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Survivin - a new target for tumor therapy

Posted by star on 2017-09-12 20:11:26



     Recently, the US Food and Drug Administration (FDA) officially awarded SurVaxM vaccine "orphan drug" qualification. The vaccine is used for the treatment of glioblastoma, which was developed by Michael Ciesielski-associate professor of the Neurosurgery and Robert Fenstermaker-director of neurosurgery, both in Roswell Park Cancer Institute.

     SurVaxM vaccine is mainly used to inhibit the expression of survivin protein. The survivin protein is a member of the family of apoptotic proteins, with a molecular weight of 16.5 kDa, which could inhibit apoptosis, promote cell proliferation, and induce or enhance angiogenesis. Survivin existed in many types of malignancies, such as lung cancer, rectal cancer, liver cancer and gastric cancer, but rarely expressed in normal human tissue. This ubiquitous expression suggested that survivin might have the anti-tumor effect by being antagonized.

     In bladder transitional cell carcinoma, survivin has become a biomarker for cancer diagnosis, prognosis and predicting bladder or systemic response. In addition, in the preclinical bladder tumor model, inhibiting the survivin expression and / or function can affect tumor cell proliferation and significantly induce spontaneous or chemotherapy-induced apoptosis.

     The products, including survivin antibody, survivin ELISA kit, anti-survivin ELISA kit, survivin CLIA kit and anti-survivin CLIA kit, have independently been developed and produced by EIAab Technology Co. Ltd.

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Zika virus has oncolytic activity against fighting brain cancer

Posted by star on 2017-09-11 19:48:45




     According to the AFP, glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. The scientists studied the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. The results suggested that ZIKV was an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.

    While Zika was known for causing birth defects like microcephaly and brain damage, it turned out that the virus might be also served as a useful purpose -- fighting brain cancer. In recent studies, researches were showed that Zika could actually take on a hard-to-treated type of brain cancers. Standard forms of therapy could be done well against the majority of the tumor cells, but left behind the stem cells that generated the tumors, allowing them to keep creating more tumors once the originals were removed. But Zika actually worked the opposite -- it targeted the stem cells and skipped over the other tumor cells. So, in......

How Protein Mutations affect the Colorectal Cancer

Posted by star on 2017-09-11 19:46:17




     Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. The research team used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, they leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, the team provides a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.

     The results offer clearer picture of the cellular processes behind bowel cancer, and may enable future tailoring of drug treatments to different bowel cancer patients. For the first time, scientists have completed a detailed study of many of the proteins in bowel cancer cells. Scientists investigated the role proteins play in predicting how common mutations affect proteins in the cancer cells and also whether such proteins are important in predicting the cancer’s response to treatment. The results, published in Cell Reports give scientists a better picture of the cellular processes behind bowel cancer, and could enable resea......

Regulating the Protein Synthesis Might Be a New Target for Aging

Posted by star on 2017-09-11 19:44:58



     In cell, expanded nucleoli and increased protein synthesis can serve as aging biomarkers, which had been confirmed from patients with Hutchinson-Gilford progeria syndrome (HGPS). This research had published on the Nature Communications at August 30th.

     HGPS is a fatal premature aging disorder. Patients with HGPS exhibit features of aging at a young chronological age, including loss of subcutaneous fat and hair, mobility deficits, and arteriosclerosis2. And complications of cardiovascular disease are fatal in the second decade of life. Before the late 20th century, there was very little information about the generation of progeria. In 2003, the progeria was discovered to be caused from a point mutation in position 1824 of the LMNA gene, in which cytosine is replaced with thymine.


Fig.1 Progerin expression drives nucleolar expansion.

     However, in the study, researchers investigated protein homeostasis in HGPS, and found a widespread increase in protein turnover in HGPS-derived cells compared to normal cells. Protein turnover is the balance between protein synthesis and protein degradation. Then increased protein synthesis was resulted from the activated nucleoli and enhanced ribosome biogenesis in fibroblasts. Either depleting normal lamin A or inducing mutant lamin A expression would drive nucleolar expansion. Furthermore, there were relevant between nucleolar size and the age of healthy individuals. Ribosomal RNA production could be increased with age. The evidence was indicated that increased nucleolar size and activity could a hallmark of premature aging. This study reported a profound shift in protein metabol......

Yigong Shi- the Spliceosome, A Protein-Directed Metalloribozyme

Posted by star on 2017-09-11 19:42:15



      The summary was published at this year by Yigong Shi, which provided the currrently important development of the spliceosome.

      The spliceosome was a large RNA-protein complex that catalyzed the removal of introns from nuclear pre-mRNA, named as the ribonucleoprotein machinery. And ribonucleoproteins (RNPs) could mediate key cellular functions, like gene expression and regulation. Although most RNP enzymes were stable in composition and harbor preformed active sites, the spliceosome followed fundamentally different strategies. The spliceosome could provide accurate recognition and flexible splicing during alternative splicing by various compositional and structural dynamics in substrate-dependent complex assembly, catalytic activation, and active site remodeling [1-2].


     But its atomic structure had not been resolved for nearly 40 years. However, the yeast spliceosome was come into light in the cryogenic electron microscopy structure now. With the atomic or near-atomic resolutions, the yeast spliceosome was found having four distinct conformational states. At the active site, there were two catalytic metal ions being coordinated by the U6 small nuclear RNA (snRNA). They also catalyzed both the branching reaction and the exon ligation. The fully assembled spliceosome had U5 and U6, along with 30 contiguous nucleotides of U2 at its 5′-end. Prp8 and 16 core protein components supported the rigidity of RNA elements, to maintain the conformation in all structurally characterized spliceosomes. The mobile site was only the sequences downstream of nucleotide 30 of U2 snRNA, which delivered the intron branch site into the close proximity of the 5′......

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