NMDA Receptor-Mediated Neuroprotective Effect of the Scutellaria baicalensis

The objective of the current research work was to evaluate the neuroprotective effect of the ethanol extract of Scutellaria baicalensis (S.B.) on the excitotoxic neuronal cell death in primary rat cortical cell cultures. The inhibitory effects of the extract were qualitatively and quantitatively estimated by phase-contrast microscopy and lactate dehydrogenase (LDH) assays. The extract exhibited a potent and dose-dependent inhibition of the glutamate-induced excitotoxicity in the culture media. Further, using radioligand binding assays, it was observed that the inhibitory effect of the extract was more potent and selective for the N-methyl-D-aspartate (NMDA) receptor-mediated toxicity. The S.B. ethanol extract competed with [3H] MDL 105,519 for the specific binding to the NMDA receptor glycine site with 50% inhibition occurring at 35.1 μg/mL. Further, NMDA receptor inactivation by the S.B. ethanol extract was concluded from the decreasing binding capability of [3H]MK-801 in the presence of the extract. Thus, S.B. extract exhibited neuroprotection against excitotoxic cell death, and this neuroprotection was mediated through the inhibition of NMDA receptor function by interacting with the glycine binding site of the NMDA receptor. Phytochemical analysis of the bioactive extract revealed the presence of six phytochemical constituents including baicalein, baicalin, wogonin, wogonoside, scutellarin, and Oroxylin A

Recurrent retroperitoneal Schwannomas displaying different differentiation from primary tumor: Case report and literature review

<p>Abstract</p> <p>Background</p> <p>Retroperitoneal Schwannomas are uncommonly found in the retroperitoneum and few of them show malignant transformation and invasion. Local recurrence are common in malignant Schwannomas with very few reports of tumor distinct differentiation at recurrences.</p> <p>Case presentation</p> <p>We report here a rare case of retroperitoneal schwannoma with multiple origins from retroperitoneum and pelvic wall. Pathological examination confirmed the case as a schwannoma with malignant transformation. Radical dissection of the tumors along with the sacrifice of adjacent sigmoid colon and left kidney failed to provide a cure for this patient. Due to tumor recurrence, a second and a third surgery of radical excision were performed 6 months and 17 months later after the first surgery, respectively. Histopathologic analysis identified that the recurrent tumors were different from the original schwannoma because of their smooth muscle-like differentiation.</p> <p>Conclusion</p> <p>Malignant schwannomas are uncommon sarcomas with a high incidence of local recurrence. Distinct immunohistochemical staining results of the tumors at recurrence indicate their potential of smooth-muscle like differentiation. Radical excision of the tumors may provide benefit for their local recurrences.</p

The effect of anti-VEGF drugs (bevacizumab and aflibercept) on the survival of patients with metastatic colorectal cancer (mCRC)

Significant progression has been achieved in the treatment of metastatic colorectal cancer (mCRC) in recent years. This has been partly attributed to successfully incorporating new drugs into combination chemotherapy. In addition to the traditional cytotoxic chemotherapeutic agents, molecularly targeted agents began to play an important role in the treatment of advanced solid tumors. To date, two classes of molecularly targeted agents have been approved for treatment of patients with mCRC: (1) antivascular endothelial growth factor (anti-VEGF) agents (such as bevacizumab and aflibercept) and (2) antiendothelial cell growth factor receptor (anti-EGFR) agents (such as cetuximab and panitumumab). Aflibercept is a new member of anti-VEGF agents which has demonstrated efficacy for treatment of mCRC. With the commencement of clinical trials and basic research into aflibercept, more data from the bedside and the bench have been obtained. This review will outline the application of anti-VEGF agents by reviewing clinic experiences of bevacizumab and aflibercept, and try to add perspectives on the use of anti-VEGF agents in mCRC

Kesesakan Dan Agresivitas Pada Remaja Di Kawasan Tambak Lorok Semarang

Penelitian ini bertujuan untuk mengetahui hubungan antara kesesakan dengan agresivitas pada remaja yang tinggal di Kawasan Tambak Lorok Semarang. Populasi dalam penelitian ini adalah remaja yang tinggal di Kawasan Tambak Lorok Semarang. Pengumpulan data menggunakan dua buah skala yaitu, Skala Agresivitas (22 aitem; α=0,864) dan Skala Kesesakan (16 aitem; α=0,828). Subjek penelitian berjumlah 230 remaja yang tinggal di Kawasan Tambak Lorok Semarang yang dipilih melalui teknik simple random sampling. Hasil analisis data menggunakan teknik analisis regresi sederhana menunjukkan terdapat hubungan positif antara kesesakan dengan agresivitas pada remaja yang tinggal Kawasan Tambak Lorok Semarang (r=0,578; p=0,000). Semakin tinggi kesesakan yang dirasakan subjek maka semakin tinggi agresivitas. Kesesakan memberikan sumbangan efektif sebesar 33,4% pada agresivitas dan sisanya sebesar 66,6% dipengaruhi oleh faktor lain yang tidak diteliti dalam penelitian ini

Assessment of a Novel VEGF Targeted Agent Using Patient-Derived Tumor Tissue Xenograft Models of Colon Carcinoma with Lymphatic and Hepatic Metastases

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents

Prevalence of JC Virus in Chinese Patients with Colorectal Cancer

BACKGROUND: JCV is a DNA polyomavirus very well adapted to humans. Although JCV DNA has been detected in colorectal cancers (CRC), the association between JCV and CRC remains controversial. In China, the presence of JCV infection in CRC patients has not been reported. Here, we investigated JCV infection and viral DNA load in Chinese CRC patients and to determine whether the JCV DNA in peripheral blood (PB) can be used as a diagnostic marker for JCV-related CRC. METHODOLOGY/PRINCIPAL FINDINGS: Tumor tissues, non-cancerous tumor-adjacent tissues and PB samples were collected from 137 CRC patients. In addition, 80 normal colorectal tissue samples from patients without CRC and PB samples from 100 healthy volunteers were also harvested as controls. JCV DNA was detected by nested PCR and glass slide-based dot blotting. Viral DNA load of positive samples were determined by quantitative real-time PCR. JCV DNA was detected in 40.9% (56/137) of CRC tissues at a viral load of 49.1 to 10.3×10(4) copies/µg DNA. Thirty-four (24.5%) non-cancerous colorectal tissues (192.9 to 4.4×10(3) copies/µg DNA) and 25 (18.2%) PB samples (81.3 to 4.9×10(3) copies/µg DNA) from CRC patients were positive for JCV. Tumor tissues had higher levels of JCV than non-cancerous tissues (P = 0.003) or PB samples (P<0.001). No correlation between the presence of JCV and demographic or medical characteristics was observed. The JCV prevalence in PB samples was significantly associated with the JCV status in tissue samples (P<0.001). Eleven (13.8%) normal colorectal tissues and seven (7.0%) PB samples from healthy donors were positive for JCV. CONCLUSIONS/SIGNIFICANCE: JCV infection is frequently present in colorectal tumor tissues of CRC patients. Although the association between JCV presence in PB samples and JCV status in tissue samples was identified in this study, whether PB JCV detection can serve as a marker for JCV status of CRC requires further study

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe