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Cancer cells show constitutive upregulation of glycolysis, and the concentration of lactate thus produced correlates with prognosis. Here, we examined whether lactate concentration and lactate transporter expression are related to migration and invasion activity. We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness. To clarify the effects of MCT1 and MCT4 expression on invasion, we performed migration and invasion assays after transfection with siRNA specific for MCT1 or MCT4. Knockdown of MCT1 or MCT4 did not influence cell migration but reduced invasion; this was also observed for knockdown of the lactate transporter‐associated protein basigin. We also demonstrated that both expression and activity of MMP9 and MMP2 were not correlated with invasion activity and not regulated by MCT1, MCT4 and basigin. Furthermore, the addition of lactate did not increase migration and invasion activity, but low concentration of 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS), a general anion channel blocker, as well as other MCT inhibitors quercetin and simvastatin, inhibited cell invasion without influencing migration activity and the cellular expression of MCT1 and MCT4. This is the first report suggesting that lactate transporters are involved in human cancer cell invasiveness. As such, these proteins may be promising targets for the prevention of cancer invasion and metastasis. (Cancer Sci 2011; 102: 1007–1013)

To facilitate return to work (RTW) in patients with stroke, a health and employment support (HES) program was started at Rosai hospitals in Japan. This study aimed to determine the rate of RTW in patients with stroke under this support program. We collected demographic and clinical data of patients with stroke from the implementation reports of the HES program. The program provided coordinated dual support, such as acute medical treatments, and stroke and vocational rehabilitation on the medical side, and management and support on the workplace side. The primary endpoint was RTW. Successful and unsuccessful RTW were examined using the χ 2 test. The RTW rate curves were analyzed using the Kaplan–Meier method. We enrolled 483 patients; 355 (73%) and 128 (27%) patients had successful and unsuccessful RTW, respectively. Stroke types, neurological findings, and activities of daily living were significant factors for RTW. The Kaplan–Meier method revealed that left hemiplegia, right hemiplegia, and neuropsychological deficits, except for combined disability (hemiplegia with neuropsychological deficits), had similar RTW curves with an RTW rate of > 70%.

BackgroundAverage female life expectancy in Japan is approximately 90 years. Occasionally, we encounter stroke patients older than 90 years.AimsTo determine the clinical features and outcomes associated with cerebral infarction in patients aged ≥ 90 years.MethodsWe examined 289 consecutive patients (163 males, 129 females; mean age 77.5 years) diagnosed with cerebral infarction. We divided them into four groups according to age in years: middle (< 65), pre-old (65–74), old (75–89), and super old (≥ 90). We divided the super old group into mild symptoms (NIHSS ≤ 5) and severe symptoms (NIHSS > 5) and examined outcomes.ResultsStatistically significant associations were observed between female sex, cardiogenic infarction, and high complication rates and super old age. NIHSS and mRS scores at 30-day post-stroke were higher in the super old group. In some cases, complications led to poor prognoses. Eighty-seven percent of patients with mild symptoms (NIHSS ≤ 5) recovered to mRS 0–2 similar to the younger age group. None of the patients with severe symptoms (NIHSS > 5) recovered to mRS 0–2.DiscussionWe investigated the clinical outcomes following cerebral infarction in patients aged 90 years or older and found that mild symptoms were consistently associated with good prognoses, regardless of patients’ age.ConclusionsPatients in the super old group had more severe symptoms and poorer outcomes than younger age groups. However, patients with mild symptoms tended to have better prognoses and returned to daily life similar to the younger age group.

Abstract BACKGROUND Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. OBJECTIVE To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. METHODS We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. RESULTS There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. CONCLUSION In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients. Graphical Abstract Graphical Abstract

5-Aminolevulinic acid (5-ALA) can accumulate protoporphyrin IX (PpIX) in tumour cell mitochondria and is well known for its utility in fluorescence-guided resection of malignant gliomas as a live molecular marker. Previously, we and other authors demonstrated that 5-ALA has a radiosensitizing effect for tumours. In the present study, we aimed to investigate the mechanism underlying the radiosensitizing effect of 5-ALA by focusing on glioma cell mitochondria. Using an enhancer (ciprofloxacin) of 5-ALA-induced PpIX accumulation, we evaluated the influence of ionizing irradiation (IR) and delayed reactive oxygen species (ROS) production 12 h after IR by colony-forming assay and flow cytometry (FCM) with different amounts of PpIX accumulation. The mitochondrial mass and mitochondrial electron transport chain (mtETC) activity were evaluated by FCM and western blot analysis. Cell death and delayed ROS production after IR in glioma cells were increased in proportion to 5-ALA-induced PpIX accumulation. Delayed ROS production enhanced by 5-ALA localized to the glioma cell mitochondria. Mitochondrial mass and mitochondrial complex III activity, among mtETC factors, were also increased 12 h after IR in glioma cells in proportion to 5-ALA-induced PpIX accumulation with some variation. These results suggest that 5-ALA enhances IR-induced mitochondrial oxidative stress and leads to increased cell death with mitochondrial changes, thereby acting as a targeting mitochondrial drug, and so-called radiosensitizer in glioma cells.

PurposeThis study aims to investigate hippocampal subfield volumes in patients with hippocampal sclerosis (HS) without visually detectable MRI abnormalities and to determine the diagnostic accuracy using hippocampal subfield volumes.Materials and methodsWe examined 46 patients with unilateral HS who had a histopathological diagnosis, and 54 controls. The patients were divided into two groups; visually detectable HS (n = 26) and undetectable HS (n = 20) on MRI. The volumes of hippocampal subfield using FreeSurfer were compared among the three groups. Diagnostic accuracy was calculated as the AUC of ROC using cutoff values for each individual subfield.ResultsCompared with the controls, visually detectable HS showed significantly reduced volumes of all the hippocampal subfields and entire hippocampus, whereas visually undetectable HS showed significant atrophy only in the CA3 and hippocampus-amygdala-transition-area. To diagnose visually undetectable HS, the CA3 volumes had AUC of 0.719, which was higher than AUC of 0.614 based on the entire hippocampal volumes.ConclusionVisually undetectable HS demonstrated volume reductions in the CA3. Further, the CA3 volumes was more useful to diagnose visually undetectable HS compared with the entire hippocampal volumes.

The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1.5–2.0 cm. The IMRT boost doses were then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO to achieve radiosensitization. The planned RT dose was completed in all patients, while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain. The toxicities were mild, no non-hematological toxicity of Grade 3–5 was observed. The 2-year overall survival (OS) and progression-free survival rates in all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1 months. In conclusion, the combined therapy of RT using IMRT boosts after HBO with chemotherapy was a feasible and promising treatment modality for patients with glioblastoma. The results justify further evaluation to clarify the benefits of this therapy.

Y‐box binding protein‐1 (YB‐1) is a member of the cold shock protein family and functions in transcription and translation. Many reports indicate that YB‐1 is highly expressed in tumor cells and is a marker for tumor aggressiveness and clinical prognosis. Here, we show clear evidence that YB‐1 is expressed in the angiogenic endothelial cells of various tumors, such as glioblastoma, esophageal cancer, gastric cancer, colon cancer, and lung cancer, as well as in tumor cells. YB‐1 was highly expressed in glomeruloid microvascular endothelial cells of brain tumors and microvessels in the desmoplastic region around multiple solid tumors. On the other hand, no or low YB‐1 expression was observed in normal angiogenic endothelial cells from fetal kidney, newborn lung, and placenta. The endothelial cells in inflammatory regions of granulomas were also weakly labeled. Knockdown of YB‐1 expression by small‐interfering RNA induced G1 cell cycle arrest and inhibited the growth of human umbilical vein endothelial cells stimulated by growth factors. Taken together, YB‐1 plays an important role in the growth of not only tumor cells but also tumor‐associated endothelial cells, suggesting that YB‐1 is a promising target for cancer therapy. (Cancer Sci 2010)

Although the etiology of classical trigeminal neuralgia is clearly understood to be neurovascular compression, the exact etiology of trigeminal neuralgia with continuous pain is often unknown. Mild sphenoid sinusitis is not usually considered to induce trigeminal neuralgia, especially when limited to the maxillary nerve. We report a rare case of trigeminal neuralgia of the maxillary nerve caused only by mild sphenoid sinusitis and discuss the significance of the anatomical structure and diagnostic procedures. A 45-year-old woman noticed a sudden onset of temporal pain followed by numbness on her right cheek. Her right gingiva also experienced sensory disturbance. The symptoms gradually subsided after the initial onset, but they persisted. She visited our hospital for further examinations and had no febrile episodes throughout the course. A tingling sensation and sensory disturbance were only identified in the maxillary nerve. No other neurological symptoms were noted. Magnetic resonance imaging revealed mild sphenoid sinusitis on the right side. The absence of the bony boundary between the sphenoid sinus and maxillary nerve was revealed using thin-sliced computed tomography (CT). The patient’s symptoms were diagnosed as maxillary neuropathy caused by mild sinusitis. The bony defect around the maxillary nerve was considered to have affected development of the pathological process. Even mild sphenoid sinusitis can cause inflammation to spread to the maxillary nerve if no bony boundary exists between it and the sphenoid sinus. A coronal CT study is highly beneficial for clarifying the pathophysiological mechanism of trigeminal neuralgia limited to the maxillary nerve.

Meningioma accounts for ~25% of all primary intracranial neoplasms and the incidence increases with age. Prvios population-based studies demonstrated that the annual incidence of intracranial meningiomas was 1.2-3.1/100,000 population. In particular, the incidence of this disease among the elderly is high. Recently, increased life expectancy and greater use of diagnostic radiological imaging led to an increased incidence in the diagnosis of intracranial meningiomas, both symptomatic and asymptomatic, in the elderly. Thus, neurosurgeons may be increasingly confronted with the management of intracranial meningiomas in the elderly. In practice, it is often difficult for physicians to determine whether traditional surgical resection is the optimal management strategy for intracranial meningiomas in the elderly. However, reported clinical studies about the outcome of surgical resection of intracranial meningiomas in the elderly are limited. Increased risk of mortality and morbidity associated with surgical treatment for intracranial meningiomas in the elderly compared with younger patients have been controversial. In the present study, the clinical features of intracranial meningiomas in 70 consecutive intracranial meningioma patients that underwent surgical treatment at the affiliated hospital of University of Occupational and Environmental Health between 2007 and 2013 were assessed. In addition, patient selection and surgical management of intracranial meningioma in elderly patients was discussed. Preoperative factors, including symptoms, tumor location, tumor size, Karnofsky Performance Scale (KPS) score and American Society of Anesthesiology (ASA) score, and postoperative factors, including pathological diagnosis, tumor proliferation index (Ki-67), resection rate (Simpson grade), length of hospital stay and discharge destination were retrospectively analyzed in patients aged ≥75 years (n=16; elderly group) and <75 years (n=54; younger group). Outcomes were assessed 6 months after surgery. Multivariate logistic regression revealed that tumor resection rate (Simpson grade III-V) was an important predictor of surgical complications (odds ratio, 5.662; 95% confidence interval, 1.323-24.236; P=0.0194). Perioperative morbidity was not correlated with age (>75 years), tumor location, tumor size, KPS score or ASA score. Thus, the present study indicated that age is not associated with surgical outcome in elderly meningioma patients. Regardless of patient age, the decision to perform surgical resection should be made on an individual basis wherein tumor characteristics and the general health of the patient are considered.