Focal adhesion kinase (p125 FAK ; 'FAK') is a tyrosine kinase that is localised to cellular focal adhesions and is associated with a number of other proteins, such as integrin adhesion receptors. We performed an immunohistochemical analysis of FAK protein expression to determine the relationship between FAK overexpression and clinicopathological factors in oesophageal squamous cell carcinoma (ESCC). We examined tissue specimens that had been removed from 91 patients with thoracic oesophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin -biotin method. Seven human ESCC cell lines -TE-1, TE-2, TE-8, TE-13, TE-15, TT, and TTn -and one immortalized human keratinocyte cell line -HaCaT -were used in Western blot analysis. Immunostaining of FAK was seen in the cytoplasm of cancer cells, particularly in cells located in the invasive fronts of cancer nests. FAK overexpression was detected in 54 of the 91 patients (59.3%). Significant correlations were observed between FAK overexpression and cell differentiation (P ¼ 0.0057), depth of tumour invasion (P ¼ 0.0023), presence of regional lymph node metastasis (P ¼ 0.0097), number of lymph node metastases (P ¼ 0.0026), and disease stage (P ¼ 0.012). The survival rates of patients with FAK-overexpressing cancer were significantly lower than those of patients without FAK-overexpression cancer (P ¼ 0.006). The 5-year survival rate of patients without FAK overexpression was 69%, whereas that of patients with FAK overexpression was 38%. On Western blot analysis, FAK was expressed at a high level in TE-1, TE-8, TE-15, and TT cells, at a moderate level in TE-2 and TTn cells, and at a low level in TE13 and HaCaT cells. FAK phosphorylation at tyrosine 397 was demonstrated in proportion to the intensity of FAK in all cell lines except TE15 and HaCaT. In conclusion, FAK overexpression of ESCC was related to cell differentiation, tumour invasiveness, and lymph node metastasis. Consequently, patients with ESCC who had FAK overexpression had a poor prognosis.

In conclusion, FDG-PET may be used as a noninvasive diagnostic technique in assessing the aggressiveness of the tumor and the prognosis in patients with esophageal SCC. During the preoperative diagnostic procedures, the sensitivity, specificity, and accuracy of lymph node staging is higher with FDG-PET than with CT imaging. In view of the high specificity of FDG-PET, it also gives useful information to guide the choice of treatment of esophageal carcinoma.

BACKGROUNDThe purpose of the current study was to assess whether [18F]fluorodeoxyglucose positron emission tomography (FDG‐PET) provides incremental value (e.g., additional information on lymph node involvement or the presence of distant metastases) compared with computed tomography (CT) in patients with esophageal carcinoma.METHODSThe authors examined 149 consecutive patients with thoracic esophageal carcinoma. Eighty‐one patients underwent radical esophagectomy without pretreatment, 17 received chemoradiotherapy followed by surgery, 3 underwent endoscopic mucosal resection, and the remaining 48 patients received definitive radiotherapy and chemotherapy. The diagnostic accuracy of FDG‐PET and CT was evaluated at the time of diagnosis.RESULTSThe primary tumor was visualized using FDG‐PET in 119 (80%) of 149 patients. Regarding lymph node metastases, FDG‐PET had 32% sensitivity, 99% specificity, and 93% accuracy for individual lymph node group evaluation and 55% sensitivity, 90% specificity, and 72% accuracy for lymph node staging evaluation. PET exhibited incremental value over CT with regard to lymph node status in 14 of 98 patients who received surgery: 6 patients with negative CT findings were eventually shown to have lymph node metastases (i.e., they had positive PET findings and a positive reference standard [RS]); 6 patients with positive CT findings were shown not to have lymph node metastases (i.e., they had negative PET findings and a negative RS); and 2 patients were shown to have cervical lymph node metastases in addition to mediastinal or abdominal lymph node metastases. Among the remaining patients, PET showed incremental value over CT with regard to distant organ metastases in six patients. The overall incremental value of PET compared with CT with regard to staging accuracy was 14% (20 of 149 patients).CONCLUSIONSFDG‐PET provided incremental value over CT in the initial staging of esophageal carcinoma. At present, combined PET‐CT may be the most effective method available for the preoperative staging of esophageal tumors. Cancer 2005. © 2004 American Cancer Society.

Struggling with nature is certainly a familiar feeling to many of us. This particular metaphor began life, however, after another wrestling bout, in a striking classical allusion by Francis Bacon in 1605. We trace the evolution of the metaphor through the centuries and the way it has been invoked in opposition to science. Is it possible to experiment without intrusion?

Transforming growth factor-␤ (TGF-␤) regulates cell growth inhibition, and inactivation of the TGF-␤ signaling pathway contributes to tumor development. In our previous study, altered expression of TGF-␤, TGF-␤-specific receptors and Smad4 was shown to correlate with tumor progression in esophageal squamous cell carcinoma (SCC). These components, however, were maintained normally in some patients with esophageal SCC. In our study, the mechanism by which aggressive esophageal SCC maintains these components was investigated, with particular emphasis on the par-

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Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syndrome (ARDS). To examine the hypothesis that interleukin-6 (IL-6) contributes to PMN infiltration and lung damage in HS, we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3. Using semiquantitative RT-PCR, we found a striking increase in IL-6 mRNA levels only in resuscitated HS, with peak levels observed 1 h after initiation of resuscitation. Increased IL-6 protein expression was localized to bronchial and alveolar cells. Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA. In situ DNA binding assay determined Stat3 activation predominantly within alveoli. Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli, marked elevation of bronchoalveolar lavage cellularity, and increased wet-to-dry ratio. These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury, including ARDS after HS.

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