Report of two cases

PI3K/Akt signalling pathway and cancer ☆

Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells. We find that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew. Under conditions promoting differentiation, individual cells are multipotent, giving rise to both neurons and glia, in proportions that reflect the tumor of origin. Unlike normal neural stem cells, however, tumor-derived progenitors have an unusual capacity to proliferate and sometimes differentiate into abnormal cells with multiple differentiation markers. Gene expression analysis reveals that both whole tumors and tumor-derived neurospheres express many genes characteristic of neural and other stem cells, including CD133, Sox2, musashi-1, bmi-1, maternal embryonic leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells migrate, produce neurons and glia, and continue to proliferate for more than 4 weeks. The results show that pediatric brain tumors contain neural stem-like cells with altered characteristics that may contribute to tumorigenesis. This finding may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.

https://www.pnas.org/content/pnas/100/25/15178.full.pdf

Cancerous stem cells can arise from pediatric brain tumors

The new edition of the World Health Organization (WHO) book on 'Histological Typing of Tumours of the Central Nervous System' reflects the progress in brain tumour classification which has been achieved since publication of the first edition in 1979. Several new tumour entities have been added, including the pleomorphic xanthoastrocytoma, central neurocytoma, the infantile desmoplastic astrocytoma/ganglioglioma, and the dysembryoplastic neuroepithelial tumour. The list of histological variants has also been expanded. In line with recent morphological and molecular data on glioma progression, the glioblastoma is now grouped together with astrocytic tumours. The classification of childhood tumours has been largely retained, the diagnosis primitive neuroectodermal tumour (PNET) only being recommended as a generic term for cerebellar medulloblastomas and neoplasms that are histologically indistinguishable from medulloblastoma but located in the CNS at sites other than the cerebellum. The WHO grading scheme was revised and adapted to new entities but its use, as before, remains optional.

The new WHO classification of brain tumours.

The health-care facility environment is rarely implicated in disease transmission, except among patients who are immunocompromised. Nonetheless, inadvertent exposures to environmental pathogens (e.g., Aspergillus spp. and Legionella spp.) or airborne pathogens (e.g., Mycobacterium tuberculosis and varicella-zoster virus) can result in adverse patient outcomes and cause illness among health-care workers. Environmental infection-control strategies and engineering controls can effectively prevent these infections. The incidence of health-care--associated infections and pseudo-outbreaks can be minimized by 1) appropriate use of cleaners and disinfectants; 2) appropriate maintenance of medical equipment (e.g., automated endoscope reprocessors or hydrotherapy equipment); 3) adherence to water-quality standards for hemodialysis, and to ventilation standards for specialized care environments (e.g., airborne infection isolation rooms, protective environments, or operating rooms); and 4) prompt management of water intrusion into the facility. Routine environmental sampling is not usually advised, except for water quality determinations in hemodialysis settings and other situations where sampling is directed by epidemiologic principles, and results can be applied directly to infection-control decisions. This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations. These include 1) evidence-based recommendations supported by studies; 2) requirements of federal agencies (e.g., Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Department of Labor, Occupational Safety and Health Administration, and U.S. Department of Justice); 3) guidelines and standards from building and equipment professional organizations (e.g., American Institute of Architects, Association for the Advancement of Medical Instrumentation, and American Society of Heating, Refrigeration, and Air-Conditioning Engineers); 4) recommendations derived from scientific theory or rationale; and 5) experienced opinions based upon infection-control and engineering practices. The report also suggests a series of performance measurements as a means to evaluate infection-control efforts.

Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC)

Primitive neuroectodermal tumors/medulloblastoma (PNET/MB) have similarities to neuroectodermal progenitor cells of the developing CNS. Since insulin-like growth factor I (IGF-I) exerts pleiotrophic effects on cells in the developing CNS, we evaluated the production, mitogenic effects and signaling pathways of IGF-I in PNET/MB cells and found that IGF-I is an autocrine growth factor in human PNET/MB cell lines tested. Stimulation of DAOY cells by IGF-I led to phosphorylation of its cognate receptor (IGF-IR) and resulted in cell proliferation. These effects of IGF-I were suppressed by IGF-IR blocking antibodies and by PD 98059, MAP kinase pathway inhibitor. The results demonstrate the existence of an autocrine IGF-I/IGF-IR loop and indicate that IGF-I promotes proliferation via MAP kinase pathway.

Autocrine secreted insulin-like growth factor-I stimulates MAP kinase-dependent mitogenic effects in human primitive neuroectodermal tumor/medulloblastoma.

Children with shunted hydrocephalus often have a myriad of other medical conditions. When these concomitant problems involve the pleura, peritoneum, and/or the venous system, placement of the distal catheter may prove to be problematic. This report presents preliminary results in three hydrocephalic children following ventriculofemoroatrial shunt placement. The peritoneal and pleural cavities in each of these children were compromised and there was no vascular access into the superior vena cava due to intercurrent disease. An alternative technique for ventriculoperitoneal shunt placement was performed via the femoral vein. Fluoroscopic guidance was used to confirm the intraatrial position of the distal end of the shunt catheter. Follow-up review to date shows no complications. This newly described technique provides a feasible alternative to distal shunt catheter placement in patients in whom more traditional sites are unavailable.

Ventriculofemoroatrial shunt: a viable alternative for the treatment of hydrocephalus. Technical note.

To evaluate potential synergistic interactions between topoisomerase I (Topo I) inhibitors, i.e. camptothecin (CPT) and topotecan (TPT), and chemotherapeutic agents known to be active in treatment of brain tumors, in vitro studies were conducted with human glioma and medulloblastoma cell lines. Tumo

Synergistic cytotoxicity of topoisomerase I inhibitors with alkylating agents and etoposide in human brain tumor cell lines.

Hydranencephaly versus Maximal HydrocephalusAn Important Clinical Distinction

OBJECTIVE: To report four children with visual impairment associated with mutism after posterior fossa surgery Mutism after posterior fossa surgery is a well-described phenomena, but to our knowledge, visual impairment has not been reported in association with it METHODS: Record review of four children (age range, 3-7 yr) who underwent posterior fossa surgery (via suboccipital craniotomies) for removal of a medulloblastoma (three patients) or ependymoma (one patient) Each presented with headache, ataxia, or nausea and vomiting, but none had preoperative visual complaints other than diplopia Postoperatively, all patients were mute, and because of apparent visual loss, neuro-ophthalmic consultation was requested Postoperative scans and examinations were also reviewed RESULTS: Each child was awake but appeared withdrawn without verbal output No child blinked to threat or fixed or followed In each case, pupillary reactivity was normal, and funduscopic examinations revealed only papilledema One child reached for money Within weeks or months postoperatively, the mutism spontaneously resolved, and visual behavior in general improved, roughly in parallel During the follow-up period, papilledema resolved and the disc color was normal in each case Magnetic resonance images obtained postoperatively revealed nothing remarkable, except surgical defects, without lesions in the retrogeniculate pathway CONCLUSION: Impaired visual behavior, mimicking cortical visual loss, may be associated with mutism after posterior fossa surgery in children The prognosis for recovery is excellent and parallels the return of normal speech The mechanism is unclear

Leslie N. Sutton

Papers

Autocrine secreted insulin-like growth factor-I stimulates MAP kinase-dependent mitogenic effects in human primitive neuroectodermal tumor/medulloblastoma.

Ventriculofemoroatrial shunt: a viable alternative for the treatment of hydrocephalus. Technical note.

Synergistic cytotoxicity of topoisomerase I inhibitors with alkylating agents and etoposide in human brain tumor cell lines.

Hydranencephaly versus Maximal HydrocephalusAn Important Clinical Distinction

Visual impairment associated with mutism after posterior fossa surgery in children.