Adhesion and cytotoxicity susceptibility of B16 melanoma cells to immune effector cells enhanced after IL-2, IL-4 or IL-6 gene-transfection

The elimination of the tumor is closely relatedwith the sensitivity of tumor cells to the cytotoxicityof immune effector cells. We supposed that cytokinegenetransfection may increase the cytotoxicitysusceptibility of tumor cells to effector cells, and as aconsequence, the tumorigenicity decreased. Beforekilling tumor cells, effector cells required first torecognize non-specific surface adhesion molecules on     

Genetic immunotherapy ot hepatocellular carcinoma ( HCC) with adenovirus or retrovirus vectors carrying interleukin 12 ( IL-12 ) or costimulatory molecule B7-1

The progressive growth of tumors in the presence ofan intact immune system suggests that immunemechanisms may have failed to defend the host fromtumor cells. One therapeutic approach to cnhanceeffective immune responses is to introduce the immuno-regulatory genes that alter the local immunologicalmicroenvironment and increase immunogenecity of tumor     

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy

Lymphoma, which is highly malignant, stems from lymph nodes and lymphoid tissue. Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2), which binds with programmed cell death 1 protein(PD-1) to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance. Recently, immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab) have been introduced into the lymphoma treatment algo...     

Augmented cytotoxicity and antigen presenting ability of macrophages by transfection with the M-CSF or/and IFN-γ gene

Since the beginning of gene therapy, most of genetransfection were focused on the tumor cells or effectorcells. We selected macrophages as the target cells of genetransfection because they are not only antitumor effectorcells but also antigen-presenting cells.They act as abridge connecting tumor cells with immune effector cells.Two cytokines we chosen are closely linkcd with thefunctions of macrophage. IFN-γis a principle factor toactivate macrophages and it incrcases MHC expression ofthem which can improve their antigen presenting ability.M-CSF is an important cytokine to keep theproliferation, differentiation and maturation ofmacrophage progenitor cells. In this study, we used a     

Large cutaneous epithelioid angiomatous nodules in a patient with nephrotic syndrome: A case report

BACKGROUND Cutaneous epithelioid angiomatous nodules(CEAN) are rare, benign, vascular lesions characterized by benign proliferation of endothelial cells with prominent epithelioid features, which can be easily confused with benign and malignant vascular tumors. However, the etiology of CEAN remains unclear, and no association with infection, trauma, or immunosuppression has been described.This case study indicated that CEAN is closely related to the patient’s impaired immune status and may be induced by cyclosporine.CASE SUMMARY A 19-year-old boy with nephrotic syndrome(NS) developed large CEAN on the left foot during treatment for NS. He had repeated relapses of edema in the past 6 years and different types of immunosuppressants were administered including methylprednisolone, mycophenolate mofetil, tacrolimus and cyclosporine;the dosages of these drugs were frequently adjusted. The patient had been receiving cyclosporine and methylprednisolone for 7 mo before he developed CEAN.Cyclosporine was discontinued due to its side effects on skin. After cessation of cyclosporine and 16 mo follow-up, the nodules gradually disappeared without any other treatment for the CEAN.CONCLUSION Impaired immune status is proposed to be a risk factor for CEAN, which may be induced by cyclosporine.     

Rare anaplastic sarcoma of the kidney:A case report

BACKGROUND Anaplastic sarcoma of the kidney(ASK)is a rare and newly recognized renal neoplasm.The tumor usually is extensive and cystic,characterized by pleomorphic spindle cells with marked atypia and associated with multinucleated cells.To date,only 27 cases have been reported in the literature.The authors present an additional case and summarize the relevant knowledge in the literature.CASE SUMMARY A 27-year-old previously healthy woman presented with a palpable mass over the abdomen and right flank soreness for one year.After the computed tomography study,the patient underwent right radical nephrectomy obtaining a 1680-g tumor with a size of 18.4 cm×14.5 cm×11 cm.The tumor is chiefly composed of anaplastic spindle cells with marked nuclear atypia admixed with multinucleated cells.Immunohistochemical evaluation of tumor cells exhibited diffuse positivity for CD56,p53,and vimentin,and focally positive for desmin.The diagnosis of ASK was established.Unfortunately,a local tumor recurrence followed by a distant metastasis developed within months.The patient died 26 months after the initial surgery.Comparing to the previously 27 cases of ASK,the current case had a relatively worse prognosis,which might be potentially associated with older patient age,larger tumor size,and the lack of en-bloc resection of adjacent organs during the initial radical nephrectomy.CONCLUSION This case points out the featured pathological findings for diagnosing ASK and suggests more aggressive management for patients with ASK.     

多灶性运动神经病的电生理分析

INTRODUCTION At present, multffocal motor neuropathy(MMN) is being graduallyrecognized, but domestic reports are rare and there is some difficultyin clinical diagnosis. The chnical manifestations are chronic asym-metric motor dysfunction, physiological characteristics of multifocalcondution blocking. Because increasing of serum GM1 antibody titreis often complicated, many authors think that it is a kind of periph-eral neuropathy mediated by immune. The following is the datasummary of 15 cases of MMN.     

Immune checkpoint inhibitor-induced colitis:A comprehensive review

Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. However,many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease,however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.     

烧伤后肠黏膜免疫组织细胞增殖分化的特征性研究

BACKGROUND: The descent of intestinal mucous membranous immune barrier will cause the translocation of opportunistic pathogen, which will lead to enterogenous infection that will affect the rehabilitation of patients‘ organisms and relevant functions, but the mechanism is still not well established.OBJECTIVE: To observe the transition of mIgA in peyer patch lymphocytes (PPL) and the conditions of proliferations in vitro of lamina properia lymphocytes(LPL) in intestinal mucous membranous immune tissues after burn,in order to increase mucous membranous immune barriers, to prevent enterogenous infections and to provide a clinical gist in speeding up rehabilitations in burn patients.DESIGN: A random control vertical study.SETTING and PARTICIPANTS; This study was completed in the Central Laboratory and Department of Burn Surgery, General Hospital of Chinese People‘s Armed Police Forces. Subjects were 20 SPF mice.INTERVENTION: The mice were randondy grouped into control group (n= 10) and burn group/n = 10). Mice in burn group were burnt with 20% of total body surface area(TBSA) in III degree burn and executed after 3-day of injury together with the mice in control group.MAIN OUTCOME MEASURE; IgA plasmoeytes in intestinal lamina propria(LP) were observed by in vivo imnmnohistochemical staining; IgA on the surface of lymphocytes in PP were counted by flow cytometry; in vitro proliferations of LP lymphocytes were assayed after burn; IL-6 in intestinal tissue was assayed b) ELISA.RESULTS: The positive rate of IgA in PP after 3-day of burn was lower than that of control group: the numbers of IgA ptasmocytes in LP after burn were significantly less than the level before burn, in vitro proliferation of the lymphocytes in LP was distinctly decreased after burn; the level of IL-6 in intestinal tissue had no significant difference compared with that of control group.CONCLUSION: Burn irffdbits the proliferation and differentiation of lymphocytes in intestinal mucous membranous immune tissues, which will lead to the depression of mucous membranous immune barrier.     

Immunogene therapy of cancer: epitope linkage requirement for the induction of T cells

Many cancer gene therapy strategies arevaccination strategies aiming at the induction ofcytolytic immune responses against the malignantcells. These strategies include modification of thetumour cells by transfection with the genes of co-stimulatory molecules for cytotoxic T lymphocytes(CTL) such as IL-2 and B7, or manipulation ofbystander cells like autologous fibroblasts byintroduction of cytokine genes and subsequent co-     

Role of oxysterol-binding protein-related proteins in malignant human tumours

The oxysterol-binding protein-related protein(ORP)family is a group of proteins that mediate oxysterol metabolism and bioactivity in cells.ORPs constitute a large family of lipid transfer proteins.Much of the current evidence indicates that certain members of the family of oxysterol-binding proteins(OSBPs)can lead to cancer.Many studies have revealed the putative roles of OSBPs in various cancer types.However,the exact effects and mechanisms of action of members of the OSBP/ORP family in cancer initiation and progression are currently unclear.This review focuses on ORP family members that can accelerate human tumour cell proliferation,migration,and invasion.The mechanisms and functions of various ORPs are introduced in detail.We also attempt to identify the roles of these proteins in malignant tumours with the ultimate aim of determining the exact role of the OSBP/ORP family in human tumour cells.     

Clinicopathologic characteristics of prostatic stromal sarcoma with rhabdoid features: A case report

BACKGROUND Prostatic stromal sarcoma presenting with rhabdoid features is extremely rare,and only four cases have been reported in the English-language literature to date.Accordingly, there is no absolute definition of this group of tumors as yet, and our overall understanding of its morphological features, therapeutic regimen and prognosis is limited.CASE SUMMARY A 34-year-old male patient was referred to our hospital to address a 2-mo history of hematuria and progressive dysuria. Pelvic computed tomography scan revealed a 6.0 cm × 5.2 cm × 7.2 cm mass in the prostate, with bladder invasion.The patient underwent transurethral prostatectomy as upfront therapy. He refused further treatment and died of uncontrollable tumor growth 3 mo after surgery. Pathology analysis revealed the stroma to be pleomorphic, with a huge number of atypical spindle cells. Rhabdomyoblastic cells, with abundant eosinophilic cytoplasm, were detected. The spindle cells were positive for vimentin, INI1 and β-catenin, and the rhabdomyoblastic cells were positive for MyoD1, myogenin and INI1. The spindle cells and epithelial cells were sporadically positive for P53.CONCLUSION The prostatic stromal sarcoma tumor was immunoreactive for β-catenin,suggesting a role for the Wnt/β-catenin pathway in this tumor type.     

T淋巴细胞内mTOR/S6途径在难治/复发再生障碍性贫血发病机制中的作用

Objective To explore the activation status of signal pathway of mTOR/S6 in bone marrow(BM) T lymphocytes of refractory/relapsed aplastic anemia patients(AA),and the effects of rapamycin (RAPA)and CTLA-4 immunoglobulin(CTLA-4 Ig)on this pathway.Methods BM was collected from 13refractory/relapsed AA patients,8 newly diagnosed severe AA(SAA)patients and 10 iron deficiency anemia (IDA)(as controls)patients,and cocultured with RAPA and CTLA-4 Ig.The expression of p-mTOR,p-S6 and Interferon γ(IFN-γ)in CD3+ T cells was measured by flow cytometry(FCM).Results ①The expression of p-mTOR,P-S6 and IFN-γ in CD3+ T cells in refractory/relapsed AA group were significantly higher than those in controls(P＜0.01).②The expression of P-mTOR and p-S6 in T cels in newly diagnosed SAA group,Was similar to those in controls(P＞0.05),but significantly lower than those in refractory/relapsed AA group(P＜0.01).The expression level of IFN-γ in T cells were significantly higher than that in controls (P＜0.01).③On exposure to RAPA,The levels of p-mTOR,p-S6 and IFN-γ in T cells in refractory/relapsed AA patients were significantly lower than those before the exposure(all P＜0.05).And so were when exposed to CTLA-4 Ig(all P＜0.01).Conclusion ①The mTOR/S6 signal pathway is activated in refractory/relapsed AA.②The expression of p-mTOR,p-S6 and IFN-γ in refractory/relapsed AA Can be suppressed by RAPA or CTLA-4 Ig.③The signal pathway of CD28/mTOR/S6/IFN-γ might take part in immune pathogenesis of refractory/relapsed AA.     

Retroviral-mediated IL-2 and IFN-γ gene transfer in human bladder tumor cells

Tumor cells may escape immune surveillance mainlyby (1) down regulation of major histocompatibilitycomplex (MHC) molecules or alteration of antigen-processing pathways; (2) low-level of cytokines in thevicinity of the tumor, which can't activate immunosystemeffectively. Recent studies have shown that geneticallyengineered tumor cells expressing cytokines such as IL-2IFN-γ can induce greater CTL activity and activate NK,LAK and TIL. Besides IFN-γ can enhance the expression     

A Study on the D-loop Region of Mitochondrial DNA (mtDNA) Mutation in Cervical Carcinomas

Objective Background-study on genesis and development of tumor is mainly concentrated on gene mutation in nucleus.In recent years,however,the role of mitochondrial DNA(mtDNA) mutation in tumor genesis has been given more and more attention,which is the only extra-nucleus DNA in cells of higher animals.Carcinoma of the uterine cervix is a common tumor in gynecology,but there are few reports of mtDNA mutation in this area.The focus of this study was to investigate the mtDNA mutation in tumor tissues of cervical carcinomas and their relationship to tumorigenesis and tumor development.Methods The D-loop region of 24 cervical carcinomas together with the adjacent normal tissues were amplified by PCR and sequenced.Results Among the 24 cervical carcinomas,30 mutations in 9 patients′ specimen were identified with the mutations rate of 37.5%(9/24).There were 8 microsatellite instabilities among the mutations and 13 new polymorphisms which were not reported previously in the Genbank.Conclusions The D-loop region of mitochondrial DNA is a highly polymorphoric and mutable region and the mutation rate is relatively high in patients with cervical carcinomas.     

Dynamic observation of bone marrow suppression and chromosomal aberrations in patients with acute colchicine poisoning

Colchicine is a neutral lipophilic tricyclic alkaloid toxic to human cells containing tubulin,[1-2]and primarily stops the proliferation of active cells in the mitotic metaphase,such as intestinal mucosal cells and hematopoietic cells.It is widely used in treating gout and familial Mediterranean fever,while it is also used in establishing animal and plant experimental model.[3]In the recent study,treatment of patients affected by coronavirus disease 2019(COVID-19)with colchicine may prove a viable path.[4]The course of colchicine poisoning can be divided into three stages,[5]and most of the patients died in the second stage(2-7 d,the multiple organ injury stage).The cause of death was heart failure[6]and bone marrow hematopoietic failure in the terminal phase.[7]Hematopoiesis is a classic sign of colchicine poisoning.Many cases of colchicine poisoning have been comprehensively reported,and the target organs included heart,digestive tract,muscle,lung,kidney,hematopoietic system,etc.[8-11]This study aimed to investigate the injury of bone marrow hematopoietic system after colchicine poisoning and evaluate the therapeutic effect of bone marrow hematopoietic stimulation drugs.     

Porphyromonas gingivalis and digestive system cancers

Porphyromonas gingivalis(P. gingivalis) is an anaerobic gram-negative bacterium that colonizes in the epithelium and has been strongly associated with periodontal disease. Recently, various degrees of associations between P.gingivalis and digestive system cancers, including oral squamous cell carcinoma in the oral cavity, oesophageal squamous carcinoma in the digestive tract, and pancreatic cancer in pancreatic tissues, have been displayed in multiple clinical and experimental studies. Since P. gingivalis has a strong association with periodontal diseases, not only the relationships between P. gingivalis and digestive system tumours but also the effects induced by periodontal diseases on cancers are well-illustrated in this review. In addition, the prevention and possible treatments for these digestive system tumours induced by P. gingivalis infection are also included in this review. At the end, we also highlighted the possible mechanisms of cancers caused by P. gingivalis. One important carcinogenic effect of P. gingivalis is inhibiting the apoptosis of epithelial cells,which also plays an intrinsic role in protecting cancerous cells. Some signalling pathways activated by P. gingivalis are involved in cell apoptosis, tumourigenesis,immune evasion and cell invasion of tumour cells. In addition, metabolism of potentially carcinogenic substances caused by P. gingivalis is also one of the connections between this bacterium and cancers.     

抗CD44单抗IM7对慢性粒细胞白血病CD34+细胞黏附和迁移能力影响的体外研究

Objective To explore the effects of anti-CD44 monoclonal antibody-IM7 on the in vitro adhesion and migration of chronic myeloid leukemia stem cell(CML-LSC) and its mechanism. Methods CD34+ CD38- CD123+ leukemic stem cells (LSC) from 20 newly-diagnosed chronic myeloid leukemia ( CML) patients BM cells and CD34+ CD38- hematopoietic stem cells (HSC) from 20 full-term newborn cord blood cells were isolated with EasySepTM magnet beads. The CD44 expression of the LSC and HSC was detected by flow cytometry (FCM), and the adhesion and migration ability of the LSC and HSC pre- and post-incubated with IM7 in vitro by MTT assay and transendothelial migration assay, respectively. Results ①After incubated with IM7, the LSC and HSC CD44 expression rates were (86.60±2.10)% vs. (25.40±1.70)% (P<0.05), respectively. ②The adhesive ability of the LSC to endothelial cells was decreased markedly after incubated with IM7, the OD value (A570) changing from pre- incubation of (0.62±0.11) to post-incubation of (0.34±0.07), while there was little change of A570 in the HSC group. ③The migration abilityof the LSC group was inhibited evidently after incubated with IM7, the inhibition rate being 46%～63%, while little change of that in HSC group was detected. ④The adhesive ability of the LSC group to marrow stromal cells was decreased markedly after incubated with IM7, while little change was found in that of HSC group. Conclusion The anti-CD44 monoclonal antibody-IM7 can effectively inhibit the adhesion and migration abilities of the LSC in vitro, which might provide a theoretical evidence for targeting therapy.     

Gut microbiota and nutrient interactions with skin in psoriasis: A comprehensive review of animal and human studies

The intestinal tract(i.e.,the gut),is where the body’s nutrients are absorbed,and is simultaneously inhabited by numerous microbes.An increasing body of literature suggests a crucial role for the gut microbiome in modulating systemic inflammatory disease.Psoriasis is a chronic systemic inflammatory disease and its pathogenesis is related to the interaction between genetic susceptibility,immune response and environmental triggers.The omics era has allowed physicians to assess different aspects of psoriasis pathogenesis such as the microbiome,infectome,and autoinfectome.Furthermore,diet appears to play an important role in modulating disease activity,perhaps by influencing gut microbes.Given these observations,we aimed to summarize the current knowledge regarding skin-microbiome-gut-nutrients and psoriasis.