Article
Oncology
Nicholas H. Chakiryan, Youngchul Kim, Anders Berglund, Andrew Chang, Gregory J. Kimmel, Ali Hajiran, Jonathan Nguyen, Carlos Moran-Segura, Daryoush Saeed-Vafa, Esther N. Katende, Neale Lopez-Blanco, Jad Chahoud, Phillip Rappold, Philippe E. Spiess, Michelle Fournier, Daniel Jeong, Liang Wang, Jamie K. Teer, Jasreman Dhillon, Fengshen Kuo, Abraham Ari Hakimi, Philipp M. Altrock, James J. Mule, Brandon J. Manley
Summary: In clear cell renal cell carcinoma (ccRCC), the clustering of CD163+M2 like TAMs into the stromal compartment at the tumor-stroma interface is associated with poor clinical outcomes and CD8+T cell terminal exhaustion.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biology
Teresa Romeo Luperchio, Leandros Boukas, Li Zhang, Genay Pilarowski, Jenny Jiang, Allison Kalinousky, Kasper D. Hansen, Hans T. Bjornsson
Summary: The study reveals shared epigenetic alterations in different MDEM diseases, primarily localized in gene promoters, which may disrupt gene expression and contribute to specific phenotypes, such as IgA deficiency. Joint study of MDEMs offers a systematic approach for mapping functional epigenetic variation in mammals.
Article
Oncology
Robert J. Motzer, Toni K. Choueiri, David F. McDermott, Thomas Powles, Yann-Alexandre Vano, Saurabh Gupta, Jin Yao, Celine Han, Ron Ammar, Simon Papillon-Cavanagh, Shruti S. Saggi, M. Brent McHenry, Petra Ross-Macdonald, Megan Wind-Rotolo
Summary: The study found that biomarkers previously associated with immune checkpoint inhibitor-containing regimens were not predictive for survival in RCC patients treated with nivolumab plus ipilimumab. However, gene expression analysis revealed an association between an inflammatory response and progression-free survival in patients receiving this treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Landon C. Brown, Jason Zhu, Kunal Desai, Emily Kinsey, Chester Kao, Yong Hee Lee, Sarabjot Pabla, Matthew K. Labriola, Jennifer Tran, Konstantin H. Dragnev, Laura J. Tafe, Farshid Dayyani, Rajan T. Gupta, Shannon McCall, Daniel J. George, Sean T. Glenn, Mary K. Nesline, Saby George, Matthew Zibelman, Carl Morrison, Moshe C. Ornstein, Tian Zhang
Summary: This study utilized the OmniSeq transcriptome-based platform to develop biomarkers of response to immunotherapy. A 5-gene panel was identified that was associated with improved objective response rate (ORR) in patients treated with nivolumab monotherapy for metastatic renal cell carcinoma (mRCC). However, this gene panel was not predictive for treatment response in patients receiving ipilimumab and nivolumab combination therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
Yuanyuan Qu, Xiaohui Wu, Aihetaimujiang Anwaier, Jinwen Feng, Wenhao Xu, Xiaoru Pei, Yu Zhu, Yang Liu, Lin Bai, Guojian Yang, Xi Tian, Jiaqi Su, Guo-Hai Shi, Da-Long Cao, Fujiang Xu, Yue Wang, Hua-Lei Gan, Shujuan Ni, Meng-Hong Sun, Jian-Yuan Zhao, Hailiang Zhang, Dingwei Ye, Chen Ding
Summary: This study provides a comprehensive understanding of the molecular landscape of tRCC through proteogenomic analysis. Dysregulation of DNA repair, mTOR signaling, and metabolic processes were identified as important factors in the development of tRCC.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Ziad Bakouny, Ananthan Sadagopan, Praful Ravi, Nebiyou Y. Metaferia, Jiao Li, Shatha AbuHammad, Stephen Tang, Thomas Denize, Emma R. Garner, Xin Gao, David A. Braun, Laure Hirsch, John A. Steinharter, Gabrielle Bouchard, Emily Walton, Destiny West, Chris Labaki, Shaan Dudani, Chun-Loo Gan, Vidyalakshmi Sethunath, Filipe L. F. Carvalho, Alma Imamovic, Cora Ricker, Natalie Vokes, Jackson Nyman, Jacob E. Berchuck, Jihye Park, Michelle S. Hirsch, Rizwan Haq, Gwo-Shu Mary Lee, Bradley A. McGregor, Steven L. Chang, Adam S. Feldman, Catherine J. Wu, David F. McDermott, Daniel Y. C. Heng, Sabina Signoretti, Eliezer M. Van Allen, Toni K. Choueiri, Srinivas R. Viswanathan
Summary: This study comprehensively defines the clinical and molecular features of translocation renal cell carcinoma (tRCC), a subtype of kidney cancer driven by MiT/TFE gene fusions. tRCCs mainly harbor MiT/TFE fusions and homozygous deletions at chromosome 9p21.3, and display a heightened NRF2-driven antioxidant response. Patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs) have worse outcomes compared to those treated with immune checkpoint inhibitors (ICI). The study findings may inspire new therapeutic hypotheses for tRCC.
Article
Oncology
Jiehui Zhong, Zezhen Liu, Chao Cai, Xiaolu Duan, Tuo Deng, Guohua Zeng
Summary: This study revealed the correlation between m(6)A modification and the tumor immune landscape in ccRCC patients. The m6Ascore was established to quantify the m(6)A modification pattern and was confirmed to be an independent prognostic factor for ccRCC. The findings provide a new approach for immunotherapeutic strategies in ccRCC patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Jani de Vos, Richard P. M. A. Crooijmans, Martijn F. L. Derks, Susan L. Kloet, Bert Dibbits, Martien A. M. Groenen, Ole Madsen
Summary: This paper aims to provide a molecular and epigenetic characterization of the IPEC-J2 and SL-29 cell lines, which are of interest for the FAANG community and future biomedical research. Whole genome sequencing, gene expression, DNA methylation, chromatin accessibility, and ChIP-seq were used to investigate these cell lines. Heteroploidy of various chromosomes was observed, and higher gene expression was found in genes located on aneuploid chromosomes compared to diploid chromosomes. Regulatory complexity of gene expression, DNA methylation, and chromatin accessibility was also explored.
Article
Oncology
Chao Lou, Kailiu Wu, Jianbo Shi, Zhenlin Dai, Qin Xu
Summary: This research reveals the mechanisms by which circulating tumor cells (CTCs) evade immune surveillance by natural killer (NK) cells and demonstrates that targeting N-cadherin is an effective strategy to prevent CTCs from homing to the primary tumor.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Mengxue Yu, Kaiyu Qian, Gang Wang, Yu Xiao, Yuan Zhu, Lingao Ju
Summary: SET domain-containing 2 (SETD2) is a lysine methyltransferase involved in histone modification and has important functions in transcriptional elongation, RNA splicing, and DNA damage repair. SETD2 mutations have been found in various cancers, including clear cell renal cell carcinoma (ccRCC). The deficiency of SETD2 is associated with cancer progression by affecting autophagy flux, metabolic activity, and replication fork speed. Consequently, SETD2 is being investigated as a potential therapeutic target for cancer treatment. This review provides an overview of the molecular functions of SETD2 in H3K36me3 regulation and its relationship with ccRCC, which may pave the way for future antitumor therapies targeting SETD2 or H3K36me3.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Scott S. Tykodi, Lucio N. Gordan, Robert S. Alter, Edward Arrowsmith, Michael R. Harrison, Ivor Percent, Rakesh Singal, Peter Van Veldhuizen, Daniel J. George, Thomas Hutson, Joshua Zhang, Jesus Zoco, Jennifer L. Johansen, Arash Rezazadeh Kalebasty
Summary: The study evaluated the safety and efficacy of nivolumab plus ipilimumab in previously untreated advanced non-clear cell renal cell carcinoma (nccRCC) patients, showing a partial response rate of 19.6%, a median progression-free survival of 3.7 months, and a median overall survival of 21.2 months.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Cell Biology
Daojun Lv, Xiangkun Wu, Ming Wang, Wenzhe Chen, Shuxin Yang, Yongda Liu, Guohua Zeng, Di Gu
Summary: This study identified immune-related biomarkers IF116, LMNB1, RHBDF2, and TACC3 in ccRCC using bioinformatics analysis, showing their upregulation in the disease and association with tumor stage and grade. These hub genes had great diagnostic and prognostic values for ccRCC, involved in immune signaling pathways, and linked to tumor immune infiltration and checkpoint expressions. The findings were validated by quantitative PCR and immunohistochemical staining.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Simone Schmid, David A. Solomon, Eilis Perez, Anne Thieme, Bette K. Kleinschmidt-DeMasters, Caterina Giannini, Annekathrin Reinhardt, Sylvia L. Asa, Ozgur Mete, Damian Stichel, Christin Siewert, Carsten Dittmayer, Martin Hasselblatt, Werner Paulus, Christoph Nagel, Patrick N. Harter, Jens Schittenhelm, Juergen Honegger, Elisabeth Rushing, Roland Coras, Stefan M. Pfister, Rolf Buslei, Arend Koch, Arie Perry, David T. W. Jones, Andreas von Deimling, David Capper, M. Beatriz Lopes
Summary: Pituicytoma, granular cell tumor, and spindle cell oncocytoma are rare tumors of the posterior pituitary. Molecular analysis revealed subtle DNA methylation differences but distinct mutation patterns and clinical outcomes, suggesting a combined histo-molecular subclassification into three subtypes based on histology, genetic alterations, and favorable outcomes. The study highlights the potential for targeted therapies based on recurrent genetic alterations in these tumors.
ACTA NEUROPATHOLOGICA
(2021)
Review
Biochemistry & Molecular Biology
Franz Sellner, Eva Comperat, Martin Klimpfinger
Summary: Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) is a rare manifestation of metastatic renal cell carcinoma, and it has unique clinical characteristics such as delayed metastasis, multiple metastases, favorable treatment outcomes, and insensitivity to risk factors associated with volume and growth rate in metastatic surgery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Nizar M. Tannir, Daniel C. Cho, Adi Diab, Mario Sznol, Mehmet A. Bilen, Arjun Balar, Giovanni Grignani, Erika Puente, Lily Tang, David Chien, Ute Hoch, Arkopal Choudhury, Danni Yu, Sue L. Currie, Mary A. Tagliaferri, Jonathan Zalevsky, Arlene O. Siefker-Radtke, Michael E. Hurwitz
Summary: This study evaluated the safety and efficacy of BEMPEG plus NIVO as first-line therapy in patients with advanced clear-cell RCC. The results showed preliminary antitumor activity and good tolerability.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Andrology
Vera Constancio, Nuno Tiago Tavares, Rui Henrique, Carmen Jeronimo, Joao Lobo
Summary: The potential and challenges of using microRNAs (miRNAs) as biomarkers in male reproductive tract cancers.
Article
Biochemistry & Molecular Biology
Sara Monteiro-Reis, Vera Miranda-Goncalves, Catarina Guimaraes-Teixeira, Claudia Martins-Lima, Joao Lobo, Diana Montezuma, Paula C. Dias, Helene Neyret-Kahn, Isabelle Bernard-Pierrot, Rui Henrique, Carmen Jeronimo
Summary: In this study, we found that the VIM promoter is epigenetically regulated in normal and neoplastic urothelium, leading to a switch in VIM expression associated with EMT and the acquisition of invasive and metastatic properties. These findings might contribute to the development of novel therapeutic strategies for bladder cancer based on epigenetics.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jan Roska, Joao Lobo, Danica Ivovic, Lenka Wachsmannova, Thomas Mueller, Rui Henrique, Carmen Jeronimo, Miroslav Chovanec, Dana Jurkovicova
Summary: Testicular germ cell tumours (TGCTs) are the most common solid malignancy among young men, and their incidence is still increasing. We identified specific miRNA expression patterns that discriminate chemoresistant phenotypes in TGCTs and proposed miR-218-5p, miR-31-5p, miR-375-5p, miR-517-3p, miR-20b-5p and miR-378a-3p as potential biomarkers for predicting chemoresistance and aggressive phenotypes in non-seminomatous TGCTs. These miRNAs were found to be upregulated in CDDP-resistant TGCT cell lines, tumor samples from metastatic TGCT patients, and plasma samples from TGCT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Oncology
Nuno Tiago Tavares, Rui Henrique, Carmen Jeronimo, Joao Lobo
Summary: Epidrugs, specifically histone deacetylase inhibitors (HDACi), have shown increasing potential in the treatment of testicular germ cell tumours (TGCTs). Recent research identified SINHCAF as a potential oncogene in TGCTs, supporting the use of HDACi and advocating for further preclinical and clinical studies with these compounds.
JOURNAL OF PATHOLOGY
(2023)
Review
Oncology
Anabela Couto-Cunha, Carmen Jeronimo, Rui Henrique
Summary: Renal cell carcinoma (RCC) is a common form of kidney cancer with silent progression and resistance to traditional treatments. Circulating tumor cells (CTCs) have the potential to serve as biomarkers for RCC, providing valuable information for diagnosis, prognosis, and therapy monitoring. However, further research and technological improvements are needed for the clinical application of CTCs in RCC patients.
Article
Oncology
Romina Silva, Kate Glennon, Michael Metoudi, Bruce Moran, Sofia Salta, Karen Slattery, Ann Treacy, Terri Martin, Jacqui Shaw, Peter Doran, Lydia Lynch, Carmen Jeronimo, Antoinette S. Perry, Donal J. Brennan
Summary: Resistance to platinum-based chemotherapy is a major cause of death in high-grade serous ovarian cancer (HGSOC). This study identified specific DNA methylation changes that can predict platinum resistance in HGSOC. The results showed that hypermethylation of NKAPL and hypomethylation of APOBEC3A were associated with relapsed HGSOC. In vitro experiments also demonstrated that demethylation of NKAPL promoter increased platinum sensitivity.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Ana Teixeira-Marques, Catarina Lourenco, Miguel Carlos Oliveira, Rui Henrique, Carmen Jeronimo
Summary: Bladder cancer is the 10th most common cancer worldwide, and current diagnostic methods have limited sensitivity and lack effective prognostic biomarkers. Extracellular vesicles (EVs) have emerged as potential tools for liquid biopsy-based diagnosis and prognosis, as they carry biomarkers and play a crucial role in intercellular communication. However, there are advantages and downsides to using EVs in this context.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Filipa D. dos Reis, Carmen Jeronimo, Margareta P. Correia
Summary: Immunoepigenetics is a rapidly growing field that focuses on the role of epigenetic mechanisms in regulating tumor immune cell recognition and anti-tumor responses. There is increasing evidence of a connection between epigenetic regulation and prostate cancer (PCa) development and progression. The role of epigenetic-related mechanisms in regulating NK cell recognition and functions in PCa is still largely unknown. However, studies have shown that modulation of epigenetic mechanisms can enhance NK cell-mediated immune responses, which may lead to the development of novel epigenetic-based therapeutic options for PCa management.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Tiago Brito-Rocha, Vera Constancio, Rui Henrique, Carmen Jeronimo
Summary: Cancer is a major cause of death worldwide due to late detection and limited therapeutic options. Existing screening procedures for most cancers have drawbacks, leading to low patient compliance and increased costs. Multi-cancer early detection (MCED) tests, combining molecular analysis and artificial intelligence, have emerged as a promising tool for early cancer detection.
Article
Biochemistry & Molecular Biology
Francisco Conceicao, Daniela M. Sousa, Sofia Tojal, Catarina Lourenco, Carina Carvalho-Maia, Helena Estevao-Pereira, Joao Lobo, Marina Couto, Mette M. Rosenkilde, Carmen Jeronimo, Meriem Lamghari
Summary: Sympathetic nervous system and β2-adrenergic receptor are implicated in breast cancer, particularly bone metastasis. Epinephrine levels are elevated in breast cancer patients. Activation of β2-adrenergic receptor inhibits osteoclast differentiation and resorption activity in non-metastatic breast cancer, but not in metastatic bone tropic breast cancer.
Article
Oncology
Jan Niklas Mink, Oybek Khalmurzaev, Alexey Pryalukhin, Carol Immanuel Geppert, Stefan Lohse, Kristof Bende, Joao Lobo, Rui Henrique, Hagen Loertzer, Joachim Steffens, Carmen Jeronimo, Heiko Wunderlich, Julia Heinzelbecker, Rainer M. Bohle, Michael Stoeckle, Vsevolod Matveev, Arndt Hartmann, Kerstin Junker
Summary: This study evaluated 297 penile cancer patients from Germany, Russia, and Portugal and found a significant association between lymph node metastasis and lymphovascular invasion with prognosis. The current TNM classification was not found to improve prognosis estimation. Revision of the TNM classification is suggested.
Article
Biochemistry & Molecular Biology
Vania Camilo, Mariana Bruett Pacheco, Filipa Moreira-Silva, Goncalo Outeiro-Pinho, Vitor M. Gaspar, Joao F. Mano, C. Joana Marques, Rui Henrique, Carmen Jeronimo
Summary: This study investigated the relationship between CpG methylation in the promoter region of androgen receptor (AR) gene and loss of AR expression. The results showed sustained methylation in the proximal promoter region of DU-145 cells, which had high resistance to demethylation treatment. Additionally, repressive histone marks significantly increased at AR region 1 in DU-145 cells after treatment. Therefore, inhibiting histone methyltransferases might hold promise for AR re-expression.
Article
Oncology
Tania Lima, Catarina Macedo-Silva, Diana Felizardo, Joao Fraga, Isa Carneiro, Carmen Jeronimo, Rui Henrique, Margarida Fardilha, Rui Vitorino
Summary: Gal-3 plays an important role in cell survival, mRNA splicing, and cell-cell and cell-matrix interactions. Depending on its cellular localization and cancer type, Gal-3 may have tumour-suppressive or tumour-promoting activities. This study evaluated Gal-3 protein expression in tumor and normal prostate tissues and found decreased staining in tumor tissues compared with normal tissues. Furthermore, Gal-3 had no significant effect on survival and relapse in these PCa patients. This work confirms Gal-3 as a promising marker for PCa diagnosis.
Letter
Pathology
Joao Lobo, Paula Lopes, Rui Henrique, Angelo Rodrigues
PATHOLOGY INTERNATIONAL
(2023)