scholarly journals Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies

2021 ◽  
Vol 15 (3) ◽  
pp. 201-217
Author(s):  
John C Flickinger ◽  
Jeffrey A Rappaport ◽  
Joshua R Barton ◽  
Trevor R Baybutt ◽  
Amanda M Pattison ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Unmet Need ◽  
Special Focus ◽  
Guanylyl Cyclase C ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Malignancies ◽  
Gastrointestinal Malignancy ◽  
Pancreatic Cancers ◽  
Current State ◽  
High Fraction

Gastrointestinal cancers encompass a diverse class of tumors arising in the GI tract, including esophagus, stomach, pancreas and colorectum. Collectively, gastrointestinal cancers compose a high fraction of all cancer deaths, highlighting an unmet need for novel and effective therapies. In this context, the transmembrane receptor guanylyl cyclase C (GUCY2C) has emerged as an attractive target for the prevention, detection and treatment of many gastrointestinal tumors. GUCY2C is an intestinally-restricted protein implicated in tumorigenesis that is universally expressed by primary and metastatic colorectal tumors as well as ectopically expressed by esophageal, gastric and pancreatic cancers. This review summarizes the current state of GUCY2C-targeted modalities in the management of gastrointestinal malignancies, with special focus on colorectal cancer, the most incident gastrointestinal malignancy.

scholarly journals Consistent expression of guanylyl cyclase-C in primary and metastatic gastrointestinal cancers

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0189953 ◽  
Author(s):  
Hadi Danaee ◽  
Thea Kalebic ◽  
Timothy Wyant ◽  
Matteo Fassan ◽  
Claudia Mescoli ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Guanylyl Cyclase C ◽  
Gastrointestinal Cancers

Adoptive Cell Therapy for Gastrointestinal Cancers

2020 ◽  
Vol 04 (04) ◽  
pp. 345-350
Author(s):  
Ryan J. Slovak ◽  
Hyun S. Kim
Keyword(s):  
Cell Therapy ◽  
Clinical Research ◽  
Solid Tumors ◽  
Immune Cells ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Hematologic Malignancies ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Malignancies ◽  
Specific Antigens

AbstractThe reinfusion of autologous or allogeneic immune cells that have been educated and/or engineered ex vivo to respond to tumor-specific antigens is termed “adoptive cell therapy.” While adoptive cell therapy has made tremendous strides in the treatment of hematologic malignancies, its utilization for solid tumors has lagged somewhat behind. The purpose of this article is to concisely review the clinical research that has been done to investigate adoptive cell therapy as a treatment for gastrointestinal malignancies.

scholarly journals In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4147
Author(s):  
Neha Gupta ◽  
Saurav Kumar Choudhary ◽  
Neeta Bhagat ◽  
Muthusamy Karthikeyan ◽  
Archana Chaturvedi
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Guanylyl Cyclase ◽  
Extracellular Domain ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Guanylyl Cyclase C ◽  
Amino Acid Residues ◽  
Lead Compounds

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

Image-Guided Intratumoral Delivery of Immunotherapeutics in Gastrointestinal Malignancies

2021 ◽  
Author(s):  
Yang Qiao ◽  
Rahul A. Sheth ◽  
Alda Tam
Keyword(s):  
Viral Vectors ◽  
Adaptive Immune System ◽  
Clinical Development ◽  
Gastrointestinal Malignancies ◽  
Robust Immune Response ◽  
Image Guided ◽  
Current State ◽  
Specific Antigens ◽  
Promising Treatment ◽  
Intratumoral Delivery

AbstractIntratumoral (IT) administration of immunotherapy is a promising treatment strategy under clinical development for gastrointestinal malignancies. Due to its targeted nature, IT immunotherapies can generate regional proinflammatory microenvironments that result in the focal recruitment of tumor-specific immune cells. Precision targeting of tumors via IT immunotherapy injection theoretically produces a more robust immune response to the treated tumor itself and to distant metastatic tumors that share tumor-specific antigens with those of the treated tumor, while also minimizing the priming of the adaptive immune system to nonspecific antigens. Diverse arrays of IT immunotherapeutic agents including but not limited to lyophilized bacteria, viral vectors, cellular-based agents, molecules, and peptides, both as monotherapies and in combination with systemic immunotherapies, are in various stages of preclinical and clinical development. In this review, we summarize the current state of the art for IT immunotherapy and highlight potential future directions and their relevance to image-guided interventionalists.

Identification of a binding region onEscherichia coli heat-stable enterotoxin to intestinal guanylyl cyclase C

1997 ◽  
Vol 4 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Makoto Hasegawa ◽  
Yuki Kawano ◽  
Kazuya Matsumoto ◽  
Yuji Hidaka ◽  
Takashi Sato ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Guanylyl Cyclase C ◽  
Binding Region ◽  
Heat Stable

Evaluation of Guanylyl Cyclase C Lymph Node Status for Colon Cancer Staging and Prognosis

2011 ◽  
Vol 18 (12) ◽  
pp. 3261-3270 ◽  
Author(s):  
Daniel J. Sargent ◽  
Murray B. Resnick ◽  
Michael O. Meyers ◽  
Atoussa Goldar-Najafi ◽  
Thomas Clancy ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Lymph Node ◽  
Guanylyl Cyclase ◽  
Cancer Staging ◽  
Lymph Node Status ◽  
Guanylyl Cyclase C ◽  
Node Status
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