Cytokine-induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche.

Peripheral blood hematopoietic stem and progenitor cells (HSPCs), mobilized by granulocyte colony-stimulating factor, are widely used as a source for both autologous and allogeneic stem cell transplantation. The use of mobilized HSPCs has several advantages over traditional bone marrow-derived HSPCs, including a less invasive harvesting process for the donor, higher HSPC yields, and faster hematopoietic reconstitution in the recipient. For years, the mechanisms by which cytokines and other agents mobilize HSPCs from the bone marrow were not fully understood.

Medical and surgical co-management - A strategy of improving the quality and outcomes of perioperative care.

With the increase of ageing population, rates of chronic diseases and complex medical conditions, the management of high-risk surgical patients is likely to become a great concern in most countries. Considering all these factors, it is certainly rational and intuitive that internists should be included into a collaborative model of medical and surgical co-management, where their multi-potentiality and synthesis capacity require them to coordinate the multidisciplinary team and to be the leading agent of change. In this regard, our aim was to present the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for implementation of this strategy of care, encouraging internists to assume an important role and to provide continuity of multidisciplinary care, from the decision to operate through to rehabilitation and recovery.

The prognostic value of tumor-stroma ratio in tumor-positive axillary lymph nodes of breast cancer patients.

The tumor-stroma ratio (TSR) has previously been found to be a strong prognostic parameter in primary breast cancer tumors. Since the presence of tumor cells in lymph nodes is important for clinical decision making, the influence of TSR in the primary breast tumor combined with the TSR in tumor-positive lymph nodes on prognosis was evaluated. Women with invasive breast cancer without distant metastasis who underwent an axillary lymph node dissection between 1985 and 1994 at the Leiden University Medical Center were retrospectively analyzed.

Mesenchymal stromal cells induce a permissive state in the bone marrow that enhances G-CSF-induced hematopoietic stem cell mobilization in mice.

Mesenchymal stromal cells (MSCs) support hematopoietic stem cells (HSCs) in vivo and enhance HSC engraftment and hematopoietic recovery upon cotransplantation with HSCs. These data have led to the hypothesis that MSCs may affect the HSC niche, leading to changes in HSC retention and trafficking. We studied the effect of MSC administration on the HSC compartment in the bone marrow (BM) in mice.

Hospital ambulatory medicine: A leading strategy for Internal Medicine in Europe.

Addressing the current collision course between growing healthcare demands, rising costs and limited resources is an extremely complex challenge for most healthcare systems worldwide. Given the consensus that this critical reality is unsustainable from staff, consumer, and financial perspectives, our aim was to describe the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for encouraging internists to lead a thorough reengineering of hospital operational procedures by the implementation of innovative hospital ambulatory care strategies. Among these, we include outpatient and ambulatory care strategies, quick diagnostic units, hospital-at-home, observation units and daycare hospitals.

Alternatively spliced tissue factor synergizes with the estrogen receptor pathway in promoting breast cancer progression.

Background: Procoagulant full-length tissue factor (flTF) and its minimally coagulant alternatively spliced isoform (asTF), promote breast cancer (BrCa) progression via different mechanisms. We previously showed that flTF and asTF are expressed by BrCa cells, resulting in autoregulation in a cancer milieu. BrCa cells often express hormone receptors such as the estrogen receptor (ER), leading to the formation of hormone-regulated cell populations.

High nuclear expression levels of histone-modifying enzymes LSD1, HDAC2 and SIRT1 in tumor cells correlate with decreased survival and increased relapse in breast cancer patients.

Background: Breast cancer is a heterogeneous disease with a highly variable clinical outcome in which both genetic and epigenetic changes have critical roles. We investigated tumor expression levels of histone-modifying enzymes LSD1, HDAC2 and SIRT1 in relation with patient survival and tumor relapse in a retrospective cohort of 460 breast cancer patients. Additionally, we correlated expression levels with tumor differentiation and tumor cell proliferation.

Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma.

Background: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients.

Comparison of frequencies and prognostic effect of molecular subtypes between young and elderly breast cancer patients.

Purpose: To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients.

Patients And Methods: Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of 142/822 fresh frozen tissues were available with good quality RNA and analyzed by gene expression microarray.

Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in patients with alpha-1-antitrypsin deficiency.

Granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic stem and progenitor cell (HSPC) mobilization is associated with the release of neutrophil-derived proteases. Previously, we have shown that alpha-1-antitrypsin (AAT) inhibits these proteases in mice, resulting in inhibition of HSPC mobilization. Here, we studied the relationship between AAT and HSPC in steady state and cytokine-induced mobilization in humans.

Tumor immune subtypes distinguish tumor subclasses with clinical implications in breast cancer patients.

There is strong evidence that the host's cellular immune response is linked to tumor progression, however its impact on patient outcome in breast cancer is poorly understood. The purpose of this study is to define tumor immune subtypes, focusing on cellular immune responses and investigate their prognostic effect in breast cancer patients. Our training (n = 440) and validation cohort (n = 382) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996.

The prognostic value of apoptotic and proliferative markers in breast cancer.

Increasing ability of early breast cancer (BC) diagnosis leading to more early stage detection, better survival, and low relapse marks one of the milestones achieved over the decades. Foregoing poses a challenge for clinicians regarding optimal treatment, in which over- and under-treatment should be avoided. Classical prognostic and predictive factors fall short for individualized adjuvant therapy selection in this patient group.

TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis.

TGF-β signaling is a therapeutic target in advanced cancers. We identified tumor necrosis factor receptor-associated factor 4 (TRAF4) as a key component mediating pro-oncogenic TGF-β-induced SMAD and non-SMAD signaling. Upon TGF-β stimulation, TRAF4 is recruited to the active TGF-β receptor complex, where it antagonizes E3 ligase SMURF2 and facilitates the recruitment of deubiquitinase USP15 to the TGF-β type I receptor (TβRI).

Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner.

Full-length tissue factor (flTF), the coagulation initiator, is overexpressed in breast cancer (BrCa), but associations between flTF expression and clinical outcome remain controversial. It is currently not known whether the soluble alternatively spliced TF form (asTF) is expressed in BrCa or impacts BrCa progression. We are unique in reporting that asTF, but not flTF, strongly associates with both tumor size and grade, and induces BrCa cell proliferation by binding to β1 integrins.

Expression of cell adhesion molecules and prognosis in breast cancer.

Background: Cell adhesion molecules (CAMs) play an important role in the process of metastasis. The prognostic value of tumour expression of N-cadherin, E-cadherin, carcinoembryonic antigen (CEA) and epithelial CAM (Ep-CAM) was evaluated in patients with breast cancer.

Methods: A tissue microarray of the patient cohort was stained immunohistochemically for all markers and analysed by microscopy.

The prognostic role of TGF-β signaling pathway in breast cancer patients.

Background: The transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-β signaling biomarkers.

Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma.

Background: Hodgkin Lymphoma (HL) is highly curable when treated accurately. The challenge is to cure patients with the minimal risk of long-term complications. For that, optimal initial diagnostics are required to determine the optimal treatment plan.

Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study.

Long interspersed element 1 (LINE-1), a non-coding genomic repeat sequence, methylation status can influence tumor progression. In this study, the clinical significance of LINE-1 methylation status was assessed in primary breast cancer in young versus old breast cancer patients. LINE-1 methylation index (MI) was assessed by absolute quantitative assessment of methylated alleles (AQAMA) PCR assay.

Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer.

Background: The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.

Methods: The study population (N = 574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.

NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study.

Background: Cell surface NKG2D ligands (NKG2DL) bind to the activating NKG2D receptor present on NK cells and subsets of T cells, thus playing a role in initiating an immune response. We examined tumor expression and prognostic effect of NKG2DL in breast cancer patients.

Methods: Our study population (n = 677) consisted of all breast cancer patients primarily treated with surgery in our center between 1985 and 1994.

Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor-positive early breast cancer patients.

Epithelial mesenchymal transition (EMT) plays an important role in the development of metastases. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by transcription factors, such as SNAIL, SLUG, and TWIST. We examined the prognostic value of these factors as well as E-cadherin and N-cadherin, in a well-described large cohort of breast cancer patients treated with primary surgery.

Allele-specific regulation of FGFR2 expression is cell type-dependent and may increase breast cancer risk through a paracrine stimulus involving FGF10.

Introduction: SNPs rs2981582 and rs2981578, located in a linkage disequilibrium block (LD block) within intron 2 of the fibroblast growth factor receptor 2 gene (FGFR2), are associated with a mildly increased breast cancer risk. Allele-specific regulation of FGFR2 mRNA expression has been reported previously, but the molecular basis for the association of these variants with breast cancer has remained elusive to date.

Methods: mRNA levels of FGFR2 and three fibroblast growth factor genes (FGFs) were measured in primary fibroblast and epithelial cell cultures from 98 breast cancer patients and correlated to their rs2981578 genotype.

Primary tumor classification according to methylation pattern is prognostic in patients with early stage ER-negative breast cancer.

Breast cancer patients with similar clinical stage may experience different disease outcomes. Aberrant DNA methylation of primary breast tumors can have impact on the clinical outcome. This study aimed to assess clinical utility of tumor-specific methylated sequences (MINT17, 31) and tumor-related gene (RARβ2) methylation classification in primary breast tumors.