Review
Oncology
Yutong Zhao, Cheng Qin, Bangbo Zhao, Yuanyang Wang, Zeru Li, Tianyu Li, Xiaoying Yang, Weibin Wang
Summary: Pancreatic cancer is a highly aggressive malignancy with self-renewal and proliferation capacity of pancreatic cancer stem cells playing a crucial role in metastasis and therapy resistance. This review focuses on the regulation of pancreatic cancer stem cells, including stemness-related signaling pathways, stimuli in tumor cells and the tumor microenvironment, and the development of innovative stemness-targeted therapies. Understanding the plasticity and molecular mechanisms of PCSCs will help identify new treatment strategies for this devastating disease.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Immunology
Jingjing Wang, Hui Ren, Wenhui Wu, Qianlin Zeng, Jingyao Chen, Juanjuan Han, Minquan Lin, Changhua Zhang, Yulong He, Mingzhe Li
Summary: The study revealed the relationship between immune infiltration and cancer stem-like properties in patients with gastrointestinal stromal tumor (GIST), with a correlation to tumor purity. The cancer stemness index can serve as a predictive biomarker for tumor metastasis and a target for drug therapy in GIST patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Alexey Ponomarev, Zarema Gilazieva, Valeriya Solovyeva, Cinzia Allegrucci, Albert Rizvanov
Summary: The study of cancer stem cells is important because they play a crucial role in cancer complexity and treatment resistance. The tumor microenvironment modulates the function and survival of cancer stem cells. This review summarizes the regulation of cancer stemness through pluripotency factors and signaling pathways, and introduces current models used for studying cancer stem cells.
Review
Immunology
Yinxi Zhou, Jinghua Xia, Shuonan Xu, Tao She, Yanning Zhang, Ying Sun, Miaomiao Wen, Tao Jiang, Yanlu Xiong, Jie Lei
Summary: The development and growth of tumors pose a significant and ongoing threat to human life globally. Despite the remarkable progress achieved by advanced therapeutic strategies such as immune checkpoint therapy and CAR-T in treating solid and hematological malignancies, the malignant initiation and progression of cancer remains controversial and requires further research. Experimental animal models not only have great advantages in simulating tumor occurrence, development, and malignant transformation mechanisms, but also can be used to evaluate the therapeutic effects of diverse clinical interventions, gradually becoming indispensable in cancer research. This paper reviews recent research progress in mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, aiming to provide guidance for future studies on malignant mechanisms and tumor prevention.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Valeria Lucarini, Daniela Nardozi, Valentina Angiolini, Monica Benvenuto, Chiara Focaccetti, Raffaele Carrano, Zein Mersini Besharat, Roberto Bei, Laura Masuelli
Summary: Gastrointestinal(GI) cancers are common and cause a significant number of cancer-related deaths. Metastasis is the primary cause of death from GI cancer, making it important to understand cancer cell migration and develop new therapies. This review summarizes the mechanisms of cancer cell migration and metastasis formation, focusing on the role of tumor microenvironment components. It also discusses the potential of microRNAs as biomarkers for prognosis, monitoring, and diagnosis in GI cancer patients. Additionally, the use of nutraceuticals as a strategy to target microRNAs and pathways involved in GI tumor invasiveness is explored.
Review
Biochemistry & Molecular Biology
Simone Brabletz, Harald Schuhwerk, Thomas Brabletz, Marc P. Stemmler
Summary: The process of epithelial-mesenchymal transition (EMT) is critical for embryonic development and plays a key role in cancer progression by inducing changes in cell characteristics and motility. Targeting EMT therapeutically could be a promising approach to interfere with tumor progression on multiple levels.
Article
Cell Biology
Meng-Ling Ye, Si-Qi Li, Yi-Xin Yin, Ke-Zhi Li, Ji-Lin Li, Bang-Li Hu
Summary: Cancer stem cells play crucial roles in colorectal cancer tumorigenesis and treatment response. This study found that the mRNA stemness index (mRNAsi) was associated with the clinical outcome in colorectal cancer (CRC) patients. A stemness-related classification based on mRNAsi scores and RNA sequence data was introduced and showed promise as a prognostic predictor for CRC patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Abdullah Husain, Yung-tuen Chiu, Karen Man-Fong Sze, Daniel Wai-Hung Ho, Yu-Man Tsui, Eliana Marry Senires Suarez, Vanilla Xin Zhang, Lo-Kong Chan, Eva Lee, Joyce Man-Fong Lee, Tan-To Cheung, Carmen Chak-Lui Wong, Clive Yik-Sham Chung, Irene Oi-Lin Ng
Summary: In hepatocellular carcinoma (HCC), the Ephrin-A3/EphA2 axis plays a significant role as a hypoxia-sensitive modulator of HCC cell metabolism and a key contributor to HCC initiation and progression.
JOURNAL OF HEPATOLOGY
(2022)
Review
Immunology
Liangliang Meng, Yingtian Wei, Yueyong Xiao
Summary: Chemical ablation involves injecting chemical agents directly into solid tumors to kill cells and is currently used for palliative treatment. The effectiveness of different drugs has been clinically tested, but their diffusion and concentration limit their efficacy. Immunotherapy shows potential, but low patient response rates and immune-related adverse effects restrict its clinical applications. Intratumoral immunotherapy addresses these issues, but its efficacy alone is uncertain. This study focuses on the research of immunosuppressive tumor microenvironment with chemoablation and intratumoral immunotherapy, aiming to propose a new concept of intratumoral chemo-immunoablation that enhances the systemic anti-tumor immune response while reducing adverse drug effects.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Agnete S. T. Engelsen, Maria L. Lotsberg, Raefa Abou Khouzam, Jean-Paul Thiery, James B. Lorens, Salem Chouaib, Stephane Terry
Summary: The development and implementation of Immune Checkpoint Inhibitors (ICI) have significantly improved the survival of metastatic cancer patients, but low response rates and limited understanding of mechanisms regulating anti-tumor immunity remain major concerns. AXL, a receptor tyrosine kinase, has been identified as a potential molecular target to overcome therapy resistance and improve ICI efficacy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Asha Kumari, Zainab Shonibare, Mehri Monavarian, Rebecca C. Arend, Nam Y. Lee, Gareth J. Inman, Karthikeyan Mythreye
Summary: Epithelial ovarian cancer is a leading cause of cancer-related death in women, with late-stage diagnosis, significant tumor burden, recurrence, and chemotherapy resistance contributing to poor prognosis, all of which are associated with epithelial-mesenchymal transition (EMT). The Transforming Growth Factor-beta (TGF beta) family of growth factors are key triggers for EMT, and TGF beta regulates EMT through various mechanisms, potentially playing a role in the treatment of ovarian cancer.
CLINICAL & EXPERIMENTAL METASTASIS
(2021)
Review
Oncology
Yang Liu, Ke Shi, Yong Chen, Xianrui Wu, Zheng Chen, Ke Cao, Yongguang Tao, Xiang Chen, Junlin Liao, Jianda Zhou
Summary: Exosomes from extracellular vesicles play a role in cancer progression by transporting various substances to recipient cells and participating in processes such as remodeling of the tumor microenvironment, promoting angiogenesis, metastasis, invasion, and regulating the immune escape of tumor cells. However, the exact molecular mechanisms of their involvement in these processes remain unclear.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Qi Zhang, Linbo Jin, Quanxin Jin, Qiang Wei, Mingyuan Sun, Qi Yue, Huan Liu, Fangfang Li, Honghua Li, Xiangshan Ren, Guihua Jin
Summary: The study found that DHA has inhibitory effects on the proliferation, migration, and metastasis of melanoma, and can also impact immune cells in the tumor microenvironment. This suggests that DHA may serve as a potential treatment for melanoma.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Therese Seidlitz, Daniel E. Stange
Summary: Organoid technology allows for the generation of patient-derived models to better understand cancer biology, guide treatment selection, and study biological pathways contributing to tumor development and disease progression.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Oncology
Shingo Kodama, Katarzyna A. Podyma-Inoue, Toshihiro Uchihashi, Kyoko Kurioka, Hitomi Takahashi, Akinari Sugauchi, Kazuki Takahashi, Toshihiro Inubushi, Mikihiko Kogo, Susumu Tanaka, Tetsuro Watabe
Summary: Melanoma, aggressive cancer originating from the skin, is driven by TGF-beta cytokine signaling leading to the progression of the disease. Chimeric receptors targeting TGF-beta signals have been shown to effectively inhibit melanoma cell migration and growth, highlighting their potential as anti-melanoma agents.
Article
Multidisciplinary Sciences
Federica Rubbino, Valentina Garlatti, Valeria Garzarelli, Luca Massimino, Salvatore Spano, Paolo Iadarola, Maddalena Cagnone, Martin Giera, Marieke Heijink, Simone Guglielmetti, Vincenzo Arena, Alberto Malesci, Luigi Laghi, Silvio Danese, Stefania Vetrano
Summary: This study highlights the role of GPR120 in the progression of colorectal cancer. Loss of GPR120 in the gut leads to increased intestinal permeability, microbiota translocation, and dysbiosis, which results in hyperproliferation of epithelial cells through the activation of beta-catenin signaling. Therefore, the loss of GPR120 is an early event in CRC development but does not promote invasive cancer.
SCIENTIFIC REPORTS
(2022)
Article
Pathology
Tommaso Cavalleri, Luana Greco, Federica Rubbino, Tsuyoshi Hamada, Maria Quaranta, Fabio Grizzi, Elisabetta Sauta, Vincenzo Craviotto, Paola Bossi, Stefania Vetrano, Lorenza Rimassa, Valter Torri, Riccardo Bellazzi, Alberto Mantovani, Shuji Ogino, Alberto Malesci, Luigi Laghi
Summary: This study examined the impact of tumor-associated macrophage density on the prognosis of colorectal cancer patients. It was found that low TAM density was associated with shorter disease-free survival after FOLFOX treatment, and it maintained an independent predictive value along with nodal status. High CD68 mRNA levels were associated with better prognosis in patients. Macrophages enhanced the cytotoxic effect of FOLFOX on colorectal cancer cells and could polarize from M2- to M1-phenotype.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Article
Medicine, General & Internal
Federica Gaiani, Roberta Minerba, Alessandra Picanza, Annalisa Russo, Alessandra Melegari, Elena De Santis, Tommaso Trenti, Lucia Belloni, Silvia Peveri, Rosalia Aloe, Carlo Ferrari, Luigi Laghi, Gian Luigi De'Angelis, Chiara Bonaguri
Summary: The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved with the use of innovative analytical techniques. This study aimed to identify the best combination of diagnostic tests for optimal PBC diagnosis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Bernhard Mlecnik, Toshihiko Torigoe, Gabriela Bindea, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Yoshihiko Hirohashi, Tomohisa Furuhata, Ichiro Takemasa, Prabhudas Patel, Hemangini Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Takayuki Yoshino, Hiroya Taniguchi, Carlo Bifulco, Alessandro Lugli, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T. Rau, Martin D. Berger, Iris D. Nagtegaal, Elisa Vink-Borger, Arndt Hartmann, Carol Geppert, Julie Kolwelter, Susanne Merkel, Robert Gruetzmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Leonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H. A. Roehrl, Pamela S. Ohashi, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradly G. Wouters, Giuseppe Masucci, Emilia Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Florence Marliot, Tessa Fredriksen, Benedicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van de Water, Shannon Van Lent-van Vliet, Nikki Knijn, Ana-Maria Muaina, Dragos-Viorel Scripcariu, Francesco M. Marincola, Paolo A. Ascierto, Bernard A. Fox, Franck Pages, Yutaka Kawakami, Jerome Galon
Summary: This study evaluated the prognostic value of Immunoscore in Asian patients with stage I-III colon cancer. The findings demonstrated a significant association between high Immunoscore and prolonged survival in this population.
Article
Gastroenterology & Hepatology
Giulia Martina Cavestro, Alessandro Mannucci, Francesc Balaguer, Heather Hampel, Sonia S. Kupfer, Alessandro Repici, Andrea Sartore-Bianchi, Toni T. Seppala, Vincenzo Valentini, Clement Richard Boland, Randall E. Brand, Tineke E. Buffart, Carol A. Burke, Riccardo Caccialanza, Renato Cannizzaro, Stefano Cascinu, Andrea Cercek, Emma J. Crosbie, Silvio Danese, Evelien Dekker, Maria Daca-Alvarez, Francesco Deni, Mev Dominguez-Valentin, Cathy Eng, Ajay Goel, Jose G. Guillem, Britt B. S. L. Houwen, Charles Kahi, Matthew F. Kalady, Fay Kastrinos, Florian Kuehn, Luigi Laghi, Andrew Latchford, David Liska, Patrick Lynch, Alberto Malesci, Gianluca Mauri, Elisa Meldolesi, Pal Moller, Kevin J. Monahan, Gabriela Moeslein, Caitlin C. Murphy, Karlijn Nass, Kimmie Ng, Cristina Oliani, Enrico Papaleo, Swati G. Patel, Marta Puzzono, Andrea Remo, Luigi Ricciardiello, Carla Ida Ripamonti, Salvatore Siena, Satish K. Singh, Zsofia K. Stadler, Peter P. Stanich, Sapna Syngal, Stefano Turi, Emanuele Damiano Urso, Laura Valle, Valeria Stella Vanni, Eduardo Vilar, Marco Vitellaro, Yi-Qian Nancy You, Matthew B. Yurgelun, Raffaella Alessia Zuppardo, Elena M. Stoffel
Summary: This study aimed to develop guidelines for early-onset colorectal cancer (eoCRC). The study found that all individuals younger than 50 should undergo CRC risk stratification and newly diagnosed eoCRC patients should receive germline genetic testing. Furthermore, the treatment of early-onset CRC, including endoscopic, surgical, and oncologic treatment, should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The study also highlighted areas for future research.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Oncology
Luana Greco, Federica Rubbino, Luigi Laghi
Summary: This article discusses the relationship between the progression of pancreatic cancer and epithelial-to-mesenchymal transition (EMT), suggesting that EMT plays an important role in the invasiveness and spread of PDAC. However, the clinical application of EMT is not yet mature and more translational data are needed to support its use. The identification of EMT markers suitable for analyzing the invasive behavior of PDAC could potentially improve the clinical scenario and enhance the diagnosis and monitoring of PDAC.
Article
Oncology
Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T. Rau, Martin D. Berger, Iris D. Nagtegaal, Elisa Vink-Borger, Arndt Hartmann, Carol Geppert, Julie Kolwelter, Susanne Merkel, Robert Grutzmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Leonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H. A. Roehrl, Pamela S. Ohashi, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradly G. Wouters, Giuseppe Masucci, Emilia K. Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Benedicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn van de Water, Shannon Van Lent-van Vliet, Nikki Knijn, Ana-Maria Musing, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H. Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M. Marincola, Paolo A. Ascierto, Bernard A. Fox, Franck Pages, Jerome Galon
Summary: This study found that the immune system status is a better predictor of prognosis in early-stage colon cancer patients than tumor cell-related parameters. The consensus Immunoscore accurately identifies early-stage colon cancer patients with different clinical outcomes, regardless of treatment bias.
Article
Gastroenterology & Hepatology
Giulia Rizzo, Federica Rubbino, Sudharshan Elangovan, Giusy Sammarco, Sara Lovisa, Silvia Restelli, Samuel Elias Pineda Chavez, Luca Massimino, Luigi Lamparelli, Marianna Paulis, Annalisa Maroli, Giulia Roda, Mohammad Shalaby, Michele Carvello, Caterina Foppa, Sheona P. Drummond, Paola Spaggiari, Federica Ungaro, Antonino Spinelli, Alberto Malesci, Alessandro Repici, Anthony J. Day, Alessandro Armuzzi, Silvio Danese, Stefania Vetrano
Summary: This study investigated the tissue changes in perianal fistula and explored the dysregulation of extracellular matrix (ECM) homeostasis in fistula formation. They found that TNFAI6 (encoding TSG-6) was significantly upregulated in the fistula and played a role in the formation of a crosslinked ECM. TSG-6 mediated changes in ECM organization and triggered the activation of the epithelial-mesenchymal transition transcription factor SNAI1 through mechano-sensitive proteins.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
L. Poliani, L. Greco, M. Barile, A. Dal Buono, P. Bianchi, G. Basso, V. Giatti, M. Genuardi, A. Malesci, L. Laghi
Summary: This study found that uncanonical variants may account for up to one-third of pathogenic variants, highlighting the urgent need for consensus on clinical advice for incidental findings in cancer-predisposing genes not related to patient phenotype.
Article
Oncology
Andrea Vittorio Emanuele Lisa, Marzia Salgarello, Alessandra Huscher, Fabio Corsi, Daniele Piovani, Federica Rubbino, Stefania Andreoletti, Giovanni Papa, Francesco Klinger, Corrado Tinterri, Alberto Testori, Marta Scorsetti, Paolo Veronesi, Maria Cristina Leonardi, Mario Rietjens, Umberto Cortinovis, Valeria Summo, Emanuele Rampino Cordaro, Pier Camillo Parodi, Paolo Persichetti, Mauro Barone, Giorgio De Santis, Matteo Murolo, Michele Riccio, Angelica Aquinati, Francesco Cavaliere, Nicola Vaia, Giulia Pagura, Erica Dalla Venezia, Franco Bassetto, Vincenzo Vindigni, Luigi Ciuffreda, Maria Alessandra Bocchiotti, Alberto Sciarillo, Nadia Renzi, Graziano Meneghini, Tajna Kraljic, Andrea Loreti, Lucio Fortunato, Valentina Pino, Valeriano Vinci, Marco Klinger
Summary: In this national multicenter study, the impact of postmastectomy radiotherapy (PMRT) on breast reconstruction was analyzed. The study found that patients receiving PMRT had a significantly increased risk of complications, especially capsular contracture in direct-to-implant (DTI) and tissue expander/immediate (TE/I) reconstruction. Autologous reconstruction was found to be the least impacted by PMRT.
Review
Genetics & Heredity
Luana Greco, Federica Rubbino, Arianna Dal Buono, Luigi Laghi
Summary: Microsatellite instability (MSI), a key feature of defective DNA mismatch repair (MMR) system, is found in 15-20% of colorectal cancers (CRC). It has been established as a unique and pivotal biomarker in the diagnosis, prognosis, and treatment of CRC. MSI tumor cells exhibit strong lymphocytic activation and a shift toward a tumor microenvironment that restrains metastasis and shows high responsiveness to immunotherapy.
Article
Oncology
Arianna Dal Buono, Laura Poliani, Luana Greco, Paolo Bianchi, Monica Barile, Valentina Giatti, Cristiana Bonifacio, Silvia Carrara, Alberto Malesci, Luigi Laghi
Summary: This study investigated the prevalence of germline mutations in cancer predisposition genes in patients with pancreatic ductal adenocarcinoma (PDAC) or suspected related hereditary syndromes. The results showed that 20.1% of the tested subjects carried at least one pathogenic variant in the genes of interest. Therefore, the incorporation of genetic testing and multiple-gene panels in the management of pancreatic cancer would be beneficial.