Citrus sudachi Peel Extract Suppresses Cell Proliferation and Promotes the Differentiation of Keratinocytes through Inhibition of the EGFR–ERK Signaling Pathway

Citrus sudachi is a well-known fruit in Tokushima Prefecture, Japan, and its peels are rich in phytochemicals, including phenolic compounds. Although it is expected that the extract of the C. sudachi peel elicits various beneficial physiological activities, the effect on the skin has not been investigated. In this study, we report that the aqueous extract from the peel of C. sudachi suppresses cell proliferation of the immortalized human keratinocyte cell line, HaCaT, and primary normal human epidermal keratinocytes. The extract of C. sudachi peel suppressed epidermal growth factor (EGF)-induced EGF receptor activation and tumor necrosis factor (TNF)-α-induced extracellular regulated kinase (ERK) 1/2 activation, which suggests that the extract exerts its inhibitory effect through inhibition of both the EGF receptor (EGFR) and its downstream molecules. Additionally, the extract of C. sudachi peel potentiated calcium-induced keratinocyte differentiation. These results suggest that the extract of C. sudachi peel may have beneficial effects against skin diseases that are characterized by hyperproliferation of epidermal keratinocytes, such as those seen in psoriasis and in cutaneous squamous cell carcinoma

Establishment and characterization of a novel treatment‐related neuroendocrine prostate cancer cell line KUCaP13

The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor (AR) pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. We established a novel NEPC cell line, KUCaP13, from tissue of a patient initially diagnosed with AC which later recurred as NEPC. The cell line has been maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering with lentivirus. KUCaP13 cells lack the expression of AR and overexpress NEPC-associated genes, including SOX2, EZH2, AURKA, PEG10, POU3F2, ENO2, and FOXA2. Importantly, the cell line maintains the homozygous deletion of CHD1, which was confirmed in the primary AC of the index patient. Loss of heterozygosity of TP53 and PTEN, and an allelic loss of RB1 with a transcriptomic signature compatible with Rb pathway aberration were revealed. Knockdown of PEG10 using shRNA significantly suppressed growth in vivo. Introduction of luciferase allowed serial monitoring of cells implanted orthotopically or in the renal subcapsule. Although H3K27me was reduced by EZH2 inhibition, reversion to AC was not observed. KUCaP13 is the first patient-derived, treatment-related NEPC cell line with triple loss of tumor suppressors critical for NEPC development through lineage plasticity. It could be valuable in research to deepen the understanding of NEPC

Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings

Carbon Ion Radiotherapy for Unresectable Sacral Chordoma

Purpose: The results of carbon ion radiotherapy for unresectable sacral chordoma were summarized to evaluate efficacy and safety. Patients and Methods: We performed a retrospective analysis on 175 patients with unresectable sacral chordomas treated with carbon ion radiotherapy between June 1996 and February 2012. All of the patients in this study presented without prior treatment. The applied carbon ion dose ranged from 64.0 GyE to 73.6 GyE (Gray equivalent, median 70.4 GyE) in a total of 16 fixed fractions over four weeks. Results: The median age of the patients was 67 ranging from 26 to 87. The study group consisted of 55 females and 120 males. The cranial extension of tumor was S2 or higher level in 70% of the patients. The median clinical target volume was 344 cm3. The median follow up period was 59 months. Five-year overall survival and 5-year local control rates were 82% and 79%, respectively. After carbon ion radiotherapy, the ambulatory in 97% of the patients remained with or without supportive devices. Two patients experienced severe skin/soft tissue complications requiring skin grafts.Conclusion: CIRT appears effective and safe in the management of patients with unresectable sacral chordoma and offers a promising alternative to surgery.Heavy Ion in Therapy and Space Radiation Symposium 2013(HITSRS2013

Relationship between the quantity of serum reactive oxygen metabolites and skin toxicity grade in the irradiated rat model

The 17th ECCO- 38th ESMO- 32nd ESTRO European Cancer Congres

First experience of carbon-ion radiotherapy for early breast cancer.

Breast cancer is increasingly being detected at earlier stages, and partial breast irradiation for patients with low-risk-group tumor has come to be applied in the US and Europe as an alternative to whole-breast irradiation. Based on those experiences, some institutes have tried using particle beams for partial breast irradiation for postoperative or radical intent for early breast cancer, but technical difficulties have hindered its progress. The National Institute of Radiological Sciences has been preparing for carbon-ion radiotherapy (C-ion RT) with radical intent for stage I breast cancer since 2011, and we carried out the first treatment in April 2013. In this case report, we explain our first experience of C-ion RT as a treatment procedure for breast tumor and present the radiation techniques and preliminary treatment results as a reference for other institutes trying to perform the same kind of treatment

Controlled Self-Assembly of Metal–Organic Frameworks on Metal Nanoparticles for Efficient Synthesis of Hybrid Nanostructures

We report a novel approach for synthesizing inorganic nanoparticle/metal–organic frameworks (MOFs) heterostructured nanocomposites by self-assembly of MOFs on nanoparticles. This approach involves the synthesis of Au nanoparticles and preferential growth of [Cu₃(btc)₂]_<i>n</i> frameworks consisting of Cu²⁺ ions and benzene-1,3,5-tricarboxylate (btc) on nanoparticles. Aggregates consisting of 11-mercaptoundecanoic acid (MUA)-stabilized Au nanoparticles linked by Cu²⁺ ions were necessary for preferential self-assembly of [Cu₃(btc)₂]_<i>n</i> frameworks on the aggregates, resulting in the formation of Au nanoparticles/[Cu₃(btc)₂]_<i>n</i> nanocomposites. The present approach was confirmed to be applicable for other hybrids consisting of Au nanoparticles and tetragonal [Cu₂(ndc)₂(dabco)]_<i>n</i> frameworks

Relationship between Serum Reactive Oxidative Metabolite Level and Skin Reaction in an Irradiated Rat Model

AbstractPurpose: Ionizing radiation generates free radicals and reactive oxygen species that induce DNA damage in vivo. This study aimed to determine the relationship between serum reactive oxygen metabolite (ROM) levels and skin reaction after irradiation in a rat model.Methods and materials: I. Female Wistar rats were classified into 0 Gy (control), 2 Gy, and 30 Gy groups; serum ROM levels were measured in the very acute phase. II. Other female Wistar rats were classified into 0 Gy (control), 30 Gy, 50 Gy, and 70 Gy groups; serum ROM levels were measured before and 3, 7, 16, 24, 31, and 38 days after irradiation. Skin reaction was evaluated according to the skin reaction score (0–5) twice every week.Results: Serum ROM levels in the subacute phase were significantly higher in the 50 and 70 Gy groups than in the 0 and 30 Gy groups [p = 0.029, repeated-measure analysis of variance (ANOVA)]. As expected, skin reaction scores increased in the order of the 0 Gy, 30 Gy, 50 Gy, and 70 Gy groups and differed significantly among these groups (p < 0.001, repeated-measure ANOVA). Peak serum ROM levels were observed 16 days after irradiation in all irradiated groups and corresponded with the appearance of visible skin reaction after irradiation.Conclusions: Serum ROM levels may be useful for evaluating radiation damage in mammals. Further investigations are required to investigate changes in intracellular metabolism after irradiation at gene and protein levels