The relationship between overexpression of glypican (GPC)-3 that is specific for hepatocellular carcinoma (HCC) and the prognosis has not yet been clarified. We attempted to determine the expression profile of GPC3 in association with the clinicopathological factors by immunohistochemical analysis in HCC patients and investigated the potential prognostic value of GPC3 by comparing the survival rate between the GPC3-positive and GPC3-negative HCC patients. Primary HCC tissue samples (n = 107) obtained from patients who had undergone hepatectomy between 2000 and 2001 were analyzed. GPC3 expression was less frequently observed in welldifferentiated HCC than in moderately and poorly differentiated HCC, the difference in the frequency being statistically significant. GPC3-positive HCC patients had a significantly lower 5-year survival rate than the GPC3-negative HCC patients (54.5 vs 87.7%, P = 0.031). Among 80 of the 107 (74.6%) patients with initial treatment who underwent hepatectomy, none of GPC3-negative HCC patients (n = 16, 20.0%) died during the follow-up period. No deaths were noted in the GPC3-negative HCC patients among the 71 (88.7%) patients with moderately and poorly differentiated HCC. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for the overall survival. We showed that GPC3 expression is correlated with a poor prognosis in HCC patients. (Cancer Sci 2009; 100: 1403-1407) H epatocellular carcinoma (HCC) is one of the most common malignancies and is ranked as the third most common cause of cancer-related death worldwide. HCC is generally associated with a poor prognosis, the 5-year survival rate after surgery has been reported to be as low as 25-39%, and systemic therapy with cytotoxic agents provides only marginal benefit.(1) Even in those patients in whom the tumor has been successfully removed, the 2-year recurrence rate can be as high as 50%. (2,3) Several clinicopathological factors including poor levels of differentiation of the cancer cells, large size of the tumor, portal venous invasion, and intrahepatic metastasis have been shown to contribute to the poor prognosis in patients of HCC. Despite the critical need for better methods for the diagnosis and treatment of HCC, the mechanisms underlying the development of HCC remain unclear.Glypican (GPC)-3 was discovered as a potential serological and histochemical marker that is specific for HCC. GPC3 is a member of the glypican family and belongs to a group of heparan sulfate proteoglycans bound to the outer surface of the cell membrane through a glycosylphosphatidylinositol anchor. (4) In mammals, this family comprises six members, GPC1 to GPC6. GPC are released from the cell surface by a lipase called Notum to regulate the signaling of Wnts, Hedgehogs, fibroblast growth factors, and bone morphogenetic proteins.(5-9) Depending on the context, their functions exerted may either be stimulatory or inhibitory through these pathways. GPC3 has been detected in the placenta and fetal liver, but not in othe...

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers.

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A 13-year-old spayed mixed-breed dog was diagnosed with a gastrointestinal stromal tumor (GIST) after histopathological examination of an abdominal mass. Five months after surgical resection of the tumor, we detected the recurrence of GIST with multiple disseminated abdominal lesions. A sequence analysis of cDNA obtained from a biopsy of the recurrent tumors revealed a mutation within exon 9 of the c-kit gene (1523A>T, Asn508Ile), which has been shown to cause ligand-independent phosphorylation of the KIT protein in GISTs and canine mast cell tumors (MCTs). Upon detection of the recurrent tumors, we initiated treatment with imatinib mesylate (10 mg/kg, q 24 hr). After 2 months, the dog achieved complete remission. Our findings indicate that canine GIST, and possibly MCT, may be responsive to molecular-targeted therapy.