Kang Jk

Inhibition of human malignant glioma growth in vivo by human recombinant plasminogen kringles 1-3.

Human malignant gliomas are highly vascularized and aggressive tumors. Angiogenesis inhibitors have been shown to induce regression of a variety of primary and metastatic tumors in vivo. However, their usefulness in treating brain tumors is not well understood. Angiostatin, a multiple kringle (1–4 of 5)–containing fragment of plasminogen, is one of the highly effective natural cryptic angiogenesis inhibitors. In our study, the therapeutic efficacy of non‐glycosylated and small molecular size recombinant kringles 1–3 (rPK1–3) was examined in the treatment of brain tumors generated by stereotactic intracerebral implantation of U‐87 human glioma cells in nude mice. Mice bearing tumors 7 days post‐implant were treated daily with rPK1–3 (100 mg/kg) s.c. for 21 days. Treated animals showed suppressed brain tumor growth by greater than 71.2% along with a 3‐fold increase of apoptotic index and suppressed vascularization by 78.9%, without any observable signs of toxicity. Analysis of bFGF and VEGF expression in the tumors of treated animals using immuno‐histochemical methods showed near complete absence of growth factors. Our results indicate that the non‐glycosylated, small molecular size rPK1–3 is an efficient tumoristatic agent for the treatment of intracranial human glioma xenografts in mice and might provide new strategies for the treatment of brain tumors. Int. J. Cancer 82:694–699, 1999.

Merlin suppresses the SRE-dependent transcription by inhibiting the activation of Ras-ERK pathway ☆

The neurofibromatosis type 2 (NF2) gene encodes an intracellular membrane-associated protein called merlin or schwannomin, which is known to be a tumor suppressor. Numerous studies have suggested that merlin is involved in the regulation of cell growth and proliferation. Previously, merlin/schwannomin was reported to block Ras-induced cell proliferation and anchorage-independent cell growth. Also, the N-terminus of merlin was found to suppress cell proliferation, although it appears to be less effective than full-length merlin. However, the inhibitory mechanism of merlin is unknown. In this report, merlin is shown to be effective at suppressing serum/Ras-induced and Elk-mediated SRE dependent transactivation, and serum-induced ERK phosphorylation in NIH3T3 cells. In addition, merlin inhibited serum-induced Elk phosphorylation, a downstream effector of ERKs. Also, the N-terminal deficient merlin mutant could not block serum-induced and Elk-mediated SRE dependent transactivation, although the C-terminal deficient merlin mutant could. These results suggest that merlin inhibits SRE dependent transactivation by repressing serum-induced ERK phosphorylation and its downstream effector, Elk phosphorylation. Also, the N-terminus of merlin may be important for its inhibitory effect. Our results show that merlin acts as a negative regulator of the SRE signaling pathway via the Ras-ERKs pathway.

Surgical management and outcome of tethered cord syndrome in school-aged children, adolescents, and young adults.

OBJECTIVE The adolescent presentation of tethered cord syndrome (TCS) is well-recognized, but continues to pose significant diagnostic and management controversies. The authors conducted a retrospective study of clinical outcomes after surgical intervention in 24 school-aged children, adolescents, and young adults with TCS. METHODS All 83 patients with a lipomyelomeningocele (LMMC) underwent untethering surgery for caudal cord tethering between 1987 and 2007. The clinical charts and follow-up data were reviewed. Of these patients, 24 school-aged children, adolescents, and young adults with TCS were studied with respect to the clinical, radiologic, pathologic features, and surgical outcomes. RESULTS Untethering procedures were performed in 24 patients (age range, 7-25 years) for TCS of various origins (lipoma, lipomyelomeningocele, and tight filum terminale). Specific circumstances involving additional tugging of the already tight conus, and direct trauma to the back precipitated the onset of symptom in 50% of the patients. Diffuse and non-dermatomal leg pain, often referred to the anorectal region, was the most common presenting symptom. Progressive sensorimotor deficits in the lower extremities, as well as bladder and bowel dysfunction, were also common findings, but progressive foot and spinal deformities were noted less frequently. The most common tethered lesions were intradural lipomas, thickened filum and fibrous band adhesions into the placode sac. The surgical outcome was gratifying in relation to pain and motor weakness, but disappointing with respect to resolution of bowel and bladder dysfunction. Of the 24 patients with TCS, pre-operative deficits improved after surgery in 14 (58.3%), remained stable in 8 (33.4%), and worsened in 2 (8.3%). CONCLUSION The pathologic lesions of tethered cord syndrome in school-aged children, adolescents, and young adults, are mostly intradural lipomas and tight filum. It is suggested that the degree of cord traction results in neurologic dysfunction in late life due to abnormal tension, aggravated by trauma or repeated tugging of the conus during exercise. Early diagnosis and adequate surgical release might be the keys to the successful outcome in school-aged children, adolescents, and young adults with TCS.

Temozolomide chemotherapy in patients with recurrent malignant gliomas.

Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.

COMPARISON BETWEEN PEDIATRIC AND ADULT NEUROSURGERY : MANAGEMENT AND FUTURE PERSPECTIVES : TETHERED CORD SYNDROME, HYDROCEPHALUS, CRANIOSYNOSTOSIS

Abstract With creation of the many subdivisions within the field of neurosurgery, neurosurgeons have taken on different roles. It is important for neurosurgeons to understand all the different subjects involved to enable them to build up long-term goals in patient management and research. As pediatric neurosurgeons, the authors give accounts of three characteristic diseases encountered in pediatric patients: spinal dysraphism with tethered cord syndrome, hydrocephalus, and craniosynostosis. Drawing on their personal experience of tethered cord syndrome, the authors stress the pathophysiological mechanisms, clinical characteristics and proper management of the pediatric disease. Because pediatric neurosurgeons cover the whole range of neurosurgical diseases of infancy and childhood, the authors emphasize that their actions can be the basis for the management of general neurosurgical patients. A comparison between pediatric and adult neurosurgery is also drawn, with special reference to the interaction between pediatric and adult neurosurgeons.

Role of bifrontal basal interhemispheric approach in recurrent suprasellar tumors; craniopharyngioma and pituitary tumors

Abstract Recurrent suprasellar tumors, including craniopharyngiomas and pituitary tumors, can be approached with minimal brain retraction, a wider operative field with better orientation and a good view of important neurovascular structures via a bifrontal basal interhemispheric approach (BFBIHA). The authors present their experience of using BFBIHA for removal of recurrent suprasellar tumors, during which they recorded the size and location of each tumor and the degree of tumor extension. Two hundred fifty-four cases of pituitary tumors and 80 cases of craniopharyngiomas were operated on. Recurrent cases were 25 (9.8%) in pituitary tumors and 14 (17.5%) in craniopharyngiomas. Among recurrent cases, nine patients (five recurrent pituitary tumors, four recurrent craniopharyngiomas) were included. Preoperatively, suprasellar extension of the tumors was measured with the aid of radiological images (MRI, MRA, CT). Using line C (mid-sella), the tumors were divided into three groups according to the direction of tumor growth. Group I (one case) contained those with a prechiasmatic location, group II (two cases), those with a suprasellar location, and group III (five cases), those with a retrochiasmatic location. All of the recurrent patients underwent operations by the same approach. All tumors but one were totally resected. There was no operative mortality. In our experience, recurrent suprasellar tumors were safely manipulated with this BFBIHA, preserving important neurovascular structures and hypothalamo–pituitary functions.

History of the Korean Neurosurgical Society and future prospects: how should we educate trainee pediatric neurosurgeons?

It is a great honor for me to have this opportunity to address you today. I think history is very important: it is full of both good things and bad. However, the life we know today would not exist if it were not for history. In other words, we cannot only look forward in life but have to look back and see how we could have lived or acted. I would like to think that history is similar to a mirror, which can show the truth. I think it would be best if we considered our past and advanced into our future life with reasonable reflection. I believe that our lives will be better after examination of our faults in the mirror of history. At this time, I would like to talk about the history of the Korean Neurosurgical Society and its future prospects,: and about how, and with what human resources, we can educate trainee pediatric neurosurgeons. I would like, briefly, to trace the development of the Korean Neurosurgical Society decade by decade, beginning with the Korean War and ending with the present. Also, I would like to talk about the characteristics of the Korean Neurosurgical Society and introduce our training policy: how and with what human resources are we to educate our trainees both to assume scientific responsibility and to become respected figures as pediatric neurosurgeons? The purposes of this address are to introduce the history of the Korean Neurosurgical Society (KNS) and its future prospects and to talk about the characteristics of the KNS and the basis of its training policy.

Deliberate termination of life of newborns with spina bifida

I think this paper “Deliberate termination of life of newborns with spina bifida” is a frightening article and also has a lot of discussion points ethically or religiously. The author Rob de Jong has well discussed concerning the historical overview of the treatment of newborns with myelomeningocele (MMC), analysis of the criteria used for life termination, and presented a newborn with a severe MMC as a reference case. Deliberate termination of a life of a newborn with MMC is allowed openly in The Netherlands. Unbearable and hopeless suffering is the single cited criterion for this termination, together with the opinion that there are no other proper medical means to alleviate this suffering. Although hopeless suffering newborns with several MMC will die finally in spite of the extensive surgical treatment; however, some infants will live and, sometimes, with physical disability, but often with a normal mentation. The nonselective treatment of newborns with MMC, which started in the early 1970s, gives us a picture of a long-term outcome of newborns with MMC [1] and also of the quality of life and health status of adults with spina bifida. Some physicians became distressed after treating children with MMC for years and seeing the degree of their quality of life, dependency, or independency. For the time being, many fetus with MMC can be detected early in pregnancy with amniocentesis and ultrasound diagnosis. Most pregnant couples decide to abort a fetus with MMC, and also, their parents agreed not to treat their child. This attitude toward the treatment for expected disabled newborns with MMC is quite wrong and an unethical social problem and inhumane attitude. Nobody knows the degree of their disability, and it is well reported that disabled children after repaired surgery have maintained a normal ranged of IQ (80–100) despite the variant degree of the disability. They still will join social activities and maintain their life with happiness and satisfaction. In my opinion, we physicians should treat newborns with severe MMC because they are not unbearable and hopeless suffering newborns and not terminally ill and hopeless in their quality-of-life judgments. As we know, a human has a right to live including a human embryo. A political, economical, and social point of view of this deliberate termination of life of newborns with MMC is not allowed, and the right of human life should be deeply reconsidered. It is a right way to continuously study with the objective for the elimination of the disability, to rehabilitate, and finally, able to let them join healthy social work. I absolutely agree with the author’s a critical reappraisal.