Unlabelled: Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell RNA sequencing of 256,379 cells, including 13,857 mesenchymal cells, from 9 treatment-naïve patients.
View Article and Find Full Text PDFMyeloid cells are known to play a crucial role in creating a tumor-promoting and immune suppressive microenvironment. Our previous study demonstrated that primary human monocytes can be polarized into immunosuppressive myeloid-derived suppressor cells (MDSCs) by cancer-associated fibroblasts (CAFs) in a 3D co-culture system. However, the molecular mechanisms underlying the immunosuppressive function of MDSCs, especially CAF-induced MDSCs, remain poorly understood.
View Article and Find Full Text PDFFrontal fibrosing alopecia (FFA) is a progressive cicatricial alopecia that can affect patients with skin of color (SOC); however, patients with SOC often are underrepresented in clinical trials and scientific publications on FFA. To better understand the management of FFA in patients with SOC, we sought to assess the clinical evidence for the efficacy of FFA treatment modalities specifically in these patients. This systematic review discusses studies on FFA characteristics and treatment outcomes in Black patients.
View Article and Find Full Text PDFPlast Reconstr Surg Glob Open
April 2022
Unlabelled: Drains are used in plastic surgery to remove excess fluid while ameliorating complications. However, there is a paucity of evidence supporting guiding parameters on when to discontinue a drain. The aim of our study was to determine whether two of the most common parameters, drain volume 24 hours before removal or postoperative day, are valid indicators for drain removal.
View Article and Find Full Text PDFEsophageal squamous cell carcinomas (ESCCs) harbor recurrent chromosome 3q amplifications that target the transcription factor SOX2. Beyond its role as an oncogene in ESCC, SOX2 acts in development of the squamous esophagus and maintenance of adult esophageal precursor cells. To compare Sox2 activity in normal and malignant tissue, we developed engineered murine esophageal organoids spanning normal esophagus to Sox2-induced squamous cell carcinoma and mapped Sox2 binding and the epigenetic and transcriptional landscape with evolution from normal to cancer.
View Article and Find Full Text PDFBackground: Numerous studies in the clinical literature have explored the link between nutrition and skin physiology. However, it is unclear whether patients visit their dermatologists with knowledge of these studies, and unknown where they obtain their skin health information. We characterized patient perceptions surrounding nutrition and skin, including what patients identified as aggravating and alleviating foods and their information sources.
View Article and Find Full Text PDFDermatomyositis is an auto-immune inflammatory myopathy that primarily affects the skin and muscle and can be triggered by exposure to various environmental factors. We present a patient with active syphilis infection who developed dermatomyositis and discuss the significance of anti-NXP2 autoantibody positivity.
View Article and Find Full Text PDFPurpose: Lung squamous cell carcinoma (LSCC) is a deadly disease for which only a subset of patients responds to immune checkpoint blockade (ICB) therapy. Therefore, preclinical mouse models that recapitulate the complex genetic profile found in patients are urgently needed.
Experimental Design: We used CRISPR genome editing to delete multiple tumor suppressors in lung organoids derived from Cre-dependent SOX2 knock-in mice.
: To investigate the impact of programmed death-ligand 1 (PD-L1) expression, oncogenic mutations, and clinical characteristics on survival after treatment with anti-PD-1/PD-L1 antibodies versus chemotherapy in non-small cell lung cancer (NSCLC). : This meta-analysis included randomized trials comparing anti-PD-1/PD-L1 antibodies with chemotherapy. Hazard ratios (HRs) and 95% confidence interval (CI) for overall survival (OS) for the trial population and prespecified subgroups were extracted.
View Article and Find Full Text PDFAutophagy has been shown to be elevated in pancreatic ductal adenocarcinoma (PDAC), and its role in promoting established tumor growth has made it a promising therapeutic target. However, due to limitations of prior mouse models as well as the lack of potent and selective autophagy inhibitors, the ability to fully assess the mechanistic basis of how autophagy supports pancreatic cancer has been limited. To test the feasibility of treating PDAC using autophagy inhibition and further our understanding of the mechanisms of protumor effects of autophagy, we developed a mouse model that allowed the acute and reversible inhibition of autophagy.
View Article and Find Full Text PDF(or ) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2% to 6% of lung adenocarcinomas. amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKI). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with aberrations.
View Article and Find Full Text PDFBackground: Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers.
View Article and Find Full Text PDF-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multitargeted therapy may offer a plausible strategy to effectively treat -driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring mutations.
View Article and Find Full Text PDFNon-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states.
View Article and Find Full Text PDFBackground: The tumor suppressor p53 is frequently inactivated in non-small cell lung cancer (NSCLC). Activation of the p53 pathway by inhibition of its negative regulator MDM2 may offer an attractive approach for NSCLC therapy. We evaluated the antitumor activity of the small-molecule MDM2 inhibitor RG7388 in patient-derived xenograft (PDX) models of NSCLC.
View Article and Find Full Text PDFKRAS is mutated in ∼40% of colorectal cancer (CRC), and there are limited effective treatments for advanced KRAS mutant CRC. Therefore, it is crucial that downstream mediators of oncogenic KRAS continue to be studied. We identified p190RhoGAP as being phosphorylated in the DLD1 CRC cell line, which expresses a heterozygous KRAS G13D allele, and not in DKO4 in which the mutant allele has been deleted by somatic recombination.
View Article and Find Full Text PDFPurpose: Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited treatment options, thus requiring development of novel targeted therapies. Our group previously identified L1 cell adhesion molecule (L1CAM) expression as a member of a prognostic multigene expression signature for NSCLC patients. However, there is little information on the biologic function of L1CAM in lung cancer cells.
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