Significance of uterine corpus tumor invasion in early-stage cervical cancer.

OBJECTIVE: To examine characteristics and survival outcomes of women with surgically-treated cervical cancer exhibiting uterine corpus tumor invasion. METHODS: We utilized The Surveillance, Epidemiology, and End Results Program to identify cervical cancer patients who underwent hysterectomy between 1973 and 2003. Logistic regression models were used to identify risk factors for uterine corpus tumor invasion on multivariable analysis. Association of uterine corpus tumor invasion and cause-specific survival (CSS) from cervical cancer was examined with Cox proportional hazard regression models on multivariable analysis. RESULTS: We identified 837 (4.9%) cases of uterine corpus invasion and 16,237 (95.1%) cases of non-invasion. Median follow-up time was 14.0 years. There were 1642 deaths due to cervical cancer. Uterine corpus invasion was independently associated with older age, non-squamous histology, high-grade tumors, large tumor size, and nodal metastasis on multivariable analysis (all, P < 0.001). On univariable analysis, uterine corpus tumor invasion was significantly associated with decreased CSS compared to the non-invasion (5-year rates, 79.0% versus 94.5%, P < 0.001). After controlling for other significant prognostic factors, uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.45, 95% confidence interval 1.21-1.74). Among stage T1b cases (n = 6730), uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.95, 95%CI 1.47-2.60). Uterine corpus tumor invasion was significantly associated with decreased CSS in stage T1b1 disease (74.5% versus 90.7%, P < 0.001) and in stage T1b2 disease (67.0% versus 79.5%, P = 0.01). CONCLUSION: Uterine corpus tumor invasion is an independent prognostic factor for decreased survival of women with early-stage cervical cancer.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Impact of multimodal therapy on the survival of patients with newly diagnosed uterine carcinosarcoma.

PURPOSE: To investigate treatment outcomes of uterine carcinosarcoma (CS) patients who underwent complete surgical resection of all visible disease and platinum-based adjuvant chemotherapy (multimodal therapy). MATERIALS AND METHODS: The authors reviewed 127 uterine CS patients treated at this institution from 1990 to 2010. They operated 123 patients in clinical Stages 1-3, 97 of which underwent complete resection and systemic lymphadenectomy. RESULTS: A total of 97 patients (FIGO 2008: Stage 1 in 50 patients, Stage 2 in six, Stage 3 in 37, and Stage 4 in four) underwent surgical staging, 74 of which were administered five cycles (median) of platinum-based adjuvant chemotherapy. The median overall survival (OS) associated with multimodal therapy 50.6 months compared with 34.9 months incomplete multimodal therapy. After multimodal treatment, 32.9% (32/97) patients showed recurrence (24/32 hematogenous). CONCLUSION: Multimodal therapy increased survival among uterine CS patients, but the recurrence rate remained high. Further consideration of treatment options for uterine CS is required.

Improved delineation of arteries in the posterior fossa of the brain by model-based iterative reconstruction in volume-rendered 3D CT angiography.

BACKGROUND AND PURPOSE: Improved CTA delineation of arteries and unruptured aneurysms is clinically desired in the posterior fossa. We present a novel model-based iterative reconstruction that models system statistics and optics to improve CT image quality. We investigated the utility of MBIR for improving delineation of arteries in the posterior fossa on 3D brain CTA. MATERIALS AND METHODS: Using filtered back-projection with a standard kernel and MBIR, we reconstructed axial images of 0.625-mm thickness of 28 consecutive patients (14 men; mean age, 58.6 ± 14.6 years) who underwent 64-detector brain CTA. We placed regions of interest on the axial images, measured the mean CT value in the basilar artery and the value and SD in the pons and bilateral cerebellar hemispheres, and calculated the contrast-to-noise ratio of the brain arteries in the posterior fossa. Using volume-rendered CTA and a 4-point scale, 2 radiologists independently graded delineation of the BA, bilateral vertebral artery, superior cerebellar artery, and anterior and posterior inferior cerebellar arteries. We compared the results between FBP and MBIR by using paired t and Wilcoxon signed-rank tests. RESULTS: Compared with FBP, MBIR significantly improved the contrast-to-noise ratio (P < .0001) and subjective delineation of all arteries in the posterior fossa except the BA (VA, SCA, AICA, and PICA; P < .05 for all). The mean visual score by MBIR was 3.0 or higher for all those arteries except the AICA assessed by reader 1 (2.6 ± 0.7). CONCLUSIONS: With 3D brain CTA, contrast-to-noise ratio and arterial delineation of the VA, SCA, AICA, and PICA in the posterior fossa are better with MBIR than FBP.

[Rib-originated fibrous dysplasia: report of a case].

The incidence of fibrous dysplasia (FD) is not frequent in the case of benign bone tumors of the chest wall, and differential diagnosis between FD and the malignancy on the basis of imaging findings is difficult. We report a case of a painful FD lesion (size, 9×8 cm) that originated from the 5th rib of a 52-year-old man and was surgically resected. His symptoms improved after the operation. Painful and large FD lesions should be resected because of a difficulty in differential diagnosis from malignant tumors.

Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of locoregional MMC injection therapy in patients with refractory esophageal strictures after ESD for SEC.

Active bleeding in acute subarachnoid hemorrhage observed by multiphase dynamic-enhanced CT.

BACKGROUND AND PURPOSE: Acute SAH is reportedly associated with rebleeding from aneurysms, and recent advances in imaging technology allow us to visualize active bleeding in SAH cases. This study aimed to retrospectively investigate the incidence and characteristics of active bleeding in patients with spontaneous SAH by using multiphase dynamic-enhanced CT. MATERIALS AND METHODS: We retrospectively surveyed a series of patients with SAH who underwent CTP with 18-phase dynamic enhancement and confirmed the presence of extravasated contrast medium in the source image. We compared clinical features between 2 groups of patients with and without extravasation. RESULTS: Active bleeding was observed with increasing enhancement in 25.5% (13/51) of patients. All patients with extravasation were in Claassen grade 3 or 4 and WFNS grades 3, 4, or 5. The other group without extravasation included patients in all grades. A significant difference was observed in Claassen grade, WFNS grade, and increase of hematomas in follow-up CT (P < .05, for each) between the 2 groups. All CTP results of patients with extravasation were obtained within 2 hours of the onset of symptoms of SAH (P < .05). There was no significant difference in mortality at 14 days between the 2 groups (P = .128). CONCLUSIONS: A high incidence of active bleeding (25.5%) was detected by multiphase dynamic-enhanced CT in patients with acute SAH. These results indicate that an awareness of active bleeding in patients with SAH has the potential to affect the treatment strategy.

Effects of up-titration of candesartan versus candesartan plus amlodipine on kidney function in type 2 diabetic patients with albuminuria.

In the present study, we tested the hypothesis that up-titrating the dose of an angiotensin receptor blocker (ARB) is superior to combined treatment with an ARB and a calcium channel blocker for the same degree of blood pressure (BP) reduction, with respect to urinary albumin excretion in diabetic patients treated with a standard dose of the ARB. Hypertensive patients with type 2 diabetes mellitus and albuminuria (≥30 mg g(-1) creatinine) were enroled in the study, and were either started on or switched to candesartan (8 mg per day) monotherapy. After a 12-week run-in period, baseline evaluations were performed and patients with BP ≥130/80 mm Hg were randomly assigned to receive either candesartan (12 mg per day) or candesartan (8 mg per day) plus amlodipine (2.5 mg per day) for a further 12 weeks. The primary end-point was a reduction in urinary albumin levels. Although there was no significant difference in the BP reduction between the two groups, the reduction in urinary albumin was greater in the up-titrated than the combination therapy group (-40±14% vs -9±38%, respectively; P<0.0001). Thus, up-titration of candesartan more effectively reduces urinary albumin excretion than combined candesartan plus amlodipine in hypertensive patients with diabetes for the same degree of BP reduction.

Lens exposure during brain scans using multidetector row CT scanners: methods for estimation of lens dose.

BACKGROUND AND PURPOSE: Some recent studies on radiation lens injuries have indicated much lower dose thresholds than specified by the current radiation protection guidelines. The purpose of this research was to measure the lens dose during brain CT scans with multidetector row CT and to assess methods for estimating the lens dose. MATERIALS AND METHODS: With 8 types of multidetector row CT scanners, both axial and helical scans were obtained for the head part of a human-shaped phantom by using normal clinical settings with the orbitomeatal line as the baseline. We measured the doses on both eyelids by using an RPLGD during whole-brain scans including the orbit with the starting point at the level of the inferior orbital rim. To assess the effect of the starting points on the lens doses, we measured the lens doses by using 2 other starting points for scanning (the orbitomeatal line and the superior orbital rim). RESULTS: The CTDIvols and the lens doses during whole-brain CT including the orbit were 50.9-113.3 mGy and 42.6-103.5 mGy, respectively. The ratios of lens dose to CTDIvol were 80.6%-103.4%. The lens doses decreased as the starting points were set more superiorly. The lens doses during scans from the superior orbital rim were 11.8%-20.9% of the doses during the scans from the inferior orbital rim. CONCLUSIONS: CTDIvol can be used to estimate the lens dose during whole-brain CT when the orbit is included in the scanning range.

Efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene combinations against Haemaphysalis longicornis ticks evaluated under in vitro and in vivo conditions.

Haemaphysalis longicornis is one of the most important ticks infesting a wide range of mammals including dogs in Japan. H. longicornis is recorded to be a vector of, for example, Babesia gibsoni. It was the aim of the study presented here to evaluate the efficacy of imidacloprid/permethrin and fipronil/(S)-methoprene against larval, nymphal and adult stages of H. longicornis under in vitro as well as in vivo conditions. In the in vitro part of the study, ticks showed avoidance behaviour to imidacloprid/permethrin-treated filter papers. The onset of acaricidal efficacy in the imidacloprid/permethrin group was recorded earlier than in the fipronil/(S)-methoprene group. In the in vivo experiment three beagles per group were treated with either imidacloprid/permethrin, fipronil/(S)-methoprene or left untreated. Each dog was infested with 30 adult female H. longicornis. Ticks were place on a shaved area of skin of the treated dogs and behaviour of the ticks was recorded as before. After 3 h all ticks were removed and placed in Petri dishes. Ticks were further examined until day 4 post-treatment (p.t.). All ticks recovered from the untreated dogs survived. At 4 h p.t. (1 h post-removal) 40 of the 90 ticks exposed to the imidacloprid/permethrin treatment and 25 of the 90 ticks in the fipronil/(S)-methoprene-treated group were found dead. At day 1 p.t., 61 ticks in the imidacloprid/permethrin- and 81 ticks in the fipronil/(S)-methoprene-treated group were recorded dead. At the final examination day 4 p.t., all 90 ticks were found dead in the imidacloprid/permethrin group, while five ticks remained alive in the fipronil/(S)-methoprene group.

Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot study.

BACKGROUND AND STUDY AIMS: A newly developed narrow-band imaging (NBI) technique, in which modified optical filters were used in the light source of a video endoscope system, was applied during colonoscopy in a clinical setting. This pilot study evaluated the clinical feasibility of the NBI system for evaluating colorectal lesions. PATIENTS AND METHODS: A total of 43 colorectal lesions in 34 patients were included in the study. The quality of visualization of colorectal lesions and the accuracy of differentiation between neoplastic and non-neoplastic lesions using the NBI system were evaluated in comparison with results from conventional colonoscopy and with chromoendoscopy. RESULTS: For pit pattern delineation, NBI was superior to conventional endoscopy (P < 0.001), but inferior to chromoendoscopy (P < 0.05). NBI achieved better visualization of the mucosal vascular network and of the hue of lesions than conventional endoscopy (P < 0.05). However there was no significant difference between NBI and chromoendoscopy in differentiating neoplastic from non-neoplastic lesions (both techniques had a sensitivity of 100 % and a specificity 75 %). This was better than the results of conventional colonoscopy (sensitivity 83 %, specificity 44 %; P < 0.05 for specificity). CONCLUSIONS: These results suggest that in the examination of colonic lesions the NBI system provides imaging features additional to those of both conventional endoscopy and chromoendoscopy. For distinguishing neoplasms from non-neoplastic lesions, NBI was equivalent to chromoendoscopy.

In-situ visualization and quantification of mineralization of cultured osteogenetic cells.

An osteoblastic cell line (HOS cells) produces a prominent osteoid matrix with mineralization. Fibroblasts, on the other hand, do not exhibit this mineralization. To evaluate the degree of mineralization, we added calcein to the culture medium and then observed the culture wells by using an image analyzer. The calcein uptake into the cell/matrix layer was detected in the HOS cells but not in the fibroblasts. The calcein uptake was also quantified in situ by using an image analyzer, which revealed high levels in the HOS cells, which correlated well with the calcium content of the mineralized matrix. Rat marrow cells were also cultured in media containing calcein, fetal bovine serum, beta-glycerophosphate, L-ascorbic acid 2-phosphate, and with or without dexamethasone. With the dexamethasone, the cells exhibited osteogenic differentiation that resulted in mineralized matrix formation after about 10 days. The matrix formation coincided with the appearance of calcein uptake into the cell/matrix layer, with the amount of calcein uptake increasing with time. By contrast, the culture without the dexamethasone did not exhibit matrix formation and the calcein uptake was negligible. In the case of both HOS cell and rat marrow cell cultures in vitro, calcein did not affect expressions of their alkaline phosphatase activity or osteocalcin production. Furthermore, histologic observation revealed that rat marrow cells subcultured with calcein could show osteogenic ability after in vivo implantation. These results suggest that the current method of detecting calcein uptake in a culture allows the monitoring of the osteogenic capacity of cultured cells, as well as the measurement of the amount of mineralization produced by the osteogenic cells. Given that osteogenic cultured cells/mineralized matrices are used in bone reconstruction surgery, the in situ monitoring method is invaluable in that it allows us to evaluate the osteogenic capacity of in vitro constructs.

Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation.

PURPOSE: The effects of the heat shock protein 90 (Hsp90) inhibitor geldanamycin (GA) were examined on the radiosensitivity and signal transduction pathways in human tumour cell lines. MATERIALS AND METHODS: Two human cell lines, SQ-5 and DLD-1, derived from lung carcinoma and colon adenocarcinoma, respectively, were incubated for 16 h at 37 degrees C in medium containing 0.2 microM GA. The cells were then irradiated with X-rays and incubated with GA for a further 8 h. Radiation sensitivity was determined by clonogenic assays and protein levels were examined by Western blotting. RESULTS: GA radiosensitized both cell lines, but potentiated X-ray sensitivity more in SQ-5 than in DLD-1 cells. It was found that GA depleted EGFR and ErbB-2 in DLD-1 cells and depleted only ErbB-2 in SQ-5 cells. GA also reduced the expression of Akt and phosphorylated Akt (pAkt) expression in SQ-5 cells. In addition, the ratio (%) of apoptotic cells and poly [ADP-ribose] polymerase cleavage increased in SQ-5 but not in DLD-1 cells after exposure to GA and X-ray irradiation. The findings suggest that GA enhances the radiation sensitivity of human tumour cells by inhibiting the EGFR signal transduction system and the Akt signalling pathway. CONCLUSION: Targeting Hsp90 with GA provides a promising experimental strategy for radiosensitization of carcinoma.

A morphologic study of Carpentier-Edwards pericardial xenografts in the mitral position exhibiting primary tissue failure in adults in comparison with Ionescu-Shiley pericardial xenografts.

OBJECTIVE: We sought to investigate the durability and mechanism of the Carpentier-Edwards pericardial xenograft in the mitral position in comparison with that of the Ionescu-Shiley pericardial xenograft. METHODS: A total of 284 patients who received the Ionescu-Shiley pericardial xenograft in the mitral position between 1980 and 1984 and 84 patients who received the Carpentier-Edwards pericardial xenograft in the mitral position between 1984 and 1999 were included in the study. The freedom from reoperation rates for both graft types were determined. For morphologic study, the pathologic findings of 23 valves of 123 explanted Ionescu-Shiley pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both were determined and compared with those of 20 explanted Carpentier-Edwards pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both. Each pathologic finding was graded and assigned a score. Both types were matched for age at reoperation (50-75 years) and duration of valve function (8-11 years). RESULTS: Freedom from reoperation caused by structural valve deterioration, nonstructural valve deterioration, or both was significantly better for Carpentier-Edwards pericardial xenografts than for Ionescu-Shiley pericardial xenografts at 8 years after the operation (Carpentier-Edwards pericardial xenografts: 91.3% vs Ionescu-Shiley pericardial xenografts: 71.9%, P =.0061), but it was similar for both types at 12 years (Carpentier-Edwards pericardial xenografts: 43.6% vs Ionescu-Shiley pericardial xenografts: 43.6%, P =.2865). No severe leaflet tears were seen among Carpentier-Edwards pericardial xenografts. The mean area percentage of tissue overgrowth was 15.3% in Carpentier-Edwards pericardial xenografts and 3.4% in Ionescu-Shiley pericardial xenografts (P =.0001). The mean calcification area percentage was 13.6% in Carpentier-Edwards pericardial xenografts and 31.5% in Ionescu-Shiley pericardial xenografts (P =.0001). CONCLUSIONS: Tissue overgrowth on the atrial surface, ventricular surface, or both was the cause of structural valve deterioration, nonstructural valve deterioration, or both of Carpentier-Edwards pericardial xenografts in adults. This was different from Ionescu-Shiley pericardial xenograft failure, which resulted from severe calcification and leaflet tears. Organized thrombi on cusps, in addition to valve design, may have contributed to such tissue overgrowth on Carpentier-Edwards pericardial xenografts.

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular matrix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfation-related genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P = 0.043, odds ratio = 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA.

Prognostic significance of carcinoembryonic antigen levels in peritoneal washes in patients with gastric cancer.

BACKGROUND: Peritoneal metastasis is the most frequent cause of death in patients with gastric cancer. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is considered to be of great value in predicting the peritoneal recurrence and accordingly in the prognosis in patients with gastric cancer. This study examined the clinical significance of intraoperative determination of carcinoembryonic antigen (CEA) levels in peritoneal washes (pCEA) in patients with gastric cancer. METHODS: CEA levels in peritoneal washes were correlated retrospectively with several clinicopathologic factors including clinical outcome in 56 patients with resectable gastric cancer. RESULTS: Among several clinicopathologic factors, the depth of tumor invasion significantly and independently correlated with pCEA levels as revealed by multivariate stepwise logistic regression analysis. A significant difference in overall survival rates was observed between pCEA-positive and pCEA-negative groups: 5-year survival rates were 95.7% in pCEA-negative and 20% in pCEA-positive patients (P <0.0001). Multivariate analysis indicated that pCEA level is a statistically significant independent prognostic factor for the survival of patients with gastric cancer, and is an important factor for predicting peritoneal recurrence. CONCLUSIONS: pCEA could be a potential predictor of a poor prognosis as well as peritoneal recurrence in patients with gastric cancer. We believe that this information could contribute to determining the optimal intraoperative and postoperative therapeutic plan including adjuvant chemotherapy of gastric cancer.

Identification of human CPI-17, an inhibitory phosphoprotein for myosin phosphatase.

CPI-17 is a phosphorylation-dependent inhibitor of myosin phosphatase. cDNA clones encoding CPI-17 were isolated from a human aorta library. Overlapping clones indicated two isoforms: CPI-17alpha was 147 residues and mass of 16.7 kDa; CPI-17beta (120 residues, mass 13.5 kDa) resulted from a deletion in the alpha-isoform of 27 residues, sequence 68-94. N-terminal 67 residues of all CPI-17 isoforms (human, porcine, rat and mouse) were highly conserved (for the human and porcine isoforms the identity was 91%). The presence of the two human isoforms was detected from cDNA sequences amplified by RT-PCR and by Western blots on human aorta. The cloned human CPI-17 gene indicated 4 coding exons and CPI-17beta was an alternative splice variant due to deletion of the second exon. FISH analysis located the human CPI-17 gene on chromosome 19q13.1.

Molecular cloning and analysis of the 5'-flanking region of the human MYPT1 gene.

We have cloned and sequenced a 5 kb genomic fragment in the 5'-flanking region of the human myosin phosphatase target subunit 1. The transcription initiation site (+1) was 268 bp upstream from the translation start site. In this promoter there are no canonical TATA or CAAT box elements but there is a high GC-rich sequence. Basal promoter activity was due to the GC-rich region that contained one Sp1 transcription factor binding site, thus demonstrating that the MYPT1 gene is a housekeeping gene. Luciferase reporter assays showed the presence of two regions for positive elements and one for a negative element.