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CAF-derived exosome-miR-3124-5p promotes malignant biological processes in NSCLC via the TOLLIP/TLR4-MyD88-NF-κB pathway

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Oncology Research 2025年第1期33卷 133-148页

作者： TAO SUN QINGHUA SONG HUA LIU department of Respiratory and Critical Care Medicine Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong226001China department of Emergency The People’s Hospital of RugaoNantong226500China department of haematology The People’s Hospital of RugaoNantong226500China

Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in *** crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent ***-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to ***:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot *** were isolated and identified from clinical NSCLC *** electron microscopy and Western Blot were used to identify exosomes from these *** in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were *** Luciferase reporter test was applied to clarify the binding of miR-3124-5p to *** TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot ***:MiR-3124-5p is overexpressed in clinical tissues and cells of ***-3124-5p was dramatically enriched in CAF-derived *** experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell ***-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of *** salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling ***:These results provide an interesting direction for the diagnosis and therapy of NSCLC.

关键词： Non-small cell lung cancer(NSCLC) Cancer-associated fibroblasts(CAFs) Exosomes miR-3124-5p Toll-interacting protein(TOLLIP)

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Elevated plasma von Willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation

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World Journal of Gastroenterology 2005年第48期11卷 7639-7645页

作者： Petros Zezos Georgia Papaioannou Nikolaos Nikolaidis Themistoclis Vasiliadis Olga Giouleme Nikolaos Evgenidis Division of Gastroenterology department of haematology

AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation ***: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was ***: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic ***: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed e

关键词： Coagulation Endothelial injury Inflammation Inflammatory bowel disease Ulcerative colitis von Willebrand factor

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Hyperhomocysteinemia in ulcerative colitis is related to folate levels

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World Journal of Gastroenterology 2005年第38期11卷 6038-6042页

作者： Petros Zezos Georgia Papaioannou Nikolaos Nikolaidis Themistoclis Vasiliadis Olga Giouleme Nikolaos Evgenidis Division of Gastroenterology department of haematology

AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC).METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 UC patients and 50 healthy controls. Clinical data regarding UC were ***: Median serum Hcys levels in UC patients were similar to those in controls (12.26 μmol/L vs 12.32 μmol/L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028). UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125;95% CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2 = 0.4; P＜0.001).CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.

关键词： Folate Homocysteine Hyperhomocysteinemia Thrombosis Ulcerative colitis Vitamin B12

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Impaired glucocorticoid receptor expression and mitochondrial metabolism in MDSCs contribute to glucocorticoid resistance in immune thrombocytopenia

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Cellular & Molecular Immunology 2022年第7期19卷 858-860页

作者： Rick Kapur Sanquin Research Department of Experimental ImmunohematologyAmsterdam and Landsteiner LaboratoryAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands

In this issue of Cellular&Molecular Immunology,Hou and coworkers provide novel insights into glucocorticoid(GC)treatment refractoriness in immune thrombocytopenia(ITP),reporting that myeloid-derived suppressor cells(MDSCs)contribute to GC resistance in ITP via impairments in their glucocorticoid receptor(GR)expression and mitochondrial metabolism[1].

关键词： metabolism glucocorticoid Immunology

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Role of von Willebrand factor levels in the prognosis of stage Ⅳ colorectal cancer: Do we have enough evidence?

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World Journal of Gastroenterology 2005年第38期11卷 6072-6073页

作者： I.Gil-Bazo J.A Díaz-González J.Rodríguez J.Cortés E.Calvo J. A. Páramo J.García-Foncillas department of Oncology Institute for Drug Development Service of haematology

Cancer patients usually present a prothrombotic condition. Several clotting-related proteins, such as von Willebrand factor （vWF）, presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover, some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer （MCRC）. In this comment article,

关键词： Von Willebrand factor Colorectal cancer Prognosis

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Metastatic colorectal cancer-past,progress and future

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World Journal of Gastroenterology 2007年第28期13卷 3806-3815页

作者： Kathryn Field Lara Lipton department of Medical Oncology and Clinical haematology Western HospitalFootscray 3011VictoriaAustralia

The clinical management of metastatic （stage IV） colorectal cancer （CRC） is a common challenge faced by surgeons and physicians. The last decade has seen exciting developments in the management of CRC, with significant improvements in prognosis for patients diagnosed with stage IV disease. Treatment options have expanded from 5-fluorouracil alone to a range of pharmaceutical and interventional therapies, improving survival, and providing a cure in selected cases. Enhanced understanding of the biologic pathways most important in colorectal carcinogenesis has led to a new generation of drugs showing promise in advanced disease. It is hoped that in the near future the treatment paradigm of metastatic CRC will be analogous to that of a chronic illness, rather than a rapidly terminal condition. This overview discusses the epidemiology of advanced CRC and currently available therapeutic options including medical, surgical, ablative and novel modalities in the management of metastatic colorectal cancer.

关键词： Colorectal cancer Metastases Chemotherapy Oncology Biological therapies

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Adjuvant therapies for colorectal cancer

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World Journal of Gastroenterology 2007年第28期13卷 3799-3805页

作者： Suzanne Kosmider Lara Lipton department of Medical Oncology and Clinical haematology Western HospitalFootscray 3011VictoriaAustralia

The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage 11 disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

关键词： Colon cancer Rectal cancer Chemotherapy Radiotherapy Adjuvant treatment

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Philadelphia chromosome-positive acute myeloid leukemia with masses and osteolytic lesions： finding of 18F-FDG PET/CT

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Frontiers of Medicine 2017年第3期11卷 440-444页

作者： Zhan Su Fengyu Wu Weiyu Hu Xiaodan Liu Shaoling Wu Xianqi Feng Zhongguang Cui Jie Yang Zhenguang Wang Hongzai Guan Hongguo Zhao Wei Wang Chunting Zhao Jun Peng department of haematology Qilu Hospital Shandong University Jinan 250012 China department of haematology The Affiliated Hospital of Qingdao University Qingdao 266000 China PET/CT Center The Affiliated Hospital of Qingdao University Qingdao 266000China department of Hepatobiliary Surgery The Affiliated Hospital of Qingdao University Qingdao 266000 China department of haematology Qingdao University Medical College Qingdao 266071 China

Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lyric lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography （18F-FDG PET/CT） result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lyric bone lesions. Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker. For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities, a diagnosis of Philadelphia-positive acute myeloid leukemia was made, although the type （de novo or blast crisis） remained unclear.

关键词： Philadelphia chromosome acute myeloid leukemia mass osteolysis positron emission tomography

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Anti-T-lymphocyte globulin-based non-myeloablative stem cell transplantation followed by HLA-identical donor lymphocyte infusion for hematologic malignancies

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Chinese Medical Journal 2003年第1期116卷 70-73页

作者：毛平王顺清王汉平李庆山许艳丽莫文健应逸朱志刚 department of haematology

Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic *** The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 10 6/kg followed by the escalated dosage in the range of (0.5-1.5)×10 8/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and *** Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.

关键词： nonmyeloablative stem cell transplantation · lymphocyte infusion · hematologic malignancy

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Multiple myeloma presenting with amyloid arthropathy as the first manifestation:Two case reports

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World Journal of Clinical Cases 2022年第35期10卷 13028-13037页

作者： Chuan He Xue-Ping Ge Xiao-Hui Zhang Ping Chen Bing-Zong Li department of haematology The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina

BACKGROUND Multiple myeloma(MM)can be accompanied by amyloidosis,which occurs in a small number of patients and is characterized by deposition of light chains in the joints,leading to multiple myeloma-associated amyloid arthropathy(MAA).As a rare complication of MM,clinical manifestations of MAA are often similar to those of rheumatoid arthritis,and the two are easily *** SUMMARY In recent years,our center treated two patients of MM with amyloid arthropathy as the first manifestation,both of whom presented with *** treatment for MM,both patients achieved complete ***,subsequently,the two patients underwent hip arthroplasty for femoral neck *** red staining and immunofluorescence of the joint tissues confirmed MAA after ***,one of the patients died of MM recurrence,while the other *** MAA should be regarded as an initial symptom of MM and should be taken seriously.

关键词： Amyloidosis Polyarthritis Monoclonal gammopathies Immunoglobulin light chain amyloidosis Multiple myeloma Case report

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