Article
Oncology
Philip A. Philip, Ibrahim Azar, Joanne Xiu, Michael J. Hall, Andrew Eugene Hendifar, Emil Lou, Jimmy J. Hwang, Jun Gong, Rebecca Feldman, Michelle Ellis, Phil Stafford, David Spetzler, Moh'd M. Khushman, Davendra Sohal, A. Craig Lockhart, Benjamin A. Weinberg, Wafi k S. El-Deiry, John Marshall, Anthony F. Shields, W. Michael Korn
Summary: KRAS WT PDAC represents 10.7% of PDAC and is enriched with potential pathogenic drivers and better treatment prognosis. Identifying KRAS WT patients can expand therapeutic options in clinical practice.
CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Shirin Hafezi, Maha Saber-Ayad, Wael M. Abdel-Rahman
Summary: The RAS gene family, especially KRAS, is the most frequently mutated oncogene family in human cancer history, with a significant impact on pancreatic cancer progression. Studying the function of KRAS and its mutations in the tumor microenvironment is crucial for understanding pancreatic cancer and developing novel therapeutic strategies.ongoing clinical trials are using the KRAS oncogene signaling network as therapeutic targets, in addition to exploring the link between diabetes and PDAC, and the potential role of vitamin D in TME modulation for the treatment of PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Health Care Sciences & Services
Darren Cowzer, Mohammed Zameer, Michael Conroy, Walter Kolch, Austin G. Duffy
Summary: This article reviews therapeutic innovations targeting RAS signaling in pancreatic cancer from a clinical perspective. Despite the strong resistance of pancreatic cancer to treatment, new approaches such as inhibiting mutated KRAS, KRAS activators, and effectors show promise in breaking this therapeutic deadlock.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
F. T. Gallina, D. Marinelli, E. Melis, D. Forcella, R. Taje, S. Buglioni, P. Visca, A. Torchia, F. L. Cecere, A. Botticelli, D. Santini, G. Ciliberto, F. Cappuzzo, F. Facciolo
Summary: This study found a significant association between the KRAS-G12C mutation and worse disease-free survival (DFS) in resected, stage I LUAD patients. This association was confirmed in multiple external cohorts.
Article
Multidisciplinary Sciences
Nicholas H. Juul, Jung-Ki Yoon, Marina C. Martinez, Neha Rishi, Yana I. Kazadaeva, Maurizio Morri, Norma F. Neff, Winston L. Trope, Joseph B. Shrager, Rahul Sinha, Tushar J. Desai
Summary: This study identifies a new cell of origin for lung adenocarcinoma, the AT1 cell, which can be reprogrammed into AT2 stem cells after expressing KRAS(G12D) and subsequently form indolent tumors. These tumor cells spread slowly along alveolar walls in a non-destructive manner and have low ERK activity, resembling human lepidic adenocarcinoma.
Article
Medicine, General & Internal
Veronica Aran, Mariano Zalis, Tatiane Montella, Carlos Augusto Moreira de Sousa, Bruno L. Ferrari, Carlos Gil Ferreira
Summary: This study investigated the incidence of KRAS mutations and concomitant mutations in advanced non-small cell lung adenocarcinoma patients. Results showed a higher prevalence of male patients, with 20.86% of samples having mutant KRAS and 33.3% of mutant KRAS samples showing other simultaneous mutations. Further research is needed to explore the significance of these genomic alterations in patient prognosis and treatment response.
MEDICINA-LITHUANIA
(2021)
Article
Oncology
Anjali Rohatgi, Ramaswamy Govindan
Summary: Lung cancer remains a major cause of cancer related deaths globally. Specific targeted therapies for driver mutations have shown significant survival benefits, but patients with KRAS mutations lacked such options until the recent FDA approval of sotorasib. This article discusses the efficacy, toxicities, acquired resistance, and novel combinatorial treatment strategies of KRAS G12C inhibitors.
Article
Cell Biology
Cheng-Yao Chiang, Songqing Fan, Hongmei Zheng, Wenjun Guo, Zehan Zheng, Yihua Sun, Chuanqi Zhong, Juan Zeng, Shuaihu Li, Min Zhang, Tian Xiao, Duo Zheng
Summary: This study reveals the tumor-suppressive role of SETD7 in non-small cell lung cancer (NSCLC) by modulating KRAS methylation and degradation. SETD7 interacts with KRAS and methylates KRAS at lysines 182 and 184, leading to KRAS degradation and attenuation of the RAS/MEK/ERK signaling cascade.
Article
Oncology
Nikolaj Frost, Jens Kollmeier, Claudia Vollbrecht, Christian Grah, Burkhard Matthes, Dennis Pultermann, Maximilian von Laffert, Heike Lueders, Elisabeth Olive, Matthias Raspe, Thomas Mairinger, Sebastian Ochsenreither, Torsten Blum, Michael Hummel, Norbert Suttorp, Martin Witzenrath, Christian Grohe
Summary: This study identified KRAS and TP53-defined mutational subgroups in PD-L1 high non-small cell lung cancer patients, revealing that patients with KRAS(G12C)/TP53 co-mutations showed long-term response while those with KRAS(other)/TP53 mutations had poor prognosis.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Kaja Kostyrko, Marta Roman, Alex G. Lee, David R. Simpson, Phuong T. Dinh, Stanley G. Leung, Kieren D. Marini, Marcus R. Kelly, Joshua Broyde, Andrea Califano, Peter K. Jackson, E. Alejandro Sweet-Cordero
Summary: In this study, researchers used RNAi screens to identify UHRF1 as an epigenetic regulator that is specifically vulnerable in KRAS mutant lung cancer cells. Knocking out UHRF1 selectively impaired the growth and induced apoptosis in KRAS mutant cells by causing global DNA hypomethylation and upregulation of tumor suppressor genes. In vivo experiments showed that UHRF1 knock-out inhibits tumor growth in KRAS-driven mouse lung cancer models. High UHRF1 expression in lung cancer patients is associated with low TSG expression and predicts worse outcomes in KRAS mutant tumors. These findings suggest that UHRF1 could be a potential target for therapeutic intervention in KRAS-driven cancer.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Jingwen Liu, Meiyan Sun, Kwang Bog Cho, Xiang Gao, Bin Guo
Summary: The research team successfully designed a new strategy by combining CRISPR-Cas9 technology with HDAC1 epigenetic silencing to silence KRAS and inhibit the growth and proliferation of cancer cells. This strategy holds promise as a potential effective approach for treating cancers driven by KRAS mutations in the future.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Cell Biology
Yu-Huei Liu, Chun-Mei Hu, Yuan-Sheng Hsu, Wen-Hwa Lee
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and deadly cancer with a lack of early detection and targeted therapy methods. Oncogenic mutations of the KRAS gene drive glucose metabolic reprogramming in cancer cells to support PDAC growth. Understanding cancer-related glucose metabolism provides a better strategy for prevention and treatment in high-risk populations.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Lisa Maria Mustachio, Anca Chelariu-Raicu, Lorant Szekvolgyi, Jason Roszik
Summary: KRAS, mutated in 25% of human cancers, is crucial for tumorigenesis. Despite difficulties in directly targeting it, success has been found in targeting other proteins in the RAS pathway. Recent findings suggest progress towards developing a direct KRAS inhibitor, highlighting the need for continued research for an optimal treatment for certain tumor types.
Article
Oncology
Asimina Koulouridi, Michaela Karagianni, Ippokratis Messaritakis, Maria Sfakianaki, Alexandra Voutsina, Maria Trypaki, Maria Bachlitzanaki, Evangelos Koustas, Michalis Karamouzis, Anastasios Ntavatzikos, Anna Koumarianou, Nikolaos Androulakis, Dimitrios Mavroudis, Maria Tzardi, John Souglakos
Summary: The study reveals that KRAS G12D mutation is associated with better overall survival, while KRAS G12C mutation may indicate worse prognosis in terms of progression-free and overall survival. KRAS exon 3 and exon 4 mutations also have different impacts on progression-free and overall survival.
Review
Cell Biology
Zining Zhang, Heng Zhang, Xiang Liao, Hsiang-i Tsai
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a common and aggressive type of pancreatic cancer with a poor survival rate. The highest mutation frequency in PDAC is observed in the KRAS gene, which plays a critical role in promoting cancer cell growth, resistance to therapy, and poor prognosis. This review focuses on the patterns of KRAS mutations in PDAC and highlights its role in signal transduction, metabolic reprogramming, therapy resistance, and prognosis, aiming to provide potential KRAS-targeted therapies for PDAC.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Editorial Material
Medicine, Research & Experimental
Renzo Boldorini, Nausicaa Clemente, Elisa Alchera, Rita Carini
Summary: Ischemia-reperfusion injury (IRI) following major liver surgery remains a challenging clinical problem. Activation of the endogenous hepatoprotection systems, such as through 'ischemic preconditioning', can mitigate the damaging effects of IRI. Recent research has identified a novel protective molecule, DUSP12, which shows promise as a therapeutic target for preventing hepatic IRI by inhibiting the ASK1/JNK-p38 MAPK pathway.
Review
Obstetrics & Gynecology
Rocco Olivadese, Antonio Ramponi, Renzo Boldorini, Giulia Dalla Dea, Andrea Palicelli
Summary: Cellular fibromas, accounting for around 10% of ovarian fibromas, usually have a benign clinical course. However, recurrence may occur after a long interval, warranting thorough sampling to exclude malignant areas in challenging cases.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
(2021)
Article
Virology
Cinzia Borgogna, Silvia Albertini, Licia Martuscelli, Filippo Poletti, Alessandro Volpe, Guido Merlotti, Vicenzo Cantaluppi, Renzo Boldorini, Marisa Gariglio
Summary: This study indicates a potential association between reactivation of BK polyomavirus (BKPyV) and cancer development in kidney transplant recipients (KTRs), particularly bladder carcinoma. By analyzing the pathological specimens of 10 clear cell renal cell carcinomas and 5 urinary bladder carcinomas from 15 KTRs using immunohistochemistry and FISH, the presence of BKPyV infection was confirmed in some cases.
Article
Oncology
Simona Crosta, Renzo Boldorini, Francesca Bono, Virginia Brambilla, Emanuele Dainese, Nicola Fusco, Andrea Gianatti, Vincenzo L'Imperio, Patrizia Morbini, Fabio Pagni
Summary: This study aimed to evaluate the performance of different PD-L1 staining protocols in head and neck squamous cell carcinoma, showing moderate interobserver reliability among the different protocols.
Review
Biochemistry & Molecular Biology
Elena Crisa, Paola Boggione, Maura Nicolosi, Abdurraouf Mokhtar Mahmoud, Wael Al Essa, Bassel Awikeh, Anna Aspesi, Annalisa Andorno, Renzo Boldorini, Irma Dianzani, Gianluca Gaidano, Andrea Patriarca
Summary: Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) present unique challenges in terms of prognosis and treatment, requiring early detection and hematopoietic stem cell transplantation to improve outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Andrea Palicelli, Lucia Giaccherini, Magda Zanelli, Maria Paola Bonasoni, Maria Carolina Gelli, Alessandra Bisagni, Eleonora Zanetti, Loredana De Marco, Federica Torricelli, Gloria Manzotti, Mila Gugnoni, Giovanni D'Ippolito, Angela Immacolata Falbo, Filomena Giulia Sileo, Lorenzo Aguzzoli, Valentina Mastrofilippo, Martina Bonacini, Federica De Giorgi, Stefano Ricci, Giuditta Bernardelli, Laura Ardighieri, Maurizio Zizzo, Antonio De Leo, Giacomo Santandrea, Dario de Biase, Moira Ragazzi, Giulia Dalla Dea, Claudia Veggiani, Laura Carpenito, Francesca Sanguedolce, Aleksandra Asaturova, Renzo Boldorini, Maria Giulia Disanto, Margherita Goia, Richard Wing-Cheuk Wong, Naveena Singh, Vincenzo Dario Mandato
Summary: Vulvar squamous cell carcinoma (VSCC) is the most common malignant vulvar tumor, with a peak incidence in the 7-8th decades of life, but can also occur in young women and pregnant patients. Treatment options for VSCCs diagnosed during pregnancy include before, after, or before-and-after delivery, with follow-up needed for patients. Larger cohorts and definite guidelines are necessary to determine the best treatment options for pregnant women with VSCC.
Article
Medicine, Research & Experimental
Rosanna Mezzapelle, Francesco De Marchis, Chiara Passera, Manuela Leo, Francesca Brambilla, Federica Colombo, Maura Casalgrandi, Alessandro Preti, Samuel Zambrano, Patrizia Castellani, Riccardo Ertassi, Marco Silingardi, Francesca Caprioglio, Veronica Basso, Renzo Boldorini, Angelo Carretta, Francesca Sanvito, Ottavio Rena, Anna Rubartelli, Lina Sabatino, Anna Mondino, Massimo P. Crippa, Vittorio Colantuoni, Marco E. Bianchi
Summary: Enhancing antitumor immunity is a powerful strategy in cancer treatment, involving the release of DAMPs and interfering with the CD47 signal to induce T-cell immune responses. Additionally, CXCR4 activation can also flag tumor cells for immune recognition.
EMBO MOLECULAR MEDICINE
(2021)
Article
Chemistry, Analytical
Elettra Barberis, Soni Joseph, Elia Amede, Michela Giulia Clavenna, Marta La Vecchia, Marika Sculco, Anna Aspesi, Pietro Occhipinti, Elisa Robotti, Renzo Boldorini, Emilio Marengo, Irma Dianzani, Marcello Manfredi
Summary: The development of colorectal cancer is highly influenced by the intestinal microbiota. Studying microbiota-produced metabolites can lead to new discoveries about the cancer. A high-throughput metabolomics method was developed to capture the metabolic complexity of microbiota metabolome adherent to adenomatous polyps and adenocarcinoma, showing great analytical performance and clinical potential.
ANALYTICA CHIMICA ACTA
(2021)
Article
Hematology
Riccardo Moia, Chiara Favini, Valentina Ferri, Gabriela Forestieri, Lodovico Terzi Di Bergamo, Mattia Schipani, Sruthi Sagiraju, Annalisa Andorno, Silvia Rasi, Ramesh Adhinaveni, Donatella Talotta, Wael Al Essa, Lorenzo De Paoli, Gloria Margiotta Casaluci, Andrea Patriarca, Renzo L. Boldorini, Davide Rossi, Gianluca Gaidano
Summary: By molecularly dissecting the anatomical heterogeneity of SLL, we found unique mutations in different compartments, with plasma ctDNA identifying additional mutations. The synchronous sources of tumor DNA complement each other in providing information on driver gene mutations in SLL, potentially offering prognostic and predictive value.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Otorhinolaryngology
Massimo Campagnoli, Michele Cerasuolo, Giorgio Arena, Valeria Dell'Era, Annalisa Andorno, Renzo Boldorini, Massimiliano Garzaro, Paolo Aluffi Valletti
Summary: Paragangliomas of the thyroid gland are rare and challenging to diagnose. Surgery is the primary treatment, with radiotherapy being considered in cases of suspected aggressive behavior. Patients should undergo systemic and genetic evaluation, and regular long-term follow-up is recommended due to the unpredictable nature of these lesions.
ENT-EAR NOSE & THROAT JOURNAL
(2021)
Article
Multidisciplinary Sciences
Steffen Grann Jensen, Samantha Epistolio, Cesilie Lind Madsen, Majbritt Hauge Kyneb, Alice Riva, Alessia Paganotti, Jessica Barizzi, Rasmus Koefoed Petersen, Michael Borgesen, Francesca Molinari, Renzo Boldorini, Jan Lorenzen, Erik Sorensen, Ulf Bech Christensen, Estrid Hogdall, Milo Frattini
Summary: The study evaluated the SensiScreen(R) EGFR Liquid assay platform for sensitivity, linearity, repeatability and accuracy for low ctDNA levels, comparing it to other established methods. Results showed that the platform has good sensitivity in detecting mutant alleles at a level as low as 1 copy.
Article
Oncology
E. Berrino, A. Balsamo, A. Pisacane, S. Gallo, P. Becco, U. Miglio, D. Caravelli, S. Poletto, L. Paruzzo, C. Debernardi, C. Piccinelli, A. Zaccagna, P. Rescigno, M. Aglietta, A. Sapino, F. Carnevale-Schianca, T. Venesio
Summary: This study found a highly heterogeneous BRAF VAF in melanoma patients, which was correlated with age, lymphocytic infiltration, melanoma thickness, and metastatic sites. A BRAF VAF >25% was associated with favorable outcomes in patients treated with anti-BRAF/anti-MEK therapy, acting as an independent prognostic factor in multivariate analysis.
Review
Oncology
Rosanna Mezzapelle, Manuela Leo, Francesca Caprioglio, Liam S. Colley, Andrea Lamarca, Lina Sabatino, Vittorio Colantuoni, Massimo P. Crippa, Marco E. Bianchi
Summary: Chemokines CXCL12 and its receptor CXCR4 play essential roles in cell migration, antigen recognition, and tumor immune response, which may provide new strategies for improving immunotherapies.
Article
Cell Biology
Enrico Berrino, Umberto Miglio, Sara Erika Bellomo, Carla Debernardi, Alberto Bragoni, Annalisa Petrelli, Eliano Cascardi, Silvia Giordano, Filippo Montemurro, Caterina Marchio, Tiziana Venesio, Anna Sapino
Summary: L1 reactivation is associated with aggressive features of breast cancer and worse clinical outcomes.
Article
Oncology
Alessandra Merlini, Maria Laura Centomo, Giulio Ferrero, Giulia Chiabotto, Umberto Miglio, Enrico Berrino, Giorgia Giordano, Silvia Brusco, Alberto Pisacane, Elena Maldi, Ivana Sarotto, Federica Capozzi, Cristina Lano, Claudio Isella, Giovanni Crisafulli, Massimo Aglietta, Angelo Paolo Dei Tos, Marta Sbaraglia, Dario Sangiolo, Lorenzo D'Ambrosio, Alberto Bardelli, Ymera Pignochino, Giovanni Grignani
Summary: The study identified an 8-gene expression signature to improve prediction of response to the trabectedin+olaparib combination in BSTS patients. The predictive role of these potential biomarkers warrants further investigation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pathology
Xiaobo Zhang, Chen Wang, Danhua Shen
Summary: This study investigated the Clinicopathological features and FH mutation in FH-dUL. FH-dUL is rare and the combination of predictive Clinicopathological evaluation, FH and 2SC IHC test, and molecular test were helpful for the screening of FH-dUL or even HLRCC.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Review
Pathology
Gaurav Dubey, Mithilesh Singh, Himmat Singh, Mohit Agarwal, Shailendra Singh Chandel, Anurag Mishra, Ravindra Pal Singh, Neelima Kukreti
Summary: SnoRNAs play a crucial role in autoimmune diseases, influencing gene expression, immune cell development, and immune regulation. They have the potential to be biomarkers or therapeutic targets for disease management. However, further research is needed to elucidate their precise molecular mechanisms.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Article
Pathology
P. Suhaj, D. Do, T. Olejar, R. Pichova, O. Lang, R. Matej
Summary: Pancreatic polypeptide cell hyperplasia (PPY-H) is a multiplication of neuroendocrine cells producing pancreatic polypeptide (PPY). The development and role of PPY-H still need to be further elucidated. This study analyzed 12 cases of PPY-H accompanying pancreatic neuroendocrine neoplasias (NEN) and found that gastrointestinal symptoms may be more related to PPY-H rather than NEN hormonal production. Strong SSTR2 expression in PPY-H suggests the potential utility of radiotracers in clinical diagnostics, but further studies are needed.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Article
Pathology
Ruyun Zhang, Xiaofei Liao, Bin Zhang, Xiaohong Huang, Guanjie Qin, Xiangyun Kong, Yuan Xie, Yunyan Mo, Jinxuan Dai, Chunqiao Gan, Zan Luo, Jingyan Lu, Wei Jiang
Summary: This study found that patients with high COV+TIL score had worse prognosis in nasopharyngeal carcinoma.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Review
Pathology
Waleed Hassan Almalki
Summary: Understanding the molecular pathways behind cardiovascular illnesses is crucial. Recent studies have revealed the role of Xist RNA in cardiovascular diseases, including epigenetic changes, gene expression, cellular identity, and sex chromosomal inactivation. Dysregulation of Xist RNA expression is associated with conditions such as atherosclerosis, hypertrophy, and cardiac fibrosis.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Article
Pathology
Yanxin Dong, Boshi Fan, Mingyang Li, Jiale Zhang, Shun Xie, Shouyin Dia, Qingge Jia, Taiqian Gong
Summary: Tescalcin (TESC) is upregulated in esophageal squamous carcinoma (ESCC) and is associated with poor prognosis, tumor infiltration, staging, and lymph node metastasis. TESC promotes proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression in ESCC, as well as activates the AKT pathway. TESC may serve as a prognostic factor and provide a new therapeutic strategy for ESCC.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Article
Pathology
Ozge Sukruoglu Erdogan, Demet Akdeniz Odemis, Zubeyde Yalniz Kayim, Orkun Gurbuz, Seref Bugra Tuncer, Seda Kilic, Betul Celik, Samuray Tuncer, Sema Buyukkapu Bay, Rejin Kebudi, Hulya Yazici
Summary: This study found that methylation of the RB1 gene promoter does not influence the hereditary transmission of familial retinoblastoma.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Review
Pathology
Syam Mohan, Mohammed Ageeli Hakami, Hamad Ghaleb Dailah, Asaad Khalid, Asim Najmi, Khalid Zoghebi, Maryam A. Halawi, Thaifallah Munahi Alotaibi
Summary: Cancer is a complex disease caused by multiple factors, and miR-155 plays a significant role as a regulator of the NF-kappa B signaling pathway, contributing to cancer development and progression.
PATHOLOGY RESEARCH AND PRACTICE
(2024)