Article
Oncology
Chaoran Zang, Yan Zhao, Ling Qin, Guihai Liu, Jianping Sun, Kang Li, Yanan Zhao, Shoupeng Sheng, Honghai Zhang, Ning He, Peng Zhao, Qi Wang, Xi Li, Yanchun Peng, Tao Dong, Yonghong Zhang
Summary: The study revealed specific T cell responses against CTAs and TAAs in HCC patients. In early-stage HCC patients, SALL4-specific response was the most prominent, followed by MAGE-A3, NY-ESO-1, MAGE-A1, and SSX2. The protective role of CTA-specific responses was suggested for one-year recurrence-free survival after treatment. As HCC progressed, CTA and SALL4-specific T cell responses decreased while AFP-specific response increased, indicating the potential of immunotherapy at an early stage of HCC.
Article
Multidisciplinary Sciences
Seiga Komiyama, Takahiro Yamada, Nobuyuki Takemura, Norihiro Kokudo, Koji Hase, Yuki Kawamura
Summary: Liver cancer is the fourth leading cause of cancer-related death, with patients exhibiting distinct tumor microbiota composition that may play a role in the pathogenesis of HCC.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Wei Jia, Cynthia Rajani, Hongxi Xu, Xiaojiao Zheng
Summary: Colorectal cancer (CRC) and hepatocellular carcinoma (HCC) are influenced by gut microbiota composition, which evolves with disease progression. Tumor survival may depend on a less pro-inflammatory tumor microenvironment.
Article
Oncology
Petros Fessas, Paolo Spina, Renzo L. Boldorini, Mario Pirisi, Rosalba Minisini, Francesco A. Mauri, Fraser Simpson, Paola Olivieri, Alessandra Gennari, Ching Ngar Wong, Abdul Siddique, Robert D. Goldin, Ayse U. Akarca, Teresa Marafioti, David J. Pinato
Summary: This study investigated the intra-tumoural heterogeneity and immune microenvironment of hepatocellular carcinoma (HCC) across primary and secondary sites, revealing that HCC metastases maintain immune exclusion characteristics and exhibit differential regulation of innate immune pathways.
Article
Endocrinology & Metabolism
Jee-Eun Choi, Carlos Sebastian, Christina M. Ferrer, Caroline A. Lewis, Moshe Sade-Feldman, Thomas LaSalle, Anna Gonye, Begona G. C. Lopez, Walid M. Abdelmoula, Michael S. Regan, Murat Cetinbas, Gloria Pascual, Gregory R. Wojtkiewicz, Giorgia G. Silveira, Ruben Boon, Kenneth N. Ross, Itay Tirosh, Srinivas V. Saladi, Leif W. Ellisen, Ruslan I. Sadreyev, Salvador Aznar Benitah, Nathalie Y. R. Agar, Nir Hacohen, Raul Mostoslavsky
Summary: The study highlights the important tumor suppressor role of NAD(+)-dependent histone deacetylase sirtuin 6 in squamous cell carcinoma, as well as the existence of a subset of highly glycolytic tumor-propagating cells with elevated antioxidant capacity. These findings emphasize the key role of metabolism in intra-tumor heterogeneity.
Article
Biochemistry & Molecular Biology
Zhiwu Jiang, Lin Cheng, Zhiping Wu, Linfu Zhou, Haitao Wang, Qilan Hong, Qiting Wu, Youguo Long, Yunlin Huang, Gaoqi Xu, Yao Yao, Zhaoyang Tang, Zhenfeng Zhang, Lili Yang, Wei Luo, Jie Yang, Likun Gong, Pentao Liu, Xinwen Chen, Shuzhong Cui, Qi Zhang, Yinxiong Li, Peng Li
Summary: The lack of in vivo models has hindered our understanding of hepatocellular carcinoma (HCC) development. In this study, we used genetic screening in an immunodeficient mouse model to identify oncogenes highly expressed in induced HCC (iHCC) samples. Overexpression of these genes transformed primary human hepatocytes into iHCC. The iHCC model recapitulates histological architecture and gene expression characteristics of clinical HCC samples, providing a biological basis for studying HCC initiation and identifying diagnostic biomarkers and targets for cellular immunotherapy.
Article
Engineering, Biomedical
Feihu Xie, Lejia Sun, Yuan Pang, Gang Xu, Bao Jin, Haifeng Xu, Xin Lu, Yiyao Xu, Shunda Du, Yanan Wang, Shi Feng, Xinting Sang, Shouxian Zhong, Xin Wang, Wei Sun, Haitao Zhao, Hongbing Zhang, Huayu Yang, Pengyu Huang, Yilei Mao
Summary: This study established a modeling system using three-dimensional bioprinting technology for patient-specific drug screening for hepatocellular carcinoma. The models retained features of parental HCCs, including stable biomarker expression and genetic alterations. Additionally, the models were capable of intuitively and quantitatively displaying drug screening results.
Article
Oncology
Tomoko Aoki, Naoshi Nishida, Yutaka Kurebayashi, Kazuko Sakai, Masahiro Morita, Hirokazu Chishina, Masahiro Takita, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Yasunori Minami, Masakatsu Tsurusaki, Takuya Nakai, Michiie Sakamoto, Kazuto Nishio, Masatoshi Kudo
Summary: This study revealed the heterogeneity of immunophenotype in HCC with Wnt/beta-catenin mutations, indicating differences in tumor traits and tumor microenvironment.
Article
Dermatology
Giulio Gualdi, Simone Soglia, Marta Fusano, Paola Monari, Federica Giuliani, Annamaria Porreca, Marta Di Nicola, Piergiacomo Calzavara-Pinton, Paolo Amerio
Summary: Basosquamous carcinoma is a rare clinical entity, comprising a small portion of all skin carcinomas. It mainly occurs on the head and neck, with significant differences compared to basal cell and squamous cell carcinomas.
ACTA DERMATO-VENEREOLOGICA
(2021)
Article
Gastroenterology & Hepatology
Lei Zhou, Ken H. O. Yu, Tin Lok Wong, Zhao Zhang, Chun Ho Chan, Jane H. C. Loong, Noelia Che, Hua Jian Yu, Kel Vin Tan, Man Tong, Elly S. Ngan, Joshua W. K. Ho, Stephanie Ma
Summary: This study utilized mouse models to investigate the heterogeneity and dynamics of Prom1+ cells in HCC, revealing their CSC-like properties and clonal expansion within tumors. Labelled Prom1+ cells showed increased tumorigenicity in 3D culture and allotransplantation, while depletion of these cells impeded tumor growth. Single-cell RNA sequencing analysis highlighted the heterogeneity of Prom1+ HCC cells and their potential role in disease progression.
Article
Gastroenterology & Hepatology
Andrea R. Mospan, Heather L. Morris, Michael W. Fried
Summary: Real-world evidence includes health-related information obtained outside of clinical trials, which can provide insights into disease progression and treatment effectiveness. Global regulatory agencies have utilized real-world data to inform drug development and refine therapeutic regimens post-marketing, especially in underrepresented populations. In the management of hepatocellular carcinoma, early detection offers the best chance for curative therapies, while novel systemic treatments have improved survival rates. Longitudinal observational studies in real-world settings can help assess the long-term safety and effectiveness of these therapies.
LIVER INTERNATIONAL
(2021)
Article
Oncology
Ryo Morisue, Motohiro Kojima, Toshihiro Suzuki, Tetsuya Nakatsura, Hidenori Ojima, Reiko Watanabe, Motokazu Sugimoto, Shin Kobayashi, Shinichiro Takahashi, Masaru Konishi, Genichiro Ishii, Naoto Gotohda, Toshiyoshi Fujiwara, Atsushi Ochiai
Summary: Sarcomatoid hepatocellular carcinoma (SHCC), a rare histological subtype of hepatocellular carcinoma (HCC), exhibits distinct clinicopathologic, transcriptomic, and immunologic characteristics compared to ordinary HCC (OHCC). Comprehensive analyses support the classification of SHCC as a histological subtype of HCC.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Markia A. Smith, Sarah C. Van Alsten, Andrea Walens, Jeffrey S. Damrauer, Ugwuji N. Maduekwe, Russell R. Broaddus, Michael Love, Melissa A. Troester, Katherine A. Hoadley
Summary: DNA repair pathways play an important role in hepatocellular carcinoma outcomes. Hepatocellular carcinomas can be divided into high and low repair groups based on the overall expression of DNA repair genes. Low repair samples can further be categorized into three subgroups, one of which shares similarities with the high repair group. High repair samples exhibit more proliferative and regenerative features and have worse outcomes compared to the low repair samples, which are more associated with genes involved in normal liver biology.
Article
Gastroenterology & Hepatology
Ronja-Melinda Komoll, Qingluan Hu, Olaniyi Olarewaju, Lena von Doehlen, Qinggong Yuan, Yu Xie, Hsin-Chieh Tsay, Joel Daon, Renyi Qin, Michael P. Manns, Amar Deep Sharma, Andrei Goga, Michael Ott, Asha Balakrishnan
Summary: This study identified miR-342-3p as a tumor suppressor miRNA in HCC, showing its therapeutic efficacy in attenuating tumor development and prolonging survival in different HCC mouse models. The downregulation of miR-342-3p in HCC tumors from patients compared with non-tumor tissues, inversely correlating with MCT1 expression, was also observed.
JOURNAL OF HEPATOLOGY
(2021)
Review
Oncology
Alona Agirre-Lizaso, Maider Huici-Izagirre, Josu Urretabizkaia-Garmendia, Pedro M. Rodrigues, Jesus M. Banales, Maria J. Perugorria
Summary: Hepatocellular carcinoma (HCC) is a highly lethal disease with a complex tumour microenvironment (TME). Tumour-associated macrophages (TAMs) play a key role in the development and progression of HCC. Reprogramming TAMs' functional state has emerged as a promising option for immunotherapy. This review focuses on the heterogeneity of TAMs in HCC, the mechanisms behind their pro-tumoural polarization, and the potential of TAMs' reprogramming in HCC therapy.
Article
Gastroenterology & Hepatology
Carla Montironi, Florian Castet, Philipp K. Haber, Roser Pinyol, Miguel Torres-Martin, Laura Torrens Fontanals, Agavni Mesropian, Huan Wang, Marc Puigvehi, Miho Maeda, Wei Qiang Leow, Elizabeth Harrod, Patricia Taik, Jigjidsuren Chinburen, Erdenebileg Taivanbaatar, Enkhbold Chinbold, Manel Sole Arques, Michael Donovan, Swan Thung, Jaclyn Neely, Vincenzo Mazzaferro, Jeffrey Anderson, Sasan Roayaie, Myron Schwartz, Augusto Villanueva, Scott L. Friedman, Andrew Uzilov, Daniela Sia, Josep M. Llovet
Summary: This study characterizes the immunogenomic contexture of hepatocellular carcinoma (HCC) and defines inflamed and non-inflamed tumors. Two distinct patterns of CTNNB1 are associated with differential immune evasion and may help predict immune response in HCC.
Letter
Gastroenterology & Hepatology
Licia Rivoltini, Sherrie Bhoori, Chiara Camisaschi, Laura Bergamaschi, Luca Lalli, Paola Frati, Davide Citterio, Chiara Castelli, Vincenzo Mazzaferro
Article
Gastroenterology & Hepatology
Miguel A. Martin-Serrano, Benjamin Kepecs, Miguel Torres-Martin, Emily R. Bramel, Philipp K. Haber, Elliot Merritt, Alexander Rialdi, Nesteene Joy Param, Miho Maeda, Katherine E. Lindblad, James K. Carter, Marina Barcena-Varela, Vincenzo Mazzaferro, Myron Schwartz, Silvia Affo, Robert F. Schwabe, Augusto Villanueva, Ernesto Guccione, Scott L. Friedman, Amaia Lujambio, Anna Tocheva, Josep M. Llovet, Swan N. Thung, Alexander M. Tsankov, Daniela Sia
Summary: We present a comprehensive stratification of iCCA based on the tumor microenvironment (TME). The tumor is divided into five stable STIM classes, including 35% inflamed and 65% non-inflamed profiles. The inflamed classes, immune classical and inflammatory stroma, differ in oncogenic pathways and extent of desmoplasia. Analysis of cell-cell interactions highlights cancer-associated fibroblast subtypes as potential mediators of immune evasion. Among the non-inflamed classes, the desert-like class has the lowest immune infiltration with abundant regulatory T cells, while the hepatic stem-like class is enriched in 'M2-like' macrophages and specific mutations. Comparative analysis reveals high similarity between a KRAS/p19 murine model and the inflammatory stroma class. The KRAS-SOS inhibitor sensitizes a KRAS-mutant iCCA murine model to anti-PD1 therapy. Our findings provide valuable insights into the TME of iCCA and offer potential therapeutic targets for future research.
Article
Surgery
Brian K. P. Goh, Ho-Seong Han, Kuo-Hsin Chen, Darren W. Chua, Chung-Yip Chan, Federica Cipriani, Davit L. Aghayan, Asmund A. Fretland, Jasper Sijberden, Mizelle D'Silva, Tiing Foong Siow, Yutaro Kato, Chetana Lim, Phan Phuoc Nghia, Paulo Herman, Marco Marino, Vincenzo Mazzaferro, Adrian K. H. Chiow, Iswanto Sucandy, Arpad Ivanecz, Sung Hoon Choi, Jae Hoon Lee, Mikel Gastaca, Marco Vivarelli, Felice Giuliante, Andrea Ruzzenente, Chee-Chien Yong, Mengqui Yin, Zewei Chen, Constantino Fondevila, Mikhail Efanov, Fernando Rotellar, Gi-Hong Choi, Ricardo R. Campos, Xiaoying Wang, Robert P. Sutcliffe, Johann Pratschke, Eric Lai, Charing C. Chong, Mathieu D'Hondt, Kazuteru Monden, Santiago F. Lopez-Ben, Fabricio F. Coelho, Thomas Peter Kingham, Rong Liu, Tran Cong Duy Long, Alessandro Ferrero, Giovanni B. Levi Sandri, Mansour Saleh, Daniel Cherqui, Olivier Scatton, Olivier Soubrane, Go I. Wakabayashi, Roberto Troisi, Tan-To Cheung, Atsushi Sugioka, Mohammad Abu Hilal, David Fuks, Bjorn Edwin, Luca Aldrighetti
Summary: This study established global benchmark outcomes for laparoscopic liver resections (L-LR) by analyzing a multicenter database of 11,983 patients. Three specific procedures were selected and 15 outcome indicators were established as benchmark cutoffs. The results provide an objective assessment of performance gaps and learning curves for centers adopting L-LR.
Article
Gastroenterology & Hepatology
Giada Aizza, Nadia Russolillo, Alessandro Ferrero, Nicholas L. Syn, Federica Cipriani, Davit Aghayan, Marco Marino, Riccardo Memeo, Vincenzo Mazzaferro, Adrian K. H. Chiow, Iswanto Sucandy, Arpad Ivanecz, Marco Vivarelli, Fabrizio Di Benedetto, Sung-Hoon Choi, Jae Hoon Lee, James O. Park, Mikel Gastaca, Constantino Fondevila, Mikhail Efanov, Fernando Rotellar, Gi-Hong Choi, Ricardo Robles-Campos, Xiaoying Wang, Robert P. Sutcliffe, Johann Pratschke, Chung Ngai Tang, Charing C. Chong, Mathieu D'Hondt, Chee Chien Yong, Andrea Ruzzenente, Paolo Herman, T. Peter Kingham, Olivier Scatton, Rong Liu, Giovanni Battista Levi Sandri, Olivier Soubrane, Alejandro Mejia, Santiago Lopez-Ben, Kazateru Monden, Go Wakabayashi, Daniel Cherqui, Roberto Troisi, Mengqiu Yin, Felice Giuliante, David Geller, Atsushi Sugioka, Bjorn Edwin, Tan-To Cheung, Tran Cong Duy Long, Mohammad Abu Hilal, David Fuks, Kuo-Hsin Chen, Luca Aldrighetti, Ho-Seong Han, Brian K. P. Goh
Summary: This study aimed to investigate the relationship between tumor size and the difficulty of laparoscopic left lateral sectionectomy (L-LLS). Three optimal tumor size cutoffs (40-, 70-, and 100-mm) were identified. As tumor size increased, there was a stepwise increase in the rates of open conversion, operative time, blood loss, intraoperative blood transfusion, Pringle maneuver use, major morbidity, and 30-day readmission.
JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
(2023)
Letter
Gastroenterology & Hepatology
Carlo Sposito, Alessandro Cucchetti, Vincenzo Mazzaferro
JOURNAL OF HEPATOLOGY
(2023)
Article
Surgery
Fabrizio Di Benedetto, Paolo Magistri, Stefano Di Sandro, Carlo Sposito, Christian Oberkofler, Ellie Brandon, Benjamin Samstein, Cristiano Guidetti, Alexandros Papageorgiou, Samuele Frassoni, Vincenzo Bagnardi, Pierre-Alain Clavien, Davide Citterio, Tomoaki Kato, Henrik Petrowsky, Karim J. Halazun, Vincenzo Mazzaferro, Robotic HPB Study Grp
Summary: This study examined the short-term and long-term outcomes of robotic liver resection (RLR) for hepatocellular carcinoma (HCC) in Western high-volume centers. The study found that RLR had shorter hospital stays and lower incidence of postoperative liver failure compared to open liver resection (OLR). Furthermore, there were no significant differences in tumor recurrence and overall survival rates between the two groups.
Review
Oncology
Marianna Maspero, Carlo Sposito, Matteo Virdis, Davide Citterio, Filippo Pietrantonio, Sherrie Bhoori, Filiberto Belli, Vincenzo Mazzaferro
Summary: Over 40% of colorectal cancer patients develop liver metastases, with poor prognosis for those with unresectable disease. Liver transplantation has shown improved survival in selected patients with unresectable colorectal liver metastases. This article provides an overview of the current status, issues, and future directions of liver transplantation for colorectal liver metastases.
Article
Surgery
Matteo Serenari, Francesca Ratti, Nicola Guglielmo, Matteo Zanello, Federico Mocchegiani, Jacopo Lenzi, Michele Colledan, Vincenzo Mazzaferro, Umberto Cillo, Alessandro Ferrero, Matteo Cescon, Fabrizio Di Benedetto, Marco Massani, Gianluca Grazi, Raffaele Dalla Valle, Marco Vivarelli, Giuseppe Maria Ettorre, Luca Aldrighetti, Elio Jovine
Summary: This study analyzed the trend and influencing factors of ALPPS in Italy. It was found that the use of ALPPS has slightly declined, but the use of minimally invasive techniques has increased, leading to a reduced 90-day mortality rate. Post-hepatectomy liver failure (PHLF) still remains an unresolved issue.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2023)
Correction
Surgery
Matteo Serenari, Francesca Ratti, Nicola Guglielmo, Matteo Zanello, Federico Mocchegiani, Jacopo Lenzi, Michele Colledan, Vincenzo Mazzaferro, Umberto Cillo, Alessandro Ferrero, Matteo Cescon, Fabrizio Di Benedetto, Marco Massani, Gianluca Grazi, Raffaele Dalla Valle, Marco Vivarelli, Giuseppe Maria Ettorre, Luca Aldrighetti, Elio Jovine, Stefania Camagni, Fabio Forchino, Enrico Gringeri, Salvatore Gruttadauria, Paolo Magistri, Bruno Nardo, Matteo Ravaioli, Fabrizio Romano, Maurizio Romano, Andrea Scarinci, Matteo Virdis, Giacomo Zanus
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2023)
Article
Gastroenterology & Hepatology
Felice Giuliante, Francesca Ratti, Elena Panettieri, Vincenzo Mazzaferro, Alfredo Guglielmi, Giuseppe M. Ettorre, Salvatore Gruttadauria, Fabrizio Di Benedetto, Umberto Cillo, Luciano De Carlis, Raffaele Dalla Valle, Alessandro Ferrero, Roberto Santambrogio, Francesco Ardito, Luca Aldrighetti
Summary: The use of minimally invasive liver surgery has greatly reduced surgical risk for hepatocellular carcinoma. This study analyzed the outcomes of minimally invasive liver surgery for small hepatocellular carcinoma tumors less than 3 cm in size.
Article
Medicine, General & Internal
Stefania Orecchioni, Paolo Falvo, Giovanna Talarico, Giulia Mitola, Giulia Bravetti, Patrizia Mancuso, Paola Nicoli, Francesco Bertolini
Summary: In this study, we demonstrated the effectiveness of a triple therapy consisting of cyclophosphamide, vinorelbine, and anti-PD-1 in controlling a highly aggressive, anti-PD-1 resistant model of B-cell non-Hodgkin's lymphoma. This therapy was able to generate an immune memory that effectively controlled tumor re-challenge, even at high inoculum doses. Furthermore, the triple therapy reshaped the immune cell landscape and reduced exhausted T cells in treated mice.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Giulia Bravetti, Paolo Falvo, Giovanna Talarico, Stefania Orecchioni, Francesco Bertolini
Summary: Chemotherapeutic agents have varying effects on cancer, stroma, and immune cells depending on dosage and schedule. Continuous administration at low dosage (metronomic) can activate antigen presenting cells and generate new T cell clones, enhancing immunotherapies. Ongoing clinical trials will confirm or dismiss this hypothesis and provide biomarker data for patient selection.
Article
Biochemistry & Molecular Biology
Paolo Rainone, Silvia Valtorta, Chiara Villa, Sergio Todde, Massimiliano Cadamuro, Gloria Bertoli, Donatella Conconi, Marialuisa Lavitrano, Rosa Maria Moresco
Summary: Breast cancer is the most common cancer in women and the second leading cause of death. Breast cancer cells show a metabolic shift towards increased glycolysis, making it an interesting target for metabolic drugs such as metformin. Recent studies have found that the antihypertensive drug syrosingopine, when combined with metformin, has a synergistic effect on various cancers. However, there is a need to develop in vivo biomarkers that can detect early clinical response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Alessandra Cattaneo, Manuela Liguori, Elena Trombetta, Ferruccio Ceriotti, Lorenza Pugni, Andrea Ronchi, Giulia Carracchia, Lucia D. Notarangelo, Francesca Ferrua, Federica Barzaghi, Chiara Giovanettoni, Gianvincenzo Zuccotti, Emilia Cirillo, Claudio Pignata, Federica Meroni, Anna Maietta, Piero Farruggia, Laura Porretti
Summary: This study retrospectively evaluated the clinical and molecular/serological findings of 83 neutropenic infants, revealing that neonatal alloimmune neutropenia (NAN) accounted for 31 cases. The median age and absolute neutrophil count were significantly lower in NAN compared to non-NAN cases. Additionally, 50% of NAN cases were due to alloantibodies against HNA-1b.
