clonal pancreatic beta cells (MIN6 cells) after pharmacologically inhibiting their K(ATP) channels with glibenclamide. RESULTS: The combination of cyclic AMP plus 16.7 mmol/l glucose evoked insulin secretion in Kir6.2(-/-) pancreases where glucose alone was ineffective as a secretagogue. The secretion was blocked by the application of niflumic acid. In K(ATP) channel-inactivated MIN6 cells, niflumic acid similarly inhibited the membrane depolarisation caused by cAMP plus glucose. Surprisingly, stepwise increases of glucose concentration triggered insulin secretion only in the presence of cAMP or GLP-1 in Kir6.2(+/+), as in Kir6.2(-/-) pancreases. CONCLUSIONS/INTERPRETATION: Niflumic acid-sensitive ion channels participate in the induction of GSIS by cyclic AMP in Kir6.2(-/-) beta cells. Cyclic AMP thus not only acts as a potentiator of insulin secretion, but appears to be permissive for GSIS via novel, niflumic acid-sensitive ion channels. This mechanism may be physiologically important for triggering insulin secretion when the plasma glucose concentration increases gradually rather than abruptly.

[Case of a giant pericardial cyst went under the thoracoscopic surgery using a double-balloon catheter].

A 45-year-old female was referred to our hospital due to right anterior chest pain. A chest X-ray and a computed tomographic examination showed a large cystic lesion in the right pleural cavity above the diaphragm. The internal surface of the cyst seemed to be smooth and the content was homogeneous suggesting clear liquid. Under the diagnosis of the benign pericardial cyst, a thoracoscopic surgery was performed using a double-balloon catheter. Aspiration of the cyst content by the double-balloon catheter minimized the spillage of the content into the thoracic cavity. Furthermore, the double-balloon catheter allowed the cyst wall to be more easily grasped and manipulated. We confirmed the usefulness of a double-balloon catheter for the thoracoscopic resection of giant cystic lesions.

Neuroendoscopic trans-third ventricle approach for lesions of the ventral brainstem surface.

Due to the establishment in recent years of neuroendoscopic third ventriculostomy (ETV), it has become possible during ETV to observe the ventral brainstem surface--particularly the prepontine cistern--in a minimally invasive manner via the third ventricular base with a neuroendoscope. As an adaptation of that technique in this study, we investigated a neuroendoscopic trans-third ventricle approach (ETTVA), which accesses lesions of the ventral brainstem surface with a neuroendoscope inserted via the stoma of the third ventricular floor. Our study included 6 cases, including one case each of neurenteric cyst, chordoma, pontine glioma (astrocytoma), ecchordosis physaliphora, endodermal cyst, and cystic schwannoma. Surgical operations performed by ETTVA included 3 cases of tumor resection, 2 cases of tumor biopsy, and 1 case of cyst puncture and aspiration. There were no complications accompanying ETTVA. Out of the 6 cases, only 1 required additional surgical treatment following ETTVA surgery. In the other 5 cases, no additional surgical procedures were performed. This study showed that ETTVA allowed access to the prepontine cistern quickly and in a minimally invasive manner. In selected cases, ETTVA can offer a new approach to these lesions.

Two novel alleles of tottering with distinct Ca(v)2.1 calcium channel neuropathologies.

The calcium channel CACNA1A gene encodes the pore-forming, voltage-sensitive subunit of the voltage-dependent calcium Ca(v)2.1 type channel. Mutations in this gene have been linked to several human disorders, including familial hemiplegic migraine, episodic ataxia 2 and spinocerebellar ataxia type 6. The mouse homologue, Cacna1a, is associated with the tottering, Cacna1a(tg), mutant series. Here we describe two new missense mutant alleles, Cacna1a(tg-4J) and Cacna1a(Tg-5J). The Cacna1a(tg-4J) mutation is a valine to alanine mutation at amino acid 581, in segment S5 of domain II. The recessive Cacna1a(tg-4J) mutant exhibited the ataxia, paroxysmal dyskinesia and absence seizures reminiscent of the original tottering mouse. The Cacna1a(tg-4J) mutant also showed altered activation and inactivation kinetics of the Ca(v)2.1 channel, not previously reported for other tottering alleles. The semi-dominant Cacna1a(Tg-5J) mutation changed a conserved arginine residue to glutamine at amino acid 1252 within segment S4 of domain III. The heterozygous mouse was ataxic and homozygotes rarely survived. The Cacna1a(Tg-5J) mutation caused a shift in both voltage activation and inactivation to lower voltages, showing that this arginine residue is critical for sensing Ca(v)2.1 voltage changes. These two tottering mouse models illustrate how novel allelic variants can contribute to functional studies of the Ca(v)2.1 calcium channel.

Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis.

In an attempt to disclose mechanisms of bladder carcinogenesis and discover novel target molecules for development of treatment, we applied a cDNA microarray to screen genes that were significantly transactivated in bladder cancer cells. Among the upregulated genes, we here focused on a novel gene, (DEPDC1) DEP domain containing 1, whose overexpression was confirmed by northern blot and immunohistochemical analyses. Immunocytochemical staining analysis detected strong staining of endogenous DEPDC1 protein in the nucleus of bladder cancer cells. Since DEPDC1 expression was hardly detectable in any of 24 normal human tissues we examined except the testis, we considered this gene-product to be a novel cancer/testis antigen. Suppression of DEPDC1 expression with small-interfering RNA significantly inhibited growth of bladder cancer cells. Taken together, these findings suggest that DEPDC1 might play an essential role in the growth of bladder cancer cells, and would be a promising molecular-target for novel therapeutic drugs or cancer peptide-vaccine to bladder cancers.

Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array.

Homozygous deletions (HD) provide an important resource for identifying the location of candidate tumor suppressor genes. To identify the tumor suppressor gene in oral cancer, we employed high-resolution comparative genomic hybridization (CGH)-array analysis. We identified a homozygous loss of FAT (4q35), a new member of the human cadherin superfamily, from genome-wide screening of copy number alterations in one primary oral cancer. This result was evaluated by genomic polymerase chain reaction in 13 oral cancer cell lines and 20 primary oral cancers and Southern blot in the cell lines. We found frequent exonic HD of FAT in the cell lines (3/13, 23%) and in primary oral cancers (16/20, 80%). FAT expression was absent in these cell lines. Homozygous deletion hot spots were observed in exon 1 (9/20, 45%) and exon 4 (7/20, 35%). Moreover, loss of gene expression was identified in other types of squamous cell carcinoma. The methylation status of the FAT CpG island in squamous cell carcinomas correlated negatively with its expression. Our results identify mutations in FAT as an important factor in the development of oral cancer and indicate the importance of FATs function in some squamous cell carcinomas.

[Usefulness of ultrasonically activated scalpel for pulmonary resection in video-assisted thoracoscopic surgery].

We evaluated the reliability and efficacy of the ultrasonically activated scalpel (Harmonic Scalpel) for pulmonary resection in video-assisted thoracoscopic surgery (VATS). Fifty-six cases of primary or metastatic lung cancer with history of lobectomy or segmentectomy from July 2003 to June 2006 were investigated. The ultrasonically activated scalpel was used to separate aborted lobulation and segment in the surgery. The outcome of the operation using the ultrasonically activated scalpel revealed the mean operation time of 224.5 minutes and mean blood loss volume of 116.7 ml. The chest drainage catheter was removed at the postoperative day 3.4 and hospitalization lasted 10.4 days on average. By means of statistical analysis, no significant differences were noted when compared with the cases using surgical stapler to separate the lobules or segments of the lungs. Histopathological results showed destruction of alveolar structures and denaturation of cells at the cut surface of the resected lung through the use of the ultrasonically activated scalpel. This method resulted in good lung expansion and preservation of the residual lung volume. Furthermore, it prevented postoperative air leakage by appropriate treatment to the cut surfaces of the residual lung. Indeed, the method appears to be useful in the separation of lung tissues in severe aborted lobulation and segmentectomy by VATS.