Safety and efficacy of sorafenib in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is frequently diagnosed in the setting of chronic liver disease and cirrhosis. The median survival after diagnosis is dismal. The treatment options that may offer cure are either resection or liver transplantation. Unfortunately most patients are not eligible for either treatment modality at diagnosis because of advanced stage and underlying liver dysfunction. Until recently, there was no effective systemic therapy for patients with advanced HCC. Sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor and Raf, has shown antitumor activity in patients with advanced HCC in phase III trials. Although objective response is not common, sorafenib promotes disease stabilization and improves overall survival. Sorafenib is well tolerated with a favorable toxicity profile. In this article we review the efficacy and safety data for sorafenib in patients with advanced HCC

Review of Photochemistry for Polyalithia longiflia

 The review was aimed to review the phytochemical of the Polyalithia longiflia. Phytochemical screening for all parts of Polyalithia longiflia have been done and shown most of the chemical group compounds such as glycosides, Sterol, Carbohydrates, terpenoids, flavonoids. 174 compounds have been isolated from five parts (leaves, steam bark, seeds, fruits, root) of Polyalithia longiflia, these compounds have been drown their structure. Leaves of Polyalithia longiflia were extracted and isolated 99 compounds most of these compounds were terpenoids, while root of Polyalithia longiflia only three articles about it. Also seeds of Polyalithia longiflia have not been studied yet its phytochemical screening. Many of these compounds were used in many biological and medical fields

Network and structural analysis of quail mucins with expression pattern of mucin 1 and mucin 4 in the intestines of the Iraqi common quail (Coturnix coturnix)

Background and Aim: In avian and other species, mucins (MUCs) play a crucial role in the gastrointestinal tract (GIT), and constitute a large group of O-glycosylated glycoproteins, are glycoconjugate proteins. MUCs present in two forms: (1) membrane-attached on cell surfaces to repel external threats and (2) detachable, gel-forming proteins in the soluble form. In quail GIT, the specific types of MUCs that are expressed remain largely unknown. We investigated the expression of MUC1 and MUC4 MUCs in the GIT of Iraqi common quails and conducted network and structural analyses of all known MUC types across quail breeds. Materials and Methods: Histological and gene expression analyses of MUC1 and MUC4 were conducted using fresh small intestine and large intestine samples from 10 quails. Using the STRING Database, Chimera software, and PrankWeb-ligand binding site prediction tool, network and structural analyses of all reported types of quail MUCs were conducted. Results: Most intestinal MUCs in quails were acidic, with few neutral MUCs detectable through Alcian blue and periodic acid-schiff stains. Acidic MUCs were more expressed in the duodenum, ileum, cecum, and colon, whereas neutral MUCs were more expressed in the jejunum. MUC1 and MUC4 messenger RNA expression was significantly higher in the jejunum and colon than in the duodenum and ileum. The analysis of the network revealed that MUC 1, 15, 16, and 24 formed homologous networks, while MUC 2, 4, 5, and 6 formed heterologous networks. Specific MUC combinations, including MUC5A-MUC6, MUC5A-MUC5B, and MUC5B-MUC6, show higher intermolecular hydrogen bond formation affinity. MUC15, MUC16, and MUC24 showed minimal interaction with other MUC types. Among the analyzed MUCs, MUC5B, and MUC6 had the highest probability for binding, while MUC2, MUC4, and MUC5A showed lower probabilities despite greater numbers of binding sites. Conclusion: This study’s results offer significant insights into quails’ MUCs’ composition, expression, network interactions, and binding sites, advancing knowledge of MUC-related processes in gastrointestinal physiology and their potential connection to gastrointestinal diseases

RAGE recycles at the plasma membrane in S100B secretory vesicles and promotes Schwann cells morphological changes

RAGE is a multiligand receptor of the immunoglobulin superfamily involved in regeneration of injured peripheral nerve and cell motility. RAGE is implicated in the development of various chronic diseases, such as neurodegenerative disorders, inflammatory responses, and diabetic complications. The correlation between RAGE endocytic trafficking and RAGE function is still uninvestigated. S100B is one of the ligands of RAGE. The molecular mechanisms responsible of S100B translocation in exocytic vesicles are still poorly investigated. In the present study we elucidate the role of RAGE endocytic trafficking in promoting S100B secretion in Schwann cells. Here we show that RAGE-induced secretion of S100B requires phosphorylated caveolin1-dependent endocytosis of RAGE. Endocytosis of RAGE in response to ligand binding promotes the fusion of endosomes with S100B-positive secretory vesicles. Src promotes the fusion of endosomes with S100B-secretory vesicles. Inhibition of src induces RAGE degradation. RAGE-mediated src activation induces cav1 phosphorylation and relocalization in the perinuclear compartment. RAGE signaling and recycling are required for S100-induced Schwann cells morphological changes and are inhibited by high-glucose, suggesting a possible link between diabetes and peripheral nerve injury. Indeed, high glucose inhibits RAGE-mediated src activation. Src inhibition blocks RAGE recycling, S100B secretion, and morphological changes. In summary, we identified a novel pathway of vesicular trafficking required for the amplification of RAGE signaling and cytoskeleton dynamics that is potentially involved in the regeneration of injured peripheral nerve. J. Cell. Physiol. 217: 60–71, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60463/1/21474_ftp.pd

Advanced Phase I/II Studies of Targeted Gene Delivery In Vivo: Intravenous Rexin-G for Gemcitabine-resistant Metastatic Pancreatic Cancer

Rexin-G, a nonreplicative pathology-targeted retroviral vector bearing a cytocidal cyclin G1 construct, was tested in a phase I/II study for gemcitabine-resistant pancreatic cancer. The patients received escalating doses of Rexin-G intravenously from 1 × 1011 colony-forming units (cfu) 2–3× a week (dose 0–1) to 2 × 1011 cfu 3× a week (dose 2) for 4 weeks. Treatment was continued if there was less than or equal to grade 1 toxicity. No dose-limiting toxicity (DLT) was observed, and no vector DNA integration, replication-competent retrovirus (RCR), or vector-neutralizing antibodies were noted. In nine evaluable patients, 3/3 patients had stable disease (SD) at dose 0–1. At dose 2, 1/6 patients had a partial response (PR) and 5/6 patients had SD. Median progression-free survival (PFS) was 3 months at dose 0–1, and >7.65 months at dose 2. Median overall survival (OS) was 4.3 months at dose 0–1, and 9.2 months at dose 2. One-year survival was 0% at dose 0–1 compared to 28.6% at dose 2, suggesting a dose–response relationship between OS and Rexin-G dosage. Taken together, these data indicate that (i) Rexin-G is safe and well tolerated, and (ii) Rexin-G may help control tumor growth, and may possibly prolong survival in gemcitabine-resistant pancreatic cancer, thus, earning US Food and Drug Administration's (FDA) fast-track designation as second-line treatment for pancreatic cancer

The long-acting COX-2 inhibitor mavacoxib (Trocoxil (TM)) has anti-proliferative and pro-apoptotic effects on canine cancer cell lines and cancer stem cells in vitro

BACKGROUND: The NSAID mavacoxib (Trocoxcil™) is a recently described selective COX-2 inhibitor used for the management of inflammatory disease in dogs. It has a long plasma half-life, requiring less frequent dosing and supporting increased owner compliance in treating their dogs. Although the use of NSAIDs has been described in cancer treatment in dogs, there are no studies to date that have examined the utility of mavacoxib specifically. RESULTS: In this study we compared the in vitro activity of a short-acting non-selective COX inhibitor (carprofen) with mavacoxib, on cancer cell and cancer stem cell survival. We demonstrate that mavacoxib has a direct cell killing effect on cancer cells, increases apoptosis in cancer cells in a manner that may be independent of caspase activity, and has an inhibitory effect on cell migration. Importantly, we demonstrate that cancer stem cells derived from osteosarcoma cell lines are sensitive to the cytotoxic effect of mavacoxib. CONCLUSIONS: Both NSAIDs can inhibit cancer cell proliferation and induce apoptosis in vitro. Importantly, cancer stem cells derived from an osteosarcoma cell line are sensitive to the cytotoxic effect of mavacoxib. Our results suggest that mavacoxib has anti-tumour effects and that this in vitro anti-cancer activity warrants further study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-014-0184-9) contains supplementary material, which is available to authorized users

PI3K/AKT/mTOR signaling in gastric cancer : epigenetics and beyond.

PI3K/AKT/mTOR pathway is one of the most important signaling pathways involved in normal cellular processes. Its aberrant activation modulates autophagy, epithelial-mesenchymal transition, apoptosis, chemoresistance, and metastasis in many human cancers. Emerging evidence demonstrates that some infections as well as epigenetic regulatory mechanisms can control PI3K/AKT/mTOR signaling pathway. In this review, we focused on the role of this pathway in gastric cancer development, prognosis, and metastasis, with an emphasis on epigenetic alterations including DNA methylation, histone modifications, and post-transcriptional modulations through non-coding RNAs fluctuations as well as H. pylori and Epstein-Barr virus infections. Finally, we reviewed different molecular targets and therapeutic agents in clinical trials as a potential strategy for gastric cancer treatment through the PI3K/AKT/mTOR pathway. [Abstract copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Characterisation of ADAMs (protein)of bovine seminal plasma by Mass Spectrometr

This study has been designed to analyse the secreted and soluble proteins in bovine seminal plasma by mass spectrometry. The majority of these proteins are produced by accessory glands, and partially by testis, epididymis, ductus deferens and vas deferens of male reproductive tract.Seminal plasma of bovine was collected freshly and isolated after centrifuged and removed the sperm.  Non boiled and boiled seminal plasma lysate were run to identify and detect the total proteins, as well as the individual single member of ADAMs protein is determined.The non-boiled lysate of seminal plasma was displayed diversity of proteins more than boiled sample lysate of seminal plasma.However, boiled and non-boiled seminal plasma have distinguished several types of ADAMs protein which are included: ADAM10, ADAM9, ADAM7, ADAM15 in non-boiled samples, while boiled lysate of bovine seminal plasma was displayed ADAM10, ADAM9, ADAM28, and ADAM22.Our finding concluded that bovine seminal plasma is very rich in different types of soluble, cleaved and shed proteins such ADAMs protein which could potentially have a biological and physiological role in protection and interactions of sperm during motility inside female reproductive tract, as it might support it to fertilise the ovum. This protection might be via immunosuppression behaviour or by block specific receptors in female reproductive tract for enhancing sperm motility, and avoid sperm the singling response of immunity. 

Investigation Extraction of the Garden Snail's Shells using GC-MS Spectrometry

This study focused on the powder of the shell of the local garden snail in Iraq to identify the chemical compounds and determine the diversity and biological contents that might be applied for other applications and studies. Thus, snails shell was collected from local rivers in Al Diwaniya city, middle of Iraq; 500 grams of the shell powder of the garden snail was smashed and grinded and analysed during this study. The shell powder was extracted by ethanol, and 250mg of the yield was injected in GC-Mass spectrometry and analyzed. The detection of chemical compounds in the garden snail shell was identified by comparison with the mass spectra library of the GC-Mass data system. Results exhibited that six chemical compounds were largely predominant among other elements of the shell powder, including hexadecanoic acid, ethyl ester, (E)-9-Octadecenoic acid ethyl ester, pentadecanoic acid, heptadecanoic acid, ethyl ester, and 9-Octadecenamide, (Z)-. Also, the analysis profiled more than 23 chemical compounds that constituted the structure of the garden snail shell with a low percentage area. These substances were classified into fatty acids, saturated fatty acids, organic compounds, natural products, and methyl and ethyl esters. Consequently, these natural materials are essential active compounds that could be used for more medical and research applications studies. However, the yield of chemical compounds was a low amount. To sum up, GC-Mass spectrometry has displayed a high biological diversity of chemical compounds substances in the shell of garden snails, which can help researchers to investigate more for different natural chemical resources in the shell of a garden snail