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https://www.readbyqxmd.com/read/29780561/triple-action-pt-iv-derivatives-of-cisplatin-a-new-class-of-potent-anticancer-agents-that-overcome-resistance
#1
Emanuele Petruzzella, Roman Sirota, Irene Solazzo, Valentina Gandin, Dan Gibson
A series of triple action Pt(iv) prodrugs was designed to test the hypothesis that multi-action compounds, where each bioactive moiety intervenes in several cellular processes, might be more effective than a single agent at killing cancer cells. In particular, "triple action" Pt(iv) derivatives of cisplatin, where the axial ligands are inhibitors of cyclooxygenase (COXi), histone deacetylase (HDACi) or pyruvate dehydrogenase kinase (PDKi) were developed. All compounds, ctc-[Pt(NH3 )2 (COXi)(PDKi)Cl2 ], ctc-[Pt(NH3 )2 (COXi)(HDACi)Cl2 ] and ctc-[Pt(NH3 )2 (HDACi)(PDKi)Cl2 ], where COXi = aspirin or ibuprofen, PDKi = dichloroacetate and HDACi = valproate or phenylbutyrate, were significantly more cytotoxic than cisplatin against all cell lines of an in-house panel of human cancer cells...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29778506/quality-of-life-symptoms-and-care-needs-in-patients-with-persistent-or-recurrent-platinum-resistant-ovarian-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#2
Vivian E von Gruenigen, Helen Q Huang, David Cella, MichaelA Zevon, Jason A LaChance, Joan L Walker, Ritu Salani, Susan C Modesitt, Robert T Morris, William H Bradley, Matthew P Boente, Lari Wenzel
OBJECTIVES: The goals of treating recurrent platinum-resistant ovarian cancer are palliative, aimed at reducing symptoms and improving progression free survival. A prospective trial was conducted to determine the prevalence and severity of symptoms, and associated care needs. METHODS: Eligible women included those with persistent or recurrent platinum-resistant ovarian cancer with an estimated life expectancy of at least 6 months. The Needs at the End-of-Life Screening Tool (NEST), FACIT-Fatigue (FACIT-F), NCCN-FACT Ovarian Symptom Index [NFOSI-18]; Disease Related Symptoms (DRS), Treatment Side Effects (TSE), and Function/Well Being (F/WB) were collected at study entry, 3 and 6 months...
May 17, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29772714/modulating-chemosensitivity-of-tumors-to-platinum-based-antitumor-drugs-by-transcriptional-regulation-of-copper-homeostasis
#3
REVIEW
Yu-Hsuan Lai, Chin Kuo, Macus Tien Kuo, Helen H W Chen
Platinum (Pt)-based antitumor agents have been effective in treating many human malignancies. Drug importing, intracellular shuffling, and exporting-carried out by the high-affinity copper (Cu) transporter ( hCtr1 ), Cu chaperone (Ato x1), and Cu exporters (ATP7A and ATP7B), respectively-cumulatively contribute to the chemosensitivity of Pt drugs including cisplatin and carboplatin, but not oxaliplatin. This entire system can also handle Pt drugs via interactions between Pt and the thiol-containing amino acid residues in these proteins; the interactions are strongly influenced by cellular redox regulators such as glutathione...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769198/mathematical-modeling-predicts-response-to-chemotherapy-and-drug-combinations-in-ovarian-cancer
#4
Emilia Kozłowska, Anniina Färkkilä, Tuulia Vallius, Olli Carpén, Jukka Kemppainen, Seija Grénman, Rainer Lehtonen, Johanna Hynninen, Sakari Hietanen, Sampsa Hautaniemi
Platinum-based chemotherapy constitutes the backbone of clinical care in advanced solid cancers such as high-grade serous ovarian cancer (HGSOC) and has prolonged survival of millions of cancer patients. Most of these patients, however, become resistant to chemotherapy, which generally leads to a fatal refractory disease. We present a comprehensive stochastic mathematical model and simulator approach to describe platinum resistance and standard-of-care (SOC) therapy in HGSOC. We used pre- and post-treatment clinical data, including 18F-FDG-PET/CT images, to reliably estimate the model parameters and simulate "virtual HGSOC patients...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29768183/ndrg1-disruption-alleviates-cisplatin-sodium-glycididazole-induced-dna-damage-response-and-apoptosis-in-ercc1-defective-lung-cancer-cells
#5
Lang He, Kang Liu, Xiaoshan Wang, Hong Chen, Jin Zhou, Xun Wu, Tao Liu, Yongxue Yang, Xuemei Yang, Dandan Cui, Guiqin Song, Jianguo Lei, Jun Wang
BACKGROUND: Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC). METHODS: We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa...
May 13, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29767464/platinum-resistant-recurrent-ovarian-cancer-with-long-survival-on-bevacizumab-and-gemcitabine
#6
Shinichi Komiyama, Tsuyoki Kugimiya, Chiaki Takeya, Rena Takahashi, Kaneyuki Kubushiro
Platinum-resistant recurrent ovarian cancer has a poor prognosis, but combined therapy with bevacizumab and anticancer agents may be useful. We report a patient with long-term disease control by the combination of bevacizumab and gemcitabine (BEV + GEM). The patient was a 77-year-old woman with high-grade Stage IIIC serous ovarian carcinoma. In 2012, a complete response (CR) was obtained by neoadjuvant and adjuvant chemotherapy using paclitaxel plus carboplatin and tumor debulking surgery. After recurrence in 2013, CR was achieved again with gemcitabine plus carboplatin...
May 16, 2018: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/29765151/apatorsen-plus-docetaxel-versus-docetaxel-alone-in-platinum-resistant-metastatic-urothelial-carcinoma-borealis-2
#7
Jonathan E Rosenberg, Noah M Hahn, Meredith M Regan, Lillian Werner, Ajjai Alva, Saby George, Joel Picus, Robert Alter, Arjun Balar, Jean Hoffman-Censits, Petros Grivas, Richard Lauer, Elizabeth A Guancial, Christopher Hoimes, Guru Sonpavde, Constantine Albany, Mark N Stein, Tim Breen, Cindy Jacobs, Kirsten Anderson, Joaquim Bellmunt, Aly-Khan A Lalani, Sumanta Pal, Toni K Choueiri
BACKGROUND: A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy. METHODS: Multicentre, phase II study with 1:1 randomisation to apatorsen (three loading doses at 600 mg intravenous followed by weekly doses) plus docetaxel (75 mg/m2 intravenous every 21 days) (A/D) or docetaxel alone...
May 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29757875/surgery-and-platinum-etoposide-based-chemotherapy-for-the-treatment-of-epithelioid-trophoblastic-tumor
#8
Janelle Sobecki-Rausch, Abigail Winder, Kruti P Maniar, Anna V Hoekstra, Emily Berry, Karen Novak, John R Lurain
OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia that develops from chorionic-type intermediate trophoblast, simulates carcinoma, presents years after a pregnancy event, is associated with low or normal human chorionic gonadotropin levels, and is relatively resistant to chemotherapy. Our aim was to identify the role of surgery in combination with platinum/etoposide-based chemotherapy in the management of both localized and metastatic ETT...
May 4, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29756633/immunotherapy-in-head-and-neck-cancer-scientific-rationale-current-treatment-options-and-future-directions
#9
Uta Rothschild, Laurent Muller, Axel Lechner, Hans A Schlösser, Dirk Beutner, Heinz Läubli, Alfred Zippelius, Sacha I Rothschild
Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms...
May 14, 2018: Swiss Medical Weekly
https://www.readbyqxmd.com/read/29749482/a-panel-of-7-prognosis-related-long-non-coding-rnas-to-improve-platinum-based-chemoresistance-prediction-in-ovarian-cancer
#10
Jing Song, Wanfeng Zhang, Sen Wang, Kun Liu, Fangzhou Song, Longke Ran
In order to study the role of long non-coding RNAs (lncRNAs) in predicting platinum-based chemoresistance in patients with high-grade serous ovarian carcinoma (HGS-OvCa), a=7-lncRNA signature was developed by analyzing 561 microarrays and 136 specimens from RNA-sequencing (RNA-seq) obtained from online databases [odds ratio (OR), 2.859; P<0.0001]. The upregulated lncRNAs (RP11-126K1.6, ZBED3-AS1, RP11-439E19.10 and RP11‑348N5.7) and downregulated lncRNAs [RNF144A-AS1, growth arrest specific 5 (GAS5) and F11-AS1] exhibited high sensitivity and specificity in predicting chemoresistance in the Gene Expression Omnibus and the Cancer Genome Atlas (area under curve >0...
May 11, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29746551/a-multi-chamber-microfluidic-intestinal-barrier-model-using-caco-2-cells-for-drug-transport-studies
#11
Hsih-Yin Tan, Sofie Trier, Ulrik L Rahbek, Martin Dufva, Jörg P Kutter, Thomas L Andresen
This paper presents the design and fabrication of a multi-layer and multi-chamber microchip system using thiol-ene 'click chemistry' aimed for drug transport studies across tissue barrier models. The fabrication process enables rapid prototyping of multi-layer microfluidic chips using different thiol-ene polymer mixtures, where porous Teflon membranes for cell monolayer growth were incorporated by masked sandwiching thiol-ene-based fluid layers. Electrodes for trans-epithelial electrical resistance (TEER) measurements were incorporated using low-melting soldering wires in combination with platinum wires, enabling parallel real-time monitoring of barrier integrity for the eight chambers...
2018: PloS One
https://www.readbyqxmd.com/read/29745031/trypanosoma-cruzi-biochemical-changes-and-cell-death-induced-by-an-organometallic-platinum-based-compound
#12
M Florencia Mosquillo, Lucía Bilbao, Fabricio Hernández, Florencia Tissot, Dinorah Gambino, Beatriz Garat, Leticia Pérez-Díaz
Chagas disease is an endemic illness in Latin America caused by the parasite Trypanosoma cruzi. Current chemotherapies are old and inadequate, and the emergence of drug resistant strains underscores the need of new drugs. Platinum-based complexes have been shown to be a promising approach against parasitic diseases. In this work, the effect of 1,1'-bis(diphenylphosphino)ferrocene pyridine-2-thiolate-1-oxide Pt(II) hexafluorophosphate, Pt-dppf-mpo, was studied on T. cruzi. A promising anti-trypanosomal activity was determined for the CL Brener strain with a low cytotoxicity determined using in vitro cultured mammal cells...
May 9, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29744485/platinum-iv-prodrugs-with-long-lipid-chains-for-drug-delivery-and-overcoming-cisplatin-resistance
#13
Qiling Chen, Yuanyuan Yang, Xun Lin, Wen Ma, Gui Chen, Wenliang Li, Xuefeng Wang, Zhiqiang Yu
Platinum(iv) prodrugs of clinically used cisplatin and oxaliplatin with two axial long lipid chains were developed for nanoparticle delivery to combat cisplatin resistance.
May 10, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29743117/a-robust-response-to-combination-immune-checkpoint-inhibitor-therapy-in-hpv-related-small-cell-cancer-a-case-report
#14
Won Jin Ho, Lisa Rooper, Sarah Sagorsky, Hyunseok Kang
BACKGROUND: Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. CASE PRESENTATION: This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies...
May 9, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29736307/a-novel-5t4-targeting-antibody-drug-conjugate-h6-dm4-exhibits-potent-therapeutic-efficacy-in-gastrointestinal-tumor-xenograft-models
#15
Ruixue Wang, Qinhuai Lai, Liangze Tang, Yiran Tao, Yuqin Yao, Yu Liu, Ying Lu, Chaoyong Shen, Ran Lu, Chuanwen Fan, Ruirui Zhang, Yuxi Wang, Lin Yu, Tinghan Yang, Yangping Wu, Yujia Peng, Xian Wei, Yuyin Fu, Weirong Lai, Lantu Gou, Jinliang Yang
5T4, also named as trophoblast glycoprotein, is often upregulated in some cancer cells. Here, we demonstrated that 5T4 was highly expressed in gastric, colorectal, and pancreatic cancer, associated with significantly poor prognosis of gastrointestinal (GI) cancer patients. To search for new targeting drugs for GI cancer, we developed a novel anti-5T4 monoclonal antibody with high affinity and robust internalization ability and conjugated it to the potent microtubule inhibitor DM4 to produce conjugate H6-DM4...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29733308/therapy-testing-in-a-spheroid-based-3d-cell-culture-model-for-head-and-neck-squamous-cell-carcinoma
#16
Jan Hagemann, Christian Jacobi, Sabine Gstoettner, Christian Welz, Sabina Schwenk-Zieger, Roland Stauber, Sebastian Strieth, Julian Kuenzel, Philipp Baumeister, Sven Becker
Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood...
April 20, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29731891/synergistic-effects-of-cisplatin-caffeic-acid-induces-apoptosis-in-human-cervical-cancer-cells-via-the-mitochondrial-pathways
#17
Amonrat Koraneekit, Temduang Limpaiboon, Arunnee Sangka, Patcharee Boonsiri, Sakda Daduang, Jureerut Daduang
Cervical cancer (CxCa) is a major health problem globally and is associated with the presence of human papillomavirus infection. Cisplatin (CDDP) is a platinum-based chemotherapeutic agent. Owing to its side effects and drug-resistance, novel anticancer agents with lower toxicity, including caffeic acid (CFC), are of interest. However, the effects of CDDP and CFC in combination are, to the best of our knowledge, uninvestigated. The present study investigated the effectiveness of CDDP and CFC in combination and its mechanism of action on four human cervical cancer cell lines, which were compared with the Chlorocebus sabaeus normal kidney Vero cell line...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29730234/microfocus-x-ray-fluorescence-mapping-of-tumour-penetration-by-an-organo%C3%A2-osmium-anticancer-complex
#18
Carlos Sanchez-Cano, Isolda Romero-Canelón, Kalotina Geraki, Peter J Sadler
Microfocus synchrotron x-ray fluorescence (SXRF) imaging focussed on detection of the Os LIII edge shows that the organo‑osmium metallodrug candidate [(ŋ6 -p-cym)Os(Azpy-NMe2 )I]+ (p-cym = p-cymene, Azpy-NMe2  = 2-(p-([dimethylamino]phenylazo)pyridine)) [1] penetrates efficiently into the interior of A2780 human ovarian cancer cell spheroids, a model for a solid tumour. The accompanying changes in Zn and Ca distribution suggest that the complex causes nuclear damage and initiates signalling events for cell death, consistent with findings for cultured cancer cell monolayers...
April 25, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29729664/complete-response-to-orally-administered-melphalan-in-malignant-pleural-effusion-from-an-occult-female-genital-organ-primary-neoplasm-with-brca1-2-mutations-a-case-report
#19
Frank S Fan, Chung-Fan Yang
BACKGROUND: Definite diagnosis of metastasis from unknown primary depends on a comprehensive immunohistochemical investigation of tumor specimen. Accurate identification of the origin site usually helps a lot in choosing the most appropriate treatment. Molecular characterization provides more chance of a cure. Echoing modern medical development, BRCA1/2 mutations have been correlated with high efficiency of poly(adenosine diphosphate-ribose) polymerase inhibitors in ovarian cancer. While a previous case report demonstrated a surprising cure of platinum-resistant ovarian cancer with BRCA2 mutation by orally administered melphalan...
May 6, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29726474/novel-platinum-based-anticancer-drug-a-complete-vibrational-study
#20
A L M Batista de Carvalho, S F Parker, L A E Batista de Carvalho, M P M Marques
The introduction of cisplatin to oncology, in the 1970s, marked the onset of the search for novel and improved metal-based anticancer drugs. Polynuclear PtII and PdII complexes with linear alkylamines as bridging ligands are a class of potential antineoplastic agents that have shown promising cytotoxicity against low-prognosis human cancers, such as metastatic breast adenocarcinoma and osteosarcoma. The present study reports an analysis of [μ-N,N'-bis(3-aminopropyl)butane-1,4-diamine-κ4 N,N':N'',N''']bis[dichloridoplatinum(II)], [Pt2 Cl4 (C10 H26 N4 )], denoted Pt2 Spm (Spm is spermine), by vibrational spectroscopy coupled to theoretical calculations...
May 1, 2018: Acta Crystallographica. Section C, Structural Chemistry
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