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J M Piepmeier

Publications and source records attributed to J M Piepmeier.

At least 19 recordsLinked to original sources
PubMed1998

Suppression of matrix metalloproteinase-2-mediated cell invasion in U87MG, human glioma cells by anti-microtubule agent: in vitro study.

Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by exposure to estramustine, a cell proliferation assay, a zymogram, a collagenolysis assay and a haptoinvasion assay were used in this study. The zymogram revealed that an activated (62 kDa) form of matrix metalloproteinase-2 diminished with increasing estramustine concentrations. The collagenolysis assay demonstrated approximately 2.5- to 21-fold lower rates of enzymatic activity suppressed by estramustine in a dose-dependent manner at estramustine concentrations of 1, 5, and 10 microM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 microM estramustine group, whereas 1-10 microM estramustine groups revealed significant suppression of invasion from 6 to 24 h in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro using the decreasing available matrix metalloproteinase-2, an effect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treatment of this disease.

Antineoplastic Agents, Alkylating↗
PubMed1997

Low-grade gliomas of chronic epilepsy: a distinct clinical and pathological entity.

The authors present a summary of their recent experience regarding the management of patients with a variety of low-grade gliomas found during the evaluation for chronic epilepsy. These tumors are notable because the long-term patient outcome in this population is significantly better than the anticipated results of patients with the same tumors who do not have chronic epilepsy. Based on the long history of preoperative seizures (median 14 years), the frequent cortical location, and the absence of tumor recurrence or anaplastic transformation and the lack of mortality in this population, low-grade gliomas of chronic epilepsy appear to define a specific pathological entity that separates them from other histologically similar low-grade gliomas. Low-grade gliomas of chronic epilepsy also are notable for the absence of morphological features that characterize with dysembryoplastic neuroepithelial tumors (DNTs). Our evidence suggests that low-grade gliomas of chronic epilepsy should be recognized as a distinct pathological entity.

Adolescent↗
PubMed1997

Low-grade gliomas: introduction and overview.

This issue of the Journal of Neuro-Oncology is devoted to recent investigations of low-grade gliomas. The purpose of this issue is not to debate the relative merits and liabilities of different management strategies for low-grade gliomas, but to present new data concerning novel and innovative approaches to evaluating these lesions. The common theme of many of these reports represents a departure from grading systems that primarily depend on a morphology-based analysis from light microscopy to classify these tumors. The purpose of this review is to present the reasoning behind the selection of authors for this issue of the Journal of Neuro-Oncology and to provide a format for presentation of new ideas concerning these interesting tumors. It is clear that standard classification systems that address only the morphological characteristics of tumor cells can not adequately represent the wide variation in biological activity that is found with these lesions. It is hoped that these articles will stimulate further interest and research into low-grade gliomas that will one day lead to more effective therapy.

Adult↗
PubMed1996

BEHAB (brain enriched hyaluronan binding) is expressed in surgical samples of glioma and in intracranial grafts of invasive glioma cell lines.

Malignant gliomas aggressively invade the surrounding normal brain, whereas brain metastases of nonglial tumors do not. The invasive behavior of gliomas may be mediated by tissue- or tumor-specific extracellular proteins. mRNA for the brain-specific extracellular brain enriched hyaluronan-binding protein (BEHAB) is not detectable in normal adult human cortex or in any nonglioma tumor examined. BEHAB is consistently expressed in surgical samples of glioma (n = 27). Glioma cell lines maintained under standard cell culture conditions or grown as s.c. tumors do not express BEHAB. When grown as intracranial grafts, glioma cell lines that invade the brain express BEHAB, whereas noninvasive cell lines do not. BEHAB is a unique and selective marker for glioma and may play a role in tumor invasion.

Adolescent↗
PubMed1996

In vitro and in vivo inhibition of glioblastoma and neuroblastoma with MDL101731, a novel ribonucleoside diphosphate reductase inhibitor.

We examined the effects of MDL101731, a novel ribonucleoside reductase inhibitor, against human glioblastomas and neuroblastoma, both in vitro and in xenograft models, to determine its activity against malignant brain tumors. MDL101731 produced a concentration-dependent inhibition of both glioblastoma cell lines (HS683 and J889H) and neuroblastoma (SK-N-MC) in nanomolar concentrations (IC50, 30-90 nM). s.c. xenografts of human glioblastoma (D54) in athymic mice increased to five times their initial volume at a median of 7.4 days in control animals, while tumor regression occurred in 12 of 12 animals treated with MDL101731 (100 mg/kg, i.p., two times/week) during 22 days of treatment (P < 0.0001). Intracerebral implants of D54 carried a median survival of 20 days in control animals, whereas animals receiving MDL101731 (100 mg/kg, i.p., two times/week, days 10-35) had a median survival of 46.5 days (P < 0.0001). Intracerebral xenografts of SK-N-MC in athymic mice resulted in a median survival of 23 days in control animals and 26 days in animals treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea 20 mg/kg/week, i.v. x 2; difference not significant). There was 90% survival in animals treated with MDL101731 (200 mg/kg, i.v., two times/week, days 7-35) up to 90 days after implant. These studies indicate that MDL101731 has potent antiproliferative activity against human malignant brain tumors.

Animals↗
PubMed1996

Tumors and approaches to the lateral ventricles. Introduction and overview.

There are a variety of tumors that arise within the lateral ventricles and they present a unique surgical challenge. These lesions commonly are benign and because they frequently are slowly expanding and cause non-specific symptoms they can grow to a large size before they reach medical attention. This report presents an introduction to and an overview of the problems caused by lateral ventricular tumors and summarizes the author's experience in the evaluation and management of these lesions. The most consistent neurological problems associated with lateral ventricular tumors are cognitive impairments commonly associated with hydrocephalus. Consequently, effective management not only requires successful surgical therapy, but also returning the patient to normal neurological and cognitive function. Recognition of these problems and minimizing further injury are the best methods of providing for an optimal outcome.

Astrocytoma↗
PubMed1996

Estramustine in malignant glioma.

Estramustine, a carbamate ester combining 17 beta-estradiol and nornitrogen mustard, has primarily been employed in the treatment of advanced prostatic carcinoma. However, a significant amount of preclinical investigation has been directed toward estramustine's activity against human malignant glioma. These studies have demonstrated that estramustine has potent antiproliferative effects against malignant glioma both in vitro and in vivo. Similar antimitotic effects also have been demonstrated for other carbamate esters. Estramustine does not impair proliferation of nonneoplastic astrocytes at concentrations that inhibit glioma cells. Although the reasons for this selective activity remain to be determined, it has been shown that malignant gliomas expresses an estramustine-specific binding site, estramustine-binding protein, more than brain tissue. In the clinical situation, an uptake and accumulation of estramustine in human glioma tissue have been demonstrated. Estramustine has been shown to enhance the cytotoxic effects of irradiation in relatively radioresistant glioma cells both in cell culture and in a rat glioma model. Estramustine has been regarded as mainly an anti-mitotic drug but recently other effects such as inhibition of DNA synthesis, induction of apoptosis, and membrane alterations have been shown. This report summarizes the preclinical observations concerning the effects of estramustine and related compounds on human malignant gliomas. These findings form the basis for proposing further laboratory and clinical investigation regarding estramustine and human malignant gliomas.

Animals↗
PubMed1996

Targeting microtubule-associated proteins in glioblastoma: a new strategy for selective therapy.

BACKGROUND: This report presents a summary of preclinical data concerning the use of estramustine, an antimicrotubule agent against human glioblastoma cells. The strategy for the investigation of estramustine is predicated on the unique affinity of this agent for microtubule-associated proteins (MAPs). METHODS: A series of laboratory investigations were used to demonstrate antiproliferative effects (MTT assay, colony forming assay, thymidine incorporation), cell cycle synchronization (flow cytometry), intracellular localization of binding sites (immunocytochemistry, electron microscopy), and activity in subcutaneous xenografts of human glioblastoma. RESULTS: Estramustine has potent in vitro activity against human glioblastoma cells and can enhance the cytotoxic effects of ionizing radiation. Estramustine-binding protein was abundantly expressed in glioblastoma cells and may contribute to the selective effects of estramustine on neoplastic cells. This agent has activity against subcutaneous xenografts of human glioblastoma. Synthesized novel estrogen carbamates also can inhibit proliferation of glioblastoma cells. CONCLUSIONS: Cytoskeletal elements (MAPs) of glioblastoma cells may provide a useful target for therapy with agents like estramustine because of the potent antimitotic effects of this agent and its affinity to a protein that is expressed in glioma cells. These observations have stimulated a search for other estrone carbamates with antimitotic activity that exceeds more conventional antimicrotubule agents.

Animals↗
PubMed1996

Yale neurosurgery program.

Organized neurosurgery at Yale began in 1918 with Dr. Sam Harvey. In 1928, Dr. William German became the first surgeon at Yale who was dedicated to neurosurgery. Both of these surgeons were trained by Harvey Cushing, and upon the arrival of Drs. Cushing and Eisenhardt in 1934, Yale developed a strong tradition in surgery of the nervous system. In 1967, Dr. William Collins established a training program for residents that integrated laboratory research and clinical experience. This tradition has continued under the guidance of Dr. Dennis Spencer since 1987. This article provides a brief overview of the history of neurosurgery at Yale, its current practice, and plans for the future.

Connecticut↗
PubMed1996

In vitro inhibition of cell proliferation, viability, and invasiveness in U87MG human glioblastoma cells by estramustine phosphate.

OBJECTIVE: Several determinants of cell motility are highly dependent on the cytoskeleton, in particular, microtubules. To our knowledge, there have been no previous reports regarding the anti-invasive ability by an antimicro-tubule agent, estramustine phosphate (EMP), on glioblastoma cell lines. We investigated the modulated cell proliferation and invasiveness by EMP in vitro. METHODS: We determined the relative survival rate by cell proliferation assay and the percent survival fraction by monotetrazolium assay. Furthermore, an invasion index was used to quantify the migrating and invasive potential of the human glioblastoma cell line, U87MG, in Boiden's chamber with reconstituted basement membrane (Matrigel; Collaborative Research, Lexington, MA). RESULTS: We found that 0.5 mumol/L EMP had no effect in any of the assays. Concentrations of 1, 5, and 10 mumol/L demonstrated a concentration- and time-dependent depression in all of the assays. A range of drug concentration of EMP, 1 to 10 mumol/L, in which cell invasiveness was successfully inhibited, was comparable with antiproliferative capacity. CONCLUSION: The data add to the findings that EMP not only offers selective antiproliferative activity against glioblastoma but also reduces invasiveness, consistent with its main mechanism of action. Such findings form the basis for the development of agents that use non-DNA targets for the treatment of glioblastomas and may improve control over tumor proliferation and invasion.

Antineoplastic Agents, Alkylating↗
PubMed1995

Verapamil treatment attenuates immunoreactive GFAP at cerebral cortical lesion site.

Cerebral cortical lesions were produced using a stereotactic injection system in Sprague-Dawley rats randomly assigned to three groups: (1) needle lesioned and uninjected (Lesioned), (2) needle lesion and simultaneous local injection of 50 or 100 microliters 0.9% saline (L/Saline), and (3) needle lesion and simultaneous local injection of 50 or 100 microliters Verapamil-HCl (VHCL) (2.5 mg/ml (5 mM) Abbott Labs, Chicago, IL), a passive, L-type calcium channel blocker (L/VHCL). The lesioning induced expression of glial fibrillary acidic protein (GFAP), a type of intermediate filament protein expressed in reactive astrocytes, at the lesion site. There was a reduction in GFAP-like immunoreactivity (GFAP-IR) in the L/VHCL group versus the Lesioned and the L/Saline groups. There was a five-fold increase of GFAP-IR at 24 h post lesion in the L/Saline group, but no statistically significant increase seen in the Lesioned or L/VHCL groups at either volume. Pretreatment of the anti-GFAP with VHCL did not impair the antigen labeling. To determine whether differences in pHs, or volume could account for these findings, a second experiment was performed using pH-matched saline or VHCL in 10 microliters volume injected into contralateral hemispheres at the time of lesioning. There was an 80% reduction in GFAP-IR in the L/VHCL group at 72 h compared with the L/Saline group. These data suggest that VHCL may suppress the early increase of GFAP-IR in response to cortical lesion and that reducing transmembrane calcium flux through L-type calcium channels may be the mechanism involved.

Animals↗
PubMed1995

Reconstruction of suboccipital craniectomy defects with hydroxyapatite cement: a preliminary report.

Hydroxyapatite cement, a new biomaterial presently under clinical investigation, has been demonstrated to have potentially wide application in cranial reconstruction. We describe our experience with this biologic bone cement in the reconstruction of suboccipital craniectomy defects in seven patients after vestibular schwannoma removal. With up to 2-year follow-up, cranial bone integrity has been reestablished in five patients. Dissolution of cement has occurred in dependent areas and appears to be technique related. Cranial bone contour appears dependent on the amount of cement used. The frequency of debilitating postoperative headache was reduced in these patients when compared to patients who had no reconstruction of the craniectomy defect. Reconstruction of the bony defect after suboccipital craniectomy with hydroxyapatite cement is not only useful to restore cranial contour, but also appears to reduce some of the functional deficits attributed to this surgical approach.

Biocompatible Materials↗
PubMed1994

Selective antimitotic effects of estramustine correlate with its antimicrotubule properties on glioblastoma and astrocytes.

Estramustine is an estradiol-based agent that accumulates in cells containing estramustine binding protein. Previous studies have shown that this binding site is expressed in human glioblastoma cells and that estramustine accumulates in glioma cells, resulting in a concentration-dependent inhibition of proliferation. We have shown that estramustine treatment results in a rapid inhibition of deoxyribonucleic acid synthesis (within 4 h) in human glioblastoma cells associated with an alteration of cell size and shape, consistent with its known antimicrotubule activity. To extend these findings, we performed an immunohistochemical analysis of microtubules with a monoclonal antibody to beta-tubulin, using a colorimetric assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to measure the antimitotic effects of estramustine on both human glioblastoma and astrocyte cultures. Within 4 hours, estramustine (10 mumol/L) caused a dramatic alteration in the tubulin staining in glioma cells, characterized by a disorganization in microtubules. Cell shape and microtubule staining in astrocytes were relatively preserved. Estramustine had a concentration-dependent cytotoxic effect in tumor cultures, whereas it had no effect on astrocyte viability at any concentration. Differences in the antimitotic effects do not appear to be related to variations in proliferation rates among these different types of cells. These data suggest that although estramustine is a potent inhibitor of proliferation in glioblastoma cells, it has modest antiproliferative effects on astrocytes and its selective activity is closely correlated with its antimicrotubule properties.

Astrocytes↗
PubMed1993

Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.

Brain Neoplasms↗
PubMed1993

Low-grade astrocytomas may arise from different astrocyte lineages.

The management of low-grade astrocytomas remains a challenge. Although the majority of these tumors have common histological features, they may have very different clinical manifestations and rates of proliferation. Because low-grade astrocytomas are composed of relatively well-differentiated neoplastic cells that closely resemble the astrocytic phenotype, it is possible that some of these lesions express antigens that characterize astrocyte lineages. The authors performed an immunohistochemical analysis of 20 low-grade astrocytomas with A2B5, a monoclonal antibody to a ganglioside found in early postnatal Type 2 (fibrillary) astrocytes, but absent in Type 1 (protoplasmic) astrocytes, and anti-glial fibrillary acidic protein to determine whether the expression of these antigens could be used to determine the histogenesis of these tumors. These findings were compared with the clinical and imaging features of these tumors. The percentages of cells positive for A2B5 and glial fibrillary acidic protein was strongly correlated with the location of the tumor within the cortex or white matter and with the length of preoperative symptoms. Tumors based in the cortex contained significantly fewer A2B5-positive and glial fibrillary acidic protein-positive cells than white matter tumors. In addition, lesions that caused a relatively short period of preoperative symptoms (< 1 year) had significantly more A2B5-positive and glial fibrillary acidic protein-positive cells than lesions responsible for a long preoperative history (mean, 12.9 years). These findings suggest that slow-growing, cortically based low-grade astrocytomas have a phenotype consistent with the Type 1 (protoplasmic) astrocyte lineage, while white matter low-grade astrocytomas express antigens consistent with the Type 2 (fibrillary) astrocyte lineage.

Adolescent↗
PubMed1990

Extensive wounds of the spine: a comprehensive approach to debridement and reconstruction.

Extensive wounds involving the spine (greater than three vertebral segments exposed) may threaten its indispensable roles of biomechanical support and vital neurologic function. Although there have been select reports of specific flap applications in this body region in the reconstructive surgical literature, there has been a paucity of comprehensive descriptions of pertinent anatomy, pathophysiology, and the perioperative care of such patients--including the degree to which the spine is suited to aggressive debridement. Four patients with complex spine wounds involving greater than three vertebral segments were treated by the authors from 1986 through 1988. These patients ranged from 28 to 80 years of age. They were all found to have multiple risk factors, including neoplasm (4), severe nutritional depletion (3), advanced age (2), wound sepsis (2), and multiple other general medical problems (4). All patients underwent wide bony and soft-tissue debridement. A new clinically essential four-pillar concept of spinal support predicted spinal instability in two of the four patients. These patients could thus be protected from neurologic compromise with internal stabilization (1) or external orthotic support (1). Wound closure was achieved with skin graft (1) or traditional or extended musculocutaneous flap coverage (3). With 7 to 20 months of follow-up, wound healing has been complete in all patients despite a 100 percent complication rate and one late postoperative death. Multisegment spine wounds tend to arise in the setting of multiple medical problems or risk factors. Despite these risk factors and a high postoperative complication rate, gratifying results may be achieved in these patients with a comprehensive understanding of regional surgical anatomy and a multidisciplinary approach to their care.

Adult↗
PubMed1988

Primary leptomeningeal sarcomatosis. Case report.

This report describes a case of primary leptomeningeal sarcomatosis in a 50-year-old man who presented with progressive deficits involving multiple cranial nerves and spinal roots. Despite the clinical evidence supporting a diffuse process involving the leptomeninges, radiological, serological, and cerebrospinal fluid examinations failed to reveal the cause of the disorder. Consequently, surgical exploration and biopsy were required to obtain a pathological diagnosis. This case report illustrates the difficulty in diagnosing this disease and supports the use of open biopsy in patients with chronic meningeal disease when the diagnosis cannot be established by less invasive methods.

Humans↗