Knee joint synovial hemangioma treated with arthroscopic resection without hemarthrosis: A case report.

INTRODUCTION: Intra-articular synovial hemangioma of the knee is a relatively rare benign tumor that if left undiagnosed and treated may be followed by degenerative cartilaginous changes and osteoarthritis. However, the non-specific symptoms of synovial hemangiomas limit its early diagnosis. We report our encounter with synovial hemangioma of the knee in which the diagnosis was based on a > 20-year history of chronic pain without joint swelling or hematoma. PRESENTATION OF CASE: A 34-year-old man with a localized vascular malformation on the upper edge of the left patella presented with pain and a restricted range of motion. CT and MRI revealed a tumorous lesion at this location. Upon excision of the lesion, the patient's symptoms disappeared, with no recurrence at the 1-year follow-up. DISCUSSION: Accurate diagnosis and appropriate early treatment are necessary for synovial hemangiomas to forestall articular cartilage degeneration due to recurrent intra-articular hemorrhages. CONCLUSION: Synovial hemangioma should be considered when a patient presents with recurrent knee pain, even in the absence of swelling or episodes of joint effusion.

Three-dimensional vessel wall imaging with 1.5-T MRI to visualize invisible occluded cerebral artery.

BACKGROUND: Endovascular thrombectomy (EVT) is performed for acute ischemic stroke (AIS) caused by large vessel occlusion; therefore, preoperative visualization of the occluded invisible vessel course reduces complications and ensures success. Three-dimensional (3D) proton density-weighted (PDW) vessel wall imaging (VWI) using variable refocusing flip angle pulse-turbo spin-echo sequences (VRFA-TSE) with 3.0-T magnetic resonance imaging (MRI) can provide this information. PURPOSE: To assess the effectiveness of 3D PDW-VWI using 1.5-T MRI without VRFA function. MATERIAL AND METHODS: Five consecutive patients with AIS caused by large vessel occlusion underwent EVT in our institute. VWI with 1.5-T MRI using 3D PDW-fast spin echo (FSE) technique was added to conventional brain imaging. RESULTS: PDW-FSE was successfully performed in all cases. 3D PDW-FSE was useful to visualize both the anterior and posterior circulations by clearly revealing invisible vessels but could not demonstrate the length and size of the clot in all five cases. CONCLUSION: 3D PDW-FSE with 1.5-T MRI without VRFA could clearly depict the course of the invisible occluded artery and might support favorable outcomes after EVT in patients with AIS.

Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice.

BACKGROUND: Diabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are known to disrupt the homeostasis of osteoblasts and osteoclasts. The purpose of this study was to identify the changes of osteoblasts and osteoclasts under long-term hyperglycaemic conditions, using a mouse fracture model of long-term hyperglycemia (LT-HG). METHODS: C57BL/6J mice and green fluorescent protein (GFP) -positive bone marrow transplanted C57BL/6J mice with LT-HG, maintained under a state of hyperglycaemia for 2 months, were used in this study. After the experimental fracture, we examined the immunohistochemical expression of proinsulin and tumor necrosis factor (TNF) -α at the fracture site. C57BL/6J fracture model mice without hyperglycaemia were used as controls. RESULTS: In the LT-HG mice, chondrocyte resorption was delayed, and osteoblasts showed an irregular arrangement at the callus site. The osteoclasts were scattered with a decrement in the number of nuclei. The expression of proinsulin was confirmed in bone marrow derived cells (BMDCs) with neovascularization 2 and 3 weeks after fracture. Immunopositivity for TNF-α was also confirmed in immature chondrocytes and BMDCs with neovascularization at 2 weeks, and the number of positive cells was not decreased at 3 weeks. Examination of GFP-grafted hyperglycaemic mice showed that the majority of cells at the fracture site were GFP-positive. Immunohistochemistry showed that the rate of double positives was 15% for GFP and proinsulin and 47% for GFP and TNF-α. CONCLUSION: LT-HG induces an increase in the number of proinsulin and TNF-α positive cells derived from BMDCs. We suggest that proinsulin and TNF-α positive cells are involved in both bone formation and bone resorption after fracture under hyperglycaemic conditions, resulting in the delay of bone healing.

Onset of Chronic Expanding Hematoma 25 Years After Total Hip Arthroplasty.

Chronic expanding hematoma (CEH) is a rare anatomical condition that gradually expands due to trauma or surgery. We report the case of a 56-year-old woman who developed CEH 25 years after metal-on-polyethylene total hip arthroplasty. She presented with swelling and radiating pain in the right inguinal region. Tocilizumab was administered for treating rheumatoid arthritis and renal amyloid A amyloidosis. Diagnostic imaging and partial resection revealed a soft tissue mass and a CEH, respectively. The symptoms recurred 6 months later; dialysis was initiated, and the CEH was resected under general anesthesia, leading to improvement. This case report emphasizes the importance of prompt diagnosis and intervention in CEH management for preventing further complications and improving the patient's quality of life.

Increased Cellular Expression of Interleukin-6 in Patients With Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL. SUMMARY OF BACKGROUND DATA: Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear. METHODS: Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors. RESULTS: Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9 , Runx2 , and SIRT1 . In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front. CONCLUSIONS: IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL.

Prophylactic Intraventricular Piping Method Prevents Entrapped Temporal Horn After Removal of Ventricle Trigone Meningioma: Technical Note.

BACKGROUND: An entrapped temporal horn (ETH) is one of the critical complications after tumor removal in the lateral ventricle trigone that sometimes becomes life threatening. OBJECTIVE: We sought to develop a novel intraoperative method of prophylactic intraventricular piping (PIP) just after tumor removal to prevent ETH. METHODS: Three patients with meningiomas in the lateral ventricle trigone were treated by a novel intraoperative method of PIP just after tumor removal to prevent ETH. Silicone catheters normally used as ventricular drainage catheters were cut to 5- to 6-cm length and inserted into the tumor cavity to ensure communication between the temporal horn and the atrium or the body of the lateral ventricle through the piping straddling the trigone. RESULTS: None of our patients developed ETH during the follow-up period without complications caused by the tube placement. CONCLUSIONS: PIP might be beneficial to prevent ETH because constant osmotic pressure and constant cerebrospinal fluid pulse wave transmission are maintained between each compartment of the lateral ventricle.

Three-dimensional vessel wall MRI to characterize thrombus prior to endovascular thrombectomy for large vessel occlusion stroke.

BACKGROUND AND PURPOSE: Endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) caused by large vessel occlusion requires rapid and reliable imaging of the vessel course including the clot to reduce complications and ensure success. However, no method to acquire this information has been established. METHODS: Six consecutive patients with AIS caused by large vessel occlusion underwent EVT in our institute. High-resolution vessel wall MRI was performed using three-dimensional (3D) variable refocusing flip angle pulse and turbo spin-echo sequences (VRFA-TSE) with the volume isotropic turbo spin-echo acquisition (VISTA) technique. This study evaluated the effectiveness of 3D proton density-weighted (PDW) VRFA-TSE (called PDW-VISTA) compared with T2-weighted (T2W) VRFA-TSE (called T2W-VISTA) to demonstrate the cerebral vessels including the occluded invisible lesion. RESULTS: PDW-VISTA and T2W-VISTA were successfully performed in all cases. PDW-VISTA was more useful to visualize the anterior circulation than T2W-VISTA by clearly revealing invisible vessels, whereas PDW-VISTA and T2W-VISTA had similar findings in the posterior circulation. The vessel courses shown by 3D PDW-VISTA imaging before treatment and digital subtraction angiography after treatment showed good agreement in all cases. Furthermore, 3D PDW-VISTA imaging demonstrated the length and size of the clot. CONCLUSIONS: PDW-VISTA imaging was found to more clearly depict the cerebral vessels including occluded lesion than T2W-VISTA imaging. Findings of thrombus size and length were important for correctly placing the stent retriever and securing safety during the procedure.

Phenotypic classification of knee osteoarthritis according to pain mechanisms; a clinical observational study.

BACKGROUND: Pain in knee osteoarthritis is considered to be nociceptive. Recently, involvement of neuropathic pain and psychosocial factors in knee osteoarthritis has been reported. However, the following details are unclear: 1) How often are neuropathic pain and psychosocial factors involved? And 2) Which patients are associated with neuropathic pain and psychosocial factors? METHODS: In 104 patients with knee osteoarthritis, we evaluated neuropathic pain factor with a painDETECT questionnaire and catastrophic thinking using the pain catastrophizing scale. Pain intensity was assessed using the visual analog scale; patients with scores below the median were defined as low-pain group and others as high-pain group. Radiographic severity was categorized according to the Kellgren-Lawrence classification, with grades I-II and III-IV defined as low- and high-grades, respectively. We compared the painDETECT and pain catastrophizing scale scores between the low- and high-pain groups and low- and high-grade groups. Furthermore, the painDETECT and pain catastrophizing scale scores were compared among the following four groups: low-grade/low-pain, low-grade/high-pain, high-grade/low-pain, and high-grade/high-pain. RESULTS: Neuropathic pain factor and catastrophic thinking were found in 16% and 34% of patients, respectively. There were no significant differences in both painDETECT and pain catastrophizing scale scores between the two pain intensity groups. Between the two groups of radiographic severity, there was no significant difference in the painDETECT scores; however, the pain catastrophizing scale score was significantly high in the low-grade group. In addition, there was no significant difference in the painDETECT scores among the four groups; however, the pain catastrophizing scale scores were significantly higher in low-grade/high-pain than in high-grade/low-pain patients. CONCLUSIONS: Therefore, 64% had only nociceptive pain factor. Catastrophic thinking was strong in patients with low radiographic severity, especially in those with high pain intensity. Patients with neuropathic pain factor could not be identified from radiographic severity and pain intensity.

Surgical treatment of wrist joint dysfunction in rheumatoid arthritis: A report of two cases.

In rheumatoid arthritis (RA), it is important to actively treat wrist dysfunction to improve patient outcomes. Herein, we report two cases of wrist dysfunction in RA patients who required partial wrist fusion soon after drug initiation. Case 1: A 38-year-old woman was referred to our hospital because of left wrist joint pain. At the time of examination, swelling and tenderness of the left wrist joint were observed. After 6 months of medication, no improvement in symptoms was noted; therefore, partial wrist fusion was performed. Case 2: A 38-year-old woman was referred to our hospital because of right wrist joint pain. A plain X-ray image showed fusion of the carpal bones. Due to previous failure of drug treatment, the patient opted for arthrodesis. The postoperative course was good in both cases, and the pain improved. In these cases of monoarthritic RA, synovitis and bone destruction were observed, but blood tests showed no features of active disease, and drug treatment was ineffective. In such cases, early surgical treatment should be considered, rather than continuing conservative treatment, to ensure the best outcomes.

Cytokine Profile From the Ligamentum Flavum in Patients with Ossification of the Posterior Longitudinal Ligament in the Cervical Spine.

STUDY DESIGN: Histological, immunohistochemical, and suspension array analyses of cytokine expression in human cervical ossification of the posterior longitudinal ligament (OPLL). OBJECTIVES: The aim of this study was to determine whether changes in the cytokine profile reflect the maturation of chondrocytes and osteoblasts are associated with OPLL development. SUMMARY OF BACKGROUND DATA: OPLL progresses gradually over a prolonged period and may lead to serious spinal cord complications. However, treatment methods only include conservative therapy for neurological symptoms or surgical decompression, whereas preventive therapy for OPLL remains nonexistent. METHODS: Ligamentous samples were harvested from 24 patients with OPLL who underwent spinal surgery, and five control samples from cervical spondylotic myelo/radiculopathy patients without OPLL. Tissue sections were used for immunohistochemical studies and primary cells were cultured from the ligamentous samples for cytokine profiling. Using a suspension array system, concentrations of 27 inflammatory cytokines or growth factors were measured to generate the cytokine profiles. RESULTS: Suspension array and immunoblot analysis revealed significant increments in the levels of interleukin (IL)-6, IL-1α, basic fibroblast growth factor, and RANTES in patients with OPLL. Immunohistochemical analysis further revealed that these factors were present in mesenchymal cells within the degenerative portion of the ligamentous matrix. CONCLUSION: Our findings suggest that specific changes in the cytokine profile during ossification promote osteoblast differentiation, thereby providing new insights into OPLL pathogenesis. Moreover, this work supports the development of a new therapeutic method for preventing OPLL progression by regulating the cytokine profiles.Level of Evidence: 3.

Knee osteoarthritis with patellar dislocation treated by total knee arthroplasty using a lateral parapatellar approach-ingenuity of exposure and closure.

Knee osteoarthritis with patellar dislocation is a rare and difficult-to-treat condition. Several reports of total knee arthroplasty (TKA) combined with various realignment procedures have been published. A 77-year-old man with knee pain was referred to our hospital. Plain radiography revealed a laterally dislocated patella, with osteoarthritic changes in the femorotibial joint. He simply underwent TKA via a lateral parapatellar approach without realignment. We devised methods of exposure and closure to maximize the effect of lateral release by the lateral parapatellar approach. TKA using the lateral parapatellar approach might be effective in treating knee osteoarthritis with patellar dislocation.

Local Application of Magnesium Sulfate Solution Suppressed Cortical Spreading Ischemia and Reduced Brain Damage in a Rat Subarachnoid Hemorrhage-Mimicking Model.

OBJECTIVE: Cortical spreading depolarization (CSD), cortical spreading ischemia (CSI), and early brain injury are involved in the occurrence of delayed brain ischemia after subarachnoid hemorrhage (SAH). We tested whether local application of magnesium (Mg) sulfate solution suppressed CSD and CSI, and decreased brain damage in a rat SAH-mimicking model. METHODS: Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) and high concentration potassium solution were topically applied to simulate the environment after SAH. We irrigated the parietal cortex with artificial cerebrospinal fluid (ACSF), containing L-NAME (1 mM), K+ (35 mM), and Mg2+ (5 mM). Forty-five rats were divided into 3 groups: sham surgery (sham group), L-NAME + [K+]ACSF (control group), and L-NAME + [K+]ACSF + [Mg2+] (Mg group). CSD was induced by topical application with 1 M KCl solution in 3 groups. The effects of Mg administration on CSD and cerebral blood flow were evaluated. Histological brain tissue damage, body weight, and neurological score were assessed at 2 days after insult. RESULTS: Mg solution significantly shortened the total depolarization time, and reduced CSI, histological brain damage, and brain edema compared with those of the control group (P < 0.05). Body weight loss was significantly suppressed in the Mg group (P < 0.05), but neurological score did not improve. CONCLUSIONS: Local application of Mg suppressed CSI and reduced brain damage in a rat SAH-mimicking model. Mg irrigation therapy may be beneficial to suppress brain damage due to CSI after SAH.

Good Postoperative Flexion Angle Improves Knee Function and Improvement of Flexion Angle Increases Patient Satisfaction After Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a well-established procedure for treating knee joint diseases. However, the postoperative range of motion (ROM) varies and is an important indicator of TKA success. Recently, patient-reported outcome measures (PROMs) and patient satisfaction have drawn attention. However, the relationship between ROM and knee function obtained by PROM and satisfaction is not well understood. METHODS: We retrospectively reviewed the data of 375 patients who underwent 500 primary TKA procedures. We measured the ROM before and after surgery. Knee joint function was evaluated using the Knee Injury Osteoarthritis Outcome Score, a PROM, and patients were classified into good function and poor function groups. Patient satisfaction was evaluated on a 5-graded scale as overall satisfaction, and patients were divided into a satisfied or a dissatisfied group according to the obtained scores. ROM was compared between the 2 groups, then significantly different factors were analyzed using multiple logistic regression analysis. Moreover, cut-off points of ROM for obtaining good function and patient satisfaction were determined using ROC curve analysis. RESULTS: The postoperative flexion angle had a significant effect on knee function (P < .001). The cut-off value of the postoperative flexion angle for good knee function was 120°. The improvement in flexion angle had a significant effect on patient satisfaction (P = .004). The cut-off value for the improvement in the flexion angle was 5°. CONCLUSION: The postoperative flexion angle had a significant effect on knee function and improvement in the flexion angle had a significant effect on patient satisfaction.

Usefulness and feasibility of repeated tail artery cannulations in the rat.

Rat ventral caudal artery (VCA, tail artery) cannulation for blood pressure monitoring and blood sampling is essential for maintaining consistent procedures in rat models. Double or triple insults are sometimes necessary, but repeated VCA cannulations have not been compared with repeated femoral artery cannulations. In addition, the collateral system for resistance to ischemia in the rat tail is unclear. Our present study revealed that repeated VCA cannulations on different days was a better technique than repeated femoral artery cannulations in terms of surgical time, postsurgical weight loss and ischemic complications. Furthermore, the lateral caudal arteries and the segmental anastomosing vessels were important for resistance to ischemic complications after VCA occlusion.

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity.

OBJECTIVES: Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. METHODS: Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). RESULTS: There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. CONCLUSION: Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

Embolic Characteristics of Imipenem-Cilastatin Particles in Vitro and in Vivo: Implications for Transarterial Embolization in Joint Arthropathies.

PURPOSE: To elucidate in vitro and in vivo characteristics and embolic properties of imipenem-cilastatin (IPM-CS) compared with hydrogel microspheres. MATERIALS AND METHODS: Particle size distribution was microscopically evaluated with 3 samples of 50 mg IPM-CS suspensions in each of 6 conditions by a mixture of contrast volume: 500 or 1000 µL and vortex mixing time: 5, 10, or 30 s. Time-dependent changes up to 3 h post-mixing were also evaluated. Fifteen male Sprague-Dawley rats (460.2 ± 5.0 g) underwent unilateral renal artery embolization using IPM-CS (n = 11) or hydrogel microspheres (n = 4). Follow-up angiography 48 h after embolization and histological evaluation, including acute tubular necrosis (ATN) and inflammation, were scored using a 5-point scale (from 0 = normal to 4 = severe). RESULTS: Over 91% of IPM-CS particles were <40 µm under all in vitro conditions. With the increased contrast volume, the average particle size also increased (mean ± standard deviation: 11.6 ± 13.9 vs 16.7 ± 18.2 µm for 500 and 1000 µL iodinated contrast, P < .001); however, the impact of the mixing/elapsed time were limited. At 48 h after embolization, all cases in the IPM-CS groups (11/11) showed major to complete recanalization versus no recanalization with hydrogel microspheres (0/4) (P < .001). The following are the median ATN and inflammation grades in the cortex (ventral/dorsal) and medulla (ventral/dorsal) in both groups: IPM-CS, ATN in cortex (2/4) and medulla (1/1), inflammation in cortex (0/0) and medulla (0/0); hydrogel microspheres, ATN in cortex (4/4) and medulla (3/2), inflammation in cortex (1/1) and medulla (1/1). CONCLUSIONS: IPM-CS suspension generated particles that were predominantly smaller than 40 µm and with unique short-term embolic effects, leaving predominantly peripheral ischemic changes.

Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. METHODS: Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. RESULTS: Serum neuron-specific enolase levels were significantly lower in the Mg+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H2 groups at 1 year. Barthel index was higher in the Mg+H2 group than in the control group. CONCLUSIONS: Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014696.

Enhanced Malignant Phenotypes of Glioblastoma Cells Surviving NPe6-Mediated Photodynamic Therapy are Regulated via ERK1/2 Activation.

To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM.