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Corinna Keup, Markus Storbeck, Siegfried Hauch, Peter Hahn, Markus Sprenger-Haussels, Mitra Tewes, Pawel Mach, Oliver Hoffmann, Rainer Kimmig, Sabine Kasimir-Bauer
Liquid biopsy analytes such as cell-free DNA (cfDNA) and circulating tumor cells (CTCs) exhibit great potential for personalized treatment. Since cfDNA and CTCs are considered to give additive information and blood specimens are limited, isolation of cfDNA and CTC in an "all from one tube" format is desired. We investigated whether cfDNA variant sequencing from CTC-depleted blood (CTC-depl. B; obtained after positive immunomagnetic isolation of CTCs (AdnaTest EMT-2/Stem Cell Select, QIAGEN)) impacts the results compared to cfDNA variant sequencing from matched whole blood (WB)...
February 18, 2019: Cancers
Takayuki Okamoto, Haruki Usuda, Tetsuya Tanaka, Koichiro Wada, Motomu Shimaoka
Angiogenesis-the sprouting and growth of new blood vessels from the existing vasculature-is an important contributor to tumor development, since it facilitates the supply of oxygen and nutrients to cancer cells. Endothelial cells are critically affected during the angiogenic process as their proliferation, motility, and morphology are modulated by pro-angiogenic and environmental factors associated with tumor tissues and cancer cells. Recent in vivo and in vitro studies have revealed that the gap junctions of endothelial cells also participate in the promotion of angiogenesis...
February 18, 2019: Cancers
Nicola Amodio, Maria Eugenia Gallo Cantafio, Cirino Botta, Valter Agosti, Cinzia Federico, Daniele Caracciolo, Domenica Ronchetti, Marco Rossi, Christoph Driessen, Antonino Neri, Pierosandro Tagliaferri, Pierfrancesco Tassone
Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro...
February 18, 2019: Cancers
Blanca Felipe-Abrio, Eva Maria Verdugo-Sivianes, Carmen Sáez, Amancio Carnero
Tumors are cellular ecosystems where different populations and subpopulations of cells coexist. Among these cells, cancer stem cells (CSCs) are considered to be the origin of the tumor mass, being involved in metastasis and in the resistance to conventional therapies. Furthermore, tumor cells have an enormous plasticity and a phenomenon of de-differentiation of mature tumor cells to CSCs may occur. Therefore, it is essential to identify genetic alterations that cause the de-differentiation of mature tumor cells to CSCs for the future design of therapeutic strategies...
February 18, 2019: Cancers
Peixin Dong, Ying Xiong, Junming Yue, Sharon J B Hanley, Noriko Kobayashi, Yukiharu Todo, Hidemichi Watari
Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways...
February 16, 2019: Cancers
Dirk Rades, Heinke C Hansen, Stefan Janssen, Steven E Schild
Diagnosis-specific survival scores including a new score developed in 157 patients with brain metastases from small-cell lung cancer (SCLC) receiving whole-brain radiotherapy (WBRT) with 30 Gy in 10 fractions (WBRT-30-SCLC) were compared. Three prognostic groups were designed based on the 6-month survival probabilities of significant or almost significant factors, (age, performance score, number of brain metastases, extra-cerebral metastasis). Six-month survival rates were 6% (6⁻11 points), 44% (12⁻14 points) and 86% (16⁻19 points)...
February 16, 2019: Cancers
Samaresh Sau, Alex Petrovici, Hashem O Alsaab, Ketki Bhise, Arun K Iyer
Targeting immune checkpoint molecules such as programmed death ligand-1 (PDL1) is an emerging strategy for anti-cancer therapy. However, transient expression of PDL1 and difficulty in tumor stroma penetration has limited the utility of anti-PDL1 therapy. To overcome these limitations, we report a new conjugate between the clinically approved PDL1 antibody (PDL1 AB) and drug Doxorubicin (Dox), named PDL1-Dox. We conjugated PDL1-Dox through a hydrazone linker containing a polyethylene glycol (PEG) spacer, which allows it to dissociate in a tumor environment and improves solubility...
February 16, 2019: Cancers
Jonathan M Fahey, Albert W Girotti
Many studies have shown that low flux nitric oxide (NO) produced by inducible NO synthase (iNOS/NOS2) in various tumors, including glioblastomas, can promote angiogenesis, cell proliferation, and migration/invasion. Minimally invasive, site-specific photodynamic therapy (PDT) is a highly promising anti-glioblastoma modality. Recent research in the authors' laboratory has revealed that iNOS-derived NO in glioblastoma cells elicits resistance to 5-aminolevulinic acid (ALA)-based PDT, and moreover endows PDT-surviving cells with greater proliferation and migration/invasion aggressiveness...
February 15, 2019: Cancers
Jackelien G M van Beek, Quincy C C van den Bosch, Nicole Naus, Dion Paridaens, Annelies de Klein, Emine Kiliç, Robert M Verdijk
The aim of this study was to investigate the presence of intraocular lymphatic vessels in patients with uveal melanomas and extrascleral extension using a panel of lymphatic markers. The following immunohistochemical markers were analyzed: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), podoplanin (D2-40), prospero-related homeobox gene-1 (Prox-1), pan-endothelial marker cluster of differentiation 31 (CD31), and blood vessel endothelium-specific CD34. Lymphatic vessels were defined as a combination of staining of the following positive markers: LYVE-1, D2-40, Prox-1, and CD31; and no staining of the negative marker CD34...
February 15, 2019: Cancers
Imelda Seminerio, Géraldine Descamps, Sophie Dupont, Lisa de Marrez, Jean-Alexandre Laigle, Jérôme R Lechien, Nadège Kindt, Fabrice Journe, Sven Saussez
Head and Neck Squamous Cell Carcinomas (HNSCC) are characterized by a large heterogeneity in terms of the location and risk factors. For a few years now, immunotherapy seems to be a promising approach in the treatment of these cancers, but a better understanding of the immune context could allow to offer a personalized treatment and thus probably increase the survival of HNSCC patients. In this context, we evaluated the infiltration of FoxP3+ Tregs on 205 human formalin-fixed paraffin-embedded HNSCC and we assessed its prognostic value compared to other potential prognostic factors, including HPV infection...
February 15, 2019: Cancers
Chloe C Lepage, Claire R Morden, Michaela C L Palmer, Mark W Nachtigal, Kirk J McManus
Chromosome instability (CIN) is defined as an increased rate of chromosome gains and losses that manifests as cell-to-cell karyotypic heterogeneity and drives cancer initiation and evolution. Current research efforts are aimed at identifying the etiological origins of CIN, establishing its roles in cancer pathogenesis, understanding its implications for patient prognosis, and developing novel therapeutics that are capable of exploiting CIN. Thus, the ability to accurately identify and evaluate CIN is critical within both research and clinical settings...
February 15, 2019: Cancers
Tae Hyun Kim, Joong-Won Park, Bo Hyun Kim, Hyunjung Kim, Sung Ho Moon, Sang Soo Kim, Sang Myung Woo, Young-Hwan Koh, Woo Jin Lee, Dae Yong Kim, Chang-Min Kim
To evaluate the role of risk-adapted proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients, a total of 243 HCC patients receiving risk-adapted PBT with three dose-fractionation regimens (regimen A [ n = 40], B [ n = 60], and C [ n = 143]) according to the proximity of their gastrointestinal organs (<1 cm, 1⁻1.9 cm, and ≥2 cm, respectively) were reviewed: The prescribed doses to planning target volume 1 (PTV1) were 50 gray equivalents (GyE) (EQD2 [equivalent dose in 2 Gy fractions], 62...
February 15, 2019: Cancers
Paweł Krzyżek, Roman Franiczek, Barbara Krzyżanowska, Łukasz Łaczmański, Paweł Migdał, Grażyna Gościniak
Helicobacter pylori (H. pylori) is a bacterium capable of inducing chronic active gastritis, which in some people, develops into gastric cancers. One of the substances that may be useful in the eradication of this microorganism is 3-Bromopyruvate (3-BP), an anticancer compound with antimicrobial properties. The aim of this article was to determine the activity of 3-BP against antibiotic-susceptible and antibiotic-resistant H. pylori strains. The antimicrobial activity was determined using a disk-diffusion method, broth microdilution method, time-killing assay, and checkerboard assay...
February 15, 2019: Cancers
Adam Stenman, Jan Zedenius, Carl Christofer Juhlin
Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia, respectively. These tumors exhibit malignant potential but seldom display evidence of metastatic spread, the latter being the only widely accepted evidence of malignancy. To counter this, pre-defined histological algorithms have been suggested to stratify the risk of malignancy: Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP)...
February 15, 2019: Cancers
Felicetto Ferrara, Federica Lessi, Orsola Vitagliano, Erika Birkenghi, Giuseppe Rossi
Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months...
February 14, 2019: Cancers
Maria Silvia Cona, Mara Lecchi, Sara Cresta, Silvia Damian, Michele Del Vecchio, Andrea Necchi, Marta Maria Poggi, Daniele Raggi, Giovanni Randon, Raffaele Ratta, Diego Signorelli, Claudio Vernieri, Filippo de Braud, Paolo Verderio, Massimo Di Nicola
Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti- Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex...
February 14, 2019: Cancers
Yusuf A Haggag, Kyle B Matchett, Robert A Falconer, Mohammad Isreb, Jason Jones, Ahmed Faheem, Paul McCarron, Mohamed El-Tanani
The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (NPs)...
February 14, 2019: Cancers
Sreeja C Sekhar, Jaganathan Venkatesh, Vino T Cheriyan, Magesh Muthu, Edi Levi, Hadeel Assad, Paul Meister, Vishnu V Undyala, James W Gauld, Arun K Rishi
Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage. Phosphorylation of histone 2AX (γH2AX) protein is involved in regulating DNA damage repair and apoptosis signaling. Adriamycin or CFM-4.16 treatments inhibited cell growth and caused elevated CARP-1 and γH2AX in human breast (HBC) and cervical cancer (HeLa) cells...
February 14, 2019: Cancers
Shu-Yu Cheng, Nan-Fu Chen, Pi-Yu Lin, Jui-Hsin Su, Bing-Hung Chen, Hsiao-Mei Kuo, Chun-Sung Sung, Ping-Jyun Sung, Zhi-Hong Wen, Wu-Fu Chen
Angiogenesis and invasion are highly related with tumor metastatic potential and recurrence prediction in the most aggressive brain cancer, glioblastoma multiforme (GBM). For the first time, this study reveals that marine-sponge-derived stellettin B reduces angiogenesis and invasion. We discovered that stellettin B reduces migration of glioblastoma cells by scratch wound healing assay and invasion via chamber transwell assay. Further, stellettin B downregulates Akt/Mammalian Target of Rapamycin (Akt/mTOR) and Signal transducer and activator of transcription 3 (Stat3) signaling pathways, which are essential for invasion and angiogenesis in glioblastoma...
February 14, 2019: Cancers
Florian Primavesi, Stefan Stättner, Tarkan Jäger, Georg Göbel, Jaroslav Presl, Katerina Tomanová, Selina Buchner, Manuel Maglione, Thomas Resch, Jörg Hutter, Dietmar Öfner, Adam Dinnewitzer
BACKGROUND: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation of oncosurgical management in a single-centre, analysing the aggregate effect of gradual implementation of surgical subspecialties and systemic treatments on mCRC patients' resection rates and prognosis...
February 14, 2019: Cancers
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