Expression level of valosin-containing protein is strongly associated with progression and prognosis of gastric carcinoma.

PURPOSE: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined. PATIENTS AND METHODS: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. RESULTS: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification. CONCLUSION: The prognostic significance of VCP expression level in GC was demonstrated.     

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.     

Reduced MLH1 expression after chemotherapy is an indicator for poor prognosis in esophageal cancers.

PURPOSE: Loss of function or expression of the mismatch repair gene MLH1 has been implicated in experimentally acquired resistance to cisplatin (CDDP) and other anticancer agents. The clinical significance of MLH1 expression was evaluated in advanced thoracic squamous cell carcinoma of the esophagus (ESCC) treated by neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: We investigated MLH1 and P53 expression by immunohistochemistry in the surgical specimens of 107 patients who had undergone preoperative chemotherapy using CDDP along with 5-FU and ADM. These findings were correlated with the clinical outcome for this treatment. Biopsy samples before chemotherapy in 20 of these patients, and another 43 surgical specimens without chemotherapy, were also examined as control samples. RESULTS: In surgical specimens of ESCC, low MLH1 expression was not frequent without chemotherapy, whereas it was commonly observed after chemotherapy (14 versus 37%, P = 0.0057). Comparison between samples before and after chemotherapy revealed that MLH1 expression was unchanged during chemotherapy in 12 of 20 patients (60%) but was from high to low in 8 of 20 patients (40%). In the surgical specimen after neoadjuvant chemotherapy, MLH1 expression was not correlated with any clinicopathological factors, including the response to chemotherapy. However, low MLH1 showed poorer prognosis than high MLH1 (5-year survival 40.6 versus 19.3%, P = 0.0393), and in multivariate analysis, MLH1 was an independent prognostic factor for this multimodal treatment, following lymph node metastasis and clinical response to chemotherapy. Positive p53 expression, which was not affected by chemotherapy, was weakly associated with a poor response and clinical outcome, although this trend was not significant. CONCLUSIONS: In advanced ESCC, expression of MLH1 is reduced during CDDP-based chemotherapy, and this may partly account for poor postoperative survival.     

Triggers of hair cell regeneration in the avian inner ear

We performed an in vitro study in order to determine possible triggers of hair cell regeneration in the chick basilar papilla following degeneration. We compared the response of sensory epithelium damaged by collagenase treatment with that damaged by acoustic trauma. The former exhibited no proliferative activity, but the latter did. The basilar papillae damaged by acoustic trauma could have proliferating activity in medium containing fetal bovine serum (FBS) or epidermal growth factor (EGF) but not in the medium without FBS or EGF. These findings indicate that regeneration of basilar papillae depends on the manner of cell death and that FBS or EGF is required for regeneration.     

A Question and Answer E-Mail System for Responding to Query from the General Public with Which the System Manager Can Identify Delayed Replies

We constructed a question and answer system for direct delivery of E-mail queries from the general public to the proper hospital representative and with which the system administrator can monitor E-mail replies. The system consists of two sub-systems; one is an E-mail questionnaire sub-system that automatically delivers E-mail queries to the proper person and an E-mail reply monitor sub-system with which the system administrator can monitor the E-mail replies. The monitor system compares the origin address of the E-mail reply and the destination address on a questionnaire filled out at the time the query is made. In a test of the system, 56 queries were received in 31 days, with 37 replied to. The interval from receipt of an E-mail query to reply was calculated. Nineteen replies were submitted within 2 days.     

(+)-cis-ε-Viniferin的结构确证

用光化学沟通方法确证了从葡萄科植物蘡薁Vitis thunbergii(Vitaceae)中分离得到的( )-cis-ε-viniferin的结构；并纠正了文献核磁共振氢谱(^1H-NMR)数据。     

Uptake of99mTc-tetrofosmin,99mTc-MIBI and201TI in malignant thymoma

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.     

Hand-assisted laparoscopic surgery for a large gastrointestinal stromal tumor of the stomach

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach that were successfully treated by hand-assisted laparoscopic surgery (HALS). Two patients, a 56-year-old woman and a 60-year-old man, were admitted to our department for the treatment of a large submucosal tumor of the stomach. After gastrointestinal endoscopy, ultrasonography, computed tomography, and magnetic resonance imaging, we suspected that the masses, measuring 7.0 cm and 8.0 cm in diameter, respectively, were GISTs in the stomach. However, preoperatively, we could not rule out the possibility of malignant neoplasms, because they had been bleeding or gradually growing. Hand-assisted laparoscopic wedge resection was safely performed for the diagnosis and treatment of the submucosal tumor of the stomach. The immunohistochemical diagnosis in both patients was GIST of the stomach with intermediate-grade malignancy. HALS may be a good indication for large GISTs of the stomach that are difficult to diagnose preoperatively, whether they are malignant or benign, because it is safe and minimally invasive, promoting rapid recovery.     

Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels.

PURPOSE: There are no available tumor markers detecting primary melanoma at an early stage. The identification of such serum markers would be of significant benefit for an early diagnosis of melanoma. We recently identified glypican-3 (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby, we focused out attention on secreted protein acidic and rich in cysteine (SPARC) overexpressed in melanoma as another candidate for tumor marker. EXPERIMENTAL DESIGN: Secreted SPARC protein was quantified using ELISA in the sera from 109 melanoma patients, five patients with large congenital melanocytic nevus, 61 age-matched healthy donors, and 13 disease-free patients after undergoing a surgical removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples and compared these markers for their diagnostic value. RESULTS: The serum SPARC concentrations in melanoma patients were greater than those in healthy donors (P = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the healthy donors, the serum SPARC was found to have increased in the sera of 36 of the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased SPARC levels were in stages 0 to II. The serum SPARC level decreased under the cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an early stage (0-II). CONCLUSIONS: SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage.