Current Status and Emerging Trends in Colorectal Cancer Screening and Diagnostics.

Colorectal cancer (CRC) is a prevalent and potentially fatal disease categorized based on its high incidences and mortality rates, which raised the need for effective diagnostic strategies for the early detection and management of CRC. While there are several conventional cancer diagnostics available, they have certain limitations that hinder their effectiveness. Significant research efforts are currently being dedicated to elucidating novel methodologies that aim at comprehending the intricate molecular mechanism that underlies CRC. Recently, microfluidic diagnostics have emerged as a pivotal solution, offering non-invasive approaches to real-time monitoring of disease progression and treatment response. Microfluidic devices enable the integration of multiple sample preparation steps into a single platform, which speeds up processing and improves sensitivity. Such advancements in diagnostic technologies hold immense promise for revolutionizing the field of CRC diagnosis and enabling efficient detection and monitoring strategies. This article elucidates several of the latest developments in microfluidic technology for CRC diagnostics. In addition to the advancements in microfluidic technology for CRC diagnostics, the integration of artificial intelligence (AI) holds great promise for further enhancing diagnostic capabilities. Advancements in microfluidic systems and AI-driven approaches can revolutionize colorectal cancer diagnostics, offering accurate, efficient, and personalized strategies to improve patient outcomes and transform cancer management.

Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway.

Prodigiosin (PG), a member of a family of natural red pigments produced by a variety of bacteria, was first discovered in Serratia marcescens. PG has been reported to have an apoptosis-inducing effect in many cancers, such as lymphoma, colon cancer and nasopharyngeal carcinoma. For this study, we used three glioblastoma (GBM) cell lines (LN229, U251 and A172) to explore the effect of prodigiosin on GBM cells. A CCK8 assay was used to evaluate cell viability. We determinedthe cell cycle distribution by flow cytometry and measured proliferation by an EdU incorporation assay. The expression of different molecules was investigated by western blotting and RT-PCR. We further confirmed our results by plasmid transfection and lentiviral transduction. The LN229 xenograft model was used to study the effect of prodigiosin in vivo. We confirmed that prodigiosin played an anticancer role in several GBM cell lines through the KIAA1524/PP2A/Akt signalling pathway. Prodigiosin inhibited the protein expression of KIAA1524 by suppressing its transcription, which led to activation of PP2A. Afterward, PP2A inhibited the phosphorylation of Akt, thereby inducing increased expression of p53/p21. Furthermore, it was verified that prodigiosin inhibited the KIAA1524/PP2A/Akt axis in vivo in the LN229 xenograft model. These data improve the understanding of the anticancer effects of prodigiosin and further highlight the potential of prodigiosin for the development of anti-glioma drugs.

Synergistic lignin construction of a long-chain branched polypropylene and its properties.

In light of current environmental pressures (referring to its destruction) and the consumption of petrochemical resources, the substitution of chemicals products with renewable natural substances has attracted extensive interest. In this paper, a synergistically constructed lignin polypropylene matrix composite with long-chain branched characteristics was prepared by a pre-irradiation and melt blending method. The effects of lignin on the crystallization, rheological behavior, foaming and aging properties of polypropylene were studied. Differential scanning calorimetry and polarized light microscopy results show that lignin undergoes heterophasic nucleation in a polypropylene matrix; rheological studies show that lignin promotes the formation of a heterogeneous polypropylene network, and thus polypropylene exhibits long-chain branching features; nucleation and a network structure endow the polypropylene-based composites with uniform cell size, thin cell walls, and a foaming ratio of 5-44 times; at the same time, a large number of hindered phenols in lignin can capture free radicals to improve the aging properties of the polypropylene. This research will help to convert industrial waste into functional composite materials.

The effects of rubber nanoparticles with different polarities on thermal properties and foaming performance of polypropylene blends.

Polypropylene blends with both polybutadiene rubber (PB) and polycarboxylbuturonile rubber (xNBR) and the required amount of acrylamide (AM) was prepared by blending with water, and the crystallinity, rheological behaviour and thermal performance were analysed and compared. The results of DSC and XRD characterization showed an obvious enhancement in the crystallization of the PP matrix in PP/xNBR/AM blends compared to PP/PB/AM blends, due to the strong incompatibility between xNBR nanoparticles and the PP polymer matrix leading to the inhibition of segmental mobility and induced formation of heterogeneous nuclei. Rheological analysis showed that the dynamical mobility of polymer chains was retarded while the AM monomer was incorporated, due to strengthening interfacial interactions by grafts through hydrogen bonding. The foaming performance was clearly improved, as reflected in the uniform cell morphology and higher cell density, and the expansion ratio achieved was 13-fold. In addition, the decomposition temperature increased from 403 °C to 465 °C by nearly 62 °C as compared with neat PP, which is ascribed to the inhibition of segmental mobility due to the cyclization reaction of nitriles. The increase in the surface energy was about 2.2-fold, which resulted in a decrease of the water contact angle from 105.3° to 83.7°, attributed due to AM addition to the composition.

Bacterial Single Cell Whole Transcriptome Amplification in Microfluidic Platform Shows Putative Gene Expression Heterogeneity.

Single cell RNA sequencing is a technology that provides the capability of analyzing the transcriptome of a single cell from a population. So far, single cell RNA sequencing has been focused mostly on human cells due to the larger starting amount of RNA template for subsequent amplification. One of the major challenges of applying single cell RNA sequencing to microbial cells is to amplify the femtograms of the RNA template to obtain sufficient material for downstream sequencing with minimal contamination. To achieve this goal, efforts have been focused on multiround RNA amplification, but would introduce additional contamination and bias. In this work, we for the first time coupled a microfluidic platform with multiple displacement amplification technology to perform single cell whole transcriptome amplification and sequencing of Porphyromonas somerae, a microbe of interest in endometrial cancer, as a proof-of-concept demonstration of using single cell RNA sequencing tool to unveil gene expression heterogeneity in single microbial cells. Our results show that the bacterial single-cell gene expression regulation is distinct across different cells, supporting widespread heterogeneity.

High expression of GALNT7 promotes invasion and proliferation of glioma cells.

Polypeptide-N-acetyl-galactosaminlytransferase 7 (GALNT7), a member of the GalNAc-transferase family, has not been previously evaluated as a prognostic factor of glioblastoma (GBM) or low-grade glioma (LGG). Based on The Cancer Genome Atlas database and bioinformatics analyses, the expression of GALNT7 was demosntrated to be higher in GBM and LGG tissues than in normal brain tissue. The expression levels of GANLT7 were associated with age, tumor grade, survival rate, disease-free survival time and overall survival time. Gene correlation and gene-set enrichment analyses suggested that GALNT7 may affect the proliferative and invasive abilities of glioma cells through multiple signaling pathways, including regulation of the actin cytoskeleton, natural killer cell-mediated cytotoxicity, the janus kinase-signal transducer and activator of transcription (STAT) signaling pathway, cell adhesion molecules and extracellular matrix receptor interaction pathways. Furthermore, 5 target genes of GALNT7 involved in these signaling pathways were identified, including Crk, Rac family small GTPase 1, STAT3, poliovirus receptor and Tenascin C. In summary, high expression of GALNT7 was associated with poor prognosis of glioma, and may be used as an effective biomarker of glioma.

Immunohistochemical characterization of lymphangiogenesis-related biomarkers in primary and recurrent gliomas: A STROBE compliant article.

Glial tumors constitute the majority of primary intracranial brain tumors. The expression of specific markers of lymphangiogenesis in gliomas still remains unclear.A total of 40 surgical specimens from 20 patients with recurrent gliomas were included in the study. The expression of D2-40, vascular endothelial growth factor (VEGF)-C, VEGF-D, and VEGF receptor-3 (VEGR-3) was detected by immunohistochemistry (IHC). The clinicopathologic data (p53 and Ki67) were also collected and analyzed.At relapse malignant transformation rate was 65% (13/20 cases). D2-40, VEGF-C, VEGF-D, and VEGFR-3 were expressed in 20%, 30%, 60%, and 20% of primary and 45%, 30%, 75%, and 35% of recurrent glioma tumors (P < .01, P = 1.00, P = .03, P = .03). In 13 cases with increased malignancy grade, the expression of Ki67 and p53 were higher at relapse compared with the primary tumors (P = .001, P = .045). Multivariate survival analysis showed VEGF-D was an independent prognostic factor for malignant transformation (HR = 0.376, P = .045).Glioma is easy to relapse with tumor progression. VEGF-D was an independent prognostic factor for malignant transformation.

Increased Expression of T Cell Immunoglobulin and Mucin Domain 3 on CD14+ Monocytes Is Associated with Systemic Inflammatory Reaction and Brain Injury in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: To study the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood immunocytes, and the relationship between Tim-3 and the systemic inflammatory response or brain injury in patients with intracerebral hemorrhage (ICH). METHODS: According to the volume of hematoma at 12 hours after onset of ICH, 60 newly diagnosed patients with ICH were divided into the small (volume of hematoma <30 mL, 30 cases) and large (volume of hematoma ≥30 mL, 30 cases) ICH groups. The expression of Tim-3 on peripheral blood immunocytes was analyzed by flow cytometry. Real-time reverse transcriptase polymerase chain reaction was used to detect Tim-3 mRNA on peripheral blood mononuclear cells (PBMCs). Meanwhile, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and S-100B protein were measured by enzyme-linked immunosorbent assay. Glasgow outcome scale (GOS) score at Day 30 was used to estimate prognosis of patients. RESULTS: The leukocyte count, neutrophil count, monocyte count, TNF-α, IL-1ß, and S-100B protein increased remarkably after ICH. However, all of them in the large ICH group increased more obviously, and there were significant differences when compared with those in the small ICH group (P < .01). The expression of Tim-3 mRNA on PBMCs in the large ICH group increased remarkably, peaked at Day 3, and was positively associated with the concentrations of TNF-α, IL-1ß, and S-100B protein (P < .01). Tim-3 was predominantly expressed itself on CD14+ monocytes. There was a negative correlation between GOS score and Tim-3 mRNA, TNF-α, IL-1ß, or S-100B protein. CONCLUSIONS: The expression of Tim-3 on CD14 + monocytes involves in systemic inflammatory reaction after ICH and may be a novel treatment target.

Role of Peroxiredoxin 2 in the Protection Against Ferrous Sulfate-Induced Oxidative and Inflammatory Injury in PC12 Cells.

Peroxiredoxin 2 (Prdx2) is a ubiquitous antioxidant enzyme in mammalian brain. Although a protective role of Prdx2 has been established in cerebral ischemia and several neurodegenerative diseases, its contribution against iron-induced neurocytotoxicity still remains to be determined. Accordingly, in this study, we aimed to investigate the effects of Prdx2 on iron-induced cytotoxicity using an in vitro model in which PC12 cells are exposed to ferrous sulfate (FS). The FS treatment increased Prdx2 expression, and promoted lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by the increase in the Bax/Bcl2 ratio, cytochrome c release, and caspase-3 cleavage. FS exposure also increased the malondialdehyde content (lipid peroxidation), 3'-nitrotyrosine expression (protein nitration), γ-H2A.X formation (DNA oxidation), and promoted nuclear factor kappa B nuclear translocation, cyclooxygenase-2 expression, and release of tumor necrosis factor-α and interleukin-1ß. Lentivirus-mediated Prdx2 knockdown intensified the FS-induced LDH release and cell apoptosis by aggravating the oxidative and inflammatory damage. In conclusion, our findings demonstrated that Prdx2 played a vital role in the protection against iron-induced cytotoxicity in PC12 cells.

Effects of over-expression of HIF-1alpha in bone marrow-derived mesenchymal stem cells on traumatic brain injury.

Mesenchymal stem cells (MSCs) have been shown to play therapeutic effect in traumatic brain injury (TBI). To augment the therapeutic effect, MSCs could be engineered to over-express genes that are beneficial for treatment. In the present study, we over-expressed hypoxia inducible factor (HIF)-1alpha in bone marrow derived MSCs (BM-MSCs) and sought to investigate whether HIF-1alpha could enhance the therapeutic effect of MSCs in a mouse model of TBI. Balb/c mice were subjected to controlled cortical impact injury and MSCs were transplanted intravenously at 6 h after injury. The lesion volume and brain water content were measured and the neurological function was assessed by modified neurologic severity score tests. Double-labeled immunofluorescence for BrdU and NeuU was performed to determine angiogenesis and neurogenesis. The expression of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) was measured by quantitative RT-PCR and western blotting. After TBI, mice received BM-MSCs over-expressing HIF-1alpha showed significantly more functional recovery, reduced brain damage, increased angiogenesis and neurogenesis and increased expression of VEGF and EPO, compared with control mice or mice treated with non-transduced BM-MSCs. Over-expression of HIF-1alpha enhanced BM-MSCs induced improvement of neurological recovery after TBI, by stimulating angiogenesis and neurogenesis.

Tripartite motif-containing protein 37 is overexpressed in human glioma and its downregulation inhibits human glioma cell growth in vitro.

Glioma is one of the most malignant tumor types worldwide. Despite great efforts made in surgery, imaging, chemotherapy, and radiation, the overall prognosis for patients with glioma remains poor. The pathogenesis of glioma is an urgent problem that must be solved. Tripartite motif-containing protein 37 (TRIM37) is an E3 ubiquitin ligase that may be involved in the tumorigenesis of several types of cancer; however, its expression pattern and biological functions in glioma remain unknown. Our previous studies indicated that the expression levels of TRIM37 were upregulated in glioma samples and were associated with a higher glioma grade. The present study demonstrates that suppression of TRIM37 by RNA-mediated interference inhibits the growth of glioma cells in vitro, which is associated with induction of apoptosis and cell cycle arrest, and with inhibition of migration and invasion. These results provide insights into understanding the role of TRIM37 in regulating the biological behavior of glioma cells and may indicate TRIM37 as a candidate target for the treatment of glioma.

CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells through activating Siah1 mediated ubiquitination and degradation of cytoplasmic p27.

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) has been reported to be up-regulated and plays an important role in promoting cell proliferation in human glioma. However, the effect of CacyBP/SIP on glioma cell motility is still unclear. Here, to our surprise, CacyBP/SIP was found to inhibit the migration and invasion of glioma cells U251 and U87. Silencing of CacyBP/SIP significantly promoted the migration and invasion behaviors of glioma cells. On the contrary, overexpression of CacyBP/SIP obviously suppressed them. Further investigation indicated that silencing of CacyBP/SIP significantly reduced the interaction between Siah1 and cytoplasmic p27, which in turn attenuated the ubiquitination and degradation of cytoplasmic p27. In contrast, overexpression of CacyBP/SIP promoted the interaction between Siah1 and cytoplasmic p27, which in turn increased the ubiquitination and degradation of cytoplasmic p27. Importantly, the degradation of p27 could be blocked by Siah1 knockdown. Finally, we found that CacyBP/SIP was reversely related to cytoplasmic p27 in human normal brain tissues and glioma tissues. Taken together, these results suggest that CacyBP/SIP plays an important role in inhibiting glioma cell migration and invasion through promoting the degradation of cytoplasmic p27.

Effects of over-expression of SOD2 in bone marrow-derived mesenchymal stem cells on traumatic brain injury.

Intravenous administration of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been shown to promote nerve cell regeneration following traumatic brain injury (TBI). As the anti-oxidant defense systems in neuronal tissue including superoxide dismutase 2 (SOD2) are crucial to defend cell against oxidative stress. We proposed a new stratege to increase the therapeutic effect of MSCs by preventing cells death from oxidative stress. We overexpressed SOD2 in BM-MSCs, transplanted these MSCs into TBI model mice, assessed the protective effect of SOD2 against oxidation-induced apoptosis in BM-MSCs both in vitro and in vivo, evaluated brain functional recovery by the rotarod behavioral test, and tested the oxidation status of TBI mice brain after BM-MSCs transplantation by monitoring the superoxide dismutase, glutathione and malonaldehyde level. We found over-expression of SOD2 protected BM-MSCs from H2O2-induced cell apoptosis. Injection of SOD2 over-expressed BM-MSCs attenuated neuro-inflammation in the ipsilateral cortex of TBI mice, and protected TBI mice against loss of blood-brain barrier integrity. Furthermore, the rotarod behavioral test showed functional recovery of TBI mice after MSC treatment. Our experiments indicated that SOD2-over-expressed BM-MSCs have an improved therapeutic effect on brain injury treatment in TBI mice.

Pathologic Progression, Possible Origin, and Management of Multiple Primary Intracranial Neuroendocrine Carcinomas.

BACKGROUND: Primary intracranial neuroendocrine carcinomas (NECs) are extremely rare malignant tumors with no previous reports of multiple ones in the literatures. CASE DESCRIPTION: The clinical presentation, preoperative and reexamined magnetic resonance imaging findings, as well as histopathologic studies of a 56-year-old female subject with multiple intracranial NECs mimicking multiple intracranial meningiomas, who underwent 3 operations with left parietal craniotomy, right occipital parietal craniotomy, and left frontal craniotomy, separately and chronologically, are presented in this article. Noteworthy, the first and second tumors were confirmed as NECs exhibiting histologic characteristics of typical anaplastic meningiomas with features of whorl formation, while the third tumor was a typical NEC with features of organoid cancer nests. In other words, the first 2 lesions were diagnosed as meningioma as opposed to NEC. It was only after the third surgery that the pathology for the first 2 cases was reviewed and had a revised diagnosis. After the third surgical resection, the patient further received whole brain radiotherapy and systemic chemotherapy (temozolomide combined with YH-16). At her 10-month follow-up, the patient achieved a good outcome. CONCLUSIONS: Multiple primary intracranial NECs are extremely rare. The tumor might be of arachnoidal or leptomeningeal origin, with histologic patterns that might lead to transformation and/or progression. Maximal surgical resection is warranted for symptomatic mass effect. Postoperative adjuvant treatments including radiotherapy and chemotherapy should be a recommended therapeutic modality.

Tert-butylhydroquinone protects PC12 cells against ferrous sulfate-induced oxidative and inflammatory injury via the Nrf2/ARE pathway.

Increasing evidence had proved the critical role of iron in the pathogenesis of numerous neurodegenerative diseases because of its capacity to promote the formation of reactive oxygen species (ROS). Tert-butylhydroquinone (tBHQ) was a metabolite of butylated hydroxyanisole, a widely used food antioxidant. This study was aimed to investigate the protective effects of tBHQ on a cellular model of neurodegenerative disease, which was established in PC12 cells by exposure to ferrous sulfate (FS), and elucidate the potential protective mechanisms. The results showed that FS exposure increased lactate dehydrogenase (LDH) release and cell apoptosis in PC12 cells, accompanied by significant increases in the bax/bcl-2 ratio, cytochrome c release, and caspase-3 cleavage. It also enhanced the ROS production, malondialdehyde (MDA) content (lipid peroxidation), γ-H2A.X formation (DNA damage), and promoted nuclear factor kappa B (NF-κB) activation and expressions of cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). tBHQ pretreatment alleviated FS-induced LDH release, cell apoptosis, oxidative stress and inflammatory response by promoting Nrf2 nuclear translocation and the protein levels of Nrf2 downstream target genes heme oxygenase-1 (Hmox-1), nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase-1 (Nqo1) and glutathione peroxidase-1 (Gpx1). tBHQ alleviated the FS-induced LDH release in control siRNA-treated PC12 cells, but failed to alleviate FS-induced LDH release in Nrf2 siRNA-treated cells. These findings suggested that pretreatment with tBHQ protected PC12 cells from FS-induced oxidative and inflammatory injury via the Nrf2/ARE pathway. tBHQ was promising as a potential therapeutic agent for neurodegenerative diseases induced by iron toxicity and should be encouraged for further research.

Combined Hyperactive Dysfunction Syndrome of the Cranial Nerves: A Retrospective Systematic Study of Clinical Characteristics in 44 Patients.

BACKGROUND: Combined hyperactive dysfunction syndrome (HDS) is defined as the combination symptoms arising from overactivity in cranial nerves, specifically, trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia (GPN), without an obvious explanatory structural lesion. This study retrospectively analyzes the clinical characteristics of combined HDS treated with microvascular decompression (MVD) in a single institution. METHODS: A total of 1450 patients with HDS were treated with MVD in our department during a 10-year period, among which 44 cases of combined HDS were identified. Clinical records and follow-ups were reviewed. RESULTS: Combined HDS comprised 3.03% (44/1450) of all HDS in our series, with female predominance compared with single HDS (P = 0.002), including combined TN-HFS (14 cases), combined TN-GPN (26 cases), bilateral TN (2 cases), and combined TN-HFS-GPN (2 cases). The average age at diagnosis of patients with combined HDS (60.9 years) was significantly older than that of patients with single HDS (53.5 years) (P = 0.035). Hypertension was closely associated with the prevalence of combined HDS compared with single HDS (P = 0.009). The curative rate was 97.7% (43/44) after MVD, and the recurrence rate was 3.33%. The incidence rates of postoperative cardiac, pulmonary, thromboembolic, and delirium complications were higher in combined HDS than in single HDS (P < 0.05). CONCLUSIONS: Combined HDS is a rarely occurring syndrome usually observed in older females, and the most common types are combined TN-GPN and combined TN-HFS. Age and gender seemed to be causes for developing combined HDS, and MVD shows potential as a favorable treatment choice.

Label-free quantitative proteomics unravels the importance of RNA processing in glioma malignancy.

Glioma, one of the most common cancers in human, is classified to different grades according to the degrees of malignancy. Glioblastoma (GBM) is known to be the most malignant (Grade IV) whereas low-grade astrocytoma (LGA, Grade II) is relatively benign. The mechanism underlying the pathogenesis and progression of glioma malignancy remains unclear. Here we report a quantitative proteomic study to elucidate the differences between GBM and LGA using liquid chromatography and tandem mass spectrometry followed by label-free quantification. A total of 136 proteins were differentially expressed in GBM for at least five folds in comparison with LGA. Ontological analysis revealed a close correlation between GBM-associated proteins and RNA processing. Interaction network analysis indicated that the GBM-associated proteins in the RNA processing were linked to crucial signaling transduction modulators including epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 1 (STAT1), and mitogen-activated protein kinase 1 (MAPK1), which were further connected to the proteins important for neuronal structural integrity, development and functions. Upregulation of 40S ribosomal protein S5 (RPS5), Ferritin Heavy chain (FTH1) and STAT1, and downregulation of tenascin R (TNR) were validated as representatives by immune assays. In summary, we revealed a panel of GBM-associated proteins and the important modulators centered at the RNA-processing network in glioma malignancy that may become novel biomarkers and help elucidate the underlying mechanism.

Preoperative albumin-to-globulin ratio and prognostic nutrition index predict prognosis for glioblastoma.

OBJECTIVE: Impaired immunonutritional status has disadvantageous effects on outcomes for cancer patients. Preoperative albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) have been used as prognostic factors in various cancers. We aimed to evaluate the clinical significance of the AGR and PNI in glioblastoma. MATERIALS AND METHODS: This retrospective analysis involved 166 patients. Demographic, clinical, and laboratory data were collected. AGR and the PNI were calculated as AGR = albumin/(total serum protein - albumin) and PNI = albumin (g/L) + 5 × total lymphocyte count (109/L). Overall survival (OS) was estimated by Kaplan-Meier analysis. Receiver-operating characteristic analysis was used to assess the predictive ability of AGR and the PNI. Cox proportional-hazard models estimating hazard ratios (HRs) and 95% confidence intervals (CIs) were used for univariable and multivariable survival analyses. RESULTS: The cutoff values of AGR and PNI were 1.75 and 48. OS was enhanced, with high AGR (>1.75) and the PNI (>48) (P<0.001 for both). Areas under the receiver-operating characteristic curve for AGR and the PNI were 0.68 and 0.631 for 1-year survival and 0.651 and 0.656 for 2-year survival (P<0.05 for all), respectively. On multivariable analyses, both AGR and the PNI were independent predictors of OS (AGR, HR 0.785, 95% CI 0.357-0.979 [P=0.04]; PNI, HR 0.757, 95% CI 0.378-0.985 [P=0.039]). On subgroup analysis, AGR and the PNI were significant prognostic factors for OS in patients with adjuvant therapy (AGR P<0.001; PNI P=0.001). CONCLUSION: Preoperative AGR and the PNI may be easy-to-perform and inexpensive indices for predicting OS with glioblastoma. AGR and the PNI could also help in developing good adjuvant-therapy schedules.

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/ß-catenin signaling and induction of apoptosis.

BACKGROUND: Gliomas are one of the most common malignant brain tumors and bring a big threat to human life as traditional therapy is unsatisfactory. RBM5 was a RNA-binding motif protein and was reported as a tumor suppressor. But the role of RBM5 in gliomas was unknown. METHODS: The mRNA level of RBM5 was determined in gliomas tissues and cell lines by real-time quantitative PCR (qRT-PCR) assay while the association of RBM5 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. Lentivirus was used to overexpress RBM5 in gliomas cells. MTT and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis when the ability of cell migration and invasion was analyzed by transwell assay with/without Matrigel. Cell apoptosis rate was determined with fluorescence-activated cell sorting (FACS) method. Then, expression of apoptosis molecules and critical members in Wnt/ß-catenin pathway were detected by western blot analysis. RESULTS: RBM5 was shown to be downregulated in gliomas tissues and gliomas cell lines. And decreased RBM5 expression was clinically correlated with tumor stage, patient age, and poor prognosis of gliomas patients. The proliferation and DNA synthesis was dramatically inhibited when RBM5 was overexpressed in SHG44 or U251 cells. Also, the ability of cell migration and invasion was disrupted. Then, the level of ß-catenin and Cyclin D1 significantly decreased when DKK1 and P-GSK-3ß increased reversely in SHG44 cells, which suggested that RBM5 inhibited canonical Wnt/ß-catenin signaling. Meanwhile, we demonstrated that caspase3-mediated apoptotic pathway was activated by RBM5 as Bax, TNF-α, and cleaved caspase3 were greatly upregulated while antiapoptotic molecule Bcl-2 was downregulated. Additionally, that apoptotic rate increased significantly from less than 1 to 32% in RBM5-overexpressed SHG44 cells further supported the pro-apoptosis role of RBM5 in gliomas cells. CONCLUSIONS: RBM5 plays a suppressor role in human gliomas by inhibiting Wnt/ß-catenin signaling and inducing cell apoptosis. This study improves our knowledge about the carcinogenesis and progression of human gliomas, which would greatly contribute to the therapy for gliomas patients.

The diagnostic value and functional roles of phosphoglycerate mutase 1 in glioma.

Previous studies indicated that phosphoglycerate mutase 1 (PGAM1) is involved in many cancer types and promotes breast cancer progression. However, the role of PGAM1 in glioma remains unclear. The present study aimed to investigate the association of PGAM1 expression with glioma grade and the role of PGAM1 in proliferation, apoptosis, migration and invasion of glioma cells. The mRNA and protein expression of PGAM1 was analysed in glioma tissues and normal brain tissues. The expression of PGAM1 was examined further by immunohistochemical analysis. In addition, we inhibited the expression of PGAM1 in glioma cell line by siRNA to evaluate its role in glioma proliferation, apoptosis, migration and invasion. The mRNA and protein expression of PGAM1 was significantly greater in glioma than normal brain tissues. PGAM1 expression was associated with the WHO grade of glioma. siRNA knockdown of PGAM1 significantly inhibited glioma cell proliferation, promoted glioma cell apoptosis, induced S phase cell cycle arrest and inhibited glioma cell migration and invasion in vitro. PGAM1 may be associated with the grade of glioma and be involved in the biological behavior of glioma cells. PGAM1 might be a novel therapeutic target in glioma.