Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-yearold female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.

A 35-year-old male presented with atypical aphasia following left anterior choroidal artery infarction associated with distal internal carotid artery dissection. He presented with 1) lexical-semantic deficit without semantic impairment, 2) frequent surface errors (both surface dyslexia and dysgraphia), and 3) intact non-word reading/repetition (preserved sub-lexical route), suggesting deficit in the phonological output lexicon. Diffusion-tensor tractography analysis revealed disruption in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus, which might serve as potential subcortical neural correlates for phonological output lexicon.

Background/Aims: Heme oxygenase-1 (HO-1) plays a central role in cellular defense against inflammatory insults, and its induction in macrophages potentiates their efferocytic activity. In this study, we explored the potential role of macrophage HO-1 in the resolution of experimentally induced colitis. Methods: To induce colitis, male C57BL/6 mice were treated with 2% dextran sulfate sodium (DSS) in the drinking water for 7 days. To investigate efferocytosis, apoptotic colon epithelial CCD 841 CoN cells were coincubated with bone marrow-derived macrophages (BMDMs). Results: Administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blunted the resolution of DSS-induced intestinal inflammation and expression of the proresolving M2 macrophage marker CD206. BMDMs treated with apoptotic colonic epithelial cells showed significantly elevated expression of HO-1 and its regulator Nrf2. Under the same experimental conditions, the proportion of CD206-expressing macrophages was also enhanced. ZnPP treatment abrogated the upregulation of CD206 expression in BMDMs engulfing apoptotic colonic epithelial cells. This result was verified with BMDMs isolated from HO-1-knockout mice. BMDMs, when stimulated with lipopolysaccharide, exhibited increased expression of CD86, a marker of M1 macrophages.Coculture of lipopolysaccharide-stimulated BMDMs with apoptotic colonic epithelial cell debris dampened the expression of CD86 as well as the pro-inflammatory cytokines in an HO-1-dependent manner. Genetic ablation as well as pharmacologic inhibition of HO-1 significantly reduced the proportion of efferocytic BMDMs expressing the scavenger receptor CD36. Conclusions HO-1 plays a key role in the resolution of experimentally induced colitis by modulating the polarization of macrophages.

Background: Acanthosis nigricans is characterized by a velvety thickening of the epidermis accompanied by different degrees of hyperpigmentation, and known to be linked to obesity and insulin resistance. Objective: We aimed to analyze obesity-related factors in acanthosis nigricans patients and to evaluate the correlations between acanthosis nigricans and various factors. Methods: From January 2004 to February 2015, 27 acanthosis nigricans patients participated in this study. Blood samples were collected from a control group of seven overweight people and from the seven acanthosis nigricans patients, and they were analyzed for different obesity-related factors. Skin samples were collected from the 23 acanthosis nigricans patients and from 11 patients with epidermal nevi, and immunohistochemistry was performed to detect the presence of adiponectin receptor 1, adiponectin receptor 2, and the leptin receptor. Results: The median serum leptin level in the acanthosis nigricans patients (13 ng/mL) was significantly higher than that in the overweight control individuals (8.9 ng/mL) (p=0.021). The acanthosis nigricans patients had significantly higher levels of insulin-like growth factor-1 in their serum samples (p=0.017). The immunohistochemical analysis determined that the skin from the acanthosis nigricans patients stained significantly more intensely for the leptin receptor compared with that seen in the skin from the patients with epidermal nevi (p=0.002). Conclusion In conclusion, this study’s findings suggest that the levels of leptin and insulin-like growth factor-1 in the serum, and the expression of the leptin receptor in the skin are elevated with acanthosis nigricans.

Many previous studies have shown reduced glucose uptake in the ischemic brain. In contrast, in a permanent unilateral common carotid artery occlusion (UCCAO) mouse model, our pilot experiments using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) revealed that a subset of mice exhibited conspicuously high uptake of glucose in the ipsilateral hemisphere at 1 week post-occlusion (asymmetric group), whereas other mice showed symmetric uptake in both hemispheres (symmetric group). Thus, we aimed to understand the discrepancy between the two groups. Cerebral blood flow and histological/metabolic changes were analyzed using laser Doppler flowmetry and immunohistochemistry/Western blotting, respectively. Contrary to the increased glucose uptake observed in the ischemic cerebral hemisphere on FDG PET (p<0.001), cerebral blood flow tended to be lower in the asymmetric group than in the symmetric group (right to left ratio [%], 36.4±21.8 vs. 58.0±24.8, p=0.059). Neuronal death was observed only in the ischemic hemisphere of the asymmetric group. In contrast, astrocytes were more activated in the asymmetric group than in the symmetric group (p<0.05). Glucose transporter-1, and monocarboxylate transporter-1 were also upregulated in the asymmetric group, compared with the symmetric group (p<0.05, respectively). These results suggest that the increased FDG uptake was associated with relatively severe ischemia, and glucose transporter-1 upregulation and astrocyte activation. Glucose metabolism may thus be a compensatory mechanism in the moderately severe ischemic brain.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

No abstract available.
Dermatitis, Atopic ; Stem Cells

Azathioprine is an immunosuppressive drug that has been widely used in dermatology for the treatment of immunobullous diseases. Myelosuppression is the most important side effect and requires close observation of the complete blood cell count. The clinical findings of myelosuppression include general weakness, poor oral intake, nausea, dyspnea, and pallor. It can occur within several weeks to years after initial azathioprine treatment; thus, a weekly full blood count for the first 4 weeks, followed by reduced frequency of monitoring to a minimum of once every 3 months is recommended. If the myelosuppression is not treated properly, it can lead to fever, secondary infection, sepsis, and even death. Herein, we present three educational cases for dermatologists to order to underline the risk of myelosuppression during azathioprine treatment.
Azathioprine* ; Blood Cell Count ; Coinfection ; Dermatology ; Dyspnea ; Fever ; Nausea ; Pallor ; Sepsis

OBJECTIVE: Although Type D personality has been associated with the prognosis of various cardiac diseases, few studies have investigated the influence of Type D personality on the cardiac and psychiatric prognoses of patients with atrial fibrillation (AF). METHODS: Depression, anxiety, and quality of life were measured at baseline and 6 months. The recurrence of AF was measured during 1-year following radiofrequency catheter ablation (RFCA) for AF. The Kaplan-Meier method with log-rank tests were used to compare the cumulative recurrence of AF. ACox proportional hazard model was conducted to identify factors that contribute to the recurrence of AF. RESULTS: A total of 236 patients admitted for RFCA were recruited. Patients with a Type D personality had higher levels of depression and anxiety and a poorer quality of life compared to controls. Although depression, anxiety, and quality of life had improved 6 months after RFCA, significant differences in psychiatric symptoms remained between patients with and without Type D personality. In the Cox models, the type of AF was the only factor that influenced the recurrence of AF. CONCLUSION: Our results suggest that Type D personality predominately influences psychological distress in patients with AF, but not the recurrence of AF.
Anxiety ; Atrial Fibrillation* ; Catheter Ablation* ; Catheters* ; Depression ; Follow-Up Studies* ; Heart Diseases ; Humans ; Methods ; Prognosis* ; Proportional Hazards Models ; Quality of Life ; Recurrence ; Type D Personality*

PURPOSE: To investigate the exchange and redistribution of hyperpolarized ¹³C metabolites between different pools by temporally analyzing the relative fraction of dual T₂* components of hyperpolarized ¹³C metabolites. MATERIALS AND METHODS: A dual exponential decay analysis of T₂* is performed for [1-¹³C] pyruvate and [1-¹³C] lactate using nonspatially resolved dynamic ¹³C MR spectroscopy from mice brains with tumors (n = 3) and without (n = 4) tumors. The values of shorter and longer T₂* components are explored when fitted from averaged spectrum and temporal variations of their fractions. RESULTS: The T₂* values were not significantly different between the tumor and control groups, but the fraction of longer T₂* [1-¹³C] lactate components was more than 10% in the tumor group over that of the controls (P < 0.1). The fraction of shorter T₂* components of [1-¹³C] pyruvate showed an increasing tendency while that of the [1-¹³C] lactate was decreasing over time. The slopes of the changing fraction were steeper for the tumor group than the controls, especially for lactate (P < 0.01). In both pyruvate and lactate, the fraction of the shorter T₂* component was always greater than the longer T₂* component over time. CONCLUSIONS: The exchange and redistribution of pyruvate and lactate between different pools was investigated by dual component analysis of the free induction decay signal from hyperpolarized ¹³C experiments. Tumor and control groups showed differences in their fractions rather than the values of longer and shorter T₂* components. Fraction changing dynamics may provide an aspect for extravasation and membrane transport of pyruvate and lactate, and will be useful to determine the appropriate time window for acquisition of hyperpolarized ¹³C images.
Animals ; Brain ; Lactic Acid ; Magnetic Resonance Spectroscopy ; Membranes ; Mice ; Pyruvic Acid