Postoperative prognosis is better for hormonal receptor-positive breast cancer than for other phenotypes; however, there are no definitive predictive factors for relapse or survival. This study aimed to evaluate the maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) and clinicopathological characteristics as possible predictors of postoperative relapse-free survival (RFS) and overall survival (OS) in hormonal receptor-positive breast cancer patients. We evaluated 262 patients with Stage I–III breast cancer diagnosed as luminal type (luminal A, 166; luminal B, 96 patients) who underwent preoperative FDG-PET/CT between January 2006 and December 2011 at two institutions. The relationships among SUVmax and clinicopathological factors (age, clinical T/N stage, nuclear grade, lymph node metastasis and vascular invasion) were evaluated. A phantom study was performed to correct differences in PET/CT analysis between two institutions. The patients were divided according to the SUVmax cutoff on receiver operating characteristic (ROC) analysis for OS (≤6.0 group vs. >6.0 group, AUC = 0.742). Clinical T-factor and nuclear grade were significantly correlated with SUVmax (p < 0.0001 and p = 0.0092, respectively). In the uni- and multivariate analyses using the Cox model for relapse, SUVmax was significant (p = 0.013 and p = 0.055, respectively) among characteristics. RFS curves showed that prognosis was significantly better for the SUVmax ≤ 6.0 group than for the SUVmax > 6.0 group (p = 0.004). Similarly, SUVmax was significant for OS (p = 0.007 and p = 0.008). OS was significantly different between the SUVmax ≤ 6.0 and >6.0 groups (p < 0.001). SUVmax was useful for predicting outcomes in patients with luminal-type breast cancer.

Hybrid EBCS can provide sufficient free margin, and its surgical curability is acceptable. Additionally, this method is superior to CBCS in terms of cosmetic outcome.

We investigated effects of human (h) GH on the proliferation of h-hepatocytes that had been engrafted in the liver of albumin enhancer/promoter driven-urokinase plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice (chimeric mice). The h-hepatocytes therein were considered to be deficient in GH, because hGH receptor (hGHR) is unresponsive to mouse GH. Actually, hIGF-1 was undetectable in chimeric mouse sera. The uPA/SCID mice were transplanted with h-hepatocytes from a 6-year (6Y)-old donor, and were injected with recombinant hGH (rhGH). rhGH stimulated the repopulation speed of h-hepatocytes; and up-regulated hIGF-1, human signal transducers and activators of transcription (hSTAT) 3, and cell cycle regulatory genes such as human forkhead box M1, human cell division cycle 25A, and human cyclin D1. To confirm the reproducibility of these effects of rhGH, similar experiments were run using h-hepatocytes from a 46-year (46Y)-old donor. rhGH similarly enhanced their repopulation speed and up-regulated the expression of the abovetested genes, especially hIGF-1 and hSTAT1. The extent of the enhancement by rhGH was much less than that in 6Y-hepatocyte-chimeric mice most probably due to the difference in GHR expression levels between the two donors. In conclusion, this study clearly demonstrated that rhGH stimulates the proliferation of h-hepatocytes in vivo.

Microwave breast imaging is a painless and nonradiation method. This pilot study aimed to evaluate the detective capability and feasibility of a prototype of a portable breast cancer detector using a radar-based imaging system. Five patients with histologically confirmed breast cancers with a minimum diameter of 1 cm were enrolled in this study. The antenna array dome of the device was placed on the breast of the patient in a supine position for 15 min per single examination. The primary endpoint was a detection rate of breast cancers. The secondary endpoints were positional accuracy and adverse event. All five targeted breast tumors were detected and were visualized at the sites confirmed by other diagnostic modalities. Among five tumors, one was not detected via mammography because of heterogeneously dense breast and another was a microinvasive carcinoma of invasive tumor size 0.5 mm. No study-related adverse events occurred. The prototype of a portable breast cancer detector has sufficient detective capability, is safe for clinical use, and might detect an early stage breast cancer, such as noninvasive carcinoma. Future developments should focus on further decreasing the size of the machine and shortening inspection time.

No abstract

We studied the usefulness of glycated albumin (GA) for decisions regarding the discontinuation of a diabetes drug in type 2 diabetic patients with good glycemic control, and the factors associated with increases in GA following discontinuation of a diabetes drug in patients with type 2 diabetes mellitus. Sixteen patients (12 males and 4 females) were enrolled in the present study and discontinued one diabetes drug. When the change in GA was less than 1 % at 4 weeks after the discontinuation of the diabetes drug (DGA4w), discontinuation was continued (the continuous group, n = 10), but when the change in GA was more than a 1 %, the discontinued diabetes drug was resumed (the resume group, n = 6). In the continuous group, HbA1c at 12 weeks after discontinuation (6.2 ± 0.6 %) remained unchanged from its value at discontinuation (6.2 ± 0.7 %) , but it was significantly elevated at 12 weeks after discontinuation in the resume group (changing from 6.3 ± 0.1 to 7.0 ± 0.6 %). Age, duration of diabetes, and GA were significantly lower while body mass index (BMI) was significantly higher in the continuous group than in the resume group, but no significant difference in HbA1c was observed between the groups. The discontinuation of a diabetes drug in patients with low insulin secretion must be performed carefully because factors such as duration of diabetes, BMI, and GA showed significant differences between the continuous group and resume group in our study, and these indicators are known to be linked with insulin secretion.

Hepatocyte transplantation is effective for treating liver failure, but healthy donors as a source of hepatocytes are quite limited. The livers of patients with hepatic fibrosis could be an alternative source; however, few reports have examined the nature of hepatocytes from fibrotic livers (f-hepatocytes). In this study, we compared the growth of f-hepatocytes and hepatocytes from normal livers (n-hepatocytes). Hepatocytes were isolated from normal and CCl(4)-treated wild-type Fischer rats that express dipeptidyl dipeptidase IV (DPPIV) gene (DPPIV(+)). The n- and f-hepatocytes proliferated in culture at similar rates. Both types of hepatocytes were transplanted into DPPIV(-) mutant Fischer rats that had been treated with retrorsine to injure the liver and were partially hepatectomized (PHx) before transplantation. Both n- and f-DPPIV(+)-hepatocytes proliferated and formed colonies. The colony sizes of f-hepatocytes 21 days posttransplantation were approximately three times those of n-hepatocytes. The hepatocytes were analyzed using a fluorescence activated cell sorter (FACS). The FACS profile differed between f- and n-hepatocytes: f-hepatocytes were less granular, less autofluorescent, and smaller than n-hepatocytes. These characteristics of f-hepatocytes resembled those reported for small-sized n-hepatocytes (SHs), which are highly proliferative and preferentially express a unique set of 10 SH genes. However, f-hepatocytes preferentially expressed only five of the SH genes. The expression profile of f-hepatocytes was rather similar to that of proliferating n-hepatocytes in the regenerating liver after PHx. The f-hepatocytes were morphologically normal and did not show any preneoplastic phenotype. These normal and proliferative natures of f-hepatocytes in vivo suggest the fibrotic liver as a source of hepatocytes for transplantation.

Background Previously, we reported that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer; its prognosis is worse than that of Wnt5a-negative breast cancer. This study aimed to investigate the mechanisms underlying the poor prognosis in Wnt5a-positive breast cancer patients. Methods In total, 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were conducted using MCF-7 cells stably expressing Wnt5a [MCF-7/Wnt5a (+)]. Based on the outcomes, cell viability/drug sensitivity assays, and mutation analysis were performed using cell cultures and breast cancer tissues. The relationship between Wnt5a and the PI3K–AKT–mTOR signaling pathway was also examined. Results The relapse-free survival rate in patients with Wnt5a-positive breast cancer was significantly lower than that in patients with Wnt5a-negative breast cancer (P = 0.047). DNA microarray data suggest that only the cytochrome P450 (CYP) pathway was significantly upregulated in MCF-7/Wnt5a (+) cells (P = 0.0440). Additionally, MCF-7/Wnt5a (+) cells displayed reduced sensitivity to the metabolic substrates of CYP, tamoxifen (P < 0.001), paclitaxel (P < 0.001), and cyclophosphamide (P < 0.001). Of note, PIK3CA mutations were not associated with the expression of Wnt5a in breast cancer tissue and culture cells. Conclusions In ER-positive breast cancer, Wnt5a upregulates the CYP metabolic pathway and suppresses tamoxifen, paclitaxel, and cyclophosphamide resistance, all of the three, standard treatment methods for ER-positive breast cancer. Wnt5a is thus potentially involved in the poor prognosis of ER-positive breast cancer independently of the PI3K–AKT–mTOR signaling pathway.