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Simon Schimmack, Sarah Kneller, Nigora Dadabaeva, Frank Bergmann, Andrew Taylor, Thilo Hackert, Jens Werner, Oliver Strobel
BACKGROUND: The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. METHODS: PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated α-tubuline and γ-tubuline...
2016: PloS One
G Sybren de Hoog, Karolina Dukik, Michel Monod, Ann Packeu, Dirk Stubbe, Marijke Hendrickx, Christiane Kupsch, J Benjamin Stielow, Joanna Freeke, Markus Göker, Ali Rezaei-Matehkolaei, Hossein Mirhendi, Yvonne Gräser
Type and reference strains of members of the onygenalean family Arthrodermataceae have been sequenced for rDNA ITS and partial LSU, the ribosomal 60S protein, and fragments of β-tubulin and translation elongation factor 3. The resulting phylogenetic trees showed a large degree of correspondence, and topologies matched those of earlier published phylogenies demonstrating that the phylogenetic representation of dermatophytes and dermatophyte-like fungi has reached an acceptable level of stability. All trees showed Trichophyton to be polyphyletic...
October 25, 2016: Mycopathologia
Subhajit Ghosh, Saswat Mohapatra, Anisha Thomas, Debmalya Bhunia, Abhijit Saha, Gaurav Das, Batakrishna Jana, Surajit Ghosh
An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics, competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find out such a unique nanocarrier and engineer all the above-mentioned features into it. In this manuscript, we have shown for the first time that Apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc) and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation...
October 26, 2016: ACS Applied Materials & Interfaces
Saswat Mohapatra, Abhijit Saha, Prasenjit Mondal, Batakrishna Jana, Subhajit Ghosh, Atanu Biswas, Surajit Ghosh
Microtubule dynamics play a crucial role in cancer cell division. Various drugs are developed to target microtubule. Although a few of them show potential in treatment of cancer, but success rate is limited due to their poor bioavailability and lack of specificity. Thus, development of highly bioavailable and target specific anticancer drug is extremely necessary. To address these key issues, here, a combination of approaches such as development of a dodecapeptide-docetaxel nanoassembly targeted to tubulin and MUC1 (mucin 1, cell surface associated glycoprotein) targeting oligonucleotide aptamer conjugated liposome for delivering peptide-docetaxel nanoassembly into the breast cancer cell have been demonstrated...
October 26, 2016: Advanced Healthcare Materials
Jinglan Liu, Matthew P Keisling, Ayman Samkari, Gregory Halligan, Judy M Pascasio, Christos D Katsetos
Central nervous system (CNS) tumors exhibiting dual features of malignant glioma (MG) and primitive neuroectodermal tumor (PNET) are rare and diagnostically challenging. Previous studies have shown that MG-PNET carry MYCN or MYC gene amplifications within the PNET component concomitant with glioma-associated alterations, most commonly 10q loss, in both components [9]. Here we confirm and extend the profile of molecular genetic findings in a MG-PNET involving the left frontal lobe of a 12-year-old male. Histologically, the PNET-like component showed morphological features akin to anaplastic medulloblastoma highlighted by widespread immunoreactivity for βIII-tubulin (TUBB3) and nonphosphorylated neurofilament protein, and to a lesser degree, Neu-N, synaptophysin, and CD99, whereas the gliomatous component was demarcated by glial fibrillary acidic protein (GFAP) labeling...
October 26, 2016: Clinical Neuropathology
Manasi Talwadekar, Sophia Fernandes, Vaijayanti Kale, Lalita Limaye
Mesenchymal stem cells (MSCs) are known to express a wide range of markers belonging to all the three lineages: mesodermal, ectodermal and endodermal. Therefore, the possibility of their transdifferentiation towards a neural lineage has been an aspect of active research. In the present study, MSCs were isolated from human placental tissue (P-MSC) and subjected them to neural differentiation. It was found that the P-MSCs differentiated towards neural lineage in appropriate differentiation conditions. However, when a histone deacetylase (HDAC) inhibitor - valproic acid (VPA) - was incorporated in the medium, there was a further increase in their neural differentiation potential...
October 25, 2016: Journal of Tissue Engineering and Regenerative Medicine
Wei Yang, Xiaoyuan Wang, Wei Zheng, Kedong Li, Haofeng Liu, Yueming Sun
Following the publication of this article, an interested reader drew to our attention anomalies associated with the data shown in Fig. 2, which presented the mRNA and protein expression levels of tropomyosin 1 (TPM1) in HuCCT1 cells. Essentially, the control bands for α-tubulin had been duplicated across from Fig. 2A to Fig. 2B, and from Fig. 2D to Fig. 2E [the experiments showing treatment of the cells with (A) manumycin A, (B) U0126, (D) 5-aza-2-deoxycytidine (DAC) and (E) trichostatin A (TSA)], respectively...
October 24, 2016: International Journal of Oncology
Sgb Furness, D L Hare, A Kourakis, A M Turnley, P J Wookey
We have discovered that the accumulation of an anti-calcitonin receptor (anti-CTR) antibody conjugated to a fluorophore (mAb2C4:AF568) provides a robust signal for cells undergoing apoptotic programmed cell death (PCD). PCD is an absolute requirement for normal development of metazoan organisms. PCD is a hallmark of common diseases such as cardiovascular disease and tissue rejection in graft versus host pathologies, and chemotherapeutics work by increasing PCD. This robust signal or high fluorescent events were verified by confocal microscopy and flow cytometry in several cell lines and a primary culture in which PCD had been induced...
2016: Cell Death Discovery
Peter E Ghaly, Rabab M Abou El-Magd, Cassandra D M Churchill, Jack A Tuszynski, F G West
Noscapine, a naturally occurring opium alkaloid, is a widely used antitussive medication. Noscapine has low toxicity and recently it was also found to possess cytotoxic activity which led to the development of many noscapine analogues. In this paper we report on the synthesis and testing of a novel noscapine analogue. Cytotoxicity was assessed by MTT colorimetric assay using SKBR-3 and paclitaxel-resistant SKBR-3 breast cancer cell lines using different concentrations for both noscapine and the novel compound...
June 28, 2016: Oncotarget
Rakesh Kumar
Professor Ferid Murad has been a remarkable colleague and a mentor. During our very first meeting, he not only shared unresolved puzzles in Nitric Oxide (NO) research but also listened to my questions pointing to protein nitration and nitrosylation. This was start of a new avenue in my laboratory involving protein nitration, inducible nitric oxide synthase and nitrite production in the context of signaling and gene expression in cancer cells. Dynamic changes in the cytoskeleton remodeling in response to the cell membrane generated signals are regulated by p21-activated kinase 1 (PAK1) which also feed into microtubules (MT) dynamic via phosphorylating Tubulin Cofactor B (CoB) on serine 65 and serine 128...
2016: Current Medicinal Chemistry
Riham I Ahmed, Essam Eldin A Osman, Fadi M Awadallah, Samir M El-Moghazy
New target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R(1)) were attached to manipulate their physicochemical properties and/or their biological activity. The designed compounds were assessed for their antitumor activity on HCT-116 and MCF-7 cancer cell lines. Compounds 4b, 5e and 5f exhibited comparable or higher potency than colchicine against colon HCT-116 and MCF-7 tumor cells...
October 24, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Alice Kunzler, Fares Zeidán-Chuliá, Juciano Gasparotto, Carolina Saibro Girardi, Karina Klafke, Lyvia Lintzmaier Petiz, Rafael Calixto Bortolin, Diana Carolina Rostirolla, Alfeu Zanotto-Filho, Matheus Augusto de Bittencourt Pasquali, Phillip Dickson, Peter Dunkley, José Cláudio Fonseca Moreira, Daniel Pens Gelain
Human neuroblastoma SH-SY5Y cells have been used as an in vitro model for neurodegenerative disorders such as Parkinson's disease and can be induced to a mature neuronal phenotype through retinoic acid (RA) differentiation. However, mechanisms of RA-induced differentiation remain unclear. Here, we investigate the role of reactive species (RS) on SH-SY5Y neuroblastoma cells under RA differentiation, using the antioxidant Trolox® as co-treatment. We found that RA treatment for 7 days reduced the cell number and proliferative capacity and induced the expression of adult catecholaminergic/neuronal markers such as tyrosine hydroxylase (TH), β-III tubulin, and enolase-2...
October 22, 2016: Molecular Neurobiology
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
Xiaoli Zhao, Changli Yue, Jiamin Chen, Cheng Tian, Dongmei Yang, Li Xing, Honggang Liu, Yulan Jin
BACKGROUND Class III β-tubulin (βIII-tubulin) has been reported to express at the invasive margin of colorectal cancer. The present study aimed to investigate the clinical implication of βIII-tubulin expression at the invasive margin of colorectal cancer. MATERIAL AND METHODS We recruited 111 patients with surgically resected colorectal carcinoma for bIII-tubulin expression analysis. The cases with bIII-tubulin-positive tumor cells found only in the invasive front tumor area were assigned to the invasive front group, while the remaining cases were all assigned to the non-invasive front group...
October 23, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Chao-Ming Hung, Ying-Chao Lin, Liang-Chih Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way
CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, DU-145 and LNCap. It had a very low IC50 about 200 nM against castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells. CWF-145 arrested cell cycle at G2/M phase by binding to the β-tubulin at the colchicine-binding site then disrupted microtubule polymerization...
October 18, 2016: Chemico-biological Interactions
Bini Mathew, Judith Varady Hobrath, Larry Ross, Michele C Connelly, Hava Lofton, Malini Rajagopalan, R Kiplin Guy, Robert C Reynolds
A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin...
2016: PloS One
Yendouban Lamboni, Kristian F Nielsen, Anita R Linnemann, Yüksel Gezgin, Kerstin Hell, Martinus J R Nout, Eddy J Smid, Manuele Tamo, Martinus A J S van Boekel, Jakob Blæsbjerg Hoof, Jens Christian Frisvad
In a previous study, raw cashew kernels were assayed for the fungal contamination focusing on strains belonging to the genus Aspergillus and on aflatoxins producers. These samples showed high contamination with Aspergillus section Nigri species and absence of aflatoxins. To investigate the diversity of secondary metabolites, including mycotoxins, the species of A. section Nigri may produce and thus threaten to contaminate the raw cashew kernels, 150 strains were isolated from cashew samples and assayed for their production of secondary metabolites using liquid chromatography high resolution mass spectrometry (LC-HRMS)...
2016: PloS One
Lotte B Pedersen
No abstract text is available yet for this article.
October 21, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Rong-Hua Yang, Shao-Hai Qi, Shu-Bin Ruan, Ze-Peng Lin, Yan Lin, Feng-Gang Zhang, Xiao-Dong Chen, Ju-Lin Xie
Epidermal growth factor (EGF)-like family members mediate a wide range of biological activities including cell proliferation and migration. Increasing evidence indicated that EGF plays an important role in the process of wound healing by stimulating fibroblast motility. The aim of this study was to see whether EGF-like domain 7 (EGFL7)-overexpressing epidermal stem cells (EGFL7-ESCs) would promote fibroblast proliferation and migration. We found that mRNA and protein levels of EGFL7 expression were significantly increased in EGFL7-ESCs...
October 20, 2016: Molecular and Cellular Biochemistry
Khaldoun Almhanna, Gopi K Prithviraj, Petter Veiby, Thea Kalebic
Antibody-directed cancer chemotherapy in the form of antibody-drug conjugates (ADCs) may improve the therapeutic index with the potential to enhance efficacy and decrease systemic toxicity. ADCs consist of three key components including an antibody that specifically binds to the target, a toxic agent and a linker which releases the toxic agent inside tumor cells. A novel ADC, MLN0264 (TAK-264) was recently investigated in patients with gastrointestinal (GI) malignancies. TAK-264 is an anti- guanylyl cyclase C (GCC) antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE) (linker and toxin licensed from Seattle Genetics)...
October 17, 2016: Pharmacology & Therapeutics
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