Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer.

BACKGROUND: Identification of tumour-associated antigens (TAAs) that induce cytotoxic T lymphocytes (CTLs) specific to cancer cells is critical for the development of anticancer immunotherapy. In this study, we aimed at identifying a novel TAA of pancreatic cancer for immunotherapy. METHODS: On the basis of the genome-wide cDNA microarray analysis, we focused on KIF20A (also known as RAB6KIFL/MKlp2) as a candidate TAA in pancreatic cancer cells. The HLA-A2 (A*02:01)-restricted CTL epitopes of KIF20A were identified using HLA-A2 transgenic mice (Tgm) and the peptides were examined to check whether they could generate human CTLs exhibiting cytotoxic responses against KIF20A(+), HLA-A2(+) tumour cells in vitro. RESULTS: KIF20A was overexpressed in pancreatic cancer and in some other malignancies, but not in their non-cancerous counterparts and many normal adult tissues. We found that KIF20A-2 (p12-20, LLSDDDVVV), KIF20A-8 (p809-817, CIAEQYHTV), and KIF20A-28 (p284-293, AQPDTAPLPV) peptides could induce HLA-A2-restricted CTLs in HLA-A2 Tgm without causing autoimmunity. Peptide-reactive human CTLs were generated from peripheral blood mononuclear cells of HLA-A2(+) healthy donors by in vitro stimulation with the three peptides, and those CTLs successfully exhibited cytotoxic responses to cancer cells expressing both KIF20A and HLA-A2. CONCLUSION: KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers.

Extraocular muscles in Graves ophthalmopathy: usefulness of T2 relaxation time measurements.

PURPOSE: To determine if T2 relaxation time measurements with magnetic resonance (MR) imaging in patients with Graves ophthalmopathy (GO) can predict response to therapy. MATERIALS AND METHODS: Studied were 84 patients with GO, 27 with Graves disease without ophthalmopathy (GD), and 12 control subjects without Graves disease. T2 times of extraocular muscles and retrobulbar fat tissue were measured. Twenty-five patients with GO were treated with systemic corticosteroids and retroorbital radiation therapy. RESULTS: T2 relaxation times of muscles in patients with GD were the same as those in controls but were longer in patients with GO (P < .05). T2 times of fat in all patients were the same as those of the controls. The predicted probability of response to treatment increased with increased mean T2 relaxation times of extraocular muscles prior to therapy. Of the 25 patients with combined therapy, only those with particularly prolonged T2 relaxation times showed impressive response. CONCLUSIONS: T2 relaxation time measurements with MR allow noninvasive detection of acute muscle inflammation and predict which patients with GO will likely benefit from antiinflammatory therapy.

Early and delayed imaging of Tc-99m HMPAO versus Tl-201 in benign and malignant thyroid tumors. Similar uptake but different retention.

The authors performed both Tc-99m HMPAO and Tl-201 scintigraphy in 30 patients with thyroid tumors (21 papillary adenocarcinoma, three solid follicular adenoma, six adenomatous goiter with cystic degeneration). Increased accumulation of both Tc-99m HMPAO and Tl-201 was seen in 14 patients with papillary adenocarcinoma and three with solid follicular adenoma, whereas two patients with papillar adenocarcinoma had low accumulation of both tracers. Of the six patients with adenomatous goiter with cystic degeneration, four had low accumulation of both Tc-99m HMPAO and Tl-201, and one patient had low accumulation of Tc-99m HMPAO only. Iso accumulation (same accumulation as the normal thyroid) of Tc-99m HMPAO was seen in five patients with papillary adenocarcinoma and one with adenomatous goiter. The distribution of Tc-99m HMPAO in the thyroid tumors and normal thyroid tissue was independent of time from 2 to 120 minutes after injection. The results of dynamic studies using Tc-99m HMPAO suggested that the accumulation of Tc-99m HMPAO in thyroid tumors reflected mainly tumor blood flow. The resultant Tc-99m HMPAO images were essentially similar to the Tl-201 images obtained 10 minutes after injection. Tc-99m HMPAO imaging can be a suitable substitute for Tl-201 imaging, and it may possibly be used to estimate tumor blood flow in patients with thyroid tumors.

Effect of athrombogenic therapy, especially high dose therapy of dipyridamole, after prosthetic valve replacement.

In order to prevent thrombo-embolism after prosthetic valve replacement, a high dose therapy with 450 mg/day of Dipyridamole and 3,000 mg/day of Aspirin was carried out for 1 year and 2 months in 91 cases (26 cases with aortic valve replacement, 40 cases with mitral valve replacement and 25 cases with multiple valve replacement). In the treated group, the incidence was 1.9% in cases more than 5 years after valve replacement and 2.9% in cases less than 5 years after valve replacement. In contrast, in the control group of 89 cases (47 cases of aortic valve replacement, 30 cases of mitral valve replacement and 12 cases of multiple valve replacement), the incidence was 9.1% and 14.7%, respectively. Thus, in both time intervals following prosthetic valve replacement the incidence of thrombo-embolism in the treated group was significantly lower than in the control group.