A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response.

Fatty acids are known to have significant effects on the properties of cancer cells. Therefore, these compounds have been incorporated into therapeutic strategies. However, few studies have examined the effects of individual fatty acids and their interactions in depth.

Structural dynamics of the N-terminal SH2 domain of PI3K in its free and CD28-bound states.

Protein conformational changes with fluctuations are fundamental aspects of protein-protein interactions (PPIs); understanding these motions is required for the rational design of PPI-regulating compounds. Src homology 2 (SH2) domains are commonly found in adapter proteins involved in signal transduction and specifically bind to consensus motifs of proteins containing phosphorylated tyrosine (pY). Here, we analysed the interaction between the N-terminal SH2 domain (nSH2) of the regulatory subunit in phosphoinositide 3-kinase (PI3K) and the cytoplasmic region of the T-cell co-receptor, CD28, using NMR and molecular dynamics (MD) simulations.

Development of healthy lifestyle consciousness index for gynecological cancer patients.

Purpose: Healthy lifestyle is related to quality of life (QOL) after cancer diagnosis and prognosis. However, there are few reports on patients conscious of healthy lifestyle and patients requiring medical providers' attention regarding healthy lifestyle. We aimed to develop a healthy lifestyle consciousness index (HLCI) for cancer patients and evaluated its validity in gynecological cancer patients.

Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells.

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC.

Directed Evolution of Sequence-Regulating Polyhydroxyalkanoate Synthase to Synthesize a Medium-Chain-Length-Short-Chain-Length (MCL-SCL) Block Copolymer.

Sequence-regulating polyhydroxyalkanoate synthase PhaC is a chimeric enzyme comprising PhaCs from and (). It spontaneously synthesizes a short-chain-length (SCL, ≤C) block copolymer poly(2-hydroxybutyrate)--poly(3-hydroxybutyrate) [P(2HB)--P(3HB)] from a mixture of monomer substrates. In this study, directed evolution of PhaC was performed to increase its activity toward a medium-chain-length (MCL, C) monomer, 3-hydroxyhexanoyl (3HHx)-coenzyme A (CoA).

Structural dynamics of a DNA-binding protein analyzed using diffracted X-ray tracking.

Diffracted X-ray tracking (DXT) is one of methods for the real-time evaluation of protein structural dynamics by detecting the movement of a gold-nanocrystal attached to a target protein. However, one of the technical concerns is the size of the gold-nanocrystals, which are larger than the protein. In our previous results of mean square angular displacement curves in DXT analysis, dynamical movements of the DNA-binding protein, c-Myb R2R3, were observed in only one population in either DNA-unbound or -bound state, and was found to decrease upon DNA binding.

Combination of gene set signatures correlates with response to nivolumab in platinum-resistant ovarian cancer.

Based on our previous phase II clinical trial of anti-programmed death-1 (PD-1) antibody nivolumab for platinum-resistant ovarian cancer (n = 19, UMIN000005714), we aimed to identify the biomarkers predictive of response. Tumor gene expression was evaluated by proliferative, mesenchymal, differentiated, and immunoreactive gene signatures derived from high-grade serous carcinomas and a signature established prior for ovarian clear cell carcinoma. Resulting signature scores were statistically assessed with both univariate and multivariate approaches for correlation to clinical response.

Images of Older Adults among University Students: a Comparison between Japan and Korea.

This study investigated the differences between Japanese and Korean college students' images of the elderly. Japan is the most aged society worldwide, while South Korea has the highest rate of aging. Japan has a more advanced elderly welfare system than Korea.

Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment.

Background: The mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy.

Methods: The frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined.

Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.

Side population (SP) cells harbor malignant phenotypes in cancer. The aim of this study was to identify genes that modulate the proportion of ovarian cancer SP cells. Using a shRNA library targeting 15,000 genes, a functional genomics screen was performed to identify genes whose suppression increased the SP percentage.

Phosphorylation of STAT1 serine 727 enhances platinum resistance in uterine serous carcinoma.

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum-cytotoxicity in USC.

Inpatient Enhanced Multidisciplinary Care Effects on the Quality of Life for Parkinson Disease: A Quasi-Randomized Controlled Trial.

Objectives: To compare the effects of inpatient enhanced multidisciplinary care (EMC) and multidisciplinary rehabilitation (MR) on the symptoms and quality of life (QOL) of patients with Parkinson disease (PD) and to clarify the relation between reduction in symptoms and the improved QOL.

Methods: This study was a quasi-randomized controlled (alternate allocation), assessor-blinded, single-center study. We recruited 80 patients with idiopathic Parkinson disease, Hoehn and Yahr stage 2 to 4, on stable medication.

Structural and functional properties of Grb2 SH2 dimer in CD28 binding.

Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein that plays a critical role in cellular signal transduction. It contains a central Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. Binding of Grb2 SH2 to the cytoplasmic region of CD28, phosphorylated Tyr (pY) containing the peptide motif pY-X-N-X, is required for costimulatory signaling in T cells.

VISTA expressed in tumour cells regulates T cell function.

Background: V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune-checkpoint protein. VISTA expression on tumour cells and the associated regulatory mechanisms remain unclear. We investigated VISTA expression and function in tumour cells, and evaluated its mechanism and activity.

DNA-binding induced conformational change of c-Myb R2R3 analyzed using diffracted X-ray tracking.

Previous structural analyses have shown that R2R3, the minimum unit of the DNA-binding domain of the transcriptional factor c-Myb, is largely flexible in solution, and changes to a more rigid structure upon DNA binding. In this study, we evaluated the structural dynamics using the diffracted X-ray tracking method, in correlation with DNA-binding abilities under different salt conditions, and compared them with the previous results. The resultant curve of the mean square angular displacements (MSD) clearly showed that the flexibility of R2R3 was decreased upon DNA binding, and the DNA-binding energies determined using the angular diffusion coefficients were in good agreement with those determined using isothermal titration calorimetry.

Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation.

Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8 tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs).

Exome Sequencing Landscape Analysis in Ovarian Clear Cell Carcinoma Shed Light on Key Chromosomal Regions and Mutation Gene Networks.

Previous studies have reported genome-wide mutation profile analyses in ovarian clear cell carcinomas (OCCCs). This study aims to identify specific novel molecular alterations by combined analyses of somatic mutation and copy number variation. We performed whole exome sequencing of 39 OCCC samples with 16 matching blood tissue samples.

Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer.

Emerging evidence has highlighted the host immune system in modulating the patient response to chemotherapy, but the mechanism of this modulation remains unclear. The aim of this study was to analyze the effect of chemotherapy on antitumor immunity in the tumor microenvironment of ovarian cancer. Treatment of ovarian cancer cell lines with various chemotherapeutic agents resulted in upregulated expression of MHC class I and programmed cell death 1 ligand 1 (PD-L1) in a NF-κB-dependent manner and suppression of antigen-specific T-cell function in vitro.

Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer.

Purpose: Programmed death-1 (PD-1), a coinhibitory immune signal receptor expressed in T cells, binds to PD-1 ligand and regulates antitumor immunity. Nivolumab is an anti-PD-1 antibody that blocks PD-1 signaling. We assessed the safety and antitumor activity of nivolumab in patients with platinum-resistant ovarian cancer.

STAT1 drives tumor progression in serous papillary endometrial cancer.

Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy.