Glut-1 glucose transporter expression in esophageal squamous cell carcinoma is associated with tumor aggressiveness

BACKGROUND: Glucose transporter (Glut) proteins, which are membrane proteins responsible for the transport of glucose across cellular membranes, have six forms. To further elucidate the role of Glut-1 expression in esophageal squamous cell carcinoma, we examined the expression of Glut-1 protein immunohistochemically. MATERIALS AND METHODS: Immunohistochemical expression of Glut-1 was examined in surgically resected tissues from 95 patients with esophageal squamous cell carcinoma. RESULTS: Of the 95 esophageal carcinomas, 91 (95.8%) had some Glut-1 immunostaining in the membranes of the cancer cells. Positive staining (> 30% of cancer cells showing Glut-1 expression) was observed in 49 (51.6%) of the cases. Comparison of Glut-1 expression and clinicopathological characteristics in the 95 patients with esophageal cancer revealed significant associations between Glut-1 expression and tumor status (p < 0.001), lymph node status (p < 0.05), metastatic status (p < 0.01), and pathological stage (p < 0.001). The survival rates of patients with Glut-1-positive tumors were significantly lower than those of patients with Glut-1-negative tumors (log-rank p < 0.05). CONCLUSION: In conclusion, the level of Glut-1 expression may be a useful marker that can provide information on tumor aggressiveness and prognosis in patients with esophageal squamous cell carcinoma.     

Breast-conserving treatment after neoadjuvant chemotherapy in large breast cancer

Several recent trials have demonstrated that neoadjuvant chemotherapy can allow more patients to successfully undergo breast-conserving treatment (BCT), and does not confer a survival disadvantage compared with standard adjuvant chemotherapy. In addition, the pathological response of primary breast tumors to neoadjuvant chemotherapy appears to be a surrogate marker for patient outcome. In our series, during the period from May 1995 to December 2000, 86 patients with tumors between 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. The margin positive rate was 14.1%(9/64), similar to the rate after BCT for early-stage breast cancers, the largest diameter of which was smaller than 3 cm. At a median follow-up of 30 months, only 3 patients in the BCT group have developed local recurrence; the local recurrence rate appears to be comparable to that after BCT for early stage breast cancers. Long term follow-up is required, however, to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.     

Clinical significance of nm23 expression and chromosome 17 numerical aberrations in primary gastric cancer

The metastasis suppressor gene nm23 located on chromosome 17 might be one of the targets in deletions of chromosome 17. In this study, we analyzed the expression of nm23 and chromosome 17 aberrations in gastric cancer and assessed their clinicopathological and prognostic significance. In 103 gastric cancer patients, we examined nm23 expression by immunohistochemistry and detected chromosome 17 aberrations by fluorescence in situ hybridization. There was a significant difference in the expression of nm23 among differentiated histologic types (well > moderately > poorly) (p < 0.01). Negative expression of nm23 correlated with depth of invasion (p < 0.01), lymph node metastasis (p < 0.05), lymphatic invasion (p < 0.05), venous invasion (p < 0.05), poor prognosis (p < 0.05), and chromosome 17 loss (p < 0.05). Chromosome 17 aberrations broadly correlated with clinicopathological variables and were associated with poor prognosis (p < 0.05). Univariate analyses identified nm23 (p < 0.05), chromosome 17 aberrations (p < 0.05), tumor size (p < 0.01), depth of invasion (p < 0.0001), lymph node metastasis (P < 0.001), hepatic metastasis (p < 0.01), peritoneal dissemination (p < 0.01), and lymphatic invasion (p < 0.01) as significant prognostic factors. Multivariate analysis showed that expression of nm23 and chromosome 17 aberrations were not independent prognostic indicators. Our results indicate that negative expression of nm23 and chromosome 17 numerical aberrations correlate with tumor progression and poor prognosis but are not independent prognostic indicators.     

Evaluation of preoperative simultaneous radiochemotherapy combined with carboplatin and tegafur.uracil

We performed preoperative radiochemotherapy including local irradiation with total dose of 40 Gy along with concomitant combination chemotherapy with carboplatin and tegafur.uracil for 11 head and neck squamous cell carcinomas and evaluated the clinical and histopathological effects as well as the side effects. Seventy-three percent of patients accomplished significant clinical effects equal to or more than PR and significant histopathological effects in surgically resected tissues. Side effects were seen in only one patient with severe hypoleukocytemia, no patients with renal dysfunction, and 34% of patients with severe oral mucositis. These results suggest that our radiochemotherapy may be useful for preoperative treatment for patients with locally advanced head and neck squamous cell carcinomas.     

Increased expression of sialyl Lewis(x) antigen in penetrating growth type A early gastric cancer

Early gastric cancer can be divided morphologically into two categories, penetrating growth type-A (Pen-A type) and other growth types (non-Pen-A types). Sialyl Lewis(x) antigen has been demonstrated to play an important role in tumor metastasis by serving as a functional ligand in the cell adhesion system. The aim of this study is to ascertain whether or not sialyl Le(x) antigen expression correlates with tumor growth patterns of early gastric carcinoma. An immunohistochemical assay was performed using monoclonal antibody CSLEX1 in 12 Pen-A type and 79 non-Pen-A type cancers. Scoring was based on the percentage of immunoreactive cells: negative, low expression (< or = 25%), and high expression (> 25%). Lymph node metastasis was found more frequently in Pen-A type than non-Pen-A type cancers (P=0.0004). Furthermore, sialyl Le(x) antigen high expression was detected more often in Pen-A type cancers (7 out of 12; 58.3%) than non-Pen-A type cancers (13 out of 79; 16.5%) (P=0.0036). Multivariate logistic regression analysis showed that these variables are related independently to the Pen-A type and the non-Pen-A type tumor growth patterns. These data suggest that the difference in sialyl Le(x) antigen expression between the Pen-A type and non-Pen-A type tumor growth patterns of early gastric cancer may, at least partially, reflect different biological behavior during tumor progression.     

Estrogen induces a rapid increase of calcium-calmodulin-dependent protein kinase II activity in the hippocampus

Molecular genetics experiments using gene targeting and transgenic technology demonstrated the importance of -calcium-calmodulin-dependent protein kinase II (CaMKII) in long-term potentiation (LTP) and memory. Little information is available though on how CaMKII activity may be regulated in vivo. We show that estradiol benzoate activates CaMKII in a dose and time-dependent manner in mouse hippocampus after 30 min stimulation. The effect of estrogen is via a very rapid nongenomic mechanism that is blocked in vitro in hippocampal primary neurons by the pure estrogen receptor antagonist, ICI 182,780. These results suggest that estrogen action in the hippocampus is linked to CaMKII activation.     

Biodirected epitaxial nanodeposition of polymers on oriented macromolecular templates

Biodirected epitaxial nanodeposition of polymers was achieved on a template with an oriented molecular surface. Acetobacter xylinum synthesized a ribbon of cellulose I microfibrils onto a fixed, nematic ordered substrate of glucan chains with unique surface characteristics. The substrate directed the orientation of the motion due to the inverse force of the secretion during biosynthesis, and the microfibrils were aligned along the orientation of the molecular template. Using real-time video analysis, the patterns and rates of deposition were elucidated. Field emission scanning electron microscopy revealed that a strong molecular interaction allowed for the deposition of nascent biosynthesized 3.5-nm cellulose microfibrils with inter-microfibrillar spacings of 7-8 nm on the surface of the template. The cellulose was deposited parallel to the molecular orientation of the template. Directed cellulose synthesis and ordered movement of cells were observed only by using a nematic ordered substrate made from cellulose, and not from ordered crystalline cellulose substrates or ordered cellulose-related synthetic polymers such as polyvinyl alcohol. This unique relationship between directed biosynthesis and the ordered fabrication from the nano to the micro scales could lead to new methodologies for the design of functional materials with desired nanostructures.