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A 33-year-old previously healthy man injured his gums and subsequently developed dyspnea and fever. A chest X-ray showed nodules and infiltrates in both lungs, and the patient was initially diagnosed with pneumonia and administered meropenem hydrate, although his symptoms did not improve. A blood culture identified Fusobacterium necrophorum, and thrombophlebitis in the internal jugular vein of the neck was observed on computed tomography and ultrasound scans. We replaced the meropenem with clindamycin, sulbactam/ampicillin and metronidazole, and the patient's symptoms improved.

The KIT, epidermal growth factor receptor (EGFR) and HER-2 oncoproteins have tyrosine kinase activity and are molecular targets in human cancer therapy. To clarify the significance of KIT, EGFR, and HER-2 in undifferentiated thyroid carcinoma (UTC), the expression of these receptors and tyrosine phosphorylation was examined immunohistochemically in resected cases of UTC and papillary thyroid carcinoma (PTC). KIT, EGFR, and HER-2 were also examined at the protein and mRNA levels in five UTC cell lines. KIT expression (1+), EGFR overexpression (2+/3+), HER-2 expression (1+), and tyrosine phosphorylation were detected immunohistochemically in 40%, 70%, 10%, and 50% of the 10 UTC. In 20 PTC, KIT, EGFR, and HER-2 were not detected, but tyrosine phosphorylation was detected in 25% of cases. In the five UTC cell lines, KIT expression (1+), EGFR overexpression (3+), HER-2 expression (1+), and tyrosine phosphorylation were detected immunocytochemically in 60%, 100%, 20%, and 40%, respectively. Western blot analysis did not detect KIT expression, but did detect EGFR and HER-2 expression in all five cell lines. Real-time polymerase chain reaction detected KIT mRNA in two of the cell lines (40%), EGFR in five (100%), and HER-2 in three (60%). The present findings suggest that EGFR overexpression was involved in the proliferation and development of UTC and was frequently accompanied by tyrosine phosphorylation. Expression of KIT and HER-2 appeared to be weak but significant, suggesting a possible role in the development of UTC. Molecular therapies targeting KIT, EGFR, HER-2, and/or tyrosine phosphorylation might be indicated for UTC.

cIAP-1, an apoptosis inhibiting protein, has been suggested to play important roles in the development of cervical and esophageal squamous cell carcinomas (SCCs). In order to clarify the subcellular localization of cIAP-1 and to investigate its clinicopathological significance in head and neck SCCs (HNSCCs), we examined cIAP-1 expression in four oral SCC cell lines by immunocytochemistry and Western blot. Expressions of nuclear and cytoplasmic cIAP-1, caspase-3, and Smac/DIABLO were also examined immunohistochemically in 57 cases of the HNSCCs. cIAP-1 expression was detected in HSC-2, HSC-3, and HSC-4 cells by immunohistochemistry and Western blot. In HSC-2 and HSC-4 cells, cIAP-1 was detected in both the nuclear and cytoplasmic fractions. Nuclear cIAP-1 expression was positive in 17 (30%) of HNSCCs, was correlated with lymph node metastasis (P=0.020) and advanced disease stage (P=0.032), and tended to be correlated with poor patient prognosis (P=0.059). Cytoplasmic cIAP-1 expression showed similar but weaker clinicopathological correlations. Nuclear cIAP-1 expression was inversely correlated with caspase-3 expression, but was correlated with Smac/DIABLO expression. Nuclear cIAP-1 expression appears to be a useful marker for predicting poor patient prognosis in HNSCCs, and may play roles in HNSCCs through the signaling pathway mediated by Smac/DIABLO and caspase-3.

Background: Our objective was to examine the utility of endoscopic biopsy specimens in judging the status of epidermal growth factor receptor (EGFR) and c-erbB-2 genes and proteins in the entire tumor. Methods: Endoscopicbiopsy specimens and specimens of whole representative cut surfaces of corresponding surgically resected tumors were obtained from 14 patients with gastric carcinoma, and immunohistochemistry and fluorescence in situ hybridization were then performed to determine the protein expression and gene amplification profiles, respectively, of EGFR and c-erbB-2 in these biopsy and surgical specimens. Results: Among the eight endoscopic biopsy specimens obtained from three gastric carcinomas in which EGFR protein overexpression and gene amplification were judged to be positive in the corresponding surgically resected tissue specimens, EGFR overexpression was detected in three specimens (38%), but EGFR amplification was not detected (0%). Among the 19 endoscopic biopsy specimens obtained from five gastric carcinomas in which c-erbB-2 protein overexpression and gene amplification were judged to be positive in the corresponding surgically resected tissue specimens, c-erbB-2 overexpression and amplification (c-erbB-2/CEP17 ratio) were detected in 14 (74%) and16 (84%) specimens, respectively. All three cases with EGFR overexpression and all five cases with c-erbB-2 overexpression showed intratumor heterogeneity with regard to their EGFR and c-erbB-2 status, respectively. Conclusions: The c-erbB-2 status could be adequately assessed not only by examining surgically resected materials, but also by examining multiple endoscopic biopsy specimens. On the other hand, to assess the EGFR status accurately, the use of surgically resected samples appeared to be more reliable than the use of multiple endoscopic biopsy samples.

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF-1alpha, a subunit of HIF-1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF-1alpha expression in esophageal squamous cell carcinoma. In 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF-1alpha protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF-1alpha messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase-polymerase chain reaction [RT-PCR]). A positive HIF-1alpha protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the 'high score' group for HIF-1alpha protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF-1alpha protein was found to have a significant effect on disease-free survival rate in our univariate analysis, but no effect on overall survival rate. In RT-PCR, HIF-1alpha mRNA scores correlated significantly with scores for HIF-1alpha protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF-1alpha protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma.