Two-Chain Mature Hepatocyte Growth Factor-Specific Positron Emission Tomography Imaging in Tumors Using 64Cu-Labeled HiP-8, a Nonstandard Macrocyclic Peptide Probe.

Two-chain hepatocyte growth factor (tcHGF), the mature form of HGF, is associated with malignancy and anticancer drug resistance; therefore, its quantification is an important indicator for cancer diagnosis. In tumors, activated tcHGF hardly discharges into the systemic circulation, indicating that tcHGF is an excellent target for molecular imaging using positron emission tomography (PET). We recently discovered HGF-inhibitory peptide-8 (HiP-8) that binds specifically to human tcHGF with nanomolar affinity. The purpose of this study was to investigate the usefulness of HiP-8-based PET probes in human HGF knock-in humanized mice. 64Cu-labeled HiP-8 molecules were synthesized using a cross-bridged cyclam chelator, CB-TE1K1P. Radio-high-performance liquid chromatography-based metabolic stability analyses showed that more than 90% of the probes existed in intact form in blood at least for 15 min. In PET studies, significantly selective visualization of hHGF-overexpressing tumors versus hHGF-negative tumors was observed in double-tumor-bearing mice. The accumulation of labeled HiP-8 into the hHGF-overexpressing tumors was significantly reduced by competitive inhibition. In addition, the radioactivity and distribution of phosphorylated MET/HGF receptor were colocalized in tissues. These results demonstrate that the 64Cu-labeled HiP-8 probes are suitable for tcHGF imaging in vivo, and secretory proteins like tcHGF can be a target for PET imaging.

Feasibility study on collecting patient-reported outcomes from breast cancer patients using the LINE-ePRO system.

Due to the increasing complexity of cancer treatment, ensuring safety and maintaining the quality of life during treatment are important issues. Patient-reported outcomes (PROs) in oncology are essential for assessing patient symptoms. A feasibility study was undertaken on breast cancer patients by building a PRO data collection system based on LINE, one of the most popular social network service applications in Japan. In this study, one or more predefined PRO questions for each breast cancer patient's clinical situation were sent to the patient's LINE application daily. The patient selected a predefined answer by tapping the screen, but no free-text answers were allowed. Seventy-three patients were enrolled. The median observation period was 435 days (84-656 days), and the total number of PROs collected was 16,417, with a mean of 224.9 reports per patient. Patients on adjuvant endocrine therapy were notified of 2.5 questions per week, and the median number of responses per week and response rate were 2.387 (1.687-11.627) and 95.5%, respectively. Analyzing the results by age group, the number of responses from those aged 60 and above was equal to or higher than that of the younger age group. It was also possible to track each patient's PROs accurately. These results suggested that the design of the system, based on an application used daily, instead of using specifically prepared applications for collecting electronic PROs, was the reason for the favorable acceptance from patients and the satisfactory response rate from all age groups, including the elderly.

Establishment of a deep-learning system to diagnose BI-RADS4a or higher using breast ultrasound for clinical application.

Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI-RADS) has become widespread worldwide, the problem of inter-observer variability remains. To maintain uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI-RADS3 or lower or BI-RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep-learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI-RADS3 or lower and BI-RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.

Comprehensive analysis of the homeobox family genes in breast cancer demonstrates their similar roles in cancer and development.

BACKGROUND: The homeobox (HOX) family consists of 39 genes whose expressions are tightly controlled and coordinated within the family, during development. We performed a comprehensive analysis of this gene family in cancer settings. METHODS: Gene correlation analysis was performed using breast cancer data available in The Cancer Genome Atlas (TCGA) and data from the patients admitted to our hospital. We also analyzed the data of normal breast tissue (GSE20437). We next collected gene expression and prognosis data of breast cancer patients (GSE11121, GSE7390, GSE3494, and GSE2990) and performed unsupervised hierarchal clustering by the HOX gene expression pattern and compared prognosis. We additionally performed this analysis to leukemia (available in TCGA) and sarcoma (GSE20196) data. RESULTS: Gene correlation analysis showed that the proximal HOX genes exhibit strong interactions and are expressed together in breast cancer, similar to the expression observed during development. However, in normal breast tissue, less interactions were observed. Breast cancer microarray meta-data classified by the HOX gene expression pattern predicted the prognosis of luminal B breast cancer patients (p = 0.016). Leukemia (p = 0.00016) and sarcoma (p = 0.018) presented similar results. The Wnt signaling pathway, one of the major upstream signals of HOX genes in development, was activated in the poor prognostic group. Interestingly, poor prognostic cancer presented stronger correlation in the gene family compared to favorable prognostic cancer. CONCLUSION: Comprehensive analysis of the HOX family demonstrated their similar roles in cancer and development, and indicated that the strong interaction of HOX genes might be specific to malignancies, especially in the case of poor prognostic cancer.

Theracurmin inhibits intestinal polyp development in Apc-mutant mice by inhibiting inflammation-related factors.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the well-known cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apc-mutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10-20 µM Theracurmin for 24 hours reduced nuclear factor-κB (NF-κB) transcriptional activity in human colon cancer DLD-1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NF-κB promoter transcriptional activity. As NF-κB is a regulator of inflammation-related factors, we next investigated the downstream targets of NF-κB: monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCP-1 and IL-6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (J-CAP-C study).

Impact of neoadjuvant and adjuvant chemotherapy on invasive lobular carcinoma: A propensity score-matched analysis of SEER data.

Invasive lobular carcinoma (ILC) has a different treatment response from invasive ductal carcinoma (IDC). We assessed whether perioperative chemotherapy was associated with improved prognosis in patients with ILC. Retrospective data of women who underwent surgery for ILC were extracted from the SEER database. Subjects were divided into non-chemotherapy and chemotherapy groups. Overall, 10 537 patients were included, and 2107 patients were stratified into each group after propensity score matching. Perioperative chemotherapy significantly improved 10-year survival rates for ILC, particularly in patients with large tumor size and lymph node metastases. Perioperative chemotherapy is effective for ILC patients with proper selection.

Effectiveness of Antiemetic Regimens for Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Network Meta-Analysis.

BACKGROUND: It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. METHODS: Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. RESULTS: We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. CONCLUSION: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. IMPLICATIONS FOR PRACTICE: Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Assessment of impact of DNA extraction methods on analysis of human remain samples on massively parallel sequencing success.

Skeletal remains recovered from missing persons' cases are often exposed to harsh environmental conditions resulting in the DNA being damaged, degraded, and/or the samples containing PCR inhibitors. In this study, the efficacy of common extraction methods was evaluated to remove high levels of PCR inhibitors commonly encountered with human remains, and their downstream compatibility with the two leading sequencing chemistries and platforms for human identification purposes. Blood, hair, and bone samples were spiked with high levels of inhibitors commonly identified in each particular substrate in order to test the efficiency of various DNA extraction methods prior to sequencing. Samples were extracted using three commercial extraction kits (DNA IQ™, DNA Investigator, and PrepFiler® BTA), organic (blood and hair only), and two total demineralization protocols (bone only)). Massively parallel sequencing (MPS) was performed using two different systems: Precision ID chemistry and a custom AmpliSeq™ STR and iiSNP panel on the Ion S5™ System and the ForenSeq DNA Signature Prep Kit on the MiSeq FGx™. The overall results showed that all DNA extraction methods were efficient and are fully compatible with both MPS systems. Key performance indicators such as STR and SNP reportable alleles, read depth, and heterozygote balance were comparable for each extraction method. In samples where CE-based STRs yielded partial profiles (bone), MPS-based STRs generated more complete or full profiles. Moreover, MPS panels contain more STR loci than current CE-based STR kits and also include SNPs, which can further increase the power of discrimination obtained from these samples, making MPS a desirable choice for the forensic analysis of such challenging samples.

Optimal use of anthracycline-free perioperative chemotherapy in HER2-positive breast cancer patients.

PURPOSE: In adjuvant settings of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, anthracycline-based chemotherapy followed by taxane and trastuzumab is a standard regimen. Recent studies have reported the use of anthracycline-free adjuvant chemotherapy in selected HER2-positive breast cancer patients. We conducted a single-center retrospective study to identify the characteristics of HER2-positive breast cancer patients for whom anthracyclines can be safely omitted. METHODS: A total of 238 women were diagnosed with HER2-positive breast cancer and treated with neoadjuvant and/or adjuvant chemotherapy between January 1, 2008 and December 31, 2015 at Keio University Hospital. They were divided in two cohorts: an "anthracycline" cohort of 112 anthracycline-treated women and a "no anthracycline" cohort of 126 anthracycline-untreated women. Survival outcomes were estimated by Kaplan-Meier method. RESULTS: The 3-year disease-free survival rates in the no-anthracycline and anthracycline cohorts were 91.3% and 93.1%, respectively (P = 0.692). After using a statistical method with inverse probability of treatment weighting to minimize the selection bias, no significant differences were observed between the two cohorts (adjusted hazard ratio for disease-free survival: 1.042; P = 0.909). Stratified by tumor size, no significant differences were observed between the two cohorts in the cT1N0 and cT2N0 subsets (P = 0.516 and P = 0.579, respectively). The recurrence rate was low among patients who achieved pathological complete response after receiving neoadjuvant chemotherapy with or without anthracyclines. CONCLUSION: Our study suggests that anthracyclines can be safely omitted in selected patients with HER2-positive breast cancer, who have cT1N0 or cT2N0 and achieved pathological complete response after receiving neoadjuvant chemotherapy.

Clinicopathologic features of hormone-receptor-positive breast cancer patients with late recurrence.

The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P < .001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P < .001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P = .0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.

Activation of NF-E2 p45-related factor-2 transcription and inhibition of intestinal tumor development by AHCC, a standardized extract of cultured Lentinula edodes mycelia.

It has been reported that activation of NF-E2 p45-related factor-2 (NRF2), a transcription factor, induces a variety of antioxidant enzymes, and plays an important role in preventing carcinogenesis. AHCC is a standardized extract of cultured Lentinula edodes mycelia and it has been demonstrated to improve cancer. However, the effects of AHCC on NRF2 have not been examined, and the effects on intestinal adenoma development are not yet fully understood. We first investigated the effects of AHCC (1-5 mg/ml) on NRF2 activity in human colon cancer cell lines by a luciferase reporter gene assay, and found NRF2 transcriptional activities were increased ~12.6-fold. In addition, AHCC dose-dependently increased HO-1 and NQO-1 mRNA levels, and decreased interleukine-6 mRNA levels. Next, we administered 1,000 ppm AHCC for 8 weeks in the diet of Apc mutant Min mice, and found that AHCC significantly reduced the total number of intestinal polyps to 57.7% and to 67.6% of the control value in male and female Min mice, respectively, with suppression of interleukine-6 in the polyp part. These data suggest that AHCC possesses an ability to suppress cellular oxidative stress through activation of NRF2, thereby lowering intestinal polyp development in Min mice.

Phase II trial of eribulin mesylate as a first- or second-line treatment for locally advanced or metastatic breast cancer: a multicenter, single-arm trial.

BACKGROUND: Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer. METHODS: The primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated. RESULTS: Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5-61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0-73.5) and 78.1% (95% CI 63.8-92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1-9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable. CONCLUSIONS: Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer. TRIAL REGISTRATIONS: This trial was retrospectively registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334 ). Date of trial registration: April 1st, 2013.

Mindfulness-based cognitive therapy for Japanese breast cancer patients-a feasibility study.

OBJECTIVES: Mindfulness-based intervention has been receiving growing attention in cancer care. This study aimed to examine feasibility and to preliminary explore effectiveness of mindfulness-based cognitive therapy (MBCT) in Japanese breast cancer patients, and to explore possible modification of the program so that it fits better with this population. METHODS: Twelve participants with diagnosis of Stage I-III breast cancer received an eight session, weekly MBCT intervention in a group therapy format. The participants were followed up until 3 months after the completion of the program. RESULTS: All the participants completed the program with high attendance rate (mean number of attended sessions = 7.7). Significant improvement in anxiety (Hospital Anxiety and Depression Scale (HADS) - anxiety subscale; effect size Cohen's d = 0.88, P < 0.05), trauma-related psychological symptoms (Impact of Event Scale-revised; d = 0.64, P < 0.01) and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer: FACT-B; d = 0.72, P < 0.01), and trend-level improvement in depression (HADS - depression subscale; d = 0.53, P = 0.054) were observed. Qualitative analyses suggested the program may be beneficial for alleviating fear of cancer recurrence and for increasing spiritual well-being. Some recommended modification of the program was indicated from the post-intervention interviews. CONCLUSIONS: Mindfulness-based cognitive therapy was well accepted by Japanese breast cancer patients and yielded favorable effect on their psychological status and quality of life. Further effectiveness study in a randomized-control design is warranted.

Preventive Effects of Heat-Killed Enterococcus faecalis Strain EC-12 on Mouse Intestinal Tumor Development.

Establishing effective methods for preventing colorectal cancer by so-called "functional foods" is important because the global burden of colorectal cancer is increasing. Enterococcus faecalis strain EC-12 (EC-12), which belongs to the family of lactic acid bacteria, has been shown to exert pleiotropic effects, such as anti-allergy and anti-infectious effects, on mammalian cells. In the present study, we aimed to evaluate the preventive effects of heat-killed EC-12 on intestinal carcinogenesis. We fed 5-week-old male and female Apc mutant Min mice diets containing 50 or 100 ppm heat-killed EC-12 for 8 weeks. In the 50 ppm treated group, there was 4.3% decrease in the number of polyps in males vs. 30.9% in females, and significant reduction was only achieved in the proximal small intestine of female mice. A similar reduction was observed in the 100 ppm treated group. Moreover, heat-killed EC-12 tended to reduce the levels of c-Myc and cyclin D1 mRNA expression in intestinal polyps. Next, we confirmed that heat-killed EC-12 suppressed the transcriptional activity of the T-cell factor/lymphoid enhancer factor, a transcriptional factor involved in cyclin D1 mRNA expression in intestinal polyps. Our results suggest that heat-killed EC-12 very weakly suppresses intestinal polyp development in Min mice, in part by attenuating ß-catenin signaling, and this implies that heat-killed EC-12 could be used as a "functional food".

Whole mitochondrial genome genetic diversity in an Estonian population sample.

Mitochondrial DNA is a useful marker for population studies, human identification, and forensic analysis. Commonly used hypervariable regions I and II (HVI/HVII) were reported to contain as little as 25% of mitochondrial DNA variants and therefore the majority of power of discrimination of mitochondrial DNA resides in the coding region. Massively parallel sequencing technology enables entire mitochondrial genome sequencing. In this study, buccal swabs were collected from 114 unrelated Estonians and whole mitochondrial genome sequences were generated using the Illumina MiSeq system. The results are concordant with previous mtDNA control region reports of high haplogroup HV and U frequencies (47.4 and 23.7% in this study, respectively) in the Estonian population. One sample with the Northern Asian haplogroup D was detected. The genetic diversity of the Estonian population sample was estimated to be 99.67 and 95.85%, for mtGenome and HVI/HVII data, respectively. The random match probability for mtGenome data was 1.20 versus 4.99% for HVI/HVII. The nucleotide mean pairwise difference was 27 ± 11 for mtGenome and 7 ± 3 for HVI/HVII data. These data describe the genetic diversity of the Estonian population sample and emphasize the power of discrimination of the entire mitochondrial genome over the hypervariable regions.

Biological markers of invasive breast cancer.

Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer.

Professional identity acquisition process model in interprofessional education using structural equation modelling: 10-year initiative survey.

The mandatory interprofessional education (IPE) programme at Gunma University, Japan, was initiated in 1999. A questionnaire of 10 items to assess the students' understanding of the IPE training programme has been distributed since then, and the factor analysis of the responses revealed that it was categorised into four subscales, i.e. "professional identity", "structure and function of training facilities", "teamwork and collaboration", and "role and responsibilities", and suggested that these may take into account the development of IPE programme with clinical training. The purpose of this study was to examine the professional identity acquisition process (PIAP) model in IPE using structural equation modelling (SEM). Overall, 1,581 respondents of a possible 1,809 students from the departments of nursing, laboratory sciences, physical therapy, and occupational therapy completed the questionnaire. The SEM technique was utilised to construct a PIAP model on the relationships among four factors. The original PIAP model showed that "professional identity" was predicted by two factors, namely "role and responsibilities" and "teamwork and collaboration". These two factors were predicted by the factor "structure and function of training facilities". The same structure was observed in nursing and physical therapy students' PIAP models, but it was not completely the same in laboratory sciences and occupational therapy students' PIAP models. A parallel but not isolated curriculum on expertise unique to the profession, which may help to understand their professional identity in combination with learning the collaboration, may be necessary.

Prognostic implications of receptor discordance between primary and recurrent breast cancer.

BACKGROUND: Discordance rates of hormone receptor (HR) and human epidermal growth factor-2 (HER2) status between primary and recurrent breast cancer were reported to be in the wide range of 10-40 %, although its prognostic relevance remains to be elucidated. METHODS: Fifty-five breast cancer patients had biopsies or resections of recurrent lesions. Pathological assessments of the HR and HER2 status of primary and recurrent lesions were performed in a single laboratory at Keio University Hospital. Tumors were classified as luminal (HR+ and HER2-), luminal/HER2 (HR+ and HER2+), HER2 (HR- and HER2+), or triple negative (HR- and HER2-). RESULTS: Discordance rates in estrogen receptor (ER), progesterone receptor (PgR) and HER2 status between primary tumors and recurrent lesions were 16.4, 30.9 and 10.2 %, respectively. Overall, 14 patients (25.5 %) changed subtypes at recurrent lesions. Patients with a gain in ER and PgR status had a significantly longer disease-free interval compared with the corresponding concordant-negative patients (ER: 99.0 vs. 18.5 months, p = 0.037, PgR: 141.0 vs. 24.4 months, p = 0.011). Patients with a loss of HER2 status experienced a trend toward shorter time to progression, compared with patients who maintained HER2 positivity (4.0 vs. 18.4 months, p = 0.051). CONCLUSIONS: Discordance in receptor status between primary and recurrent breast cancers were seen in 10-30 %. A gain in HR status was significantly associated with better prognosis.

Filamentous structures in skeletal muscle: anchors for the subsarcolemmal space.

In skeletal muscle fibers, intermediate filaments and actin filaments provide structural support to the myofibrils and the sarcolemma. For many years, it was poorly understood from ultrastructural observations that how these filamentous structures were kept anchored. The present study was conducted to determine the architecture of filamentous anchoring structures in the subsarcolemmal space and the intermyofibrils. The diaphragms (Dp) of adult wild type and mdx mice (mdx is a model for Duchenne muscular dystrophy) were subjected to tension applied perpendicular to the long axis of the muscle fibers, with or without treatment with 1% Triton X-100 or 0.03% saponin. These experiments were conducted to confirm the presence and integrity of the filamentous anchoring structures. Transmission electron microscopy revealed that these structures provide firm transverse connections between the sarcolemma and peripheral myofibrils. Most of the filamentous structures appeared to be inserted into subsarcolemmal densities, forming anchoring connections between the sarcolemma and peripheral myofibrils. In some cases, actin filaments were found to run longitudinally in the subsarcolemmal space to connect to the sarcolemma or in some cases to connect to the intermyofibrils as elongated thin filaments. These filamentous anchoring structures were less common in the mdx Dp. Our data suggest that the transverse and longitudinal filamentous structures form an anchoring system in the subsarcolemmal space and the intermyofibrils.