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https://www.readbyqxmd.com/read/29774126/autophagy-deficient-breast-cancer-shows-early-tumor-recurrence-and-escape-from-dormancy
#1
Hussein F Aqbi, Liliya Tyutyunyk-Massey, Rebecca C Keim, Savannah E Butler, Theresa Thekkudan, Supriya Joshi, Timothy M Smith, Dipankar Bandyopadhyay, Michael O Idowu, Harry D Bear, Kyle K Payne, David A Gewirtz, Masoud H Manjili
Breast cancer patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu-overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting response to immunotherapy...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764451/phenotypic-and-genotypic-characterization-of-thai-isolates-of-plasmodium-falciparum-after-an-artemisinin-resistance-containment-project
#2
Thunyapit Thita, Pimrat Jadsri, Jarupatr Thamkhantho, Toon Ruang-Areerate, Nantana Suwandittakul, Naruemon Sitthichot, Kittiya Mahotorn, Peerapan Tan-Ariya, Mathirut Mungthin
BACKGROUND: In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone® , a combination of atovaquone-proguanil (ATQ-PG), has been used to cease artemisinin pressure in some areas along Thai-Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai-Cambodia border after the artemisinin resistance containment project compared with those collected before...
May 15, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29756273/expanding-the-sar-of-non-toxic-antiplasmodial-indolyl-3-ethanone-ethers-and-thioethers
#3
Mayibongwe J Lunga, Ruramai L Chisango, Carli Weyers, Michelle Isaacs, Dale Taylor, Adrienne L Edkins, Setshaba D Khanye, Heinrich C Hoppe, Clinton Veale
Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by reduced efficacy of artemisinin combination therapies (ACT). Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery compounds 13 and 14 whose activity was equipotent to chloroquine against the P...
May 13, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29754074/structure-activity-relationship-of-new-antimalarial-1-aryl-3-susbtituted-propanol-derivatives-synthesis-preliminary-toxicity-profiling-parasite-life-cycle-stage-studies-target-exploration-and-targeted-delivery
#4
Miguel Quiliano, Adriana Pabón, Ernest Moles, Leonardo Bonilla-Ramirez, Isabelle Fabing, Kim Y Fong, Diego A Nieto-Aco, David W Wright, Juan C Pizarro, Ariane Vettorazzi, Adela López de Cerain, Eric Deharo, Xavier Fernández-Busquets, Giovanny Garavito, Ignacio Aldana, Silvia Galiano
Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50 s < 0...
April 24, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29750967/evaluation-of-four-novel-isothermal-amplification-assays-towards-simple-and-rapid-genotyping-of-chloroquine-resistant-plasmodium-falciparum
#5
Madhvi Chahar, Anup Anvikar, Rajnikant Dixit, Neena Valecha
Loop mediated isothermal amplification (LAMP) assay is sensitive, prompt, high throughput and field deployable technique for nucleic acid amplification under isothermal conditions. In this study, we have developed and optimized four different visualization methods of loop-mediated isothermal amplification (LAMP) assay to detect Pfcrt K76T mutants of P. falciparum and compared their important features for one-pot in-field applications. Even though all the four tested LAMP methods could successfully detect K76T mutants of P...
May 8, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29749510/inhibition-of-endoplasmic-reticulum-stress-induced-autophagy-sensitizes-melanoma-cells-to-temozolomide-treatment
#6
Oxana Ryabaya, Anastasia Prokofieva, Dmitry Khochenkov, Ivan Abramov, Alexander Zasedatelev, Evgenia Stepanova
The incidence of malignant melanoma is increasing. The discovery of agents specifically targeting the mutated cascades has provided a good response for patients with oncogenic B-Raf proto-оncogene, serine/threonine kinase (BRAF). However, numerous studies continue to focus on novel methods of treatment to overcome acquired resistance to novel drugs. Recently, it has been revealed that inhibition of endoplasmic reticulum (ER) stress chaperon 78 kDa glucose-regulated protein 78 (GRP78) leads to down-regulation of autophagy and increased sensitivity to temozolomide (TMZ) treatment...
May 9, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29748013/loss-of-c-ebp-%C3%AE-lip-drives-cisplatin-resistance-in-malignant-pleural-mesothelioma
#7
Joanna Kopecka, Iris C Salaroglio, Luisella Righi, Roberta Libener, Sara Orecchia, Federica Grosso, Vladan Milosevic, Preeta Ananthanarayanan, Luisa Ricci, Enrica Capelletto, Monica Pradotto, Francesca Napoli, Massimo Di Maio, Silvia Novello, Menachem Rubinstein, Giorgio V Scagliotti, Chiara Riganti
OBJECTIVES: Cisplatin-based chemotherapy is moderately active in malignant pleural mesothelioma (MPM) due to intrinsic drug resistance and to low immunogenicity of MPM cells. CAAT/enhancer binding protein (C/EBP)-β LIP is a pro-apoptotic and chemosensitizing transcription factor activated in response to endoplasmic reticulum (ER) stress. MATERIALS AND METHODS: We investigated if LIP levels can predict the clinical response to cisplatin and survival of MPM patients receiving cisplatin-based chemotherapy...
June 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29725750/characterization-of-the-endolysosomal-system-in-human-chordoma-cell-lines-is-there-a-role-of-lysosomes-in-chemoresistance-of-this-rare-bone-tumor
#8
Dagmar Kolb-Lenz, Robert Fuchs, Birgit Lohberger, Ellen Heitzer, Katharina Meditz, Dominique Pernitsch, Elisabeth Pritz, Andrea Groselj-Strele, Andreas Leithner, Bernadette Liegl-Atzwanger, Beate Rinner
Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes...
May 3, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29723168/malaria-surveillance-united-states-2015
#9
Kimberly E Mace, Paul M Arguin, Kathrine R Tan
PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission...
May 4, 2018: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/29720184/correction-to-polymorphisms-in-chloroquine-resistance-associated-genes-in-plasmodium-vivax-in-ethiopia
#10
Lemu Golassa, Berhanu Erko, Frederick N Baliraine, Abraham Aseffa, Göte Swedberg
After publication of the original article [1], it came to the authors' attention that the primers mentioned in Table 1 for the amplification of the pvcrt-o gene of Plasmodium vivax are not the ones actually used for the experiments. The correct primers and PCR product size are as below.
May 2, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29719377/attenuation-of-everolimus-induced-cytotoxicity-by-a-protective-autophagic-pathway-involving-erk-activation-in-renal-cell-carcinoma-cells
#11
Yizhou Zeng, Xiaofang Tian, Quan Wang, Weiyang He, Jing Fan, Xin Gou
Aim: The mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). However, the limited efficacy of RAD001 has led to the development of drug resistance. Autophagy is closely related to cell survival and death, which may be activated under RAD001 stimulation. The aim of the present study was to identify the underlying mechanisms of RAD001 resistance in RCC cells through cytoprotective autophagy involving activation of the extracellular signal-regulated kinase (ERK) pathway...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29713246/autophagy-inhibition-improves-the-cytotoxic-effects-of-receptor-tyrosine-kinase-inhibitors
#12
Sanja Aveic, Marcella Pantile, Pierfrancesco Polo, Viktoryia Sidarovich, Marilena De Mariano, Alessandro Quattrone, Luca Longo, Gian Paolo Tonini
Background: A growing field of evidence suggests the involvement of oncogenic receptor tyrosine kinases (RTKs) in cell transformation. Deregulated activity of RTKs in tumors can determine disease progression and therapeutic responses in several types of cancer, including neuroblastoma (NB). Therefore, RTKs targeting is a worthwhile challenge for the oncologists. Nevertheless, acquired resistance to RTK inhibitors (RTKi) remains a serious problem. Autophagy activation is among the possible obstacles for good efficacy of the therapy with RTKi...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29684045/autophagic-flux-blockage-by-accumulation-of-weakly-basic-tenovins-leads-to-elimination-of-b-raf-mutant-tumour-cells-that-survive-vemurafenib
#13
Marcus J G W Ladds, Andrés Pastor-Fernández, Gergana Popova, Ingeborg M M van Leeuwen, Kai Er Eng, Catherine J Drummond, Lars Johansson, Richard Svensson, Nicholas J Westwood, Anna R McCarthy, Fredrik Tholander, Mihaela Popa, David P Lane, Emmet McCormack, Gerald M McInerney, Ravi Bhatia, Sonia Laín
Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules...
2018: PloS One
https://www.readbyqxmd.com/read/29658588/autophagy-inhibition-potentiates-saha%C3%A2-mediated-apoptosis-in-glioblastoma-cells-by-accumulation-of-damaged-mitochondria
#14
Kovooru Lohitesh, Heena Saini, Abhilasha Srivastava, Sudeshna Mukherjee, Aniruddha Roy, Rajdeep Chowdhury
Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ...
April 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29653033/organometallic-conjugates-of-the-drug-sulfadoxine-for-combatting-antimicrobial-resistance
#15
Peter J Sadler, Prinessa Chellan, Vicky Avery, Sandra Duffy, James Triccas, Gayathri Nagalingam, Christina Tam, Luisa Cheng, Jenny Liu, Kirkwood Land, Guy Clarkson, Isolda Romero
Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by x-ray crystallography. Rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10 - 2.0 µM in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes), but were only moderately active towards Trichomonas vaginalis...
April 13, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29649190/updated-cdc-recommendations-for-using-artemether-lumefantrine-for-the-treatment-of-uncomplicated-malaria-in-pregnant-women-in-the-united-states
#16
Sarah-Blythe Ballard, Allison Salinger, Paul M Arguin, Meghna Desai, Kathrine R Tan
Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications. In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria in pregnant women are limited to mefloquine or quinine plus clindamycin (1). However, limited availability of quinine and increasing resistance to mefloquine restrict these options. Strong evidence now demonstrates that artemether-lumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in pregnancy...
April 13, 2018: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29626674/pharmacological-activity-of-curarea-toxicofera-in-combination-with-classical-antimalarial-treatments
#17
Yinneth Victoria Rodríguez, Maria Helena Arias, José Octavio García, Eric Deharo, Giovanny Garavito
ETHNOPHARMACOLOGICAL RELEVANCE: In the Leticia-Amazonas area, Uitoto indigenous people use a preparation of Curarea toxicofera (Wedd) Barneby & Krukoff (Menispermaceae) combined with prescribed medications to prevent and treat malaria. AIM OF STUDY: To determine the in vitro and in vivo antiplasmodial activity of traditional preparations of Curarea toxicofera alone and in combination with classical antimalarials. MATERIAL AND METHODS: The traditional preparation was evaluated in vitro against P...
April 4, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29615047/potent-antiplasmodial-extracts-and-fractions-from-terminalia-mantaly-and-terminalia-superba
#18
Cedric D J Mbouna, Rufin M T Kouipou, Rodrigue Keumoe, Lauve R Y Tchokouaha, Patrick V T Fokou, Brice M T Tali, Dinkar Sahal, Fabrice F Boyom
BACKGROUND: The emergence and spread of malaria parasites resistant to artemisinin-based combination therapy stresses the need for novel drugs against malaria. Investigating plants used in traditional medicine to treat malaria remains a credible option for new anti-malarial drug development. This study was aimed at investigating the antiplasmodial activity and selectivity of extracts and fractions from Terminalia mantaly and Terminalia superba (Combretaceae) that are used in Cameroon to treat malaria...
April 3, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29614990/improved-effects-of-honokiol-on-temozolomide-induced-autophagy-and-apoptosis-of-drug-sensitive-and-tolerant-glioma-cells
#19
Chung-Ching Chio, Kung-Yen Chen, Cheng-Kuei Chang, Jian-Ying Chuang, Chih-Chung Liu, Shing-Hwa Liu, Ruei-Ming Chen
BACKGROUND: Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that honokiol, a major bioactive constituent of Magnolia officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms. METHODS: TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to honokiol and TMZ, and cell viability and LC50 of honokiol were assayed...
April 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29606144/in-vitro-evaluation-of-chloroquine-loaded-and-heparin-surface-functionalized-solid-lipid-nanoparticles
#20
Joseph O Muga, Jeremiah W Gathirwa, Matshawandile Tukulula, Walter G Z O Jura
BACKGROUND: Use of chloroquine, an otherwise safe and relatively affordable anti-malarial drug, was discontinued due to widespread prevalence of resistant parasites. Many entrant anti-malarial drugs for treatment of chloroquine resistant malaria raises the concerns of cost and safety among other challenges. Innovative ways of circumventing chloroquine resistance is of paramount importance. Such may include nanoparticulate delivery strategies and targeting. This study evaluated physicochemical properties and in vitro antiplasmodial activity of chloroquine encapsulated heparin functionalized solid lipid nanoparticles (CQ-Hep-SLNs) and non-heparin functionalized SLNs (CQ-SLN) against Plasmodium falciparum...
April 2, 2018: Malaria Journal
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