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Cancer Microenvironment

Section edited by Davide Bedognetti

© © nopparit / Getty Images / iStock

The Cancer microenvironment section publishes research on the cellular and molecular components of the cancer microenvironment, with a particular focus on translational research that has important implications for the prevention, diagnosis and treatment of human neoplasms.

Submissions that relate to the characterisation of the molecular profile and regulation of cancers at different tumour stages are especially welcome, as are those which identify specific cancer microenvironments that predict tumour incidence, response to therapy and outcome. Laboratory studies of new drugs and biological agents that target cancer microenvironments will also be considered.

Featured articles


microRNA-1271 impedes the development of prostate cancer by downregulating PES1 and upregulating ERβ

Research | Zhenming Jiang et al


Tumor microenvironment differences between primary tumor and brain metastases

Review | Bernardo Cacho-Díaz et al


Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis

Research | Jianying Pei et al

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  1. Deregulated inflammation and immune deficit both intricately associate with cancer initiation and progression, which have been increasingly exploited as prognostic biomarkers and therapeutic targets. Recently,...

    Authors: Pengfei Diao, Yaping Wu, Jin Li, Wei Zhang, Rong Huang, Chen Zhou, Yanling Wang and Jie Cheng
    Citation: Journal of Translational Medicine 2018 16:365
    Content type: Research Published on:

  2. Because patient-derived xenografts (PDXs) are grown in immunodeficient mouse strains, PDXs are regarded as lacking an immune microenvironment. However, whether patients’ immune cells co-exist in PDXs remains u...

    Authors: Xingxiang Pu, Ran Zhang, Li Wang, Yungchang Chen, Yi Xu, Apar Pataer, Ismail M. Meraz, Xiaoshan Zhang, Shuhong Wu, Lin Wu, Dan Su, Weimin Mao, John V. Heymach, Jack A. Roth, Stephen G. Swisher and Bingliang Fang
    Citation: Journal of Translational Medicine 2018 16:328
    Content type: Research Published on:

  3. Incomplete thermal ablation may induce invasiveness of hepatocellular carcinoma (HCC). Here, we investigated whether activated hepatic stellate cells (HSCs) would accelerate the progression of residual HCC aft...

    Authors: Rui Zhang, Xia-Hui Lin, Min Ma, Jie Chen, Jun Chen, Dong-Mei Gao, Jie-Feng Cui and Rong-Xin Chen
    Citation: Journal of Translational Medicine 2018 16:302
    Content type: Research Published on:

  4. Hepatocyte growth factor (HGF) plays a pivotal role in breast cancer cell motility, invasion and angiogenesis. These pro-metastatic events are triggered through HGF coupling and activation of the c-Met recepto...

    Authors: Christian Parr and Ahmed Y. Ali
    Citation: Journal of Translational Medicine 2018 16:281
    Content type: Research Published on:

  5. The mainstay of treatment of advanced ovarian cancer (AOC) involves chemotherapy, and debulking surgery. However, despite optimal surgical procedure and adjuvant chemotherapy, 60% of patients with AOC will rel...

    Authors: Jennifer Pasquier, Fabien Vidal, Jessica Hoarau-Véchot, Claire Bonneau, Emile Daraï, Cyril Touboul and Arash Rafii
    Citation: Journal of Translational Medicine 2018 16:271
    Content type: Research Published on:

  6. Approximately half of the documented increases in differentiated thyroid carcinoma is due to identification of papillary thyroid microcarcinomas (PTMCs). Knowing whether PTMC is aggressive is required for prop...

    Authors: Jianlu Song, Shouxin Wu, Xiaotian Xia, Yu Wang, Youben Fan and Zhili Yang
    Citation: Journal of Translational Medicine 2018 16:269
    Content type: Research Published on:

  7. The American Joint Committee on Cancer has recently revised the tumor-node-metastasis (TNM) staging system on thyroid cancer, which illustrated that the cut-off age for predicting mortality has elevated from 4...

    Authors: Weiheng Wen, Peili Wu, Jitong Li, He Wang, Jia Sun and Hong Chen
    Citation: Journal of Translational Medicine 2018 16:261
    Content type: Research Published on:

  8. Hyaluronan (HA), a major component of the extracellular matrix, has been proven to play a crucial role in tumor progression. However, it remains unknown whether HA exerts any effects in myelodysplastic syndrom...

    Authors: Cheng-Ming Fei, Juan Guo, You-Shan Zhao, Si-Da Zhao, Qing-Qing Zhen, Lei Shi, Xiao Li and Chun-Kang Chang
    Citation: Journal of Translational Medicine 2018 16:234
    Content type: Research Published on:

  9. Multiple myeloma (MM) is a cancer of terminally differentiated plasma that is part of a spectrum of blood diseases. The role of the micro-environment is crucial for MM clonal evolution.

    Authors: Angelina Boccarelli, Flavia Esposito, Mauro Coluccia, Maria Antonia Frassanito, Angelo Vacca and Nicoletta Del Buono
    Citation: Journal of Translational Medicine 2018 16:217
    Content type: Research Published on:

  10. Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism...

    Authors: Shou-Sheng Liu, Yuan-Zhong Yang, Chang Jiang, Qi Quan, Qian-Kun Xie, Xiao-Pai Wang, Wen-Zhuo He, Yu-Ming Rong, Ping Chen, Qiong Yang, Lin Yang, Bei Zhang, Xiao-Jun Xia, Peng-Fei Kong and Liang-Ping Xia
    Citation: Journal of Translational Medicine 2018 16:195
    Content type: Research Published on:

  11. Vimentin (VIM) is a type III intermediate filament that maintains cell integrity, and is involved in cell migration, motility and adhesion. When overexpressed in solid cancers, vimentin drives epithelial to me...

    Authors: Sharon Wu, Yang Du, John Beckford and Houda Alachkar
    Citation: Journal of Translational Medicine 2018 16:170
    Content type: Research Published on:

  12. Hypoxia-mediated chemoresistance has been regarded as an important obstacle in the development of cancer treatment. Knockdown of krüppel-like factor 5 (KLF5) was reported to inhibit hypoxia-induced cell surviv...

    Authors: Tianxiao Gong, Liuqing Cui, Haili Wang, Haoxun Wang and Na Han
    Citation: Journal of Translational Medicine 2018 16:164
    Content type: Research Published on:

  13. Tumor-promoting inflammation is an emerging hallmark of cancer, which participates in both cancer progression and immune escape. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer with an ...

    Authors: Chun Xu, Xian Lu, Wei Liu, Anxian Chen, Gang Meng, Hailin Zhang, Binghua Li, Yonghui Zhang, Junhua Wu and Jiwu Wei
    Citation: Journal of Translational Medicine 2018 16:132
    Content type: Research Published on:

  14. It has been reported mesenchymal stem cells (MSCs) are recruited to and become integral parts of the tumor microenvironment. MSCs might have an active role in solid tumor progression, especially cancer metasta...

    Authors: Jing-Huan Li, Wen-Shuai Fan, Mi-Mi Wang, Yan-Hong Wang and Zheng-Gang Ren
    Citation: Journal of Translational Medicine 2018 16:113
    Content type: Review Published on:

  15. Cisplatin is a widely used chemotherapeutic agent for treatment of various cancers. However, treatment with cisplatin is associated with drug resistance and several adverse side effects such as nephrotoxicity,...

    Authors: Iman W. Achkar, Nabeel Abdulrahman, Hend Al-Sulaiti, Jensa Mariam Joseph, Shahab Uddin and Fatima Mraiche
    Citation: Journal of Translational Medicine 2018 16:96
    Content type: Review Published on:

  16. Stromal gene expression patterns predict patient outcomes in colorectal cancer. TRIM28 is a transcriptional co-repressor that regulates an abundance of genes through the KRAB domain family of transcription fac...

    Authors: Seán Fitzgerald, Virginia Espina, Lance Liotta, Katherine M. Sheehan, Anthony O’Grady, Robert Cummins, Richard O’Kennedy, Elaine W. Kay and Gregor S. Kijanka
    Citation: Journal of Translational Medicine 2018 16:89
    Content type: Research Published on:

  17. The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer....

    Authors: Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa and Masaichi Ohira
    Citation: Journal of Translational Medicine 2018 16:86
    Content type: Research Published on:

  18. Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Pre...

    Authors: Shinichiro Kashiwagi, Gen Tsujio, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa and Masaichi Ohira
    Citation: Journal of Translational Medicine 2018 16:54
    Content type: Research Published on:

  19. CD133 is a marker of stem cells as well cancer stem cells. This study investigated the association between CD133 expression in cancer cells and the clinical outcome of non-mucin producing intrahepatic cholangi...

    Authors: Xiaobo Cai, Jun Li, Xiaodong Yuan, Jingbo Xiao, Steven Dooley, Xinjian Wan, Honglei Weng and Lungen Lu
    Citation: Journal of Translational Medicine 2018 16:50
    Content type: Research Published on:

  20. Esophageal carcinoma is the eighth prevalent malignancy and ranks the sixth in carcinoma-related death worldwide. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) has been identified as a tumor suppres...

    Authors: Linan Zhu, Xudong Zhang, Xiaorui Fu, Zhaoming Li, Zhenchang Sun, Jingjing Wu, Xinhua Wang, Feng Wang, Xiangke Li, Songtao Niu, Mengjie Ding, Zhenzhen Yang, Wanqiu Yang, Meifeng Yin, Lei Zhang and Mingzhi Zhang
    Citation: Journal of Translational Medicine 2018 16:7
    Content type: Research Published on:

  21. Prostate cancer (PCa) is a complex disorder resulting from the combined effects of multiple environmental and genetic factors. Small non-coding RNAs (sRNAs), particularly microRNAs (miRNAs), regulate several c...

    Authors: Jingxuan Shan, Khalid Al-Rumaihi, Karim Chouchane, Issam Al-Bozom, Danny Rabah, Karim Farhat and Lotfi Chouchane
    Citation: Journal of Translational Medicine 2017 15:260
    Content type: Research Published on:

  22. Metastasis is a major threat to colorectal cancer (CRC) patients. We have reported that peroxiredoxin-2 (PRDX2) is associated with CRC invasion and metastasis. However, the mechanisms regulating PRDX2 expressi...

    Authors: Zhenbing Lv, Jinlai Wei, Wenxian You, Rong Wang, Jingkun Shang, Yongfu Xiong, Hua Yang, Xuanhua Yang and Zhongxue Fu
    Citation: Journal of Translational Medicine 2017 15:257
    Content type: Research Published on:

  23. Studies investigating the oxygenation status and the development of hypoxia in microscopic tumors are sparse. The purpose of this study was to measure the extent of hypoxia in microscopic melanoma xenografts a...

    Authors: Jon-Vidar Gaustad, Trude G. Simonsen, Lise Mari K. Andersen and Einar K. Rofstad
    Citation: Journal of Translational Medicine 2017 15:241
    Content type: Research Published on:

  24. Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH) was frequently overexpressed in ICC compared with non...

    Authors: Jing Tang, Yan Liao, Shuying He, Jie Shi, Liang Peng, Xiaoping Xu, Fang Xie, Na Diao, Jinlan Huang, Qian Xie, Chuang Lin, Xiaoying Luo, Kaili Liao, Juanjuan Ma, Jingyi Li, Daichao Zhou…
    Citation: Journal of Translational Medicine 2017 15:238
    Content type: Research Published on:

  25. The use of patient-derived primary cell cultures in cancer preclinical assays has increased in recent years. The management of resected tumor tissue remains complex and a number of parameters must be respected...

    Authors: Giacomo Miserocchi, Laura Mercatali, Chiara Liverani, Alessandro De Vita, Chiara Spadazzi, Federica Pieri, Alberto Bongiovanni, Federica Recine, Dino Amadori and Toni Ibrahim
    Citation: Journal of Translational Medicine 2017 15:229
    Content type: Review Published on:

  26. Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contras...

    Authors: Anette Hauge, Catherine S. Wegner, Jon-Vidar Gaustad, Trude G. Simonsen, Lise Mari K. Andersen and Einar K. Rofstad
    Citation: Journal of Translational Medicine 2017 15:225
    Content type: Research Published on:

  27. There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the associati...

    Authors: Yu-Suo Tong, Juan Tan, Xi-Lei Zhou, Ya-Qi Song and Ying-Jian Song
    Citation: Journal of Translational Medicine 2017 15:221
    Content type: Research Published on:

  28. The predictive accuracy of the traditional staging system is based on disease progression as a tumour cell-autonomous process, but it fails to incorporate the effects of the host immune response. A precise ana...

    Authors: Jerome Galon, Alessandro Lugli, Carlo Bifulco, Franck Pages, Giuseppe Masucci, Francesco M. Marincola and Paolo A. Ascierto
    Citation: Journal of Translational Medicine 2017 15:212
    Content type: Meeting report Published on:

  29. Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be ...

    Authors: Chuang Yang, Jing-Jing Zhang, Yun-Peng Peng, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Wen-Tao Gao, Kui-Rong Jiang and Yi Miao
    Citation: Journal of Translational Medicine 2017 15:211
    Content type: Research Published on:

  30. The mitochondrial protein p32 is a validated therapeutic target of cancer overexpressed in glioma. Therapeutic targeting of p32 with monoclonal antibody or p32-binding LyP-1 tumor-homing peptide can limit tumo...

    Authors: Venkata Yenugonda, Natsuko Nomura, Valentina Kouznetsova, Igor Tsigelny, Valentina Fogal, Elmar Nurmemmedov, Santosh Kesari and Ivan Babic
    Citation: Journal of Translational Medicine 2017 15:210
    Content type: Research Published on:

  31. Extracellular acidosis is a condition found within the tumor microenvironment due to inadequate blood perfusion, hypoxia, and altered tumor cell metabolism. Acidosis has pleiotropic effects on malignant progre...

    Authors: Calvin R. Justus, Edward J. Sanderlin, Lixue Dong, Tianai Sun, Jen-Tsan Chi, Kvin Lertpiriyapong and Li V. Yang
    Citation: Journal of Translational Medicine 2017 15:204
    Content type: Research Published on:

  32. Malignant melanoma of the skin can metastasize through blood vessels and lymphatics. The primary tumor develops a vascular microenvironment characterized by abnormal blood vessels and lymphatics and a physicoc...

    Authors: Ruixia Huang, Lise Mari K. Andersen and Einar K. Rofstad
    Citation: Journal of Translational Medicine 2017 15:203
    Content type: Research Published on:

  33. Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been...

    Authors: Joana Vieira de Castro, Eduardo D. Gomes, Sara Granja, Sandra I. Anjo, Fátima Baltazar, Bruno Manadas, António J. Salgado and Bruno M. Costa
    Citation: Journal of Translational Medicine 2017 15:200
    Content type: Research Published on:

  34. SLFN11 is a recently discovered protein with a putative DNA/RNA helicase function. First identified in association with the maturation of thymocytes, SLFN11 was later causally associated, by two independent gr...

    Authors: Alberto Ballestrero, Davide Bedognetti, Domenico Ferraioli, Paola Franceschelli, Sana Intidhar Labidi-Galy, Elisabetta Leo, Junko Murai, Yves Pommier, Petros Tsantoulis, Valerio Gaetano Vellone and Gabriele Zoppoli
    Citation: Journal of Translational Medicine 2017 15:199
    Content type: Meeting report Published on:

  35. In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identifi...

    Authors: Shutong Liu, Bo Ren, Hang Gao, Suchan Liao, Ying-Xian Zhai, Shirong Li, Xue-Jin Su, Ping Jin, David Stroncek, Zhixiang Xu, Qinghua Zeng and Yulin Li
    Citation: Journal of Translational Medicine 2017 15:189
    Content type: Research Published on:

  36. Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitous...

    Authors: Yongjie Shi, Nan Qin, Qiang Zhou, Yanqiu Chen, Sicong Huang, Bo Chen, Gang Shen and Hongyun Jia
    Citation: Journal of Translational Medicine 2017 15:176
    Content type: Research Published on:

  37. The coiled-coil domain is a structural motif found in proteins that participate in a variety of biological processes. Aberrant expression of such proteins has been shown to be associated with the malignant beh...

    Authors: Ran Xu, Mingzhi Han, Yangyang Xu, Xin Zhang, Chao Zhang, Di Zhang, Jianxiong Ji, Yuzhen Wei, Shuai Wang, Bin Huang, Anjing Chen, Qing Zhang, Wenjie Li, Tao Sun, Feng Wang, Xingang Li…
    Citation: Journal of Translational Medicine 2017 15:165
    Content type: Research Published on:

  38. Dendritic cells (DC) and tumour-associated macrophages (TAM) are essential in linking the innate and adaptive immune response against tumour cells and tumour progression. These cells are also potential target ...

    Authors: Sebastian Lundgren, Emelie Karnevi, Jacob Elebro, Björn Nodin, Mikael C. I. Karlsson, Jakob Eberhard, Karin Leandersson and Karin Jirström
    Citation: Journal of Translational Medicine 2017 15:152
    Content type: Research Published on:

  39. The interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is considered to be a major driver of lymphangiogenesis, however the mechanism of this process remains unclear. We aimed ...

    Authors: Haruhisa Kitano, Joon-Yong Chung, Kyung Hee Noh, Young-Ho Lee, Tae Woo Kim, Seok Hyung Lee, Soo-Heang Eo, Hyung Jun Cho, Chel Hun Choi, Shuhei Inoue, Jun Hanaoka, Junya Fukuoka and Stephen M. Hewitt
    Citation: Journal of Translational Medicine 2017 15:138
    Content type: Research Published on:

  40. Shikonin, a natural naphthoquinone pigment purified from Lithospermum erythrorhizon, induces necroptosis in various cancer types, but the mechanisms underlying the anticancer activity of shikonin in lung cancer a...

    Authors: Hyo-Jin Kim, Ki-Eun Hwang, Do-Sim Park, Seon-Hee Oh, Hong Young Jun, Kwon-Ha Yoon, Eun-Taik Jeong, Hak-Ryul Kim and Young-Suk Kim
    Citation: Journal of Translational Medicine 2017 15:123
    Content type: Research Published on:

  41. Imatinib causes increased turnover of stromal collagen, reduces collagen fibril diameter, enhances extracellular fluid turnover and lowers interstitial fluid pressure (IFP) in the human colonic carcinoma KAT-4...

    Authors: Mikhail Burmakin, Tijs van Wieringen, P. Olof Olsson, Linda Stuhr, Aive Åhgren, Carl-Henrik Heldin, Rolf K. Reed, Kristofer Rubin and Carina Hellberg
    Citation: Journal of Translational Medicine 2017 15:47
    Content type: Research Published on:

  43. In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived...

    Authors: Yana G. Najjar, Fei Ding, Yan Lin, Robert VanderWeele, Lisa H. Butterfield and Ahmad A. Tarhini
    Citation: Journal of Translational Medicine 2017 15:39
    Content type: Research Published on:

  44. The robust desmoplasia associated with head and neck squamous cell carcinoma (HNSCC) suggests that the tumor microenvironment may be an important component in the pathophysiology of this cancer. Moreover, the ...

    Authors: Tammara L. Watts, Ruwen Cui, Peter Szaniszlo, Vicente A. Resto, Don W. Powell and Irina V. Pinchuk
    Citation: Journal of Translational Medicine 2016 14:337
    Content type: Research Published on:

  45. Non-Hodgkin lymphomas (NHL) are the most frequent hemato-oncological malignancies. Despite recent major advances in treatment, a substantial proportion of patients relapses highlighting the need for new therap...

    Authors: Thais Bascuas, María Moreno, Amy Mónaco, Laura Reyes, Andrea Paolino, Patricia Oliver, María G. Kramer, Henry Engler, José P. Pacheco, Sofía Grille and José A. Chabalgoity
    Citation: Journal of Translational Medicine 2016 14:323
    Content type: Research Published on:

  46. E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the ...

    Authors: Hager Memni, Yosra Macherki, Zahra Klayech, Ahlem Ben-Haj-Ayed, Karim Farhat, Yassmine Remadi, Sallouha Gabbouj, Wijden Mahfoudh, Nadia Bouzid, Noureddine Bouaouina, Lotfi Chouchane, Abdelfattah Zakhama and Elham Hassen
    Citation: Journal of Translational Medicine 2016 14:320
    Content type: Research Published on:

  47. In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other “classic” sources have been described. However, the phenotypic and functional properties of tumo...

    Authors: María de Lourdes Mora-García, Rosario García-Rocha, Omar Morales-Ramírez, Juan José Montesinos, Benny Weiss-Steider, Jorge Hernández-Montes, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Marco Antonio Velasco-Velázquez, Vianey Gutiérrez-Serrano and Alberto Monroy-García
    Citation: Journal of Translational Medicine 2016 14:302
    Content type: Research Published on:

  48. Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific surviv...

    Authors: Sarah A. Weiss, Joseph Han, Farbod Darvishian, Jeremy Tchack, Sung Won Han, Karolina Malecek, Michelle Krogsgaard, Iman Osman and Judy Zhong
    Citation: Journal of Translational Medicine 2016 14:299
    Content type: Research Published on:

  49. Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small ve...

    Authors: Zhen Wang, Jun-Qiang Chen, Jin-lu Liu and Lei Tian
    Citation: Journal of Translational Medicine 2016 14:297
    Content type: Review Published on:

  50. Several cellular functions relate to ion-channels activity. Physiologically relevant chains of events leading to angiogenesis, cell cycle and different forms of cell death, require transmembrane voltage contro...

    Authors: Antonella Biasiotta, Daniela D’Arcangelo, Francesca Passarelli, Ezio Maria Nicodemi and Antonio Facchiano
    Citation: Journal of Translational Medicine 2016 14:285
    Content type: Research Published on:
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