Article
Oncology
Mark Primeaux, Xiangdong Liu, Saiprasad Gowrikumar, Iram Fatima, Kurt W. Fisher, Dhundy Bastola, Alex J. Vecchio, Amar B. Singh, Punita Dhawan
Summary: High expression of CLDN1 in CRC is associated with cancer stemness and chemoresistance signaling pathways. CLDN1 promotes stemness and chemoresistance through a direct interaction with EPHA2 tyrosine kinase.
Article
Oncology
Zachary R. Visco, Gregory Sfakianos, Carole Grenier, Marie-Helene Boudreau, Sabrina Simpson, Isabel Rodriguez, Regina Whitaker, Derek Y. Yao, Andrew Berchuck, Susan K. Murphy, Zhiqing Huang
Summary: The study found a stronger correlation between Claudin-1 (CLDN1) expression and methylation in recurrent and primary ovarian cancer. This inverse correlation was more prominent in short-term survivors and recurrent tumors, indicating its potential predictive value for disease prognosis. The relationship between CLDN1 methylation and expression plays a crucial role in ovarian cancer aggressiveness and recurrence.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Saiprasad Gowrikumar, Mark Primeaux, Kristina Pravoverov, Chao Wu, Bryan C. Szeglin, Charles-Etienne Gabriel Sauve, Ishwor Thapa, Dhundy Bastola, Xi Steven Chen, J. Joshua Smith, Amar B. Singh, Punita Dhawan
Summary: Identifying a molecular signature based on claudin-1 and claudin-7 can help predict patient survival and response to treatment in colorectal cancer. This signature is associated with poor prognosis and characteristics of treatment-resistant CRC.
Article
Chemistry, Medicinal
Zhuming Zhang, Avijit Ghosh, Peter J. Connolly, Peter King, Thomas Wilde, Jianyao Wang, Yawei Dong, Xueliang Li, Daohong Liao, Hao Chen, Gaochao Tian, Javier Suarez, William G. Bonnette, Vineet Pande, Karen A. Diloreto, Yifan Shi, Shefali Patel, Beth Pietrak, Lawrence Szewczuk, Carlo Sensenhauser, Shannon Dallas, James P. Edwards, Kurtis E. Bachman, David C. Evans
Summary: This study reported a series of gut-restricted, selective COX-2 inhibitors characterized by high colonic exposure and minimized systemic exposure, showing significant inhibition of adenoma progression and survival extension in an APC(min/+) mouse model. However, their chemoprotective effects were mainly driven by systemic COX-2 inhibition, resulting in less than expected efficacies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yue Chen, LvYuwei Tang, Xinrong Ye, Yimeng Chen, Enfang Shan, Hongyu Han, Caiyun Zhong
Summary: This study reveals for the first time the interaction between ZO-1 and beta-catenin in colorectal cancer stem cells. ZO-1 can inhibit sphere formation and expression of CSC markers, thus attenuating the progression of colorectal cancer.
Article
Cell Biology
Wei Liu, Jin Meng, Rongjun Su, Changjun Shen, Shuai Zhang, Yantao Zhao, Wenqi Liu, Jiang Du, Shuai Zhu, Pan Li, Zhigang Wang, Xiaoxia Li
Summary: This study elucidates the mechanism by which long non-coding RNA TUG1 promotes tumor formation in colorectal cancer. SP1 regulates TUG1 and the miR-421/KDM2A/ERK axis, providing novel insights into the development of colorectal cancer.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Hideki Chiba, Naoki Ichikawa-Tomikawa, Tetsuya Imura, Kotaro Sugimoto
Summary: The neurovascular unit (NVU) is a complex structure consisting of different types of cells, with microvascular endothelial cells and pericytes playing a crucial role in maintaining the blood-brain barrier (BBB). CLDN5, the most abundantly expressed tight-junction protein in brain microvascular endothelial cells, is essential for BBB integrity and its regional dysregulation may contribute to CNS disorders. The link between cell adhesion and transcription factor signalings, particularly involving CLDN5-adhesion signaling, is explored as a potential mechanism in brain health and disorders.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Iram Fatima, Jaya Prakash Uppada, Yashpal S. Chhonker, Saiprasad Gowrikumar, Susmita Barman, Sourav Roy, Kirsten T. Tolentino, Nicholas Palermo, Amar Natarajan, Daniel R. Beauchamp, Alex Vecchio, Daryl J. Murry, Amar B. Singh, Corey R. Hopkins, Punita Dhawan
Summary: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and there is an urgent need for developing novel and targeted therapies to inhibit CRC progression and metastasis. Through rigorous analysis and testing, we identified a specific inhibitor called PDS-0330, which can inhibit claudin-1-dependent CRC progression and has favorable pharmacokinetic properties. In conclusion, our study suggests that PDS-0330 interferes with the association of claudin-1 and Src to inhibit CRC progression and metastasis.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cell Biology
Mai Iwaya, Hiroyuki Hayashi, Tomoyuki Nakajima, Kazuyuki Matsuda, Yasuhiro Kinugawa, Yosuke Tobe, Yoko Tateishi, Yugo Iwaya, Takeshi Uehara, Hiroyoshi Ota
Summary: CLDN18 expression in CACs is associated with lymph node metastasis, MUC5AC expression, and loss of special AT-rich sequence-binding protein 2 expression. CACs are more likely to express CLDN18 compared to CRCs, while only a small percentage of CACs are immunoreactive for HER2 with no differences identified in sporadic CRCs. These findings suggest potential candidates for targeted zolbetuximab therapy among certain CAC cases.
Review
Oncology
Ali Zubair Siddiqui, Khaldoun Almhanna
Summary: Gastric and esophageal cancers are often diagnosed at an advanced stage, leading to poor prognoses. Treatment options prioritize improving survival and quality of life, with ongoing research focusing on targeted therapies to exploit oncogenic tendencies and enhance patient outcomes. The development of new treatment alternatives and the investigation of potential biomarkers aim to address the unmet needs of these lethal cancers.
Article
Oncology
Matjaz Rokavec, Stephanie Jaeckel, Heiko Hermeking
Summary: The study found that NID1 is associated with poor prognosis and advanced tumor stage in colorectal cancer (CRC) patients, and its receptor ITGAV represents a potential therapeutic target for CRC.
Article
Multidisciplinary Sciences
Hibah Shaath, Salman M. Toor, Mohamed Abu Nada, Eyad Elkord, Nehad M. Alajez
Summary: The study revealed alterations in miRNA, mRNA, and lncRNA expression in CRC, identified activated signaling networks and characteristics in CRC through computational analysis and functional annotation. It also uncovered complex associations between miRNAs and mRNAs as well as potential interactions between lncRNAs and miRNAs.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Bohan Chen, Yiping Ma, Jinfang Bi, Wenbin Wang, Anshun He, Guangsong Su, Zhongfang Zhao, Jiandang Shi, Lei Zhang
Summary: The study revealed the regulatory network of colorectal-cancer-specific enhancers, which are associated with changes in over 50% of the topological associated domains (TADs) and interact with 152 genes that are significantly highly expressed in colorectal cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Chen Wang, Na Wu, Beibei Pei, Xiaoyan Ma, Wenhui Yang
Summary: Due to lack of timely and accurate screening methods and treatments, pancreatic cancer patients often experience rapid disease progression. The claudin family, specifically expressed in tight junctions of various tumors including pancreatic cancer, can affect tumor progression by altering cell junctions. Some members of the claudin family, such as claudin-18.2 and claudin-4, are significantly dysregulated in pancreatic tumors and have been implicated in diagnosis and treatment. Different targets of claudin proteins, combined with chemotherapy, can enhance tumor cell necrosis and inhibit invasion and metastasis. This literature review focuses on the functional characteristics and clinical applications of claudin proteins in pancreatic cancer cells, with particular attention to claudin-18.2 and claudin-4.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jun Tian, Jonathan H. H. Chen, Sherry X. X. Chao, Karin Pelka, Marios Giannakis, Julian Hess, Kelly Burke, Vjola Jorgji, Princy Sindurakar, Jonathan Braverman, Arnav Mehta, Tomonori Oka, Mei Huang, David Lieb, Maxwell Spurrell, Jill N. N. Allen, Thomas A. A. Abrams, Jeffrey W. W. Clark, Andrea C. C. Enzinger, Peter C. C. Enzinger, Samuel J. J. Klempner, Nadine J. J. McCleary, Jeffrey A. A. Meyerhardt, David P. P. Ryan, Matthew B. B. Yurgelun, Katie Kanter, Emily E. E. Van Seventer, Islam Baiev, Gary Chi, Joy Jarnagin, William B. B. Bradford, Edmond Wong, Alexa G. G. Michel, Isobel J. J. Fetter, Giulia Siravegna, Angelo J. J. Gemma, Arlene Sharpe, Shadmehr Demehri, Rebecca Leary, Catarina D. D. Campbell, Omer Yilmaz, Gad A. A. Getz, Aparna R. R. Parikh, Nir Hacohen, Ryan B. B. Corcoran
Summary: Combining PD-1, BRAF, and MEK inhibitors in BRAF(V600E) colorectal cancer patients resulted in a favorable overall response rate and durability. Translational analyses suggest that induction of tumor-intrinsic immune programs contributes to improved outcomes via MAPK inhibition.