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Peter B Dirks

Publications and source records attributed to Peter B Dirks.

15 recordsLinked to original sources
PubMed2006

IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme.

The accurate identification and thorough characterization of tumorigenic cells in glioblastomas are essential to enhance our understanding of their malignant behavior and for the design of strategies that target this important cell population. We report here that, in rat brain, the scaffolding protein IQGAP1 is a marker of brain nestin+ amplifying neural progenitor cells. In a rat model of glioma, IQGAP1 also characterizes a subpopulation of nestin+ amplifying tumor cells in glioblastoma-like tumors but not in tumors with oligodendroglioma features. We next confirmed that IQGAP1 represents a new marker that may help to discriminate human glioblastoma from oligodendrogliomas. In human glioblastoma exclusively, IQGAP1 specifies a subpopulation of amplifying nestin+ cancer cells. Neoplastic IQGAP1+ cells from glioblastoma can be expanded in culture and possess all the characteristics of cancer stem-like progenitors. The similarities between amplifying neural progenitors and glioblastoma amplifying cancer cells may have significant implications for understanding the biology of glioblastoma.

Animals↗
PubMed2004

Identification of human brain tumour initiating cells.

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

AC133 Antigen↗
PubMed2004

Cancer stem cells in nervous system tumors.

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and more recently in solid tumors such as breast cancer suggests that the tumor cell population is heterogeneous with respect to proliferation and differentiation. Recently, several groups have described the existence of a cancer stem cell population in human brain tumors of different phenotypes from both children and adults. The finding of brain tumor stem cells (BTSCs) has been made by applying the principles for cell culture and analysis of normal neural stem cells (NSCs) to brain tumor cell populations and by identification of cell surface markers that allow for isolation of distinct tumor cell populations that can then be studied in vitro and in vivo. A population of brain tumor cells can be enriched for BTSCs by cell sorting of dissociated suspensions of tumor cells for the NSC marker CD133. These CD133+ cells, which also expressed the NSC marker nestin, but not differentiated neural lineage markers, represent a minority fraction of the entire brain tumor cell population, and exclusively generate clonal tumor spheres in suspension culture and exhibit increased self-renewal capacity. BTSCs can be induced to differentiate in vitro into tumor cells that phenotypically resembled the tumor from the patient. Here, we discuss the evidence for and implications of the discovery of a cancer stem cell in human brain tumors. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC. Specific genetic and molecular analyses of the BTSC will further our understanding of the mechanisms of brain tumor growth, reinforcing parallels between normal neurogenesis and brain tumorigenesis.

Adult↗
PubMed2004

Patients with primary brain tumors as organ donors: case report and review of the literature.

Malignancy is considered a contra-indication to organ donation, with a few possible exceptions. We present the case of a child with fatal intracranial hemorrhage from a primary brain tumor (PBT) whose organs were denied for transplant after recovery. We review the literature of organ donors with PBTs in the context of the current organ shortage and discuss the implications for the practicing oncologist. Transmission of donor brain tumor to organ recipients has been documented but the incidence appears to be very low. Risk factors for tumor transmission include underlying donor tumor histology, history of craniotomy and/or shunt placement, use of systemic chemotherapy and radiation therapy, and duration of disease prior to donation. Ongoing data collection by national registries will provide more information on the potential risk to organ recipients. It may be appropriate to expand the donor pool to include donors with PBTs in certain situations. The transplantation team ultimately decides upon the use of organs from specific donors. Many families will appreciate the opportunity to donate specific tissues even if solid organ transplantation is prohibited.

Brain Neoplasms↗
PubMed2004

Measuring the health status of children with hydrocephalus by using a new outcome measure.

OBJECT: In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus. In the present study, they present their initial experience in using the HOQ to quantify the health status in a typical cohort of children with hydrocephalus. METHODS: The mothers of children with hydrocephalus completed the HOQ and, with the child's attending surgeon, provided a global rating of their children's health. An exploratory analysis was performed using a multivariate analysis of variance (ANOVA) to determine which variables might be associated with worse health status. The mothers of 80 children, ranging in age from 5 to 17 years, participated in the study. The mean HOQ Overall Health score was 0.68, a value estimated to be equivalent to a mean health utility score of 0.77. The global health ratings provided by the mothers and the surgeons were moderately correlated with the HOQ scores (Pearson correlations 0.58 and 0.57, respectively). Results of the multivariate ANOVA indicated that the presence of epilepsy was strongly associated with a worse health status (p < 0.0001, F-test). CONCLUSIONS: The health status of a typical sample of children with hydrocephalus was measured using the HOQ. The only consistently significant association with health status found was the presence of epilepsy.

Adolescent↗
PubMed2003

Identification of a cancer stem cell in human brain tumors.

Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.

AC133 Antigen↗
PubMed2003

Slow-flow spinal epidural AVF with venous ectasias: two pediatric case reports.

We report the clinical and imaging findings in the cases of two children who initially presented with back pain related to epidural AVF in the cervicothoracic spine. Both lesions were of particular interest because of their exclusive epidural and paraspinal venous drainage and the presence of the prominent venous pouches in the epidural space. Angiography revealed that one was multifocal and of relatively slow flow. We think that these unusual features have important implications for treatment.

Angiography↗
PubMed2002

p16(ink4a) and retinoic acid modulate rhoA and GFAP expression during induction of a stellate phenotype in U343 MG-A astrocytoma cells.

We previously showed that the expression of p16(ink4a) (p16), in conjunction with retinoic acid (RA) treatment in the p16-deficient astrocytoma cell line, U343 MG-A, induced a potent cell cycle arrest in G(1) associated with changes in morphology. In this study, we investigated the effects of p16 expression and RA treatment on the expression and distribution of actin, glial fibrillary acidic protein (GFAP), and vimentin within the U343 MG-A astrocytoma cytoskeleton. Changes in expression and location of the small GTPase, rhoA, were also examined after p16 expression and RA treatment. We showed that p16 expression and RA treatment led to an increase in the expression of GFAP, as well as its reorganization but that it did not significantly affect actin or vimentin expression. p16 induction in combination with RA treatment resulted in a decreased expression and activation of rhoA as determined by immunocytochemistry and Western blot analysis of soluble and insoluble fractions of cell lysates. Endogenous levels of rhoA expression varied among samples in a panel of astrocytoma cell lines as determined by Western blot analysis. Introduction of a dominant active rhoA mutant into p16-induced, RA-treated U343 MG-A astrocytoma cells was associated with the loss of long astrocytic processes and stellate morphology. These data are among the first to report the pattern of rhoA expression in human astrocytoma cell lines. They furthermore suggest that the stellate cell phenotype observed in U343 MG-A astrocytoma cells after cyclin-dependent kinase inhibitor (CKI) induction and RA treatment is accompanied by an inhibition and inactivation of rhoA in this cell system.

Actin Cytoskeleton↗
PubMed2002

Evaluation of proliferative index and cell cycle protein expression in choroid plexus tumors in children.

Choroid plexus tumors are papillary neoplasms originating from the epithelium of the choroid plexus within the cerebral ventricles. They may be highly proliferative tumors, but detailed studies confirming their proliferative potential are lacking. Accordingly, we performed a clinicopathological correlation study of neoplasms arising from the choroid plexus in children using immunohistochemistry to characterize both their proliferative potential and their degree of cell cycle dysregulation when compared to non-neoplastic choroid epithelium. Twelve children with choroid plexus papillomas (CPPs) and 11 with choroid plexus carcinomas (CPCs) were identified from the time period 1982-1997. The outcome and survival of these children following treatment was determined from the medical record. Immunohistochemical studies were performed on CPPs and CPCs in this patient population and on non-neoplastic choroid epithelium using antibodies to MIB-1, p53, cyclin E, retinoblastoma protein (pRB), p107, and E2F-1. In 5 children with CPCs, tumor tissue was available for immunohistochemistry at a second surgery after cycles of chemotherapy had been given. The mean survival for patients with CPPs was 8.5 years, and with CPCs 5.2 years with a minimum follow-up of 4 years for the group. The expression of cell cycle markers and MIB-1 was greater in CPCs than in CPPs or normal choroid plexus. The expression of MIB-1, p53, pRB, and E2F-1 was significantly lower in patients with CPCs after chemotherapy than before. The MIB-1 labeling index for CPC patients who are alive and well after treatments was 15.19+/-3.2 compared to 22.63+/-3.04 for patients who have died from their disease (P<0.05). We conclude that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than are CPPs. Chemotherapy may work in part on CPCs to decrease their proliferative potential and expression of cell cycle regulatory proteins.

Adolescent↗
PubMed2002

Avulsion transverse ligament injuries in children: successful treatment with nonoperative management. Report of three cases.

Neck injuries in children most commonly affect the upper cervical spine. Injuries of the transverse ligament and its attachments may result in C1-2 instability, but the optimum form of treatment is unknown. Three patients, who ranged in age from 5 to 11 years, sustained transverse atlantal ligament injuries with unilateral avulsion fracture of the osseous tubercle of C-1. One child was injured in a fall and two were involved in motor vehicle accidents. Although all patients presented with neck pain, none exhibited neurological deficits. Plain radiography demonstrated no evidence of osseous injury, but an increased predental interval was noted in each case. Computerized tomography (CT) scanning demonstrated the avulsion fractures, and magnetic resonance imaging revealed evidence of soft-tissue injuries in the occipital-C2 ligamentous complex. All children were managed with external immobilization (halo vest in two and a Sterno-Occipito-Mandibular Immobilizer brace in one), for 6 to 12 weeks. Follow-up CT scanning demonstrated reattachment of the avulsed osseous tubercle, and dynamic cervical spine radiographs revealed the absence of C1-2 instability. The results of these cases suggest a role for external immobilization in the treatment of osseous avulsion injuries of the transverse atlantal ligament in children.

Cervical Vertebrae↗