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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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Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania Department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly clinical and experimental Medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly Department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

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FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis

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Science China Life Sciences 2025年

作者： Rongmei Gao Kanchao Chen Yimin Wang Rongxia Guo Xiaoyu Zhang Peng Wu Weili Wang Qingxiang Huang Xuemei Xie Shangda Yang Yanling Lü Qian Ren Fei Liu Song Chen Fengxia Ma Tao Cheng Hui Cheng State Key Laboratory of experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College CAMS Center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative Medicine

Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation, which is crucial for maintaining homeostasis. Acute infections can prompt a hematopoietic response known as emergency myelopoiesis. In this study, using a Candida albicans (C. albicans) infection model, we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates. Impaired myeloid hematopoiesis and immune cell production were evident, as proved by the decreased numbers of hematopoietic stem and progenitor cells (HSPCs) and granulocytes in the bone marrow of Fhl2-deficient mice. In conclusion, FHL2 regulated emergency myelopoiesis in response to C. albicans, affecting the host’s defense against pathogens.

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Androgens and estrogens in skeletal sexual dimorphism

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Asian Journal of Andrology 2014年第2期16卷 213-222,I0008页

作者： Michael Laurent Leen Antonio Mieke Sinnesael Vanessa Dubois Evelien Gielen Frank Classens Dirk Vanderschueren Laboratory of Molecular Endocrinology Department of Cellular and Molecular Medicine Gerontology and Geriatrics Department of Clinical and Experimental Medicine KU Leuven Leuven Begum Geriatric Medicine University Hospitals Leuven Leuven Belgium clinical and experimental endccrinology Department of Clinical and Experimental Medicine KU Leuven Leuven Belgium Endocrinology and Andrology Centre for Metabolic Bone Diseases Laboratory Medicine University Hospitals Leuven Leuven Belgium.

Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone （T） to estradiol （E2） by aromatase, or to dihydrotestosterone by 5（x-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of （high resolution） peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis.

关键词： androgen receptor bone mineral density estradiol estrogen receptor male osteoblast osteoclast osteocyte osteoporosis sex hormone-binding globulin testosterone

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Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

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World Journal of Gastroenterology 2017年第12期23卷 2185-2193页

作者： Peter Macinga Adela Pulkertova Lukas Bajer Jana Maluskova Martin Oliverius Martin Smejkal Maria Heczkova Julius Spicak Tomas Hucl Department of Gastroenterology and Hepatology Institute for Clinical and Experimental Medicine Department of Pathology Institute for Clinical and Experimental Medicine Department of Transplant Surgery Institute for Clinical and Experimental Medicine Department of Radiodiagnostics and Interventional Radiology Institute for Clinical and Experimental Medicine Center for experimental Medicine Institute for Clinical and Experimental Medicine

AIM To assess the occurrence of autoimmune pancreatitis(AIP) in pancreatic resections performed for focal pancreatic *** We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic *** Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients(5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma(PC) was also present in six patients with AIP(40%), all six were men. Patients with AIP + PC were significantly older(60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes(67% vs 11%, P = 0.09), and had experienced greater weight loss(15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.

关键词： Chronic pancreatitis Pancreatic cancer Ig G4related disease Autoimmune pancreatitis Malignancy

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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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Etiology and functional status of liver cirrhosis by ^(31)P MR spectroscopy

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World Journal of Gastroenterology 2005年第44期11卷 6926-6931页

作者： Monika Dezortova Pavel Taimr Antonin Skoch Julius Spicak Milan Hajek MR Unit Institute for clinical and experimental Medicine Prague Czech Republic Department of Hepatogastroenterology Institute for clinical and experimental Medicine

AIM: To assess the functional status and etiology of liver cirrhosis by quantitative 31p magnetic resonance spectroscopy (MRS).METHODS: A total of 80 patients with liver cirrhosis of different etiology and functional status described by Child-Pugh score were examined and compared to 11 healthy volunteers. MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging *** concentrations of phosphomonoesters (PME),phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were ***: MRS changes reflected the degree of liver dysfunction in all the patients as well as in individual etiological groups. The most important change was a decrease of PDE. It was possible to distinguish alcoholic,viral and cholestatic etiologies based on MR *** and viral etiology differed in PDE (alcoholic,viral, controls: 6.5±2.3, 6.5±3.1, 10.8±2.7 mmol/L,P＜0.001) and ATP (alcoholic, viral, controls: 2.9±0.8, 2.8±0.9, 3.7±1.0 mmol/L, P＜0.01) from the control *** viral etiology, patients with alcoholic etiology also differed in Pi (alcoholic, controls: 1.2±0.4, 1.6±0.6mmol/L, P＜0.05) from controls. No significant changes were found in patients with cholestatic disease and controls; nevertheless, this group differed from both alcoholic and viral groups (cholestatic, alcoholic, viral: 9.4±2.7, 6.5±2.3, 6.5±3.1 mmol/L, P＜0.005) in ***: 31p MRS can significantly help in noninvasive separation of different etiological groups leading to liver cirrhosis. In addition, MRS changes reflect functional liver injury.

关键词： Liver cirrhosis ^ 31p MR spectroscopy Absolute concentration Child-Pugh score Etiology

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Fat:A matter of disturbance for the immune system

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World Journal of Gastroenterology 2010年第38期16卷 476-4772页

作者： Alessandro Federico Elena D’Aiuto Francesco Borriello Giusi Barra Antonietta Gerarda Gravina Marco Romano Raffaele De Palma Section of Gastroenterology Department of Clinical and Experimental MedicineSecond University of Naples Section of clinical Immunology Department of Clinical and Experimental Medicine Second University of Naples

Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and in? ammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic in? ammation, mainly as a result of increased adipocytes as well as fat resident-and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steato-hepatitis in the absence of signif icant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesityrelated pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specif ic immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as "a matter of disturbance for the immune system" with a focus on hepat

关键词： Adipocytokine Adipose tissue Fat Immune system Kupffer cell Natural killer Steatosis

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Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease

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World Journal of Gastroenterology 2018年第43期24卷 4939-4949页

作者： Lukas Bajer Antonij Slavcev Peter Macinga Eva Sticova Jan Brezina Matej Roder Radim Janousek Pavel Trunecka Julius Spicak Pavel Drastich Department of Gastroenterology and Hepatology Institute for Clinical and Experimental MedicinePrague Department of Immunogenetics Institute for Clinical and Experimental Medicine Department of clinical and Transplant Pathology Institute for Clinical and Experimental MedicinePrague Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental MedicinePrague

AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical *** Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective *** De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.

关键词： Primary sclerosing cholangitis Inflammatory bowel disease Liver transplantation Acute cellular rejection Autoimmune hepatitis Human leukocyte antigen Immunosuppression

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Evolving strategies for liver fibrosis staging: Non-invasive assessment

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World Journal of Gastroenterology 2017年第2期23卷 191-196页

作者： cristina Stasi Stefano Milani Department of experimental and clinical Medicine University of Florence Department of Biomedical Experimental and Clinical SciencesUniversity of Florence

Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either noninvasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change- even in the event of fibrosis regression. Therefore, future studies are needed to validate noninvasive methods in predicting the different phases of liver cirrhosis.

关键词： Elastography Non-invasive methods Chronic liver diseases Stiffness Non-invasive serum markers

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