Brain Astrocytoma Research Articles

Expression of Ki 67 and P53 immunohistochemical markers in central nervous system astrocytoma

Background: Astrocytic tumors are the most common primary tumors of the central nervous system. Several grading systems are used to grade astrocytomas. The most widely used system is the World Health Organization (WHO) classification (1979, 1993, 2000, and 2007) that grades astrocytomas (I-IV) based on cytological atypia, mitotic activity, vascular proliferation, and necrosis: pilocytic astrocytoma (grade I), diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV).Objectives: The aim of this study is to evaluate p53 over expression , Ki-67 expression in astrocytomas and Correlate these two markers with histologic grade of astrocytomas.Methods: Formalin fixed, paraffin-embedded blocks from 40 patients with brain astrocytoma included in this retrospective study. LSAB (Labeled Strept-Avidin, Biotin) method was employed for immunohistochemical detection of Ki – 67 and P53.Results: P53 was detected in (25%) of the cases and was significantly positively correlated with grade IV. Ki-67 labeling index was (>5%) in (50%) of the cases. Both biomarkers were positively correlated with each other, and the grade of astrocytoma; however, Ki67 is a better marker for differentiating (diagnostic marker) between the grades of astrocytoma than p53.Conclusion: P53 overexpression and ki-67 expression plays an important role in pathogenesis of astrocytoma evolution, as they positively associated with higher tumor grade.

PM-10 * CDCA7L FUNCTIONS AS A MALE-SPECIFIC ONCOGENE IN ASTROCYTOMA

The most common types of primary brain tumors, astrocytoma and glioblastoma multiforme (GBM), are currently incurable. Both astrocytoma and GBM show male predominance, with a male to female ratio of 1.42:1 and 1.58:1, respectively. We performed linkage analysis in the Nf1-/ + ;Trp53-/ + cis (NPcis) mouse model of astrocytoma/GBM to identify a male-specific gliomagenesis modifier and further used combinatorial bioinformatics approaches as well as cross-species comparisons to prioritize male-specific candidate gene(s). Here, we showed that Cell division cycle-associated 7-like (CDCA7L), a myc cotranscription factor, is a male-specific oncogene in astrocytoma/GBM. CDCA7L expression is up-regulated in astrocytoma cells compared to normal brain, with males showing higher levels than females in both human and mouse. shRNA-mediated CDCA7L knockdown led to the decreased cell growth and viability of male-derived astrocytoma cells, but not female tumor cells in both human and mouse. Further mechanistic studies showed that CDCA7L depletion in male-derived astrocytoma cells led to the induction of cleaved Caspase-3 and p27 expression and reduction of Cyclin D1 expression. Furthermore, Cdca7l overexpression promotes the growth of WT mouse primary astrocytes only in males by inducing Cyclin D1 expression, but not in female astrocytes, suggesting a male-specific oncogenic role for CDCA7L in astrocytoma/GBM. Strikingly, CDCA7L depletion in human female U87MG GBM cells caused the increase of both growth and viability opposite to what is seen in male cells. Because male-female differences in CDCA7L action are hormone-independent, we examined whether the male-specific histone demethylase KDM5D regulates the effects of CDCA7L. We found that knockdown of KDM5D inhibits male-specific effects of CDCA7L on p27 and Cyclin D1 expression. Our data highlight the sex-specificity of CDCA7L in astrocytoma/GBM tumorigenesis and show that CDCA7L signaling pathways can be oncogenic in males, while being neutral or tumor suppressive in females. This has important implications for the application of therapies to human GBM patients.

Induction of a unique isoform of the NCOA7 oxidation resistance gene by interferon β-1b.

We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress.

DNA-binding and cytotoxic efficacy studies of organorhenium pentylcarbonate compounds

Seven organorhenium pentylcarbonate compounds (PC1-PC7) have been synthesized. DNA-binding studies of the PC-series compounds using electronic spectroscopy and gel electrophoresis suggest that the compounds presumably bind to DNA in an intercalative mode. The intrinsic binding constants for PC4, PC6, and PC7 were found to be 1.6 × 10(4), 3.9 × 10(4), and 4.2 × 10(4) M(-1), respectively. The X-ray structure determinations and density functional theory calculations indicate that the polypyridyl ligands in the compounds are nearly planar facilitating DNA binding through an intercalation mechanism. Cytotoxicity studies of 10 µM pentylcarbonate compounds against HTB-12 human astrocytoma brain cancer cells were studied for 48 h. It was observed that each of the pentylcarbonate compounds is active against the cancer cells. However, under analogous conditions, CRL-2005 rat astrocyte normal brain cells are not affected significantly.

Proteomic study of pilocytic astrocytoma pediatric brain tumor intracystic fluid.

Liquid chromatography in coupling with high-resolution ESI-LTQ-Orbitrap mass spectrometry was applied for a proteomic study of pediatric pilocytic astrocytoma brain tumor intracystic fluid by an integrated top-down/bottom-up platform. Both of the proteomic strategies resulted complementary and support each other in contributing to a wide characterization of the protein and peptide content of the tumor fluid. Top-down approach allowed to identify several proteins and peptides involved in different biological activities together with the characterization of interesting proteoforms such as fibrinopeptide A and its truncated form, fibrinopeptide B, complement C3f fragments, β-thymosin peptides, ubiquitin, several apolipoproteins belonging to A and C families, apolipoprotein J and D, and cystatin C. Of particular interest resulted the identification of a N-terminal truncated cystatin C proteoform, likely involved in immune response mechanism modulations and the identification of oxidized and glycosylated apolipoproteins including disulfide bridge dimeric forms. The bottom-up approach confirmed some of the experimental data findings together with adding the characterization of high-molecular-mass proteins in the samples. These data could contribute to elucidate the molecular mechanisms involved in onset and progression of the disease and cyst development.

Mechanisms of U87 astrocytoma cell uptake and trafficking of monomeric versus protofibril Alzheimer's disease amyloid-β proteins.

A significant hallmark of Alzheimer’s disease is the formation of senile plaques in the brain due to the unbalanced levels of amyloid-beta (Aβ). However, although how Aβ is produced from amyloid precursor proteins is well understood, little is known regarding the clearance and metabolism of various Aβ aggregates from the brain. Similarly, little is known regarding how astrocytes internalize and degrade Aβ, although astrocytes are known to play an important role in plaque maintenance and Aβ clearance. The objective of this study is to investigate the cellular mechanisms that mediate the internalization of soluble monomeric versus oligomeric Aβ by astrocytes. We used a combination of laser confocal microscopy and genetic and pharmacological experiments to dissect the internalization of sAβ42 and oAβ42 and their postendocytic transport by U87 human brain astrocytoma cell line. Both Aβ42 species were internalized by U87 cells through fluid phase macropinocytosis, which required dynamin 2. Depleting LDL receptor-related protein 1 (LRP1) decreased sAβ42 uptake more significantly than that of oAβ42. We finally show that both Aβ42 species were rapidly transported to lysosomes through an endolytic pathway and subjected to proteolysis after internalization, which had no significant toxic effects to the U87 cells under relatively low concentrations. We propose that macropinocytic sAβ42 and oAβ42 uptake and their subsequent proteolytic degradation in astroglial cells is a significant mechanism underlying Aβ clearance from the extracellular milieu. Understanding the molecular events involved in astrocytic Aβ internalization may identify potential therapeutic targets for Alzheimer’s disease.

Clinical application of BOLD-FMRI in guiding protection of the motor cortex during postoperative radiotherapy for brain astrocytoma

Objective To investigate the clinical value of blood oxygen level-dependent functional magnetic resonance imaging (BOLD-FMRI) in guiding the dose reduction and functional protection of the motor cortex during postoperative radiotherapy for brain astrocytoma.Methods This study included 27 brain astrocytoma patients with tumors near the motor cortex,who underwent routine MRI and BOLD-FMRI before postoperative radiotherapy.The location and scope of the motor cortex,which were acquired based on BOLD-FMRI results,were marked on positioning CT images,so that the motor cortex would be dealt with as organs at risk.The dose to the motor cortex was reduced as much as possible while ensuring the therapeutic dose to the target area.Finally,the radiotherapy plan that would reduce the mean received dose of the motor cortex was formulated and compared with the routine plan that could not reduce the received dose.Results With the protective radiotherapy plan,the mean received dose of the motor cortex decreased 0.76％-59.20％ (mean 30.78％) on the affected side and 23.33％-68.30％ (mean 48.07％) on the unaffected side;the coefficients of variation were 71.41％ on the affected side and 36.71％ on the unaffected side.Conclusions BOLD-FMRI can help to reduce the received dose of the motor cortex while ensuring the therapeutic dose to the target area when formulating the postoperative radiotherapy plan for brain astrocytoma,thus protecting the motor function and improving patients' quality of life. Key words: Magnetic resonance imaging; Blood oxygenation level dependent; Brain neoplasms/radiotherapy; Dosimetry

Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells.

In the present study, we designed and conducted a series of assays to determine the expression of voltage-gated sodium channel (VGSC) neonatal isoform Nav1.5 (nNav1.5) in human brain astrocytoma and its effect on the proliferation, migration, invasion and apoptosis of astrocytoma U251 cells. The results showed that nNav1.5 mRNA and protein were expressed in both human brain astrocytoma and normal brain tissues, but their expression levels in astrocytoma were significantly higher (P<0.05). In astrocytomas, nNav1.5 mRNA and protein levels were also different (P<0.05) and were correlated with pathological grades. The immunofluorescence confocal microscopy observations demonstrated that nNav1.5 protein was expressed in the nucleus, cytoplasm and membrane of the astrocytoma cells. After transfection, the small interfering RNA (siRNA) targeted to nNav1.5 significantly reduced the expression levels of SCN5A/nNav1.5 mRNA and protein by 57.2% (P<0.05) and 66.6% (P<0.05), respectively. The MTT, wound healing, Matrigel invasion and flow cytometric assays confirmed that following siRNA downregulation of the expression of the SCN5A/nNav1.5 gene, the invitro proliferation and invitro invasiveness of the U251 cells were significantly reduced (P<0.05 for both comparisons), and the apoptosis rate was significantly increased (P<0.05). These results revealed that nNav1.5 expression in human brain astrocytoma was upregulated, and its expression was positively correlated with the degree of malignancy. Additionally, reduced nNav1.5 expression significantly suppressed the proliferation and invasiveness of astrocytoma cells, indicating a new target in the molecular diagnosis and therapy of astrocytoma.

The investigation of changes in proteins expression (Apolipoprotein A1 and albumin) in malignant astrocytoma brain tumor.

Angiogenesis performs a critical role in the development of cancer. Angiogenesis research is a cutting-edge field in cancer research. Proteomics is a powerful tool in identifying multiple proteins that are altered following a neuropharacological intervention in a disease of the central nervous system. Diagnostic oncoproteomics is the application of proteomic techniques for the diagnosis of malignancies. We extracted proteins of tumor and normal brain tissues and then evaluated the protein purity by Bradford test and spectrophotometery method. In this study, we separated proteins by two-dimensional (2D) gel electrophoresis method and the spots were then analyzed and compared using statistical data and specific software, after providing three-dimensional images of spots alteration. Spots were identified by pH isoelectric, molecular weights, and data banks. Simple statistical test were used to establish a putative hierarchy in which the change in protein level were ranked according a cutoff point with P < 0.05. Apolipoprotein A1 (apo A1) protein and albumin were consistently upregulated in astrocytoma brain tumors. The vascular microenvironment of glioma play a major role in determining the pathophysiological character is tics of the tumor. apo A1 and albumin are very significant due to their functional consequences in glioma tumor growth, migration and angiogenesis.

The Sensitivity of Computerized Tomography in Diagnosis of Brain Astrocytomas

Astrocytomas are tumors that arise from astrocytes—star-shaped cells that make up the “glue-like” or supportive tissue of the brain. Astrocytomas can appear in various parts of the brain and nervous system, including the cerebellum, the cerebrum, the central areas of the brain, the brainstem and the spinal cord. The main objective of this study was to detect the sensitivity of the CT scan in diagnosis of the brain astrocytoma, in patients who were confirmed as brain gliomas using computerized tomography of the brain versus brain tissue biopsy after surgery. One hundred and one patients were included in this study. Bio-data collected for these patients (age, gender), radiographic appearance, contrast enhancement and the site of the tumor, were statistically analyzed. Out of the 101 patients with brain gliomas, 52 (51.5%) were male whose ages ranged between 1 and 80 years, and 64 (63.4%) cases were diagnosed as astrocytoma by CT. This study concluded that the CT brain was sensitive in the diagnosis of brain astrocytomas.

Plasma levels of glucose and insulin in patients with brain tumors.

In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors.

Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma

Glioblastoma multiforme (GBM) is a neurologically debilitating disease that culminates in death 14 to 16 months after diagnosis. An incomplete understanding of how cataloged genetic aberrations promote therapy resistance, combined with ineffective drug delivery to the central nervous system, has rendered GBM incurable. Functional genomics efforts have implicated several oncogenes in GBM pathogenesis but have rarely led to the implementation of targeted therapies. This is partly because many "undruggable" oncogenes cannot be targeted by small molecules or antibodies. We preclinically evaluate an RNA interference (RNAi)-based nanomedicine platform, based on spherical nucleic acid (SNA) nanoparticle conjugates, to neutralize oncogene expression in GBM. SNAs consist of gold nanoparticles covalently functionalized with densely packed, highly oriented small interfering RNA duplexes. In the absence of auxiliary transfection strategies or chemical modifications, SNAs efficiently entered primary and transformed glial cells in vitro. In vivo, the SNAs penetrated the blood-brain barrier and blood-tumor barrier to disseminate throughout xenogeneic glioma explants. SNAs targeting the oncoprotein Bcl2Like12 (Bcl2L12)--an effector caspase and p53 inhibitor overexpressed in GBM relative to normal brain and low-grade astrocytomas--were effective in knocking down endogenous Bcl2L12 mRNA and protein levels, and sensitized glioma cells toward therapy-induced apoptosis by enhancing effector caspase and p53 activity. Further, systemically delivered SNAs reduced Bcl2L12 expression in intracerebral GBM, increased intratumoral apoptosis, and reduced tumor burden and progression in xenografted mice, without adverse side effects. Thus, silencing antiapoptotic signaling using SNAs represents a new approach for systemic RNAi therapy for GBM and possibly other lethal malignancies.

Combined value of susceptibility-weighted and perfusion-weighted imaging in assessing who grade for brain astrocytomas.

To assess the value of combining susceptibility-weighted imaging (SWI) and dynamic susceptibility weighted contrast-enhanced (DSC) perfusion-weighted MRI (PWI) in assessing World Health Organization (WHO)grade for brain astrocytoma . A total of 94 patients with pathologically confirmed astrocytomas underwent SWI and DSC scans. The evaluation included intratumoral susceptibility signal intensity (ITSS) and relative cerebral blood volume (rCBV) max. The receiver operating characteristic curve (ROC) was used to assess the efficacy of combining two sequences in astrocytoma grading. ITSS within astrocytomas showed significant correlations with rCBV max (r ¼ 0.72; P < 0.01) and with tumor grades (r ¼ 0.92; P < 0.01), and there was also a significant correlation between rCBV and tumor grade (r= 0.77; P < 0.001). The area under the ROC, SWI, PWI,SWI, and PWI, in differentiation of the grades II and III astrocytomas were 0.995, 0.942, and 1.000, respectively;identifying grades III and IV were 0.773, 0.919, and 0.978, respectively; and identifying high and low-grade astrocytomas were 0.999, 0.992, 1.000, respectively. ITSS was useful for assessing the WHO tumor grade in this cohort of patients with astrocytoma.The combination of SWI and PWI may improve the diagnostic accuracy of astrocytoma grading.

Zinc finger protein 667 expression is upregulated by cerebral ischemic preconditioning and protects cells from oxidative stress

Brain ischemic injury is associated with clinical emergencies such as acute ischemic and hemorrhagic stroke, head trauma, prolonged severe hypotension and cardiac arrest. Ischemic preconditioning (IPC) is the most powerful endogenous mechanism against ischemic injury. However, the majority of IPC treatments are invasive and thus impractical in the clinical setting. Identifying the endogenous neuroprotective mechanism induced by IPC is important for developing new strategies to reduce stroke severity. Zinc finger protein 667 (ZNF667) is a novel zinc finger protein that is upregulated by myocardial IPC. However, its functional role in neuronal ischemia has not been elucidated. In this study, the changes of ZNF667 expression on cerebral IPC and its potential neuroprotective function were investigated. The cerebral ischemia model was established by ameliorated four-vessel occlusion in rats. The northern blot results demonstrated that ZNF667 expression was increased in the hippocampus and cortex at 12 and 24 h after cerebral ischemic pretreatment. To investigate the neuroprotective function of ZNF667, enhanced green fluorescent protein (EGFP)-ZNF667 fusion protein was expressed in C2C12 and brain astrocytoma cells and its subcellular localization was detected by confocal microscopy. EGFP-ZNF667 fusion proteins were localized in the nucleus of C2C12 and brain astrocytoma cells, indicating that ZNF667 may act as a transcription factor in neural cells. To mimic oxidative stress associated with ischemia/reperfusion injury, hydrogen peroxide (H2O2) was used to treat cells. Cell viability was measured by the lactate dehydrogenase (LDH) and WST-1 assays. A decrease in viability was detected in C2C12 and astrocytoma cells following H2O2 treatment, whereas ZNF667 gene overexpression significantly improved cell viability following H2O2 treatment. These results suggested that ZNF667 plays a neuroprotective role by acting as a transcription factor in cerebral IPC.

Expression and Functional Significance of Ezrin in Human Brain Astrocytoma

Ezrin is overexpressed in a variety of neoplastic cells and is involved in the later stages of tumor progression and metastasis. The present study investigated the expression and functional significance of ezrin in human brain astrocytoma. Ezrin expression was examined in specimens from healthy human brains (10 autopsies) or human astrocytoma (107 cases) by immunohistochemistry. All healthy specimens were negative for ezrin expression, while this expression was positive in a great majority of human astrocytoma tissues (96/107; 89.7%; p < 0.05 vs. healthy). Ezrin expression was positively correlated with tumor grade (r = 0.551, p < 0.01). Analysis of clinicopathologic data revealed that the post-operation disease-free survival times were significantly (p < 0.001) different between those with a strong positive ezrin expression and those with a weak or negative expression. Specifically, median DFS in patients with a strongly positive ezrin expression was 13 months (range 2-46 months), while it was significantly (p < 0.001) longer in patients with weakly positive or negative expression (median of 28 months, range 6-56 months). In conclusion, there is a strong association between ezrin expression and increased malignancy in astrocytoma. Thus, enhanced ezrin expression may play an important role in the development of astrocytoma. Our results further indicate that ezrin may be useful for grading of astrocytoma and as a molecular marker for the prognosis.

Microvascular permeability of brain astrocytoma with contrastenhanced magnetic resonance imaging: correlation analysis with histopathologic grade

Background The degree of pathological microvascular proliferation is an important element in evaluation of the astrocytoma grade. This study was aimed to quantitatively assess the microvascular permeability of brain astrocytoma with the volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (Ve) from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to evaluate the effectiveness of the Ktrans and Ve in the grading of astrocytoma. Methods The highest values of the Ktrans and Ve of 67 patients with astrocytoma (27 with grade II, 12 with grade III, and 28 with grade IV) were obtained. The comparisons of the differences of the Ktrans and Ve between the different grades were conducted using the Mann-Whitney rank-sum tests. Spearman's rank correlation coefficients were determined between Ktrans values, Ve values and astrocytoma grades. Receiver operating characteristic (ROC) curve analyses were performed to determine the cut-off values for the Ktrans and Ve to distinguish between the different grades of astrocytoma. Results There were significant differences (P&lt;0.001) between the different grades in the Ktrans values and Ve values, except for grades III and IV. The Ktrans values and Ve values were both correlated with astrocytoma grades (both P&lt;0.001). The ROC curve analyses showed that the cut-off values for the Ktrans and Ve provided the best combination of sensitivity and specificity in distinguishing between grade II and grade III or IV astrocytomas. Conclusions DCE-MRI can play an important role in assessing the microvascular permeability and the grading of brain astrocytoma.

Expression of brain-specific angiogenesis inhibitor 1 is inversely correlated with pathological grade, angiogenesis and peritumoral brain edema in human astrocytomas

As the most common intracranial malignant neoplasms, astrocytomas are characterized by high neovascularization and severe peritumoral brain edema (PTBE). Angiogenesis is a prerequisite for the growth of solid tumors, including astrocytoma, and brain-specific angiogenesis inhibitor 1 (BAI1) is a novel angiogenesis inhibitor. In the present study, the expression levels of BAI1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were investigated using immunohistochemical methods in 90 human brain astrocytoma specimens of various pathological grades and in 11 normal human brain tissues. Vascular endothelial cells were stained for CD105 and the microvessel density (MVD) was assessed. The volume of astrocytoma and PTBE in each case was evaluated by magnetic resonance imaging (MRI). The results showed that BAI1 was highly expressed in the normal brain tissues, but that the expression decreased with the rising pathological grades of astrocytoma, MVD number and PTBE, indicating that BAI1 expression was inversely correlated with these factors. Furthermore, it was observed that the expression of VEGF and bFGF were inversely correlated with BAI1 expression in the human brain astrocytomas. These results indicate that the BAI1 gene may be used as a marker of decreased tumor progression and tumoral neovascularization, as well as PTBE.

Hemiparesis after Operation of Astrocytoma Grade II in Adults: Effects of Acupuncture on Sensory-Motor Behavior and Quality of Life

To evaluate the effect of acupuncture on hemiparesis and quality of life for adults with brain astrocytoma grade II, we conducted a randomized, observer-blinded clinical trial. Fifty-eight patients were randomized to standard rehabilitation (SR) therapy without acupuncture (n = 20), SR plus standard acupuncture (SA) (n = 19), and SR plus individualized acupuncture (IA) (n = 19). SA points were PC6, SP6, HT1, LU5, BL40, and ST36, while a special concept called “connecting and regulation Ren and Du” and “Jin-3-needling” served as IA. This treatment was individualized according to the clinical syndrome. The outcome was measured by the Barthel Index (BI), the Fugl-Meyer scale (FM), and the EORTC Core Quality of Life Questionnaire (QLQ-C30) with the Brain Cancer Module (BCM20). IA + SR reached significantly higher BI scores than SA + SR, which reached significantly higher BI scores than SR. IA + SR was significantly superior to SA + SR and to SR at the 8th week for the scores of FM motor and sensory assessments and most QLQ-C30-BCM20 items. In conclusion, the individualized acupuncture concept of “connecting and regulating Ren and Du” combined with “Jin-3-needling” offers a promising possibility for the treatment of hemiparesis due to astrocytoma, but further evaluation is mandatory.

Cytotoxicity of Blended Versus Single Medicinal Mushroom Extracts on Human Cancer Cell Lines: Contribution of Polyphenol and Polysaccharide Content

The use of mushrooms contributes to human nutrition by providing low lipid content of lipids and high dietary fiber content, as well as significant content of other biologically active compounds such as polysaccharides, minerals, vitamins, and polyphenolic antioxidants. This study aimed to determine the content of polyphenols and polysaccharides, as well as the cytotoxic and antioxidative properties of several medicinal mushroom preparations. The content of total phenols and flavonoids of preparations of blended mushroom extracts (Lentifom, Super Polyporin, Agarikon, Agarikon Plus, Agarikon.1, and Mykoprotect.1) was evaluated quantitatively by using ultraviolet-visible spectroscopy spectrophotometric methods. The antioxidant capacity of the preparations was evaluated using the ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and ferric reducing/antioxidant power assays. The content of water-soluble polysaccharides was determined using a specific gravimetric method, based on ethanol precipitation. To determine cytotoxic effects of single and blended mushroom extracts, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red assays were conducted using human small cell lung cancer, lung adenocarcinoma, colon cancer, and brain astrocytoma cancer cells. The obtained results suggest that due to the significant content of beneficial polyphenolic antioxidants and soluble polysaccharides, use of these mushroom preparations is beneficial in maintaining good health, as well as in the prevention and adjuvant biotherapy of various human pathological aberrations. These results reveal that these extracts exhibit different cytotoxic effects on tumor cells originating from different tissues. In addition, the comparison of investigated blended mushroom extracts with three well-known commercial mushroom products derived from single mushroom species or single mushroom compounds shows that blended mushroom extracts exhibit significantly stronger cytotoxic effects on human tumor cell lines.

Validation of soft classification models using partial class memberships: An extended concept of sensitivity & co. applied to grading of astrocytoma tissues

We use partial class memberships in soft classification to model uncertain labeling and mixtures of classes. Partial class memberships are not restricted to predictions, but may also occur in reference labels (ground truth, gold standard diagnosis) for training and validation data.Classifier performance is usually expressed as fractions of the confusion matrix, like sensitivity, specificity, negative and positive predictive values. We extend this concept to soft classification and discuss the bias and variance properties of the extended performance measures. Ambiguity in reference labels translates to differences between best-case, expected and worst-case performance. We show a second set of measures comparing expected and ideal performance which is closely related to regression performance, namely the root mean squared error RMSE and the mean absolute error MAE.All calculations apply to classical crisp as well as to soft classification (partial class memberships as well as one-class classifiers). The proposed performance measures allow to test classifiers with actual borderline cases. In addition, hardening of e.g. posterior probabilities into class labels is not necessary, avoiding the corresponding information loss and increase in variance.We implemented the proposed performance measures in R package “softclassval” which is available from CRAN and at softclassval.r-forge.r-project.org.Our reasoning as well as the importance of partial memberships for chemometric classification is illustrated by a real-word application: astrocytoma brain tumor tissue grading (80 patients, 37,000 spectra) for finding surgical excision borders. As borderline cases are the actual target of the analytical technique, samples which are diagnosed to be borderline cases must be included in the validation.