Need to Take Heart? Talk to Your Psychiatrist for 20 Minutes.

ABSTRACT: A powerful correlation exists between the equilibrium of the sympathetic and parasympathetic nervous systems and heart rate variability (HRV). Thus, HRV is useful as a physiological index of both physical and emotional health; autonomic nervous system dysregulation, with a sympathetic predominance and a low HRV, has been associated with a variety of physical (cardiovascular, neurological) and psychiatric disorders. We used a validated algorithm of measuring the HRV (noninvasive, 2-minute approach) in new psychiatric outpatients in first author's private practice. The subjects had an initial measurement, followed by a 20-minute consultation with minimal supportive psychotherapy, followed by an exit measurement. The initial study spanned the "COVID months"; to control for this variable, an identical study was performed in 2023. There was a highly significant decrease in the sympathetic predominance in the test groups; no such trend was found in the control groups. A short psychiatry consultation may be sufficient to decrease patients' sympathetic hyperactivity and improve their well-being.

Beware of Osteogenesis Imperfecta: Subdural Hematoma in a 10-Year-Old Child With Minor Head Trauma.

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by disruption of normal collagen formation resulting in varying degrees of ligamentous laxity and skeletal vulnerability; the low bleeding potential is easily overlooked. Subdural hematoma (SDH) is a common neurosurgical condition, classically related to the rupture of bridging cortico-dural veins after trauma. In the pediatric population, the age distribution shows a massive preponderance for children in their early first decade. We report a very unusual case of SDH in a 10-year-old boy with OI type I, with history of minor trauma. SDH remains exceedingly rare in OI, and its pathophysiology is unclear. To the best of our knowledge, this is the first report of a unilateral subacute SDH associated with OI in a child of such advanced age. These cases may also carry legal ramifications, including misdiagnosis of child abuse in ambiguous situations that are not thoroughly investigated.

Challenges in a case of ophthalmic artery aneurysm associated with abnormal internal carotid arteries.

Ophthalmic artery aneurysms account for 5% of all cerebral aneurysms and are an important cause of morbidity and mortality related to subarachnoid hemorrhage. The diagnosis is often made only when the aneurysm is large enough to become symptomatic. They remain technically challenging for both neurosurgeon and interventional radiologist. We present the case of a 62-year-old woman admitted for transient loss of consciousness, followed by generalized tonic-clonic seizures. Computed tomography (CT) showed a subarachnoid hemorrhage (SAH), clinically graded as Hunt and Hess III. Magnetic resonance imaging (angioMR) and the four-vessel digital subtraction angiography (DSA) identified a ruptured, 8 mm left ophthalmic artery aneurysm. Embolization was the first therapeutic choice. Nevertheless, the attempt had to be aborted due to a combination of a hypoplastic right internal carotid artery (ICA) and an irregular atheromatous plaque on the left ICA, rendering the procedure unduly hazardous. Therefore, microsurgical clipping of the aneurysm became the procedure of choice. Postoperatively, the patient was in good condition, with no visual and neurological deficits. At 6 months follow up, she was assigned maximum scores of 5 and 8 on the Glasgow Outcome Scale (GOS) and Extended GOS (GOS-E), respectively. Aneurysm rupture represents a neurosurgical emergency and an early intervention (less than 48 h) is recommended to maximize the chances of deficit-free survival. The peculiarities of this case consisted in the combination between the size and the location of the aneurysm, abrupt presentation, and the impossibility of embolization due to bilateral ICA abnormalities, congenital (hypoplastic right ICA) and acquired (extensively atherosclerotic left ICA).

The dangers of gastritis: a case of clarithromycin-associated brief psychotic episode.

We present a rare occurrence of brief psychotic episode associated with clarithromycin treatment. This 49-year-old lady with no psychiatric history commenced "triple therapy" for gastritis with Helicobacter pylori infection. After 1 week, a dispensing error became obvious; she was advised to start taking the drug missing for the first week-clarithromycin. Twenty-four hours later, she started acting irrationally and became increasingly disorganized, irritable, and delusional and wrote a 16-page letter to her employer, incoherent but focused on persecutory delusions. She developed auditory and visual hallucinations linked to the death of a neighbor's child. After 6 days, she deteriorated to the point where family sought professional help, and voluntary admission was arranged. The only pharmacological intervention needed was one dose of lorazepam and haloperidol for acute agitation. Twenty-four hours after last clarithromycin dose, she had improved dramatically. In 48 hours, she was "unrecognizable" (her "old self") and was discharged. Follow-up at 1 week showed no active psychosis. For the next 6 months, she did not come again to the attention of mental health services. Clarithromycin-induced psychosis is an extremely rare but recognized side effect with yet unclear pathogenesis. Raising awareness is important in both psychiatric and general practice.

In memoriam Ladislau Steiner, neurosurgeon: some people from transylvania do live forever.

We review the extraordinary professional trajectory of Ladislau Steiner, a prolific neurosurgeon and radiosurgeon, who died earlier this year. Dr. Steiner trained and practiced as a neurosurgeon in his native Romania until he was 42, before moving to Stockholm. After 25 years at the Karolinska Institute, when most people consider retirement, he spent the following 25 years of his life as director of the Lars Leksell Center for Gamma Knife Radiosurgery at the University of Virginia, Charlottesville, Virginia. At 90, nostalgia for Europe made him accept the position of director of the Gamma Knife Center at the International Neuroscience Institute in Hannover, Germany. His life was dedicated to the 15,000 patients whose lives he saved in his lengthy career.

Constantin N. Arseni (1912-1994) centenary: the birth of modern neurosurgery in Romania.

Prof. Dr. Constantin N. Arseni and his mentor, Prof. Dr. D. Bagdasar, are revered by later generations of doctors as the forefathers of Romanian neurosurgery. In 2012, we have celebrated 100 years since Prof. Arseni's birth in a small village within a deprived area of the country. Through his talents and perseveration, he rose to be a neurosurgical school creator and one of the most prominent figures in 20th-century Eastern European neurosurgery. This historical vignette is a modest tribute to his legacy and tells the story of his titanic endeavor.

Gamma knife surgery for pediatric arteriovenous malformations: a 25-year retrospective study.

OBJECT: The authors present their 25-year experience in treating pediatric arteriovenous malformations (AVMs) to allow comparisons with other historic studies and data in adults. METHODS: Data were collected from a prospectively maintained departmental database selected for age and supplemented by case note review and telephone interviews as appropriate. RESULTS: Three hundred sixty-three patients, ages 1-16 years (mean ± SD, 12 ± 3.2 years), underwent 410 treatments; 4 had planned 2-stage treatments and 43 were retreated subsequent to an initial partial response. Fifty-eight percent received general anesthesia for the procedure. Sixteen percent had previously undergone embolization. The most common presenting symptoms were as follows: hemorrhage (80.2%), epilepsy (8.3%; overall seizure prevalence 19.9%), and migrainous headaches (6.3%). Only 0.28% of the AVMs were incidental findings. The mean lesion volume was 3.75 ± 5.3 cm3 (range 0.01-32.8 cm3), with a median Spetzler-Martin grade of III (range I-V). The mean peripheral (therapeutic) dose was 22.7 ± 2.3 Gy (range 15-25 Gy), corresponding to a mean maximum dose of 43.6 ± 6 Gy (range 25-51.4 Gy). The obliteration rate was 71.3% in patients who received one treatment and 62.5% for retreated patients, with a mean obliteration time of 32.4 and 79.6 months, respectively. The overall obliteration rate was 82.7%. No follow-up data are as yet available for the 4 patients who underwent the staged treatments. Only 4 patients received peripheral doses below 20 Gy, and the AVM was obliterated in 3 of these patients. The other patients received 20, 22.5, or 25 Gy and had obliteration rates of 82.6%, 77.7%, and 86.3%, respectively. The bleeding rate postradiosurgery was 2.2%, and the cumulative complication rate was 3.6%, with radionecrosis being the most common complication (1.1%). CONCLUSIONS: Surprisingly, there was no correlation (p = 0.43) between outcome and radiosurgical dose when that dose was between 20 and 25 Gy, thus suggesting that the lower of these 2 doses may be effective. Radiosurgery for pediatric AVM is safe and effective.

Gamma Knife® radiosurgery for recurrent intracranial olfactory neuroblastoma (esthesioneuroblastoma): a case report.

BACKGROUND: We report the use of salvage radiosurgery to manage an aggressive olfactory neuroblastoma (esthesioneuroblastoma) with multiple recurrences and intracranial extension. CASE PRESENTATION: A 43-year-old Caucasian woman presented 11 years ago with progressive nasal blockage and headaches. A necrotic polyp originating in her left middle meatus and extending to the ethmoid air cells and cribriform plate (Kadish stage C) was radically resected via a craniofacial approach. Four years later, a local recurrence extending into her left cavernous sinus was identified and deemed inoperable. She received vincristine, ifosfamide, doxorubicin and etoposide chemotherapy (with minimal benefit) and external beam radiotherapy (60Gy in 30 fractions) to her skull base. Two years later, tumour extension in her left neck was treated with radical radiotherapy. She developed visual disturbances in her left eye, which progressed to blindness in the next two years. Having exhausted chemoradiotherapy, the left cavernous sinus esthesioneuroblastoma was treated with Gamma Knife® radiosurgery 2 years ago (20Gy at 50% isodose, tumour volume 7.5cm3). At one year, there was dramatic reduction in the tumour and no new symptoms; however, there were new tumour foci (in her left frontal lobe and above her right orbital apex). These were again treated with radiosurgery (20Gy at 50% isodose, total tumour volume 0.67cm3). Repeat imaging at six months showed no further disease progression. CONCLUSION: Whilst rare, olfactory neuroblastoma (esthesioneuroblastoma) can present management challenges and Gamma Knife® radiosurgery may prove a useful strategy in controlling intracranial spread.

Survival and complications following γ knife radiosurgery or enucleation for ocular melanoma: a 20-year experience.

BACKGROUND: We present our experience in treating ocular melanoma at the National Centre for Stereotactic Radiosurgery in Sheffield, UK over the last 20 years. METHOD: We analysed 170 patients treated with Gamma Knife radiosurgery, recorded the evolution of visual acuity and complication rates, and compared their survival with 620 patients treated with eye enucleation. Different peripheral doses (using the 50% therapeutic isodose) were employed: 50-70 Gy for 24 patients, 45 Gy for 71 patients, 35 Gy for 62 patients. FINDINGS: There was no significant difference in survival between the 35-Gy, 45-Gy and 50- to 70-Gy groups when compared between themselves (p = 0.168) and with the enucleation group (p = 0.454). The 5-year survival rates were: 64% for 35 Gy, 62.71% for 45 Gy, 63.6% for 50-70 Gy and 65.2% for enucleated patients. Clinical variables influencing survival for radiosurgery patients were tumour volume (p = 0.014) and location (median 66.4 vs 37.36 months for juxtapapillary vs peripheral tumours, respectively; p = 0.001), while age and gender did not prove significant. Regarding complications, using 35 Gy led to more than a 50% decrease, when compared with the 45-Gy dose, in the incidence of cataract, glaucoma and retinal detachment. Retinopathy, optic neuropathy and vitreous haemorrhage were not significantly influenced. Blindness decreased dramatically from 83.7% for 45 Gy to 31.4% for 35 Gy (p = 0.006), as well as post-radiosurgery enucleation: 23.9% for 45 Gy vs 6.45% for 35 Gy (p = 0.018). Visual acuity, recorded up to 5 years post-radiosurgery, was significantly better preserved for 35 Gy than for 45 Gy (p = 0.0003). CONCLUSIONS: Using 35 Gy led to a dramatic decrease in complications, vision loss and salvage enucleation, while not compromising patient survival.

Transient global amnesia as a revealing sign of giant transtentorial meningioma: case report and review of the literature.

Since 1974, only 14 papers in MEDLINE-indexed journals have linked transient global amnesia (TGA) to a brain tumor. Among these, two described the entity of transient epileptic amnesia (TEA), whereas most reports lacked the functional investigations that might differentiate the two conditions. Only six cases have linked TGA or TEA to a meningioma, and none of them were transtentorial. We report the case of a 75-year-old woman who presented with one episode of TGA as a sole symptom of a giant transtentorial meningioma in the right hemisphere. A sudden attack of TGA with a rather typical clinical presentation--anterograde amnesia with selective retrograde features that lasted for a few hours, with stereotypic questions, no associated symptoms or neurological impairment, and no recurrence--occurred while she was at home; this was witnessed by her husband. The neurological examination was unremarkable, with the exception of a slight left homonymous superior quadrantonopia. Brain imaging (computed tomography and magnetic resonance imaging) showed a huge meningioma originating from the right tentorium, extending from the cerebellar hemisphere to the midst of the temporal lobe. An electroencephalogram did not reveal temporal spikes. The tumor was completely excised, and she has remained asymptomatic for 6 months. Although TGA is generally a functional entity, without an organic substrate to prompt surgical sanction, a full investigation may be warranted to rule out the possibility of a silent intracranial tumor.

Bioluminescence imaging of invasive intracranial xenografts: implications for translational research and targeted therapeutics of brain tumors.

Despite decades of study, the etiology of brain cancer remains elusive. However, extensive molecular characterization of primary brain tumors has been accomplished, outlining recurrent features that are proving useful for devising targeted therapies. There are far too few patients available for comparing the efficacy of therapeutic combinations, especially when variations in dosing, frequency, and sequencing are taken into account. Consequently, there is a substantial need for increasing preclinical testing throughput using clinically relevant models. We review luminescent optical imaging for its potential in facilitating in vivo assessment of intracranial tumor growth and response to therapy in rodent orthotopic xenograft models of primary brain malignancies. We review the rationale behind the need of an in vivo model, why orthotopic tumor models displaying an invasive phenotype may be a superior choice when compared to flank-implanted tumors, and what advantages may be drawn from the use of modified cells, suitable for sequential monitoring by in vivo optical imaging. Studies show that luminescent signal correlates highly both with tumor burden and Kaplan-Meier survival curves of rodents bearing intracranial xenografts. We conclude that bioluminescent imaging is a highly sensitive technique for assessment of tumor burden, response to therapy, tumor recurrence, and behavior to salvage therapy, making it a superior option for longitudinal monitoring in intracranial rodent models of primary brain tumors.

A human brainstem glioma xenograft model enabled for bioluminescence imaging.

Despite the use of radiation and chemotherapy, the prognosis for children with diffuse brainstem gliomas is extremely poor. There is a need for relevant brainstem tumor models that can be used to test new therapeutic agents and delivery systems in pre-clinical studies. We report the development of a brainstem-tumor model in rats and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to therapy as part of this model. Luciferase-modified human glioblastoma cells from five different tumor cell sources (either cell lines or serially-passaged xenografts) were implanted into the pontine tegmentum of athymic rats using an implantable guide-screw system. Tumor growth was monitored by BLI and tumor volume was calculated by three-dimensional measurements from serial histopathologic sections. To evaluate if this model would allow detection of therapeutic response, rats bearing brainstem U-87 MG or GS2 glioblastoma xenografts were treated with the DNA methylating agent temozolomide (TMZ). For each of the tumor cell sources tested, BLI monitoring revealed progressive tumor growth in all animals, and symptoms caused by tumor burden were evident 26-29 days after implantation of U-87 MG, U-251 MG, GBM6, and GBM14 cells, and 37-47 days after implantation of GS2 cells. Histopathologic analysis revealed tumor growth within the pons in all rats and BLI correlated quantitatively with tumor volume. Variable infiltration was evident among the different tumors, with GS2 tumor cells exhibiting the greatest degree of infiltration. TMZ treatment groups were included for experiments involving U-87 MG and GS2 cells, and in each case TMZ delayed tumor growth, as indicated by BLI monitoring, and significantly extended survival of animal subjects. Our results demonstrate the development of a brainstem tumor model in athymic rats, in which tumor growth and response to therapy can be accurately monitored by BLI. This model is well suited for pre-clinical testing of therapeutics that are being considered for treatment of patients with brainstem tumors.

Fyn and SRC are effectors of oncogenic epidermal growth factor receptor signaling in glioblastoma patients.

Activating epidermal growth factor receptor (EGFR) mutations are common in many cancers including glioblastoma. However, clinical responses to EGFR inhibitors are infrequent and short-lived. We show that the Src family kinases (SFK) Fyn and Src are effectors of oncogenic EGFR signaling, enhancing invasion and tumor cell survival in vivo. Expression of a constitutively active EGFR mutant, EGFRvIII, resulted in activating phosphorylation and physical association with Src and Fyn, promoting tumor growth and motility. Gene silencing of Fyn and Src limited EGFR- and EGFRvIII-dependent tumor cell motility. The SFK inhibitor dasatinib inhibited invasion, promoted tumor regression, and induced apoptosis in vivo, significantly prolonging survival of an orthotopic glioblastoma model expressing endogenous EGFRvIII. Dasatinib enhanced the efficacy of an anti-EGFR monoclonal antibody (mAb 806) in vivo, further limiting tumor growth and extending survival. Examination of a large cohort of clinical samples showed frequent coactivation of EGFR and SFKs in glioblastoma patients. These results establish a mechanism linking EGFR signaling with Fyn and Src activation to promote tumor progression and invasion in vivo and provide rationale for combined anti-EGFR and anti-SFK targeted therapies.

Pathologic correlates of primary central nervous system lymphoma defined in an orthotopic xenograft model.

PURPOSE: The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. EXPERIMENTAL DESIGN: We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. RESULTS: Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. CONCLUSION: Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor.

Current data and strategy in glioblastoma multiforme.

Glioblastoma multiforme (GBM) or astrocytoma grade IV on WHO classification is the most aggressive and the most frequent of all primary brain tumors. Glioblastoma is multiforme, resistant to therapeutic interventions illustrating the heterogeneity exhibited by this tumor in its every aspect, including clinical presentation, pathology, genetic signature. Current data and treatment strategy in GBM are presented focusing on basic science data and key clinical aspects like surgery, including personal experience; adjuvant modalities: radiotherapy, chemotherapy, but also for experimental approaches. Therapeutic attitude in recurrent GBM is also widely discussed.

p53 Small-molecule inhibitor enhances temozolomide cytotoxic activity against intracranial glioblastoma xenografts.

In this study, we investigated the precursor and active forms of a p53 small-molecule inhibitor for their effects on temozolomide (TMZ) antitumor activity against glioblastoma (GBM), using both in vitro and in vivo experimental approaches. Results from in vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased when p53 wild-type (p53(wt)) GBMs were cotreated with the active form of p53 inhibitor, and this heightened cytotoxic response was accompanied by increased poly(ADP-ribose) polymerase cleavage as well as elevated cellular phospho-H2AX. Analysis of the same series of GBMs, as intracranial xenografts in athymic mice, and administering corresponding p53 inhibitor precursor, which is converted to the active compound in vivo, yielded results consistent with the in vitro analyses: TMZ + p53 inhibitor precursor cotreatment of three distinct p53(wt) GBM xenografts resulted in significant enhancement of TMZ antitumor effect relative to treatment with TMZ alone, as indicated by serial bioluminescence monitoring as well as survival analysis (P < 0.001 for cotreatment survival benefit in each case). Mice receiving intracranial injection with p53(null) GBM showed similar survival benefit from TMZ treatment regardless of the presence or absence of p53 inhibitor precursor. In total, our results indicate that the p53 active and precursor inhibitor pair enhances TMZ cytotoxicity in vitro and in vivo, respectively, and do so in a p53-dependent manner.

An orthotopic skull base model of malignant meningioma.

Meningioma tumor growth involves the subarachnoid space that contains the cerebrospinal fluid. Modeling tumor growth in this microenvironment has been associated with widespread leptomeningeal dissemination, which is uncharacteristic of human meningiomas. Consequently, survival times and tumor properties are varied, limiting their utility in testing experimental therapies. We report the development and characterization of a reproducible orthotopic skull-base meningioma model in athymic mice using the IOMM-Lee cell line. Localized tumor growth was obtained by using optimal cell densities and matrigel as the implantation medium. Survival times were within a narrow range of 17-21 days. The xenografts grew locally compressing surrounding brain tissue. These tumors had histopathologic characteristics of anaplastic meningiomas including high cellularity, nuclear pleomorphism, cellular pattern loss, necrosis and conspicuous mitosis. Similar to human meningiomas, considerable invasion of the dura and skull and some invasion of adjacent brain along perivascular tracts were observed. The pattern of hypoxia was also similar to human malignant meningiomas. We use bioluminescent imaging to non-invasively monitor the growth of the xenografts and determine the survival benefit from temozolomide treatment. Thus, we describe a malignant meningioma model system that will be useful for investigating the biology of meningiomas and for preclinical assessment of therapeutic agents.

Bioluminescence monitoring of intracranial glioblastoma xenograft: response to primary and salvage temozolomide therapy.

OBJECT: Bioluminescence imaging (BLI) offers a rapid and accurate means for longitudinal study of tumor cell growth and response to therapy in rodent models. Because this technology has only recently come into use in the field of small animal imaging, applications in this area have been limited. In the current study we have applied BLI to the analysis of clinically relevant issues involving use of the DNA methylating agent temozolomide (TMZ) in a mouse model. METHODS: An invasive glioblastoma multiforme xenograft was modified for BLI via transduction with a luciferase-encoding lentivirus. Supratentorial tumors were established in athymic nude mice that were subsequently assigned randomly to control and TMZ treatment groups, and the extent of intracranial tumor was monitored using BLI. RESULTS: In an experiment designed to compare the extent of antitumor effect between a single high-dose TMZ treatment and a protracted low-dose TMZ regimen, BLI revealed the protracted regimen as having superior antitumor effect, and this interpretation was consistent with results from a survival comparison between the two TMZ treatment groups. In a second experiment designed to assess the utility of BLI for testing therapies against recurrent glioblastoma multiforme, mice with intracranial tumors were retreated with TMZ at a time when BLI monitoring revealed tumor regrowth following initial TMZ treatment, and retreatment was successful in providing additional survival benefit. CONCLUSIONS: The results of these experiments indicate that BLI monitoring can be used as a surrogate for predicting survival benefit from TMZ treatment, permits early determination of relative survival benefit associated with distinct TMZ therapeutic regimens, and offers a means of investigating secondary/salvage therapy efficacy following tumor regrowth from initial therapy.

Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel.

In the current study, we examined a panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR.