Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle.

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

Delayed diagnosis of traumatic cervical subluxation in patients with mandibular fractures: a 5-year retrospective study.

BACKGROUND: Mandibular bone fracture associated with traumatic cervical subluxation is a rare injury. The diagnosis of a traumatic cervical subluxation is more easily delayed than other conditions in patients with mandibular bone fractures. The aim of this study is to investigate the incidence of traumatic cervical subluxation associated with mandibular bone fractures. METHODS: This is a retrospective cohort study of 653 consecutive emergency department patients with mandibular bone fractures investigated for evidence of concomitant traumatic cervical subluxation. RESULTS: This study reports on 7 patients (1.07%) with a diagnosis of traumatic cervical subluxation from a cohort of 653 with mandibular bone fractures as a result of motor vehicle accidents. Two of seven patients had their diagnosis made while in the emergency room, thus, 71.43% of these injuries were discovered on studies done up to 10 days after the trauma, including after surgical correction of the mandibular bone fracture. CONCLUSION: The importance of a thorough initial examination (both physical and radiologic) and suspicion of traumatic cervical subluxation in patients with mandibular bone fractures is worth emphasizing as delayed diagnosis and management could result in permanent neurologic injury. We suggest dynamic flexion-extension cervical radiographs and thin-slice computerized tomography scans in patients with mandibular fractures routine as an important and routine practice protocol.

Targeted concurrent and sequential delivery of chemotherapeutic and antiangiogenic agents to the brain by using drug-loaded nanofibrous membranes.

Glioblastoma is the most frequent and devastating primary brain tumor. Surgery followed by radiotherapy with concomitant and adjuvant chemotherapy is the standard of care for patients with glioblastoma. Chemotherapy is ineffective, because of the low therapeutic levels of pharmaceuticals in tumor tissues and the well-known tumor-cell resistance to chemotherapy. Therefore, we developed bilayered poly(d,l)-lactide-co-glycolide nanofibrous membranes that enabled the sequential and sustained release of chemotherapeutic and antiangiogenic agents by employing an electrospinning technique. The release characteristics of embedded drugs were determined by employing an in vitro elution technique and high-performance liquid chromatography. The experimental results showed that the fabricated nanofibers showed a sequential drug-eluting behavior, with the release of high drug levels of chemotherapeutic carmustine, irinotecan, and cisplatin from day 3, followed by the release of high concentrations of the antiangiogenic combretastatin from day 21. Biodegradable multidrug-eluting nanofibrous membranes were then dispersed into the cerebral cavity of rats by craniectomy, and the in vivo release characteristics of the pharmaceuticals from the membranes were investigated. The results suggested that the nanofibrous membranes released high concentrations of pharmaceuticals for more than 8 weeks in the cerebral parenchyma of rats. The result of histological analysis demonstrated developmental atrophy of brains with no inflammation. Biodegradable nanofibrous membranes can be manufactured for long-term sequential transport of different chemotherapeutic and anti-angiogenic agents in the brain, which can potentially improve the treatment of glioblastoma multiforme and prevent toxic effects due to systemic administration.

Diagnosis of traumatic internal carotid artery injury: the role of craniofacial fracture.

Optimally, internal carotid artery (ICA) injury associated with craniofacial trauma should be treated soon after diagnosis. However, diagnosis is difficult and often delayed. The typical symptoms and signs for diagnosis of traumatic ICA injuries are sometimes easily neglected. Clinically, some patients were initially diagnosed by craniofacial fracture nearby the course of ICA. This investigation retrospectively reviews clinical experience in patients with traumatic ICA injury with a focus on the importance of craniofacial fracture nearby the course of ICA observed on brain or facial bone computed tomography. Eighteen patients with traumatic ICA injury were diagnosed at Chang Gung Memorial Hospital, Taiwan, from June 1998 to April 2004, including 10 patients with pseudoaneurysm formation, seven patients with occlusion, and one patient with laceration. Brain or facial bone computed tomography was reviewed retrospectively. The sample included 14 (78%) patients with skull base fractures involving the intracranial course of ICA and three (17%) patients with mandibular and cervical spine fractures near the course of extracranial ICA. Only one (5%) patient did not have evident fracture. Fractures involving the carotid canal were noted in three (17%) patients. Eight patients received interventional treatments. No further interventional treatments for traumatic ICA occlusion were performed as a result of good collateral flow from contralateral ICA or large infarction noted when diagnosed. Three patients with pseudoaneurysm received expectant management. One patient with arterial laceration with extravasation received no further management. Through meticulously evaluating routine brain and facial bone computed tomography, craniofacial fracture involving intracranial or extracranial course of ICA may be an adjuvant indicator of traumatic ICA injury for early diagnosis.