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Clinical & Experimental Metastasis

Bushra Abu-Helil, Louise van der Weyden
Humans are not the only species to spontaneously develop metastatic cancer as cases of metastasis have been reported in a wide range of animals, including dinosaurs. Mouse models have been an invaluable tool in experimental and clinical metastasis research, with the use of genetically-engineered mouse models that spontaneously develop metastasis or ectopic/orthotopic transplantation of tumour cells to wildtype or immunodeficient mice being responsible for many key advances in our understanding of metastasis...
February 9, 2019: Clinical & Experimental Metastasis
Miguel Alberto, Andreas Brandl, Pankaj Kumar Garg, Safak Gül-Klein, Mathias Dahlmann, Ulrike Stein, Beate Rau
This manuscript aspires to portray a review of the current literature focusing on manifest peritoneal metastasis (PM) derived from gastric cancer and its treatment options. Despite the development of chemotherapy and multimodal treatment options during the last decades, mortality remains high worldwide. After refreshing important epidemiological considerations, the molecular mechanisms currently accepted through which PM occurs are revised. Palliative chemotherapy is the only recommended treatment option for patients with PM of gastric cancer according to the National Comprehensive Cancer Network guidelines, although cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy demonstrated promising results in selected patients with regional PM and localized intraabdominal tumor spread...
February 4, 2019: Clinical & Experimental Metastasis
Anne Kauffels, Marie Kitzmüller, Andrea Gruber, Hannah Nowack, Hanibal Bohnenberger, Melanie Spitzner, Anja Kuthning, Thilo Sprenger, Martin Czejka, Michael Ghadimi, Jens Sperling
Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept® S and Tandem™...
January 24, 2019: Clinical & Experimental Metastasis
Thomas Beadnell, Lucia Borriello, Jessica Christenson, Jaime Fornetti, Ian Guldner, Ann Hanna, Lenka Kyjacova, Kristina Marinak-Whately, Poliana Cristina de Melo Martins, Mirja Rotinen, Veronika Te Boekhorst, Thomas R Cox
The Metastasis Research Society (MRS) 17th Biennial conference on metastasis was held on the 1st to the 5th of August 2018 at Princeton University, NJ, USA. The meeting was held around themes addressing notable aspects of the understanding and treatment of metastasis and metastatic disease covering basic, translational, and clinical research. Importantly, the meeting was largely supported by our patient advocate partners including Susan G. Komen for the Cure, Theresa's Research Foundation and METAvivor. There were a total of 85 presentations from invited and selected speakers spread across the main congress and presentations from the preceding Young Investigator Satellite Meeting...
January 23, 2019: Clinical & Experimental Metastasis
Wu-Gui Chen, Jing Sun, Wei-Wei Shen, Si-Zhen Yang, Ying Zhang, Xu Hu, Hao Qiu, Shang-Cheng Xu, Tong-Wei Chu
Most lung cancer bone metastasis are characterized by osteolytic destruction and osteoblastic activity is significantly decreased, suggesting that hypoxia may play a critical role in the process, but the underlying mechanisms remain unknown. Semaphorin 4D (Sema4D) is a recently discovered osteogenic inhibitory factor that is expressed at high levels in lung cancers. Here, CoCl2 -induced hypoxia significantly enhanced the inhibitory effect of lung cancer cell conditioned media on osteoblast differentiation by inducing the expression and secretion of Sema4D in a HIF-1α- but not HIF-2α-dependent manner...
January 7, 2019: Clinical & Experimental Metastasis
Shiue-Wei Lai, Oluwaseun Adebayo Bamodu, Wen-Chiuan Tsai, Yi-Ming Chang, Wei-Hwa Lee, Chi-Tai Yeh, Tsu-Yi Chao
In the original publication, the affiliations of authors were published incorrectly. The corrected affiliations are given in this Correction.
January 4, 2019: Clinical & Experimental Metastasis
Quirine F Manson, Willemijne A M E Schrijver, Natalie D Ter Hoeve, Cathy B Moelans, Paul J van Diest
Programmed death-1 (PD-1) is an immune checkpoint that is able to inhibit the immune system by binding to its ligand programmed death-ligand 1 (PD-L1). In many cancer types, among which breast cancer, prognostic and/or predictive values have been suggested for both PD-1 and PD-L1. Previous research has demonstrated discrepancies in PD-L1 expression between primary breast tumors and distant metastases, however data so far have been scarce. We therefore evaluated immunohistochemical expression levels of PD-1 and PD-L1 in primary breast tumors and their paired distant metastases, and evaluated prognostic values...
December 13, 2018: Clinical & Experimental Metastasis
Jonathan P Sleeman
The impact of diet and associated lifestyle choices on the risk of developing cancer is well established. However, whether these parameters also affect cancer recurrence and survival is less well investigated. Virtually nothing is known about the impact of diet on the development of metastases. It is therefore significant that a study in this issue of Clinical and experimental metastasis reports that breast cancer-bearing mice fed on a diet rich in long-chain omega-3 fatty acids had a lower incidence of metastasis than control mice, which was associated with modified infiltration of immune cells into the tumors...
December 2018: Clinical & Experimental Metastasis
L M Füreder, G Widhalm, B Gatterbauer, K Dieckmann, J A Hainfellner, R Bartsch, C C Zielinski, M Preusser, A S Berghoff
Symptomatic brain metastases (BM) are a frequent and late complication in cancer patients. However, a subgroup of cancer patients presents with BM as the first symptom of metastatic cancer. Here we aimed to analyze the clinical course and prognostic factors of this particular BM patient population. Patients presenting with newly diagnosed BM without a history of metastatic cancer were identified from the Vienna Brain Metastasis Registry. Clinical characteristics and overall survival were retrieved by chart review...
December 2018: Clinical & Experimental Metastasis
Lewis A Quayle, Penelope D Ottewell, Ingunn Holen
Metastatic recurrence in breast cancer is a major cause of mortality and often occurs many years after removal of the primary tumour. This process is driven by the reactivation of disseminated tumour cells that are characterised by mitotic quiescence and chemotherapeutic resistance. The ability to reliably isolate and characterise this cancer cell population is critical to enable development of novel therapeutic strategies for prevention of breast cancer recurrence. Here we describe the identification and characterisation of a sub-population of slow-cycling tumour cells in the MCF-7 and MDA-MB-231 human breast cancer cell lines based on their ability to retain the lipophilic fluorescent dye Vybrant® DiD for up to six passages in culture...
December 2018: Clinical & Experimental Metastasis
Robin Boiy, Jonas Steenbrugge, Jan Van Deun, An Hendrix, Evelyne Meyer, Olivier De Wever
Metastasis is key to cancer mortality. Understanding its biology is vital for developing strategies to prevent and treat metastasis. Phenotypic assays to either study metastasis or evaluate anti-metastatic drugs are widely used in preclinical research. This technical note discusses the adherence of reporting essential experimental and methodological parameters in chemotactic invasion assays in vitro and spontaneous metastasis assays in vivo. Following the analysis of 130 recent (< 5 years) research papers, several shortcomings in reporting were identified...
December 2018: Clinical & Experimental Metastasis
Kirsten Nguyen Knudsen, Jan Lindebjerg, Alexandra Kalmár, Béla Molnár, Flemming Brandt Sørensen, Torben Frøstrup Hansen, Boye Schnack Nielsen
MicroRNA-21 (miR-21) expression in stromal fibroblastic cells in colorectal cancer is well-documented, whereas miR-21 expression in tumor budding cells (TBCs) is poorly described. TBCs are locally invasive carcinoma cells with increased metastatic properties and characteristics of epithelial to mesenchymal transition. This study was conducted to better characterize the expression of miR-21 in TBCs. First, chromogenic miR-21 in situ hybridization (ISH) staining was performed in 58 colon adenocarcinomas with evident TBCs...
December 2018: Clinical & Experimental Metastasis
Wangmi Liu, Jiayan Wu
The present study used the Surveillance, Epidemiology and End Results (SEER) database to identify demographic and prognostic characteristics of lung cancer with bone metastases in the United States from 2010 to 2014. 30,364 patients with metastatic lung cancer to bones were identified in the SEER database. Their information on the basic characteristics and the histological signatures of the cancer was extracted and analyzed. Joinpoint analysis was used to test the trends in annual percentage change (APC) of the incidence...
December 2018: Clinical & Experimental Metastasis
Saraswoti Khadge, Geoffrey M Thiele, John Graham Sharp, Timothy R McGuire, Lynell W Klassen, Paul N Black, Concetta C DiRusso, Leah Cook, James E Talmadge
Epidemiological studies show a reduced risk of breast cancer (BC) in women consuming high levels of long-chain (LC) omega-3 (ω-3) fatty acids (FAs) compared with women who consumed low levels. However, the regulatory and mechanistic roles of dietary ω-6 and LC-ω-3 FAs on tumor progression, metastasis and survival are poorly understood. Female BALB/c mice (10-week old) were pair-fed with a diet containing ω-3 or an isocaloric, isolipidic ω-6 diet for 16 weeks prior to the orthotopic implantation of 4T1 mammary tumor cells...
December 2018: Clinical & Experimental Metastasis
C Liedtke, Hans-Christian Kolberg, L Kerschke, D Görlich, I Bauerfeind, T Fehm, B Fleige, G Helms, A Lebeau, A Stäbler, S Schmatloch, M Hausschild, L Schwentner, Gunter von Minckwitz, S Loibl, M Untch, T Kühn
Optimization of axillary staging among patients converting from clinically node-positive disease to clinically node-negative disease through primary systemic therapy is needed. We aimed at developing a nomogram predicting the probability of positive axillary status after chemotherapy based on clinical/pathological parameters. Patients from study arm C of the SENTINA trial were included. Univariable/multivariable analyses were performed for 13 clinical/pathological parameters to predict a positive pathological axillary status after chemotherapy using logistic regression models...
December 2018: Clinical & Experimental Metastasis
Eleonora Farina, Gabriella Macchia, Milly Buwenge, Giambattista Siepe, Alice Zamagni, Silvia Cammelli, Savino Cilla, Tigeneh Wondemagegnhu, Aynalem A Woldemariam, A F M Kamal Uddin, Mostafà Aziz Sumon, Francesco Cellini, Francesco Deodato, Alessio G Morganti
The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I-II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥ 3 toxicity based on the RTOG scale...
December 2018: Clinical & Experimental Metastasis
Rui-Cheng Ji, Yuki Eshita, Takashi Kobayashi, Shinya Hidano, Naganori Kamiyama, Yasuhiko Onishi
Lymphangiogenesis plays a crucial role in promoting cancer metastasis to sentinel lymph nodes (LNs) and beyond. Increasing data have shown that simvastatin, a cholesterol-lowering medication for the prevention of cardiovascular diseases, is involved in tumor growth and dissemination, and endothelial functions. This study aimed to investigate the potential effect of simvastatin on lymphatic formation and LN metastasis. Tumor models were established by subcutaneous injection of B16-F10 melanoma cells into mouse hind footpads...
December 2018: Clinical & Experimental Metastasis
Gabriella Macchia, Milena Ferro, Savino Cilla, Milly Buwenge, Anna Ianiro, Mariangela Boccardi, Vincenzo Picardi, Marica Ferro, Eleonora Arena, Alice Zamagni, Silvia Cammelli, Vincenzo Valentini, Alessio G Morganti, Francesco Deodato
Half-body irradiation (HBI) represented a standard treatment for multiple painful bone metastases (BMs). However, its use has progressively reduced due to the associated toxicity rates. The aim of this paper was to evaluate HBI delivered by conformal radiotherapy (RT) technique in a large patients population with widespread BMs. HBI was delivered in 3 Gy fractions, bid, ≥ 6 h apart, on 2 consecutive days (total dose: 12 Gy) using 3-dimensional conformal RT (3D-CRT) box technique. The target included pelvic bones, lumbar-sacral vertebrae and upper third of femurs...
December 2018: Clinical & Experimental Metastasis
Mariz Kasoha, Rainer M Bohle, Anita Seibold, Christoph Gerlinger, Ingolf Juhasz-Böss, Erich-Franz Solomayer
Dysregulation of the Wnt inhibitor dickkopf-1 protein (Dkk1) has been reported in a variety of cancers. In addition, it has been linked to the progression of malignant bone disease by impairing osteoblast activity. This study investigated serum- and tissue levels of Dkk1 in breast cancer patients with- or without bone metastases. Serum Dkk1 levels were measured by ELISA in 89 breast cancer patients and 86 healthy women. Tissue levels of Dkk1 and β-catenin, a major downstream component of Wnt transduction pathway, were tested with immunohistochemical staining in 143 different tissues, including adjacent non-tumoral breast tissues, primary breast tumours, lymph nodes metastases, and bone metastases...
December 2018: Clinical & Experimental Metastasis
Jennifer Hazel Elizabeth Baker, Alastair Hugh Kyle, Stefan Alexander Reinsberg, Firas Moosvi, Haley Margaret Patrick, Jordan Cran, Katayoun Saatchi, Urs Häfeli, Andrew Ivor Minchinton
Most HER2-positive metastatic breast cancer patients continue to relapse. Incomplete access to all target HER2-positive cells in metastases and tumor tissues is a potential mechanism of resistance to trastuzumab. The location of locally bound trastuzumab was evaluated in HER2-positive tissues in vivo and as in vivo xenografts or metastases models in mice. Microenvironmental elements of tumors were related to bound trastuzumab using immunohistochemical staining and include tight junctions, vasculature, vascular maturity, vessel patency, hypoxia and HER2 to look for correlations...
October 2018: Clinical & Experimental Metastasis
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