In vivo functional screens reveal loss as a driver of chemoresistance in small cell lung cancer.

Exquisitely chemosensitive initially, small cell lung cancer (SCLC) exhibits dismal outcomes owing to rapid transition to chemoresistance. Elucidating the genetic underpinnings has been challenging owing to limitations with cellular models. As SCLC patient-derived xenograft (PDX) models mimic therapeutic responses, we perform genetic screens in chemosensitive PDX models to identify drivers of chemoresistance.

The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.

Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options.

Dual-signal output biosensor for the detection of program death-ligand 1 and therapy progress monitoring of cancer.

A disposable dual-output biosensor to detect program death-ligand 1 (PD-L1) was developed for immunotherapy progress monitoring and early cancer detection in a single experimental setup. The aptamer probe was assembled on rGO composited with carboxylated terthiophene polymer (rGO-pTBA) to specifically capture PD-L1 protein labeled with a new redox mediator, ortho-amino phenol para sulphonic acid, for amperometric detection. Each sensing layer was characterized through electrochemical and surface analysis experiments, then confirmed the sensing performance.

Clinical values of diaphragmatic movement in patients with chronic obstructive pulmonary disease.

Background: The limitation of activity due to dyspnea in chronic obstructive pulmonary disease (COPD) patients is affected by diaphragmatic dysfunction and reduced lung function. This study aimed to analyze the association between diaphragm function variables and forced expiratory volume in the first second (FEV1) and to estimate the clinical significance of diaphragm function in the correlation between COPD severity and lung function.

Methods: This prospective, single-center, cross-sectional observational study enrolled 60 COPD patients in a respiratory outpatient clinic.

Multiarray Biosensor for Diagnosing Lung Cancer Based on Gap Plasmonic Color Films.

Adaptable and sensitive materials are essential for the development of advanced sensor systems such as bio and chemical sensors. Biomaterials can be used to develop multifunctional biosensor applications using genetic engineering. In particular, a plasmonic sensor system using a coupled film nanostructure with tunable gap sizes is a potential candidate in optical sensors because of its simple fabrication, stability, extensive tuning range, and sensitivity to small changes.

MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.

Background: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC.

Methods: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma.

The feasibility of granzyme B levels using an amperometric immunosensor for lung cancer detection.

Background: Low-dose computed tomography (LDCT) has improved the early detection of lung cancer. However, LDCT scans present several disadvantages, including the abundance of false-positive results, which lead to a high socioeconomic cost, psychological burden, and repeated exposure to radiation. Therefore, the identification of complementary biomarkers is needed to select high-risk individuals for LDCT.

Exosomal microRNAs array sensor with a bioconjugate composed of p53 protein and hydrazine for the specific lung cancer detection.

For the early diagnosis of lung cancer, a novel strategy to detect microRNAs encapsulated in exosomes with immunomagnetic isolation was demonstrated for the selective extraction of exo-miRNAs from patient serum. Here, miRNA was captured from lysed exosomes in specially designed capture probe modified magnetic beads, followed by T4 DNA polymerase-mediated in situ formation of chimeric 5'-miRNA-DNA-3' (Target). The poly-(2,2':5',2''-terthiophene-3'-(p-benzoic acid)) (pTBA)-modified electrode harbors Probe-1 DNA that hybridizes to the 5' end of the chimera, followed by hybridization of Probe-2 DNA to the 3' end of the chimera, resulting in the formation of a 20-nucleotide-long dsDNA consensus sequence for p53 protein binding.

Granzyme B for predicting the durable clinical benefit of anti-PD-1/PD-L1 immunotherapy in patients with non-small cell lung cancer.

Background: To identify immunotherapy biomarkers, we examined granzyme B levels in peripheral blood PD-1 CD8 T cells and their relationship with treatment outcomes in patients with non-small cell lung cancer (NSCLC).

Methods: To evaluate the association of granzyme B with response to immunotherapy, we tested blood samples obtained from 16 patients with stage IIIC to IV NSCLC receiving immune-checkpoint inhibitor treatment. We used flow cytometry to measure the change in the percentage of PD1 CD8 T cells expressing granzyme B before (t0) and after (t1) immunotherapy, and we evaluated for an association with tumor response to therapy, progression-free survival (PFS) and overall survival (OS).

Disposable amperometric immunosensor with a dual monomers-based bioconjugate for granzyme B detection in blood and cancer progress monitoring of patients.

A disposable amperometric biosensor with a dual monomers-based bioconjugate was developed for granzyme B (GzmB) detection and for monitoring of the cancer progression of patients before and after immunotherapy. The biosensor was fabricated by immobilizing a GzmB monoclonal antibody (Ab) on a poly3'-(2-aminopyrimidyl)-2,2':5',2''-terthiophene/gold nanoparticle (pPATT/AuNP) layer. The bioconjugate nanoparticles were synthesized through self-assembly of a monomer mixture of 2,2:5,2-terthiophene-3-(p-benzoic acid) (TBA) and PATT onto AuNPs, followed by chemical binding of brilliant cresyl blue (BCB) on TBA and GzmB polyclonal antibody (Ab) on the PATT layer.

Head-to-Head Comparison between Xpert MTB/RIF Assay and Real-Time Polymerase Chain Reaction Assay Using Bronchial Washing Specimens for Tuberculosis Diagnosis.

Background: With the introduction of Xpert MTB/RIF assay (Xpert), its incorporation into tuberculosis (TB) diagnostic algorithm has become an important issue. The aim of this study was to evaluate the performance of the Xpert assay in comparison with a commercial polymerase chain reaction (PCR) assay.

Methods: Medical records of patients having results of both Xpert and AdvanSure TB/NTM real-time PCR (AdvanSure) assays using the same bronchial washing specimens were retrospectively reviewed.

A DNA-derived phage nose using machine learning and artificial neural processing for diagnosing lung cancer.

There is a growing interest in electronic nose-based diagnostic systems that are fast and portable. However, existing technologies are suitable only for operation in the laboratory, making them difficult to apply in a rapid, non-face-to-face, and field-suitable manner. Here, we demonstrate a DNA-derived phage nose (DpNose) as a portable respiratory disease diagnosis system requiring no pretreatment.

Cancer Testis Antigen, NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer.

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis.

PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer.

P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung cancer (NSCLC). We evaluated PAK1 mRNA and protein expression in NSCLC cells and resected tumor specimens, as well as in healthy human bronchial epithelial cells and adjacent healthy lung tissues, respectively, for effective comparison.

Unilateral Diaphragm Paralysis Associated With Neurosyphilis: A Case Report.

Diaphragm dysfunction can originate from various etiologies, and bilaterality of the dysfunction depends on the cause. Symptoms of diaphragm dysfunction vary depending on the degree of phrenic nerve denervation, spinal cord lesion, and involvement of the diaphragm. Several infectious diaphragmatic dysfunctions have been reported, including the human immunodeficiency virus, poliovirus, West Nile virus, and dengue virus.

Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept.

Age-associated chronic inflammation is characterized by unresolved and uncontrolled inflammation with multivariable low-grade, chronic and systemic responses that exacerbate the aging process and age-related chronic diseases. Currently, there are two major hypotheses related to the involvement of chronic inflammation in the aging process: molecular inflammation of aging and inflammaging. However, neither of these hypotheses satisfactorily addresses age-related chronic inflammation, considering the recent advances that have been made in inflammation research.

FoxO6-mediated IL-1β induces hepatic insulin resistance and age-related inflammation via the TF/PAR2 pathway in aging and diabetic mice.

FoxO has been proposed to play a role in the promotion of insulin resistance, and inflammation. FoxO is a pro-inflammatory transcription factor that is a key mediator of generation of inflammatory cytokines such as IL-1β in the liver. However, the detailed association of FoxO6 with insulin resistance and age-related inflammation has not been fully documented.

Receptor-interacting protein kinase 3 as a predictive adjuvant chemotherapy marker after lung adenocarcinoma resection.

Background: This study assessed the predictive value of receptor-interacting protein kinase 3 (RIPK3) expression and its correlation with clinicopathological characteristics, disease-free survival, and overall survival of patients with cisplatin-based adjuvant chemotherapy after lung adenocarcinoma resection.

Methods: This study included 50 patients who underwent cisplatin-based adjuvant chemotherapy after lung adenocarcinoma (stage IB-IIIA) resection. Immunohistochemical analysis was performed by probing tumor tissue microarrays with anti-RIPK3 antibody.

Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma.

Background/aims: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1-cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms.

Methods: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC.

Treatment of Pulmonary Tumor Embolism from Choriocarcinoma: Extracorporeal Membrane Oxygenation as a Bridge through Chemotherapy.

A 22-year-old woman with a 1-month history of shortness of breath that was treated as a case of tuberculosis and pulmonary embolism was referred to the authors' hospital. Because of the hemodynamic instability in this patient, venoarterial extracorporeal membrane oxygenation (ECMO) was administered in the intensive care unit. She underwent a pulmonary embolectomy for the treatment of progressive circulatory collapse secondary to a pulmonary embolism.

Reversible Cerebellar Ataxia Related to Extrapontine Myelinolysis without Hyponatremia after Cisplatin-Based Chemotherapy for Cholangiocarcinoma.

A 60-year-old woman presented with cerebellar signs including dysarthria and ataxia, after intravenous infusion of cisplatin-based chemotherapy. Several blood tests showed mild neutropenia, normocytic normochromic anemia, but no evidence of a marked hyponatremia. Brain magnetic resonance imaging with diffusion-weighted sequences showed hyper-intense signal abnormalities in the extrapontine region, sparing the basis pontis.

Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver.

Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin E2 (PGE2) in lipopolysaccharides (LPS)-challenged RAW264.

Inhibition of endothelial cell adhesion by the new anti-inflammatory agent alpha-iso-cubebene.

The current study explored if alpha-iso-cubebene, a novel cubebene sesquiterpene compound purified from Schisandra chinensis, could attenuate the activities of adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs). The study was performed on HUVECs that were pretreated with 25 microg/ml of alpha-iso-cubebene before TNF-alpha treatment. Treatment of HUVECs with alpha-iso-cubebene for 6 h significantly inhibited TNF-alpha-induced reactive oxygen species (ROS) formation.

Peroxisome proliferator-activated receptor activation by a short-term feeding of zingerone in aged rats.

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, are key regulators of various metabolic pathways related to lipid and glucose metabolism as well as inflammation. We examined the effect of zingerone, a major ingredient of ginger, on PPAR, hepatic nuclear factor-4 (HNF-4), and nuclear factor-kappaB (NF-kappaB) expression in 21-month-old male Sprague-Dawley rats. Two experimental groups receiving doses of either 2 or 8 mg/kg/day zingerone for 10 days were compared with young rats (6 months old) and an age-matched control group.