• The Microorganisms and Industry
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• v.19 no.4
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• pp.32-35
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• 1993

ras는 활성화 형태인 GTP bound form과 비활성화 형태인 GDP bound form의 두 형태로 존재하며 두 형태를 매개하는 regulatory protein들에 의해 그 activity가 조절된다. 또한 ras는 GTP와 GDP에 강한 친화성이 있으며 세포내에는 GTP보다 GDP가 더 많이 있어서 평소에는 ras가 GDP와 결합하고 있다가 활성화될때만 GTP와 결합하는 것으로 추정된다. GDP bound ras는 guanine nucloetide exchange protein(GEP)에 의해 활성화된 GTP bound form으로 전환되며 ras의 기능이 발휘된 후에는 GTPase activating protein(GAP)에 의해 비활성화된다. Yeast의 경우 IRA1과 2의 product가 GAP의 역할을 하는 것으로 알려져 있고 CDC25 gene의 product가 GEP의 기능을 담당하는 것으로 알려져 있다. NF1 gene은 Von Recklinghausen Neurofibromatosis Type I 질병을 가진 환자에게서 발견되었는데 부분적으로 sequencing한 결과에 따르면 yeast의 IRA1/2, mammalian GAP gene product와 protein homology가 높은 것으로 나타났다. Yeast의 경우 IRA1/2 gene의 손실이나 mammalian ras gene의 transformation으로 인한 heat shock sensitivity가 NF1 gene(2,3) 혹은 GAP(4)의 expression으로 suppression된 것으로 보아 NF1이 GAP protein으로서 ras를 불활성화 시킨다는 것이 판명되었다. 결론적으로 ras의 활성은 GTP bound 혹은 GDP bound의 양쪽형태를 이동하면서 조절되는데 이 기능은 GAP과 GEP 또는 그의 유사 protein들에 의해 수행되며 이러한 regulatory protein들은 growth factor, cytokine 그리고 protein kinase 같은 signal에 의해 활성화된다고 생각된다. 본 총설에서는 ras protein의 여러가지 성질보다는 ras의 modification과 관련하여 항암제로 사용할 수 있는 ras에 specific한 약품개발의 가능성과 현재 알려진 ras의 inhibitor를 중심으로 논하고자 한다.

• Archives of Plastic Surgery
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• v.38 no.3
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• pp.257-262
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• 2011

Purpose: In neurofibromatosis patients, complete surgical excision of the mass is almost impossible and surgical treatment usually consists of multiple serial excisions that only result in a debulking effect. Remnant tumor mass has a gravitational effect on facial soft tissues that leads to sagging of skin and soft tissue, and eventually, facial disfigurement and asymmetry. The purpose of our surgical method is to perform soft tissue lifting with longer lasting effect with less surgical risk of damaging facial nerve and vessels. With external fixation using K-wire or surgical screw, the procedure only called for a short incision length and had additional adhesive properties that enabled anchoring of soft tissue in a lifted position for a longer postoperative period. Methods: A total of 5 neurofibromatosis patients (NF-1) visited our clinic for mass reduction and face lifting. The age of patients ranged from 13 to 42 (mean 28.8 years), and most patients had a long history of multiple excisions in the past. Face lifting was performed in 2 different areas, the periorbital area in 3 patients, and the midface in 2 patients. The materials used in fixation of retaining ligament were K-wire (n=3) and titanium screw (n=2). Results: Follow up period was from 5 month to 3 years and 1 month (mean=2 years and 1 month). All patients conveyed satisfaction with the results and no major complications were reported. The lifting effect lasted for as long as 3 years, and there were no complaints of relapse of soft tissue depression or sagging within the operated area. 1 patient (M/13) needed secondary k-wire insertion and additional mass excision in 1 year and 10 months postoperatively due to tumor growth. In two patients with K-wire fixation, mild dimpling and tenderness were observed in the follow up period, but in about 2 months postoperatively, dimpling was relieved and there was no need for removal of fixating material. Conclusion: Surgical lifting in neurofibromatosis patients can be challenging, for mass excision cannot be done completely and gravitational effect by residual mass can be persistent. External fixation of the retaining ligament in patients with neurofibromatosis can give satisfactory results-for incision length is relatively shorter, and the lifting effect can last longer compared to other various face lifting techniques.

• Archives of Plastic Surgery
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• v.40 no.1
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• pp.57-61
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• 2013

Background Von Recklinghausen disease or neurofibromatosis type 1 is an autosomal dominant genetic disorder of chromosome 17q11.2. The most common characteristic findings of NF 1 include multiple and recurrent cutaneous neurofibromas associated with psychosocial distress. Methods Sixteen patients (9 female, 7 male; average age, 31 years; range, 16 to 67 years) with multiple cutaneous neurofibromas between March 2010 and February 2012 were included in the study. All patients were treated with radiosurgical ablation and excision under general anesthesia. Results All 16 patients were satisfied with the results, when questioned directly during the outpatient department follow-up. The only complaint from a few patients was minimal scarring, but acceptable results were obtained in the end. Conclusions The radiofrequency procedure is almost bloodless and quick, creating a smaller necrotizing zone. Therefore, instead of employing the time consuming traditional surgery, such as laser therapy and electrosurgical excision, that produces uncertain results and can affect normal adjacent tissue, treatment of neurofibromas with radiofrequency ablation and excision can be an alternative choice of treatment for patients with a large number of neurofibromas.

• Journal of Chest Surgery
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• v.49 no.2
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• pp.130-133
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• 2016

The rupture of an internal mammary artery (IMA) aneurysm in a patient with type 1 neurofibromatosis (NF-1) is a rare but life-threatening complication requiring emergency management. A 50-year-old man with NF-1 was transferred to the emergency department of Kyungpook National University Hospital, where an IMA aneurysmal rupture and hemothorax were diagnosed and drained. The IMA aneurysmal rupture and hemothorax were successfully repaired by staged management combining endovascular treatment and subsequent video-assisted thoracoscopic surgery (VATS). The patient required cardiopulmonary cerebral resuscitation, the staged management of coil embolization, and a subsequent VATS procedure. This staged approach may be an effective therapeutic strategy in cases of IMA aneurysmal rupture.

• Archives of Plastic Surgery
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• v.36 no.4
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• pp.512-515
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• 2009

Purpose: Neurofibromatosis(NF) is an autosomal - dominant systemic disease. Up to fifty percent of patients with NF are reported to have concomitant vascular abnormalities. In the resection of a larger NF, the risk of uncontrolled hemorrhage is much higher due to the difficulty of hemostasis of large vessels within the tumor. We ligated the base of the giant NF with a simple loop - shaped ligation before removal of the giant NF in both buttocks. And then we could successfully reduce the amount of hemorrhage during the operation. Methods: A 46 - year - old female patient presented for giant masses of both gluteal area, which has been growing slowly for the last ten years. Each mass was about $30{\times}20cm$ in size. After designing the elliptical resection margin, we tightened the tumor base by using continuous loop - shaped suture ligation(weaving the thread up and down in a loop - shaped pattern, leaving a space of 2 cm between each loop) with a straight needle and prolene 2 - 0. After skin incision, we proceeded the dissection toward the central and inferior side of the mass obliquely while we avoided breaking large vascular sinuses. We resected the tumor in a wedged - shape. Subcutaneous tissue was sutured layer by layer and skin was closed by vertical mattress and interrupted suture. The loop - shaped ligation of the base was removed and compressive dressing was done with gauzes and elastic bandages. Results: Postoperative complications such as infection, hemorrhage, hematoma, and dehiscense did not occur. Perioperatively the patient was sufficiently transfused with five units of blood and two units of fresh frozen plasma. During the subsequent 1 year follow - up, the functional and cosmetic result was excellent. Conclusion: A continuous loop - shaped suture ligation procedure along the base of the giant NF effectively reduced the amount of hemorrhage during the operation, made dissection and ligation of vessels easily and quickly, and shorten the operating time and postoperative recovery time.

• Journal of Korean Neurosurgical Society
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• v.30 no.5
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• pp.642-646
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• 2001

A 12-years-old female admitted to the hospital with the complaint of pain on the right upper chest area which persisted about 1 month prior to admission. $Caf{\acute{e}}$-au-lait spots of various size laying on a whole body and freckling on the axilla were found on physical examination. A huge mass was found on the plain chest X-ray and on chest MRI. The mass encroached thoracic spine, posterior rib, back muscles, and then into the neural canal and compressed thoracic spinal cord. On the 5th day of hospitalization, the patient complained tingling on the both legs and 2 days later, monoparesis on the right leg. Open thoracotomy and decompressive laminectomy was done to remove mass. Pathologic reports confirmed rhabdomyosarcoma, embryonal type.

• Korean Journal of Head & Neck Oncology
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• v.29 no.2
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• pp.54-57
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• 2013

Malignant triton tumor(MTT) is a rare type of malignant peripheral nerve sheath tumor(MPNST) with focal rhabdomyoblastic differentiation. MTT constitutes about 5% of all MPNSTs and described the first case of a MTT in a patient with Von Recklinghausen disease by Masson in 1932. MTT is commonly seen in the head, neck, extremities and trunk. It can occur in sporadic form or over a setting of neurofibromatosis-1(NF-1). The diagnosis can be confirmed based on morphologic grounds supported by an immunostain such as S-100 protein. Desmin, myo-D1 and myogenin are immunostains positive for rhabdomyoblasts. MTT has an aggressive biological behavior so prognosis of this rare and highly malignant tumor is poor and optimal treatment remains unclear. But modern treatment consisted of radical excision and postoperative radiotherapy has improved the prognosis of such cases.

• Molecules and Cells
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• v.40 no.4
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• pp.254-261
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• 2017

Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs post-transcriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells. It was observed that miR-296-5p potentiated the invasion of various GBM cells including LN229, T98G, and U87MG. Through bioinformatics approaches, two genes were identified as miR-296-5p targets: caspase-8 (CASP8) and nerve growth factor receptor (NGFR). From results obtained from Ago2 immunoprecipitation and luciferase assays, we found that miR-296-5p downregulates CASP8 and NGFR through direct interaction between seed sequence of the miRNA and 3'UTR of the target mRNA. Knockdown of CASP8 or NGFR also increased the invasive ability of GBM cells, indicating that CASP8 and NGFR are involved in potentiation of invasiveness by miR-296-5p. Consistent with our findings, CASP8 was downregulated in brain metastatic lung cancer cells, which have a high level of miR-296-5p, compared to parental cells, suggesting that miR-296-5p may be generally associated with the acquisition of invasiveness. Collectively, our results implicate miR-296-5p as a potential cause of invasiveness in cancer and suggest it as a promising therapeutic target for GBM.