To assess the expression of vascular normalization genes in different molecular subtypes of breast cancer and to determine whether molecular subtypes with a higher vascular normalization gene expression can be identified using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI).This prospective study evaluated 306 female (mean age ± standard deviation, 50 ± 10 years), recruited between January 2014 and August 2017, who had de novo breast cancer larger than 1 cm in diameter (308 tumors). DCE MRI followed by IVIM DWI studies using 11 different b-values (0 to 1200 s/mm²) were performed on a 1.5T MRI system. The Tofts model and segmented biexponential IVIM analysis were used. For each tumor, the molecular subtype (according to six [I-VI] subtypes and PAM50 subtypes), expression profile of genes for vascular normalization, pericytes, and normal vascular signatures were determined using freshly frozen tissue. Statistical associations between imaging parameters and molecular subtypes were examined using logistic regression or linear regression with a significance level of p = 0.05.Breast cancer subtypes III and VI and PAM50 subtypes luminal A and normal-like exhibited a higher expression of genes for vascular normalization, pericyte markers, and normal vessel function signature (p < 0.001 for all) compared to other subtypes. Subtypes III and VI and PAM50 subtypes luminal A and normal-like, versus the remaining subtypes, showed significant associations with Ktrans, kep, vp, and IAUGCBN90 on DEC MRI, with relatively smaller values in the former. The subtype grouping was significantly associated with D, with relatively less restricted diffusion in subtypes III and VI and PAM50 subtypes luminal A and normal-like.DCE MRI and IVIM parameters may identify molecular subtypes of breast cancers with a different vascular normalization gene expression.
BACKGROUND: Most previous studies on white cell (WBC) reduction by filtration have been small‐scale studies conducted under tightly controlled laboratory conditions. Their results would be the ideal, rather than what might be expected during routine operation. STUDY DESIGN AND METHODS: To obtain information on routine filtration of blood components, data have been collected from a large‐scale, ongoing, multicenter clinical trial designed to determine the effectiveness of WBC reduction in or ultraviolet B radiation of platelet concentrates before transfusion in preventing platelet alloimmunization and platelet transfusion refractoriness. The WBC content of blood components both before and after filtration was determined by automated cell counters and a manual propidium iodide‐staining method, respectively. Platelet and red cell losses during filtration were measured. RESULTS: The average platelet losses after filtration were 24 +/− 15 percent and 20 +/− 9 percent for apheresis platelets and pooled platelets, respectively. The frequencies at which filtered platelet concentrates contained high levels of residual WBCs (> 5 × 10(6)) were 7 percent and 5 percent for apheresis platelets and pooled platelets, respectively. Further analysis of the platelet filtration data showed that greater numbers of total initial WBCs in the pooled platelets were associated with increased percentages of filtration failure (> 5 × 10(6) residual WBCs). For packed red cells, the average losses during filtration were 23 +/− 4 percent and 15 +/− 3 percent for CPDA‐1 units and Adsol units, respectively. The frequencies at which filtered red cells contained > 5 × 10(6) residual WBCs were 2.7 percent for one type of filter and 0.3 percent for another type of filter. CONCLUSION: There were significant losses of platelets during filtration, which could add to the costs of WBC reduction and lead to possible increases in donor exposures. Filtration failures still occurred, despite careful observation of the standard filtration procedures. The number of total WBCs in pooled platelets before filtration has been identified as an important factor in determining the success of WBC reduction.
Poster: ECR 2016 / B-0424 / B1+ field correction of T1 estimation is necessary for quantitative breast DCE MRI even at 1.5T by: W. Tsai , K. Kao, K. Chang, C. E. Lin; Taipei/TW
Hec1 (NDC80) is an integral part of the kinetochore and is overexpressed in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. A highly potent first-in-class compound targeting Hec1, TAI-1, was identified and is characterized in this study to determine its potential as an anticancer agent for clinical utility. The in vitro potency, cancer cell specificity, synergy activity, and markers for response of TAI-1 were evaluated with cell lines. Mechanism of action was confirmed with western blotting and immunofluorescent staining. The in vivo potency of TAI-1 was evaluated in three xenograft models in mice. Preliminary toxicity was evaluated in mice. Specificity to the target was tested with a kinase panel. Cardiac safety was evaluated with hERG assay. Clinical correlation was performed with human gene database. TAI-1 showed strong potency across a broad spectrum of tumor cells. TAI-1 disrupted Hec1-Nek2 protein interaction, led to Nek2 degradation, induced significant chromosomal misalignment in metaphase, and induced apoptotic cell death. TAI-1 was effective orally in in vivo animal models of triple negative breast cancer, colon cancer and liver cancer. Preliminary toxicity shows no effect on the body weights, organ weights, and blood indices at efficacious doses. TAI-1 shows high specificity to cancer cells and to target and had no effect on the cardiac channel hERG. TAI-1 is synergistic with doxorubicin, topotecan and paclitaxel in leukemia, breast and liver cancer cells. Sensitivity to TAI-1 was associated with the status of RB and P53 gene. Knockdown of RB and P53 in cancer cells increased sensitivity to TAI-1. Hec1-overexpressing molecular subtypes of human lung cancer were identified. The excellent potency, safety and synergistic profiles of this potent first-in-class Hec1-targeted small molecule TAI-1 show its potential for clinically utility in anti-cancer treatment regimens.
Barcelona Clinic Liver Cancer (BCLC) staging has been an important clinical guideline for the management of hepatocellular carcinoma (HCC). BCLC 0 and A stages (BCLC 0/A) have been designated as the early-stage HCC, and the curative treatment is recommended as the primary therapeutic modality. However, a recent study indicated that a significant number of BCLC 0/A patients were not initially managed with the curative treatment without knowing why.We, therefore, conducted a study on BCLC 0/A patients who had and had not received initial curative treatment cared at our cancer center from January 2011 to December 2015 and analyzed causes contributing to not having the initial curative treatment.One hundred and sixty-nine BCLC 0/A patients were identified and included in the study. Seventy two patients (43%) received the initial curative treatment and 97 patients (57%) did not. After careful review of medical records, all 97 patients without the initial curative treatment had identifiable reasons for not having the initial curative treatment. Two main reasons for not having the initial curative treatment were "probable presence of additional HCC and requiring diagnostic angiography" (28%) and "difficult or complicating anatomical location of tumors" (17%). When the relevant clinical parameters were compared between the 2 groups of patients, it was found that patients without the initial curative treatment had more serious clinical conditions and worse overall and recurrence-free survival outcomes compared with those who had the initial curative treatment.Our finding indicates that a significant fraction of the BCLC 0/A HCC patients is unable to have initial curative treatment as recommended by BCLC guidelines. These early stages of HCC patients represent a distinctive subpopulation and are in need of further investigation to improve their survival outcomes.
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