Article
Gastroenterology & Hepatology
Maria Reig, Giuseppe Cabibbo
Summary: The potential impact of DAAs in BCLC-B/C stage patients with HCC is understudied, as HCC patients have been excluded from DAA trials. The decision on using DAAs should be made based on individual patient profiles.
JOURNAL OF HEPATOLOGY
(2021)
Review
Gastroenterology & Hepatology
Aurelie Beaufrere, Julien Calderaro, Valerie Paradis
Summary: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumor with both hepatocytic and biliary differentiation, whose diagnosis is primarily based on morphology and immunostaining, with a prognosis worse than hepatocellular carcinoma and treatment limited to surgery.
JOURNAL OF HEPATOLOGY
(2021)
Article
Medicine, General & Internal
Po-Li Wei, Chin-Sheng Hung, Hsuan-Hsuan Lu, Uyanga Batzorig, Chien-Yu Huang, Yu-Jia Chang
Summary: The study demonstrated that Areca nut extract (ANE) may be a potential new compound for hepatocellular carcinoma (HCC) therapy. ANE treatment resulted in reduced cell viability, increased cell apoptosis, and suppressed tumor progression in xenograft models. Mechanistically, ANE treatment induced ROS-mediated autophagy and lysosome formation.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Oncology
Jianjun Xu, Zhe Su, Xiang Cheng, Shaobo Hu, Wenjie Wang, Tianhao Zou, Xing Zhou, Zifang Song, Yun Xia, Yang Gao, Qichang Zheng
Summary: The study found that PPT1 is highly expressed in HCC and is associated with poor prognosis. The PPT1 inhibitor DC661 can enhance the sensitivity of HCC cells to sorafenib and enhance anti-tumor immune response by promoting immune cell activation. The combination of DC661 and sorafenib also shows good efficacy in tumor models in immunized mice.
CANCER CELL INTERNATIONAL
(2022)
Article
Oncology
Sonia Brun, Jean-Marc Pascussi, Elena Patricia Gifu, Eloine Bestion, Zuzana Macek-Jilkova, Guanxiong Wang, Firas Bassissi, Soraya Mezouar, Jerome Courcambeck, Philippe Merle, Thomas Decaens, Julie Pannequin, Philippe Halfon, Claude Caron de Fromentel
Summary: The new autophagy inhibitor GNS561 showed significant activity against both the tumor bulk and a sub-population displaying CSC features, offering great promise for cancer therapy. Results were confirmed in vivo in a cirrhotic rat model, and a global phase 1b clinical trial in liver cancers has been completed.
Article
Radiology, Nuclear Medicine & Medical Imaging
Venkata S. Katabathina, Lokesh Khanna, Venkateswar R. Surabhi, Marta Minervini, Krishna Shanbhogue, Anil K. Dasyam, Srinivasa R. Prasad
Summary: Hepatocellular adenomas, hepatocellular carcinomas, and intrahepatic cholangiocarcinomas are a highly heterogeneous group of liver tumors with diverse pathomolecular features and prognoses. The use of high-throughput gene sequencing techniques has allowed for the identification of distinct subtypes with varied clinicobiologic behaviors and imaging findings. The understanding of morphomolecular features of these tumors has important implications for diagnosis, treatment, and prognosis.
Article
Cell Biology
Sonia Brun, Eloine Bestion, Eric Raymond, Firas Bassissi, Zuzana Macek Jilkova, Soraya Mezouar, Madani Rachid, Marie Novello, Jennifer Tracz, Ahmed Hamai, Gilles Lalmanach, Lise Vanderlynden, Raphael Legouffe, Jonathan Stauber, Thomas Schubert, Maximilian G. Plach, Jerome Courcambeck, Cyrille Drouot, Guillaume Jacquemot, Cindy Serdjebi, Gael Roth, Jean-Pierre Baudoin, Christelle Ansaldi, Thomas Decaens, Philippe Halfon
Summary: The new autophagy inhibitor GNS561 shows high liver tropism and potent antitumor activity, particularly against hepatocellular carcinoma. Its mechanism of action involves lysosomal disruption and induction of cell death in tumor cells.
Article
Oncology
Daw-Shyong Perng, Chao-Ming Hung, Hung-Yu Lin, Paul Morgan, Yao-Chun Hsu, Tsung-Chin Wu, Pei-Min Hsieh, Jen-Hao Yeh, Pojen Hsiao, Chih-Yuan Lee, Yu-Chan Li, Ya-Chin Wang, Yaw-Sen Chen, Chih-Wen Lin
Summary: The study found that high LC3 expression in tumors of cHCC-CC patients is significantly associated with favorable clinical prognosis, including prolonged overall survival and disease-free survival.
Article
Radiology, Nuclear Medicine & Medical Imaging
Xiaoyang Liu, Farzad Khalvati, Khashayar Namdar, Sandra Fischer, Sara Lewis, Bachir Taouli, Masoom A. Haider, Kartik S. Jhaveri
Summary: Machine learning analysis on MRI and CT radiomics features showed promising predictive performance in differentiating cHCC-CC from other liver cancers, with MRI features demonstrating the best performance. Radiologists read had a high misdiagnosis rate for cHCC-CC.
EUROPEAN RADIOLOGY
(2021)
Review
Oncology
Florian Rossner, Bruno Valentin Sinn, David Horst
Summary: This review discusses the histomorphological classification and diagnosis methods of combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA), as well as the molecular foundation for potential therapeutic approaches. cHCC-CCA is a rare primary liver cancer composed of hepatocellular and cholangiocellular differentiated cells. The classification of this cancer has evolved over time, with the latest WHO classification emphasizing morphological diagnosis and introducing new subtypes. Immunohistochemical markers have limited value for diagnosis, but recent discoveries in molecular pathway regulation may lead to new therapeutic approaches for this challenging disease.
Article
Cell Biology
Zhihua Zheng, Man Zhao, Hao Shan, Dongmei Fang, Zuyi Jin, Jiuge Tang, Zhiping Liu, Liang Hong, Peiqing Liu, Min Li
Summary: In this study, the researchers found that STING1 activation can induce both canonical and non-canonical autophagy. They also discovered that STING1-induced NCA is an efficient antiviral pathway that can effectively inhibit DNA virus HSV-1.
Review
Biochemistry & Molecular Biology
Thi Ha Nguyen, Tuan Minh Nguyen, Dinh Thi Minh Ngoc, Taesik You, Mi Kyung Park, Chang Hoon Lee
Summary: This review discusses the molecular mechanisms of autophagy and mitophagy in hepatocellular carcinoma (HCC) and highlights the dual role of autophagy in tumor initiation and progression. Additionally, a detailed analysis of autophagy- and mitophagy-related molecules reveals their specific functions during tumorigenesis and the progression of HCC cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Fan Ying, Mandy Sze Man Chan, Terence Kin Wah Lee
Summary: Primary liver cancer (PLC) is the sixth most common cancer worldwide with poor prognosis. Cancer-associated fibroblasts (CAFs) are a major component of the abundant stromal reaction in PLC. CAFs play a crucial role in tumor progression and are often correlated with poor clinical outcomes. However, the origins, heterogeneity, and specific markers of CAFs are not well understood, hindering efficient CAF-specific therapy. This review explores recent advances in understanding CAF diversity, their regulatory roles, and their crosstalk with immune cells in the tumor microenvironment in PLC. The review also discusses current CAF-targeted therapies and future perspectives.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
Lea Penzkofer, Lisa-Katharina Groeger, Maria Hoppe-Lotichius, Janine Baumgart, Stefan Heinrich, Jens Mittler, Tiemo S. Gerber, Beate K. Straub, Arndt Weinmann, Fabian Bartsch, Hauke Lang
Summary: Mixed hepatocellular cholangiocarcinoma (mHC-CC) is a rare tumor with limited data on its prognosis. This study compared the recurrence and survival of mHC-CC with pure hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The cholangiocarcinoma component of mHC-CC appears to be the defining factor for prognosis. Liver transplant within the Milan criteria may offer a good long-term outcome for mHC-CC.
Review
Biochemistry & Molecular Biology
Joon Hyuk Choi, Jae Y. Ro
Summary: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer with aggressive behavior and poor prognosis compared to classic hepatocellular carcinoma (HCC). The morphologic and phenotypic diversity of cHCC-CCA poses diagnostic challenges for pathologists. Accurate diagnosis is crucial for patient management and prognostication.
Article
Immunology
Emmanuelle Lesieur, Julia Torrents, Frederic Fina, Christine Zandotti, Julie Blanc, Sophie Collardeau-Frachon, Celine Gazin, Delphine Sirgant, Soraya Mezouar, Myriem Otmani Idrissi, Hubert Lepidi, Florence Bretelle, Jean-Louis Mege, Laurent Daniel, Radia Fritih
Summary: This study reports a case of fetal death during pregnancy after the diagnosis of symptomatic SARSCoV-2 infection in the mother. The incriminating virus was isolated from fetal tissues using immunohistochemistry and molecular techniques, and the variant analysis of the SARS-CoV-2 genome was performed. This is the first report to provide a pathological description of placental and fetal tissue damage caused by vertical transmission of SARSCoV-2.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Michael D. Farwell, Raymond F. Gamache, Hasan Babazada, Matthew D. Hellmann, James J. Harding, Ron Korn, Alessandro Mascioni, William Le, Ian Wilson, Michael S. Gordon, Anna M. Wu, Gary A. Ulaner, Jedd D. Wolchok, Michael A. Postow, Neeta Pandit-Taskar
Summary: This study demonstrates that CD8 PET imaging with Zr-89-Df-IAB22M2C is a safe and effective method for visualizing the whole-body biodistribution of CD8+ leukocytes in tumors and reference tissues, and may predict early response to immunotherapy.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Bastien Nguyen, Christopher Fong, Anisha Luthra, Shaleigh A. Smith, Renzo G. DiNatale, Subhiksha Nandakumar, Henry Walch, Walid K. Chatila, Ramyasree Madupuri, Ritika Kundra, Craig M. Bielski, Brooke Mastrogiacomo, Mark T. A. Donoghue, Adrienne Boire, Sarat Chandarlapaty, Karuna Ganesh, James J. Harding, Christine A. Iacobuzio-Donahue, Pedram Razavi, Ed Reznik, Charles M. Rudin, Dmitriy Zamarin, Wassim Abida, Ghassan K. Abou-Alfa, Carol Aghajanian, Andrea Cercek, Ping Chi, Darren Feldman, Alan L. Ho, Gopakumar Iyer, Yelena Y. Janjigian, Michael Morris, Robert J. Motzer, Eileen M. O'Reilly, Michael A. Postow, Nitya P. Raj, Gregory J. Riely, Mark E. Robson, Jonathan E. Rosenberg, Anton Safonov, Alexander N. Shoushtari, William Tap, Min Yuen Teo, Anna M. Varghese, Martin Voss, Rona Yaeger, Marjorie G. Zauderer, Nadeem Abu-Rustum, Julio Garcia-Aguilar, Bernard Bochner, Abraham Hakimi, William R. Jarnagin, David R. Jones, Daniela Molena, Luc Morris, Eric Rios-Doria, Paul Russo, Samuel Singer, Vivian E. Strong, Debyani Chakravarty, Lora H. Ellenson, Anuradha Gopalan, Jorge S. Reis-Filho, Britta Weigelt, Marc Ladanyi, Mithat Gonen, Sohrab P. Shah, Joan Massague, Jianjiong Gao, Ahmet Zehir, Michael F. Berger, David B. Solit, Samuel F. Bakhoum, Francisco Sanchez-Vega, Nikolaus Schultz
Summary: This study investigates the genomic mechanisms driving metastasis in cancer patients. By analyzing a cohort of over 25,000 patients with metastatic diseases, the researchers identify associations between genomic alterations and patterns of metastatic dissemination across different tumor types. The study highlights the complex role of chromosomal instability in cancer progression and provides valuable insights for further research on metastatic spread.
Article
Oncology
Funda Meric-Bernstam, Nizar M. Tannir, Othon Iliopoulos, Richard J. Lee, Melinda L. Telli, Alice C. Fan, Angela DeMichele, Naomi B. Haas, Manish R. Patel, James J. Harding, Martin H. Voss, Taofeek K. Owonikoko, Bradley Carthon, Ramaprasad Srinivasan, Johanna C. Bendell, Yonchu Jenkins, Sam H. Whiting, Keith Orford, Mark K. Bennett, Todd M. Bauer
Summary: TelaE and TelaC showed promising clinical activity and tolerability in heavily pretreated metastatic renal cell carcinoma patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Valentina Boni, Mary J. Fidler, Hendrik-Tobias Arkenau, Alexander Spira, Funda Meric-Bernstam, Nataliya Uboha, Rachel E. Sanborn, Randy F. Sweis, Patricia LoRusso, Misako Nagasaka, Javier Garcia-Corbacho, Shadia Jalal, James J. Harding, Stella K. Kim, Iris H. C. Miedema, Danielle J. Vugts, Marc C. Huisman, Gerben J. C. Zwezerijnen, Guus A. M. S. van Dongen, C. Willemien Menke van der Houven van Oordt, Song Wang, Tam Dang, Ivan A. Zein, Olga Vasiljeva, Susan K. Lyman, Virginia Paton, Alison Hannah, Joyce F. Liu
Summary: The purpose of this study was to evaluate the efficacy and safety of Praluzatamab ravtansine (CX-2009) in patients with advanced solid tumors. The results showed that breast cancer was the most prevalent subtype among the 99 patients enrolled in the study.
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
James J. Harding, Hooman Yarmohammadi, Kim Anna Reiss, Joanne F. Chou, Marinela Capanu, Richard K. G. Do, Danny Khalil, Imane H. El Dika, Christine S. Ferrer, Olivia Heffernan, J. Daniel Giardina, Taha Merghoub, William R. Jarnagin, Gregory Nadolski, Joseph Patrick Erinjeri, Michael C. Soulen, Benjamin R. Tan, Ghassan K. Abou-Alfa
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
James J. Harding, Ralf-Dieter Hofheinz, Elena Elez, Yasutoshi Kuboki, Drew W. Rasco, Michael Cecchini, Lin Shen, Elizabeth Dowling, Shorena Archuadze, Bruna Andrade de Pereira, Shubham Pant
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
James J. Harding, Danny N. Khalil, Luca Fabris, Ghassan K. Abou-Alfa
Summary: Biliary tract cancers are rare gastrointestinal malignancies associated with high morbidity and mortality rates. Various treatments, including chemotherapy, precision medicine, and immunotherapy, are used in both standard-of-care and investigational settings. Recent research has shown that the combination of durvalumab with gemcitabine and cisplatin improves survival outcomes. Precision medicine is utilized in patients with specific genetic alterations, while fluoropyridine doublets are used in patients without targetable genetic alterations. Next-generation sequencing is crucial for patient care and understanding resistance mechanisms. Ongoing clinical trials seek to improve treatment standards and develop effective combination drug therapies for the future.
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aissatou Bailo Diallo, Benjamin Coiffard, Raoul Desbriere, Maria Katsogiannou, Xavier Donato, Florence Bretelle, Soraya Mezouar, Jean-Louis Mege
Summary: This study demonstrates that placental macrophages exhibit circadian rhythms and melatonin production, and the disruption of these rhythms is associated with preeclampsia. Additionally, both macrophages and trophoblasts produce melatonin and express melatonin receptors. These findings have significant implications for the prevention and treatment of obstetrical pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
James J. J. Harding, Christiane Jungels, Jean-Pascal Machiels, David C. C. Smith, Chris Walker, Tao Ji, Ping Jiang, Xin Li, Ekaterine Asatiani, Eric Van Cutsem, Ghassan K. K. Abou-Alfa
Summary: This study investigated the safety, tolerability, and maximum tolerated dose of INCB062079, an oral selective FGFR4 inhibitor, in patients with advanced solid tumors. The results showed that the drug demonstrated a manageable safety profile and inhibited tumor growth at appropriate doses. However, the study was terminated prematurely due to difficulties in patient recruitment.
Article
Multidisciplinary Sciences
James J. Harding, Sarina A. Piha-Paul, Ronak H. H. Shah, Jessica J. Murphy, James M. Cleary, Geoffrey I. Shapiro, David I. Quinn, Irene Brana, Victor Moreno, Mitesh Borad, Sherene Loi, Iben Spanggaard, Haeseong Park, James M. Ford, Monica Arnedos, Salomon M. Stemmer, Christelle de la Fouchardiere, Christos Fountzilas, Jie Zhang, Daniel DiPrimeo, Casey Savin, S. Duygu Selcuklu, Michael F. Berger, Lisa D. Eli, Funda Meric-Bernstam, Komal Jhaveri, David B. Solit, Ghassan K. Abou-Alfa
Summary: In patients with biliary tract cancer, HER2 alterations correlate with poor prognosis. A phase II clinical trial showed that the tyrosine kinase inhibitor neratinib has some efficacy in treating advanced biliary tract cancers with HER2-mutation positive. The objective response rate to neratinib was 16% (95% CI 4.5-36.1%).
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Kevin C. Soares, Joshua S. Jolissaint, Sarah M. McIntyre, Kenneth P. Seier, Mithat Gonen, Carlie Sigel, Naaz Nasar, Andrea Cercek, James J. Harding, Nancy E. Kemeny, Louise C. Connell, Bas Groot Koerkamp, Vinod P. Balachandran, Michael I. D'Angelica, Jeffrey A. Drebin, T. Peter Kingham, Alice C. Wei, William R. Jarnagin
Summary: The role of locoregional therapy versus systemic chemotherapy for unresectable intrahepatic cholangiocarcinoma remains controversial. This study compared overall survival in patients treated with resection, hepatic arterial infusion pump chemotherapy, or systemic chemotherapy, and evaluated the efficacy of locoregional salvage therapy. The findings highlight the importance of hepatic disease control and the potential benefits of liver-directed therapy.
Article
Ophthalmology
Jasmine H. Francis, William Foulsham, Julia Canestraro, James J. Harding, Eli L. Diamond, Alexander Drilon, David H. Abramson
Summary: This study compared the clinical and morphologic characteristics of serous retinal disturbances in patients taking different types of MAPK inhibitors. It found that all patients exhibited bilateral, fovea-involving, and reversible subretinal fluid foci, regardless of the type of inhibitor used. The downstream targets (MEK or ERK inhibitors) showed higher incidence, more fluid foci, more intraretinal edema, and more symptomatic patients compared to the upstream target (FGFR inhibitors).
OCULAR ONCOLOGY AND PATHOLOGY
(2023)
Article
Oncology
Bruno Almeida Costa, Paulino Tallon de Lara, Wungki Park, Fergus Keane, James J. Harding, Danny N. Khalil
Summary: Despite advances in surveillance and management, advanced cholangiocarcinoma still has a poor prognosis. Recent studies have identified actionable genomic alterations, such as homologous recombination deficiency (HRD), that can affect treatment response. This case report discusses a patient with BRCA2-mutant CCA who showed a durable response to olaparib, a PARP inhibitor, after intolerable toxicity with gemcitabine/cisplatin. Further clinical trials are needed to confirm the role of PARP inhibition in similar patients.
ONCOLOGY RESEARCH AND TREATMENT
(2023)
Article
Medical Laboratory Technology
Enaksha Wickremsinhe, Antoniu Fantana, Erwin Berthier, Brook A. Quist, Diego Lopez de Castilla, Charles Fix, Kahlil Chan, Jing Shi, Michael G. Walker, Jennifer F. Kherani, Holly Knoderer, Arie Regev, James J. Harding
Summary: This study evaluated the use of the capillary blood collection device Tasso+ for measuring abnormal liver function. The results showed that Tasso+ demonstrated high concordance with standard venipuncture and provided a positive patient experience.
JOURNAL OF APPLIED LABORATORY MEDICINE
(2023)