Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Functional outcome of the low vision aids for visual impairment secondary to central nervous system tumors in children

To assess functional outcomes of optical low vision aids(LVAs) for pediatric visual impairment due to central nervous system(CNS) tumors. A prospective case study was conducted on 15 children with history of CNS tumors with mean age of 10.47±1.85 y. Lighthouse distance, near visual acuity tests, cycloplegic refraction, reading speed measurement and visual field examination were done. Prescription of far and near LVAs followed by training sessions. LVPrasad-functional vision questionnaire was done to evaluate performance. Visual impairment was moderate(13.3%), severe(73.3%), profound(6.7%) and near blindness in 6.7%. Telescopes prescribed in 33.4%, video magnifier in 46.7%. Questionnaire scores were significantly improved for distant rather than near tasks(P≤0.05) after training. LVAs rehabilitation is an effective method of improving vision in pediatric visual defects secondary to CNS tumors.

Cell Replication and Angiogenesis in Central Nervous System Tumors and Their Relationship with the Expression of Tissue Prolactin and Hyperprolactinemia

This study aimed to assess the effect of intracellular prolactin (ICPRL) and hyperprolactinemia on cell replication, using an immunohistochemical (IHC) technique for Ki-67 and Mcm-2, and angiogenesis, using IHC for endoglin CD-105, in central nervous system (CNS) tumors. This cross-sectional study included 79 cases of surgically excised primary CNS tumors of neuroepithelial origin (41.8% of all cases: 10.2% astrocytomas, 24% glioblastomas and 7.6% oligodendrogliomas) and meningeal origin (58.2% of all cases). Ki-67 and Mcm-2 indexes were calculated as a percentage of marked cells. The medians for Ki-67 and Mcm-2 indexes were significantly lower in meningiomas than in glioblastomas (p S = 0.60) replication markers. There were no significant differences in vascular density between the different histological types. Immunohistochemistry for ICPRL was positive in 45.6% of the tumors. Serum prolactin (PRL) was elevated in 30.6% of the cases. Multiple regression analysis revealed no important correlation of ICPRL and serum PRL on Ki-67 and Mcm-2 indexes or vascular density. The analysis of the combined impact of ICPRL and serum PRL variables revealed a trend towards an increase in microvessel density in tumor tissue and a significant increase in cell replication markers (p = 0.009 for Ki-67 and p = 0.05 for Mcm-2). PRL in tumor tissue may be one of the modulating factors of cell proliferation in the CNS.

Inflammatory myofibroblastic tumor of the central nervous system:A case report

BACKGROUND An inflammatory myofibroblastic tumor(IMT)occurring in the central nervous system is very rare,and thus its pathogenesis is unknown.This case report and literature review aimed to explore the pathogenesis,clinical features,imaging findings,pathological characteristics,immunohistochemical characteristics,diagnoses,treatments,and risks of postoperative recurrence of IMT in the central nervous system.CASE SUMMARY A 67-year-old woman was admitted to the hospital with an exophthalmic protrusion and double vision in the left eye that had persisted for 3 mo.Magnetic resonance imaging(MRI)showed a 2.4 cm×1.3 cm heterogeneous large mass in the bottom of the left anterior cranial fossa,which was closely related to the dura mater.Before surgery,we suspected the mass to be meningioma.The entire mass was successfully removed under neuronavigation and electrophysiological monitoring,and postoperative pathology indicated an IMT with extensive infiltration of chronic inflammatory cells and scattered multinucleated giant cells.Head MRI at the 3-mo follow-up showed that the tumor at the bottom of left anterior cranial fossa had been completely resected without recurrence.CONCLUSION From the histological,immunohistochemical,and genetic analyses,the present case suggests that the pathogenesis of IMT-CNS is related to autoimmunity.

Analysis of Present Situation and Influencing Factors of Coping Methods by Parents of Children with Central Nervous System Tumors

Background: Central nervous system (CNS) tumors are the most common solid tumors among children. Due to the severity of the tumors and the complexity of therapeutic regimes, it is very important to examine whether parents of the children with CNS tumors have positive coping methods against the disease. This study aims to analyze the coping methods of the parents and the factors influencing the methods. Methods: A total of 108 parents of brain cancer children admitted from January 2019 to September 2020 were selected as subjects. After collecting the general information of the parents, they were studied using the Coping Health Inventory for Parents (CHIP, Chinese version). Additionally, their coping pattern and the influencing factors were analyzed. Results: The average scores of the three subscales of the CHIP were (4.25 ± 0.939), (3.11 ± 1.205) and (3.60 ± 1.187), respectively. Univariate analysis showed that parents’ education, medical payment methods, places of residence and economic concerns were the main factors influencing the coping methods (all P < 0.05). Conclusions: Healthcare staff should fully evaluate the coping methods adopted by the parents having children with CNS tumors, take targeted nursing measures accordingly, and assist the parents in seeking social support and learning disease-related knowledge. In addition, public education on disease is equally important.

Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.

Pediatric Application of Dynamic Contrast-Enhanced MR Imaging (DCE-MR) in the Management of Extra-Cranial Tumor: Experience in Routine Clinical Practice

Background: Dynamic contrast-enhanced MR imaging (DCE-MR) is becoming a widely accepted complementary method for diagnosing breast cancer and other cancers in adults. It is useful to predict tumor response to anticancer therapy and monitor the tumor response to the therapy. This form of imaging techniques has not been adequately explored in pediatric oncology patients. Objective: To determine the potential role of dynamic contrast-enhanced MR imaging (DCE-MR) in the diagnosis and treatment response monitoring of childhood and young adult extra-cranial tumors in routine clinical setting. Methods: Children with suspected extra-cranial solid tumors, including newly diagnosed or follow-up cases of confirmed tumors, were recruited. DCE-MR was performed with intravenous injection of 0.1 mmol/kg contrast. The enhancement time curves were plotted and the enhancement patterns were categorized into type 1, 2 and 3 curves. Enhancement curve patterns and maximal enhancement intensity were compared with types of tumor in newly diagnosed cases. The preoperative percentiles of inactive area on the colour map were compared with the necrotic areas on histologic sections of the resected specimens in follow-up cases. Pearson Chi-square test and Unpaired two-sample t-test were used for statistical analysis. Results: There were 36 patients, involving 28 malignant and 8 benign cases. There were 14 type 3 curves, (all of them were malignant tumors), 6 type 2 curves and 16 type 1 curves. All the benign cases (n = 8) demonstrated type 1 curve (accuracy & negative predictive value = 100%). All the malignant cases after treatment showed type 2 or 1 curve. For those cases with operation done afterwards, the extent of tumor necrosis was correlated closely with pathology findings (accuracy = 93.3%). Conclusion: Type 1 curve was a good predictor of benign lesion. DEC-MR may have a role to play in the monitoring of the progress of treatment and extent of tumor necrosis.

Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients

Microsatellite instability (MSI) is used as a molecular marker for defective DNA mismatch repair (MMR) genes.We report here alterations of MSI in 15 malignant astrocytomas (WHO grade Ⅲ) and glioblastomas (GBM; WHO grade Ⅳ) of pediatric patients (2-21 years) and 12 GBM from adults (44-68 years) by comparative analysis of BAT25/BAT26 loci and 10 other microsatellite markers. High-level microsatellite instability (MSI-H) occurred in 4 of the 15 pediatric cases (26.7%) and in 1 of the 12 adult GBM cases (8.3%). Low-level mi-

Central nervous system relapse in a pediatric anaplastic large cell lymphoma patient with CLTC/ALK translocation treated with alectinib: A case report

BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.

Disseminated Presentation of Primary Lymphoblastic Lymphoma of the Bone in a Pediatric Patient

Primary non-Hodgkin’s lymphoma of the bone (PLB) is extremely rare in the pediatric population with less than 100 cases reported in the English literature. Most commonly, patients present with atraumatic bone pain and grossly normal radiographic findings. PLB is in the histopathological class of “small round cell tumors of bone”, as with most common bone tumors. The diagnosis is confirmed by immunohistochemical or flow cytometry based detection of tumor-specific proteins. We present a case of stage IV PLB of B-lymphoblastic type with an excellent response to chemotherapy to increase awareness among general pediatricians and pathologists about the importance of making the correct diagnosis, given the excellent prognosis for this disease.

Pediatric schwannoma of the tongue:A case report and review of literature

BACKGROUND Neurogenic tumors account for about ten percent of all tumors of childhood,and benign tumor originating from Schwann cells is rare in peripheral nerves.Schwannoma of the tongue is quite rare in children.CASE SUMMARY We present the case of an 8-year-old male with schwannoma in the anterolateral tongue.The mass was slow-growing for one year with no pain and discomfort.He underwent transoral mass excision under general anesthesia.Gross examination revealed a smooth surfaced,17 mm×14 mm×7 mm sized,encapsulated nodule with a clear resection margin.Schwannoma of the tongue was confirmed by the pathological exam.He reported no motor or sensory change,such as dysgeusia or paresthesia,or phonation difficulty during postoperative 12 mo follow-up.CONCLUSION Schwannoma of the tongue is a rare benign neoplasm in childhood.If a painless firm mass is encountered in the tongue of a child,solid tumors like schwannoma should be considered in the differential diagnosis.

Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling

Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis.Glioblastoma,the most common primary tumor in adults,is associated with poor survival and remains one of the least treatable neoplasms.These tumors are highly heterogenous and complex in their nature.Due to this complexity,traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’behavior in vivo.Two-dimensional models lack the spatial arrangement,the heterogeneity in cell types,and the microenvironment that play a large role in tumor cell behavior and response to treatment.Recently,scientists have turned towards three-dimensional culturing methods,namely spheroids and organoids,as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts.Moreover,tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing.In this review,we will discuss the current available literature on in vitro threedimensional culturing models in CNS tumors,in addition to presenting their advantages and current limitations.We will also elaborate on the future implications of these models and their benefit in the clinical setting.

Primary malignant vascular tumors of the liver in children:Angiosarcoma and epithelioid hemangioendothelioma

Primary malignant vascular neoplasms of the liver,angiosarcoma and epithelioid hemangioendothelioma,are extremely rare entities in the pediatric population.International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group.In this article,we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population.Hepatic angiosarcoma in children shows a slight female predominance with an average age of 40 mo at diagnosis.The distinct histologic features include whorls of atypical spindled cells and eosinophilic globules,in addition to the general findings of angiosarcoma.Histologic diagnosis of pediatric hepatic angiosarcoma is not always straightforward,and the diagnostic challenges are discussed in the article.Hepatic epithelioid hemangioendothelioma also demonstrates a female predominance,but is more commonly identified in adolescents(median age at diagnosis:12 years).Histologically,the lesion is characterized by epithelioid cells and occasional intracytoplasmic lumina with a background of fibromyxoid stroma.While WWTR1-CAMTA1 and YAP1-TFE3 fusions have been associated with epithelioid hemangioendothelioma,there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma.Advancement in molecular pathology,particularly for pediatric hepatic angiosarcoma,is necessary for a better understanding of the disease biology,diagnosis,and development of targeted therapies.

Treatment of Pediatric Brain Tumors in Brazzaville (Congo) about a Case Series

Introduction: Tumors of the central nervous system are the most common group of solid neoplasm in children and account for 20% to 25%. They are common in Sub-Saharan countries, despite the insufficiency of histological diagnosis. No study has been performed concerning the pediatric brain tumors in the Republic of Congo. The aim of this study was to describe the conditions of neurosurgical management of pediatric tumors in Brazzaville. Materials and Methods: We performed a retrospective and descriptive study, from January 2014 to December 2017 (48 months), into the neurological unit of the surgical department of Brazzaville. We included all patients aged from 17 years old and below, hospitalized for a brain tumor. Results: We have identified 11 cases of brain tumors. The average age was 8.1 ± 4.3 years old, a sex ratio of 0.57. Ten out of the eleven patients of our series have intracranial hypertension. We found six cases of infratentorial tumors and five of supratentorial location. Only three cases had histology. Ten patients were operated, limited by ventriculoperitoneal shunt in 6 cases, surgical resection in three cases, biopsy in one case. There were no possibilities of radiotherapy and chemotherapy during this period of study. Conclusion: A multidisciplinary team must be organized to improve the management of pediatric brain tumors in our context. Histological diagnosis and possibilities of radiotherapy are imperatively needed.

The Application and Indications for Sentinel Lymph Node Biopsy in Pediatric Solid Tumors: Current Status and Future Directions

Oncologic staging of many solid organ malignancies involves an understanding of how cancers spread via the lymphatic system, and ultimately may involve evaluation of the primary nodal drainage basin by performing a sentinel lymph node biopsy. In the adult population, there are well established indications for sentinel lymph node biopsy in diseases like melanoma and breast cancer. However, its use and relevance in the pediatric population is less defined. This review details the history and development of sentinel lymph node biopsy technique, advanced lymph node mapping techniques currently under investigation, and the applications of sentinel node biopsy towards childhood cancers.

Current therapy of pediatric Crohn's disease

Inflammatory bowel diseases(IBD), including Crohn's disease(CD) and ulcerative colitis, are chronic relapsing and remitting diseases of the bowel, with an unknown etiology and appear to involve interaction between genetic susceptibility, environmental factors and the immune system. Although our knowledge and understanding of the pathogenesis and causes of IBD have improved significantly, the incidence in the pediatric population is still rising. In the last decade more drugs and treatment option have become available including 5-aminosalicylate,antibiotics, corticosteroids, immunomodulators and biological agents. Before the use of anti-tumor necrosis factor(TNF)-α became available to patients with IBD, the risk for surgery within five years of diagnosis was very high, however, with anti-TNF-α treatment the risk of surgery has decreased significantly. In the pediatric population a remission in disease can be achieved by exclusive enteral nutrition. Exclusive enteral nutrition also has an important role in the improvement of nutritional status and maintained growth. In this review we summarize the current therapeutic treatments in CD. The progress in the treatment options and the development of new drugs has led to optimized tactics for achieving the primary clinical goals of therapy- induction and maintenance of remission while improving the patient's growth and overall well-being.

Theatment strategies for pediatric patients with primary cardiac tumors

Objective To analyze the experience of treatment strategies for pediatric patients with primary cardiac tumors. Methods The clinical data of 27 patients with primary cardiac tumors which detected by echocardiography from May 1999 to May 2009 was analyzed retrospectively. There were 20 male and 7 female patients,aged from 24 d to 12. 6 years. There were 59. 2% less than 1 year old at the time of diagnosis. A single tumor were present in 22 cases and multiple in 5 cases. Surgery was performed on 22 patients due to the varied

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Current management of pediatric soft tissue sarcomas

Pediatric soft tissue sarcomas are a group of malignant neoplasms arising within embryonic mesenchymal tissues during the process of differentiation into muscle, fascia and fat. The tumors have a biphasic peak for age of incidence. Rhabdomyosarcoma(RMS) is diagnosed more frequently in younger children, whereas adult-type non-RMS soft tissue sarcoma is predominately observed in adolescents. The latter group comprises a variety of rare tumors for which diagnosis can be difficult and typically requires special studies, including immunohistochemistry and molecular genetic analysis. Current management for the majority of pediatric sarcomas is based on the data from large multi-institutional trials, which has led to great improvements in outcomes over recent decades. Although surgery remains the mainstay of treatment, the curative aim cannot be achieved without adjuvant treatment. Pre-treatment staging and risk classification are of prime importance in selecting an effective treatment protocol. Tumor resectability, the response to induction chemotherapy, and radiation generally determine the risk-group, and these factors are functions of tumor site, size and biology. Surgery provides the best choice of local control of small resectable tumors in a favorable site. Radiation therapy is added when surgery leaves residual disease or there is evidence of regional spread. Chemotherapy aims to reduce the risk of relapse and improve overall survival. In addition, upfront chemotherapy reduces the aggressiveness of the required surgery and helps preserve organ function in a number of cases. Long-term survival in low-risk sarcomas is feasible, and the intensity of treatment can be reduced. In high-risk sarcoma, current research is allowing more effective disease control.