A combined endovascular and surgical approach conducted in a hybrid OR provides a new strategy for the treatment of complex neurovascular diseases.

Ischemic preconditioning (IPC) has protective effects against ischemia-perfusion injury of organs. In the present study, we investigated the associated mechanisms after performing remote IPC (rIPC) of lower limbs by clamping abdominal aorta in mice. Subsequent experiments showed decreased damage and paralysis of lower limbs following spinal cord injury (SCI). Concomitantly, plasma vascular endothelial growth factor (VEGF) levels were increased 24 h after rIPC compared with those in sham-operated animals. In subsequent microRNA analyses, thirteen microRNAs were downregulated in exosomes 24 h after rIPC. Further studies of femoral CD34-positive bone marrow (BM) cells confirmed downregulation of these seven microRNAs 24 h after rIPC compared with those in sham-operated controls. Subsequent algorithm-based database searches suggested that two of the seven microRNAs bind to the 3′ UTR of VEGF mRNA, and following transfection into CD34-positive BM cells, anti-miR-762, and anti-miR-3072-5p inhibitors led to increased VEGF concentrations. The present data suggest that rIPC transiently increases plasma VEGF levels by downregulating miR-762 and miR-3072-5p in CD34-positive BM cells, leading to protection against organ ischemia.

Abstract. Although gemcitabine (GEM) is frequently used in the treatment of pancreatic cancer, the effects are limited. To increase the inhibitory effect of GEM, the identification of a molecular target is needed. Recent studies have revealed that doublecortin-like kinase 1 (Dclk1) positively regulates tumor growth, invasion, metastasis, factors related to epithelialmesenchymal transition (EMT), pluripotency, angiogenesis, and anti-apoptosis in pancreatic cancer cells. Therefore, Dclk1 is a potential therapeutic target for pancreatic cancer. However, the Dclk1-signaling pathway including its substrate proteins remains to be elucidated. To identify the candidate substrate proteins phosphorylated by Dclk1, we performed a cancer-related phosphorylated protein microarray using Dclk1-inhibited MIA Paca2 cells. Expression levels of phosphorylated cdc25A (p-cdc25A) and phosphorylated Chk1 (p-Chk1), belonging to the ATR pathway, were decreased by treatment with Dclk1 inhibitor LRRK2-IN-1 (LRRK), indicating Dclk1 involvement in the ATR pathway. Consistent with this finding, the GEM-induced p-Chk1 expression was significantly decreased by treatment with LRRK. Notably, combined treatment with GEM and LRRK allowed cell cycle progression without arresting at S phase, while individual treatment with GEM induced cell cycle arrest at S phase. In addition, combined treatment with GEM and LRRK increased the number of γ-H2AX-positive cells compared with that upon individual treatments. Moreover, LRRK alone, and combined treatment with GEM and LRRK, induced caspase-3 activation and PARP1 cleavage, in contrast to treatment with GEM alone. Finally, combined treatment with GEM and LRRK significantly reduced cell survival compared to individual treatment with GEM. These results indicate that Dclk1 inhibition in combination with GEM treatment offers a novel approach to treat pancreatic cancer cells.

The report describes a rare case of a patient with a calcified cerebellar metastasis arising from a primary ovarian cancer. The patient was a 33-year-old woman with a long history of stage IIIc ovarian cancer who had undergone transabdominal hysterectomy and bilateral oophorectomy followed by chemotherapy with gemcitabine hydrochloride. Incidentally, computed tomography (CT) revealed a cerebellar tumor with calcification. The size of the tumor gradually increased, and lateral suboccipital craniotomy was performed for gross total removal of the tumor. The histological diagnosis was ovarian mucinous adenocarcinoma. The patient's postoperative course was uneventful, and she was discharged two days after surgery. Brain metastases from ovarian cancer are rare. In the review of metastatic brain tumors arising from a primary ovarian cancer in the Department of Obstetrics and Gynecology at our institution, this phenomenon was noted in only 10 cases (0.24%) of 4,158 patients with ovarian cancer seen at our center over a period of 8 years. Moreover, only three cases of calcified metastatic brain tumor have been reported previously. In conclusion, complete tumor resection may be an acceptable approach for patients with calcified metastatic tumors both for therapeutic considerations and to obtain tissue for confirmation of histopathological diagnosis. Metastatic brain tumors can be calcified, and should be considered within the differential diagnosis of calcified intracranial lesions to avoid any delay in diagnosis or treatment.

Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages (from 2 to 83 years old). We collected fresh right atria and cultured cardiosphere-derived cells (CDCs), which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age. The expression of senescence-associated b-galactosidase and the DNA damage marker, gH2AX, showed a slightly higher trend in CDCs from older patients (≥65 years). The expression of VEGF, HGF, IGF-1, SDF-1, and TGF-b varied among samples, and the expression of these beneficial factors did not decrease with age. An in vitro angiogenesis assay also showed that the angiogenic potency of CDCs was not impaired, even in those from older patients. Our data suggest that the impact of age on the quantity and quality of CDCs is quite limited. These findings have important clinical implications for autologous stem cell transplantation in elderly patients.