Coexpression of erythropoietin and its receptor in endolymphatic sac tumors

2005 ◽  
Vol 103 (2) ◽  
pp. 284-288 ◽  
Author(s):  
Timothy W. A. Vogel ◽  
Alexander O. Vortmeyer ◽  
Irina A. Lubensky ◽  
Youn-Soo Lee ◽  
Makoto Furuta ◽  
...  
Keyword(s):  
Immunohistochemical Analysis ◽  
Endolymphatic Sac ◽  
Organ Distribution ◽  
Cell Of Origin ◽  
Endolymphatic Sac Tumor ◽  
Content Type ◽  
Gene Deficiency ◽  
Vhl Disease ◽  
Associated Tumors ◽  
Fine Print

Object. Von Hippel—Lindau (VHL) disease is characterized by multiple tumors in specific organs. The cell of origin and the reason for the particular organ distribution of the tumors remains unknown. Endolymphatic sac tumor (ELST) is one of the lesions associated with VHL disease. Data from previous studies of VHL disease—associated hemangioblastomas (HBs) and renal cell carcinomas (RCCs) have indicated that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth. Methods. The authors studied ELSTs from five patients with VHL germline mutations. Analysis of the five ELST samples revealed loss of the wild-type allele, consistent with Knudson's two-hit hypothesis for tumorigenesis. All five ELST specimens were characterized microscopically and by immunohistochemical analysis. Coexpression of Epo and Epo-R was found in all five tumors on immunohistochemical studies and confirmed through reverse transcription—polymerase chain reaction and Western blot analysis. Conclusions. Expression of Epo appears to be a result of VHL gene deficiency, whereas the simultaneous coexpression of Epo-R may reflect a developmental mechanism of tumorigenesis. Coexpression of Epo and Epo-R in ELSTs together with the morphological and genetic similarities of these lesions with other VHL disease—associated tumors indicates that VHL disease—associated tumors in different organs share common pathogenetic pathways.

Endolymphatic sac tumors in von Hippel—Lindau disease

2004 ◽  
Vol 100 (3) ◽  
pp. 480-487 ◽  
Author(s):  
Daniel Choo ◽  
Lawrence Shotland ◽  
Maryann Mastroianni ◽  
Gladys Glenn ◽  
Carter van Waes ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Family Members ◽  
Magnetic Resonance Images ◽  
Endolymphatic Sac ◽  
Specific Gene ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Vhl Disease ◽  
Fine Print

Object. Von Hippel—Lindau (VHL) disease is a hereditary multiple-neoplasia syndrome mapping to chromosome 3p25–26. Endolymphatic sac (ELS) tumors have been identified as a neoplastic manifestation of VHL disease. The purpose of this study was to evaluate comprehensively the natural history of inner ear disease in a large population of patients with confirmed or suspected VHL disease and to correlate the clinical features with the VHL genotype. Methods. The authors collated and analyzed clinical and genotypic data obtained in patients enrolled in an Institutional Review Board—approved protocol in which families and individuals affected by VHL disease were studied. These data included results from multidisciplinary history workups and physical examinations, imaging studies, and a battery of audiological tests. One hundred seventy-five patients were enrolled in the study, 129 with confirmed VHL disease and 46 of their family members in whom test results for VHL disease were negative and who served as controls. Twenty-one patients had ELS tumors that were evident on magnetic resonance images; three of them had bilateral ELS lesions. Hearing loss, often sudden in onset and severe to profound in nature, vestibulopathy, aural fullness, and tinnitus represented the primary symptoms of ELS tumor. Distinct patterns of auditory and vestibular dysfunction occurred at different stages of the disease. Phenotypic data showed that 17 of 21 patients with ELS tumors did not have pheochromocytomas, whereas all had VHL disease affecting the kidney, all but two had VHL disease affecting the central nervous system, and all but one had disease affecting the pancreas. Genotyping revealed 10 rearrangements (partial deletions), eight single bp substitutions, and one 3-bp insertion. Although there was no difference in the incidence of hearing loss between populations, symptoms of imbalance and aural fullness were more common in patients with VHL disease but without imaging evidence of ELS tumor than they were in family members who did not have VHL disease (p < 0.01). Conclusions. Endolymphatic sac tumors are frequently associated with VHL disease. Symptoms of disequilibrium or aural fullness in patients with VHL disease may be an early indication of endolymphatic dysfunction. Patients with VHL disease provide a unique opportunity to examine the effects of specific gene mutations and a discrete neoplastic process on the human inner ear. The study of ELS tumors in this group also provides a pathological model of ELS function and supplies evidence for a role of the ELS in clinical Ménière-like disease(s).

Endolymphatic sac tumors in patients with and without von Hippel—Lindau disease: the role of genetic mutation, von Hippel—Lindau protein, and hypoxia inducible factor-1α expression

2004 ◽  
Vol 100 (3) ◽  
pp. 488-497 ◽  
Author(s):  
Randy L. Jensen ◽  
David Gillespie ◽  
Paul House ◽  
Lester Layfield ◽  
Clough Shelton
Keyword(s):  
Gene Expression ◽  
Tumor Tissue ◽  
Hypoxia Inducible Factor ◽  
Endolymphatic Sac ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Ca Ix ◽  
Vhl Disease ◽  
Fine Print

Object. Endolymphatic sac (ELS) tumors are low-grade malignancies of the temporal bone that are associated with von Hippel—Lindau (VHL) disease but can also occur sporadically. The VHL gene product VHL protein is important in the regulation of hypoxia inducible factor (HIF)-1α, which controls expression of molecules that are important in angiogenesis and cell metabolism. In this study the authors examine the role of VHL and HIF-1 in ELS tumors. Methods. The ELS tumors from three patients were examined using the following method: DNA from tumor tissue was isolated, amplified by polymerase chain reaction and the VHL gene sequence was compared with the known wild-type sequence. Loss of heterozygosity (LOH) studies were performed to confirm the sequencing data. Immunohistochemical evaluation for VHL, HIF-1α, vascular endothelial growth factor (VEGF), and carbonic anhydrase IX (CA IX) was performed. Snap-frozen tumor tissue was examined using Western blot and HIF-1 immunoassays for HIF-1α and VHL expression. Two patients had sporadic ELS tumors and the other one suffered from VHL disease. Results of VHL gene sequencing were normal in the tissue derived from the sporadic ELS tumors. The ELS tumor, pheochromocytoma, and spinal hemangioblastoma were heterozygous for the same C-to-A transversion found in the germline carried by the patient with VHL disease. No LOH was detected in the tumor tissue obtained in the patient with VHL disease. Expression of HIF-1α, VEGF, and CA IX evaluated using immunohistochemical studies was elevated in the VHL-associated tumors. Nevertheless, Western blots and immunoassays for HIF-1α did not show elevated expression in these tumors. Conclusions. The sporadic and VHL disease—associated ELS tumors in this study had normal VHL-mediated HIF-1 regulation. This is a result of normal VHL gene expression in the case of the sporadic ELS tumor. In the VHL-associated ELS tumor, this is due to one normal copy of the VHL gene and adequate VHL gene expression.

Endolymphatic sac tumor metastatic to the spine

2005 ◽  
Vol 3 (1) ◽  
pp. 68-70 ◽  
Author(s):  
Nicholas C. Bambakidis ◽  
Tina Rodrigue ◽  
Cliff A. Megerian ◽  
Robert A. Ratcheson
Keyword(s):  
Present Report ◽  
Posterior Cranial Fossa ◽  
Endolymphatic Sac ◽  
Invasive Growth ◽  
Distinct Entity ◽  
Endolymphatic Sac Tumor ◽  
Content Type ◽  
Papillary Lesions ◽  
Cranial Fossa ◽  
Fine Print

✓ Endolymphatic sac tumors (ELSTs) are aggressive papillary lesions of the temporal bone. Although histologically benign, they may exhibit invasive growth and destruction of the skull base. Patients generally present with symptoms referable to the lesion's location within the middle or posterior cranial fossa. Although well characterized as a distinct entity, ELSTs involved in metastatic dissemination have never been reported. In the present report the authors describe a case of ELST metastatic to the spine treated with resection.

Tumors of the endolymphatic sac in patients with von Hippel—Lindau disease: implications for their natural history, diagnosis, and treatment

2005 ◽  
Vol 102 (3) ◽  
pp. 503-512 ◽  
Author(s):  
H. Jeffrey Kim ◽  
John A. Butman ◽  
Carmen Brewer ◽  
Christopher Zalewski ◽  
Alexander O. Vortmeyer ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Natural History ◽  
Tumor Resection ◽  
Endolymphatic Sac ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Cranial Nerve Dysfunction ◽  
Vestibular Symptoms ◽  
Vhl Disease ◽  
Fine Print

Object. Endolymphatic sac tumors (ELSTs), which often are associated with von Hippel—Lindau (VHL) disease, cause irreversible hearing loss and vestibulopathy. Clinical and imaging surveillance protocols provide new insights into the natural history, mechanisms of symptom formation, and indications for the treatment of ELSTs. To clarify the uncertainties associated with the pathophysiology and treatment of ELSTs, the authors describe a series of patients with VHL disease in whom serial examinations recorded the development of ELSTs. Methods. Patients with VHL disease were included if serial clinical and imaging studies captured the development of ELSTs, and the patients underwent tumor resection. The patients' clinical, audiological, and imaging characteristics as well as their operative results were analyzed. Five consecutive patients (three men and two women) with a mean age at surgery of 34.8 years and a follow-up period of 6 to 18 months were included in this study. Audiovestibular symptoms were present in three patients before a tumor was evident on neuroimaging. Imaging evidence of an intralabyrinthine hemorrhage coincided with a loss of hearing in three patients. Successful resection of the ELSTs was accomplished by performing a retrolabyrinthine posterior petrosectomy (RLPP). Hearing stabilized and vestibular symptoms resolved after surgery in all patients. No patient has experienced a recurrence. Conclusions. Audiovestibular symptoms, including hearing loss, in patients with VHL disease can be the result of microscopic ELSTs. Once an ELST has been detected, it can be completely resected via an RLPP with preservation of hearing and amelioration of vestibular symptoms. Early detection and surgical treatment of small ELSTs, when hearing is still present, should reduce the incidence and severity of hearing loss, tinnitus, vertigo, and cranial nerve dysfunction, which are associated with these tumors.

Surgical management of spinal cord hemangioblastomas in patients with von Hippel—Lindau disease

2003 ◽  
Vol 98 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Russell R. Lonser ◽  
Robert J. Weil ◽  
John E. Wanebo ◽  
Hetty L. Devroom ◽  
Edward H. Oldfield
Keyword(s):  
Spinal Cord ◽  
Surgical Management ◽  
Postoperative Outcome ◽  
Tumor Location ◽  
Neurological Dysfunction ◽  
Autosomal Dominant Disorder ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Vhl Disease ◽  
Fine Print

Object. Von Hippel—Lindau (VHL) disease is an autosomal-dominant disorder frequently associated with hemangioblastomas of the spinal cord. Because of the slow progression, protean nature, and high frequency of multiple spinal hemangioblastomas associated with VHL disease, the surgical management of these lesions is complex. Because prior reports have not identified the factors that predict which patients with spinal cord hemangioblastomas need surgery or what outcomes of this procedure should be expected, the authors have reviewed a series of patients with VHL disease who underwent resection of spinal hemangioblastomas at a single institution to identify features that might guide surgical management of these patients. Methods. Forty-four consecutive patients with VHL disease (26 men and 18 women) who underwent 55 operations with resection of 86 spinal cord hemangioblastomas (mean age at surgery 34 years; range 20–58 years) at the National Institutes of Health were included in this study (mean clinical follow up 44 months). Patient examination, review of hospital charts, operative findings, and magnetic resonance imaging studies were used to analyze surgical management and its outcome. To evaluate the clinical course, clinical grades were assigned to patients before and after surgery. Preoperative neurological status, tumor size, and tumor location were predictive of postoperative outcome. Patients with no or minimal preoperative neurological dysfunction, with lesions smaller than 500 mm3, and with dorsal lesions were more likely to have no or minimal neurological impairment. Syrinx resolution was the result of tumor removal and was not influenced by whether the syrinx cavity was entered. Conclusions. Spinal cord hemangioblastomas can be safely removed in the majority of patients with VHL disease. Generally in these patients, hemangioblastomas of the spinal cord should be removed when they produce symptoms or signs.

Interleukin-6 overexpression as a marker of malignancy in human gliomas

2001 ◽  
Vol 94 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Christine Rolhion ◽  
Frédérique Penault-Llorca ◽  
Jean-Louis Kémény ◽  
Jean-Jacques Lemaire ◽  
Christiane Jullien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interleukin 6 ◽  
Vascular Endothelial Cells ◽  
Immunohistochemical Analysis ◽  
Vascular Endothelial ◽  
Content Type ◽  
Major Interest ◽  
Polymerase Chain ◽  
The Relationship ◽  
Fine Print

Object. Glioblastomas multiforme (GBMs) grow rapidly and are highly resistant to treatment compared with other glioma types and grades. Consequently, it is of major interest to identify markers of aggressiveness in these tumors that could represent new therapeutic targets. Interleukin (IL)—6 is frequently produced in gliomas and, given its manifold properties, could be considered as a candidate marker. Expression of IL-6 may be involved in cell growth, resistance to chemotherapy and radiotherapy (via an antiapoptotic pathway), and angiogenesis. This study was conducted to test this hypotheses and to evaluate the suitability of IL-6 as a target in the treatment of GBMs. Methods. The authors studied the relationship between the level of IL-6 gene expression as assessed using semiquantitative reverse transcription—polymerase chain reaction and by determining various histological types and grades in a series of 59 gliomas. It was found that GBMs displayed a significantly higher level of IL-6 expression than other types of glioma (p < 0.001). Immunohistochemical analysis revealed that IL-6 was produced mainly by malignant cells and a few vascular endothelial cells. Conclusions. It can be inferred from these findings that IL-6 gene expression is related to glioma aggressiveness and that IL-6 may play a central role in GBM behavior. Interleukin-6, therefore, could be considered as a new potential target in the treatment of GBMs.

The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain

2005 ◽  
Vol 102 ◽  
pp. 225-229 ◽  
Author(s):  
En-Min Wang ◽  
Li Pan ◽  
Bing-Jiang Wang ◽  
Nan Zhang ◽  
Liang-Fu Zhou ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Tumor Control ◽  
Content Type ◽  
Prescription Dose ◽  
The Mean ◽  
Vhl Disease ◽  
The Brain ◽  
Fine Print

Object. The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. Methods. Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel—Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5–55 mm). The mean follow up after GKS was 66 months (range 24–114 months). The mean prescription dose was 17.2 Gy (range 12–24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. Conclusions. Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.

Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation

2005 ◽  
Vol 102 (3) ◽  
pp. 522-525 ◽  
Author(s):  
Gabriel C. Tender ◽  
Stuart Walbridge ◽  
Zoltan Olah ◽  
Laszlo Karai ◽  
Michael Iadarola ◽  
...  
Keyword(s):  
Motor Function ◽  
High Intensity ◽  
Rhesus Monkeys ◽  
Neurogenic Inflammation ◽  
Pain Perception ◽  
Function Analysis ◽  
Immunohistochemical Analysis ◽  
Content Type ◽  
Nociceptive Neurons ◽  
Fine Print

Object. Neuropathic pain is mediated by nociceptive neurons that selectively express the vanilloid receptor 1 (VR1). Resiniferatoxin (RTX) is an excitotoxic VR1 agonist that causes destruction of VR1-positive neurons. To determine whether RTX can be used to ablate VR1-positive neurons selectively and to eliminate hyperalgesia and neurogenic inflammation without affecting tactile sensation and motor function, the authors infused it unilaterally into the trigeminal ganglia in Rhesus monkeys. Methods. Either RTX (three animals) or vehicle (one animal) was directly infused (20 µl) into the right trigeminal ganglion in Rhesus monkeys. Animals were tested postoperatively at 1, 4, and 7 weeks thereafter for touch and pain perception in the trigeminal distribution (application of saline and capsaicin to the cornea). The number of eye blinks, eye wipes, and duration of squinting were recorded. Neurogenic inflammation was tested using capsaicin cream. Animals were killed 4 (one monkey) and 12 (three monkeys) weeks postinfusion. Histological and immunohistochemical analyses were performed. Throughout the duration of the study, response to high-intensity pain stimulation (capsaicin) was selectively and significantly reduced (p < 0.001, RTX-treated compared with vehicle-treated eye [mean ± standard deviation]): blinks, 25.7 ± 4.4 compared with 106.6 ± 20.8; eye wipes, 1.4 ± 0.8 compared with 19.3 ± 2.5; and squinting, 1.4 ± 0.6 seconds compared with 11.4 ± 1.6 seconds. Normal response to sensation was maintained. Animals showed no neurological deficit or sign of toxicity. Neurogenic inflammation was blocked on the RTX-treated side. Immunohistochemical analysis of the RTX-treated ganglia showed selective elimination of VR1-positive neurons. Conclusions. Nociceptive neurons can be selectively ablated by intraganglionic RTX infusion, resulting in the elimination of high-intensity pain perception and neurogenic inflammation while maintaining normal sensation and motor function. Analysis of these findings indicated that intraganglionic RTX infusion may provide a new treatment for pain syndromes such as trigeminal neuralgia as well as others.

The natural history of hemangioblastomas of the central nervous system in patients with von Hippel—Lindau disease

2003 ◽  
Vol 98 (1) ◽  
pp. 82-94 ◽  
Author(s):  
John E. Wanebo ◽  
Russell R. Lonser ◽  
Gladys M. Glenn ◽  
Edward H. Oldfield
Keyword(s):  
Spinal Cord ◽  
Natural History ◽  
Mass Effect ◽  
Content Type ◽  
Von Hippel Lindau ◽  
History Of ◽  
The Central Nervous System ◽  
Brainstem Tumors ◽  
Vhl Disease ◽  
Fine Print

Object. The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel—Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment. Methods. The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts. Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia. The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts. Conclusions. In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect—producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.

Tenascin-C—coated platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model

2005 ◽  
Vol 103 (4) ◽  
pp. 681-686 ◽  
Author(s):  
Naoki Toma ◽  
Kyoko Imanaka-Yoshida ◽  
Taku Takeuchi ◽  
Satoshi Matsushima ◽  
Hiroo Iwata ◽  
...  
Keyword(s):  
Smooth Muscle Actin ◽  
Immunohistochemical Analysis ◽  
Endovascular Embolization ◽  
Male Rats ◽  
Content Type ◽  
Tenascin C ◽  
Platinum Coil ◽  
Common Carotid Arteries ◽  
Platinum Coils ◽  
Fine Print

Object. Detachable platinum coils are widely used in the endovascular treatment of intracranial aneurysms. The use of coil placement produces a higher incidence of aneurysm recurrence compared with surgical clipping. To reduce the incidence of recurrence by promoting clot organization, the authors designed a platinum coil coated with tenascin-C (TNC), an extracellular matrix glycoprotein, and then histologically examined tissue responses. Methods. Platinum coils were prepared by successive coatings with cationic polyethyleneimine and anionic heparin and then TNC or basic fibroblast growth factor (bFGF) was immobilized by affinity binding to the heparin. Six unmodified, six heparin-coated, six bFGF-coated, or eight TNC-coated platinum coils were inserted into ligated common carotid arteries (CCAs) of adult male rats, and CCA segments were harvested after 14 or 28 days. The percentages of organized areas occupying the luminal cavity in unmodified, heparin-coated, bFGF-coated, and TNC-coated groups were 4.8 ± 4.6, 1.6 ± 1.1, 17.9 ± 10.7, and 93.4 ± 6.9%, respectively. In addition, the mean lumen size in the TNC-coated group (0.35 ± 0.23 mm2) was reduced to less than half that of the unmodified group (0.72 ± 0.21 mm2). Immunohistochemical analysis revealed that α—smooth muscle actin—positive cells were a major cellular component of the organized tissue within the TNC-coated coils but not in the bFGF group. Collagen fibrils in the organized areas were also much thicker and denser with TNC-coated coils than with bFGF-coated coils. Conclusions. Placement of TNC-coated coils can remarkably accelerate organization of luminal cavities and reduce their volume, providing improved efficacy of these coils for endovascular embolization.

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