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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...
November 17, 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...
November 12, 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...
October 30, 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...
October 28, 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...
October 25, 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...
October 19, 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...
October 16, 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...
October 15, 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...
October 8, 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...
September 25, 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...
September 24, 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...
September 20, 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
Verena Kirn, Leonie Strake, Fabinshy Thangarajah, Lisa Richters, Hannah Eischeid, Ulrike Koitzsch, Margarete Odenthal, Jochen Fries
The role of ESR1 methylation in breast cancer and its influence on disease progression is not yet fully understood. Healthy breast tissue usually does not show ESR1 promoter methylation, whereas the frequency of ESR1 methylation appears to increase in primary breast cancer and in metastatic disease. Although women with ER positive breast cancer have a good prognosis, some will relapse. We aimed to evaluate the methylation status of ESR1 in primary breast cancer and its corresponding metastases by a methylation-specific real-time PCR and to correlate the methylation status with clinical outcome...
October 2018: Clinical & Experimental Metastasis
Joaquín Araos, Jonathan P Sleeman, Boyan K Garvalov
Hypoxia is a characteristic feature of many cancer types, which ensues when the growth of a tumour outpaces its oxygen supply. The cellular response to reduced oxygen tension is centred around the hypoxia-inducible transcription factors (HIFs), which become stabilized under hypoxic conditions. In addition, a number of oxygen-independent mechanisms of HIF regulation have been described, which also play a role at distinct stages of tumour progression. Hypoxia and HIF activity have been linked to the control of all hallmarks of cancer, and increased levels of hypoxia or HIFs in human tumours are typically associated with poor prognosis...
October 2018: Clinical & Experimental Metastasis
Filippo Alongi, Alba Fiorentino, Ruggero Ruggieri, Francesco Ricchetti, Patrick Kupelian
In the last few years, the major change has occurred in the expansion of indications for radiosurgery (SRS) to include patients with more than four brain metastases (BM). To address the expanding indications for SRS in the treatment of multiple BMs, HyperArcTM (Varian Medical System, Palo Alto, CA, U.S.) was recently introduced in order to automate and simplify sophisticated treatments such as SRS/FSRT for multiple lesions (up to 20 BM). In this editorial some consideration about HyperArc cost-effectiveness were discussed in terms of reduction of treatment delivery time (multiple intracranial targets can be treated in a few minutes), the reduction of overall treatment time (treatment course of SRS of multiple BMs in a single session, rather than having to irradiate lesion per lesion during separate sessions on different days); reduction of costs for health systems...
October 2018: Clinical & Experimental Metastasis
Jessica M Pastoriza, George S Karagiannis, Juan Lin, Sonali Lanjewar, David Entenberg, John S Condeelis, Joseph A Sparano, Xiaonan Xue, Thomas E Rohan, Maja H Oktay
Black race compared to white race is associated with more advanced stage and biologically aggressive breast cancer. Consequently, black patients are more frequently treated with neoadjuvant chemotherapy (NAC) than white patients. However, it is unclear how distant recurrence-free survival (DRFS) of black patients treated with NAC, compares to DRFS of black patients treated with adjuvant chemotherapy (AC). We evaluated the association between race, distant recurrence, and type of chemotherapy (AC or NAC) in localized or locally advanced breast cancer...
October 2018: Clinical & Experimental Metastasis
Kotaro Matsuda, Hiroaki Miyoshi, Mayuko Moritsubo, Koji Hiraoka, Tetsuya Hamada, Naoto Shiba, Koichi Ohshima
Autoimmune regulator (AIRE) is a transcription factor that is expressed in medullary thymic epithelial cells. It plays an essential role in central tolerance by eliminating self-reactive T cells. Recently, extrathymic AIRE-expressing cells have been revealed, which are associated with peripheral tolerance. Moreover, AIRE expression has been demonstrated in skin tumors and breast cancer. However, the expression of AIRE in osteosarcoma is unknown. We used immunohistochemistry to investigate AIRE expression in biopsy samples from 43 patients with conventional osteosarcoma and statistically analyzed the association between AIRE expression and clinicopathological characteristics...
October 2018: Clinical & Experimental Metastasis
Jenny Capuccini, Gabriella Macchia, Eleonora Farina, Milly Buwenge, Domenico Genovesi, Luciana Caravatta, Nam P Nguyen, Silvia Cammelli, Savino Cilla, Tigeneh Wondemagegnhu, A F M Kamal Uddin, Mostafà Aziz Sumon, Francesco Cellini, Vincenzo Valentini, Francesco Deodato, Alessio G Morganti
Metastases with soft tissues invasion, impending fractures or spinal cord compression (complicated bone metastases) represent a common clinical problem in advanced cancers and frequently lead to deterioration of patients' quality of life (QoL). A phase I-II study was planned to define the maximum tolerated dose (MTD) of a short-course radiotherapy (RT) and its efficacy in palliation of complicated bone metastases. A phase I trial was designed with three dose-escalation steps: 16, 18, and 20 Gy. Total dose at each level was delivered in 2 days, twice daily...
October 2018: Clinical & Experimental Metastasis
Philipp Horvath, Stefan Beckert, Florian Struller, Alfred Königsrainer, Marc André Reymond
Data on the effectivness of PIPAC in patients with peritoneal metastases of pancreaticobiliary origin is scarce. We here present further proof of treatment efficacy in this subset of patients. Repetitive PIPAC treatment with low-dose cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 body surface area every 6 weeks and prospective data collection. Documentation included microscopic histological regression, median overall survival and treatment-related adverse events. Twelve patients with a median age of 57 years (range 43-78 years) were included...
October 2018: Clinical & Experimental Metastasis
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