Biomedical subjects

R Meyermann

Publications and source records attributed to R Meyermann.

At least 55 records · Page 3Linked to original sources

PubMed2000

Differential regulation of the monocytic calcium-binding peptides macrophage-inhibiting factor related protein-8 (MRP8/S100A8) and allograft inflammatory factor-1 (AIF-1) following human traumatic brain injury.

Intracellular calcium (Ca2+) has been shown to function as second messenger and to be associated with activation of different cell types including microglia. Previously, in human focal cerebral infarctions an early expression of macrophage-related protein-8 (MRP8/ S100A8), a member of the Ca2+-binding S100-protein family, in microglia has been reported. On the other hand, a delayed activation of microglia was observed following traumatic brain injury (TBI). We therefore examined immunohistochemically microglial expression of MRP8 and allograft inflammatory factor-1 (AIF-1), identical to microglial response factor-1 (mrf-1) and ionized calcium binding adaptor molecule-1 (ibal) in human brains after TBI and in control brains. Both, MRP8 and AIF-1 are Ca2+-binding peptides which have been associated with microglial activation in experimental models and in human cerebral infarctions. Detection of AIF-1 in controls confirmed constitutive expression of this peptide in a subset of microglial cells. After TBI, the density of AIF-1+ microglia did not increase significantly. Lesional expression of AIF-1 did not significantly differ from other brain regions. Furthermore, following TBI, we found no significant differences in the density of AIF-1+ microglia as compared to controls. Microglial MRP8 expression was not detectable in controls and within the first 3 days post TBI, but increased rapidly after 3 days post TBI, suggesting a subpopulation of microglial cells to be AIF-1-/MRP8+. We conclude that the delayed expression of MRP8 and the lack of AIF-1 up-regulation in microglia after TBI is in contrast to ischemic brain lesions and might reflect different activation cascades of microglia.

Adolescent↗

PubMed2000

Allograft inflammatory factor-1 defines a distinct subset of infiltrating macrophages/microglial cells in rat and human gliomas.

Allograft inflammatory factor-1 (AIF-1) is a Ca2+-binding peptide that constitutes a potential modulator of macrophage activation and function during the immune response of the brain. Peptides termed microglia response factor-1 or ionized calcium-binding adaptor molecule- have been reported to be identical with AIF-1. We have investigated the expression of AIF-1 in the rat C6 glioblastoma and 9L gliosarcoma tumor models and additionally assessed AIF- expression in a diverse range of human astrocytomas by immunohistochemistry. AIF-1 was expressed by activated microglial cells and a subset of infiltrating macrophages in areas of infiltrative tumor growth and in compact tumor areas in both rat and human gliomas. Double-labeling experiments in rats and humans characterized the nature and the functional status of AIF-1+ cells. AIF-1 expression was detected in cells expressing major histocompatibility complex class II molecules and in a subset of activated macrophages/microglial cells. All MRP-8+ cells coexpressed AIF-1. In humans, there was a strong correlation of AIF-1-expressing activated macrophages/microglial cells with tumor malignancy (P < 0.0001). These results suggest that AIF-1 defines a distinct subset of tumor-associated activated macrophages/ microglial cells.

Adult↗

PubMed2000

Evidence for a constitutive, verapamil-sensitive, non-P-glycoprotein multidrug resistance phenotype in malignant glioma that is unaltered by radiochemotherapy in vivo.

Human malignant gliomas are commonly resistant to chemotherapy. Here, we examined the role of the multidrug resistance (mdr) mechanism in the chemo-resistance of these tumors, using a twofold approach: (i) by assessing a possible mdr phenotype before and after chronic drug exposure of glioma cells in vitro, and (ii) by assessing the modulation of expression of the mdr-associated P-glycoprotein (Pgp) using radiotherapy and serial cycles of chemotherapy in human glioblastoma patients in vivo. T98G, and to a lesser degree, LN-229 human malignant glioma cells exhibit a constitutive mdr phenotype as determined by the modulation of dye transport and by the augmentation of chemosensitivity by the mdr antagonist, verapamil. Thus, coexposure to verapamil enhances the cytotoxicity of vincristine, doxorubicin and VM26 in T98G cells and that of vincristine in LN-229 cells. Chronic exposure of the cells to low concentrations of vincristine and doxorubicin, but not VM26, topotecan or BCNU, moderately enhances the mdr-like phenotype, as assessed by drug expulsion assays. However, chronic exposure to increasing drug concentrations does not significantly alter the sensitivity to the respective drugs. These data are consistent with a constitutive, but not drug-inducible, mdr-like drug resistance in glioma cells in vitro. Immunocytochemical analysis of human malignant gliomas in vivo reveals that Pgp expression is more abundant in endothelial cells within the gliomas, than in the glioma cells proper. Importantly, Pgp expression is unaltered by radiochemotherapy, assessed by comparative immunocytochemistry of glioma specimens obtained serially before and after radiochemotherapy. We conclude that (i) glioma cells exhibit constitutive mdr-like drug resistance that is not significantly altered by chronic drug exposure in vitro; (ii) endothelial cells may play an important role in Pgp-mediated drug resistance of gliomas in vivo; (iii) radiotherapy and repeated chemotherapy cycles do not modulate Pgp expression in human malignant gliomas in vivo; (iv) there is preliminary evidence for a non-Pgp, verapamil-sensitive drug transport activity in glioma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Selective accumulation of cyclooxygenase-1-expressing microglial cells/macrophages in lesions of human focal cerebral ischemia.

Cyclooxygenases (COX; prostaglandin endoperoxide H synthases) are key enzymes in the conversion of arachidonic acid into prostanoids which mediate inflammation, immunomodulation, mitogenesis, ovulation, fewer, apoptosis and blood flow. Here, we report COX-1 expression following focal cerebral infarctions (FCI). In healthy control brains, COX-1 was localized by immunohistochemistry to a few endothelial cells, single neurons and rare, evenly distributed brain microglia/macrophages. In infarctioned brains, COX-1+ cells accumulated highly significantly (P < 0.0001) in peri-infarctional areas and in the developing necrotic core early after infarction. Here, cell numbers remained persistently elevated up to several months post infarction. Further, clusters of COX-1+ cells were located in perivascular regions related to the Virchow-Robin space. Double-labeling experiments confirmed co-expression of COX-1 by CD68+ microglia/macrophages. Co-expression of the activation antigens HLA-DR, -DP, -DQ (MHC class II) or the macrophage inhibitor factor-related protein MRP-8 (S100A8) by most COX-1+ microglia/macrophages was only seen early after infarction. Thus, COX-1 appeared to be expressed in microglial cells regardless of their activation state. However, the prolonged accumulation of COX-1+ microglia/macrophages restricted to peri-infarctional areas enduring the acute post-ischemic inflammatory response points to a role of COX-1 in tissue remodeling or in the pathophysiology of secondary injury. We have identified localized, accumulated COX-1 expression as a potential pharmacological target following FCI. Therefore we suggest that therapeutic approaches based on selective COX-2 blocking might not be sufficient for suppressing the local synthesis of prostanoids.

Aged↗

PubMed2000

Central nervous system Hodgkin's lymphoma without systemic manifestation: case report and review of the literature.

A 66-year-old woman treated for ocular myasthenia gravis with azathioprine for 12 years presented with a left fronto-parietal mass. Histology revealed primary Hodgkin's lymphoma of the central nervous system with CD30, Epstein-Barr virus (EBV) latent membrane protein and CD20-positive, CD45 (LCA)-negative Reed-Sternberg cells surrounded by T cells. Moreover, EBV-encoded RNA-1 (EBER-1) sequences and a monoclonal rearrangement of the immunoglobulin heavy chain CDR2 locus were detected.

Aged↗

PubMed2000

Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14.

Human traumatic brain injury (TBI) is ideally suited for investigation of the kinetics of human microglial cell activation as the onset of lesion formation is precisely defined. The present study provides evidence of a distinct delay in macrophage/microglia response following TBI. Eighteen brains of patients who had survived TBI for 1 h to 6 months were analysed by immunohistology. Samples of contusional and non-contusional areas were studied using antibodies directed against antigens of microglia/ macrophages [major histocompatibility complex class II, CD4, interleukin (IL)-16, macrophage-related protein (MRP) 8 and MRP14]. IL-16, a natural ligand to CD4, was expressed constitutively by numerous microglial cells in all cases throughout the brain. CD4 could be detected regularly on perivascular cells. MRP8 and MRP14, which are only expressed on activated macrophages and microglial cells, could be detected only within brains with a survival time of more than 72 h post TBI. In addition, proliferation of microglia detected by MIB-1 was not present until 72 h. This delayed expression of the activation markers MRP8 and MRP14 and the proliferation marker MIB-1 is comparable to experimental closed head injuries but strictly different from acute activation found in ischemic brains.

Adolescent↗

PubMed2000

Demonstration of morphine in ganglion cells of the hippocampus from victims of heroin overdose by means of anti-morphine antiserum.

To investigate the topography of morphine distribution in the human brain, a method has been developed to detect morphine immunohistochemically. In this study hippocampus tissue from victims of heroin overdose (blood morphine concentrations 220 ng/g-1500 ng/g; 6-MAM positive urine sample), known for its high concentration of mu-opiate receptors was used. The immunohistochemical staining was performed with an anti-morphine antiserum originally developed for radio-immunoassays. In comparison with control specimens from cases of sudden death without morphine exposition or a history of heroin abuse, the brains from victims of heroin overdose showed selectively stained ganglion cells, axons and dendrites, suggesting a massive concentration of morphine in the neuronal structures.

Adult↗

PubMed2000

A role for preirradiation PCV chemotherapy for oligodendroglial brain tumors.

Oligodendroglial tumors have been identified as a subgroup of glial neoplasms with a distinctly better response to chemotherapy and overall survival than purely astrocytic gliomas. Here we report our experience with adjuvant postirradiation and preirradiation chemotherapy using procarbazine, lomustine, and vincristine (PCV) in 27 patients with WHO grade II or III oligodendroglioma or oligoastrocytoma. The efficacy of chemotherapy was assessed according to the Macdonald response criteria (complete response, CR; partial response, PR; stable disease, SD; progressive disease, PD) and progression-free survival intervals by computed tomography or magnetic resonance imaging. First, we confirm that PCV salvage therapy for patients progressing after radiotherapy is highly effective (n = 11, 1 CR, 5 PR, 5 SD; median progression-free survival has not yet been reached, but is longer than 18 months). Second, 3 patients who received radiotherapy plus PCV as first-line therapy achieved CR and 2 achieved SD, and all 5 are progression-free with a median follow-up of 12 months. Third, given these encouraging results, 11 patients received postoperative preirradiation PCV chemotherapy and were given radiotherapy only upon progression. Preirradiation PCV chemotherapy was also effective (2 CR, 3 PR, 6 SD; median progression-free survival has not been yet reached, but is longer than 14 months). Patients with anaplastic oligoastrocytomas were as likely to respond to PCV chemotherapy, as were patients with anaplastic oligodendroglioma. Three patients who had previously responded to PCV were successfully treated with a second course of PCV upon recurrence. PCV chemotherapy was also effective in patients with leptomeningeal spread of oligodendrogliomas. A randomized prospective trial is required to compare the effectiveness and neurotoxicity of first-line PCV chemotherapy followed by radiotherapy to the traditional reverse sequence.

Adolescent↗

PubMed2000

Leukocyte-endothelium-interaction in pial vessels following global, cerebral ischaemia.

BACKGROUND: Investigations have shown an increase of leukocyte-endothelium-interaction in a variety of organs following an ischaemic insult. To elucidate the role of leukocyte-endothelium-interaction following global, cerebral ischaemia the present study was performed. METHODS: Global, cerebral ischaemia was induced for twenty minutes by four-vessel-occlusion (PULSINELLI). Leukocyte-endothelium-interaction was studied in the cerebral microcirculation using a rat closed cranial window and intravital microscopy. Leukocytes were stained intravenously using rhodamine 6G. Diameters of pial vessels, leukocyte centreline velocity and number of rolling or adhering leukocytes were determined off-line up to 2 h following global cerebral ischaemia. To confirm these results immunohistochemistry of the brain was performed. FINDINGS: Four-vessel-occlusion induced an iso-electric EEG, venular stasis and minimal rest flow in arterioles. Reperfusion yielded a significant increase of the arteriolar (p < 0.001) and a smaller increase of the venular diameters (p < 0.01). Up to 2 h after ischaemia no significant increase of the number of rolling or adhering leukocytes was measured which was confirmed by immunohistochemistry. INTERPRETATION: In contrast to other studies, in particular regarding focal cerebral ischaemia, an increase of leukocyte-endothelium-interaction in rat brain following 20 min of global cerebral ischaemia was not observed despite histological evidence of ischaemic damage. Thus in our model leukocytes seem not to contribute to the brain damage following global ischaemia.

Animals↗

PubMed2000

Analysis of mdm2 and p53 gene alterations in glioblastomas and its correlation with clinical factors.

Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with probably prognostic implications. To elucidate the involvement of murine-double-minute (mdm)2 gene amplifications and mutations of the tumor suppressor gene p53 in the tumorigenesis of malignant gliomas we analyzed a series of 75 glioblastomas. The p53 mutations occur in one-third of glioblastomas, mdm2 amplifications were found in 13% of cases. Our analysis revealed a hot spot in the p53 gene locus in codon 156, the same point mutation was detected in 4 tumor samples. None of the mdm2 amplified tumors had p53 mutations, supporting the hypothesis, that mdm2 amplifications are alternative mechanisms for p53 inactivation. Patients with p53 mutated tumors were significantly younger characterized by a mean age of 44 years. Additionally association with longer overall survival could be detected for this subgroup of patients. In our study, survival estimation revealed a significant correlation of mdm2 gene amplification with shorter survival time, and support the hypothesis, that mdm2 oncogene activation appears to occur late in tumor progression and may be characteristic as negative prognostic marker.

Adult↗

PubMed2000

A case of spinal glioblastoma multiforme: immunohistochemical study and review of the literature.

A 31-year old female underwent subtotal resection of a spinal glioblastoma multiforme (GBM) at level D 10/11 in June 1997. Immunohistochemistry revealed increased MIB-1 labeling index and accumulation of p53 protein. Routine MRI in February 1998 showed multiple tumors of the lumbar spinal cord. At open biopsy, diffuse infiltration of multiple radices was seen. Histologically and immunohistochemically, the tumor was similar to the primary. In May 1998, MRI revealed multiple intracranial metastases and meningeal involvement. The patient died in June 1998, 13 months after the onset of symptoms. The lifes of patients with spinal gliomas are not endangered by direct compression of the brain stem, and systemic metastases are extremely uncommon with gliomas. Yet, survival times in the reported case and in the literature are not better than with cerebral localization. Analysis of the present case and a survey of the literature indicate that CSF involvement and consecutive intracranial seeding determine the prognosis of patients with spinal GBM. Thus, regular monitoring of CSF-cytology and/or spinal MRI appear to be advisable in spinal GBM.

Adult↗

PubMed2000

Distinct radiochemotherapy protocols differentially influence cellular proliferation and expression of p53 and Bcl-2 in glioblastoma multiforme relapses in vivo.

Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB- 1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p = 0.013). Irradiation caused the reduction of MIB-1+ (p = 0.0015), DO-7+ (p = 0.0043) and the increase of Bcl-2+ cells (p = 0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p = 0.0186) and no treatment (p = 0.0158), low ISNT scores (p = 0.0018) and high DO-1 scores (p = 0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-I and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.

Adult↗

PubMed2000

Lesion-associated accumulation of uPAR/CD87- expressing infiltrating granulocytes, activated microglial cells/macrophages and upregulation by endothelial cells following TBI and FCI in humans.

Urokinase-type plasminogen activator receptor (uPAR/CD87) together with its ligand, urokinase-type plasminogen activator (uPA), constitutes a proteolytic system associated with tissue remodelling and leucocyte infiltration. uPAR is a member of the glycosyl phosphatidyl inositol (GPI) anchored protein family. The functional role of uPAR comprises fibrinolysis by conversion of plasminogen to plasmin. In addition, uPAR promotes cell adhesion, migration, proliferation, re-organization of the actin cytoskeleton, and angiogenesis. Furthermore, uPAR is involved in prevention of scar formation and is chemoattractant to macrophages and leucocytes. In order to investigate the pathophysiological role of uPAR following human CNS injury we examined necrotic brain lesions resulting from traumatic brain injury (TBI; n = 28) and focal cerebral infarctions (FCI; n = 17) by immunohistochemistry. Numbers of uPAR+ cells and uPAR+ blood vessels were counted. Following brain damage, uPAR+ cells increased significantly within 12 h, reached a maximum after 3-4 days and remained elevated until later stages. uPAR was expressed by infiltrating granulocytes, activated microglia/macrophages and endothelial cells. Numbers of uPAR+ vessels increased in parallel subsiding earlier following FCI than post TBI. The restricted, lesion-associated accumulation of uPAR+ cells in the brain parenchyma and upregulated expression by endothelial cells suggests a crucial role for the influx of inflammatory cells and blood-brain barrier (BBB) disturbance. Through a failure in BBB function, uPAR participates in formation of brain oedema and thus contributes to secondary brain damage. In conclusion, the study defines the localization, kinetic course and cellular source of uPAR as a potential pharmacological target following human TBI and FCI.

Adolescent↗

PubMed2000

Connective tissue growth factor is expressed by a subset of reactive astrocytes in human cerebral infarction.

Connective tissue growth factor (CTGF), a transforming growth factor (TGF)-beta1 downstream mediator, is a secreted cell matrix-inducing peptide involved in both tissue regeneration mechanisms, such as wound repair, and also in aberrant deposition of extracellular matrix. The present study reports CTGF expression by cells associated with matrix deposition and glial scar formation in human cerebral infarction. CTGF was localized by immunohistochemistry in 17 brains of patients after focal infarction and in three neuropathologically normal control brains. CTGF expression was selectively localized to the cytoplasm of stellate reactive astrocytes. Compared to peripheral areas and brain controls without neuropathological findings, the total number CTGF+ astrocytes was significantly higher (P < 0.0001) in border zones adjacent to the core, corresponding to the penumbra. These numbers were significantly increased at day 1 and day 3 and remained persistently elevated up to several months post-infarction (P < 0.0001). The restricted expression and accumulation of CTGF+ reactive astrocytes adds convincing evidence for CTGF participation in the gliotic astrocyte CNS injury response involved in glial scar formation. CTGF can be considered a sensitive marker of early human astrocyte activation and a possible target for pharmacological intervention of aberrant matrix deposition.

Aged↗

PubMed2000

Allograft inflammatory factor-1 is expressed by macrophages in injured skeletal muscle and abrogates proliferation and differentiation of satellite cells.

Secretion of regulatory peptides by macrophages in injured skeletal muscle constitutes a pivotal determinator of tissue homeostasis. We analyzed expression of a novel Ca2+- binding peptide expressed by activated macrophages, the allograft inflammatory factor-1 (AIF-1), in rat devascularized skeletal muscle. AIF-1 expression was observed in 94% of all macrophages at the site of the injury 48 hours postdevascularization. The physiological function of AIF-1 in injured skeletal muscle was analyzed using a rat in-vitro model of satellite cell proliferation and differentiation. Addition of AIF-1 to the culture medium resulted in a concentration-dependent and reversible reduction of the total number of cells expressing M-cadherin (p < or = 0.0001), a mediator of the differentiation process of skeletal muscle cells, the proliferation associated PCNA (p < or = 0.0001), and the initiator of muscle differentiation myogenin (p < or = 0.0001). These results provide convincing evidence that activated AIF-1 expressing macrophages constitute the predominant cell type in skeletal muscle 48 hours postinjury, and that AIF-1 regulates reduced proliferation, differentiation, and activation of satellite cells.

Animals↗

PubMed2000

Bag-1 and Bcl-2 gene transfer in malignant glioma: modulation of cell cycle regulation and apoptosis.

Bag-1 is a heat shock 70 kDa (Hsp70)-binding protein that can collaborate with Bcl-2 in suppressing apoptosis under some conditions. Here, we report that 11 of 12 human glioma cell lines express Bag-1 protein in vitro. Moreover, 15 of 19 human glioblastomas expressed Bag-1 as assessed by immunohistochemistry in primary tumor specimens. To examine the biological effects of Bag-1 in glioma cells, we expressed Bag-1 or Bcl-2 transgenes in 2 human malignant glioma cell lines, LN-18 and LN-229. Bag-1 significantly slowed glioma cell growth and reduced clonogenicity of both cell lines in vitro. Coexpressed Bcl-2 abrogated these effects of Bag-1. Intracranial LN-229 glioma xenografts implanted into nude mice revealed a substantial growth advantage afforded by Bcl-2. Bag-1 had no such effect, either in the absence or presence of Bcl-2. Upon serum starvation in vitro, Bcl-2 prevented cell death whereas Bag-1 did not. Both Bcl-2 and Bag-1 slowed proliferation of serum-starved cells when expressed alone. Importantly, coexpression of Bcl-2 and Bag-1 provided a distinct growth advantage under conditions of serum starvation that is probably the result of (i) the death-preventing activity of Bcl-2 and (ii) the property of Bag-1 to overcome a Bcl-2-mediated enhancement of exit from the cell cycle. In contrast to these Bcl-2/Bag-1 interactions observed under serum starvation conditions, Bag-1 did not further enhance the strong protection from staurosporine-, CD95 (Fas/Apo1) ligand-, Apo2 ligand (TRAIL)- or chemotherapeutic drug-induced apoptosis afforded by Bcl-2. Taken together, these results indicate a role for Bag-1/Bcl-2 interactions in providing a survival advantage to cancer cells in a deprived microenvironment that may be characteristic of ischemic/hypoxic tumors such as human glioblastoma multiforme, and suggest that Bcl-2/Bag-1 interactions also modulate cell proliferation.

Animals↗

PubMed1999

Antiapoptotic Bcl-2 family protein expression increases with progression of oligodendroglioma.

BACKGROUND: Altered expression of Bcl-2 family proteins has been associated with tumorigenesis and tumor progression as well as resistance to radiotherapy and chemotherapy. In the current study, Bcl-2 family protein expression was examined in oligodendrogliomas and anaplastic oligodendrogliomas, and an attempt was made to determine whether these proteins accumulate during disease progression and to search for protein expression patterns predictive of time to progression and overall survival. METHODS: A total of 42 oligodendroglioma tissue samples, 26 de novo World Health Organization (WHO) Grade 2 oligodendrogliomas, and 16 de novo WHO Grade 3 anaplastic oligodendrogliomas were studied. Nineteen Grade 2 tumors progressed: 10 again were Grade 2 oligodendrogliomas and 8 had progressed to higher grade lesions. Eight anaplastic oligodendrogliomas progressed: five again were WHO Grade 3 tumors and three were glioblastoma multiforme. Expression of Bcl-2, Bax, Bcl-X, and Mcl-1 proteins and of the proliferation marker Ki-67 was evaluated by immunohistochemistry. Apoptotic cells were quantified by in situ nick translation (ISNT). RESULTS: De novo WHO Grade 2 oligodendrogliomas had higher Bcl-2 scores (P = 0.037), lower MIB-1 scores (P = 0.0012), and lower ISNT scores (P = 0.049) compared with de novo WHO Grade 3 anaplastic oligodendrogliomas. In de novo oligodendrogliomas, low numbers of Bax positive cells were associated with a short time to disease progression (P = 0.043). In de novo anaplastic oligodendrogliomas, low numbers of Bcl-2 positive cells correlated with short survival (P = 0.029). In tumors that had progressed from WHO Grade 3 anaplastic oligodendrogliomas, the authors found significantly more Bcl-X positive (P = 0.005), Mcl-1 positive (P = 0.002), and Bax positive (P = 0.03) cells. CONCLUSIONS: The results of the current study show that progression of oligodendrogliomas and anaplastic oligodendrogliomas is associated with an enhanced expression of antiapoptotic Bcl-2 family proteins.

Adult↗

PubMed1999

p27 modulates cell cycle progression and chemosensitivity in human malignant glioma.

The cell cycle regulatory protein p27, an inhibitor of cyclin-dependent kinases (CDK), has been attributed a role in (i) prognosis in breast and colon cancer, (ii) induction of apoptosis in cancer cells, and (iii) resistance to cancer chemotherapy. Here we report that p27 is widely expressed in human malignant gliomas in vivo and in glioma cell lines in vitro. Serum deprivation or confluency promotes p27 protein accumulation in vitro. Neither baseline p27 levels nor p27 levels induced by confluency or serum deprivation correlate with p53 status or drug sensitivity of human glioma cell lines. Expression of antisense p27 mRNA increased the doubling times in T98G glioma cells, whereas sense p27 mRNA had no such effect. There was a density-dependent and drug-specific modulation of chemosensitivity by sense or antisense mRNA expression in T98G cells. Taken together, these data define a strong p27 response to altered growth conditions and suggest a role for p27 in modulating response to chemotherapy in human malignant glioma cells.

Antineoplastic Agents↗