Preferred catalysis distinctly determined by metals doped with nitrogen in three-dimensionally ordered porous carbon materials.

Three-dimensionally ordered nanoporous structures were generated in carbon materials doped with metals and nitrogen as catalytically active sites for electrochemical reactions. Free-base and metal phthalocyanines with a strategically designed molecular structure were used as carbon sources to obtain an ordered porous structure via homogeneous self-assembly with Fe3O4 nanoparticles as the pore template and the prevention of melting away during carbonization. The doping of Fe and nitrogen was achieved by a reaction between the free-base phthalocyanine and Fe3O4 through carbonization at 550 °C, while Co and Ni were doped using the corresponding metal phthalocyanines. The preference of these three types of ordered porous carbon materials for catalytic reactions was distinctly determined by the doped metals. Fe-N-doped carbon showed the highest activity for O2 reduction. Additional heat treatment at 800 °C enhanced this activity. CO2 reduction and H2 evolution were preferred by the Ni- and Co-N-doped carbon materials, respectively. A change in the template particle size was capable of controlling the pore size to enhance mass transfer and improve performance. The technique presented in this study enabled systematic metal doping and pore size control in the ordered porous structures of carbonaceous catalysts.

Efficacy and Safety of Monthly Minodronate Therapy in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors.

BACKGROUND/AIM: Post-menopausal breast cancer (BC) patients who receive adjuvant aromatase inhibitor (AI) therapy may be at increased risk of bone loss, osteoporosis, and bone fracture. We aimed to evaluate the efficacy and safety of oral bisphosphonate minodronate in preventing bone loss complications. PATIENTS AND METHODS: Patients receiving AI and 80% of those with suboptimal bone mineral density (BMD) were prescribed monthly oral minodronate 50 mg every 4 weeks for 72 weeks. BMD, bone metabolism markers, incidence of bone fractures, medication compliance, and other adverse events (AE) were examined every 24 weeks following administration. RESULTS: Fifty postmenopausal BC patients with a median age of 64.0 years were enrolled. The mean value of lumbar spine BMD was higher than that of the value before the minodronate administration at each observation point. Before and after the treatment, the median serum values of Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) (mU/dl) and serum type I collagen cross-linked N-telopeptide (NTX) (nmolBCE/l) were decreased from 535.7 and 18.5 to 230.1 and 11.9, respectively. No adverse grade 2 or higher event was observed throughout this study. CONCLUSION: The combined administration of minodronate and AIs was safe and effective in preventing bone loss complications in postmenopausal BC patients.

Plasma level of prostate related-antigen peptide-reactive IgG is a prognostic factor of patients with breast cancer treated with personalized peptide vaccines.

The present study assessed plasma IgG in patients with metastatic recurrent breast cancer (mrBC) that is reactive to various T-cell epitope peptides of prostate-related antigens (PRAs), such as prostate-specific antigen, prostate-specific membrane antigen and prostate acid phosphatase. Patients were treated with personalized peptide vaccines (PPVs) which were selected and administered from a panel of candidate peptides based on human leukocyte antigen-types and prevaccination IgG levels to each peptide. The peptide panel consisted of 27 cytotoxic T-lymphocyte-epitope peptides derived from tumor-associated antigens, not including PRA. PRA peptides and peptide panels were retrospectively analyzed in 77 PPV-treated patients. The results revealed that PRA reactive IgG levels were increased after vaccination in 31 of the 97 patients included in the present study. Although there was no significant association between anti-PRA peptide levels and progression-free survival (PFS) or overall survival, anti-PRA peptide levels were significantly associated with PFS (P=0.009) in estrogen-receptor positive (ER+) patients with cancer. The results suggested that plasma anti-PRA IgG levels may be a useful prognostic marker for monitoring PPVs, particularly for ER+ patients with mrBC (trial registration no. from the UMIN Clinical Trials Registry, UMIN000001844).

[Triple-Tracer Technique of Sentinel Lymph Node Biopsy Using Blue Dye plus Radioisotope Combined with Real-Time Indocyanine Green(ICG)Fluorescence Imaging Procedures for Patients with Breast Cancer Treated with Neoadjuvant Chemotherapy].

Clinical evidence has indicated that, after neo-adjuvant chemotherapy(NAC), sentinel node(SN)identification rates(IR) were lower and false-negative rates(FNR)were higher for patients(pts)with local advanced breast cancer(BC)than for pts with early stage BC who did not receive NAC. Our previous clinical trial indicated that the real-time indocyanin green (RT-ICG)fluorescence imaging technique could improve the diagnostic sensitivity and detection accuracy of sentinel node biopsy(SNB). Nine pts with histologically confirmed Stage ⅡA to ⅢB, T1-T3, N0-2, M0 BC were selected to receive NAC, and the standard surgeries were performed after NAC completion. The SNs were detected by using conventional procedures with the blue dye(indigo carmine)plus 99mTc radioisotope techniques combined with concurrent RT-ICG. Clinically positive nodes were diagnosed by the radiologists using axillary ultrasound, MRI, and/or CT scans. All pts provided written informed consent before surgery. The surgical SNB was guided via RT-ICG fluorescence under standard light conditions by using the HEMS imaging system as previously published. All pts underwent SNB followed by completion node dissection(CND). The IR and FNR were calculated by comparing the results of the SNB and the histopathology of the resection specimens obtained via CND. The IR and FNR for each procedure of SNB were, respectively, 35.3% and 41.7% when indigo carmine blue was used, 82.4% and 0 when ICG fluorescence was used, and 58.8% and 5% when RI was used. In contrast, the total calculation of the triple tracer showed that IR reached 100% and FNR was 0. These data suggest that IR and FNR of SNB might be improved in pts with BC treated with NAC by using the novel triple tracer technique.

Early phase II study of mixed 19-peptide vaccine monotherapy for refractory triple-negative breast cancer.

We undertook an early phase II study of mixed 19-peptide cancer vaccine monotherapy for 14 advanced metastatic triple-negative breast cancer (mTNBC) patients refractory to systemic chemotherapy to develop a new type of cancer vaccine. The treatment protocol consisted of a weekly vaccination for 6 weeks, and there were no severe adverse events related to the vaccination throughout the trial. Increase of peptide-specific IgG against the vaccinated human leukocyte antigen-matched peptides, but not against the nonmatched peptides, was positively correlated with overall survival (OS) (P < .01). The median OS was 11.5 or 24.4 months in all 14 patients or the 10 patients who completed the vaccination. The patients with lower C-reactive protein levels or 3 or fewer systemic chemotherapies were favorable candidates for this treatment. Advancement of this therapy to the next stage of study could be warranted based on the safety and immune boosting determined herein (clinical trial registration number: UMIN000014616).

Controlling the Polarity of Fullerene Derivatives to Optimize Nanomorphology in Blend Films.

Developing a design strategy to establish the compatibility of acceptor materials with donor materials is important for the rational development of organic solar cells. We synthesized 2,6-dimethoxyphenyl methanofullerene derivatives to realize an enhanced open-circuit voltage, and we investigated polarities and their effects on the film morphology of the active layer. The polarities of the synthesized fullerene derivatives were affected significantly by the presence of functional groups, such as methoxy, ether, and ester groups. Macro/nanoscopic morphological investigation and spectroscopic analysis of the blend films of the poly(3-hexylthiophene)(P3HT)/fullerene derivatives showed that a balanced polarity between materials results in the formation of optimized nanomorphology without grains and robust phase separation. Measurements of the device performance of the photovoltaic cells composed of P3HT and the fullerene derivatives confirmed the same tendency as that shown in the morphological analysis. This finding enables us to obtain an improved power conversion efficiency because of the enhanced open circuit voltage derived from the fullerene derivatives.

Design of fullerene derivatives for stabilizing LUMO energy using donor groups placed in spatial proximity to the C60 cage.

A series of arylated dihydrofullerene derivatives were synthesized to elucidate the effective design of fullerene derivatives for enhancing the performance of organic photovoltaics. The LUMO energy of the fullerenes was estimated by the first reduction potential and theoretical calculations. The results showed that the methoxy groups substituted at spatial proximity to the fullerene core offered significant stabilization of the LUMO level. The stabilizing effect of the directly arylated fullerenes is more significant than that of conventional methanofullerenes. The theoretical investigation was performed with regard to the electronic interaction between the methoxy and fullerene moieties.

[A case of large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix successfully treated by postoperative CPT-11+CDDP chemotherapy after non-curative surgery].

A 31-year-old woman, gravida 3 para 3, visited a local clinic because of post-coital bleeding. She was diagnosed as having a uterine-cervical tumor and was referred to our hospital. Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix was pathologically shown by biopsy. The patient was initially treated by radical hysterectomy. Postoperative pathological examination revealed a direct invasion to the parametrium and the positive resection margin. Postoperatively, she was treated by CPT-11+CDDP. One course of treatment was 60mg/m² of CPT-11 administered on day 1, 8 and 15, and 60 mg/m² of CDDP on day 1, with an intermission after administration for 7 days. Six courses were carried out. This treatment resulted in complete remission. A follow-up at the outpatient clinic revealed the patient had been tumor-free for one year and three months after the first treatment. We suggest that postoperative chemotherapy with CPT-11+CDDP might be useful in the treatment of patients with LCNEC of the uterine cervix.

Synthesis of thienyl analogues of PCBM and investigation of morphology of mixtures in P3HT.

Novel [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) analogues containing benzo[b]thiophene (3a, 3b) and thieno[3,2-b]thiophene (3c, 3d) were synthesized and characterized. The morphology of the thin films prepared from the mixtures of these methanofullerenes with regioregular poly(3-hexylthiophene) (P3HT) was investigated by AFM measurement and UV-Vis absorption spectroscopy. A solubility test of these methanofullerenes was performed by using dichloromethane as a solvent. es-TThCBM (3d) exhibited 1.4 times greater solubility in dichloromethane than PCBM.