Bone mineral density affects tumor growth by shaping microenvironmental heterogeneity.

Breast cancer bone metastasis is a major cause of mortality in patients with advanced breast cancer. Although decreased mineral density is a known risk factor for bone metastasis, the underlying mechanisms remain poorly understood because studying the isolated effect of bone mineral density on tumor heterogeneity is challenging with conventional approaches. Moreover, mineralized biomaterials are commonly utilized for clinical bone defect repair, but how mineralized biomaterials affect the foreign body response and wound healing is unclear.

Brain Metastases as Inaugural Sign of Non-Small Cell Lung Carcinoma: Case Series and Review of Literature.

In the era of immune checkpoint inhibitors (ICI), managing non-oncogene driven non-small cell lung cancer (NSCLC) with brain metastases (BM) is challenging, especially when brain involvement is the initial sign. Patients with newly diagnosed brain metastatic NSCLC without epidermal growth factor receptor (EFGR) nor anaplastic lymphoma kinase (ALK) alterations were retrospectively included. Twenty-five patients were analyzed; 15 (60%) had symptomatic BM as the first sign (group 1), while 10 (40%) had BM discovered during complementary examinations (group 2).

A scoping review of the legal and ethical challenges with the use of normothermic regional perfusion in controlled donation after circulatory determination of death from 2005 to 2023.

Use of normothermic regional perfusion (NRP) to enable organ reconditioning and assessment in donation after circulatory determination of death is controversial. We conducted a scoping review of peer-reviewed articles, news media, legal literature, and professional society position statements addressing ethical and/or legal issues in use of NRP in controlled donation after circulatory determination of death from January 1, 2005, to January 5, 2024. Thematic analysis, assessing the 4 principles of bioethics (autonomy, beneficence, nonmaleficence, and justice) and subthemes identified within each, was conducted for the 112 publications meeting inclusion criteria.

Pragmatic Trial of Palliative Care Support Using Extension for Community Healthcare Outcomes Mentoring.

Increasing rates of chronic diseases and an aging population have placed palliative care at the forefront of public health efforts. The major goal of palliative care is to achieve the best possible quality of life for patients and their families or caregivers. To reduce barriers and improve palliative care, the From Advance Care Planning Toward Palliative Care coalition was first formed in South Dakota in 2017.

Protocol to fabricate elastomer microwells for three-dimensional culture of primary adipocytes.

Our understanding of how adipocytes influence metabolic signaling, immune function, and cancer progression remains limited as the culture of primary adipocytes is challenging. Here, we present a protocol to fabricate elastomer microwells for three-dimensional culture of collagen-embedded adipocytes. We describe steps to cure and functionalize elastomer microwells and to isolate and embed primary adipocytes.

Bone mineral density affects tumor growth by shaping microenvironmental heterogeneity.

Breast cancer bone metastasis is the leading cause of mortality in patients with advanced breast cancer. Although decreased mineral density is a known risk factor for bone metastasis, the underlying mechanisms remain poorly understood because studying the isolated effect of bone mineral density on tumor heterogeneity is challenging with conventional approaches. Here, we investigate how bone mineral content affects tumor growth and microenvironmental complexity by combining single-cell RNA-sequencing with mineral-containing or mineral-free decellularized bone matrices.

Computational modeling of the physical features that influence breast cancer invasion into adipose tissue.

Breast cancer invasion into adipose tissue strongly influences disease progression and metastasis. The degree of cancer cell invasion into adipose tissue depends on both biochemical signaling and the mechanical properties of cancer cells, adipocytes, and other key components of adipose tissue. We model breast cancer invasion into adipose tissue using discrete element method simulations of active, cohesive spherical particles (cancer cells) invading into confluent packings of deformable polyhedra (adipocytes).

Outcomes of non-small cell lung cancer patients with non-V600E mutations: a series of case reports and literature review.

Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of cases of lung cancer. The standard first-line therapy for patients without oncogenic driver metastatic NSCLC is anti PD-L1 immune checkpoint inhibition (ICI) with platinum-based chemotherapy. Approximately 4% of NSCLC patients harbor mutations; the V600E mutation is the most common.

Computational modeling of the physical features that influence breast cancer invasion into adipose tissue.

Breast cancer invasion into adipose tissue strongly influences disease progression and metastasis. The degree of cancer cell invasion into adipose tissue depends on numerous biochemical and physical properties of cancer cells, adipocytes, and other key components of adipose tissue. We model breast cancer invasion into adipose tissue as a physical process by carrying out simulations of active, cohesive spherical particles (cancer cells) invading into confluent packings of deformable polyhedra (adipocytes).

COLLAGEN MINERALIZATION DECREASES NK CELL-MEDIATED CYTOTOXICITY OF BREAST CANCER CELLS VIA INCREASED GLYCOCALYX THICKNESS.

Skeletal metastasis is common in patients with advanced breast cancer, and often caused by immune evasion of disseminated tumor cells (DTCs). In the skeleton, tumor cells not only disseminate to the bone marrow, but also to osteogenic niches in which they interact with newly mineralizing bone extracellular matrix (ECM). However, it remains unclear how mineralization of collagen type I, the primary component of bone ECM, regulates tumor-immune cell interactions.

Collagen Mineralization Decreases NK Cell-Mediated Cytotoxicity of Breast Cancer Cells via Increased Glycocalyx Thickness.

Skeletal metastasis is common in patients with advanced breast cancer and often caused by immune evasion of disseminated tumor cells (DTCs). In the skeleton, tumor cells not only disseminate to the bone marrow but also to osteogenic niches in which they interact with newly mineralizing bone extracellular matrix (ECM). However, it remains unclear how mineralization of collagen type I, the primary component of bone ECM, regulates tumor-immune cell interactions.

Endothelial cells metabolically regulate breast cancer invasion toward a microvessel.

Breast cancer metastasis is initiated by invasion of tumor cells into the collagen type I-rich stroma to reach adjacent blood vessels. Prior work has identified that metabolic plasticity is a key requirement of tumor cell invasion into collagen. However, it remains largely unclear how blood vessels affect this relationship.

Phosphoproteomic Changes Induced by Cell-Derived Matrix and Their Effect on Tumor Cell Migration and Cytoskeleton Remodeling.

Increased fibrotic extracellular matrix (ECM) deposition promotes tumor invasion, which is the first step of the metastatic cascade. Yet, the underlying mechanisms are poorly understood as conventional studies of tumor cell migration are often performed in 2D cultures lacking the compositional and structural complexity of native ECM. Moreover, these studies frequently focus on select candidate pathways potentially overlooking other relevant changes in cell signaling.

Anaplastic Lymphoma Kinase Inhibitor-Induced Neutropenia: A Systematic Review.

Lung cancers with ALK rearrangement represent less than 5% of all lung cancers. ALK inhibitors are currently used to treat first-line metastatic non-small cell lung cancer with ALK rearrangement. Compared to chemotherapy, ALK inhibitors have improved progression-free survival, overall survival, and quality of life for patients.

Bone-matrix mineralization dampens integrin-mediated mechanosignalling and metastatic progression in breast cancer.

In patients with breast cancer, lower bone mineral density increases the risk of bone metastasis. Although the relationship between bone-matrix mineralization and tumour-cell phenotype in breast cancer is not well understood, mineralization-induced rigidity is thought to drive metastatic progression via increased cell-adhesion forces. Here, by using collagen-based matrices with adjustable intrafibrillar mineralization, we show that, unexpectedly, matrix mineralization dampens integrin-mediated mechanosignalling and induces a less proliferative stem-cell-like phenotype in breast cancer cells.

Selective Accumulation of Near Infrared-Labeled Multivalent Quinidine Copolymers in Tumors Overexpressing P-Glycoprotein: Potential for Noninvasive Diagnostic Imaging.

P-glycoprotein (P-gp) is a promiscuous small molecule transporter whose overexpression in cancer is associated with multidrug resistance (MDR). In these instances, anticancer drugs can select for P-gp-overexpressing cells, leading to cancer recurrence with an MDR phenotype. To avoid selection for MDR cancers and inform individual patient treatment plans, it is critical to noninvasively identify P-gp-overexpressing tumors prior to administration of chemotherapy.

Capecitabine efficacy after cycline-dependent-kinase 4/6 inhibitor plus endocrine therapy in metastatic hormone receptor-positive breast cancer.

Background: The combination of endocrine treatment with cycline-dependent-kinase 4/6 inhibitor is the new standard of treatment in hormone receptor-positive HER2 negative metastatic breast cancer. The optimal subsequent treatment after CDK4/6 inhibitor remain unclear. As recommended by standard guidelines, capecitabine, an oral chemotherapy is a therapeutic option in endocrine resistant metastatic breast cancer.

Biomineralogical signatures of breast microcalcifications.

Microcalcifications, primarily biogenic apatite, occur in cancerous and benign breast pathologies and are key mammographic indicators. Outside the clinic, numerous microcalcification compositional metrics (e.g.

A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer.

Purpose: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules.

Convergent Approaches to Delineate the Metabolic Regulation of Tumor Invasion by Hyaluronic Acid Biosynthesis.

Metastasis is the leading cause of breast cancer-related deaths and is often driven by invasion and cancer-stem like cells (CSCs). Both the CSC phenotype and invasion are associated with increased hyaluronic acid (HA) production. How these independent observations are connected, and which role metabolism plays in this process, remains unclear due to the lack of convergent approaches integrating engineered model systems, computational tools, and cancer biology.

IGF2BP2 promotes cancer progression by degrading the RNA transcript encoding a v-ATPase subunit.

IGF2BP2 binds to a number of RNA transcripts and has been suggested to function as a tumor promoter, although little is known regarding the mechanisms that regulate its roles in RNA metabolism. Here we demonstrate that IGF2BP2 binds to the 3' untranslated region of the transcript encoding ATP6V1A, a catalytic subunit of the vacuolar ATPase (v-ATPase), and serves as a substrate for the NAD-dependent deacetylase SIRT1, which regulates how IGF2BP2 affects the stability of the ATP6V1A transcript. When sufficient levels of SIRT1 are expressed, it catalyzes the deacetylation of IGF2BP2, which can bind to the ATP6V1A transcript but does not mediate its degradation.

Regulation of Tumor Invasion by the Physical Microenvironment: Lessons from Breast and Brain Cancer.

The success of anticancer therapies is often limited by heterogeneity within and between tumors. While much attention has been devoted to understanding the intrinsic molecular diversity of tumor cells, the surrounding tissue microenvironment is also highly complex and coevolves with tumor cells to drive clinical outcomes. Here, we propose that diverse types of solid tumors share common physical motifs that change in time and space, serving as universal regulators of malignancy.