Glioblastoma(GBM)remains a major clinical challenge due to limited therapeutic success despite standard treatments including surgery,radiotherapy,and temozolomide(TMZ).Recent evidence links hyperglycemia to cancer pro...Glioblastoma(GBM)remains a major clinical challenge due to limited therapeutic success despite standard treatments including surgery,radiotherapy,and temozolomide(TMZ).Recent evidence links hyperglycemia to cancer progression,and altered glucose metabolism has emerged as a key factor in GBM development.Metformin,an antidiabetic drug,has shown promise in improving survival in GBM patients,possibly due to its ability to cross the blood-brain barrier and target metabolic pathways involved in tumor growth.Preclinical studies suggest metformin may enhance TMZ efficacy by acting on glioma stem cells and overcoming resistance mechanisms.Its activation of AMPK and modulation of Wnt signaling further support its therapeutic potential.However,while early studies and clinical trials have explored metformin’s safety and efficacy,its direct impact on GBM survival remains unclear.Ongoing research aims to clarify its mechanisms and identify responsive patient subgroups.Novel strategies,including PPARγagonists and nanoerythrosome-based drug delivery systems,are also under investigation to improve metformin’s therapeutic profile.Rigorous clinical trials and mechanistic studies are essential to determine the role of metformin as adjunct therapy in GBM treatment.展开更多
Gliomas are the most common primary tumors of the central nervous system;among them,glioblastoma multiforme stands out as the most aggressive and lethal subtype,characterized by high therapeutic resistance and frequen...Gliomas are the most common primary tumors of the central nervous system;among them,glioblastoma multiforme stands out as the most aggressive and lethal subtype,characterized by high therapeutic resistance and frequent recurrences.Glioblastoma’s complex pathology is driven by biological and molecular factors that compromise conventional therapies,including blood-brain and bloodtumor barriers,angiogenesis,immune evasion,and aberrant signaling pathways,along with genetic drivers of drug resistance.In cancer therapy,mesoporous silica nanoparticles(MSNs)have shown promise as nanocarriers thanks to the unique attributes of their mesostructure,including large surfaces,uniform pore sizes,high loading efficiency,and flexibility of chemical modifications.Several studies have proposed MSNs to address a number of challenges facing drug delivery in gliomas,including limited penetration across the blood-brain barrier,non-specific biodistribution,and systemic adverse reactions.Moreover,MSNs can be functionalized with tumor-targeting ligands so that cancer cells are selectively taken up,while they can also release therapeutic agents in response to internal and external stimuli,enabling controlled drug delivery within tumor microenvironments.Herein,we review the integration of the MSN-based delivery approach with advances in molecular oncology to improve clinical outcomes for glioma therapeutics,while highlighting the concerns around their limited clinical translation and potential toxicity.展开更多
Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymer...Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)nanoparticles.The successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake assays.We demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo studies.The combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse models.Our findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.展开更多
Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are i...Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases(MMPs) were found in glioblastoma(GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma(LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory dataavailable. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.展开更多
Multiform single chain variable fragments （scFvs） including different length linker scFvs and bispecific scFv were constructed. The linker lengths of 0, 3, 5, 8, 12, and 15 amino acids between VH and VL of antideoxy...Multiform single chain variable fragments （scFvs） including different length linker scFvs and bispecific scFv were constructed. The linker lengths of 0, 3, 5, 8, 12, and 15 amino acids between VH and VL of antideoxynivalenol （anti-DON） scFv were used to analyze the affinities of scFvs. The affinity constants of these scFvs increased when the linker was lower than 12 amino acids. The affinity constant would not change when the linker was longer than 12 amino acids. Fusion gene of anti-DON scFv and antizearalenone （anti-ZEN） scFv was also constructed through connection by a short peptide linker DNA to express a bispecific scFv. The affinity constants assay showed that the two scFvs of fusion bispecific scFv remained their own affinity compared to their parental scFvs. Competitive direct enzyme linked immunosorbent assay was used to detect DON and ZEN in contaminated wheat （Triticum aestivum L.） samples, and the results indicated that this bispecific scFv was applicable in DON and ZEN detection. This work confirmed that bispecific scFv could be successfully obtained, and might also have an application in diagnosing fungal infection, and breeding transgenic plants.展开更多
Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on...Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.展开更多
Glioblastoma multiforme （GBM） is the most aggressive primary brain tumor in adults.Current therapy includes surgery,radiation and chemotherapy with temozolomide （TMZ）.Major determinants of clinical response to TMZ...Glioblastoma multiforme （GBM） is the most aggressive primary brain tumor in adults.Current therapy includes surgery,radiation and chemotherapy with temozolomide （TMZ）.Major determinants of clinical response to TMZ include methylation status of the O6-methylguanine-DNA methyltransferase （MGMT） promoter and mismatch repair （MMR） status.Though the MGMT promoter is methylated in 45% of cases,for the first nine months of follow-up,TMZ does not change survival outcome.Furthermore,MMR deficiency makes little contribution to clinical resistance,suggesting that there exist unrecognized mechanisms of resistance.We generated paired GBM cell lines whose resistance was attributed to neither MGMT nor MMR.We show that,responding to TMZ,these cells exhibit a decoupling of DNA damage response （DDR） from ongoing DNA damages.They display methylation-resistant synthesis in which ongoing DNA synthesis is not inhibited.They are also defective in the activation of the S and G2 phase checkpoint.DDR proteins ATM,Chk2,MDC1,NBS1 and gammaH2AX also fail to form discrete foci.These results demonstrate that failure of DDR may play an active role in chemoresistance to TMZ.DNA damages by TMZ are repaired by MMR proteins in a futile,reiterative process,which activates DDR signaling network that ultimately leads to the onset of cell death.GBM cells may survive genetic insults in the absence of DDR.We anticipate that our findings will lead to more studies that seek to further define the role of DDR in ultimately determining the fate of a tumor cell in response to TMZ and other DNA methylators.展开更多
Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as w...Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.展开更多
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents...Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.展开更多
Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special ...Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special attention to RGBM patients treated with Antineoplastons (ANP) A10 and AS2-1 injections. The study was conducted according to Protocol BT-21, which accrued patients who failed standard radiation therapy (RT) and chemotherapy. There were 40 candidates registered in the study. Among the intent-to-treat (ITT) population, there were 30 cases of RGBM that progressed during and after prior treatment, 4 patients with anaplastic astrocytoma (AA), 1 with anaplastic mixed glioma (AMG), and 5 with persistent GBM. The aim of this paper is to evaluate the responses, survival and toxicity of all 40 patients, the efficacy in 30 patients with RGBM, and in 24 patients with RGBM who received at least 28 days of ANP (ERGBM). All RGBM patients were treated before with RT and chemotherapy, except one patient who only had surgery (patient refused radiation). In this group, 63% had one recurrence, 30% had two recurrences, and 7% had three recurrences. The median duration of ANP and ITT was 12 weeks and the median dosage of ANP A10 was 6.52 g/kg/d and ANP AS2-1 was 0.23 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging (MRI) repeated every eight weeks. In the ITT population, objective responses (ORs) were determined in 10% of cases (complete response—CR, and partial response—PR in 5% each). Progression-free survival (PFS) in ITT at six months was 17.5%. Overall survival (OS) was 28.3% at one year, 2.6% at two years, five and ten years. In the RGBM population, objective responses (ORs) were determined in 13.3% of cases (CR and PR in 6.7% each). PFS in RGBM at six months was 16.7%. OS was 34.7% at one year, 3.47% at two years, five?and ten years. In the ERGBM population, ORs were determined in 16.7% of cases (CR and PR in?8.3% each). PFS in ERGBM at six months was 20.8%, OS was 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well-tolerated with reversible Grades 3 and 4 toxicity in 17.5% of patients (7 patients who experienced multiple toxicities) and no chronic toxicity. In conclusion, the study reached efficacy endpoint. ANP is well-tolerated and compares favorably to the current treatment for RGBM.展开更多
Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5^(th) and 6^(th) d...Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5^(th) and 6^(th) decades of life and extremely rare in children. It is highly aggressive tumour and managed like glioblastoma multiforme. A 12-year-old female child presented with complaints of headache and vomiting from 15d and blurring of vision from 3d. Magnetic resonance imaging of brain shows heterogeneous mass in right parieto-occipital cortex. A right parieto-occipito-temporal craniotomy with complete excision of mass revealed a primary glioblastoma on histopathological investigation. Treatment consists of maximum surgical excision followed by adjuvant radiotherapy. The etiopathogenesis, treatment modalities and prognosis is discussed. The available literature is also reviewed.展开更多
Objective To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma lnultiforme （GBM）, Methods The magnetic resonance imaging （MRI） images of 30 glioblastoma p...Objective To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma lnultiforme （GBM）, Methods The magnetic resonance imaging （MRI） images of 30 glioblastoma patients were collected. Imaging features including degrees of contrasted area, edema surrounding the tumor; and intensity in T2-weighted imaging were selected to determine their correlation with patient survival. The relationship between imaging and survival time was studied using SPSS 19.0 software. Kaplan- Meier survival analysis and log-rank test were used to compare the survival curves. Results Patients with 〈5% contrasted enhancement area of tumor had longer overall survival （OS） than those with 〉5% contrasted enhancement area of tumor. Patients without edema surrounding the tumor had longer OS than those with edema. Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. Conclusions Some MR imaging features including degrees of contrasted area, edema surrounding the tumor, and intensity in T2- weighted imaging are correlated with the survival of patients with GBM. These features can serve as prognostic indicators for GBM patients.展开更多
The 21st century is referred to as a"century for cities" or "era for cities" and China hasalso speeded up its process of urbanization. It is veryimportant to choose a scientific urbanization patter...The 21st century is referred to as a"century for cities" or "era for cities" and China hasalso speeded up its process of urbanization. It is veryimportant to choose a scientific urbanization patternto exert the function of cities and realize our dreamfor China to become a powerful modernized country.It’s concluded from history since 1800 that the patternof the world urbanization has transformed from"extensive" to "intensive". However, it is still anextensive pattern in China, and there are manyproblems behind the splendid achievements, reflectedon the urbanization process of our country since1949. Today, sustainable development and theknowledge economy are the themes of the cities; itis inevitable to change our urbanization pattern.Based on the dialectic relationship of quality andquantity, the article points out that urbanizationshould not only focus on quantity but also on qualityin China. High quality and multiform urbanizationpattern is an inevitable choice of China, and thedevelopment of the region can also be exalted by theradiation of the cities. But what’s the real meaningof the new pattern? What’s its difference from thewestern countries’? The article discusses its contentaccording to the reality of China.展开更多
Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized t...Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.展开更多
Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and prog...Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival(PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-yearold patient who presented with progressive slurring of speech and features of raised intracranial pressure. Computed tomography(CT) scan revealed a large heterogeneously enhancing lesion in the left front-temporalperisylvian region with solid, cystic areas, suggestive of malignant glioma. Partial tumor-excision was followed by concurrent chemo-radiotherapy. Histopathologically, the tumor was astrocytoma grade-IV. Patient had an extended PFS of 12 mo, with an overall survival of 26 mo. Primary-GBM was confirmed using molecular markers and the immunophenotypic signature was defined by evaluating systemic expression of human telomerase reverse transcriptase, interleukin-6, neutrophil-lymphocyte ratio, tissue inhibitor of metalloproteinases-1, human chitinase-3-like-protein-1(YKL-40) and high mobility group-A1. Current findings suggest that this signature can identify worst outcomes, independent of clinical criteria.展开更多
High?grade gliomas of the spinal cord represent a rare entity in children.Their biology,behavior,and controversial treatment options have been discussed in a few pediatric cases.These tumors are associated with severe...High?grade gliomas of the spinal cord represent a rare entity in children.Their biology,behavior,and controversial treatment options have been discussed in a few pediatric cases.These tumors are associated with severe disability and poor prognosis.We report a case of a 4?year?old child diagnosed with an isolated glioblastoma multiforme of the conus medullaris.The patient underwent subtotal surgical excision,followed by adjuvant radiotherapy and oral chem?otherapy.He is alive with mild neurologic deficits at 52 months after diagnosis.We describe the peculiar characteris?tics of this rare condition in pediatric oncology.We also provide an overview of current multidisciplinary therapeutic approaches and prognostic factors for this disease.展开更多
Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.展开更多
Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). T...Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). To our knowledge, this is the first report on DCI after GBM resection. A 52-year-old female patient with headache for one month underwent subtotal resection of a left temporal GBM encasing the proximal middle cerebral artery (MCA). She was well during the immediate postoperative period but developed right upper limb dense monoparesis on postoperative day four with computed tomographic angiography confirming left MCA vasospasm. Symptoms were significantly alleviated with weeklong hypertensive therapy and nimodipine administration;however they recurred soon after cessation of treatment. A high index of clinical suspicion is needed for the diagnosis of post-tumor resection DCI. Any new postoperative neurological deficit that cannot be explained by hemorrhage, seizures or infection should be expeditiously investigated by angiography or transcranial Doppler sonography. Prompt initiation of hypertensive and nimodipine therapy can possibly reverse neurological deficit. Treatment should be guided by Doppler, angiographic or perfusion imaging studies and not by clinical improvement alone.展开更多
Glioblastoma multiforme(GBM)is the most common malignant primary brain tumor with a poor prognosis and limited survival.Patients with GBM have a high demand for palliative care.In our present case,a 21-year-old female...Glioblastoma multiforme(GBM)is the most common malignant primary brain tumor with a poor prognosis and limited survival.Patients with GBM have a high demand for palliative care.In our present case,a 21-year-old female GBM patient received inpatient palliative care services including symptom management,mental and psychological support for the patient,psychosocial and clinical decision support for her family members,and pre-and post-death bereavement management for the family.Furthermore,we provided the family members with comprehensive psychological preparation for the patient's demise and assisted the patient's family throughout the mourning period.The aim of this study is to provide a reference and insights for the clinical implementation of palliative care for patients with malignant brain tumors.展开更多
Objective: To investigate the expression of immune- related molecules in glioblastoma multiform(GBM) cells. Methods: The expression of major histocompatibility complex (MHC), b2-microglobulin, Fas, CD80 and CD86 molec...Objective: To investigate the expression of immune- related molecules in glioblastoma multiform(GBM) cells. Methods: The expression of major histocompatibility complex (MHC), b2-microglobulin, Fas, CD80 and CD86 molecules on the surface of GBM cells were evaluated by flow cytometry. The expression of TAP-1, TAP-2 and Tapasin in the GBM cells were evaluated by RT-PCR method. Results: MHC class I, b2 microglobulin, TAP-1, TAP-2 and tapasin were expressed in most GBM cell lines. Except U87, there was no MHC class II molecule expression on any of the other GBM cell lines. Fas was expressed on all the GBM cell lines examined. Conclusion: The mechanism by which GBM escapes immune surveillance may involve down regulation of expression of MHC class I molecules and MHC class II molecules. MHC class I positive GBM may be the suitable target of immunotherapy.展开更多
文摘Glioblastoma(GBM)remains a major clinical challenge due to limited therapeutic success despite standard treatments including surgery,radiotherapy,and temozolomide(TMZ).Recent evidence links hyperglycemia to cancer progression,and altered glucose metabolism has emerged as a key factor in GBM development.Metformin,an antidiabetic drug,has shown promise in improving survival in GBM patients,possibly due to its ability to cross the blood-brain barrier and target metabolic pathways involved in tumor growth.Preclinical studies suggest metformin may enhance TMZ efficacy by acting on glioma stem cells and overcoming resistance mechanisms.Its activation of AMPK and modulation of Wnt signaling further support its therapeutic potential.However,while early studies and clinical trials have explored metformin’s safety and efficacy,its direct impact on GBM survival remains unclear.Ongoing research aims to clarify its mechanisms and identify responsive patient subgroups.Novel strategies,including PPARγagonists and nanoerythrosome-based drug delivery systems,are also under investigation to improve metformin’s therapeutic profile.Rigorous clinical trials and mechanistic studies are essential to determine the role of metformin as adjunct therapy in GBM treatment.
文摘Gliomas are the most common primary tumors of the central nervous system;among them,glioblastoma multiforme stands out as the most aggressive and lethal subtype,characterized by high therapeutic resistance and frequent recurrences.Glioblastoma’s complex pathology is driven by biological and molecular factors that compromise conventional therapies,including blood-brain and bloodtumor barriers,angiogenesis,immune evasion,and aberrant signaling pathways,along with genetic drivers of drug resistance.In cancer therapy,mesoporous silica nanoparticles(MSNs)have shown promise as nanocarriers thanks to the unique attributes of their mesostructure,including large surfaces,uniform pore sizes,high loading efficiency,and flexibility of chemical modifications.Several studies have proposed MSNs to address a number of challenges facing drug delivery in gliomas,including limited penetration across the blood-brain barrier,non-specific biodistribution,and systemic adverse reactions.Moreover,MSNs can be functionalized with tumor-targeting ligands so that cancer cells are selectively taken up,while they can also release therapeutic agents in response to internal and external stimuli,enabling controlled drug delivery within tumor microenvironments.Herein,we review the integration of the MSN-based delivery approach with advances in molecular oncology to improve clinical outcomes for glioma therapeutics,while highlighting the concerns around their limited clinical translation and potential toxicity.
基金supported by the National Natural Science Foundation of China(Grant Nos.82073308 and 82104089)。
文摘Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment options.To improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)nanoparticles.The successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake assays.We demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo studies.The combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse models.Our findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.
基金Supported by Interdisziplinres Zentrum für Klinische Forschung der Universitt Würzburg,Project B25
文摘Glioblastomas are characterized by an aggressive local growth pattern, a marked degree of invasiveness and poor prognosis. Tumor invasiveness is facilitated by the increased activity of proteolytic enzymes which are involved in destruction of the extracellular matrix of the surrounding healthy brain tissue. Elevated levels of matrix metalloproteinases(MMPs) were found in glioblastoma(GBM) cell-lines, as well as in GBM biopsies as compared with low-grade astrocytoma(LGA) and normal brain samples, indicating a role in malignant progression. A careful review of the available literature revealed that both the expression and role of several of the 23 human MMP proteins is controversely discussed and for some there are no data available at all. We therefore screened a panel of 15 LGA and 15 GBM biopsy samples for those MMPs for which there is either no, very limited or even contradictory dataavailable. Hence, this is the first complete compilation of the expression pattern of all 23 human MMPs in astrocytic tumors. This study will support a better understanding of the specific expression patterns and interaction of proteolytic enzymes in malignant human glioma and may provide additional starting points for targeted patient therapy.
基金the National High Technology Research and Development Program of China （No. 2007AA10Z430） Chinese National Natural Science Foundation （No. 30771400 and 30500325）+2 种基金Key Scientific and Technology Project of Fujian Province of China （No. 2005K030 , 2007Y0002） Postdoctoral Sciences Foundation of China （No. 20060390183） Program for New Century Excellent Talents in Fujian Province University.
文摘Multiform single chain variable fragments （scFvs） including different length linker scFvs and bispecific scFv were constructed. The linker lengths of 0, 3, 5, 8, 12, and 15 amino acids between VH and VL of antideoxynivalenol （anti-DON） scFv were used to analyze the affinities of scFvs. The affinity constants of these scFvs increased when the linker was lower than 12 amino acids. The affinity constant would not change when the linker was longer than 12 amino acids. Fusion gene of anti-DON scFv and antizearalenone （anti-ZEN） scFv was also constructed through connection by a short peptide linker DNA to express a bispecific scFv. The affinity constants assay showed that the two scFvs of fusion bispecific scFv remained their own affinity compared to their parental scFvs. Competitive direct enzyme linked immunosorbent assay was used to detect DON and ZEN in contaminated wheat （Triticum aestivum L.） samples, and the results indicated that this bispecific scFv was applicable in DON and ZEN detection. This work confirmed that bispecific scFv could be successfully obtained, and might also have an application in diagnosing fungal infection, and breeding transgenic plants.
基金supported by grants from the National Institutes of Health (NIH) [No. K25CA129173 (MMA), R01CA122031 (ASA), and 1R01CA160216 (ASA)]
文摘Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.
基金supported by NIH grants 5-P50-NS20023 and NS030245 (Darell D. Bigner)a grant from the Pediatric Brain Tumor Foundation (Henry S. Friedman)
文摘Glioblastoma multiforme （GBM） is the most aggressive primary brain tumor in adults.Current therapy includes surgery,radiation and chemotherapy with temozolomide （TMZ）.Major determinants of clinical response to TMZ include methylation status of the O6-methylguanine-DNA methyltransferase （MGMT） promoter and mismatch repair （MMR） status.Though the MGMT promoter is methylated in 45% of cases,for the first nine months of follow-up,TMZ does not change survival outcome.Furthermore,MMR deficiency makes little contribution to clinical resistance,suggesting that there exist unrecognized mechanisms of resistance.We generated paired GBM cell lines whose resistance was attributed to neither MGMT nor MMR.We show that,responding to TMZ,these cells exhibit a decoupling of DNA damage response （DDR） from ongoing DNA damages.They display methylation-resistant synthesis in which ongoing DNA synthesis is not inhibited.They are also defective in the activation of the S and G2 phase checkpoint.DDR proteins ATM,Chk2,MDC1,NBS1 and gammaH2AX also fail to form discrete foci.These results demonstrate that failure of DDR may play an active role in chemoresistance to TMZ.DNA damages by TMZ are repaired by MMR proteins in a futile,reiterative process,which activates DDR signaling network that ultimately leads to the onset of cell death.GBM cells may survive genetic insults in the absence of DDR.We anticipate that our findings will lead to more studies that seek to further define the role of DDR in ultimately determining the fate of a tumor cell in response to TMZ and other DNA methylators.
基金partially supported by the National Natural Science Foundation of China(81702457)the Clinical Medical University and Hospital Joint Construction of Disciplinary Projects 2021(2021lcxk017)+4 种基金the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)the Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University(2021J008)the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2021xkjT028)the Open Fund of Key Laboratory of Antiinflammatory and Immune Medicine(KFJJ-2021-11)Grants for Scientific Research of BSKY from Anhui Medical University(1406012201)。
文摘Glioblastoma multiforme(GBM) is the most common primary malignant brain tumor, and it is associated with poor prognosis. Its characteristics of being highly invasive and undergoing heterogeneous genetic mutation, as well as the presence of the blood–brain barrier(BBB), have reduced the efficacy of GBM treatment. The emergence of a novel therapeutic method, namely, sonodynamic therapy(SDT), provides a promising strategy for eradicating tumors via activated sonosensitizers coupled with low-intensity ultrasound. SDT can provide tumor killing effects for deep-seated tumors, such as brain tumors. However, conventional sonosensitizers cannot effectively reach the tumor region and kill additional tumor cells, especially brain tumor cells. Efforts should be made to develop a method to help therapeutic agents pass through the BBB and accumulate in brain tumors. With the development of novel multifunctional nanosensitizers and newly emerging combination strategies, the killing ability and selectivity of SDT have greatly improved and are accompanied with fewer side effects. In this review, we systematically summarize the findings of previous studies on SDT for GBM, with a focus on recent developments and promising directions for future research.
基金supported by Natural Science Foundation of Shaanxi Province(Grant No.:2019ZY-CXPT-03-01)to Ping Zhu and Key Research and Development Program of Shaanxi Province(Grant No.:2020ZDLSF03-02)to Zhi-Nan Chen and Huijie Bian as well as Tricision Biotherapeutics Inc.
文摘Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex(MHC)class I and II antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4t and CD8t T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
文摘Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special attention to RGBM patients treated with Antineoplastons (ANP) A10 and AS2-1 injections. The study was conducted according to Protocol BT-21, which accrued patients who failed standard radiation therapy (RT) and chemotherapy. There were 40 candidates registered in the study. Among the intent-to-treat (ITT) population, there were 30 cases of RGBM that progressed during and after prior treatment, 4 patients with anaplastic astrocytoma (AA), 1 with anaplastic mixed glioma (AMG), and 5 with persistent GBM. The aim of this paper is to evaluate the responses, survival and toxicity of all 40 patients, the efficacy in 30 patients with RGBM, and in 24 patients with RGBM who received at least 28 days of ANP (ERGBM). All RGBM patients were treated before with RT and chemotherapy, except one patient who only had surgery (patient refused radiation). In this group, 63% had one recurrence, 30% had two recurrences, and 7% had three recurrences. The median duration of ANP and ITT was 12 weeks and the median dosage of ANP A10 was 6.52 g/kg/d and ANP AS2-1 was 0.23 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging (MRI) repeated every eight weeks. In the ITT population, objective responses (ORs) were determined in 10% of cases (complete response—CR, and partial response—PR in 5% each). Progression-free survival (PFS) in ITT at six months was 17.5%. Overall survival (OS) was 28.3% at one year, 2.6% at two years, five and ten years. In the RGBM population, objective responses (ORs) were determined in 13.3% of cases (CR and PR in 6.7% each). PFS in RGBM at six months was 16.7%. OS was 34.7% at one year, 3.47% at two years, five?and ten years. In the ERGBM population, ORs were determined in 16.7% of cases (CR and PR in?8.3% each). PFS in ERGBM at six months was 20.8%, OS was 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well-tolerated with reversible Grades 3 and 4 toxicity in 17.5% of patients (7 patients who experienced multiple toxicities) and no chronic toxicity. In conclusion, the study reached efficacy endpoint. ANP is well-tolerated and compares favorably to the current treatment for RGBM.
文摘Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5^(th) and 6^(th) decades of life and extremely rare in children. It is highly aggressive tumour and managed like glioblastoma multiforme. A 12-year-old female child presented with complaints of headache and vomiting from 15d and blurring of vision from 3d. Magnetic resonance imaging of brain shows heterogeneous mass in right parieto-occipital cortex. A right parieto-occipito-temporal craniotomy with complete excision of mass revealed a primary glioblastoma on histopathological investigation. Treatment consists of maximum surgical excision followed by adjuvant radiotherapy. The etiopathogenesis, treatment modalities and prognosis is discussed. The available literature is also reviewed.
基金supported by a grant from the Chinese National Key Project of Science(No.30772238)
文摘Objective To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma lnultiforme （GBM）, Methods The magnetic resonance imaging （MRI） images of 30 glioblastoma patients were collected. Imaging features including degrees of contrasted area, edema surrounding the tumor; and intensity in T2-weighted imaging were selected to determine their correlation with patient survival. The relationship between imaging and survival time was studied using SPSS 19.0 software. Kaplan- Meier survival analysis and log-rank test were used to compare the survival curves. Results Patients with 〈5% contrasted enhancement area of tumor had longer overall survival （OS） than those with 〉5% contrasted enhancement area of tumor. Patients without edema surrounding the tumor had longer OS than those with edema. Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. Conclusions Some MR imaging features including degrees of contrasted area, edema surrounding the tumor, and intensity in T2- weighted imaging are correlated with the survival of patients with GBM. These features can serve as prognostic indicators for GBM patients.
文摘The 21st century is referred to as a"century for cities" or "era for cities" and China hasalso speeded up its process of urbanization. It is veryimportant to choose a scientific urbanization patternto exert the function of cities and realize our dreamfor China to become a powerful modernized country.It’s concluded from history since 1800 that the patternof the world urbanization has transformed from"extensive" to "intensive". However, it is still anextensive pattern in China, and there are manyproblems behind the splendid achievements, reflectedon the urbanization process of our country since1949. Today, sustainable development and theknowledge economy are the themes of the cities; itis inevitable to change our urbanization pattern.Based on the dialectic relationship of quality andquantity, the article points out that urbanizationshould not only focus on quantity but also on qualityin China. High quality and multiform urbanizationpattern is an inevitable choice of China, and thedevelopment of the region can also be exalted by theradiation of the cities. But what’s the real meaningof the new pattern? What’s its difference from thewestern countries’? The article discusses its contentaccording to the reality of China.
基金supported by National Natural Science Foundation of China (Grant No. 82003764 to L.F.)Universities Natural Science Research Project of Jiangsu Province (Grant No. 19KJB350001to L.F.)。
文摘Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.
基金Supported by M.P.Biotech Council,M.P.for financial assistance and BMHRC for infrastructural facilities,No.249
文摘Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival(PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-yearold patient who presented with progressive slurring of speech and features of raised intracranial pressure. Computed tomography(CT) scan revealed a large heterogeneously enhancing lesion in the left front-temporalperisylvian region with solid, cystic areas, suggestive of malignant glioma. Partial tumor-excision was followed by concurrent chemo-radiotherapy. Histopathologically, the tumor was astrocytoma grade-IV. Patient had an extended PFS of 12 mo, with an overall survival of 26 mo. Primary-GBM was confirmed using molecular markers and the immunophenotypic signature was defined by evaluating systemic expression of human telomerase reverse transcriptase, interleukin-6, neutrophil-lymphocyte ratio, tissue inhibitor of metalloproteinases-1, human chitinase-3-like-protein-1(YKL-40) and high mobility group-A1. Current findings suggest that this signature can identify worst outcomes, independent of clinical criteria.
文摘High?grade gliomas of the spinal cord represent a rare entity in children.Their biology,behavior,and controversial treatment options have been discussed in a few pediatric cases.These tumors are associated with severe disability and poor prognosis.We report a case of a 4?year?old child diagnosed with an isolated glioblastoma multiforme of the conus medullaris.The patient underwent subtotal surgical excision,followed by adjuvant radiotherapy and oral chem?otherapy.He is alive with mild neurologic deficits at 52 months after diagnosis.We describe the peculiar characteris?tics of this rare condition in pediatric oncology.We also provide an overview of current multidisciplinary therapeutic approaches and prognostic factors for this disease.
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well as with clinical manifestations,like epileptogenicity,and a favorable prognosis of GBM.Based on our data,HIF-1αor VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression.Finally,HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy,including combined first-line treatment with histone deacetylase inhibitors,thimerosal,or an active metabolite of irinotecan,as well as STAT3 inhibitors alone,and resulting in a favorable tumor prognosis and patient survival.These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes.Data limitations may include the use of less sensitive detection methods in some cases.Overall,our data support HIF-1α/VEGF’s role as biomarkers of GBM prognosis and treatment efficacy.
文摘Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). To our knowledge, this is the first report on DCI after GBM resection. A 52-year-old female patient with headache for one month underwent subtotal resection of a left temporal GBM encasing the proximal middle cerebral artery (MCA). She was well during the immediate postoperative period but developed right upper limb dense monoparesis on postoperative day four with computed tomographic angiography confirming left MCA vasospasm. Symptoms were significantly alleviated with weeklong hypertensive therapy and nimodipine administration;however they recurred soon after cessation of treatment. A high index of clinical suspicion is needed for the diagnosis of post-tumor resection DCI. Any new postoperative neurological deficit that cannot be explained by hemorrhage, seizures or infection should be expeditiously investigated by angiography or transcranial Doppler sonography. Prompt initiation of hypertensive and nimodipine therapy can possibly reverse neurological deficit. Treatment should be guided by Doppler, angiographic or perfusion imaging studies and not by clinical improvement alone.
基金National High Level Hospital Clinical Research Funding(2022-PUMCH-B-113).
文摘Glioblastoma multiforme(GBM)is the most common malignant primary brain tumor with a poor prognosis and limited survival.Patients with GBM have a high demand for palliative care.In our present case,a 21-year-old female GBM patient received inpatient palliative care services including symptom management,mental and psychological support for the patient,psychosocial and clinical decision support for her family members,and pre-and post-death bereavement management for the family.Furthermore,we provided the family members with comprehensive psychological preparation for the patient's demise and assisted the patient's family throughout the mourning period.The aim of this study is to provide a reference and insights for the clinical implementation of palliative care for patients with malignant brain tumors.
文摘Objective: To investigate the expression of immune- related molecules in glioblastoma multiform(GBM) cells. Methods: The expression of major histocompatibility complex (MHC), b2-microglobulin, Fas, CD80 and CD86 molecules on the surface of GBM cells were evaluated by flow cytometry. The expression of TAP-1, TAP-2 and Tapasin in the GBM cells were evaluated by RT-PCR method. Results: MHC class I, b2 microglobulin, TAP-1, TAP-2 and tapasin were expressed in most GBM cell lines. Except U87, there was no MHC class II molecule expression on any of the other GBM cell lines. Fas was expressed on all the GBM cell lines examined. Conclusion: The mechanism by which GBM escapes immune surveillance may involve down regulation of expression of MHC class I molecules and MHC class II molecules. MHC class I positive GBM may be the suitable target of immunotherapy.
