Cure rates for children and young adults with osteosarcoma have remained stagnant over the past three decades. Targeting glycoprotein non-metastatic b (GPNMB) with the antibody-drug conjugate glembatumumab vedotin has improved outcomes for patients with melanoma and breast cancer. The potential utility of targeting GPNMB in osteosarcoma was explored.
GPNMB protein expression was evaluated by immunohistochemistry in human osteosarcoma tumor samples and by enzyme-linked immunosorbent assay (ELISA) in osteosarcoma cell lines. mRNA expression was measured by quantitative PCR in primary osteosarcoma samples and cell lines. Surface GPNMB expression was evaluated by flow cytometry and correlated with in vitro and in vivo cytotoxicity of glembatumumab vedotin.
Sixty seven human osteosarcoma samples were evaluated by immunohistochemistry, including 12 samples from initial biopsy, 38 samples from definitive surgery, and 17 from the time of disease recurrence. GPNMB was expressed in 92.5% (62/67) of osteosarcoma samples. All primary osteosarcoma samples expressed high levels of GPNMB mRNA. Glembatumumab induced cytotoxic effects in 74% (14/19) of osteosarcoma cell lines, and GPNMB protein levels correlated with glembatumumab in vitro cytotoxicity (r = -0.46, P = 0.04). All osteosarcoma cell lines demonstrated surface GPNMB expression.
GPNMB is expressed in osteosarcoma and targeting GPNMB with the antibody-drug conjugate glembatumumab vedotin demonstrates osteosarcoma cytotoxic activity. Clinical trials are indicated to assess the efficacy of targeting GPNMB in patients with osteosarcoma.
© 2015 Wiley Periodicals, Inc.

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Type I Interferon (IFN) is a critical pathogenic factor during the progression of Lupus Nephritis (LN). Although microRNAs (miRNAs) have been shown to control IFN response in immune cells of LN, the role of miRNAs in resident renal cells remain unclear. Here, we investigated the role of miR-130b in IFN pathway in renal cells, and its therapeutic effect in LN.
Kidney tissues from patients and mouse model of LN were collected for detecting miR-130b levels. Primary renal mesangial cells (RMCs) were used to determine the role of miR-130b in IFN pathway. We overexpressed miR-130b by administrating miR-130b agomir in an IFNα-accelerated LN mouse model to test its therapeutic efficacy.
Downregulated miR-130b expression was observed in kidney tissues from patients and mouse model of LN. Further analysis showed that underexpression of miR-130b negatively correlated with abnormal activation of IFN response in LN patients. In vitro, overexpressing miR-130b suppressed the downstream of type I IFN pathway in RMCs by targeting interferon regulatory factor 1 (IRF1). The opposite effect was observed when inhibited internal miR-130b expression. The inverse correlation between IRF1 and miR-130b levels was detected in renal biopsies from LN patients. More importantly, in vivo administration of miR-130b agomir reduced IFNα-accelerated LN progression, including decreased proteinuria, lower levels of complexes deposition and lack of glomeruli lesion.
miR-130b is a novel negative regulator of type I IFN pathway in renal cells. Overexpression of miR-130b in vivo ameliorates IFNα-accelerated LN, providing potential novel strategies for LN therapeutic intervention. This article is protected by copyright. All rights reserved.
© 2016, American College of Rheumatology.

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Breast cancer is the most frequently occurring disease among women worldwide. The early stage of breast cancer identification is the key challenge in cancer control and prevention procedures. Although gene expression profiling helps to understand the molecular mechanism of diseases or disorder in the living system, gene expression pattern alone is not sufficient to predict the exact mechanisms. Current proteomics tools hold great application for analysis of cancerous conditions. Hence, the generation of differential protein expression profiles has been optimized for breast cancer and normal tissue samples in our organization. Normal and tumor tissues were collected from 20 people from a local hospital. Proteins from the diseased and normal tissues have been investigated by 2D gel electrophoresis and MALDI-TOF-MS. The peptide mass fingerprint data were fed into various public domains like Mascot, MS-Fit, and Pept-ident against Swiss-Prot protein database and the proteins of interest were identified. Some of the differentially expressed proteins identified were human annexin, glutathione S-transferase, vimentin, enolase-1, dihydrolipoamide dehydrogenase, glutamate dehydrogenase, Cyclin A1, hormone sensitive lipase, beta catenin, and so forth. Many types of proteins were identified as fundamental steps for developing molecular markers for diagnosis of human breast cancer as well as making a new proteomic database for future research.

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Ewing’s sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG(TM) (Vigil(TM)) vaccine, in which 12 advanced stage Ewing’s patients were safely treated and went on to achieve a predicted immune response (IFN? ELISPOT). We describe follow-up through year 3 of a prospective, non-randomized study comparing an expanded group of Vigil-treated advanced disease Ewing’s sarcoma patients (n=16) with a contemporaneous group of Ewing’s sarcoma patients (n=14) not treated with Vigil. Long-term follow up results show a survival benefit without evidence of significant toxicity (no = grade 3) to Vigil when administered once monthly by intradermal injection (1x10e(6) cells/injection to 1x10e(7) cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2 month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing’s sarcoma.

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To describe treatment patterns, outcomes and healthcare resource use in patients with metastatic and/or locally recurrent, unresectable gastric cancer (MGC) in Taiwan.
Patients who had received first-line therapy (platinum and/or fluoropyrimidine) followed by second-line therapy or best supportive care (BSC) only were eligible. Participating physicians provided de-identified information from patient charts. Data were summarized descriptively and Kaplan-Meier analysis was used to describe time to events.
Overall, 37 physicians contributed 122 patient charts. Of the 122 patients (median age, 61 years; 62% male), 43 (35%) received BSC only following first-line therapy, whereas 79 (65%) received second-line therapy. There was heterogeneity in second-line treatment, although fluoropyrimidine with or without a platinum agent was most frequently used. Median survival was 12.5 (interquartile range [IQR], 8.2-20.8) months from MGC diagnosis for patients receiving second-line therapy and 8.0 (IQR, 5.6-not reached) months for patients receiving BSC only. The most common treatment-related symptoms were nausea/vomiting (58%); the most common cancer-related symptoms were pain (61%), ascites (35%) and nausea/vomiting (33%). Inpatient and outpatient hospitalizations were numerically more common for patients receiving second-line therapy than for those receiving BSC only; the prevalence of hospice and skilled nursing facility stays were numerically more common for patients receiving BSC only.
In this Taiwanese MGC population, 65% received active second-line therapy with heterogeneity seen in the regimen used. Clinical outcomes suggest an unmet medical need in this population. This study may help inform clinical practice and future research to ultimately improve patient outcomes in Taiwan.
© 2016 John Wiley & Sons Australia, Ltd.

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