hMSC-mediated Concurrent Delivery of Endostatin and Carboxylesterase to Mouse Xenografts Suppresses Glioma Initiation and Recurrence

Glioma stem cells (GSCs) are known to be maintained within a “vascular niche” thereby, disruption of this microenvironment using antiangiogenesis agents is a promising therapeutic modality. However, this regimen leads to treatment failure and tumor recurrence in patients with glioblastoma multiforme (GBM). Therefore, more effective therapeutic approaches that can eradicate GSCs and the bulk tumors are needed. Toward this goal, we examined the antitumor effects of an antiangiogenesis approach combined with conventional chemotherapy on suppressing glioma xenograft growth. We established three genetically engineered mesenchymal stem cell (MSC) lines (GE-AF-MSCs) by stably transducing the gene encoding endostatin (an antiangiogenesis factor), the gene encoding secretable form of carboxylesterase 2 (sCE2, a prodrug-activating enzyme), or a mixture of both genes. Among the three GE-AF-MSC cell lines, injection of amniotic fluid (AF)-MSCs-endostatin-sCE2 cells into U87MG-EGFRvIII-driven orthotopic brain tumor and postsurgery tumor recurrence models, and subsequent CPT11 treatment yielded the strongest antitumor responses, including diminished angiogenesis, increased cell death, and a reduced Nestin-positive GSC population. Therefore, our antitumor strategy provides a novel basis for designing stem cell-mediated therapeutic approaches to target and eradicate GSCs and the bulk tumors.     

Arginase Inhibition by Ethylacetate Extract of Caesalpinia sappan Lignum Contributes to Activation of Endothelial Nitric Oxide Synthase

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.     

Region-based diagnostic performance of multidetector CT for detecting peritoneal seeding in ovarian cancer patients

Purpose  

To determine the accuracy of multi-detector CT (MDCT) compared with the surgical findings, such as peritoneal seeding and metastatic lymph nodes, in ovarian cancer patients.     

Robotic-Assisted versus Laparoscopic Surgery for Low Rectal Cancer: Case-Matched Analysis of Short-Term Outcomes

Purpose  

The aim of this study is to compare short-term outcomes and surgical quality of robot-assisted (RAP) and laparoscopic (LAP) total mesorectal excision (TME) in patients with low rectal cancer.     

Measurement of glucose and fructose in clinical samples using gas chromatography/mass spectrometry

Objective:The impact of increased fructose consumption on carbohydrate metabolism is a topic of current interest, but determination of serum level has been hindered due to low concentration and interference from serum glucose. We are reporting a method for the quantification of glucose and fructose in clinical samples using gas chromatography/mass spectrometry (GC/MS). The accuracy and precision of GC/MS and an enzymatic assay were compared.Design and methods:Mass spectrometry fragmentation patterns of methyloxime peracetate derivatized aldose and ketose were determined. Unique fragments for glucose and fructose were used for quantitative analysis using isotope labeled recovery standards.Results:Methyloxime peracetate derivatives of glucose and fructose showed characteristic loss of acetate (M-60) or ketene (M-42) under chemical ionization (CI). Under electron impact (EI) ionization, a unique C1–C2 fragment of glucose was formed, while a C1–C3 fragment was formed from keto-hexoses. These unique fragments were used in the quantitative assay of glucose and fructose in clinical samples. In clinical samples, the GC/MS assay has a lower limit of detection than that of the enzymatic assay. In plasma samples from patients evaluated for diabetes the average serum glucose and fructose were 6.19 ± 2.72 mM and 46 ±  25.22 μM. Fructose concentrations in many of these samples were below the limit of detection of the enzymatic method.Conclusion:Derivatization of aldose and ketose monosaccharides to their respective O-methyloxime acetates for GC/MS analysis is a facile method for determination of serum/plasma glucose and fructose samples.     

Post‐Liver Transplantation Multicentric Castleman Disease Treated with Valganciclovir and Weaning of Immunosuppression

Multicentric Castleman disease is a lymphoproliferative disorder which when seen in the setting of HIV/AIDS is often associated with human herpes virus 8 (HHV‐8) infection. We describe the case of a HIV‐negative man who developed HHV‐8‐associated multicentric Castleman disease 11 years after liver transplantation. The patient presented with fevers and weight loss. Physical examination revealed enlarged cervical, axillary and inguinal lymph nodes. Widespread lymphadenopathy was confirmed on computed tomography (CT) scanning. Histology of an enlarged lymph node showed a polymorphous infiltrate with mature plasma cells, plasmacytoid lymphocytes and occasional blasts within the cortex and paracortex. The diagnosis of Castleman disease was confirmed by the finding of numerous HHV‐8‐immunopositive cells around the regressed lymph node follicles and the detection of HHV‐8 on plasma PCR. Although the conventional treatment for this condition has been combination chemotherapy, in the post‐transplant context it was decided to treat the patient with valganciclovir and cessation of immunosuppression. His symptoms resolved rapidly and repeat plasma PCR done 3 months after starting treatment was negative for HHV‐8. A follow‐up CT scan showed a dramatic reduction in the size and amount of lymphadenopathy. After 15 months of treatment, he remains well with no evidence of graft dysfunction or rejection.