Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non‐taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M‐phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation‐induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient‐derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas.

Clinical response predictions through image examinations after neoadjuvant chemotherapy (NAC) for breast cancer is important. The present study aimed to evaluate the utility of a novel imaging modality, positron-emission tomography/magnetic resonance imaging (PET/MRI), in predicting the pathological complete response (pCR) to NAC in patients with early breast cancer. A total of 74 patients underwent PET/MRI, mammography (MG), including tomosynthesis, and ultrasound (US) after NAC. The complete response was predicted using each modality and these outcomes were compared accordingly. In terms of PET/MRI, complete response (CR) was defined as the disappearance of 18F-fluorodeoxyglucose uptake and the absence of enhanced lesions with contrast enhanced MRI. In MG and US, undetectable lesions were considered as CR. The background and tumor characteristics of patients were also analyzed between the pCR and non-pCR cases. Overall, 18 (24.3%) of the 74 patients achieved pCR. The overall sensitivity and specificity of PET/MRI were 72.2 and 78.6%, respectively. Both the sensitivity in hormone receptor (HR)-positive cases and the specificity in HR-negative cases were 100%. HR-negative and human epidermal growth factor receptor 2 (HER2)-positive cases demonstrated a significant association with pCR compared with HR-positive cases and triple negative cases (P=0.017). Furthermore, patients with ‘mass’ type lesions evaluated by MRI before NAC experienced pCR with a higher frequency than those with ‘non-mass’ type lesions. There was a statistically significant difference between the two groups (P=0.018). In conclusion, PET/MRI is a different diagnostic approach that utilizes a multi-modality system. It demonstrates reasonable diagnostic accuracies of the responses of NAC with reference to hormonal subtypes in breast cancer.

Background:Small bowel adenocarcinoma (SBA) accounts for <2% of all gastrointestinal malignancies. The most common organs of SBA metastases are the abdominal lymph node, liver, and peritoneum. There have been almost no reports of brain metastases of SBA. Dabaja et al. reported 1 case of brain metastasis out of 217 SBA cases, but details of the clinical course of the case were unclear. Our case might be the first report covering the full clinical course, pathological findings, and genetic data. Here, we report a very rare case of brain metastasis from poorly differentiated SBA.Case Description:A 54-year-old man who suffered from abdominal pain and melena visited a nearby hospital. This patient had no risk factors for SBA. He underwent partial resection of the jejunum with regional lymphadenectomy and combined resection of the transverse colon. Pathological diagnosis was poorly differentiated adenocarcinoma, pT4N2M0 Stage IIIB (UICC-TNM: 8th edition). One month after curative surgery, liver metastasis was detected by a computed tomography (CT) scan, and then, palliative chemotherapy was started. During the third-line chemotherapy, a brain tumor on the left cerebellum was detected by the CT scan. Tumor resection was performed, and the histopathological features coincided with the primary jejunum tumor. Based on surgical, radiological, pathological, and genetic findings, this brain tumor was comprehensively diagnosed as a metastasis from poorly differentiated SBA.Conclusion:Here, we experienced a very rare case of brain metastasis from poorly differentiated SBA.

Purpose A single dose of N-ethyl-N-nitrosourea (ENU) during late prenatal or early postnatal development induces a high incidence of malignant schwannomas and gliomas in rats. Although T -&gt; A mutations in the transmembrane domain of the neu (c-ErbB-2) gene are the driver mutations in ENU-induced malignant schwannomas, the molecular basis of ENU-induced gliomas was unknown. The objectives of this study were to identify driver mutations in ENU-induced rat gliomas. Methods We performed whole-genome sequencing of gliomas that developed in three BDIV and two BDIX rats exposed to a single dose of 80 mg ENU/kg body weight on postnatal day one. Results T:A-&gt;A:T and T:A-&gt;C:G mutations, which are typical for ENU-induced mutagenesis, were predominant (41-55% of all somatic single nucleotide mutations). T-&gt;A mutations were detected in all 5 rat gliomas at Braf codon 545 (V545E), which corresponds to the human BRAF V600E. Additional screening revealed that 33 gliomas in BDIV rats and 12 gliomas in BDIX rats all carried a Braf V545E mutation, while peritumoral brain tissue of either strain (n=16) had the wild-type sequence. The gliomas were immunoreactive to BRAF V600E antibody. Conclusions Braf mutation is a frequent early event in the development of rat gliomas caused by a single dose of ENU. Citation Format: Kaishi Satomi, Qi Wang, Ji Eun Oh, Barbara Hutter, Benedikt Brors, Nicolle Diessl, Hai-Kun Liu, Stephan Wolf, Otmar Wiestler, Paul Kleihues, Bernd Koelsch, Andrea Kindler-Rohrborn, Hiroko Ohgaki. Braf mutations initiate the development of rat gliomas induced by postnatal exposure to N-ethyl-N-nitrosourea (ENU) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4807. doi:10.1158/1538-7445.AM2017-4807

background: IDH mutant astrocytoma has good prognosis compared with IDH wildtype one. In IDH mutant astrocytoma, However, patients with CDKN2A/B homozygous deletion (HD) are worse prognosis than non CDKN2A/B HD. Here we analyzed the prognosis of glioma patients identified with CDKN2A/B HD in our hospital. method: There were 62 cases, and female was 26. Mean age of all cases was 41.2 and median age was 38. In IDH gene status, R132H was 59 cases (95.2%), R172K 2 (3.2%) and R132S 1 (1.6%). All 62 cases were TERT wildtype. CDKN2A/B HD were 12 cases (19.4%). In log-rank test, the group of CDKN2A/B HD was poor prognosis than non HD. In astrocytoma grade 3, CDKN2A/B HD had significantly poor prognosis (p=0.002). In Cox proportional hazard model analysis, CDKN2A/B HD was effective predictive prognostic factor as well as age and grading (p=0.03). discussion/conclusion: We showed that CDKN2A/B HD was good predictive prognostic factor in IDH mutant astrocytoma.