Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Light- and electron microscopical investigations of the pathogenesis of Recklinghausen's neurofibromatosis can support those views which consider the Schwanncells in these tumors to develop from mesenchymal cells, that means from reticular fibroblasts. It seems to be of special interest that these cells while transforming to Schwann cells become successive coated with a glycocalyx (surface coat); The whirle-or onion skin like formation of the tumor cells lead to a splitting of the ground substance into numerous compartments accompanied by a change in ground substance composition. This obviously cohere with an increasing number of mast cells within the tumor. It may be that these arrangements of the tumor tissue plays an important part in tumor growth. With this, the great importance of a regular composition of the extracellular matrix and cell surface coats for an undisturbed flow of information from cell to cell is discussed.
 ...
PMID:[Pathogenesis of neurofibromatosis. Light- and electron microscopical investigations (author's transl)]. 82 88

Four cases of malignant schwannoma arising in Recklinghausen's disease are described. The 4 patients, aged 38, 41, 44 and 38, 2 men and 2 women, had up to child-head-sized tumors in the neck, back, axilla and retroperitoneum. Oncostatic chemotherapy and irradiation were ineffective against the malignant schwannoma. In three, surgically tumor-resected cases, local recurrence and rapid tumor growth occurred. Histologically, malignant schwannoma was characterized by the presence of a few collagen fibers among the tumor cells, but abundant argentaffin fibers. Numerous mast cells are frequently seen in neurofibroma, but almost never in malignant schwannoma. In Case 3, with mild atypism, tumor cells were positive for S100 protein.
 ...
PMID:[Malignant schwannoma arising in Recklinghausen's disease--report of 4 cases]. 392 28

To assess the natural history of optic pathway tumors (OPT) in children with neurofibromatosis type 1 (NF-1), from January 1985 through May 1993 we performed a prospective, longitudinal study of OPT in an unselected population of children with NF-1. Of 227 children with NF-1 seen in a specialty clinic, 176 (77%) underwent neuroimaging. Children in whom tumors were identified were followed closely by both repeated neuroimaging and ophthalmologic examinations to detect tumor growth or visual deterioration. Thirty-three children (19%) were found to have OPT at a median age of 4.2 years. The median age of children who had ophthalmologic complaints was significantly lower than that of children who had no such complaints (1.9 vs 5.3 years; p < 0.001). Although eight tumors were discovered because of ophthalmologic complaints or evidence of precocious puberty, 25 children (76%) were free of symptoms at the time of diagnosis. Twenty-one children (64%) had normal ophthalmologic findings at diagnosis; six children, all with chiasmal tumors, had previously unrecognized decreased visual acuity. Only three children (9%) had evidence of either tumor growth or deteriorating vision after diagnosis; the median duration of neuroimaging follow-up was 2.4 years (range, 0.2 to 7.2 years) and of ophthalmologic examinations 3.4 years (range, 0.2 to 8.1 years). All symptomatic OPT were diagnosed before 6 years of age. We conclude that OPT rarely progress during the next few years in children with NF-1 once the OPT have been discovered. The utility of screening neuroimaging for OPT in symptom-free children with NF-1 appears very limited.
 ...
PMID:Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study. 765 89

We present a series of 31 cases of optic glioma associated with neurofibromatosis type 1 in patients under 11 years of age. They represent 64% of all the optic gliomas seen in our service between September 1965 and September 1993. The optic nerves were affected in 25 cases (83%); 9 children (30%) had a isolated, unilateral tumor; 16 (53%) had involvement of the optic chiasm as well as of one or both optic nerves. In 6 cases (19%) only the chiasm was affected, with or without involvement of other intracerebral structures. A coincidental orbital plexiform neurofibroma was associated with a poor prognosis. Other complications included 8 cases (26%) presenting with slowly developing aqueductal stenosis requiring treatment with a shunt. High-resolution computed-tomographic scans provided well-defined images for the diagnosis of optic nerve glioma, but magnetic resonance imaging was the preferred procedure for the diagnosis of gliomas involving the chiasm and the optic tracts and radiations, particularly if there was no mass effect. In our patients, tumor growth was hardly noticeable during follow-up even up to 20 years, with no difference between patients who were treated with radiation and those who were not treated. However, endocrine disturbances developed in all cases subjected to radiotherapy, and were less frequent in untreated patients. Aqueductal stenosis was observed with similar frequency among both treated or untreated patients. Three patients died, two due to complications of hydrocephalus secondary to aqueductal stenosis and one because of respiratory problems due to compression of the hypothalamus and brainstem by the chiasm tumor. Two of the 3 patients who died had orbital plexiform neurofibroma.
 ...
PMID:Optic gliomas in neurofibromatosis type 1 (NF-1). Presentation of 31 cases. 802 21

Although most visual pathway tumors are low-grade gliomas their biologic behavior is highly unpredictable. In order to determine whether assessment of proliferative activity can assist in predicting tumor behavior, we studied the MIB-1 labeling indices (MIB-1 LIs) in surgical specimens and monitored tumor growth in 31 consecutive children operated on between 1978 and 1997. The MIB-1 LIs at diagnosis varied from 0-10.6% (mean +/- SD, 3.27 +/- 2.49%). Tumor progression occurred in 19 patients leading to death in seven, three of whom had neurofibromatosis type 1 (NF1). No association between MIB-1 LI at initial diagnosis and both progression free and overall survival was apparent. However, the MIB-1 LIs increased to 15.2% and 18% in two patients with NF1 who developed highly malignant gliomas 6 and 6.5 years after irradiation. In the remaining patients the MIB-1 LIs did not change significantly over time in a total of 17 repeat surgeries. Three patients with LIs of 6.8%, 10.6% and 8.8% are stable after 6, 4.5 and 3.5 years with partial resection, biopsy and subtotal resection, respectively, and no further therapy in the first two and chemotherapy in the latter. Three patients (10%) with LIs of 6.4%, 4.8% and 2.2% either presented with or developed leptomeningeal spread during follow-up. While MIB-1 LI does not appear to assist in clinical decision making patient numbers were too small to find out whether response to chemotherapy varies with proliferative potential.
 ...
PMID:Proliferative activity as measured by MIB-1 labeling index and long-term outcome of visual pathway astrocytomas in children. 1042 Oct 72

Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of < 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2-3%, and a p53 LI of < 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2-12%, a p53 LI of 2-8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI < 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2-3% and a p53 LI of < 1%. Diffuse astrocytomas have both Ki-67 and p53 LI > 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of > 1% appears to favor the diagnosis of diffuse astrocytoma.
 ...
PMID:Gliomas of the optic nerve: histological, immunohistochemical (MIB-1 and p53), and MRI analysis. 1080 2

Neurofibromatosis type 1 (NF1) represents a major risk factor for development of malignancy, particularly malignant peripheral nerve sheath tumors (MPNST), optic gliomas, other gliomas, and leukemias. The oncologist will see NF1 patients referred for treatment of malignancy, and should be alert to the possibility of undiagnosed NF1 among patients with cancer. Brain tumors tend to have a more indolent course in NF1 than in the general population, and hence are best managed conservatively. MPNST, in contrast, do not respond to standard chemotherapy or radiation therapy. The most effective treatment of MPNST appears to be early diagnosis and surgery, but early diagnosis is hampered by frequent occurrence within preexisting large tumors, making new growth or change difficult to detect. New insights into pathogenesis now offer hope of development of specific methods of treatment with reduced toxicity and more precise molecular targeting. There is an urgent need, however, to develop methods to measure tumor growth and monitor outcomes, develop preclinical drug screening systems, and further explore the pathogenesis of the disorder to determine whether mechanisms other than Ras regulation may be important in pathogenesis.
 ...
PMID:Malignancy in neurofibromatosis type 1. 1111 May 99

Loss of the tumor suppressor gene NF1 in neurofibromatosis type 1 (NF1) contributes to the development of a variety of tumors, including malignant peripheral nerve sheath tumors (MPNST) and benign neurofibromas. Of the different cell types found in neurofibromas, Schwann cells usually provide between 40 and 80%, and are thought to be critical for tumor growth. Here we describe the identification of growth factors that are upregulated in NF1-/- mouse Schwann cells and are potential regulators of angiogenesis and cell growth. Basic fibroblast growth factor (FGF-2), platelet-derived growth factor (PDGF) and midkine (MK) were found to be induced by loss of neurofibromin and MK was further characterized. MK was induced in human neurofibromas, schwannomas, and various nervous system tumors associated with NF1 or NF2; midkine showed an expression pattern overlapping but distinct from its homolog pleiotrophin (PTN). Immunohistochemistry revealed expression of MK in S-100 positive Schwann cells of dermal and plexiform neurofibromas, and in endothelial cells of tumor blood vessels, but not in normal blood vessels. Furthermore, MK demonstrated potent mitogenic activity for human systemic and brain endothelial cells in vitro and stimulated proliferation and soft agar colony formation of human MPNST derived S100 positive cells and fibroblastoid cells derived from an NF1 neurofibroma. The data support a possible central role for MK as a mediator of angiogenesis and neurofibroma growth in NF1. Oncogene (2001) 20, 97 - 105.
 ...
PMID:The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells. 1124 8

Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic diseases affecting adults and children. Neurofibromas are one of the most common of the protean manifestations of NF1. Plexiform neurofibromas, which will frequently cause cosmetic abnormalities, pain, and neurologic deficits, are composed of "neoplastic" Schwann cells accompanied by other participating cellular and noncellular components. There is increasing evidence that loss of NF1 expression in neoplastic Schwann cells is associated with elevated levels of activated RAS, supporting the notion that the NF1 gene product, neurofibromin, acts as a growth regulator by inhibiting ras growth-promoting activity. In addition, there is increasing evidence that other cooperating events, which may be under cytokine modulation, are important for neurofibroma development and growth. Treatment of plexiform neurofibromas has been empiric, with surgery being the primary option for those with progressive lesions causing a major degree of morbidity. The efficacy of alternative treatment approaches, including the use of antihistamines, maturation agents, and antiangiogenic drugs, has been questionable. More recently, biologic-based therapeutic approaches, using drugs that target the molecular genetic underpinnings of plexiform neurofibromas or cytokines believed important in tumor growth, have been initiated. Evaluation of such trials is hindered by the unpredictable natural history of plexiform neurofibromas and difficulties in determining objective response in tumors that are notoriously large and irregular in shape. Innovative neuroimaging techniques and the incorporation of quality-of-life scales may be helpful in evaluation of therapeutic interventions. The ability to design more rational therapies for NF1-associated neurofibromas is heavily predicated on an improved understanding of the molecular and cellular biology of the cells involved in neurofibroma formation and growth.
 ...
PMID:Plexiform neurofibromas in NF1: toward biologic-based therapy. 1204 25

Neurofibromas are benign tumors arising from neuroectodermal tissues. They may occur as solitary lesions, or multiple, in which case they are referred to as neurofibromatosis, or von Recklinghausen's disease. We report about a 17-year-old patient with neurofibromatous elephantiasis located in the lateral aspect of the left hemithorax. CT showed massive chest wall infiltration and retroperitoneal tumor growth, but no abnormalities of the cranium. Our surgical treatment consisted of a two-stage, palliative tumor debulking and defect coverage with a splitthickness skin graft. The operative and postoperative course was uneventful.
 ...
PMID:[Elephantiasis of the thoracic wall within the scope of von Recklinghausen neurofibromatosis, case report]. 1262 92


1 2 3 4 5 Next >>