Takayuki Sueta

Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein.

Eph receptor tyrosine kinases are considered candidate therapeutic targets in cancer, but they can exert opposing effects on cell growth. In the presence of its ligands, Eph receptor EphA2 suppresses signaling by other growth factor receptors, including ErbB, whereas ligand-independent activation of EphA2 augments ErbB signaling. To deploy EphA2-targeting drugs effectively in tumors, the anti-oncogenic ligand-dependent activation state of EphA2 must be discriminated from its oncogenic ligand-independent state. Because the molecular basis for the latter is little understood, we investigated how the activation state of EphA2 can be switched in tumor tissue. We found that ligand-binding domain of EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP, a powerful modulator of the pericellular environment in tumor cells. EphA2 immunostaining revealed a significant loss of the N-terminal portion of EphA2 in areas of tumor tissue that expressed MT1-MMP. Moreover, EphA2 phosphorylation patterns that signify ligand-independent activation were observed specifically in these areas of tumor tissue. Mechanistic experiments revealed that processing of EphA2 by MT1-MMP promoted ErbB signaling, anchorage-independent growth, and cell migration. Conversely, expression of a proteolysis-resistant mutant of EphA2 prevented tumorigenesis and metastasis of human tumor xenografts in mice. Overall, our results showed how the proteolytic state of EphA2 in tumors determines its effector function and influences its status as a candidate biomarker for targeted therapy.

Advantage of early induction of opioid to control pain induced by irradiation in head and neck cancer patients

OBJECTIVE Although radiotherapy is effective for head and neck cancer patients, the local pain evoked by the irradiation itself reduces food intake and frequently halts the treatment. Thus, pain control is an important problem in radiotherapy for head and neck cancer. We performed to examine whether early induction of low-dose, opioid from mild pain improves dietary and caloric intake, while reducing weight loss. METHODS The subjects were 43 patients who were hospitalized for head and neck cancer from 2004 to 2008. They were patients who underwent radiation treatment but those who did not undergo preoperative treatment. They were divided into two groups, depending on whether the pain was mild or moderate when an opioid was introduced (MILD and MODERATE, N=23 and 20, respectively). RESULTS The visual analog scale scores for pain were significantly lower in the MILD than in the MODERATE group at between 25 and 50 Gy. The amount of oxycodone used for pain was significantly lower in the MILD than the MODERATE group. A regular diet was maintained for significantly longer in the MILD group. Caloric intake was significantly higher in the MILD group at over 20 Gy. Weight loss was significantly lower in the MILD group at over 20 Gy. The incidence of side effects was equal in both groups. CONCLUSION Our results indicated that the introduction of opioids for mild pain during radiotherapy controls the level of pain, improving food intake in head and neck cancer patients.

Tumor budding and laminin5-γ2 in squamous cell carcinoma of the external auditory canal are associated with shorter survival

Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is rare, usually presents at an advanced stage, and is a more aggressive tumor with poor prognosis. The University of Pittsburgh TNM staging system commonly used in prognostication is not perfect, and more accurate biomarkers predicting prognosis are needed. Tumor budding is an established negative prognostic factor at the invasive front in colorectal cancer. Moreover, immunohistochemical studies showed that laminin 5-γ2 (Ln5-γ2) is expressed at the invasive front in tumor or tumor budding cells. We assessed the prognostic significance of tumor budding and Ln5-γ2 expression by performing Ln5-γ2 immunohistochemistry and evaluated the degree of tumor budding in pre-treatment biopsy specimens, and investigated their correlations to clinicopathological parameters in patients with SCC of the EAC. Patients whose tumors had high budding grade and Ln5-γ2 expression had significantly shorter survival times. Budding grade was significantly correlated with Ln5-γ2 expression. Multivariate analysis revealed that high budding grade predicted poorer prognosis regardless of disease stage. Our results suggested that budding grade and Ln5-γ2 expression can be used as indicators of poor prognosis in patients with SCC of the EAC.

Severe intraoperative bleeding from a site on the displaced ophthalmic artery: A case report

Severe intraoperative bleeding from a site on the displaced ophthalmic artery : A case report : Takayuki Sueta1), Souta Umeno1), Yoshikazu Sugiyama1), Tetsuko Ueno1), Tsutomu Fukuzaki1), Takashi Nakagawa1), Kenji Fukuda2) and Toshio Higashi2). 1)Department of Otorhinolaryngology, School of Medicine, Fukuoka University, Fukuoka, 2)Department of Neurosurgery, School of Medicine, Fukuoka University, Fukuoka

Gastric metastasis from salivary duct carcinoma mimicking primary gastric cancer.

Highlights • In salivary duct carcinoma, distant metastases are frequent.• The most frequent sites involved (in the order of occurrence) are the lung, bone, and brain, whereas the stomach is an unusual site for metastases.• We present a rare case of surgically resected gastric metastasis originating from the salivary duct carcinoma.