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Brain tumor drug

Juan Li, Yang Du, Zhenqi Jiang, Yuchen Tian, Nianxiang Qiu, Yinjie Wang, Muhammad Zubair Lqbal, Menying Hu, Ruifen Zou, Lijia Luo, Shiyu Du, Jie Tian, Aiguo Wu
Due to the molecular and cellular heterogeneity of glioma, discovery of novel targeted sites and ligands for glioma imaging and therapy remains challenging. Neuropeptide Y (NPY) Y1 receptors (Y1 Rs) are highly over expressed in various brain tumors including glioma, and can serve as potential targeting sites for glioma imaging and therapy. Here, we show by in vivo fluorescent imaging that a highly selective Y1 R ligand, [Asn6 , Pro34 ] NPY (AP-NPY), facilitated circumvention of the blood brain barrier (BBB) by nanomicelles specifically targeting glioma...
March 15, 2018: Nanoscale
Yingying Liu, Yudiao Huang, Yueyue Xu, Peng Qu, Minghua Wang
Increased transendothelial permeability and subsequent blood-brain barrier damage play a key role in the pathological progression of human brain ischemia and secondary reperfusion. Memantine is a licensed drug providing clinically relevant efficacy in patients with Alzheimer's disease. However, little information is known regarding its effects on brain endothelial permeability. In this study, we investigated the effects of memantine on endothelial permeability and the underlying mechanisms in an ischemia-reperfusion (I/R) injury model in primary human brain microvascular endothelial cells...
March 15, 2018: IUBMB Life
Liza Brown, Jennifer David, Stanley Skopit
Basal cell carcinoma (BCC) is a common skin malignancy comprising 80% of non-melanoma skin cancers.1 Over 2.8 million cases are estimated to be diagnosed in the United States alone each year. Advanced BCCs are comprised of BCCs that have metastasized to local or distant lymph nodes or organs, or locally invasive BCCs that are extensive and infiltrate vital structures such as eyes, nose, or brain. Advanced BCC tumors represent roughly 1-10% of BCCs today. Two severe case presentations and treatment options will be discussed in this case report series and review...
March 1, 2018: Journal of Drugs in Dermatology: JDD
Guna Proboka, Andra Tilgase, Sergejs Isajevs, Agnija Rasa, Pēteris Alberts
Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease. Melanoma brain metastases have many severe side effects and, unfortunately, any disease related to the brain has limited therapeutic options due to the blood-brain barrier. The course of the disease after a treatment course is complicated to predict, and it is difficult to obtain long-lasting remission...
2018: Frontiers in Oncology
Tia H Turner, Mohammad A Alzubi, Sahib S Sohal, Amy L Olex, Mikhail G Dozmorov, J Chuck Harrell
PURPOSE: Basal-like breast cancers are aggressive and often metastasize to vital organs. Treatment is largely limited to chemotherapy. This study aims to characterize the efficacy of cancer therapeutics in vitro and in vivo within the primary tumor and metastatic setting, using patient-derived xenograft (PDX) models. METHODS: We employed two basal-like, triple-negative PDX models, WHIM2 and WHIM30. PDX cells, obtained from mammary tumors grown in mice, were treated with twelve cancer therapeutics to evaluate their cytotoxicity in vitro...
March 12, 2018: Breast Cancer Research and Treatment
Marie Duhamel, Mélanie Rose, Franck Rodet, Adriana-Nathalia Murgoci, Lea Zografidou, Anne Régnier-Vigouroux, Fabien Vanden Abeele, Firas Kobeissy, Serge Nataf, Laurent Pays, Maxence Wisztorski, Dasa Cizkova, Isabelle Fournier, Michel Salzet
High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune cells towards a pro-tumoral and anti-inflammatory phenotype. Therefore, the current challenge for cancer therapy is to find a way to reorient macrophages toward an anti-tumoral phenotype. Previously, we demonstrated that macrophages secreted anti-tumoral factors when they were invalidated for the proprotein converstase 1/3 (PC1/3) and treated with LPS...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Ornella Franzese, Fiorenzo Battaini, Grazia Graziani, Lucio Tentori, Maria Luisa Barbaccia, Angelo Aquino, Mario Roselli, Maria Pia Fuggetta, Enzo Bonmassar, Francesco Torino
In recent years, immune checkpoint inhibitors (ICpI) have provided the ground to bring tumor immunity back to life thanks to their capacity to afford a real clinical benefit in terms of patient's survival. Essential to ICpI success is the presence of tumor-associated neoantigens generated by non-synonymous mutations, since a direct relationship between mutation load of malignant cells and susceptibility to ICpI has been confidently established. However, it has been also suggested that high intratumor heterogeneity (ITH) associated with subclonal neoantigens could not elicit adequate immune responses...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Chrysoula Vraka, Monika Dumanic, Teresa Racz, Florian Pichler, Cecile Philippe, Theresa Balber, Eva-Maria Klebermass, Karl-Heinz Wagner, Marcus Hacker, Wolfgang Wadsak, Markus Mitterhauser
In drug development, biomarkers for cerebral applications have a lower success rate compared to cardiovascular drugs or tumor therapeutics. One reason is the missing blood brain barrier penetration, caused by the tracer's interaction with efflux transporters such as the P-gp (MDR1 or ABCB1). Aim of this study was the development of a reliable model to measure the interaction of radiotracers with the human efflux transporter P-gp in parallel to the radiolabeling process. LigandTracer® Technology was used with the wildtype cell line MDCKII and the equivalent cell line overexpressing human P-gp (MDCKII-hMDR1)...
February 14, 2018: Nuclear Medicine and Biology
Luisa Iacovelli, Rosamaria Orlando, Alessandro Rossi, Paola Spinsanti, Daniela Melchiorri, Ferdinando Nicoletti
In spite of the recent advancement in the molecular characterization of malignant gliomas and medulloblastomas, the treatment of primary brain tumors remains suboptimal. The use of small molecule inhibitors of intracellular signaling pathways, inhibitors of angiogenesis, and immunotherapic agents is limited by systemic adverse effects, limited brain penetration, and, in some cases, lack of efficacy. Thus, adjuvant chemo-therapy and radiotherapy still remain the gold standard in the treatment of grade-IV astrocytoma (glioblastoma multiforme) and medulloblastoma...
March 8, 2018: Current Opinion in Pharmacology
Xiaobing Jiang, Yinsheng Chen, Zhihuan Zhou, Liping Luo, Wanming Hu, Huirong Zheng, Zhe Zhu, Jian Wang, Zhongping Chen
BACKGROUND: The pineal gland has been demonstrated to be involved in the development of mood and psychotic disorders. However, few studies have looked at the relationship between pineal region tumors and psychiatric disorders. Intracranial epidermoid cysts usually arise in cerebellopontine angle area, and are extremely rare in the pineal region. The case of pineal epidermoid cyst presenting as schizophrenia has never been reported before. CASE PRESENTATION: We described the case of a 23-year old man who presented to hospital with symptoms suggestive of schizophrenia...
March 7, 2018: World Neurosurgery
Aditi Jhaveri, Pranali Deshpande, Bhushan Pattni, Vladimir Torchilin
Glioblastomas (GBMs) are highly aggressive brain tumors with a very grim prognosis even after multi-modal therapeutic regimens. Conventional chemotherapeutic agents frequently lead to drug resistance and result in severe toxicities to non-cancerous tissues. Resveratrol (RES), a natural polyphenol with pleiotropic health benefits, has proven chemopreventive effects in all the stages of cancer including initiation, promotion and progression. However the poor physico-chemical properties of RES severely limit its use as a free drug...
March 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ryota Kurogi, Akira Nakamizo, Satoshi O Suzuki, Masahiro Mizoguchi, Koji Yoshimoto, Toshiyuki Amano, Takeo Amemiya, So Takagishi, Koji Iihara
OBJECTIVE Human bone marrow-derived mesenchymal stem cells (hMSCs) show tropism for brain tumors and may be a useful vehicle for drug or gene delivery to malignant gliomas. Recently, some microRNAs (miRNAs) have been shown to suppress the invasiveness of malignant gliomas. METHODS To test their potential to become vehicles for the delivery of miRNA to malignant gliomas, hMSCs were engineered so that hMSC secretion of miRNAs that inhibit glioma cell invasion was enabled without altering the hMSC tropism for glioma cells...
March 9, 2018: Journal of Neurosurgery
Xin Yao Qiu, Dian Xing Hu, Wen-Qiang Chen, Ruo Qiao Chen, Shi Rui Qian, Chun Yang Li, Yuan Jun Li, Xin Xin Xiong, Di Liu, Feng Pan, Shang Bin Yu, Xiao Qian Chen
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor due to the lack of effective therapeutic drugs. Cancer therapy targeting programmed cell death protein 1 (PD-1) or programmed death ligand-1 (PD-L1) is of revolutionary. However, the role of intrinsic PD-L1, which determines immune-therapy outcomes, remains largely unclear. Here we demonstrated an oncogenic role of PD-L1 via binding and activating Ras in GBM cells. RNA-sequencing transcriptome data revealed that PD-L1 significantly altered gene expression enriched in cell growth/migration/invasion pathways in human GBM cells...
March 3, 2018: Biochimica et Biophysica Acta
Xinyi Jiang, Christine Wang, Sergio Fitch, Fan Yang
Hypoxia, a hallmark of malignant tumors, often correlates with increasing tumor aggressiveness and poor treatment outcomes. Due to a lack of vasculature, effective drug delivery to hypoxic tumor regions remains challenging. Signaling through the chemokine SDF-1α and its receptor CXCR4 plays a critical role in the homing of stem cells to ischemia for potential use as drug-delivery vehicles. To harness this mechanism for targeting tumor hypoxia, we developed polymeric nanoparticle-induced CXCR4-overexpressing human adipose-derived stem cells (hADSCs)...
2018: Theranostics
Shubaash Anthiya, Audrey Griveau, Claire Loussouarn, Patrick Baril, Martin Garnett, Jean-Paul Issartel, Emmanuel Garcion
MicroRNAs (miRNAs) are key regulatory elements encoded by the genome. A single miRNA can downregulate the expression of multiple genes involved in diverse functions. Because cancer is a disease with multiple gene aberrations, developing novel approaches to identify and modulate miRNA pathways may result in a breakthrough for cancer treatment. With a special focus on glioblastoma (GBM), this review provides an up-to-date summary of miRNA biogenesis, the role of miRNA in cancer resistance, and essential tools for modulating miRNA expression, as well as of clinically promising RNAi delivery systems and how they can be adapted for therapy...
March 2018: Trends in Cancer
Z Y Wei, M M Feng, B Yang, Z Y Yan, B Q Wang, X Y Bu
Glioma is the most common primary tumor in the brain, accounting for about 40~50% of intracranial primary tumors. Most chemotherapeutic drugs have difficulty in penetrating the blood-brain barrier, and their clinical applications are greatly limited. We evaluated the effects of methylmercury-L-cysteine (MeHg-L-cys) and methylmercury chloride (MMC) on apoptosis of C6 glioma cells. L-type amino acid transporter (LAT1) was used to investigate the targeted transport function and cytotoxicity of MeHg- L-cys in glioma...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Xingmei Zhang, Li Peng, Zhiman Liang, Zhewen Kou, Yue Chen, Guangwei Shi, Xiaowen Li, Yanling Liang, Fang Wang, Yusheng Shi
Glioblastoma multiforme (GBM) is the most prevalent and lethal malignant intracranial tumor in the brain, with very poor prognosis and survival. The epidermal growth factor receptor variant III (EGFRvIII) contributes to increased oncogenicity that does not occur through binding EGFR ligands and instead occurs through constitutive activation, which enhances glioma tumorigenicity and resistance to targeted therapy. Aptamers are nucleic acids with high affinity and specificity to targets selected by systematic evolution of ligands by exponential enrichment (SELEX), and are usually developed as antagonists of disease-associated factors...
March 2, 2018: Molecular Therapy. Nucleic Acids
Mohammad Norouzi
Despite much effort to treat glioblastoma multiforme (GBM), the median survival of patients has not significantly improved. The high rate of tumor recurrence after tumor resection and the blood-brain barrier (BBB) decrease treatment efficacy. Local drug delivery at the surgical resection site via implantable electrospun nanofibers not only circumvents the BBB, but can also reduce the rate of tumor recurrence. Nanofibers can provide the sustained release and high concentration of chemotherapeutics at the tumor vicinity, while decreasing their systemic exposure and toxicity...
February 27, 2018: Drug Discovery Today
Kenny Kwok-Hei Yu, Jessica T Taylor, Omar N Pathmanaban, Amir Saam Youshani, Deniz Beyit, Joanna Dutko-Gwozdz, Roderick Benson, Gareth Griffiths, Ian Peers, Peter Cueppens, Brian A Telfer, Kaye J Williams, Catherine McBain, Ian D Kamaly-Asl, Brian W Bigger
BACKGROUND: Glioblastoma (GBM) is the most common primary brain malignancy in adults, yet survival outcomes remain poor. First line treatment is well established, however disease invariably recurs and improving prognosis is challenging. With the aim of personalizing therapy at recurrence, we have established a high content screening (HCS) platform to analyze the sensitivity profile of seven patient-derived cancer stem cell lines to 83 FDA-approved chemotherapy drugs, with and without irradiation...
2018: PloS One
Snehalata V Gajbhiye, Raakhi K Tripathi, Anup Uttam Petare, Anirudha Vyankatesh Potey, Arun Shankar
INTRODUCTION: Anxiety and negative sensations due to alcohol withdrawal are factors leading to alcohol relapse and addiction. Minocycline, an antibiotic, can decrease alcohol consumption in rats, however, its effects on alcohol withdrawal anxiety and relapse have not been studied. MATERIAL AND METHODS: Part 1: Forced alcohol drinking in gradually increasing concentration was administered till day 22 in rats. Effect of drugs on anxiety was assessed using elevated plus maze (EPM) and two chambered box apparatus, after removal of alcohol...
February 27, 2018: Current Clinical Pharmacology
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