Review
Oncology
Axel Bengtsson, Roland Andersson, Jonas Rahm, Karthik Ganganna, Bodil Andersson, Daniel Ansari
Summary: This review outlines the most important challenges in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging, and liquid handling robotics. An optimized organoid workflow inspired by all technical solutions presented in the article is also proposed.
Article
Oncology
Jaqueline Loaeza-Loaeza, Berenice Illades-Aguiar, Oscar del Moral-Hernandez, Yaneth Castro-Coronel, Marco A. Leyva-Vazquez, Roberto Dircio-Maldonado, Julio Ortiz-Ortiz, Daniel Hernandez-Sotelo
Summary: This study analyzed the methylation of 8 genes involved in maintaining cell normality and found that high CIMP is significantly associated with the risk of HSIL and CC.
CLINICAL EPIGENETICS
(2022)
Review
Oncology
Xiaofei Zhang, Wenjun Zhang, Pingan Cao
Summary: As the population ages in China, the incidence of colorectal cancer is on the rise, with CpG island methylator phenotype (CIMP) playing an important role in its development. Recent studies have shown a close relationship between CIMP and specific clinicopathological phenotypes and multiple molecular phenotypes in colorectal cancer. This paper introduces the latest progress on CIMP colorectal cancer in terms of chemotherapeutic drugs, targeted agents, and small molecular methylation inhibitors, aiming to provide potential clinical treatment strategies for personalized and precise treatment of colorectal cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Zeenat Jahan, Fahad A. Benthani, Nicola Currey, Hannah W. Parker, Jane E. Dahlstrom, C. Elizabeth Caldon, Maija R. J. Kohonen-Corish
Summary: DNA hypermethylation can cause gene silencing, which is an important mechanism in promoting cancer. This study found that MCC gene silencing is present in a subset of colorectal cancers that display high levels of methylation. The absence or reduction of MCC expression was also observed in tumors with hypomethylated regions of the gene. In cell culture experiments, the deletion of MCC increased the sensitivity of cancer cells to the chemotherapy drug irinotecan, and this effect was further enhanced by a targeted cancer drug, Olaparib. The findings suggest that MCC methylation may be a valuable biomarker for identifying colorectal cancers suitable for irinotecan therapy, potentially in combination with PARP inhibitors.
Article
Oncology
Irene Fernandez-De-Los-Reyes, Marisa Gomez-Dorronsoro, Inaki Monreal-Santesteban, Agustin Fernandez-Fernandez, Mario Fraga, Pablo Azcue, Laura Alonso, Beatriz Fernandez-Marlasca, Javier Suarez, Alicia Cordoba-Iturriagagoitia, David Guerrero-Setas
Summary: This study discovered the presence of aberrant methylation in genes associated with CMS classification in colon cancer. It is the first evidence that ZEB1 is hypermethylated in colon cancer and this alteration serves as an independent factor for good prognosis.
CLINICAL EPIGENETICS
(2023)
Review
Medicine, General & Internal
Eisuke Iwasaki, Seiichiro Fukuhara, Masayasu Horibe, Shintaro Kawasaki, Takashi Seino, Yoichi Takimoto, Hiroki Tamagawa, Yujiro Machida, Atsuto Kayashima, Marin Noda, Hideyuki Hayashi, Takanori Kanai
Summary: Pancreatic cancer is a deadly solid malignancy that often does not respond to traditional chemotherapy, highlighting the urgent need for personalized medicine. While personalized treatments for pancreatic cancer are still in development, the integration of genomic testing and high-throughput drug sensitivity testing in precision medicine is expected to revolutionize the treatment of this disease.
Article
Cell Biology
Cheng Du, XinLi Liu, Mingwei Li, Yi Zhao, Jie Li, Zhikang Wen, Min Liu, Meina Yang, Boshi Fu, Minjie Wei
Summary: The study revealed a close connection between 5mC regulators and oncogenic pathways in colon cancer, with a specific gene signature identified for colorectal cancer diagnosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Dannel Yeo, Althea Bastian, Heidi Strauss, Payal Saxena, Peter Grimison, John E. J. Rasko
Summary: This review summarizes the data on the utility of CTCs in PDAC and discusses the molecular profiling and culture methods of CTCs. CTCs have the potential to be used in screening, early diagnosis, prognostic assessment, and personalized management of PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Josephine Yates, Valentina Boeva
Summary: This study utilized a pan-cancer approach to define and explore CpG island methylator phenotype (CIMP) in 26 cancer types. The results confirmed the existence of CIMP in 19 cancers, showed its association with survival differences in eight cancer types, and identified potential drivers of CIMP. The study also found that CIMP was strongly correlated with tumor microenvironment characteristics.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Gastroenterology & Hepatology
Shounak Majumder, William R. Taylor, Patrick H. Foote, Brianna J. Gysbers, Xiaoming Cao, Douglas W. Mahoney, Kelli N. Burger, Karen A. Doering, Rondell P. Graham, Fergus J. Couch, Gloria M. Petersen, John B. Kisiel
Summary: This study compares the distribution of MDMs in tissue samples from PDAC cases carrying germline mutations with non-carriers, demonstrating high discrimination similar to sporadic PDAC. These results provide a scientific rationale for studying plasma MDMs in high-risk individuals with the aim of developing a minimally-invasive early detection test.
Review
Biochemistry & Molecular Biology
Susan Morand, Monika Devanaboyina, Hannah Staats, Laura Stanbery, John Nemunaitis
Summary: Response to immunotherapy in ovarian cancer is limited, but stratification by tumor biomarkers may improve predictiveness. Future directions include utilizing these biomarkers to select ideal candidates, increasing the likelihood of success with immunotherapy in ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Manoj Kumar Gupta, He Peng, Yang Li, Cheng-Jian Xu
Summary: Epigenetics serves as a connection between genetic and environmental factors, and DNA methylation, in particular, has been associated with many immune-related diseases. It has great potential for personalized medicine in disease prevention, diagnosis, and treatment.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Chemistry, Medicinal
Alessandro Di Federico, Valentina Tateo, Claudia Parisi, Francesca Formica, Riccardo Carloni, Giorgio Frega, Alessandro Rizzo, Dalia Ricci, Mariacristina Di Marco, Andrea Palloni, Giovanni Brandi
Summary: Pancreatic cancer is a challenging disease with a complex genomic landscape that affects tumor microenvironment, leading to tumor growth and drug resistance. Despite chemotherapy being the mainstay of treatment, personalized medicine has shown promising results with some drugs.
Article
Gastroenterology & Hepatology
Cancan Zhou, Nancy Porter, Michael Borges, Christian Gauthier, Lindsey Ferguson, Bo Huang, Neha Nanda, Jin He, Daniel Laheru, Ralph H. Hruban, Michael Goggins, Alison P. Klein, Nicholas J. Roberts
Summary: This study did not find evidence of germline promoter methylation for the pancreatic susceptibility genes ATM, BRCA1, and BRCA2 in patients with pancreatic cancer, indicating that constitutive germline methylation of promoter CpG islands is rare in pancreatic cancer.
Review
Oncology
Nayeralsadat Fatemi, Sascha Tierling, Hamidreza Aboulkheyr Es, Maryam Varkiani, Ehsan Nazemalhosseini Mojarad, Hamid Asadzadeh Aghdaei, Joern Walter, Mehdi Totonchi
Summary: Colorectal cancer, the second leading cause of cancer death worldwide, is closely associated with epigenetic changes such as DNA methylation. Studies have shown that DNA methylation markers have high accuracy and reproducibility in noninvasive biosamples, making them promising for early diagnosis and personalized treatment of CRC. Further research and development of methylation biomarkers and detection methods are crucial for CRC diagnosis.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Bhuwan Giri, Anthony Ferrantella, Prateek Sharma, Tejeshwar Jain, Harrys K. C. Jacob, Shrey Modi, Saba Kurtom, Pooja Roy, Vrishketan Sethi, Sulagna Banerjee, Nipun Merchant, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
Summary: The study developed a clinically relevant and immunocompetent model of PDAC resection that recapitulates human disease in morphology and recurrence patterns. This model can be used to evaluate therapy and study factors responsible for disease recurrence, providing a useful tool for clinical scenarios associated with surgical resection.
JOURNAL OF GASTROINTESTINAL SURGERY
(2021)
Article
Chemistry, Analytical
Joon Soo Park, Thomas Pisanic, Ye Zhang, Tza-Huei Wang
Summary: LiNC PCR is a novel strategy for achieving high-dimensional multiplexing in PCR assays, utilizing a simple ligation reaction and target-specific multicolor fluorescence signals for identifying amplified targets.
ANALYTICAL CHEMISTRY
(2021)
Review
Immunology
Tejeshwar Jain, Prateek Sharma, Abhi C. Are, Selwyn M. Vickers, Vikas Dudeja
Summary: Microbiome has significant impacts on tumor biology, affecting tumor initiation and progression, response to therapies, and disease prognosis. Modulation of the microbiome can enhance immunotherapy efficacy and reduce toxicity, highlighting its importance in cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Marina Baretti, Enusha Karunasena, Marianna Zahurak, Rosalind Walker, Yang Zhao, Thomas R. Pisanic, Tza-Huei Wang, Tim F. Greten, Austin G. Duffy, Elske Gootjes, Gerrit Meijer, Henk M. W. Verheul, Nita Ahuja, James G. Herman, Nilofer S. Azad
Summary: A Phase 2 trial of gemcitabine and docetaxel in patients with CHFR-methylated, MSI-high CRC did not show tumor responses according to RECIST criteria. The median progression-free survival was 1.79 months, and the median overall survival was 15.67 months. Despite the negative results, this study demonstrates the potential of using epigenetic biomarkers as inclusion criteria for optimizing combinatorial strategies in personalized medicine.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Biophysics
Pengfei Zhang, Liben Chen, Jiumei Hu, Alexander Y. Trick, Fan-En Chen, Kuangwen Hsieh, Yang Zhao, Branch Coleman, Kate Kruczynski, Thomas R. Pisanic, Christopher D. Heaney, William A. Clarke, Tza-Huei Wang
Summary: The study introduces a rapid and sensitive magnetofluidic immuno-PCR platform for point-of-care serological testing of COVID-19, which achieved high sensitivity and specificity in clinical sample evaluation.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Gastroenterology & Hepatology
Tara Keihanian, Prateek Sharma, Dalbir S. Sandhu, Daniel A. Sussman, James H. Tabibian, Mohit Girotra
Summary: COVID-19 has significantly impacted gastroenterology healthcare workers in the United States, leading to reduced work hours, duty reassignment, and furlough. Uncertainty about job and future wages/benefits was noted in 41% of participants, which was significantly associated with physical and mental/emotional symptoms.
GASTROENTEROLOGY NURSING
(2021)
Article
Biochemical Research Methods
Alejandro Stark, Thomas R. Pisanic, James G. Herman, Tza-Huei Wang
Summary: This research developed an automated protocol that can generate high-quality bisulfite-treated DNA samples in a high-throughput and clean environment with minimal user intervention.
Article
Medicine, Research & Experimental
Ejas Palathingal Bava, John George, Mohammad Tarique, Srikanth Iyer, Preeti Sahay, Beatriz Gomez Aguilar, Dujon B. Edwards, Bhuwan Giri, Vrishketan Sethi, Tejeshwar Jain, Prateek Sharma, Utpreksha Vaish, Harrys K. C. Jacob, Anthony Ferrantella, Craig L. Maynard, Ashok K. Saluja, Rajinder K. Dawra, Vikas Dudeja
Summary: This study evaluated the efficacy of pirfenidone in treating acute pancreatitis. The results showed that pirfenidone can reduce local and systemic injury and inflammation caused by pancreatitis, suggesting its potential therapeutic effects. Pirfenidone acts by decreasing cytokine release and disrupting cellular interactions.
Article
Gastroenterology & Hepatology
Ejas Palathingal Bava, John George, Srikanth Iyer, Preeti Sahay, Mohammad Tarique, Tejeshwar Jain, Utpreksha Vaish, Bhuwan Giri, Prateek Sharma, Ashok K. Saluja, Rajinder K. Dawra, Vikas Dudeja
Summary: The study aimed to evaluate the therapeutic efficacy of pirfenidone in mouse models of CP. The results suggest that pirfenidone improves CP-related changes in the pancreas, reduces fibrosis and inflammation. It also reduces the pro-fibrotic phenotype of macrophages and collagen secretion in pancreatic stellate cells.
Article
Gastroenterology & Hepatology
Tejeshwar Jain, Prateek Sharma, Bhuwan Giri, Srikanth Iyer, Vrishketan Sethi, Ejas P. Bava, Utpreksha Vaish, Preeti Sahay, Jashodeep Datta, Sushanth Reddy, John Bart Rose, Anam Khan, Nipun Merchant, Suresh T. Chari, Vikas Dudeja
Summary: This study surveyed pancreatic surgeons on their use of pancreatic enzyme replacement therapy (PERT) in patients with pancreatic cancer (PDAC). The results showed that most surgeons prescribe PERT for resectable/borderline resectable PDAC cases, but few order investigations or believe in the effect of PERT on survival outcomes.
Article
Oncology
Jason M. Foster, Chunmeng Zhang, Shahyan Rehman, Prateek Sharma, H. Richard Alexander
Summary: Peritoneal metastasis is a common problem with treatment challenges. Recent developments in systemic therapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy have improved the treatment outcomes for peritoneal metastasis. This article provides a comprehensive review of the contemporary approach for tumors with a high frequency of peritoneal metastasis and explores the role of precision medicine technology in its management.
CA-A CANCER JOURNAL FOR CLINICIANS
(2023)
Article
Biochemistry & Molecular Biology
Jashodeep Datta, Anna Bianchi, Iago De Castro Silva, Nilesh U. Deshpande, Long Long Cao, Siddharth Mehra, Samara Singh, Christine Rafie, Xiaodian Sun, Xi Chen, Xizi Dai, Antonio Colaprico, Prateek Sharma, Austin R. Dosch, Asha Pillai, Peter J. Hosein, Nagaraj S. Nagathihalli, Krishna Komanduri, Julie M. Wilson, Yuguang Ban, Nipun B. Merchant
Summary: Co-occurrent KRAS and TP53 mutations are common in patients with pancreatic ductal adenocarcinoma (PDAC) and are associated with worse survival. These mutations lead to innate immune enrichment and CD8(+) T-cell exclusion, as well as affecting transcriptomes and cell migration in the tumor microenvironment. These molecular characteristics can predict chemoresistance and overall survival in patients with metastatic PDAC.
Review
Oncology
Juliane M. Liberto, Sheng-Yin Chen, Ie-Ming Shih, Tza-Huei Wang, Tian-Li Wang, Thomas R. Pisanic
Summary: Ovarian high-grade serous carcinoma (HGSC) has a high mortality rate due to delays in diagnosis and a lack of sensitive and specific biomarkers for early-stage detection. This review provides an overview of the current landscape of ovarian cancer diagnostics and focuses on emerging methodologies for non-invasive detection of HGSC, particularly in high-risk populations.
Article
Biology
Iago de Castro Silva, Anna Bianchi, Nilesh U. Deshpande, Prateek Sharma, Siddharth Mehra, Vanessa Tonin Garrido, Shannon Jacqueline Saigh, Jonathan England, Peter Joel Hosein, Deukwoo Kwon, Nipun B. Merchant, Jashodeep Datta
Summary: This study investigates the predictive role of neutrophil-to-lymphocyte ratio (NLR) in pancreatic cancer chemotherapy, and discovers that combining NLR-attenuating anti-Ly6G with chemotherapy can improve pathologic response and survival, potentially by suppressing inflammatory cancer-associated fibroblast (CAF) polarization and chemoresistant signaling.
Letter
Gastroenterology & Hepatology
Ingrid Schwartz, Prateek Sharma, Preksha Vankawala, Nicole Cruz, Rtika R. Abraham, Daniel A. Sussman, Mohit Girotra