Review
Biochemistry & Molecular Biology
Yoonkyung Won, Eunyoung Choi
Summary: This review summarizes the progress in genetically engineered mouse models for studying Kras gene in gastric, pancreatic, and colorectal cancers. These models have greatly contributed to understanding the role of Kras activation in the carcinogenic process in different cell lineages or organs, and the identification of potential molecular markers associated with Kras activation.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Junshu Li, Yanhong Ji, Na Chen, Huiling Wang, Chao Fang, Xiaonan Yin, Zhiyuan Jiang, Zhexu Dong, Dan Zhu, Jiamei Fu, Wencheng Zhou, Ruiyi Jiang, Ling He, Zhang Hantao, Gang Shi, Lin Cheng, Xiaolan Su, Lei Dai, Hongxin Deng
Summary: This study identified a specific upregulated lncRNA (SURC) in colorectal cancer (CRC), and its high expression was associated with poorer prognosis in CRC patients. Further investigation revealed that mutated adenomatous polyposis coli (APC) genes can promote the transcription of SURC by reducing the degradation of beta-catenin protein. Functional assays showed that knockdown of SURC impaired CRC cell proliferation and tumor growth. Additionally, SURC promotes CCND2 expression by inhibiting the expression of miR-185-5p in CRC cells.
Article
Medicine, Research & Experimental
Jungang Liu, Xiaoliang Huang, Haizhou Liu, Chunyin Wei, Haiming Ru, Haiquan Qin, Hao Lai, Yongsheng Meng, Guo Wu, Weishun Xie, Xianwei Mo, Caroline H. Johnson, Yawei Zhang, Weizhong Tang
Summary: This study revealed that KRAS mutation in CRC is associated with suppressed immune pathways and immune infiltration, with increased Tregs and decreased M1 macrophages and activated CD4 memory T cells. An immune risk model was established to classify CRC patients with distinct clinical outcomes based on gene expression and immune cell abundance.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Seo-Hyun Choi, Jin K. Kim, Chin-Tung Chen, Chao Wu, Michael R. Marco, Francisco M. Barriga, Kevin O'Rourke, Raphael Pelossof, Xuan Qu, Qing Chang, Elisa de Stanchina, Jinru Shia, J. Joshua Smith, Francisco Sanchez-Vega, Julio Garcia-Aguilar
Summary: KRAS-mutant colorectal cancer upregulates integrin a6/b4 to promote aggressive tumor behavior and lung metastasis, while knocking out ITGB4 diminishes these features and reduces pulmonary metastasis.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Joao Augusto Freitas, Irene Gullo, Diogo Garcia, Sara Miranda, Louisa Spaans, Lidia Pinho, Joana Reis, Fabiana Sousa, Manuela Baptista, Carlos Resende, Dina Leitao, Cecilia Duraes, Jose Luis Costa, Fatima Carneiro, Jose Carlos Machado
Summary: The study found that the sporadic colorectal ACS is characterized by a gradual decrease in immune cell counts, an increase in TMB and MHC-I expression, and lower PD-L1 expression. Similar patterns were observed in FAP lesions, with the exception of an increase in TMB along the ACS and lower Foxp3+ T cell counts in FAP LGD lesions compared to sporadic ones. PD-L1 expression decreased earlier in FAP lesions than in sporadic ones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Pariyada Tanjak, Amphun Chaiboonchoe, Tharathorn Suwatthanarak, Onchira Acharayothin, Kullanist Thanormjit, Jantappapa Chanthercrob, Thanawat Suwatthanarak, Bundit Wannasuphaphol, Kemmapon Chumchuen, Bhoom Suktitipat, Somponnat Sampattavanich, Krittiya Korphaisarn, Ananya Pongpaibul, Naravat Poungvarin, Harald Grove, Woramin Riansuwan, Atthaphorn Trakarnsanga, Asada Methasate, Manop Pithukpakorn, Vitoon Chinswangwatanakul
Summary: This study investigates the transcriptomic impact of KRAS mutations in colorectal cancers, focusing on the tumor microenvironment and pathways beyond metabolic deregulation. It is found that CRC patients with KRAS mutations are mainly enriched in CMS3 and exhibit specific immune gene signatures in an immunosuppressive TME, leading to worse overall survival. Activation of TGF beta signaling by KRAS mutations is associated with reduced pro-inflammatory and cytokine gene signatures, suppressing immune infiltration. Spatially resolved gene expression profiling suggests up-regulated immune suppression genes in the TME of KRAS-mutated CMS3-classified tissues. This study provides important insights into the complex transcriptomic profile of KRAS mutations in an immunosuppressive TME.
Article
Oncology
Kenechukwu Chudy-Onwugaje, Wen-Yi Huang, L. Joseph Su, Mark P. Purdue, Christine C. Johnson, Lingxiao Wang, Hormuzd A. Katki, Kathryn Hughes Barry, Sonja I. Berndt
Summary: In this study, a beneficial role for both aspirin and ibuprofen in preventing advanced adenoma and curbing progression to recurrence and cancer among older adults was observed during long-term follow-up.
Article
Oncology
Margherita Pergolizzi, Laura Bizzozero, Federica Maione, Elena Maldi, Claudio Isella, Marco Macagno, Elisa Mariella, Alberto Bardelli, Enzo Medico, Caterina Marchio, Guido Serini, Federica Di Nicolantonio, Federico Bussolino, Marco Arese
Summary: This study revealed that NLGN1 is expressed in human colorectal tumors and promotes CRC cell migration and metastasis. Mechanistically, NLGN1 promotes the localization of APC to the cell membrane, stimulates beta-catenin translocation to the nucleus, and induces an EMT phenotype in CRC cell lines. This novel finding suggests NLGN1 as a potential therapeutic target for CRC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Oxana Dmitrieva-Posocco, Andrea C. Wong, Patrick Lundgren, Aleksandra M. Golos, Helene C. Descamps, Lenka Dohnalova, Zvi Cramer, Yuhua Tian, Brian Yueh, Onur Eskiocak, Gabor Egervari, Yemin Lan, Jinping Liu, Jiaxin Fan, Jihee Kim, Bhoomi Madhu, Kai Markus Schneider, Svetlana Khoziainova, Natalia Andreeva, Qiaohong Wang, Ning Li, Emma E. Furth, Will Bailis, Judith R. Kelsen, Kathryn E. Hamilton, Klaus H. Kaestner, Shelley L. Berger, Jonathan A. Epstein, Rajan Jain, Mingyao Li, Semir Beyaz, Christopher J. Lengner, Bryson W. Katona, Sergei I. Grivennikov, Christoph A. Thaiss, Maayan Levy
Summary: The study identifies a metabolite signalling pathway that can be used as a strategy for preventing and treating colorectal cancer. Ketogenic diets and the ketone body BHB show a strong inhibitory effect on tumor growth by reducing cell proliferation. The findings suggest that BHB-triggered pathway could play a crucial role in regulating intestinal tumorigenesis.
Article
Biochemistry & Molecular Biology
Felix Manirakiza, Eric Rutaganda, Hidetaka Yamada, Yuji Iwashita, Belson Rugwizangoga, Benoit Seminega, Vincent Dusabejambo, Gervais Ntakirutimana, Deogratias Ruhangaza, Annette Uwineza, Kazuya Shinmura, Haruhiko Sugimura
Summary: Cancer research in Rwanda is lacking, especially in regards to colorectal cancer (CRC). This study aimed to investigate the mutational status of CRC tissues in Rwandan patients and compare it with other populations. Sanger sequencing was performed on adenocarcinoma samples from 54 patients, revealing new mutations in APC, HOXB13, and KRAS genes. The findings contribute to genetic variation data and clinicopathological information on CRC in Rwanda.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Review
Medical Laboratory Technology
Yu-Shen Yang, Chu-Yun Liu, Dan Wen, Da-Zhi Gao, Shu Lin, He-Fan He, Xue-Feng Zhao
Summary: Despite progress in prevention and treatment, colorectal cancer remains a common malignancy worldwide. Various mouse models, including transplant mouse models, have been established to study the characteristics of colorectal cancer and its clinical behavior and therapeutic progress.
TRANSLATIONAL RESEARCH
(2022)
Article
Oncology
Jianlei Wang, Jianping Song, Zeyang Liu, Tingxiao Zhang, Yanfeng Liu
Summary: This study investigates the prognostic value of tumor mutation burden (TMB) in colorectal cancer (CRC) and finds that high TMB indicates better prognosis for CRC patients with KRAS mutations. The study also develops a prognostic model using TMB as a predictive indicator, which shows good accuracy and potential clinical applications.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Donatella Lucchetti, Ina Valeria Zurlo, Filomena Colella, Claudio Ricciardi-Tenore, Mariantonietta Di Salvatore, Giampaolo Tortora, Ruggero De Maria, Felice Giuliante, Alessandra Cassano, Michele Basso, Antonio Crucitti, Ilaria Laurenzana, Giulia Artemi, Alessandro Sgambato
Summary: Liquid biopsy using circulating exosomes DNA has shown clinical utility in managing metastatic colorectal cancer (mCRC) patients. The study found a correlation between disease progression and exosomes level, as well as a prognostic value of KRAS mutational status. Additionally, a high percentage of mutated mCRC patients reverted back to wild type after chemotherapy, but many cases reverted back to mutated status upon disease progression.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Naoki Yorita, Ryo Yuge, Hidehiko Takigawa, Atsushi Ono, Toshio Kuwai, Kazuya Kuraoka, Yasuhiko Kitadai, Shinji Tanaka, Kazuaki Chayama
Summary: This study found that the combination of anti-PD-1 antibody and imatinib has an anti-tumor effect on excluded-type tumors in colorectal cancer. The combination therapy suppressed stromal reaction and increased the number of CD8-positive T cells in the tumor nest, suggesting potential efficacy for CRC cases resistant to anti-PD-1 monotherapy.
Article
Oncology
John R. P. Knight, Constantinos Alexandrou, George L. Skalka, Nikola Vlahov, Kathryn Pennel, Leah Officer, Ana Teodosio, Georgios Kanellos, David M. Gay, Sebastian May-Wilson, Ewan M. Smith, Arafath K. Najumudeen, Kathryn Gilroy, Rachel A. Ridgway, Dustin J. Flanagan, Rachael C. L. Smith, Laura McDonald, Craig MacKay, Anne Cheasty, Kerri McArthur, Emma Stanway, Joshua D. Leach, Rene Jackstadt, Joseph A. Waldron, Andrew D. Campbell, Georgios Vlachogiannis, Nicola Valeri, Kevin M. Haigis, Nahum Sonenberg, Christopher G. Proud, Neil P. Jones, Martin E. Swarbrick, Heather J. McKinnon, William J. Faller, John Le Quesne, Joanne Edwards, Anne E. Willis, Martin Bushell, Owen J. Sansom
Summary: KRAS-mutant colorectal cancers exhibit resistance to therapeutics, but targeting the mTORC1 and MNK pathways can sensitize them to rapalogs. This approach has shown effectiveness in mouse models and human organoids, offering a potential strategy for patients with elevated c-MYC expression.
Article
Biochemistry & Molecular Biology
Stephanie A. Atkinson, James C. Fleet
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Erica Mandell, Sharon Ryan, Gregory J. Seedorf, Tania Gonzalez, Steven H. Abman, James C. Fleet
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
J. C. Fleet, G. N. Burcham, R. D. Calvert, B. D. Elzey, T. L. Ratliff
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
H. Jiang, R. L. Horst, N. J. Koszewski, J. P. Goff, S. Christakos, J. C. Fleet
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
James C. Fleet, Perla Reyes-Fernandez
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
James C. Fleet, Dennis Aldea, Lei Chen, Sylvia Christakos, Michael Verzi
Summary: This study identified the regulatory sites controlling intestine-specific Vdr gene expression using ATAC-Seq technology. The results showed that these sites vary during intestinal development and are associated with intestinal transcription factors. Comparison with DNAse-Seq data from other tissues revealed that these regulatory sites are highly conserved in humans as well.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Zachary K. Criss, Nobel Bhasin, Sara C. Di Rienzi, Anubama Rajan, Kali Deans-Fielder, Ganesh Swaminathan, Nabiollah Kamyabi, Xi-Lei Zeng, Harsha Doddapaneni, Vipin K. Menon, Deepavali Chakravarti, Clarissa Estrella, Xiaomin Yu, Ketki Patil, Joseph F. Petrosino, James C. Fleet, Michael P. Verzi, Sylvia Christakos, Michael A. Helmrath, Sumimasa Arimura, Ronald A. DePinho, Robert A. Britton, Anthony W. Maresso, K. Jane Grande-Allen, Sarah E. Blutt, Sue E. Crawford, Mary K. Estes, Sasirekha Ramani, Noah F. Shroyer
Summary: The study investigated the impact of common variations in culture methods on the transcriptome of human intestinal epithelial organoids, finding that substrate and format had the largest effects on transcriptomic variation, while patient heterogeneity and specific experimental manipulations had smaller effects. Results show that variations in culture conditions can significantly influence intestinal organoids and should be considered when designing experiments and comparing results between laboratories.
PHYSIOLOGICAL GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Rohit Aita, Dennis Aldea, Sohaib Hassan, Joseph Hur, Oscar Pellon-Cardenas, Evan Cohen, Lei Chen, Noah Shroyer, Sylvia Christakos, Michael P. Verzi, James C. Fleet
Summary: This study used RNA-seq and ChIP-seq to investigate the effects of VD on gene expression and VDR genomic binding in different compartments of the intestine. The results showed that VD regulated the expression of shared and compartment-specific transcripts in the small intestine crypt, small intestine villi, and colon. Bioinformatic analysis identified unique biological functions regulated by VD in each compartment. Additionally, VDR-binding sites were found to be associated with upregulated genes in the colon and small intestine villi. These findings provide insights into the spatial patterns and mechanisms of VD action in the intestine.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Nutrition & Dietetics
James C. Fleet
Summary: Vitamin D plays a critical role in regulating calcium and bone homeostasis, especially in the absorption of calcium in the intestines. The intestinal absorption of calcium is regulated by the hormone 1,25 dihydroxyvitamin D, which activates gene transcription by binding to the intestinal vitamin D receptor. Various physiological and disease states can affect the regulation of intestinal calcium absorption by vitamin D.
Article
Endocrinology & Metabolism
Heng Jiang, Krittikan Chanpaisaeng, Sylvia Christakos, James C. Fleet
Summary: This study investigated the role of vitamin D receptor-mediated 1,25(OH)(2)D-3 signaling in adult calcium absorption and bone health. The results showed that intestinal vitamin D receptor prevents bone loss under low calcium intake but is dispensable under adequate calcium intake.
Article
Endocrinology & Metabolism
Krittikan Chanpaisaeng, Perla C. Reyes-Fernandez, Brian Dilkes, James C. Fleet
Summary: Genetics and dietary calcium both play critical roles in regulating bone mass and microarchitecture, with genetics impacting bone traits significantly and influencing the physiological response of bone to dietary calcium restriction. The study identified novel genetic loci controlling bone mass/microarchitecture and their adaptation to inadequate dietary calcium intake.
Article
Biochemistry & Molecular Biology
Shanshan Li, Jessica De La Cruz, Steven Hutchens, Somshuvra Mukhopadhyay, Zachary K. Criss, Rohit Aita, Oscar Pellon-Cardenas, Joseph Hur, Patricia Soteropoulos, Seema Husain, Puneet Dhawan, Lieve Verlinden, Geert Carmeliet, James C. Fleet, Noah F. Shroyer, Michael P. Verzi, Sylvia Christakos
Summary: Transgenic expression of vitamin D receptor (VDR) in the distal intestine is crucial for normalizing serum calcium levels and rescuing rickets in VDR null mice. The activation of certain genes in the proximal and distal intestine by 1,25(OH)(2)D-3 indicates an interrelationship between vitamin D and intestinal calcium transport. Additionally, the conservation of the effects of 1,25(OH)(2)D-3 in mice and humans suggests a significant role of distal intestinal segments in vitamin D action.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Meeting Abstract
Endocrinology & Metabolism
James Fleet, Sylvia Christakos, Michael Verzi
JOURNAL OF BONE AND MINERAL RESEARCH
(2020)
Meeting Abstract
Endocrinology & Metabolism
Heng Jiang, Sylvia Christakos, James Fleet
JOURNAL OF BONE AND MINERAL RESEARCH
(2020)
Review
Cell Biology
Paloma E. Garcia, Michael K. Scales, Benjamin L. Allen, Marina Pasca di Magliano
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.