Characteristics of the magnetic resonance imaging findings of cervical gastric-type adenocarcinoma.

AIMS: This study identified the distinct magnetic resonance imaging findings of cervical gastric-type adenocarcinoma (GAS) that can help differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA) and reveal the radiologic-pathologic correlation. MATERIALS AND METHODS: All consecutive patients with cervical GAS treated at our hospital from November 2009 to August 2021 were included. The SCC and UEA cases were considered controls. Tumor location, tumor shape, presence and size of cysts, presence of uterine fluid, and apparent diffusion coefficient (ADC) were evaluated. RESULTS: Overall, 18 GAS, 55 SCC, and 23 UEA cases were evaluated. The tumor was located in the entire cervix in 13/18 GAS cases, whereas it was predominantly located in the lower cervix in 38/55 SCC cases and 14/23 UEA cases. Most GAS cases exhibited a diffuse infiltration growth pattern (17/18), whereas most SCC and UEA cases exhibited a mass-forming pattern (39/55 and 20/23, respectively). Moreover, the percentages of cases presenting microcysts or macrocysts and undergoing uterine fluid collection were significantly higher in the GAS group (14/18 and 13/18) than in the SCC and UEA groups. ADC was significantly higher in the GAS group than in the SCC group (1.092 × 10-3 vs. 0.819 × 10-3 mm2/s). CONCLUSION: This study revealed that GAS is characterized by tumor presence in the entire cervix, infiltrative growth pattern, intrauterine fluid collection, and frequent microcyst or macrocyst formation. Moreover, ADC was significantly higher in the GAS group than in the SCC group.

Nationwide investigation of Shiga toxin-producing Escherichia coli among cattle in Japan revealed the risk factors and potentially virulent subgroups.

A nationwide study of Shiga toxin-producing Escherichia coli (STEC) was performed to determine the prevalence, characteristics and risk factors for fecal shedding of STEC among cattle in Japan. Information on rearing practices was also collected to identify risk factors for fecal shedding of STEC. STEC was isolated from 24·1% of samples (133/551) collected from 59·1% of farms (65/110). Bayesian clustering using the virulence marker profiles of the isolates subdivided the isolates into four genetically distinct groups, two of which corresponded to eae- or saa-positive STEC, which can cause severe disease in human. Both STEC groups exhibited characteristic phylogeny and virulence marker profiles. It is noteworthy that the tellurite resistance gene was not detected in all saa-positive STEC isolates, suggesting that the standard isolation method using tellurite might lead to an underestimation of the prevalence of saa-positive STEC. A multivariate logistic regression model using epidemiological information revealed a significantly (P < 0·01) high odds ratio on STEC fecal shedding in tie-stall housing and a low odds ratio in flat feed box and mechanical ventilation. Information on isolate characteristics of the two major pathotypes and risk factors in rearing practices will facilitate the development of preventative measures for STEC fecal shedding from cattle.

Distribution of extended-spectrum cephalosporin resistance determinants in Salmonella enterica and Escherichia coli isolated from broilers in southern Japan.

This study was conducted to investigate the distribution and diversity of extended-spectrum cephalosporin (ESC) resistance determinants in Salmonella enterica and Escherichia coli obtained from the same cecal samples and to provide evidence of transmission of the resistance determinants among these bacteria in broiler farms in southern Japan. Salmonella enterica and E. coli were characterized by serotyping and multilocus sequence typing, respectively. An antimicrobial susceptibility test, plasmid analysis, and identification and localization of resistance genes were performed to determine the relatedness of ESC resistance determinants among the isolates. Of 48 flocks examined, 14 had S. enterica. In total, 57 S. enterica isolates were obtained, 45 of which showed ESC resistance. Extended-spectrum cephalosporin-resistant E. coli were also obtained from all of these ESC-resistant Salmonella-positive samples. ß-Lactamase genes, blaTEM-52 (38 isolates), blaCTX-M-14 (1 isolate), and blaCMY-2 (6 isolates), were carried by conjugative untypable or IncP plasmids detected in the S. enterica serovars Infantis and Manhattan. The ß-lactamase genes blaCTX-M-14 (3 isolates), blaCTX-M-15 (3 isolates), blaSHV-2 (1 isolate), blaSHV-12 (2 isolates), and blaCMY-2 (32 isolates) associated with IncI1-Iγ, IncFIB, IncFIC, IncK, IncB/O, and IncY plasmids were detected in E. coli co-isolates. Restriction mapping revealed similar plasmids in Salmonella Infantis and Salmonella Manhattan and in different sequence types of E. coli. Intraspecies transmission of plasmids was suggested within S. enterica and E. coli populations, whereas interspecies transmission was not observed. This study highlights the importance of plasmids as carriers of ESC resistance determinants.

Analysis of matrix metalloproteinase (MMP-8 and MMP-2) activity in gingival crevicular fluid from children with Down's syndrome.

BACKGROUND AND OBJECTIVE: High levels of colonization by periodontopathic bacteria and a high prevalence of chronic inflammatory periodontal disease have been reported in children with Down's syndrome. Matrix metalloproteinases (MMPs) are mediators of extracellular matrix degradation and remodelling, and are deeply involved in the course of periodontal disease. To clarify the relationship between Down's syndrome and periodontitis, we investigated levels of MMP-2 and MMP-8 in gingival crevicular fluid (GCF) and detection of periodontopathic bacteria from subgingival plaque. MATERIAL AND METHODS: Samples of GCF and plaque were isolated from central incisors. Levels of MMPs were evaluated by enzyme-linked immunosorbent assay, and periodontopathic bacteria were detected by polymerase chain reaction. RESULTS: Levels of MMP-2 and MMP-8 in Down's syndrome patients were higher than those in healthy control subjects. In the Down's syndrome group, increases in these MMPs were observed in GCF from patients with an oral hygiene index score of < 2 and in GCF from sites that were negative for bleeding on probing. The detection rate of periodontopathic bacteria in Down's syndrome patients was higher than that in the control subjects. Matrix metalloproteinase-2 levels in sites harbouring Porphyromonas gingivalis or Aggregatibacter (Actinobacillus) actinomycetemcomitans were lower than in those without these microorganisms. CONCLUSION: These results suggest an increase in MMP-2 and MMP-8 in Down's syndrome patients, regardless of whether inflammation of periodontal tissue is present or not.

Diagnostic Value of Model-Based Iterative Reconstruction Combined with a Metal Artifact Reduction Algorithm during CT of the Oral Cavity.

BACKGROUND AND PURPOSE: Metal artifacts reduce the quality of CT images and increase the difficulty of interpretation. This study compared the ability of model-based iterative reconstruction and hybrid iterative reconstruction to improve CT image quality in patients with metallic dental artifacts when both techniques were combined with a metal artifact reduction algorithm. MATERIALS AND METHODS: This retrospective clinical study included 40 patients (men, 31; women, 9; mean age, 62.9 ± 12.3 years) with oral and oropharyngeal cancer who had metallic dental fillings or implants and underwent contrast-enhanced ultra-high-resolution CT of the neck. Axial CT images were reconstructed using hybrid iterative reconstruction and model-based iterative reconstruction, and the metal artifact reduction algorithm was applied to all images. Finally, hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithm data were obtained. In the quantitative analysis, SDs were measured in ROIs over the apex of the tongue (metal artifacts) and nuchal muscle (no metal artifacts) and were used to calculate the metal artifact indexes. In a qualitative analysis, 3 radiologists blinded to the patients' conditions assessed the image-quality scores of metal artifact reduction and structural depictions. RESULTS: Hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithms yielded significantly different metal artifact indexes of 82.2 and 73.6, respectively (95% CI, 2.6-14.7; P < .01). The latter algorithms resulted in significant reduction in metal artifacts and significantly improved structural depictions(P < .01). CONCLUSIONS: Model-based iterative reconstruction + metal artifact reduction algorithms significantly reduced the artifacts and improved the image quality of structural depictions on neck CT images.

Bone Subtraction Iodine Imaging Using Area Detector CT for Evaluation of Skull Base Invasion by Nasopharyngeal Carcinoma.

BACKGROUND AND PURPOSE: Conventional CT has generally lower detectability of bone marrow invasion than MR imaging due to lower tissue contrast. The purpose of this study was to compare the diagnostic performance of conventional CT alone or in combination with bone subtraction iodine imaging using area detector CT for the evaluation of skull base invasion in patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: Forty-four consecutive patients who underwent contrast-enhanced CT using 320-row area detector CT and contrast-enhanced MR imaging for nasopharyngeal carcinoma staging between April 2012 and November 2017 were enrolled in this retrospective study. Bone subtraction iodine images were generated by subtracting pre- and postcontrast volume scans using a high-resolution deformable registration algorithm. Two blinded observers evaluated skull base invasion at multiple sites (sphenoid body, clivus, bilateral base of the pterygoid process, and petrous bone) using conventional CT images alone or in combination with bone subtraction iodine images. Examination of MR and CT images by an experienced neuroradiologist was the reference standard for evaluating sensitivity, specificity, and area under the receiver operating characteristic curve. RESULTS: Twenty-six patients (59%) showed skull base invasion at 84 sites on the reference standard. Conventional CT plus bone subtraction iodine images showed higher sensitivity (92.9% versus 78.6%, P = .02) and specificity (95.6% versus 86.1%, P = .01) than conventional CT images alone for evaluating skull base invasion. The area under the receiver operating characteristic curve for conventional CT plus bone subtraction iodine (0.98) was significantly larger (P < .001) than the area under the receiver operating characteristic curve for conventional CT alone (0.90). CONCLUSIONS: Conventional CT plus bone subtraction iodine performs more closely to the accuracy of combining CT and MR imaging compared with conventional CT alone.

Colonization pattern of periodontal bacteria in Japanese children and their mothers.

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine the time of infection by anaerobic gram-negative rods associated with periodontal disease, and to clarify their transmission from mother to child. MATERIAL AND METHODS: Seventy-eight Japanese children (including 10 siblings), aged from 3 to 9 years, and 68 mothers, were enrolled in this study. Colonization by 11 periodontal bacterial species was determined using polymerase chain reaction amplification of samples of subgingival plaque obtained from the children and their mothers. RESULTS: The detection rates of Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola increased in children after the age of 6 years. We found a high consistency in colonization by P. gingivalis, T. denticola, Prevotella intermedia and Prevotella nigrescens in 9 of the 10 siblings. The average number of bacterial species in plaque samples harboring Fusobacterium nucleatum and/or Fusobacterium periodonticum was significantly greater than in those without, in both children and mothers. Kappa statistical analysis revealed that the detection of Capnocytophaga gingivalis, Capnocytophaga ochracea, Campylobacter rectus and T. denticola in children was consistent with that in the mother. CONCLUSION: Periodontal bacterial colonization in Japanese children increased with age and was associated with F. nucleatum and/or periodonticum, and the bacterial flora in children was similar to that in their mothers.

VALIDATION OF MONTE CARLO DOSE CALCULATION FOR PAEDIATRIC CT EXAMINATIONS USING TUBE CURRENT MODULATION BASED ON IN-PHANTOM DOSIMETRY.

The aim of this study is to estimate tube current modulation (TCM) profiles in paediatric computed tomography (CT) examinations with a TCM scheme (Volume-EC) and evaluate the estimation accuracy of TCM profiles. Another aim is to validate organ doses calculated using Monte Carlo-based CT dosimetry software and estimated TCM profiles by comparing them with those measured using 5-year-old and 10-year-old anthropomorphic phantoms and radio-photoluminescence glass dosemeters. Dose calculations were performed by inputting detailed descriptions of a CT scanner, scan parameters and CT images of the phantoms into the software. Organ doses were evaluated from the calculated dose distribution images. Average relative differences (RDs) between the estimated and actual TCM profiles ranged from -3.6 to 5.6%. RDs between the calculated and measured organ doses ranged from -4.2 to 13.0% and -18.1 to 4.9% for 5-year-old and 10-year-old phantoms, respectively. These results validate dose calculations for paediatric CT scans using TCM.

Comparison of MR Imaging and Dual-Energy CT for the Evaluation of Cartilage Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: Dual-energy CT can distinguish iodine-enhanced tumors from nonossified cartilage and has been investigated for evaluating cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinomas. In this study, we compared the diagnostic accuracy of MR imaging and of a combination of weighted-average and iodine overlay dual-energy CT images in detecting cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinomas, in particular thyroid cartilage invasion. MATERIALS AND METHODS: Fifty-five consecutive patients who underwent 3T MR imaging and 128-slice dual-energy CT for preoperative initial staging of laryngeal or hypopharyngeal squamous cell carcinomas were included. Two blinded observers evaluated laryngeal cartilage invasion on MR imaging and dual-energy CT using a combination of weighted-average and iodine-overlay images. Pathologic findings of surgically resected specimens were used as the reference standard for evaluating sensitivity, specificity, and the areas under the receiver operating characteristic curve of both modalities for cartilage invasion by each type of cartilage and for all cartilages together. Sensitivity and specificity were compared using the McNemar test and generalized linear mixed models. RESULTS: Dual-energy CT showed higher specificity than MR imaging for diagnosing all cartilage together (84% for MR imaging versus 98% for dual-energy CT, P < .004) and for thyroid cartilage (64% versus 100%, P < .001), with a similar average area under the curve (0.94 versus 0.95, P = .70). The sensitivity did not differ significantly for all cartilages together (97% versus 81%, P = .16) and for thyroid cartilage (100% versus 89%, P = .50), though there was a trend toward increased sensitivity with MR imaging. CONCLUSIONS: Dual-energy CT showed higher specificity and acceptable sensitivity in diagnosing laryngeal cartilage invasion compared with MR imaging.

Solitary pulmonary granuloma caused by Mycobacterium avium-intracellulare complex.

OBJECTIVES: To analyse the clinical features and high resolution computed tomography (HRCT) findings of solitary pulmonary granulomas caused by the Mycobacterium avium-intracellulare (MAI) complex. METHODS: We retrospectively analysed a series of 73 consecutive patients with solitary pulmonary granuloma and negative sputum smear and culture results, in whom the diagnosis was established by histological examination of specimens obtained by partial pulmonary resection or lobectomy. We compared the clinical features and HRCT findings of the solitary pulmonary granulomas definitively diagnosed to be caused by the MAI complex with those of granulomas of other causes by univariate and multivariate analyses. RESULTS: In this study series of 24 patients with solitary pulmonary granuloma, the aetiological agent was established as being the MAI complex. According to the results of the multivariate analysis, 'female sex', 'pleural indentation' and 'lobulation' on the HRCT images were significantly associated with solitary pulmonary granuloma caused by the MAI complex. CONCLUSION: This study demonstrated several characteristics of solitary pulmonary granulomas caused by the MAI complex, and suggested that it might be a subtype of pulmonary MAI complex infection without the typical radiographic features of the infection.

Organ Dose Evaluations Based on Monte Carlo Simulation for CT Examinations Using Tube Current Modulation.

The aims of this study were to estimate tube current values for each X-ray projection angle used in adult chest computed tomography (CT) and abdomen-pelvis CT examinations with tube current modulation (TCM) and to validate organ doses determined using Monte Carlo (MC) simulations through comparisons with the doses measured using in-phantom dosimetry. For dose simulations, dose distribution images were obtained by inputting the geometry of a CT scanner, scan parameters including estimated TCM curves and CT images of an adult anthropomorphic phantom into MC simulation software. Organ doses were then determined from the dose distribution images. For dose measurements, organ doses were evaluated using radio-photoluminescence glass dosemeters located at various organ positions within the phantom. Relative differences between the simulated and measured organ doses were -2.5 to 11.0% and -1.5 to 10.5% for organs in chest and abdomen-pelvis CT scan ranges, respectively. Thus, the simulated and measured doses agreed well.

Centrosome abnormalities in pancreatic ductal carcinoma.

The centrosome plays an important role in microtubule nucleation and organization, ensuring the establishment of cell polarity and balanced chromosome segregation. Recent studies have suggested that the loss of cell polarity and/or chromosome missegregation (aneuploidy) in human malignant tumors could result from defects in centrosome function. Using immunofluorescence analysis with an antibody to gamma-tubulin (a well-characterized centrosomal component), we examined surgically resected human pancreatic tissues for centrosome abnormalities. The tissues included ductal carcinomas (n = 13), adenomas (n = 3), endocrine tumors (n = 3), chronic pancreatitis (n = 5), and normal pancreatic tissues (n = 12). We found that most (85%) carcinomas and some adenomas displayed abnormal centrosome profiles, characterized by an increase in size and number of centrosomes, and by their irregular distribution. In contrast, none of normal ductal and stromal tissues showed these abnormalities. These findings suggest that centrosome abnormalities may develop at a relatively early stage of pancreatic ductal carcinogenesis.

Adenovirus-mediated p53 gene transduction inhibits telomerase activity independent of its effects on cell cycle arrest and apoptosis in human pancreatic cancer cells.

Evidence for a relationship between overexpression of wild-type p53 and telomerase activity remains controversial. We investigated whether p53 gene transduction could cause telomerase inhibition in pancreatic cancer cell lines, focusing on the relation of transduction to growth arrest, cell cycle arrest, and apoptotic cell death. The cells were infected with recombinant adenovirus expressing wild-type p53 or p21WAF1 at a multiplicity of infection of 100 or were continuously exposed to 10 microM VP-16, which is well known to induce apoptosis. Adenovirus-mediated p53 gene transduction caused G1 cell cycle arrest, apoptosis, and resultant growth inhibition in MIA PaCa-2 cells; the cell number 2 days after infection was 50% of preinfection value, and 13% of the cells were dead. Moreover, the transduction resulted in complete depression of telomerase activity through down-regulation of hTERT mRNA expression. In contrast, p21WAF1 gene transduction only arrested cell growth and cell cycle at G1 phase, and VP-16 treatment inhibited cell growth with G2-M arrest and apoptosis; after treatment, the cell number was 73% of pretreatment, and 12% of the cells were dead. Neither p21WAF1 gene transduction nor VP-16 treatment caused telomerase inhibition. Similar results were obtained in two other pancreatic cancer cell lines, SUIT-2 and AsPC-1. Thus, our results demonstrate that the p53 gene transduction directly inhibits telomerase activity, independent of its effects on cell growth arrest, cell cycle arrest, and apoptosis.

Crystallographic Characterization of the DNA-Binding Domain of Interferon Regulatory Factor-2 Complexed with DNA.

Interferon regulatory factors (IRFs) are transcription factors for interferon-related genes, which manifest both antiviral and tumor-suppressor activities and regulate cell growth in response to DNA damage. For the transcription initiation of the interferon-beta gene, IRFs form a macromolecular assembly bound to the promoter DNA, referred to as an enhancesome, together with several other transcription factors and DNA-binding proteins. The three-dimensional structure of IRF-DNA complex would provide insights into the structure and function of the enhancesome. In this study, we crystallized the DNA-binding domain of interferon regulatory factor-2 complexed with a DNA fragment. The crystals reproducibly grew by the vapor diffusion technique with 2-methyl-pentanediol from solutions containing small detergents, such as n-octyl-beta-d-glucoside. Cryocrystallographic experiments showed that crystals belong to space group P212121 with a = 90.66 Å, b = 101.01 Å, c = 171.58 Å and diffract up to 2.8 Å resolution. The absorption measurements of a solution in which the crystals were dissolved indicate that the DNA-binding domain binds to the DNA as a dimer. The calculated values of the solvent contents suggest that the protein-DNA complexes form a multimer in the crystal. These features may reflect the association of the complexes in the enhancesome. Copyright 1998 Academic Press.

Resistance to cerebral ischemia in developing gerbils.

Two-, three-, four-, five-, and twelve-week-old gerbils were subjected to various periods of bilateral carotid occlusion (BCO). Rectal and cranial temperatures were maintained at 37 degrees C during BCO, and only rectal temperature was monitored for 30 min of reperfusion. Seven days after ischemia, animals were perfusion-fixed and the neuronal densities in the hippocampal CA1 subfields were counted. The extent of cerebral ischemia during BCO was evaluated with [14C]iodoantipyrine autoradiography. The rectal temperature spontaneously fell to 33-34 degrees C during reperfusion in 2-week-old gerbils, although animals over 3 weeks old presented postischemic hyperthermia. Two-week-old animals therefore were divided into three experimental groups: In one group (2-week-old group I) rectal temperature was not regulated during 30 min of reperfusion, while in the other two groups (2-week-old groups II and III) rectal temperature was regulated at 37 and 38 degrees C, respectively, during reperfusion. Five-minute BCO produced almost complete destruction of the CA1 neurons in 12-week-old animals. In contrast, most CA1 neurons survived 30 min of BCO in 2-week-old group I and 15 min of BCO in 2-week-old groups II and III. [14C]Iodoantipyrine autoradiography revealed that BCO produced severe forebrain ischemia in 2-week-old gerbils as well as in 12-week-old gerbils. These findings indicate that developing gerbils have a greater tolerance to cerebral ischemia and that such ischemic tolerance is not due to a collateral network between the vertebrobasilar and the carotid circulations previously reported to develop more abundantly in developing gerbils.

Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men.

BACKGROUND AND OBJECTIVES: Fluvoxamine, a selective serotonin reuptake inhibitor, is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by CYP1A2. Our objective was to study the potential pharmacokinetic interaction between fluvoxamine and mexiletine. METHODS: A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the one phase, 6 healthy Japanese men received an oral dose of 200 mg of mexiletine alone (study 1); in the other phase, the men received fluvoxamine (50 mg twice a day) for 7 days, and on the eighth day they received oral mexiletine (200 mg) and fluvoxamine concomitantly (study 2). The concentrations of mexiletine were measured with HPLC. RESULTS: The area under the concentration-time curve and serum peak concentration of mexiletine in study 2 were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus 6.70 +/- 3.21 microg x h/mL, P =.006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164 microg/mL, P =.008, respectively). CONCLUSION: The effect of fluvoxamine on the mexiletine disposition is comparatively large, and when mexiletine and fluvoxamine are coadministered careful monitoring of mexiletine is needed.

9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells.

There is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53.

Quantitative determination of apoptotic death in cultured human pancreatic cancer cells by propidium iodide and digitonin.

We present here the efficacy of an in vitro cytotoxicity assay which can measure rapidly both apoptotic dead cells and cell growth rate, quantitatively. Using a multi-well plate reader, the fluorescence intensity of propidium iodide (PI) corresponding to dead cells and to total cells after digitonin treatment were measured in cultured human pancreatic cancer cells following exposure to etoposide. The percentage of dead cells measured by this assay was well correlated to that determined by Trypan blue staining. Furthermore, the cell growth rate determined simultaneously was also correlated to the cell number counted directly using a microscope. We demonstrate that this method, which was originally established for evaluating necrosis, could be applied to measure apoptotic cell death. Taken together, this simple assay is useful for testing the efficacy of anti-cancer agents and for investigating the molecular mechanisms of apoptosis in the cultured cells.

Establishment of a new human pancreatic cancer cell line, NOR-P1, with high angiogenic activity and metastatic potential.

We present here a new cell line, NOR-P1, established from a metastatic subcutaneous tumor of a patient with pancreatic cancer. The cells show rapid growth in culture with a doubling time of 16 h and high migration activity. Genetic and molecular analyses revealed high telomerase activity and a mutation in the K-ras oncogene. Of particular interest, the cells express markedly elevated mRNA levels of angiogenic factors, vascular endothelial growth factor and platelet-derived growth factor, as well as other tumor growth-related factors. Subcutaneous transplantation of the NOR-P1 cells into nude mice formed solid, hemorrhagic tumors which were histologically diagnosed as adenocarcinoma with dense blood vessels and severe extravasation of blood. Furthermore, when NOR-P1 cell suspension was injected directly into the pancreas of nude mice, the cells grew rapidly to form intra-pancreatic tumors associated with liver metastases and peritoneal dissemination that resulted in cachexia and subsequent death. These properties suggest that NOR-P1 is an aggressive pancreatic cancer cell line with a high metastatic potential and may serve as a useful experimental model for studying tumor angiogenesis and metastasis of pancreatic cancer.