The progression of gliomas is associated with cancer stem cell phenotype.

Kong, Doo-Sik,Kim, Mi Hyun,Park, Woong-Yang,Suh, Yeon-Lim,Lee, Jung-Il,Park, Kwan,Kim, Jong Hyun,Nam, Do-Hyun National Hellenic Research Foundation 2008 ONCOLOGY REPORTS Vol.19 No.3

<P>Since cancer stem cells in brain tumors were introduced, there have been few explanations regarding the role of cancer stem cells in the progression of glioma. Here, we investigated their major molecular changes in tumor progression in relation to the stem cell subpopulation. Using 12 surgical specimens of gliomatosis cerebri (GC) in the early and advanced stages, we measured the expression of a panel of cell proliferation, microvessel density, microvessel areas, angiogenic factors and their associated receptors. In addition, expression of neural stem cell markers and associated cytokines were examined in tumor tissues by quantitative real-time RT-PCR. Comparing the biological characteristics between the initial infiltrating lesions (n=7) and progressed lesions (n=5), Sox2 and Musashi-1 were expressed in the tumor tissue at an early and a progressed state. Contrary to the early infiltrative phase representing angiogenesis-independent growth, GC with progression showed that nestin (+), PCNA (+) cells and total vessel area (angioectasia) were markedly increased with a higher expression of proangiogenic molecules and their receptors. These results suggest that tumor progression is mediated by cancer stem cells and cross-talk of cancer stem cells along with their environment and are closely associated with angiogenesis-dependent progression and -independent growth.</P>

Hemifacial Spasm : A Neurosurgical Perspective

Kong, Doo-Sik,Park, Kwan The Korean Neurosurgical Society 2007 Journal of Korean neurosurgical society Vol.42 No.5

Hemifacial spasm (HFS) is characterized by tonic clonic contractions of the muscles innervated by the ipsilateral facial nerve. Compression of the facial nerve by an ectatic vessel is widely recognized as the most common underlying etiology. HFS needs to be differentiated from other causes of facial spasms, such as facial tic, ocular myokymia, and blepharospasm. To understand the overall craniofacial abnormalities and to perform the optimal surgical procedures for HFS, we are to review the prevalence, pathophysiology, differential diagnosis, details of each treatment modality, usefulness of brainstem auditory evoked potentials monitoring, debates on the facial EMG, clinical course, and complications from the literature published from 1995 to the present time.

Antitumor activity of ZD6474 in a metastatic orthotopic brain tumor model.

Kong, Doo-Sik,Kim, Mi-Hyun,Jeon, Ji-Won,Kim, Shi-Yeon,Kim, Maeng Sup,Joo, Kyeung Min,Park, Kwan,Nam, Do-Hyun D. A. Spandidos 2008 MOLECULAR MEDICINE REPORTS Vol.1 No.3

<P>The objective of this study was to examine the antitumor effect of ZD6474, an orally available inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR-2) and the epidermal growth factor receptor (EGFR), on tumor growth in an orthotopic metastatic brain tumor model. In order to determine the antitumor mechanism of ZD6474 treatment, in vitro and in vivo studies were performed. Human breast carcinoma cells (MDA-MB-435) were injected using direct intracranial (IC) inoculation (5x105 cells/100 ?l) and internal carotid artery (ICA) injection (5x104 cells/100 ?l) in Balb/c-nu female mice. Daily oral treatment with ZD6474 (50 mg/kg) was initiated on day 14 after the establishment of micrometastasis. Mice (n=12 per group) were sacrificed on day 28. Western blot analysis revealed that the autophosphorylation of EGFR and Akt was increasingly decreased with ZD6474 treatment in lung and brain endothelial cells and the MDA-MB-435 cell line. MTT assay also showed that the in vitro antitumor activity of ZD6474 was dependent on EGFR tyrosine kinase inhibition at a higher dose. Daily oral treatment with ZD6474 led to marked inhibition of metastatic tumor growth in the ICA injection and the direct IC inoculation models (median size 3.5 mm3, range 1.6-13.9 mm3) as compared to the control group (median size 62.4 mm3, range 11.5-206.9 mm3). These results suggest that simultaneous inhibition of both the EGFR and VEGFR-2 signaling pathways has a valuable therapeutic effect through its inhibition of the growth of metastatic brain tumors.</P>

Challenging reconstructive techniques for skull base defect following endoscopic endonasal approaches

Kong, Doo-Sik,Kim, Hyo Yeol,Kim, Se-Hwan,Min, Jin-Young,Nam, Do-Hyun,Park, Kwan,Dhong, Hun-Jong,Kim, Jong Hyun Springer-Verlag 2011 Acta neurochirurgica Vol.153 No.4

One-year Outcome Evaluation after Interspinous Implantation for Degenerative Spinal Stenosis with Segmental Instability

Doo Sik Kong,김은상,어환 대한의학회 2007 Journal of Korean medical science Vol.22 No.2

The authors hypothesized that the placement of the interspinous implant would show a similar clinical outcome to the posterior lumbar interbody fusion (PLIF) in patients having spinal stenosis with mild segmental instability and that this method would be superior to PLIF without significantly affecting degeneration at the adjacent segments. Forty two adult patients having degenerative spinal stenosis with mild segmental instabilit who underwent implantation of CoflexTM (Spine motion, Germany) or PLIF at L4-5 between January 2000 and December 2003 were consecutively selected and studied for one-year clinical outcome. At 12 months after surgery, both groups showed a significant improvement in the visual analogue scale score and Oswestry disability index score for both lower extremity pain and low back pain. However, the range of motion at the upper adjacent segments (L3-4) increased significantly after surgery in the PLIF group, which was not manifested in the CoflexTM group during the follow-up. The authors assumed that interspinous implantation can be an alternative treatment for the spinal stenosis with segmental instability in selected conditions posing less stress on the superior adjacent level than PLIF.

반측성 안면 경련증에 대한 미세 혈관 감압술 후 발생한 지연성 안면 신경 마비의 임상적 특징

공두식(Doo-Sik Kong),이덕주(Deok-Joo Lee),박재성(Jae-Sung Park),이정아(Jeong-A Lee),박관(Kwan Park) 대한두개저학회 2006 대한두개저학회지 Vol.1 No.2

Background : Microvascular decompression for hemifacial spasm provides a long- term cure rate. Delayed facial palsy has only been sporadically described in the literature. The purpose of this report is to evaluate the incidence of delayed facial palsy after MVD and its clinical course. Methods : From January, 1998 to April, 2005, 500 consecutive patients underwent microvascular decompression for hemifacial spasm in our institute. The male: female ratio was about 1:3 (131:369) and their mean age was 44.7 years (range: 19-75 years). We investigated the following clinical characteristics for all the patients: age, gender, side of spasm, the offending structures (the compressing vessels), and infection with herpes simplex virus. Their medical recording and radiological data were reviewed. Results : During this period, 49 patients (9.8%) developed delayed facial palsy after microvascular decompression. There were 38 women and 11 men in this study. The onset of palsy occurred between postoperative day 7 and 23 (average: 12.5 days). The palsy was at least Grade II or worse on the House-Brackmann scale. The mean time to recovery was 5.2 weeks (range: 25 days-17 weeks); delayed facial palsy in 48 patients were improved to the complete recovery, but only one patient had remained weakness at the follow-up examination. Conclusion : The incidence of delayed facial palsy (9.8%) was not so low as has been reported the literatures. Although the degree of facial palsy was variable, almost all patients exhibited a complete recovery without any further special treatment.

Prognostic significance of c‐Met expression in glioblastomas

Kong, Doo‐,Sik,Song, Sang‐,Yong,Kim, Duk‐,Hwan,Joo, Kyeung Min,Yoo, Jin‐,San,Koh, Jong Sung,Dong, Seung Myung,Suh, Yeon‐,Lim,Lee, Jung‐,Il,Park, Kwan,Kim, Jong Hyun Wiley Subscription Services, Inc., A Wiley Company 2009 Cancer Vol.115 No.1

<P><B>Abstract</B></P><P><B>BACKGROUD:</B></P><P>The authors investigated whether expression of c‐Met protein in glioblastomas is associated with overall survival and biologic features representing tumor invasiveness in patients with glioblastomas.</P><P><B>METHODS:</B></P><P>Paraffin‐embedded specimens of glioblastomas from 62 patients treated in a single institution were assessed by immunohistochemical (IHC) analysis of c‐Met expression. On the basis of the clinical data for these patients, the association between c‐Met expression and clinicobiologic features representing tumor invasiveness was analyzed.</P><P><B>RESULTS:</B></P><P>c‐Met overexpression was detected in 29.0% (18 of 62) of glioblastomas. In patients with c‐Met overexpression, the median survival was 11.7 months (95% confidence interval [95% CI], 9.9 months‐13.5 months), compared with a median survival of 14.3 months (95% CI, 7.6 months‐21.0 months) for patients whose tumors had no or little expression of c‐Met (<I>P</I> = .031). On the radiographic analysis, 9 of 18 patients (50%) with tumors overexpressing c‐Met demonstrated invasive and multifocal lesions on the initial magnetic resonance images, whereas only 9 of 44 patients (20.5%) with tumors that expressed no or little c‐Met demonstrated these features (<I>P</I> = .030). Using immunohistochemistry, we also found a significant association between c‐Met expression and matrix metalloproteinase‐2,‐9 (<I>P</I> = .020 and <I>P</I> = .013). Furthermore, Myc overexpression was found to be closely correlated with c‐Met overexpression on IHC analysis (<I>P</I> = .004).</P><P><B>CONCLUSIONS:</B></P><P>The authors suggest that c‐Met overexpression is associated with shorter survival time and poor treatment response in glioblastomas, the mechanism for which is elevated tumor invasiveness on the molecular and clinical phenotypes. This implies that more effective therapeutic strategies targeting c‐Met receptors may have important clinical implication. Cancer 2009. © 2008 American Cancer Society.</P>

Clinical and Radiological Characteristics of Angiomatous Meningiomas

( Juyoung Hwang ),( Doo-sik Kong ),( Ho Jun Seol ),( Do-hyun Nam ),( Jung-il Lee ),( Jung Won Choi ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2016 Brain Tumor Research and Treatment Vol.4 No.2

Background Angiomatous meningioma is a rare histological subtype of meningioma. Therefore, this specific medical condition is rarely reviewed in the literature. In the present work, we report the clinical and radiological features with postoperative outcomes of angiomatous meningioma. Methods This retrospective study included the patients who were pathologically diagnosed with angiomatous meningioma after surgical resection between February 2010 and September 2015 in our institute. We analyzed the clinical data, radiological manifestation, treatment and prognosis of all patients. Results The 15 patients (5 males and 10 females) were diagnosed with angiomatous meningioma during the study period. The median age of patients at the time of surgery was 63 years (range: 40 to 80 years). According to Simpson classification, 7, 5, and 3 patients achieved Simpson grade I, II, and IV resection, respectively. In the follow-up period, recurrence was noted in one patient. Ten out of the 15 patients showed homogeneous enhancement. Two patients demonstrated cystic changes. There was no occurrence of calcification or hemorrhage in our patients. Characteristically, 14 out of 15 patients showed signal voids of vessels. Significant peritumoral edema was observed in the majority of tumors (67%). Conclusion Angiomatous meningiomas are rare benign meningioma. Brain images of angiomatous meningioma usually demonstrate signal void signs and peritumoral edema. In the present study, angiomatous meningiomas showed good prognosis after surgical resection.

이동질량을 받는 단순지지보의 퍼지제어

공용식(Yong-Sik Kong),류봉조(Bong-Jo Ryu),이규섭(Gyu-Seop Lee),류두현(Doo-Hyun Ryu) 한국소음진동공학회 2002 한국소음진동공학회 학술대회논문집 Vol.2002 No.5

The Efficacy and Safety of Microvascular Decompression for Hemifacial Spasm in Elderly Patients

Jeon, Chul-Jin,Kong, Doo-Sik,Lee, Jeong-A,Park, Kwan The Korean Neurosurgical Society 2010 Journal of Korean neurosurgical society Vol.47 No.6

Objective : The purpose of this study was to examine the efficacy and safety of microvascular decompression (MVD) for hemifacial spasm (HFS) in elderly patients. Methods : Between 1997 and June 2008, 1,174 patients had undergone MVD for HFS at our institute. Among these, 53 patients were older than 65 years. We retrospectively reviewed and compared the complication and the cure rates of these patients with those of younger patients. Results : There were 38 females and 15 males. The mean duration of symptoms of HFS of these patients was 94.6 months (range, 12-360 months), compared with 67.2 months (range, 3-360 months) in the younger group. The overall cure rate in elderly patients who underwent MVD for HFS during this period was 96.2%. Permanent cranial nerve dysfunctions, such as hearing loss and facial palsy, were seen in 2 patients (3.8%, 2/53) in the elderly group and 19 patients (1.7%, 19/1121) in the younger group. The difference in permanent cranial nerve dysfunction between the two groups was not statistically significant. There was no operative mortality in either group. Conclusion : Microvascular decompression is the most effective surgical modality available for the treatment of HFS. Results of this study indicate that such technique can be performed in the elderly without higher rates of morbidity or mortality. Any patient with HFS, whose general health is acceptable for undergoing general anesthesia, should be considered as a candidate for MVD.