In vitro vascularized tumor platform for modeling tumor-vasculature interactions of inflammatory breast cancer.

Inflammatory breast cancer (IBC), a rare form of breast cancer associated with increased angiogenesis and metastasis, is largely driven by tumor-stromal interactions with the vasculature and the extracellular matrix (ECM). However, there is currently a lack of understanding of the role these interactions play in initiation and progression of the disease. In this study, we developed the first three-dimensional, in vitro, vascularized, microfluidic IBC platform to quantify the spatial and temporal dynamics of tumor-vasculature and tumor-ECM interactions specific to IBC.

Multiparametric Analysis of Longitudinal Quantitative MRI data to Identify Distinct Tumor Habitats in Preclinical Models of Breast Cancer.

This study identifies physiological tumor habitats from quantitative magnetic resonance imaging (MRI) data and evaluates their alterations in response to therapy. Two models of breast cancer (BT-474 and MDA-MB-231) were imaged longitudinally with diffusion-weighted MRI and dynamic contrast-enhanced MRI to quantify tumor cellularity and vascularity, respectively, during treatment with trastuzumab or albumin-bound paclitaxel. Tumors were stained for anti-CD31, anti-Ki-67, and H&E.

Gallbladder Neuroendocrine Carcinoma: A Rare Endocrine Tumor.

Gallbladder neuroendocrine neoplasms (GB-NEN) are very rare neuroendocrine tumors (NETs). GB-NEN can present as carcinoid or typical/atypical carcinoid or small cell carcinoma. Most of the GB-NENs present as gall bladder polyps or stones with right upper quadrant pain, nausea and non-specific symptoms which leads to clinical misdiagnosis.

Anti-HER2 induced myeloid cell alterations correspond with increasing vascular maturation in a murine model of HER2+ breast cancer.

Background: Therapy targeted to the human epidermal growth factor receptor type 2 (HER2) is used in combination with cytotoxic therapy in treatment of HER2+ breast cancer. Trastuzumab, a monoclonal antibody that targets HER2, has been shown pre-clinically to induce vascular changes that can increase delivery of chemotherapy. To quantify the role of immune modulation in treatment-induced vascular changes, this study identifies temporal changes in myeloid cell infiltration with corresponding vascular alterations in a preclinical model of HER2+ breast cancer following trastuzumab treatment.

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry.

Many biological cells/tissues sense the mechanical properties of their local environments via mechanoreceptors, proteins that can respond to forces like pressure or mechanical perturbations. Mechanoreceptors detect their stimuli and transmit signals via a great diversity of mechanisms. Some of the most common roles for mechanoreceptors are in neuronal responses, like touch and pain, or hair cells which function in balance and hearing.

Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer.

The purpose of this study is to investigate imaging and histology-based measurements of intratumoral heterogeneity to evaluate early treatment response to targeted therapy in a murine model of HER2+ breast cancer. BT474 tumor-bearing mice (N = 30) were treated with trastuzumab or saline and imaged longitudinally with either dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) or F-fluoromisonidazole (FMISO) positron emission tomography (PET). At the imaging study end point (day 4 for MRI or 7 for PET), each tumor was excised for immunohistochemistry analysis.

Mathematical modelling of trastuzumab-induced immune response in an in vivo murine model of HER2+ breast cancer.

The goal of this study is to develop an integrated, mathematical-experimental approach for understanding the interactions between the immune system and the effects of trastuzumab on breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2+). A system of coupled, ordinary differential equations was constructed to describe the temporal changes in tumour growth, along with intratumoural changes in the immune response, vascularity, necrosis and hypoxia. The mathematical model is calibrated with serially acquired experimental data of tumour volume, vascularity, necrosis and hypoxia obtained from either imaging or histology from a murine model of HER2+ breast cancer.

Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets.

Immune thrombocytopenia (ITP) is a prevalent autoimmune disease characterized by autoantibody-induced platelet clearance. Some ITP patients are refractory to standard immunosuppressive treatments such as intravenous immunoglobulin (IVIg). These patients often have autoantibodies that target the ligand-binding domain (LBD) of glycoprotein Ibα (GPIbα), a major subunit of the platelet mechanoreceptor complex GPIb-IX.

Imaging Considerations and Interprofessional Opportunities in the Care of Breast Cancer Patients in the Neoadjuvant Setting.

Objective: To discuss standard-of-care and emerging imaging techniques employed for screening and detection, diagnosis and staging, monitoring response to therapy, and guiding cancer treatments.

Data Sources: Published journal articles indexed in the National Library of Medicine database and relevant websites.

Conclusion: Imaging plays a fundamental role in the care of cancer patients and specifically, breast cancer patients in the neoadjuvant setting, providing an excellent opportunity for interprofessional collaboration between oncologists, researchers, radiologists, and oncology nurses.

Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system.

Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete water droplet to a tissue surface for efficient extraction of biomolecules.

A Review on Community-Based Knowledge Transfer and Exchange (KTE) Initiatives for Promoting Well-Being in Older Adults.

Knowledge transfer and exchange (KTE) processes can facilitate evidence-informed community-based care for seniors, but understanding effective KTE in gerontology is limited. A scoping review was conducted to evaluate the current state of KTE in the community-based sector for seniors. Twelve articles met the inclusion criteria, which addressed a broad variety of topics including caregiving, elder abuse, falls prevention, home-rehabilitation, hospice and dementia care.

Social Isolation in Chinese Older Adults: Scoping Review for Age-Friendly Community Planning.

Chinese older adults may be at increased risk of social isolation and loneliness, and a fragmented understanding exists about the challenges they face for social participation in their neighbourhoods and communities. A scoping review was undertaken to describe the current knowledge on social isolation and loneliness in urban-dwelling Chinese older adults living in Western societies to inform future research, practice, and policy in Canada. Nineteen articles met the inclusion criteria.

Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor.

Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIbα subunit of GPIb-IX was identified.

Quantitative [F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer.

Purpose: Evaluation of [F]fluoromisonidazole ([F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer.

Procedures: Mice with BT474, HER2+ tumors, were imaged with [F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging.

Inhibiting GPIbα Shedding Preserves Post-Transfusion Recovery and Hemostatic Function of Platelets After Prolonged Storage.

Objective: The platelet storage lesion accelerates platelet clearance after transfusion, but the underlying molecular mechanism remains elusive. Although inhibiting sheddase activity hampers clearance of platelets with storage lesion, the target platelet protein responsible for ectodomain shedding-induced clearance is not definitively identified. Monoclonal antibody 5G6 was developed recently to bind specifically human platelet receptor glycoprotein (GP)Ibα and inhibit its shedding but not shedding of other receptors.

Non-genetic Purification of Ventricular Cardiomyocytes from Differentiating Embryonic Stem Cells through Molecular Beacons Targeting IRX-4.

Isolation of ventricular cardiomyocytes (vCMs) has been challenging due to the lack of specific surface markers. Here we show that vCMs can be purified from differentiating mouse embryonic stem cells (mESCs) using molecular beacons (MBs) targeting specific intracellular mRNAs. We designed MBs (IRX4 MBs) to target mRNA encoding Iroquois homeobox protein 4 (Irx4), a transcription factor specific for vCMs.