BACKGROUND: The thoracic small biopsy sampling procedure including transbronchial forceps lung biopsy (TBLB) and endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) can be accompanied by rapid on-site evaluation (ROSE) of sample material to provide immediate feedback for the proceduralist. The present study aims to investigate the supplemental effect of ROSE smear samples for lung cancer molecular test. METHODS: In a retrospective study, 308 patients admitted to our hospital from August 2020 to December 2022 undergoing diagnostic TBLB and EBUS-TBNA with ROSE and subsequently diagnosed as non-small cell lung cancer (NSCLC) were analyzed. The matched formalin-fixed paraffin-embedding (FFPE) tissue section and ROSE smears for tumor cellularity were compared. DNA yields of smears were determined. Real-time polymerase chain reaction (PCR) and next-generation sequencing (NGS) were performed on adequate smear samples. RESULTS: ROSE smear samples were enriched in tumor cells. Among 308 biopsy samples, 78 cases (25.3%) exhibited inadequate FFPE tissue sections, whereas 44 cases (14.3%) yielded adequate smear samples. Somatic mutations detected in the FFPE tissue section samples were also detected in the matching adequate smear sample. CONCLUSIONS ROSE smear samples of the thoracic small biopsies are beneficial supplemental materials for ancillary testing of lung cancer. Combined use of cytology smear samples with traditional FFPE section samples can enhance the detection rate of informative mutations in patients with advanced NSCLC. We recommend that the laboratory could further evaluate the ROSE cell smears of the patient when FFPE tissue sections are inadequate, and that adequate cell smears can be used as a supplemental source for the molecular testing of NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Rapid On-site Evaluation ; Retrospective Studies ; Molecular Diagnostic Techniques ; Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods*

Female ; Humans ; Carcinoma, Endometrioid/pathology* ; Endometrial Neoplasms/pathology* ; Molecular Typing/methods*

methods, including biochemical assays, immunoassays, and molecular diagnostics. Despite its strong advantage as an analytical method, many laboratory physicians and clinical laboratories are unwilling to introduce it. Fundamental elements, such as instruments, reagents, facilities, skilled human resources are required to implement mass spectrometry. This review contains considerations for the introduction of liquid chromatography-mass spectrometry to support the clinical laboratories interested in or planning to implement mass spectrometry.]]>
Humans ; Immunoassay ; Indicators and Reagents ; Mass Spectrometry ; Methods ; Pathology, Molecular ; Spectrum Analysis

PURPOSE: The disease entity mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by an early onset of stroke-like episodes. MELAS is the most dominant subtype of mitochondrial disease. Molecular genetic testing is important in the diagnosis of MELAS. The mitochondrial DNA (mtDNA) 3243A>G mutation is found in 80% of MELAS patients. Nevertheless, molecular analysis alone may be insufficient to diagnose MELAS because of mtDNA heteroplasmy. This study aimed to evaluate whether muscle biopsy is useful in MELAS patients as an initial diagnostic evaluation method. MATERIALS AND METHODS: The medical records of patients who were diagnosed with MELAS at the Department of Pediatrics of Gangnam Severance Hospital between January 2006 and January 2017 were reviewed. The study population included 12 patients. They were divided into two subgroups according to whether the results of muscle pathology were in accordance with mitochondrial diseases. Clinical variables, diagnostic evaluations, and clinical outcomes were compared between the two groups. RESULTS: Of the 12 patients, seven were muscle pathology-positive for mitochondrial disease. No statistically significant difference in clinical data was observed between the groups that were muscle pathology-positive and muscle pathology-negative for mtDNA 3243A>G mutation. Additionally, the patients with weakness as the initial symptom were all muscle pathology-positive. CONCLUSION: The usefulness of muscle biopsy appears to be limited to an initial confirmative diagnostic evaluation of MELAS. Muscle biopsy can provide some information in MELAS patients with weakness not confirmed by genetic testing.
Biopsy* ; Diagnosis ; DNA, Mitochondrial ; Genetic Testing ; Humans ; Medical Records ; MELAS Syndrome* ; Methods ; Mitochondrial Diseases ; Mitochondrial Encephalomyopathies* ; Molecular Biology ; Pathology ; Pediatrics

Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.
Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Autoanalysis ; Biological Availability ; Biomarkers ; Biomarkers, Pharmacological ; Databases, Chemical ; Drug Combinations ; Drug Discovery ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Machine Learning ; Molecular Docking Simulation ; Neural Networks, Computer ; Peptide Fragments ; chemistry ; Permeability

Targeted therapy is one of the major treatment modalities in advanced non-small cell lung cancer (NSCLC) with sensitive driver gene mutations. BRAF is considered a promising oncogenic driver in NSCLC after the discovery of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion and ROS1 rearrangement. BRAF V600E mutation accounts for more than half of BRAF mutations, which is a potential therapeutic target for advanced NSCLC. This review aims to summarize the advancements of BRAF gene mutation and targeted therapy for BRAF mutation in NSCLC.
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Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; pathology ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Molecular Targeted Therapy ; methods ; Mutation ; Proto-Oncogene Proteins B-raf ; genetics

Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.
Animals ; Biomarkers, Tumor ; metabolism ; Drug Resistance, Neoplasm ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; drug therapy ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism

With high morbidity and mortality, lung cancer is a major threat to human health and one of the focuses of tumor researches. Lung cancer stem cells (LCSCs) are regarded as a subpopulation of cells within lung cancer tissues with the capacity of self-renewal and differentiation, and might be related to tumorigenesis and heterogeneity of lung cancer. Tumor recurrence, metastasis and drug resistance of lung cancers could be clarified by LCSC hypothesis. Thus it's therapeutically prospective to target at these cells. This review summarizes the biomarkers of LCSCs and their aberrant signal pathways, as well as the therapeutic strategies targeting at LCSCs.
Animals ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Molecular Targeted Therapy ; methods ; Neoplastic Stem Cells ; drug effects ; pathology ; Signal Transduction ; drug effects

BACKGROUND: Early detection of tuberculosis (TB) is challenging in resource-poor settings because of limited accessibility to molecular diagnostics. The aim of this study was to evaluate the performance of the loop-mediated isothermal amplification kit (TB-LAMP) for TB diagnosis compared with conventional and molecular tests. METHODS: A total of 290 consecutive sputum samples were collected from May till September, 2015. All samples were processed using the N-Acetyl-L-cysteine (NALC) NaOH method and tested by smear microscopy, solid and liquid culture, real-time PCR, and TB-LAMP. RESULTS: The sensitivity of TB-LAMP for smear-positive and smear-negative samples with culture positivity was 92.0% and 58.8%, respectively. TB-LAMP was positive in 14.9% of TB culture-negative samples; however, all those samples were also positive by real-time PCR. In addition, none of the samples positive for nontuberculous mycobacteria by culture were positive by TB-LAMP. The overall agreement between TB-LAMP and real-time PCR was good; however, the concordance rate was significantly lower for real-time PCR positive samples with Ct values of 30–35. CONCLUSIONS: TB-LAMP could replace smear microscopy and increase TB diagnostic capacity when Xpert MTB/RIF is not feasible because of poor infrastructure.
Acetylcysteine ; Diagnosis ; Methods ; Microscopy ; Nontuberculous Mycobacteria ; Pathology, Molecular ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Sputum ; Tuberculosis ; Tuberculosis, Pulmonary*

The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types.
Animals ; Citric Acid Cycle ; drug effects ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Oncogenes ; genetics ; Tumor Suppressor Proteins ; metabolism