ニンシンチュウ ニ チリョウ オ オコナッタ ニュウガン ノ 1レイ

The patient was 33-year-old woman, who was diagnosed as having left breast cancer at the 12th week of pregnancy and referred to our hospital. In palpation and ultrasonography, we found a tumor but no swelling lymph nodes in the C area of the left breast. Core needle biopsy showed invasive ductul carcinoma with ER(-), PgR(-) and HER2+(3+). At 16th week of pregnancy, partial resection and the sentinel lymph node biopsy of left breast were performed to the patient. After the surgery, she received 4 courses of doxorubicin+cyclophosphamide therapy (AC therapy), and at 35th week of pregnancy, she delivered her baby by cesarean section. During the pregnancy and operation, there had not been any problems with the patient and her baby. After the childbirth, she underwent 4 courses of docetaxel+trastumab therapy (TH therapy) and the remaining tumor was removed. Now, she is undergoing radiotherapy and neither recurrence nor metastasis is observed

Systems Analysis of ATF3 in Stress Response and Cancer Reveals Opposing Effects on Pro-Apoptotic Genes in p53 Pathway

Stress-inducible transcription factors play a pivotal role in cellular adaptation to environment to maintain homeostasis and integrity of the genome. Activating transcription factor 3 (ATF3) is induced by a variety of stress and inflammatory conditions and is over-expressed in many kinds of cancer cells. However, molecular mechanisms underlying pleiotropic functions of ATF3 have remained elusive. Here we employed systems analysis to identify genome-wide targets of ATF3 that is either induced by an alkylating agent methyl methanesulfonate (MMS) or over-expressed in a prostate tumour cell line LNCaP. We show that stress-induced and cancer-associated ATF3 is recruited to 5,984 and 1,423 targets, respectively, in the human genome, 89% of which are common. Notably, ATF3 targets are highly enriched for not only ATF/CRE motifs but also binding sites of several other stress-inducible transcription factors indicating an extensive network of stress response factors in transcriptional regulation of target genes. Further analysis of effects of ATF3 knockdown on these targets revealed that stress-induced ATF3 regulates genes in metabolic pathways, cell cycle, apoptosis, cell adhesion, and signalling including insulin, p53, Wnt, and VEGF pathways. Cancer-associated ATF3 is involved in regulation of distinct sets of genes in processes such as calcium signalling, Wnt, p53 and diabetes pathways. Notably, stress-induced ATF3 binds to 40% of p53 targets and activates pro-apoptotic genes such as TNFRSF10B/DR5 and BBC3/PUMA. Cancer-associated ATF3, by contrast, represses these pro-apoptotic genes in addition to CDKN1A/p21. Taken together, our data reveal an extensive network of stress-inducible transcription factors and demonstrate that ATF3 has opposing, cell context-dependent effects on p53 target genes in DNA damage response and cancer development

Microrna-9-5p-CDX2 axis: A useful prognostic biomarker for patients with stage II/III colorectal cancer

A lack of caudal-type homeobox transcription factor 2 (CDX2) protein expression has been proposed as a prognostic biomarker for colorectal cancer (CRC). However, the relationship between CDX2 levels and the survival of patients with stage II/III CRC along with the relationship between microRNAs (miRs) and CDX2 expression are unclear. Tissue samples were collected from patients with stage II/III CRC surgically treated at Kyoto University Hospital. CDX2 expression was semi-quantitatively evaluated by immunohistochemistry (IHC). The prognostic impacts of CDX2 expression on overall survival (OS) and relapse-free survival (RFS) were evaluated by multivariable statistical analysis. The expression of miRs regulating CDX2 expression and their prognostic impacts were analyzed using The Cancer Genome Atlas Program for CRC (TCGA-CRC). Eleven of 174 CRC tissues lacked CDX2 expression. The five-year OS and RFS rates of patients with CDX2-negative CRC were significantly lower than those of CDX2-positive patients. Multivariate analysis of clinicopathological features revealed that CDX2-negative status is an independent marker of poor prognosis in stage II/III CRC. miR-9-5p was shown to regulate CDX2 expression. TCGA-CRC analysis showed that high miR-9-5p expression was significantly associated with poor patient prognosis in stage II/III CRC. In conclusion, CDX2, the post-transcriptional target of microRNA-9-5p, is a useful prognostic biomarker in patients with stage II/III CRC

Identification of mutations through dominant screening for obesity using C57BL/6 substrains

The discovery of leptin substantiated the usefulness of a forward genetic approach in elucidating the molecular network regulating energy metabolism. However, no successful dominant screening for obesity has been reported, which may be due to the influence of quantitative trait loci between the screening and counter strains and the low fertility of obese mice. Here, we performed a dominant screening for obesity using C57BL/6 substrains, C57BL/6J and C57BL/6N, with the routine use of in vitro fertilization. The screening of more than 5000 mutagenized mice established two obese pedigrees in which single nucleotide substitutions in Mc4r and Sim1 genes were identified through whole-exome sequencing. The mutation in the Mc4r gene produces a premature stop codon, and the mutant SIM1 protein lacks transcriptional activity, showing that the haploinsufficiency of SIM1 and MC4R results in obesity. We further examined the hypothalamic neuropeptide expressions in the mutant pedigrees and mice with diet-induced obesity, which showed that each obesity mouse model has distinct neuropeptide expression profiles. This forward genetic screening scheme is useful and applicable to any research field in which mouse models work

How Can We Improve Oncofertility Care for Patients? A Systematic Scoping Review of Current International Practice and Models of Care

© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. BACKGROUND: Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the literature on the components of oncofertility care as defined by patient and clinician representatives, and identify the barriers, facilitators and challenges, so as to improve the implementation of oncofertility services. SEARCH METHODS: A systematic scoping review was conducted on oncofertility MOC literature published in English between 2007 and 2016, relating to 10 domains of care identified through consumer research: communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, training, supportive care during treatment, reproductive care after cancer treatment, psychosocial support and ethical practice of oncofertility care. A wide range of electronic databases (CINAHL, Embase, PsycINFO, PubMed, AEIPT, Education Research Complete, ProQuest and VOCED) were searched in order to synthesize the evidence around delivery of oncofertility care. Related citations and reference lists were searched. The review was undertaken following registration (International prospective register of systematic reviews (PROSPERO) registration number CRD42017055837) and guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). OUTCOMES: A total of 846 potentially relevant studies were identified after the removal of duplicates. All titles and abstracts were screened by a single reviewer and the final 147 papers were screened by two reviewers. Ten papers on established MOC were identified amongst the included papers. Data were extracted from each paper and quality scores were then summarized in the oncofertility MOC summary matrix. The results identified a number of themes for improving MOC in each domain, which included: the importance of patients receiving communication that is of a higher quality and in different formats on their fertility risk and FP options; improving provision of oncofertility care in a timely manner; improving access to age-appropriate care; defining the role and scope of practice of all HCPs; and improving communication between different HCPs. Different forms of decision aids were found useful for assisting patients to understand FP options and weigh up choices. WIDER IMPLICATIONS: This analysis identifies core components for delivery of oncofertility MOC. The provision of oncofertility services requires planning to ensure services have safe and reliable referral pathways and that they are age-appropriate and include medical and psychological oncofertility care into the survivorship period. In order for this to happen, collaboration needs to occur between clinicians, allied HCPs and executives within paediatric and adult hospitals, as well as fertility clinics across both public and private services. Training of both cancer and non-cancer HCPs is needed to improve the knowledge of HCPs, the quality of care provided and the confidence of HCPs with these consultations

ネコ ノ スイブン セッシュリョウ ト ニョウリョウ ニョウ ヒジュウチ ニ カンスル ケンキュウ

Domestic cats (Felissilvestriscatus ) are known to have lesser and hypertonic urine excretion(urine volume: 22–30 mL/kg per day; specific gravity: 1.015–1.050) than those of domestic dogs( Canislupus familiaris); urine volume: 24–40 mL/kg perday; specific gravity: 1.015–1.040). These have been implicated as factors for feline incidence of struviteurolithiasis and felinelower urinary tract disease, which are diseases that affect the bladder or urethra. We conducted comparative studies on therelationship between fluid intake and urine volume/urine specific gravity under 2 conditions—diet (condition A) comprising"dry food"( 5.6% moisture) and ad libitum drinking water and diet( condition B) comprising" wet food"( 74.8% moisture) andad libitum drinking water—in acclimated cats( n=7) kept separately in cat cages in an animal rearing room at 25°C. The perdiem water intake (apparent water intake) in condition A was on an average 66.9 ± 22.1(mL), while the totalfluid intake (absolute water intake), which is the sum of the amounts of water in the food and the water intake, was on anaverage68.2 ± 23.3(mL).Further, the average water intake under condition B was only 22.7 ± 20.13( mL), but the absolutewater intake was on average 95.6 ± 37.6( mL), meaning that wet food resulted in a higher absolute water intake amountthan dry food. Regarding the urine volume and the urine specific gravity, urine volume and urine specific gravity with the dry food diet(condition A) were 28.8 ± 11.8 (mL) and 1.049 ± 0.01, respectively, but the mean urine volume and urine specific gravityunder condition B were 49.5 ± 31.4(mL) and 1.030 ± 0.01, respectively, showing that compared to the dry food group, thewet food group had a significantly higher urine volume and lower urine specific gravity. The present study proves that in an average rearing environment, the urine volume does not increase and urine specificgravity is hypertonic when the cats are provided dry food diet, despite increase in the apparent water intake. Further, theurine volume increases and urine specific gravity decreases when the cats are provided wet food diet( canned or pouched),although the apparent water intake is low. The present study shows that differences in the diet are factors for the increasedincidence of struviteurolithiasis and FLUTD in cats

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts