Radio Tracking Reveals the Home Range and Activity Patterns of Nutria (Myocastor coypus) in the Macdo Wetland in South Korea.

Nutria (Myocastor coypus) are semi-aquatic rodents that were introduced in South Korea for commercial farming but significantly damaged aquatic ecosystems. Understanding nutria ecological behavior is essential for developing effective control and eradication strategies to mitigate their impacts. Thus, this study aimed to investigate the home range and activity patterns of 24 nutria (12 males and 12 females) in the Macdo wetland in South Korea from 2015-2016 through radio tracking. The average minimum convex polygon home range of the nutria was 0.29 ± 0.55 km2, with a 95% kernel density estimation (KDE) home range of 0.43 ± 0.85 km2 and a 50% KDE home range of 0.05 ± 1.1 km2. The home range of males was larger than that of females; however, the winter home range of females was as large as that of males. The home range also varied seasonally, with the smallest observed in winter. The nutria showed crepuscular and nocturnal activity patterns throughout the year, with no significant difference between sexes. The activities in spring, summer, and autumn showed no significant differences, but the activity in winter was significantly different from that in the other seasons. This study may serve as a basis for developing appropriately timed and scaled management strategies to mitigate the impacts of nutria on ecosystems. In conclusion, several environmental and biological factors contribute to the behavior of nutria in South Korea.

Slowly growing solitary neurofibroma of the thumb: A case report.

RATIONALE: Neurofibromas can develop as part of neurofibromatosis or as a solitary tumor. Although solitary neurofibromas generally grow slowly, they rarely grow for more than 10 years, and such tumors have not been described in the hand. PATIENT CONCERNS: A 60-year-old woman presented with a mass on the dorsum of the proximal phalanx of the right thumb that had been enlarging since more than a decade. DIAGNOSES: Preoperative imaging revealed a moderately defined soft tissue mass, which measured 1.5 cm × 1.5 cm × 0.7 cm, with no bone and joint abnormalities on the right thumb. The final diagnosis of the tumor was solitary neurofibroma without evidence of neurofibromatosis. INTERVENTION: En bloc resection of the tumor was performed through a longitudinal skin incision. OUTCOMES: After surgery, the patient had no complaints of pain but had a temporary tingling sensation. After 14 months of follow-up, no signs of recurrence of the tumor were observed and she was highly satisfied with the results of the surgery. LESSONS: Solitary neurofibroma is quite rare, especially one in the hand. However, in dealing with soft tissue tumors of the hand, particularly those with neurologic symptoms, neurofibroma should be included in the differential diagnosis.

Association between Vitamin B12 levels and cognitive function in the elderly Korean population.

Vitamin B12 (B12), also known as cobalamin, is a water-soluble vitamin. It is a cofactor in DNA synthesis and is involved in the metabolism of every cell of the human body, including the central nervous system. Those with a deficiency of B12 can present with peripheral neuropathy, pernicious anemia, or a cognitive disorder. Previous studies have revealed that a deficiency of B12 is associated with cognitive decline or Alzheimer disease.The data of 2991 people were evaluated from 2 years of the Korean Frailty and Aging Cohort Study, a nationwide multicenter survey. To assess cognitive function, a short form of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) was used. Of the CERAD-K tests, we included the Mini-Mental State Examination in the Korean version of the CERAD assessment packet (MMSE-KC), the word list: memory/recall/recognition, digit span (forward, backward), trail making test-A, and the frontal assessment battery. B12 concentrations were classified into clinically relevant categories, insufficient (<350 pg/mL) and sufficient (≥350 pg/mL). A linear regression analysis was used to evaluate the relationship between cognitive function and B12 levels.The mean age of the 2991 participants was 76.4 ±â€Š3.9 years old. Overall, 414 (13.8%) were classified as B12 insufficient, and 2577 (86.2%) as B12 sufficient. The sufficient B12 group performed better in the MMSE-KC, Wordlist: memory, Wordlist: recognition, TMT-A test, digit span, and FAB tests. This was statistically significant (P < .05). However, in the multivariable linear regression analysis, after adjusting for age, sex, education period, marriage, smoking and drinking habits, and comorbidities, the association between the B12 group and cognitive function was not statistically significant.Although our study does not show that B12 insufficiency is a direct risk factor to cognitive decline, B12 levels could be a contributing factor to cognitive function. Our results suggest that cognition was affected by the B12 levels, along with demographic and sociological variables.

Extracranial Meningioma Presenting as an Eyebrow Mass.

Meningiomas originate in the central nervous system and are the most common intracranial benign tumor. However, although rarely, they can develop extracranially. Primary extracranial meningiomas are frequently misdiagnosed, resulting in inappropriate clinical management. The most common sites of extracranial meningiomas include the skull, scalp, orbit, nose, paranasal sinuses, middle ear, neck, and skin. A 77-year-old woman presented with a mass on her left eyebrow. Computed tomography revealed an enhancing soft tissue mass in the left frontal area. The differential diagnoses included benign and malignant tumors. The patient underwent surgical excision by a direct approach, with dissection through the galea plane. Histological examination showed tumor cells arranged in sheets or whorls, with occasional psammoma bodies. The margins were free of tumor. The mass measured 2.1 × 1.1 × 2 cm, and was diagnosed as an extracranial meningioma. The patient had no recurrence 1 year later. Extracranial meningiomas are rare; nonetheless, ectopic meningioma should be considered in the differential diagnosis of any mass lesion in the eyebrow region.

Post-Traumatic Peripheral Giant Osteoma in the Frontal Bone.

Osteomas are benign, slow-growing tumors that most frequently occur in the craniomaxillofacial region. These tumors are mostly asymptomatic and are generally found incidentally. A giant osteoma is generally considered to be greater than 30 mm in diameter or 110 g in weight. A 35-year-old female presented to us with complaints of a firm mass that showed continuous growth on the forehead following trauma. A hairline incision was made to expose the osteoma. Biopsy of the tumor confirmed a osteoma. There were no complications after surgery. Postoperative computed tomography revealed that the tumor was completely removed. Because a peripheral giant osteoma of the frontal bone with a history of trauma is a rare finding, thorough history-taking, physical examination, and preoperative imaging tests are needed for patients with a history of trauma to rule out a giant osteoma.

Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in the Adult Central Nervous System.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor central to axon regrowth with an enigmatic ability to act in different subcellular regions independently of its transcriptional roles. However, its roles in mature CNS neurons remain unclear. Here, we show that along with nuclear translocation, STAT3 translocates to mitochondria in mature CNS neurons upon cytokine stimulation. Loss- and gain-of-function studies using knockout mice and viral expression of various STAT3 mutants demonstrate that STAT3's transcriptional function is indispensable for CNS axon regrowth, whereas mitochondrial STAT3 enhances bioenergetics and further potentiates regrowth. STAT3's localization, functions, and growth-promoting effects are regulated by mitogen-activated protein kinase kinase (MEK), an effect further enhanced by Pten deletion, leading to extensive axon regrowth in the mouse optic pathway and spinal cord. These results highlight CNS neuronal dependence on STAT3 transcriptional activity, with mitochondrial STAT3 providing ancillary roles, and illustrate a critical contribution for MEK in enhancing diverse STAT3 functions and axon regrowth.

The Versatility of Cheek Rotation Flaps.

BACKGROUND: The cheek rotation flap has sufficient blood flow and large flap size and it is also flexible and easy to manipulate. It has been used for reconstruction of defects on cheek, lower eyelid, or medial and lateral canthus. For the large defects on central nose, paramedian forehead flap has been used, but patients were reluctant despite the remaining same skin tone on damaged area because of remaining scars on forehead. However, the cheek flap is cosmetically superior as it uses the adjacent large flap. Thus, the study aims to demonstrate its versatility with clinical practices. METHODS: This is retrospective case study on 38 patients who removed facial masses and reconstructed by the cheek rotation flap from 2008 to 2015. It consists of defects on cheek (16), lower eyelid (12), nose (3), medial canthus (3), lateral canthus (2), and preauricle (2). Buccal mucosa was used for the reconstruction of eyelid conjunctiva, and skin graft was processed for nasal mucosa reconstruction. RESULTS: The average defect size was 6.4 cm2, and the average flap size was 47.3 cm2. Every flap recovered without complications such as abnormal slant, entropion or ectropion in lower eyelid, but revision surgery required in three cases of nasal side wall reconstruction due to the occurrence of dog ear on nasolabial sulcus. CONCLUSION: The cheek rotation flap can be applicable instead of paramedian forehead flap for the large nasal sidewall defect reconstruction as well as former medial and lateral canthal defect reconstruction.

Rational Polypharmacology: Systematically Identifying and Engaging Multiple Drug Targets To Promote Axon Growth.

Mammalian central nervous system (CNS) neurons regrow their axons poorly following injury, resulting in irreversible functional losses. Identifying therapeutics that encourage CNS axon repair has been difficult, in part because multiple etiologies underlie this regenerative failure. This suggests a particular need for drugs that engage multiple molecular targets. Although multitarget drugs are generally more effective than highly selective alternatives, we lack systematic methods for discovering such drugs. Target-based screening is an efficient technique for identifying potent modulators of individual targets. In contrast, phenotypic screening can identify drugs with multiple targets; however, these targets remain unknown. To address this gap, we combined the two drug discovery approaches using machine learning and information theory. We screened compounds in a phenotypic assay with primary CNS neurons and also in a panel of kinase enzyme assays. We used learning algorithms to relate the compounds' kinase inhibition profiles to their influence on neurite outgrowth. This allowed us to identify kinases that may serve as targets for promoting neurite outgrowth as well as others whose targeting should be avoided. We found that compounds that inhibit multiple targets (polypharmacology) promote robust neurite outgrowth in vitro. One compound with exemplary polypharmacology was found to promote axon growth in a rodent spinal cord injury model. A more general applicability of our approach is suggested by its ability to deconvolve known targets for a breast cancer cell line as well as targets recently shown to mediate drug resistance.

3D Imaging of Axons in Transparent Spinal Cords from Rodents and Nonhuman Primates

The histological assessment of spinal cord tissue in three dimensions has previously been very time consuming and prone to errors of interpretation. Advances in tissue clearing have significantly improved visualization of fluorescently labelled axons. While recent proof-of-concept studies have been performed with transgenic mice in which axons were prelabeled with GFP, investigating axonal regeneration requires stringent axonal tracing methods as well as the use of animal models in which transgenic axonal labeling is not available. Using rodent models of spinal cord injury, we labeled axon tracts of interest using both adeno-associated virus and chemical tracers and performed tetrahydrofuran-based tissue clearing to image multiple axon types in spinal cords using light sheet and confocal microscopy. Using this approach, we investigated the relationships between axons and scar-forming cells at the injury site as well as connections between sensory axons and motor pools in the spinal cord. In addition, we used these methods to trace axons in nonhuman primates. This reproducible and adaptable virus-based approach can be combined with transgenic mice or with chemical-based tract-tracing methods, providing scientists with flexibility in obtaining axonal trajectory information from transparent tissue.

Mammalian target of rapamycin's distinct roles and effectiveness in promoting compensatory axonal sprouting in the injured CNS.

Mammalian target of rapamycin (mTOR) functions as a master sensor of nutrients and energy, and controls protein translation and cell growth. Deletion of phosphatase and tensin homolog (PTEN) in adult CNS neurons promotes regeneration of injured axons in an mTOR-dependent manner. However, others have demonstrated mTOR-independent axon regeneration in different cell types, raising the question of how broadly mTOR regulates axonal regrowth across different systems. Here we define the role of mTOR in promoting collateral sprouting of spared axons, a key axonal remodeling mechanism by which functions are recovered after CNS injury. Using pharmacological inhibition, we demonstrate that mTOR is dispensable for the robust spontaneous sprouting of corticospinal tract axons seen after pyramidotomy in postnatal mice. In contrast, moderate spontaneous axonal sprouting and induced-sprouting seen under different conditions in young adult mice (i.e., PTEN deletion or degradation of chondroitin proteoglycans; CSPGs) are both reduced upon mTOR inhibition. In addition, to further determine the potency of mTOR in promoting sprouting responses, we coinactivate PTEN and CSPGs, and demonstrate that this combination leads to an additive increase in axonal sprouting compared with single treatments. Our findings reveal a developmental switch in mTOR dependency for inducing axonal sprouting, and indicate that PTEN deletion in adult neurons neither recapitulates the regrowth program of postnatal animals, nor is sufficient to completely overcome an inhibitory environment. Accordingly, exploiting mTOR levels by targeting PTEN combined with CSPG degradation represents a promising strategy to promote extensive axonal plasticity in adult mammals.

The first case of Capillaria hepatica infection in a nutria (Myocastor coypus) in Korea.

This study reports the first case of Capillaria hepatica infection in a nutria in Korea. Ten nutrias, captured near the Nakdong River, were submitted to our laboratory for necropsy. White-yellowish nodules were found in the liver of 1 of the nutrias at necropsy. Histologically, the lesions were granulomatous, and infiltrations of lipid-laden macrophages, eosinophils, and several multinucleated giant cells were observed. The lesions consisted of numerous eggs and necrotic hepatocytes. The eggs were lemon-shaped and had polar plugs at the ends of both long sides. The eggs were morphologically identified as those of C. hepatica. Worldwide, C. hepatica infection in nutrias is very rare. Nutrias are a kind of livestock, as well as wildlife; therefore, an epidemiological study for parasitic infections needs to be conducted.

In vivo bioluminescence imaging for prolonged survival of transplanted human neural stem cells using 3D biocompatible scaffold in corticectomized rat model.

Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA) scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc) were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.

Double suicide gene therapy using human neural stem cells against glioblastoma: double safety measures.

With recent advancements in stem cell-based gene therapy, concerns about safety have grown. Stem cell-based gene therapies may pose the risk of immunological problems and oncogenesis. We investigated the feasibility of treating glioblastomas with neural stem cells [(NSCs), HB1.F3 cells] expressing double prodrug enzymes [cytosine deaminase (CD) and tyrosine kinase (TK)] to eliminate the NSCs following treatment for safety purposes. First, the in vitro and in vivo therapeutic efficacies of NSCs engineered with double prodrug enzymes (HB1.F3-CD.TK cells) were compared to cells expressing a single prodrug enzyme (HB1.F3-CD). Second, the degree of safety achieved by NSC elimination was compared with an in vitro viability assay of the NSCs after treatment with the double prodrugs. We further compared the differences in in vivo proliferation of control, single prodrug enzyme and double prodrug enzyme expressing NSCs. HB1.F3-CD.TK cells showed a better or comparable treatment outcome than HB1.F3-CD cells in vitro and in vivo. For safety, HB1.F3-CD.TK cells showed the least viability in vitro after treatment with prodrugs compared to HB1.F3 and HB1.F3-CD cells. Additionally, the in vivo proliferation among the injected NSCs found in the tumor was the smallest for HB1.F3-CD.TK cells. Double-prodrug enzyme-directed gene therapy shows good therapeutic efficacy as well as efficient eradication of the NSCs to ensure safety for clinical applications of stem cell-based gene therapies.

Functional recovery after injury of motor cortex in rats: effects of rehabilitation and stem cell transplantation in a traumatic brain injury model of cortical resection.

PURPOSE: Experimental studies and clinical trials designed to help patients recover from various brain injuries, such as stroke or trauma, have been attempted. Rehabilitation has shown reliable, positive clinical outcome in patients with various brain injuries. Transplantation of exogenous neural stem cells (NSCs) to repair the injured brain is a potential tool to help patient recovery. METHODS: This study aimed to evaluate the therapeutic efficacy of a combination therapy consisting of rehabilitation and NSC transplantation compared to using only one modality. A model of motor cortex resection in rats was used to create brain injury in order to obtain consistent and prolonged functional deficits. The therapeutic results were evaluated using three methods during an 8-week period with a behavioral test, motor-evoked potential (MEP) measurement, and measurement of the degree of endogenous NSC production. RESULTS: All three treatment groups showed the effects of treatment in the behavioral test, although the NSC transplantation alone group (CN) exhibited slightly worse results than the rehabilitation alone group (CR) or the combination therapy group (CNR). The latency on MEP was shortened to a similar extent in all three groups compared to the untreated group (CO). However, the enhancement of endogenous NSC proliferation was dramatically reduced in the CN group compared not only to the CR and CNR groups but also to the CO group. The CR and CNR groups seemed to prolong the duration of endogenous NSC proliferation compared to the untreated group. CONCLUSIONS: A combination of rehabilitation and NSC transplantation appears to induce treatment outcomes that are similar to rehabilitation alone. Further studies are needed to evaluate the electrophysiological outcome of recovery and the possible effect of prolonging endogenous NSC proliferation in response to NSC transplantation and rehabilitation.

Therapeutic efficacy and safety of TRAIL-producing human adipose tissue-derived mesenchymal stem cells against experimental brainstem glioma.

Mesenchymal stem cells (MSCs) have an extensive migratory capacity for gliomas, which is comparable to that of neural stem cells. Among the various types of MSCs, human adipose tissue-derived MSCs (hAT-MSC) emerge as one of the most attractive vehicles for gene therapy because of their high throughput, lack of ethical concerns, and availability and ease of isolation. We evaluated the therapeutic potential and safety of genetically engineered hAT-MSCs encoding the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against brainstem gliomas. Human AT-MSCs were isolated from human fat tissue, characterized, and transfected with TRAIL using nucleofector. The therapeutic potential of TRAIL-producing hAT-MSCs (hAT-MSC.TRAIL) was confirmed using in vitro and in vivo studies. The final fate of injected hAT-MSCs was traced in long-survival animals. The characterization of hAT-MSCs revealed the expression of MSC-specific cell-type markers and their differentiation potential into mesenchymal lineage. Short-term outcomes included a 56.3% reduction of tumor volume (P < .001) with increased apoptosis (3.03-fold, P < .05) in animals treated with hAT-MSC.TRAIL compared with the control groups. Long-term outcomes included a significant survival benefit in the hAT-MSC.TRAIL-treated group (26 days of median survival in the control group vs 84 days in the hAT-MSC.TRAIL-treated group, P < .0001), without any evidence of mesenchymal differentiation in vivo. Our study demonstrated the therapeutic efficacy and safety of nonvirally engineered hAT-MSCs against brainstem gliomas and showed the possibility of stem-cell-based targeted gene therapy for clinical application.

Enhanced reclosure of surgically induced spinal open neural tube defects in chick embryos by injecting human bone marrow stem cells into the amniotic cavity.

OBJECTIVE: To evaluate the reclosure-promoting capacity of a neural stem cell line (F3) and a human bone marrow stem cell line (B10) injected into the amniotic cavity of spinal open neural tube defects (ONTDs) of chick embryos of Hamburger and Hamilton stage 18 or 19. METHODS: Fifteen chick embryos that survived the procedure were obtained for each of 4 groups: untreated control, F3-, B10-, and HFF-1 (human foreskin fibroblast)-treated groups. Embryos in the control group underwent ONTD surgery but no cell injection. RESULTS: Compared with the untreated control and HFF-1 groups, the B10 group showed enhanced reclosure at 3, 5, and 7 days after injection, whereas the F3 group did not. B10 cells were not incorporated into reclosed neural tubes but simply covered ONTDs during the process of reclosure. F3 cells did not cover ONTDs. The cell survival of F3 cells exposed to the chick amniotic fluid in vitro for 48 hours was significantly lower than that of B10 cells. CONCLUSION: The results confirmed that B10 cells enhance reclosure of ONTDs by covering and protecting neural tissues, not by direct cell incorporation. The lack of reclosure capacity in the F3 group may be related to the poor survival of F3 cells in the amniotic fluid.

Expression of neuronal antigens and related ventral and dorsal proteins in the normal spinal cord and a surgically induced open neural tube defect of the spine in chick embryos: an immunohistochemical study.

OBJECTIVE: The aims of this study were to elucidate the processes of neuronal differentiation and ventrodorsal patterning in the spinal cord of the chick embryo from embryonic day (E) 3 to E17 and to study the effect of a prenatal spinal open neural tube defect (ONTD) on these processes. METHOD: Expression patterns of neuronal antigens (neuronal nuclear antigen, neurofilament-associated protein (NAP), and synaptophysin) and related ventral markers [sonic hedgehog, paired box gene (PAX)6, and islet-1], and dorsal markers (bone morphogenetic protein, Notch homolog 1, and PAX7) were investigated in the normal spinal cord and in a surgically induced spinal ONTD in chick embryos. Four normal and ONTD chick embryos were used for each antigen group. RESULT & CONCLUSION: There were no differences in the expression of neuronal and ventrodorsal markers between the control and ONTD groups. NAP and synaptophysin were useful for identifying dorsal structures in the distorted anatomy of the ONTD chicks.

Targeting rat brainstem glioma using human neural stem cells and human mesenchymal stem cells.

PURPOSE: Brainstem gliomas are usually inoperable and have a dismal prognosis. Based on the robust tropisms of neural stem cells (NSC) and mesenchymal stem cells (MSC) to brain tumors, we compared the tumor-tropic migratory capacities of these stem cells and evaluated the therapeutic potential of genetically engineered human NSCs encoding cytosine deaminase (CD) and IFNbeta against brainstem gliomas. EXPERIMENTAL DESIGN: The directed migratory capacities of NSCs and MSCs to brainstem glioma (F98) were evaluated both in vitro and in vivo. The human NSCs (HB1.F3) and various human MSCs, such as bone marrow-derived MSCs (HM3.B10), adipose tissue-derived MSCs, and umbilical cord blood-derived MSCs, were tested. Human fibroblast cells (HFF-1) were used as the negative control. As a proof of concept, the bioactivity of HB1.F3-CD-IFNbeta was analyzed with a cell viability assay, and animals with brainstem gliomas were injected with HB1.F3-CD-IFNbeta cells followed by systemic 5-fluorocytosine treatment. RESULTS: In an in vitro modified Transwell migration assay and in vivo stem cell injection into established brainstem gliomas in rats, all the stem cells showed a significant migratory capacity compared with that of the control (P < 0.01). Histologic analysis showed a 59% reduction in tumor volume in the HB1.F3-CD-IFNbeta-treated group (P < 0.05). Apoptotic cells were increased 2.33-fold in animals treated with HB1.F3-CD-IFNbeta compared with the respective control groups (P < 0.01). CONCLUSION: The brainstem glioma-tropic migratory capacities of MSCs from various sources were similar to those of NSCs. Genetically engineered NSCs show therapeutic efficacy against brainstem gliomas.

Sox2 expression in brain tumors: a reflection of the neuroglial differentiation pathway.

Sox2 is a key transcription factor that maintains the proliferation of neuroglial stem cells and inhibits neuronal fate commitment. Moreover, it was recently found that brain tumors contain stem cells that resemble normal neuroglial stem cells in many respects. This study was undertaken to describe Sox2 expression in various brain tumors, and to determine whether Sox2 expression is a universal feature of brain tumors, or whether its expression is limited to a specific lineage of brain tumors. Sox2 immunohistochemistry was performed on 194 brain tumor tissues of various kinds. Fetal and adult normal brain tissues obtained by autopsy and brain tissues of epilepsy patients with cortical dysplasia were used as controls. Semiquantitative reverse transcription polymerase chain reaction was used to confirm the immunohistochemical results. Double immunofluorescence was performed to characterize the lineage of Sox2-positive cells. Sox2 was found to be expressed in various glial tumors, including those with astroglial, oligodendroglial, and ependymal lineages, and in the glial components of mixed neuroglial tumors, regardless of pathologic grade. In brain tumors of embryonal origin, supratentorial primitive neuroectodermal tumors showed robust Sox2 expression, whereas medulloblastomas and pineoblastomas did not. The majority of Sox2-positive tumor cells coexpressed glial fibrillary acidic protein, and most Sox2-negative cells in medulloblastomas and pineoblastomas showed neuronal differentiation. This study suggest that Sox2 may be a tumor marker of glial lineages rather than a universal brain tumor stem cell marker, because its expression pattern was found to correspond to differentiation pathways. On the other hand, the aberrant coexpressions of Sox2 and of a neuronal marker were widely observed in glioblastomas, which reflects a disorganized differentiation pattern that characterizes highly malignant tumors.

Expression of Sox2 in mature and immature teratomas of central nervous system.

Sox2 is a transcription factor that plays a critical role in the maintenance of the self-renewal capability of neural stem cells. This study was undertaken to investigate the expression pattern of Sox2 in mature and immature teratomas of the central nervous system. Sox2 immunohistochemistry was performed in 14 cases of central nervous system teratoma: five mature, five immature teratomas, and four mixed germ cell tumors with a prominent teratoma component. Fetal brain tissue was used as a normal control. Immunofluorescence with double labeling of stem cells and neuroglial cell markers was used for phenotyping of Sox2-positive cells. In all cases of immature teratomas, positive reactivity to Sox2 was observed in primitive neuroepithelial tissues. Sox2 was not expressed in mature tissues, except in some cuboidal or columnar epithelium of endodermal origin. In mature teratomas, Sox2 expression was limited to some endodermal epithelium in two cases, and no Sox2 expression was observed in the other three cases. The majority of Sox2-positive neuroepithelial cells also expressed neural stem cell markers, nestin and vimentin. Sox2 and neuronal and oligodendroglial markers were expressed in a mutually exclusive manner. However, mature astroglial cells coexpressed Sox2 and GFAP. In fetal brain, Sox2 was mainly expressed in ventricular and subventricular zones. Since Sox2 is strongly expressed in the primitive neuroepithelial tissues of central nervous system immature teratomas, it may be a useful biomarker for the diagnosis and quantitative grading of central nervous system immature teratomas.