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https://www.readbyqxmd.com/read/27913947/preclinical-evaluation-of-cathepsin-based-fluorescent-imaging-system-for-cytoreductive-surgery
#1
Carlos H F Chan, Lukas F Liesenfeld, Isabel Ferreiro-Neira, James C Cusack
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal surface malignancies. The ability to detect microscopic foci of peritoneal metastasis intraoperatively may ensure the completeness of cytoreduction. In this study, we evaluated the suitability of a hand-held cathepsin-based fluorescent imaging system for intraoperative detection of appendiceal and colorectal peritoneal metastasis. METHODS: Peritoneal tumors and normal peritoneal tissues were collected from patients with appendiceal and colorectal peritoneal metastasis...
December 2, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27907907/expression-analysis-and-clinical-significance-of-eif4e-vegf-c-e-cadherin-and-mmp-2-in-colorectal-adenocarcinoma
#2
Minna Gao, Xiong Zhang, Dan Li, Ping He, Wenguang Tian, Bo Zeng
The underlying mechanisms of colorectal carcinoma (CRC) metastasis remain to be elucidated. The aim of this study is to investigate clinical significance and the expression of eIF4E, VEGF-C, MMP-2, and E-cadherin in the CRC metastasis. We investigated their expressions in 108 patients, analyzed the relationships between their expressions in CRC and evaluated the relationships between their expressions and clinical pathogenic parameters. Furthermore, their roles in patient survival and in CRC metastasis were also investigated...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904779/generation-characterization-and-maintenance-of-trastuzumab-resistant-her2-breast-cancer-cell-lines
#3
Sandra Zazo, Paula González-Alonso, Ester Martín-Aparicio, Cristina Chamizo, Ion Cristóbal, Oriol Arpí, Ana Rovira, Joan Albanell, Pilar Eroles, Ana Lluch, Juan Madoz-Gúrpide, Federico Rojo
Trastuzumab became the therapy of choice for patients with HER2-positive breast cancer in 1998, and it has provided clinical benefit ever since. However, a significant percentage of patients show primary resistance to trastuzumab at diagnosis, and most patients with metastatic disease that initially respond to trastuzumab eventually progress (acquired resistance). Consequently, there is an urgent need to improve our knowledge of the mechanisms governing resistance, so that specific therapeutic strategies can be developed to provide improved efficacy...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903751/microdose-induced-drug-dna-adducts-as-biomarkers-of-chemotherapy-resistance-in-humans-and-mice
#4
Maike Zimmermann, Si-Si Wang, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Ted Ognibene, Hongyuan Yang, Susan Airhart, Kenneth W Turteltaub, George D Cimino, Clifford G Tepper, Alexandra Drakaki, Karim Chamie, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27903750/nuclear-export-of-ubiquitinated-proteins-determines-the-sensitivity-of-colorectal-cancer-to-proteasome-inhibitor
#5
Tingyu Wu, Wei Chen, Yongwang Zhong, Xiaodan Hou, Shengyun Fang, Chen-Ying Liu, Guanghui Wang, Tong Yu, Yu-Yang Huang, Xuesong Ouyang, Henry Q X Li, Long Cui, Yili Yang
Although proteasome inhibitors such as Bortezomib had significant therapeutic effects in multiple myeloma and mantel cell lymphoma, they exhibited minimal clinical activity as a mono-therapy for solid tumors, including colorectal cancer. We found in the present study that proteasome inhibition induced a remarkable nuclear exportation of ubiquitinated proteins. Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of Bortezomib on colon cancer cells containing wild type p53, which underwent G2/M cell cycle block and apoptosis...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27903250/effectiveness-of-bovine-derived-xenograft-versus-bioactive-glass-with-periodontally-accelerated-osteogenic-orthodontics-in-adults-a-randomized-controlled-clinical-trial
#6
Maha A Bahammam
BACKGROUND: Periodontally accelerated osteogenic orthodontics (PAOO) combines periodontal therapy with orthodontic therapy, which minimises treatment time. This study compared the effectiveness of a bovine-derived xenograft with that of bioactive glass when combined with PAOO for the treatment of adult patients with moderate crowding of the teeth. METHODS: In this prospective, single-masked clinical trial, 33 orthodontic patients (20 women, 13 men; mean age 21.2 ± 1...
November 30, 2016: BMC Oral Health
https://www.readbyqxmd.com/read/27902970/activity-of-the-novel-polo-like-kinase-4-inhibitor-cfi-400945-in-pancreatic-cancer-patient-derived-xenografts
#7
I Lohse, J M Mason, P J Cao, Melania Pintilie, M R Bray, D W Hedley
BACKGROUND: Polo-like kinase 4 (PKL4) plays a key role in centriole replication. Hence PLK4 inhibition disrupts mitosis, and offers a novel approach to treating chromosomally unstable cancers, including pancreatic cancer. CFI-400945 is a first in class small molecule PLK4 inhibitor, currently undergoing early phase clinical trials. RESULTS: Treatment with CFI-400945 significantly reduced tumor growth and increased survival in four out of the six models tested. Consistent with PLK4 inhibition, we observed reduced expression of the proliferation marker Ki-67 associated with an increase in nuclear diameter during treatment with CFI-400945...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#8
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#9
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901481/human-pancreatic-cancer-xenografts-recapitulate-key-aspects-of-cancer-cachexia
#10
Daniel Delitto, Sarah M Judge, Andrea E Delitto, Rachel L Nosacka, Fernanda G Rocha, Bayli B DiVita, Michael H Gerber, Thomas J George, Kevin E Behrns, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia represents a debilitating syndrome that diminishes quality of life and augments the toxicities of conventional treatments. Cancer cachexia is particularly debilitating in patients with pancreatic cancer (PC). Mechanisms responsible for cancer cachexia are under investigation and are largely derived from observations in syngeneic murine models of cancer which are limited in PC. We evaluate the effect of human PC cells on both muscle wasting and the systemic inflammatory milieu potentially contributing to PC-associated cachexia...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900284/effect-of-pantethine-on-ovarian-tumor-progression-and-choline-metabolism
#11
Marie-France Penet, Balaji Krishnamachary, Flonne Wildes, Yelena Mironchik, Delia Mezzanzanica, Franca Podo, Max de Reggi, Bouchra Gharib, Zaver M Bhujwalla
Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27894958/poly-adp-ribose-polymerase-inhibitors-selectively-induce-cytotoxicity-in-tcf3-hlf-positive-leukemic-cells
#12
Jinhua Piao, Shiori Takai, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Domenico Delia, Mitsuko Masutani, Shuki Mizutani, Masatoshi Takagi
Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA repair machinery. PARP inhibitors are used as cutting-edge treatments for patients with homologous recombination repair (HRR)-defective breast cancers harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including some hematological malignancies, are predicted to be good candidates for treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed that lymphoid lineage-derived leukemia cell lines, except for those derived from mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively sensitive to PARP inhibitors...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894339/the-identification-of-human-pituitary-adenoma-initiating-cells
#13
Branavan Manoranjan, Sujeivan Mahendram, Saleh A Almenawer, Chitra Venugopal, Nicole McFarlane, Robin Hallett, Thusyanth Vijayakumar, Almunder Algird, Naresh K Murty, Doron D Sommer, John P Provias, Kesava Reddy, Sheila K Singh
Classified as benign central nervous system (CNS) tumors, pituitary adenomas account for 10% of diagnosed intracranial neoplasms. Although surgery is often curative, patients with invasive macroadenomas continue to experience significant morbidity and are prone to tumor recurrence. Given the identification of human brain tumor-initiating cells (TICs) that initiate and maintain tumor growth while promoting disease progression and relapse in multiple CNS tumors, we investigated whether TICs also drive the growth of human pituitary adenomas...
November 28, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27890933/preclinical-activity-of-cpi-0610-a-novel-small-molecule-bromodomain-and-extra-terminal-protein-inhibitor-in-the-therapy-of-multiple-myeloma
#14
K T Siu, J Ramachandran, A J Yee, H Eda, L Santo, C Panaroni, J A Mertz, R J Sims, M R Cooper, N Raje
Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through suppression of MYC transcription and activity. However, suppression of the transcription of additional genes also contributes to the anti-tumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing Phase I clinical testing, in multiple myeloma (MM)...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890855/linker-stability-influences-the-anti-tumor-activity-of-acetazolamide-drug-conjugates-for-the-therapy-of-renal-cell-carcinoma
#15
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27889646/mirvetuximab-soravtansine-imgn853-a-folate-receptor-alpha-targeting-antibody-drug-conjugate-potentiates-the-activity-of-standard-of-care-therapeutics-in-ovarian-cancer-models
#16
Jose F Ponte, Olga Ab, Leanne Lanieri, Jenny Lee, Jennifer Coccia, Laura M Bartle, Marian Themeles, Yinghui Zhou, Jan Pinkas, Rodrigo Ruiz-Soto
Elevated folate receptor alpha (FRα) expression is characteristic of epithelial ovarian cancer (EOC), thus establishing this receptor as a candidate target for the development of novel therapeutics to treat this disease. Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FRα for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamics. Here, combinations of IMGN853 with approved therapeutics were evaluated in preclinical models of EOC...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27888804/niclosamide-and-its-analogs-are-potent-inhibitors-of-wnt-%C3%AE-catenin-mtor-and-stat3-signaling-in-ovarian-cancer
#17
Rebecca C Arend, Angelina I Londoño-Joshi, Abhishek Gangrade, Ashwini A Katre, Chandrika Kurpad, Yonghe Li, Rajeev S Samant, Pui-Kai Li, Charles N Landen, Eddy S Yang, Bertha Hidalgo, Ronald D Alvarez, J Michael Straughn, Andres Forero, Donald J Buchsbaum
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer mortality worldwide. Platinum-based therapy is the standard first line treatment and while most patients initially respond, resistance to chemotherapy usually arises. Major signaling pathways frequently upregulated in chemoresistant cells and important in the maintenance of cancer stem cells (CSCs) include Wnt/β-catenin, mTOR, and STAT3. The major objective of our study was to investigate the treatment of ovarian cancer with targeted agents that inhibit these three pathways...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888545/anti-angiogenic-therapy-affects-the-relationship-between-tumor-vascular-structure-and-function-a-correlation-study-between-micro-computed-tomography-angiography-and-dynamic-contrast-enhanced-mri
#18
Eugene Kim, Jana Kim, Gunhild Mari Maelandsmo, Berit Johansen, Siver Andreas Moestue
PURPOSE: To compare the effects of two anti-angiogenic drugs, bevacizumab and a cytosolic phospholipase A2-α inhibitor (AVX235), on the relationship between vascular structure and dynamic contrast enhanced (DCE)-MRI measurements in a patient-derived breast cancer xenograft model. METHODS: Mice bearing MAS98.12 tumors were randomized into three groups: bevacizumab-treated (n = 9), AVX235-treated (n = 9), and control (n = 8). DCE-MRI was performed pre- and post-treatment...
November 25, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/27880910/cdk12-inhibition-reverses-de-novo-and-acquired-parp-inhibitor-resistance-in-brca-wild-type-and-mutated-models-of-triple-negative-breast-cancer
#19
Shawn F Johnson, Cristina Cruz, Ann Katrin Greifenberg, Sofia Dust, Daniel G Stover, David Chi, Benjamin Primack, Shiliang Cao, Andrea J Bernhardy, Rhiannon Coulson, Jean-Bernard Lazaro, Bose Kochupurakkal, Heather Sun, Christine Unitt, Lisa A Moreau, Kristopher A Sarosiek, Maurizio Scaltriti, Dejan Juric, José Baselga, Andrea L Richardson, Scott J Rodig, Alan D D'Andrea, Judith Balmaña, Neil Johnson, Matthias Geyer, Violeta Serra, Elgene Lim, Geoffrey I Shapiro
Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27877237/near-infrared-fluorescent-nanoparticles-derived-from-hyaluronic-acid-improve-tumor-contrast-for-image-guided-surgery
#20
Tanner K Hill, Sneha S Kelkar, Nicholas E Wojtynek, Joshua J Souchek, William M Payne, Kristina Stumpf, Frank C Marini, Aaron M Mohs
Tumor tissue that remains undetected at the primary surgical site can cause tumor recurrence, repeat surgery, and treatment strategy alterations that impose a significant patient and healthcare burden. Intraoperative near infrared fluorescence (NIRF) imaging is one potential method to identify remaining tumor by visualization of NIR fluorophores that are preferentially localized to the tumor. This requires development of fluorophores that consistently identify tumor tissue in different patients and tumor types...
2016: Theranostics
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