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SBL-JP-0004:A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

Oncology Research 2025年第1期33卷 235-243页

作者： HASSAN M.OTIFI Department of pathology College of MedicineKing Khalid UniversityAbha62521Saudi Arabia

Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional *** phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic ***:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD *** and SNU-5 GC cells were used for in vitro ***:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics *** interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target ***-JP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nM against JAK2 kinase and 200.9 nM against PI3KCD ***-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nM,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-JP-0004 treatment compared to 2.1%and 2.83%in their respective ***:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Gastric cancer(GC) Dual inhibition JAK2 PI3KCD SBL-JP-0004 molecular docking molecular dynamics simulation

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Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

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Genetic signatures of ERCC1 and ERCC2 expression,along with SNPs variants,unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology Research 2025年第1期33卷 45-55页

作者： ENRICO CALIMAN SARA FANCELLI FEDERICO SCOLARI ADRIANO PASQUI CLARA MANNESCHI DANIELE LAVACCHI FRANCESCA MAZZONI FRANCESCA GENSINI VALERIA PASINI CAMILLA EVA COMIN LUCA VOLTOLINI SERENA PILLOZZI LORENZO ANTONUZZO Clinical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence50134Italy Department of Health Sciences University of FlorenceFlorence50134Italy Medical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Biomedical Sciences“Mario Serio” University of FlorenceFlorence50134Italy Section of Anatomic pathology Department of Health SciencesUniversity of FlorenceFlorence50139Italy Section of Surgery Histopathology and Molecular PathologyUniversity of FlorenceFlorence50139Italy Thoracic Surgery Unit Careggi University HospitalFlorence50134Italy

Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum *** in this repair mechanism may affect patients’*** and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to *** expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor ***:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy *** with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant ***:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： Small cell lung cancer(SCLC) Nucleotide excision repair(NER)pathway ERCC genes Single nucleotide polymorphisms(SNPs) Platinumchemotherapy(CT)

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Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

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World Journal of Gastroenterology 2015年第36期21卷 10468-10474页

作者： Andrea Cacciato Insilla Pinuccia Faviana Luca Emanuele Pollina Paolo De Simone Laura Coletti Franco Filipponi Daniela Campani Department of Surgical MedicalMolecular Pathology and Critical AreaDivision of Surgical PathologyUniversity Hospital of Pisa Department of Surgical MedicalMolecular Pathology and Critical AreaDivision of Liver Surgery and TransplantationUniversity Hospital of Pisa

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here,a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy,the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2,CK8,CK18,CEA(polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3,CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors(GISTs).The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here,we report the clinicopathological features of our case,along with a review of the few cases present in the literature.

关键词： Lymphoepithelioma Lymphoepithelioma-like Hepatocel

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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz Węgrzyn Department of molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

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Comparing role of ATP between acute pain in neuromyelitis optica spectrum disorder and peripheral neuropathic pain

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Neural Regeneration Research 2025年第1期20卷 184-185页

作者： Teruyuki Ishikura Tatsusada Okuno Department of molecular Neuroscience Graduate School of MedicineOsaka UniversityOsakaJapan Department of Neurology Osaka University Graduate School of MedicineOsaka UniversityOsakaJapan

In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.

关键词： pain acute pathology

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Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization

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World Journal of Gastroenterology 2005年第9期11卷 1303-1316页

作者： Christine Fallsehr Christina Zapletal Michael Kremer Resit Demir Magnus von Knebel Doeberitz Ernst Klar Institute of molecular pathology Department of Surgery

AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI). RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context. CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.

关键词： Organ injury Liver ischemia AP-1 transcription factor Heat shock protein Gadd45A Suppression subtractive hybridization

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Purinergic signaling systems across comparative models of spinal cord injury

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Neural Regeneration Research 2022年第3期17卷 2391-2398页

作者： Eva E.Stefanova Angela L.Scott Department of pathology and molecular Medicine McMaster UniversityHamiltonONCanada

Within the last several decades,the scientific community has made substantial progress in elucidating the complex pathophysiology underlying spinal cord ***,despite the many advances using conventional mammalian models,both cellular and axonal regeneration following spinal cord injury have remained out of *** this sense,turning to non-mammalian,regenerative species presents a unique opportunity to identify pro-regenerative cues and chara cterize a spinal cord microenvironment permissive to *** the signaling pathways hypothesized to be dysregulated during spinal cord injury is the purinergic signaling *** addition to its well-known role as energy currency in cells,ATP and its metabolites are small molecule neurotransmitte rs that mediate many diverse cellular processes within the central nervous *** our unde rstanding of the roles of the purinergic system following spinal cord injury is limited,this signaling pathway has been implicated in all injury-induced secondary processes,including cellular death,inflammation,reactive gliosis,and neural *** that the purinergic system is also evolutionarily conserved between mammalian and non-mammalian species,comparisons of these roles may provide important insights into conditions responsible for recovery ***,we compare the secondary processes between key model species and the influence of purinergic signaling in each *** our understanding of this signaling system and pro-regenerative conditions continues to evolve,so does the potential for the development of novel therapeutic interventions for spinal cord injury.

关键词： cell death differenriation glia inflammation neurogenesis proliferation purinergic signaling reactive gliosis regeneration spinal cord injury teleost

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Chemically oligomerizable TDP-43:a novel chemogenetic tool for studying the pathophysiology of amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第11期17卷 2434-2436页

作者： Kohsuke Kanekura Yoshiaki Yamanaka Tamami Miyagi Masahiko Kuroda Department of molecular pathology Tokyo Medical University

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of both upper and lower motor *** ALS cases are sporadic,but approximately 5-10%of patients have a f... 详细信息

关键词： sclerosis familial

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