Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients.

INTRODUCTION: Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC. METHODS: Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination. RESULTS: No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively. CONCLUSIONS: PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000001844 (Registration Date: April 5, 2009).

Evaluation of contrast Sonazoid-enhanced ultrasonography for the detection of hepatic metastases in breast cancer.

BACKGROUND: The present study was aimed to evaluate the usefulness of contrast Sonazoid-enhanced ultrasonography (US) for the detection of hepatic metastases in breast cancer patients and compare the clinical efficacy and sensitivity of this technique with conventional contrast unenhanced B-mode US in follow-up examinations of breast cancer patients with liver metastasis. METHODS: We assessed a total of 84 hepatic tumors from 24 patients diagnosed with or suspected of having metastatic cancer. These hepatic nodules were diagnosed through imaging, including dynamic magnetic resonance imaging (MRI), contrast-enhanced computed tomography (CECT) scan, B-mode US or contrast Sonazoid-enhanced US (SEUS). Differences in the sensitivity between US and SEUS were compared using MR imaging, CECT, and follow-up imaging. RESULTS: A total of 79 nodules were diagnosed as metastatic tumors. The remaining nodules were diagnosed as benign tumors (hepatic hemangioma: n = 3; local fatty change: n = 2). SEUS precisely detected the presence or absence of hepatic tumors in the 24 patients examined, showing a sensitivity of 98.8 % (83 of 84 lesions) for total imaged solid liver lesions, with an accuracy of 98.7 % (78 of 79 lesions) for total metastatic breast cancer lesions. In contrast, conventional B-mode US imaging revealed hepatic tumor lesions at a sensitivity of 66.7 % (56 of 84 lesions) and an accuracy of 64.6 % (51 of 79 lesions), respectively. Furthermore, the false positive and false negative rates were, respectively, 6.33 and 29.1 % for B-mode US and 0 and 1.3 % for SEUS. Moreover, twenty-seven metastatic tumors and five benign lesions (3 hemangiomas and 2 focal fatty changes/sparings) were imaged using SEUS but not conventional B-mode US. Significant differences in diagnostic accuracy rates between contrast Sonazoid-enhanced US and conventional B-mode US were observed (Wilcoxon signed rank test: p = 0.0009). No severe adverse events occurred during SEUS after the administration of Sonazoid, except for a grade 1 skin reaction and nausea in one patient. CONCLUSION: These results suggested that Sonazoid could be safely administrated to breast cancer patients with liver metastatic disease. Thus, contrast Sonazoid-enhanced US is a feasible and more effective method than B-mode US for the detection of hepatic metastasis, particularly for small metastatic breast cancer lesions less than 14 mm in diameter, showing significant high sensitivity and accuracy.

Photophysical insights into supramolecular interaction of a designed bisporphyrin with fullerenes C60 and C70.

The present paper reports the photophysical investigations of a designed bisporphyrin (1), and its supramolecular complexes with C60 and C70 in toluene medium. UV-vis studies reveal appreciable ground state interaction between fullerenes and 1. The stoichiometry of the fullerene complexes of 1 is found to be 1:1. Steady state fluorescence studies elicit quenching of fluorescence of 1 in the presence of fullerenes. The binding constants of the C60/1 and C70/1 complexes are estimated to be 3760 and 31,222.5 dm3 mol(-1), respectively. Time resolved emission studies establish relatively long-lived charge separated state for the C70/1 complex. Molecular mechanics calculations in vacuo evoke the stereoscopic structures of the fullerene/1 complexes and interpret the stability difference between C60 and C70 complexes of 1 in terms of heat of formation values.