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BACKGROUND: Telehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. OBJECTIVE: The primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician's perspective. METHODS: A telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform's registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. RESULTS: Over a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. CONCLUSIONS: This study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.
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The management of non-small cell lung cancer (NSCLC), specifically targeting the anaplastic lymphoma kinase (ALK) with tyrosine kinase inhibitors (TKIs), is challenged by the emergence of therapeutic resistance. Resistance mechanisms to ALK TKIs can be broadly classified into ALK-dependent and ALK-independent pathways. Here, we present a case with lung adenocarcinoma (LUAD) harboring an ALK rearrangement. The patient had developed resistance to sequential ALK TKI therapies, with an acquired ETV6-NTRK3 (E4:N14) fusion as a potential mechanism of ALK-independent resistance to lorlatinib. Subsequently, the patient was treated with the combination of brigatinib plus entrectinib and demonstrated a positive response, achieving an 8-month progression-free survival. Our case provides a potential treatment option for LUAD patients with ALK rearrangements and highlights the utility of next-generation sequencing (NGS) in uncovering genetic alterations that can guide the selection of effective treatment strategies.
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The emergence of targeted therapies and immunotherapies has improved the overall survival of patients with nonsmall cell lung cancer (NSCLC), but the 5-year survival rate remains low. New drugs are needed to overcome this dilemma. Moreover, the significant correlation between various client proteins of heat-shock protein (HSP) 90 and tumor occurrence, progression, and drug resistance suggests that HSP90 is a potential therapeutic target for NSCLC. However, the outcomes of clinical trials for HSP90 inhibitors have been disappointing, indicating significant toxicity of these drugs and that further screening of the beneficiary population is required. NSCLC patients with oncogenic-driven gene mutations or those at advanced stages who are resistant to multi-line treatments may benefit from HSP90 inhibitors. Enhancing the therapeutic efficacy and reducing the toxicity of HSP90 inhibitors can be achieved via the optimization of their drug structure, using them in combination therapies with low-dose HSP90 inhibitors and other drugs, and via targeted administration to tumor lesions. Here, we provide a review of the recent research on the role of HSP90 in NSCLC and summarize relevant studies of HSP90 inhibitors in NSCLC.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Proteínas HSP90 de Choque Térmico/metabolismo , Mutación , Línea Celular TumoralRESUMEN
Dendrocalamus liboensis Hsueh & D. Z. Li 1985 is a unique member of the Bambusoideae subfamily found in Guizhou, China. The species has both economic importance and ornamental value. This study represents the first report of the sequencing and assembly of the complete chloroplast genome of D. liboensis. The total length of the genome was 139,483 bp, with a conventional quadripartite framework consisting of a large single-copy (LSC) region (83,001 bp in length), a small single-copy (SSC) region (12,896 bp in length), and two inverted repeats (IR) regions (both 21,793 bp in length). Overall, the D. liboensis chloroplast genome contained 128 functional genes, including 83 protein-coding genes, 37 tRNAs, and 8 rRNAs. Phylogenetic analysis showed that D. liboensis closely resembled D. sapidus, with both found on a strongly supported branch of the phylogenetic tree.
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BACKGROUND: Acyl-coenzyme A cholesterol acyltransferase (ACAT) is a membrane-binding enzyme localized in the endoplasmic reticulum. ACAT2 can promote the development of colon cancer, but its efficacy in lung adenocarcinoma (LUAD) remains uncertain. METHOD: ACAT2 expression was performed by using the TIMER2.0 database. The GEPIA database was utilized to analyze the correlation between ACAT2 expression and pathological stage of the tumor. Clinical prognosis was assessed through the Kaplan-Meier analysis. The CancerSEA database was employed to scrutinize the correlations between the ACAT2 expression and the functional status of various tumors, which were subsequently visualized as a heatmap. Furthermore, molecular interaction network analysis was performed by the STRING tool. RESULTS: High ACAT2 expression was associated with a poor DFS and OS in LUAD patients. Cox regression analysis indicated that the poor outcomes may be related to tumor stage, nodal stage, distant metastatic stage. ACAT2 was found to play a crucial role in various biological processes, including the cell cycle, DNA repair, DNA damage response, and proliferation. Enrichment pathway analysis revealed four ACAT2 related genes, ACOX1, EHHADH, OXCT1, and DLAT. CONCLUSION: Our study showed that ACAT2 was upregulated in LUAD, and had a worse survival. ACAT2 could be a novel predictive biomarker and therapeutic target in LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Esterol O-Aciltransferasa 2 , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/patología , PronósticoRESUMEN
For advanced non-small cell lung cancer (NSCLC) patients with common epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or the exon 21 L858R mutation), tyrosine kinase inhibitors (TKIs) are the standard therapies. However, EGFR germline mutations are extremely rare in lung cancer, and the effective therapy is unclear. This study reports a patient with primary breast and lung cancer carried rare germline EGFR R776H and somatic L861Q mutation, who benefit from EGFR TKIs. Her family cancer history review demonstrated that her three out of four sisters with lung cancer were positive for EGFR R776H. Interestingly, only her healthy sister had type O blood, different from other sisters with type B blood. Our study provides a meaningful insight into the potential treatment option for patients with germline EGFR R776H and somatic L861Q mutation and highlights the importance of next-generation sequencing (NGS) in discovering rare genetic alterations to guide the prevention of genetic disease.
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Chimonobambusa utilis (Keng) Keng F is an endemic species distributed only in the Daluoshan Mountains, southwest China. Ch. utilis is popular due to its unique flavor and deliciousness and plays an important role in the industrial revolution in many counties in China. A total of 20 natural populations were sampled from the entire distribution range of Ch. utilis. In the present study, we used five EST-SSR molecular markers, three chloroplast DNA (trnH-psbA, atpF-atpH, and psbK-psbI), and one ITS molecular marker to elucidate the genetic diversity and phylogeography analyses of these Ch. utilis populations. The results exhibited that Ch. utilis populations showed lower genetic diversity than other angiosperms (HT = 0.752, HS = 0.364, and FST = 0.05021 for EST-SSR; HT = 0.956, Hs = 0.507, and FST = 0.70121 for cpDNA; HT = 0.868, Hs = 0.495, and FST = 0.70121 for nrDNA). A total of 40 alleles were detected for five polymorphic loci. We detected 20 polymorphic sites and 11 haplotypes within 1,398 bp of cpDNA and 59 polymorphic sites and 32 haplotypes within the 589 bp of the ITS sequence. Based on the haplotype distribution, we infer that there were at least two glacial refuges of Ch. utilis populations during the Quaternary Ice Age. The genetic and geographic distance were correlated (p < 0.05), indicating that narrow distribution might be the primary cause of the low genetic differentiation of Ch. utilis populations. Based on the genetic diversity of Ch. utilis populations, we recommend implementing effective genetic resource management and sustainable utilization.
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The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the first line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC), but drug resistance will be acquired within 1-2 years, and the following treatment efficacy is poor. The invention of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors has dramatically changed the situation of tumor treatment. PD-1/PD-L1 inhibitors are less effective in patients with NSCLC harboring EGFR mutation. It is a challenge to make patients with EGFR-mutated advanced NSCLC benefit from anti-PD-1/PD-L1 therapy. In this paper, the research progress on the impact of EGFR mutation on the immune status of NSCLC and related clinical studies in recent 5 years are reviewed.â©.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Puntos de Control Inmunológico , Ligandos , Mutación , Receptores ErbB/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
PURPOSE: The epidermal growth factor receptor (EGFR) represents a top therapeutic target in the treatment of non-small cell lung cancer. EGFR expression is intricately modulated by receptor endocytosis, during which EGFR ubiquitylation and deubiquitylation play fundamental roles to govern receptor fate. This study aims to uncover novel aspects of the endocytic regulation of EGFR trafficking by deubiquitylases. METHODS: The expression and ubiquitylation of EGFR in non-small cell lung cancer cells treated with deubiquitylase inhibitors were assessed by immunoblotting, immunoprecipitation and mass spectrometry analyses. The intracellular EGFR distribution was investigated using immunofluorescence and confocal microscopy assays, and colocalizations with endocytic compartments were examined using GFP-tagged Rab proteins as markers. The influence of the proteasomal deubiquitylase inhibitor b-AP15 on EGF- and HSP90 inhibitor-induced EGFR downregulation was evaluated by immunoblotting. The anticancer effects of b-AP15 were assessed by cell proliferation, colony formation and flow cytometry assays, as well as xenograft animal models. RESULTS: We found that b-AP15 caused a dramatically enhanced ubiquitylation of EGFR in lung cancer cells. Treatment with b-AP15 decreased cell surface EGFR levels and accumulated EGFR on recycling endosomes marked with Rab4A and Rab11A. b-AP15 effectively repressed EGF- and HSP90 inhibitor-induced EGFR degradation. Lung cancer cells exposed to b-AP15 showed markedly reduced cell propagation and significantly increased cell apoptosis. Furthermore, b-AP15 effectively inhibited tumor xenograft growth in nude mice. CONCLUSION: Proteasomal USP14 and UCHL5 act collectively to promote cell surface recovery of EGFR. Inhibition of proteasomal deubiquitylase activity induces increased EGFR ubiquitylation and retention on recycling endosomes. The USP14 and UCHL5 dual inhibitor b-AP15 elicits potent tumor-suppressive effects to deter cell proliferation and induce apoptotic cell death in lung cancer.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Factor de Crecimiento Epidérmico/farmacología , Receptores ErbB/metabolismo , Neoplasias Pulmonares/patología , Ratones Desnudos , Inhibidores de Proteasoma/farmacología , Ubiquitina Tiolesterasa/metabolismoRESUMEN
Chimonobambusa luzhiensis (Poaceae: Bambusoideae) is an endangered plant endemic to Guizhou Province, China. Here, we report the complete chloroplast genome of C. luzhiensis. The plastid genome revealed a typical quadripartite structure with a length of 139,896 bp, including a large single-copy (LSC, 83,191 bp) region, a small single-copy (SSC, 12,811 bp) region, and a pair of inverted repeat (IR) regions (IRa and IRb, 21,797 bp). A total of 131 genes, including 86 protein-coding genes (PCGs), eight ribosomal RNA (rRNA) genes, and 37 transfer RNA (tRNA) genes were annotated, and the overall GC content was 38.8%. Phylogenetic analysis showed that the relationship between C. luzhiensis is sister to C. tumidisinoda.
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Chimonobambusa hirtinoda, a threatened species, is only naturally distributed in Doupeng Mountain, Duyun, Guizhou, China. Next-generation sequencing (NGS) is used to obtain the complete chloroplast (cp) genome sequence of C. hirtinoda. The sequence was assembled and analyzed for phylogenetic and evolutionary studies. Additionally, we compared the cp genome of C. hirtinoda with previously published Chimonobambusa species. The cp genome of C. hirtinoda has a total length of 139, 561 bp and 38.90% GC content. This genome included a large single -copy (LSC) region of 83, 166 bp, a small single-copy (SSC) region of 20, 811 bp and a pair of inverted repeats of 21,792 bp each. We discovered 130 genes in the cp genome, including 85 protein-coding genes, 37 tRNA, and 8 rRNA genes. A total of 48 simple sequence repeats (SSRs) were detected. The A/U preference of the third nucleotide in the cp genome of C. hirtinoda was obtained by measuring the codon usage frequency of amino acids. Furthermore, phylogenetic analysis using complete cp sequences and matK gene revealed a genetic relationship within the Chimonobambusa genus. This study reported the chloroplast genome of the C. hirtinoda.
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Genoma del Cloroplasto , Composición de Base , Repeticiones de Microsatélite/genética , Filogenia , Poaceae/genéticaRESUMEN
BACKGROUND: We compared the efficacy, safety, and immunogenicity of MIL60 with reference bevacizumab as first-line treatment in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in this phase 3, randomized, double-blind study. METHODS: Patients with untreated advanced or recurrent NSCLC were randomized (1:1 ratio) to receive either MIL60 or bevacizumab in combination with paclitaxel/carboplatin. Patients with non-progressive disease continued maintenance single-agent MIL60 until disease progression, or intolerable toxicity. The primary endpoint was the 12-week objective response rates (ORR12) by independent review committee (IRC) using RECIST 1.1. Bioequivalence was established if the ORR ratio located between 0.75 and 1/0.75. The trial was registered with clinicaltrials.gov (NCT03196986). FINDINGS: Between Aug 23, 2017, and May 8, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and bevacizumab group (n=260). In the full analysis set (FAS) population including all randomized and evaluable patients who received at least one dose of MIL60 or bevacizumab, the ORR12 in MIL60 group and bevacizumab group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for bevacizumab. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. No patient detected positive for Anti-drug antibody (ADA). INTERPRETATION: The efficacy, safety and immunogenicity of MIL60 were similar with bevacizumab, providing an alternative treatment option for advanced or recurrent non-squamous NSCLC. FUNDING: This study was sponsored by Betta Pharmaceutical Co., Ltd.
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Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is effective in EGFR T790M positive non-small-cell lung cancer (NSCLC). Despite the efficacy of osimertinib, patients inevitably develop resistance and the mechanisms of osimertinib resistance are heterogeneous. Here, we report that a lung adenocarcinoma patient with EGFR L858R mutation who was treated with second-line osimertinib therapy acquired multiple resistance to osimertinib by the non-invasive circulating tumor DNA (ctDNA) genotyping. This case provides the possible mechanisms of osimertinib resistance that occur during the disease progression and supports the longitudinal monitoring of ctDNA for the detection of novel acquired resistance and tumor heterogeneity.
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Screening and detection of early lung cancer is important for diagnosis and prognosis. Intervention in early stage of lung cancer can significantly improve the cure and survival of patients. Surface-enhanced Raman spectroscopy (SERS) is an increasingly popular method of diagnosing cancer. We used silver nanoparticles (AgNPs) as the Raman-enhanced substrate to increase Raman signals, which contributes to the subsequent classification of lung cancer and normal serum. SERS acquired from the serum indicated the difference in biochemical components between cancerous (n = 51) lung serum and normal (n = 18) serum. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were utilized to establish the identification model, and the various indicators of PLS-DA were all superior to those of the PLS model. Our study offers a new proposal for the universal applicability of analysis and identification with SERS of serum samples in clinical diagnosis.
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Neoplasias Pulmonares , Nanopartículas del Metal , Análisis Discriminante , Humanos , Plata , Espectrometría RamanRESUMEN
Chimonobambusa hejiangensis is a kind of bamboo that has excellent edible and economic value, which is endemic to southwest China. The study used next-generation sequencing to obtain the complete chloroplast (cp) genome sequence of C. hejiangensis. The cp genome of C. hejiangensis has a total length of 138,908 bp, and consisted of an 82,495-bp large single-copy region, an 12,743-bp small single-copy region, and two 21,835-bp IR regions. In total, 112 unique genes were found in the cp genome, including 77 protein coding, 31 tRNA, and 4 rRNA genes. Phylogenetic analysis indicated that C.hejiangensis and C. tumidissinoda are sister species within the Arundinarieae genus, where Chimonocalamus and Ampelocalamus are more closely related to them.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas Tirosina Quinasas Receptoras , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Inhibidores de Proteínas QuinasasRESUMEN
BACKGROUND: The mortality rate of lung cancer meningeal metastasis is extremely high. Circulating tumor DNA (ctDNA) has been confirmed to be contain the genomic alterations present in tumors and has been used to monitor tumor progression and response to treatments. Due to the presence of blood-brain barrier and other factors, peripheral blood ctDNA cannot reflect the information of brain lesions for patients with meningeal metastases. However, cerebrospinal fluid ctDNA as a test sample can better reflect the genetic status of intracranial tumors and guide clinical targeted treatment of intracranial lesions. This study explored the feasibility of cerebrospinal fluid ctNDA for evaluating non-small cell lung cancer (NSCLC) meningeal metastasis and the potential clinical value of cerebrospinal fluid ctDNA detection in NSCLC meningeal metastasis. METHODS: A total of 21 patients with NSCLC meningeal metastasis were included. Tumor genomic variation was performed on the cerebrospinal fluid and peripheral blood samples of patients by second-generation gene sequencing technology. The situation was examined, and pathological evaluation of cerebrospinal fluid cytology and head magnetic resonance imaging (MRI) enhanced examination were performed. RESULTS: ctDNA was detected in the cerebrospinal fluid of 21 patients. The sensitivity of cerebrospinal fluid ctDNA detection was superior to cytology in the diagnosis of meningeal metastasis (P<0.001). The detection rate and gene mutation abundance of cerebrospinal fluid were higher than plasma (P<0.001). Cerebro-spinal fluid had a unique genetic profile. In 6 patients with dynamic detection, changes of ctDNA allele fraction occurred at the same time or earlier than clinical disease changes, which could timely monitor drug resistance mechanism and relapse trend. CONCLUSIONS: The detection rate of ctDNA in cerebrospinal fluid is higher than that in cytology and imaging. The detection of ctDNA in cerebrospinal fluid can reveal the specific mutation map of meningeal metastasis lesions. The dynamic monitoring of ctDNA in cerebrospinal fluid has hint significance for clinical response of lung cancer patients.
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Carcinoma de Pulmón de Células no Pequeñas/patología , ADN Tumoral Circulante/líquido cefalorraquídeo , Neoplasias Pulmonares/patología , Carcinomatosis Meníngea/líquido cefalorraquídeo , Carcinomatosis Meníngea/secundario , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition, mostly caused by germline TP53 mutations. Lung adenocarcinoma (ADC) has been identified as the most frequent LFS-related cancer outside the common LFS core spectrum. EGFR-kinase domain duplication (KDD) is rare in lung cancer and the effective therapy for LFS patients with EGFR-KDD mutated ADC is unclear. This study reports the first case of a TP53-mutated LFS patient with confirmed family history, developing advanced lung ADC harboring EGFR-KDD. MATERIALS AND METHODS: The patient's lung tumor, lymph nodes, liquid biopsies and germline control sample at various disease stages were subjected to next-generation sequencing (NGS). The TP53 germline mutation was confirmed using the peripheral blood of the patient's relatives by Sanger sequencing. RESULTS: A rare EGFR-KDD somatic mutation that was missed in the routine EGFR hotspots test, and a TP53-E285K temperature-sensitive germline mutation were identified by NGS. The patient was diagnosed with breast cancer in 2006 and her family cancer history review revealed that seven out of 13 relatives were diagnosed or died from LFS-spectrum cancers before the age of 45 years. Three of the six relatives were positive for the TP53-E285K germline mutation. This patient received multi-line chemotherapy followed by anlotinib, a multi-target tyrosine kinase inhibitor, upon the identification of EGFR-KDD, and achieved an overall survival of 18 months. CONCLUSIONS: Our study highlights the importance of NGS in discovering rare genetic alterations to guide treatment decision-making, and provides meaningful insight into the potential treatment options for LFS patients with EGFR-KDD mutations.
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Precise regulation of stem cell activity is crucial for tissue homeostasis. In Drosophila, intestinal stem cells (ISCs) maintain the midgut epithelium and respond to oxidative challenges. However, the connection between intestinal homeostasis and redox signaling remains obscure. Here we find that Caliban (Clbn) functions as a regulator of mitochondrial dynamics in enterocytes (ECs) and is required for intestinal homeostasis. The clbn knock-out flies have a shortened lifespan and lose the intestinal homeostasis. Clbn is highly expressed and localizes to the outer membrane of mitochondria in ECs. Mechanically, Clbn mediates mitochondrial dynamics in ECs and removal of clbn leads to mitochondrial fragmentation, accumulation of reactive oxygen species, ECs damage, activation of JNK and JAK-STAT signaling pathways. Moreover, multiple mitochondria-related genes are differentially expressed between wild-type and clbn mutated flies by a whole-genome transcriptional profiling. Furthermore, loss of clbn promotes tumor growth in gut generated by activated Ras in intestinal progenitor cells. Our findings reveal an EC-specific function of Clbn in regulating mitochondrial dynamics, and provide new insight into the functional link among mitochondrial redox modulation, tissue homeostasis and longevity.
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Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Mitocondrias/genética , Células Madre/citología , Proteínas Supresoras de Tumor/genética , Animales , Proliferación Celular/genética , Drosophila melanogaster/crecimiento & desarrollo , Enterocitos/metabolismo , Técnicas de Inactivación de Genes , Homeostasis , Intestinos/citología , Intestinos/crecimiento & desarrollo , Quinasas Janus/genética , Longevidad/genética , MAP Quinasa Quinasa 4/genética , Mitocondrias/metabolismo , Dinámicas Mitocondriales , Oxidación-Reducción , Factores de Transcripción STAT/genética , Transducción de Señal/genética , Células Madre/metabolismo , Factores de Transcripción/genéticaRESUMEN
Long non-coding RNAs (lncRNAs) are known to be potential factors in promoting tumor progression. However, the function and mechanism of lncRNA XIST in non-small cell lung cancer (NSCLC) remains poorly understood. The expression levels of lncRNA XIST in NSCLC tissues and cell lines were detected with real-time PCR, and the correlation of the expression level of XIST with histopathological characteristics and prognosis was analyzed. The biological function of lncRNA XIST was validated through assays in vivo and in vitro The expression of lncRNA XIST was significantly up-regulated in NSCLC tissues. In addition, overexpression of XIST was positively correlated with the advanced clinical status of tumors, as well as poor overall survival and DFS. A tumor suppressive effect was presented via functional knockdown of lncRNA XIST. Up-regulation of XIST enhanced the proliferation, migration, and invasion ability of NSCLC cells both in vivo and in vitro Mechanically, it was indicated that XIST could serve as an endogenous competitive RNA modulating miR-744, leading to the miR-744/RING1 signaling pathway inhibition and Wnt/ß-catenin signaling pathway activation. Taken together, it was confirmed here that XIST overexpression is associated with tumor progression phenotype and the newly discovered XIST/miR-744/RING1 axis, which could serve as a potential biomarker and therapeutic target for NSCLC.