BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.

Background: Bone morphogenetic protein (BMP) signaling cascade is a phylogenetically conserved stem cell regulator that is aberrantly expressed in non-small cell lung cancer (NSLC) and leukemias. BMP signaling negatively regulates mitochondrial bioenergetics in lung cancer cells. The impact of inhibiting BMP signaling on mitochondrial bioenergetics and the effect this has on the survival of NSLC and leukemia cells are not known.

An evaluation of the usability and durability of 3D printed versus standard suture materials.

The capability to produce suture material using three-dimensional (3D) printing technology may have applications in remote health facilities where rapid restocking of supplies is not an option. This is a feasibility study evaluating the usability of 3D-printed sutures in the repair of a laceration wound when compared with standard suture material. The 3D-printed suture material was manufactured using a fused deposition modelling 3D printer and nylon 3D printing filament.

Locally Advanced Lung Cancer.

Consolidation immunotherapy after concurrent chemoradiation has improved five-year survival rates in unresectable, locally advanced lung cancer, but disease progression and treatment personalization remain challenges. New treatment approaches with concurrent immunotherapy and consolidative novel agents are being investigated and show promising efficacy data, but at the risk of additive toxicity. Patients with PD-L1 negative tumors, oncogenic driver mutations, intolerable toxicity, or limited performance status continue to require innovative therapies.

Incidence of unknown COVID-19 infection in a cohort of emergency physicians and advance practice providers.

Introduction: In United States, health care workers have been immersed in the COVID-19 pandemic since February 2020. Since availability of COVID-19 vaccines, there is limited literature investigating the incidence of unknown COVID-19 infections in physicians and Advanced Practitioner Providers (APPs) working in emergency departments (EDs). The primary objective is to determine the incidence unknown COVID-19 infection within a cohort of emergency physicians (EPs) and APPs.

Ym155 localizes to the mitochondria leading to mitochondria dysfunction and activation of AMPK that inhibits BMP signaling in lung cancer cells.

The imidazolium compound Ym155 was first reported to be a survivin inhibitor. Ym155 potently induces cell death of many types of cancer cells in preclinical studies. However, in phase II clinical trials Ym155 failed to demonstrate a significant benefit.

Bone morphogenetic protein inhibitors and mitochondria targeting agents synergistically induce apoptosis-inducing factor (AIF) caspase-independent cell death in lung cancer cells.

Background: Bone morphogenetic proteins (BMP) are evolutionarily conserved morphogens that are reactivated in lung carcinomas. In lung cancer cells, BMP signaling suppresses AMP activated kinase (AMPK) by inhibiting LKB1. AMPK is activated by mitochondrial stress that inhibits ATP production, which is enhanced 100-fold when phosphorylated by LKB1.

Bone morphogenetic protein signaling regulation of AMPK and PI3K in lung cancer cells and C. elegans.

Background: Bone morphogenetic protein (BMP) is a phylogenetically conserved signaling pathway required for development that is aberrantly expressed in several age-related diseases including cancer, Alzheimer's disease, obesity, and cardiovascular disease. Aberrant BMP signaling in mice leads to obesity, suggesting it may alter normal metabolism. The role of BMP signaling regulating cancer metabolism is not known.

Bone morphogenetic protein receptor inhibitors suppress the growth of glioblastoma cells.

Glioblastomas (GBMs) are aggressive brain tumors that are resistant to chemotherapy and radiation. Bone morphogenetic protein (BMP) ligand BMP4 is being examined as a potential therapeutic for GBMs because it induces differentiation of cancer stem cells (CSCs) to an astrocyte phenotype. ID1 is reported to promote self-renewal and inhibit CSC differentiation.

Bone morphogenetic protein receptor 2 inhibition destabilizes microtubules promoting the activation of lysosomes and cell death of lung cancer cells.

Background: Recent studies have shown that bone morphogenetic protein receptor 2 (BMPR2) regulates cell survival signaling events in cancer cells independent of the BMP type 1 receptor (BMPR1) or the Smad-1/5 transcription factor. Mutations in BMPR2 trafficking proteins leads to overactive BMP signaling, which leads to neurological diseases caused by BMPR2 stabilization of the microtubules. It is not known whether BMPR2 regulates the microtubules in cancer cells and what effect this has on cell survival.

Combining radiation therapy and immunotherapy for lung cancers: a narrative review.

Lung cancer remains the leading cause of cancer morbidity and mortality worldwide among both men and women. While surgical resection remains the standard of care for early stage NSCLC, chemoradiation has been a mainstay of treatment for locally advanced non-small-cell lung cancer (LA-NSCLC) patients for decades. Consolidation immunotherapy has improved survival in this subset of patients after conventional chemoradiation, and has emerged as the new standard.

Novel Barrier Enclosure for Both Aerosol and Droplet Protection Model.

Emergency physicians are on the front lines of treating patients with highly infectious respiratory diseases. Personal protective equipment is one defense against contamination from droplet and aerosol secretions. Intubation is a procedure that greatly can increase provider's risk of exposure.

Tumor volume reduction evaluated by cone beam computed tomography during stereotactic body radiotherapy for early stage non-small cell lung cancer.

Background: We hypothesized that significant tumor volume reduction (TVR) occurs over the course of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), and that TVR correlates with clinical outcomes.

Methods: We conducted a retrospective review of patients treated with SBRT for early stage NSCLC across two academic centers. For each patient, we contoured the tumor volume (TV) on cone beam computed tomography (CBCT) images obtained before each treatment fraction.

Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies.

Paravertebral Nerve Block With Liposomal Bupivacaine for Pain Control Following Video-Assisted Thoracoscopic Surgery and Thoracotomy.

Background: Some surgeons have adopted the use of video-assisted thoracoscopic surgery (VATS) or robotic surgery to perform resections for lung cancer. VATS is associated with less pain and a decrease in pulmonary complications compared with open thoracotomies. Long-acting liposomal bupivacaine (LB) intercostal nerve blocks are reported to provide superior pain relief compared with epidural catheters in the first 3 d after a thoracotomy.

Synchronous Oligometastatic Non-small Cell Lung Cancer Managed With Curative-Intent Chemoradiation Therapy: Long-term Outcomes From a Single Institution.

Purpose: We examined long-term clinical outcomes among patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) treated at our institution with definitive thoracic chemoradiation therapy (CRT) and local therapy to all oligometastatic lesions.

Methods And Materials: A retrospective review identified 38 patients with synchronous oligometastatic NSCLC (≤3 metastatic lesions) who were treated with definitive CRT to the primary tumor and regional lymph nodes between 1999 and 2017 at our institution. Of the 38 patients, 27 patients (71%) received induction chemotherapy, all of whom responded or stabilized with initial systemic therapy before consideration of CRT.

Vertebral body irradiation during chemoradiation therapy for esophageal cancer contributes to acute bone marrow toxicity.

Background: Hematologic toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer. We sought to determine radiation doses that correlate with declines in blood counts due to vertebral body (VB) irradiation during CRT.

Methods: We analyzed 53 esophageal cancer patients who were treated with weekly neoadjuvant carboplatin, paclitaxel and RT with weekly complete blood counts (CBC) available during treatment.

Double-Humanized Mouse Model to Study Bone Morphogenetic Protein (BMP) Signaling in Tumor Xenografts.

The activation of the bone morphogenic protein (BMP) signaling pathway in cancer cells has been shown to enhance migration and tumor angiogenesis and promote survival. The BMP signaling pathway regulates benign cells in the tumor microenvironment and is a known regulator of immune cells. The development of BMP receptor inhibitors has allowed the study of tumor xenografts in mice.

Variations in Initiation Dates of Chemotherapy and Radiation Therapy for Definitive Management of Inoperable Non-Small Cell Lung Cancer Are Associated With Decreases in Overall Survival.

Background: We evaluated trends in administration of concurrent chemoradiation therapy (CRT) and how variations in start dates of chemotherapy and radiotherapy affected overall survival (OS) in patients with non-small cell lung cancer (NSCLC) undergoing a course of definitive CRT.

Materials And Methods: Cases of NSCLC treated with definitive CRT were obtained from the National Cancer Database. A survival analysis was performed with Kaplan-Meier curves and Cox proportional hazards models.

Novel bone morphogenetic protein receptor inhibitor JL5 suppresses tumor cell survival signaling and induces regression of human lung cancer.

BMP receptor inhibitors induce death of cancer cells through the downregulation of antiapoptotic proteins XIAP, pTAK1, and Id1-Id3. However, the current most potent BMP receptor inhibitor, DMH2, does not downregulate BMP signaling in vivo because of metabolic instability and poor pharmacokinetics. Here we identified the site of metabolic instability of DMH2 and designed a novel BMP receptor inhibitor, JL5.

Modern radiotherapy using image guidance for unresectable non-small cell lung cancer can improve outcomes in patients treated with chemoradiation therapy.

Background: To investigate the impact of advances in image-guided radiotherapy (IGRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT).

Methods: We retrospectively reviewed 91 patients with NSCLC treated with definitive CRT using image guidance with daily orthogonal kilovoltage (kV) imaging compared to standard weekly megavoltage (MV) portal verifications. Kaplan-Meier curves for overall survival and locoregional failure were computed and stratified by image guidance techniques.

Modern induction chemotherapy before chemoradiation for bulky locally-advanced nonsmall cell lung cancer improves survival.

Background: We seek to investigate whether carboplatin-based induction chemotherapy before modern day concurrent chemoradiotherapy (CCRT) improves survival in patients with bulky, locally advanced nonsmall cell lung cancer (NSCLC).

Materials And Methods: This analysis included 105 patients with Stage II and III NSCLC treated with definitive CCRT from 2003 to 2013. All patients underwent definitive treatment with weekly platinum-based doublet chemotherapy delivered concurrently with 60-66 Gy of thoracic radiotherapy.

Inhibition of BMP and of TGFβ receptors downregulates expression of XIAP and TAK1 leading to lung cancer cell death.

Background: Bone morphogenetic proteins (BMP) are embryonic proteins that are part of the transforming growth factor (TGFβ) superfamily, which are aberrantly expressed in many carcinomas. Inhibition of BMP receptors with small molecule inhibitors decreases growth and induces death of lung cancer cells, which involves the downregulation of Id1 and Id3 by a Smad dependent mechanism. Developmentally, BMP and TGFβ signaling utilizes Smad-1/5 independent mechanisms to stabilize the expression of X-linked inhibitor of apoptosis protein (XIAP) and activate TGFβ activated kinase 1 (TAK1), which are known to be potent inhibitors of apoptosis.

Fluid administration and morbidity in transhiatal esophagectomy.

Background: Esophagectomy is associated with significant morbidity. Optimizing perioperative fluid administration is one potential strategy to mitigate morbidity. We sought to investigate the relationship of intraoperative fluid (IOF) administration to outcomes in patients undergoing transhiatal esophagectomy with particular attention to malnourished patients, who may be more susceptible to the effects of fluid overload.