Vitamin D Receptor Antagonist MeTC7 Inhibits PD-L1.

Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells.

Prevention of Radiation-Induced Bladder Injury: A Murine Study Using Captopril.

Purpose: Pelvic radiation therapy (RT) can cause debilitating bladder toxicities but few clinical interventions exist to prevent injury or alleviate symptoms. From a large genome-wide association study in patients with prostate cancer it was previously reported that SNPs tagging AGT, part of the renin-angiotensin system (RAS), correlated with patient-reported late hematuria, identifying a potential targetable pathway to prevent RT-induced bladder injury. To investigate this association, we performed a preclinical study to determine whether RAS modulation protected the bladder against RT injury.

Referral to and receipt of allogeneic hematopoietic stem cell transplantation in older adults with acute myeloid leukemia.

Introduction: Recent data have shown improved outcomes in selected older adults with acute myeloid leukemia (AML) following allogeneic hematopoietic stem cell transplantation (HSCT). Nonetheless, practice patterns for referring and performing HSCT vary. We aimed to evaluate referral, utilization, and reasons for not referring/proceeding to HSCT in older adults with AML.

Prostate Cancer Stem Cells: The Role of CD133.

Prostate cancer stem cells (PCSCs), possessing self-renewal properties and resistance to anticancer treatment, are possibly the leading cause of distant metastasis and treatment failure in prostate cancer (PC). CD133 is one of the most well-known and valuable cell surface markers of cancer stem cells (CSCs) in many cancers, including PC. In this article, we focus on reviewing the role of CD133 in PCSC.

The Potential Role of 3D In Vitro Acute Myeloid Leukemia Culture Models in Understanding Drug Resistance in Leukemia Stem Cells.

The complexity of the bone marrow (BM) microenvironment makes studying hematological malignancies in vitro a challenging task. Three-dimensional cell cultures are being actively studied, particularly due to their ability to serve as a bridge of the gap between 2D cultures and animal models. The role of 3D in vitro models in studying the mechanisms of chemotherapeutic resistance and leukemia stem cells (LSCs) in acute myeloid leukemia (AML) is not well-reviewed.

Magmas Inhibition in Prostate Cancer: A Novel Target for Treatment-Resistant Disease.

The purpose of our study was to evaluate Magmas as a potential target in prostate cancer. In addition, we evaluated our synthetic Magmas inhibitor (BT#9) effects on prostate cancer and examined the molecular mechanism of BT#9. A cell viability assay showed that treatment with BT#9 caused a significant decrease in the viability of DU145 and PC3 prostate cancer cells with little effect on the viability of WPMY-1 normal prostate cells.

Portable medical orders and end-of-life measures in acute myeloid leukemia and myelodysplastic syndromes.

Patients with acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS) experience high rates of hospitalization, intensive care unit (ICU) admission, and in-hospital death at the end of life. Early goals-of-care (GOC) discussions may reduce the intensity of end-of-life (EOL) care. Portable Medical Order forms, known as Medical Orders for Life-Sustaining Treatment (MOLST) forms in New York state, assist patients in translating GOC discussions into specific medical orders that communicate their wishes during a medical emergency.

Oral Graft-Versus-Host Disease: A Pictorial Review and a Guide for Dental Practitioners.

Introduction: Graft-versus-host disease (GVHD) is a complication of haematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues.

Remission of anti-TIF1γ dermatomyositis after allogeneic hematopoietic stem cell transplant for myelodysplastic syndrome.

DM, an autoimmune inflammatory myopathy, can be associated with a number of malignancies, including, rarely, myelodysplastic syndromes. Allo-HCT presents a novel approach to treat refractory DM in patients with a coexisting malignancy through the GvA effect.

Barriers to Hematopoietic Cell Transplantation for Adults in the United States: A Systematic Review with a Focus on Age.

Hematopoietic cell transplantation (HCT) is an effective treatment for many hematologic malignancies, and its utilization continues to rise. However, due to the difficult logistics and high cost of HCT, there are significant barriers to accessing the procedure; these barriers are likely greater for older patients. Although numerous factors may influence HCT access, no formal analysis has detailed the cumulative barriers that have been studied thus far.

Autologous Stem Cell Rescue recipient with neutrophil tissue delivery detected prior to blood engraftment: a case report.

Neutrophil recovery after autologous hematopoietic cell transplantation (auto-HCT) is affirmed with achievement of an Absolute Neutrophil Count (ANC) of ≥500/uL. There is growing evidence that neutrophils may be observed despite undetectable peripheral ANC counts following autologous hematopoietic cell transplant and are preferentially delivered to sites of inflammation. We report an interesting case that confirms neutrophil tissue delivery to the skin two days prior to evidence of blood engraftment after an auto-HCT.

Stem cell homing: From physiology to therapeutics.

Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs). This multistep process involves cell migration and is essential for hematopoietic stem cell transplantation. The process can be manipulated to enhance ultimate engraftment potential, and understanding stem cell homing is also important to the understanding of stem cell mobilization.

Results of the First Clinical Study in Humans That Combines Hyperbaric Oxygen Pretreatment with Autologous Peripheral Blood Stem Cell Transplantation.

Patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) are at risk for multiple morbidities, including mucosal inflammation and neutropenic fever, both related to neutropenia. Evidence from our preclinical work in an umbilical cord blood (UCB) transplantation murine model suggests that treatment with hyperbaric oxygen (HBO) before UCB infusion improves UCB CD34 cell engraftment by reducing erythropoietin levels. A pilot clinical trial using HBO in patients undergoing UCB transplantation showed improvement in kinetics of blood count recovery.

Decellularized Wharton jelly matrix: a biomimetic scaffold for ex vivo hematopoietic stem cell culture.

Hematopoietic stem progenitor cells (HSPCs) reside in the bone marrow (BM) hematopoietic "niche," a special 3-dimensional (3D) microenvironment that regulates HSPC self-renewal and multipotency. In this study, we evaluated a novel 3D in vitro culture system that uses components of the BM hematopoietic niche to expand umbilical cord blood (UCB) CD34 cells. We developed this model using decellularized Wharton jelly matrix (DWJM) as an extracellular matrix (ECM) scaffold and human BM mesenchymal stromal cells (MSCs) as supporting niche cells.

Post-Transfusion Purpura Mimicking Idiopathic Thrombocytopenic Purpura: A Case Report.

The main clinical distinction between post-transfusion purpura (PTP) and idiopathic thrombocytopenic purpura (ITP) is the sudden development of severe thrombocytopenia in the days after transfusion. Herein, we report the case of a 53-year-old Caucasian woman who developed multiple myeloma (MM) after peripheral blood-stem-cell transplant (PBSCT), along with severe thrombocytopenia (with a nadir of 1 × 109/L); she also experienced severe adverse events after each platelet transfusion, including the first one. These reactions were absent with any other transfused blood products.

Long-term results of a pilot study evaluating hyperbaric oxygen therapy to improve umbilical cord blood engraftment.

Umbilical cord blood (UCB) transplantation is a promising option for hematopoietic stem cell transplantation in patients with hematologic malignancies who lack an HLA-matched sibling or well-matched unrelated donor; however, it has a higher incidence of delayed or failed engraftment because cell doses are low and bone marrow homing is inefficient. We have demonstrated that pre-treating irradiated immune-deficient mice with hyperbaric oxygen (HBO) prior to UCB CD34+ cell transplantation lowered host systemic erythropoietin (EPO) and improved UCB CD34+ cell homing and engraftment. These findings suggested that EPO-EPO-R signaling plays a role in UCB CD34+ homing and engraftment.

A novel extracellular matrix-based leukemia model supports leukemia cells with stem cell-like characteristics.

Acute myeloid leukemia (AML) relapse results from the survival of chemotherapy-resistant and quiescent leukemia stem cells (LSC). These LSCs reside in the bone marrow microenvironment, comprised of other cells and extracellular matrix (ECM), which facilitates LSC quiescence through expression of cell adhesion molecules. We used decellularized Wharton's jelly matrix (DWJM), the gelatinous material in the umbilical cord, as a scaffolding material to culture leukemia cells, because it contains many components of the bone marrow extracellular matrix, including collagen, fibronectin, lumican, and hyaluronic acid (HA).

Hyperbaric oxygen treatment effects on in vitro cultured umbilical cord blood CD34 cells.

Background Aims: Umbilical cord blood (UCB) provides an alternative source for hematopoietic stem/progenitor cells (HSPCs) in the treatment of hematological malignancies. However, clinical usage is limited due to the low quantity of HSPCs in each unit of cord blood and defects in bone marrow homing. Hyperbaric oxygen (HBO) is among the more recently explored methods used to improve UCB homing and engraftment.

Wharton's Jelly Matrix Decellularization for Tissue Engineering Applications.

Scaffolds, both natural and synthetic, used in tissue engineering provide mechanical support to cells. Tissue decellularization has been used to provide natural extracellular matrix scaffolds for tissue engineering purposes. In this chapter we focus on describing the methodology used to decellularize Wharton's jelly matrix, the mucous connective tissue that surrounds umbilical cord vessels, to obtain decellularized Wharton's jelly matrix (DWJM); an extracellular matrix that can be used for tissue engineering purposes.

Decellularized Wharton's Jelly from human umbilical cord as a novel 3D scaffolding material for tissue engineering applications.

In tissue engineering, an ideal scaffold attracts and supports cells thus providing them with the necessary mechanical support and architecture as they reconstruct new tissue in vitro and in vivo. This manuscript details a novel matrix derived from decellularized Wharton's jelly (WJ) obtained from human umbilical cord for use as a scaffold for tissue engineering application. This decellularized Wharton's jelly matrix (DWJM) contained 0.