Purpose: The carcinoembryonic antigen glypican-3 (GPC3) is an ideal target of anticancer immunotherapy against hepatocellular carcinoma (HCC). In this nonrandomized, open-label, phase I clinical trial, we analyzed the safety and efficacy of GPC3 peptide vaccination in patients with advanced HCC.Experimental Design: Thirty-three patients with advanced HCC underwent GPC3 peptide vaccination (intradermal injections on days 1, 15, and 29 with dose escalation). The primary endpoint was the safety of GPC3 peptide vaccination. The secondary endpoints were immune response, as measured by IFN-g ELISPOT assay, and the clinical outcomes tumor response, time to tumor progression, and overall survival (OS).Results: GPC3 vaccination was well-tolerated. One patient showed a partial response, and 19 patients showed stable disease 2 months after initiation of treatment. Four of the 19 patients with stable disease had tumor necrosis or regression that did not meet the criteria for a partial response. Levels of the tumor markers a-fetoprotein and/or des-g-carboxy prothrombin temporarily decreased in nine patients. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 30 patients. Furthermore, GPC3-specific CTL frequency after vaccination correlated with OS. OS was significantly longer in patients with high GPC3-specific CTL frequencies (N ¼ 15) than in those with low frequencies (N ¼ 18; P ¼ 0.033).Conclusions: GPC3-derived peptide vaccination was well-tolerated, and measurable immune responses and antitumor efficacy were noted. This is the first study to show that peptide-specific CTL frequency can be a predictive marker of OS in patients with HCC receiving peptide vaccination.

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...

Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm.Conclusions: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC.Clinical Trial number: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index. htm), number UMIN000010667.

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Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed for an appropriate time when the lesion is small without the presence of mural nodules.

These findings suggest that PDAC concomitant with IPMN and PDAC derived from IPMN may have more favorable biological behaviors or be diagnosed earlier than ordinary PDAC.

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The onset symptom of patients with pancreatic carcinoma closely correlates with prognosis.