Article
Oncology
Amrita M. Nargund, Chang Xu, Amit Mandoli, Atsushi Okabe, Gao Bin Chen, Kie Kyon Huang, Taotao Sheng, Xiaosai Yao, Jia Ming Nickolas Teo, Raghav Sundar, Yee Jiun Kok, Yi Xiang See, Manjie Xing, Zhimei Li, Chern Han Yong, Aparna Anand, A. I. Zul Fazreen, Lai Fong Poon, Michelle Shu Wen Ng, Javier Yu Peng Koh, Wen Fong Ooi, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Heike Grabsch, Melissa J. Fullwood, Tean Bin Teh, Xuezhi Bi, Atsushi Kaneda, Shang Li, Patrick Tan
Summary: Mutations in the MSH2 gene are causative in gastric cancer, and MSH2 has a novel epigenomic function in regulating gene expression. MSH2 binds to tumor-associated superenhancers in early-stage gastric cancer, playing a role in chromatin rewiring and cell adhesion pathway expression. Loss of MSH2 in advanced gastric cancer leads to deficient cell adhesion pathway expression and enhanced tumorigenesis. Additionally, MSH2-deficient gastric cancer cells show addiction to BET inhibition.
Article
Medicine, General & Internal
Yoshiaki Usui, Yukari Taniyama, Mikiko Endo, Yuriko N. Koyanagi, Yumiko Kasugai, Isao Oze, Hidemi Ito, Issei Imoto, Tsutomu Tanaka, Masahiro Tajika, Yasumasa Niwa, Yusuke Iwasaki, Tomomi Aoi, Nozomi Hakozaki, Sadaaki Takata, Kunihiko Suzuki, Chikashi Terao, Masanori Hatakeyama, Makoto Hirata, Kokichi Sugano, Teruhiko Yoshida, Yoichiro Kamatani, Hidewaki Nakagawa, Koichi Matsuda, Yoshinori Murakami, Amanda B. Spurdle, Keitaro Matsuo, Yukihide Momozawa
Summary: This study reveals that certain genetic variants associated with Helicobacter pylori infection can increase the risk of gastric cancer. Individuals carrying these genetic variants and infected with H. pylori have an even higher risk of developing gastric cancer.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Silvia Salvatori, Irene Marafini, Federica Laudisi, Giovanni Monteleone, Carmine Stolfi
Summary: H. pylori infection contributes to the onset and development of gastric cancer through the mechanisms of chronic inflammation and DNA damage to gastric epithelial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Qian Cao, Sheng-Yuan Lai, Nan Xu, Yang Lu, Shuai Chen, Xin-Sheng Zhang, Xiang Li
Summary: The study found distinct CT features in GC patients with dMMR, compared to the pMMR group. These differences mainly include the location in the stomach, tumor thickness, and number of lymph nodes, indicating potential diagnostic value in clinical practice.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Jie-Yu Chen, Ya-Han Tong, Hai-Yan Chen, Yong-Bo Yang, Xue-Ying Deng, Guo-Liang Shao
Summary: This study aimed to develop a computed tomography (CT)-based nomogram for preoperatively predicting DNA mismatch repair deficiency (dMMR) status in gastric cancer (GC). Clinical and CT imaging features associated with dMMR GC were analyzed, and a nomogram with four potential predictors was constructed. The nomogram showed good predictive performance, as confirmed by receiver operating characteristic curve analysis, decision curve analysis, and internal validation.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Shuangshuang Zhao, Lingli Chen, Yuqin Zang, Wenlu Liu, Shiqi Liu, Fei Teng, Fengxia Xue, Yingmei Wang
Summary: Lynch syndrome (LS) is caused by germline pathogenic variants in mismatch repair (MMR) genes, leading to LS-associated endometrial cancer (LS-EC) which has specific clinicopathologic features. Screening, diagnosis, surveillance, prevention and treatment for LS-EC have significantly advanced, with recommendations for universal LS screening among EC patients.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Marta Mendiola, Victoria Heredia-Soto, Ignacio Ruz-Caracuel, Amparo Baillo, Jorge Luis Ramon-Patino, Francisco Javier Escudero, Maria Miguel, Alberto Pelaez-Garcia, Alicia Hernandez, Jaime Feliu, David Hardisson, Andres Redondo
Summary: This study aimed to establish and compare different approaches for assessing the MMR status in endometrial carcinomas. A total of 126 early-stage EC samples were analyzed using immunohistochemistry, PCR-based MSI, methylation-specific multiplex ligation-dependent probe amplification, and targeted next-generation sequencing. The study found that approximately 53.2% of the samples were MMR deficient, while 46.8% were MMR proficient. Additionally, 44.3% of the samples showed genetic or epigenetic alterations, with MLH1 promoter methylation being the most common event.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Qingwen Zeng, Yanyan Zhu, Leyan Li, Zongfeng Feng, Xufeng Shu, Ahao Wu, Lianghua Luo, Yi Cao, Yi Tu, Jianbo Xiong, Fuqing Zhou, Zhengrong Li
Summary: The study developed a CT-based radiomic nomogram for accurately predicting MMR protein status in gastric cancer preoperatively. The model showed good performance in validation across multiple independent cohorts.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Hui Wu, Wenyuan Ma, Congfa Jiang, Ning Li, Xin Xu, Yongfeng Ding, Haiping Jiang
Summary: Gastric cancer is a common and fatal malignant tumor. Microsatellite instability (MSI) has become a major molecular typing approach for gastric cancer, especially in advanced cases. However, its value in resectable gastric cancer is still unclear, and there is no consensus on postoperative adjuvant therapy for MSI-H/dMMR resectable GC patients.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Giammanco, Rita Anzalone, Nicola Serra, Giuseppa Graceffa, Salvatore Vieni, Nunzia Scibetta, Teresa Rea, Giuseppina Capra, Teresa Fasciana
Summary: Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases, such as Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) infection. A study on Italian patients showed significant differences in methylation status and p53 mutation among coinfected patients. The relationship between infection and genetic factors was found to be significant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Surgery
Elvira L. Vos, Steven B. Maron, Robert W. Krell, Masaya Nakauchi, Megan Fiasconaro, Marinela Capanu, Henry S. Walch, Walid K. Chatila, Nikolaus Schultz, David H. Ilson, Yelena Y. Janjigian, Geoffrey Y. Ku, Sam S. Yoon, Daniel G. Coit, Chad M. Vanderbilt, Laura H. Tang, Vivian E. Strong
Summary: This study evaluated the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer. The results showed that patients with MSI-high tumors had better overall survival compared with those with microsatellite stable (MSS) tumors, despite a worse response to chemotherapy.
Review
Immunology
Jiao-Ting Chen, Yu-Wen Zhou, Ting-Rui Han, Jun-Lun Wei, Meng Qiu
Summary: Surgical resection is essential for achieving good prognoses in colorectal cancer (CRC), but some patients fail to meet surgical indications or achieve pathological complete response after surgery. Perioperative therapy can effectively decrease tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown satisfactory efficacy and safety in patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR), while the therapeutic effect is minimal in patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS). Additional predictors are needed to screen patients with potential clinical benefits. Different combinations of immunotherapy in perioperative clinical trials for CRC have been comprehensively summarized in this review, focusing on efficacy and safety, and pointing out future directions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Dung T. Le, Luis A. Diaz Jr, Tae Won Kim, Eric Van Cutsem, Ravit Geva, Dirk Jaeger, Hiroki Hara, Matthew Burge, Bert H. O'Neil, Petr Kavan, Takayuki Yoshino, Rosine Guimbaud, Hiroya Taniguchi, Elena Elez, Salah-Eddin Al-Batran, Patrick M. Boland, Yi Cui, Pierre Leconte, Patricia Marinello, Thierry Andre
Summary: The study demonstrated that Pembrolizumab had durable clinical benefit and manageable safety in previously treated MSI-H/dMMR colorectal cancer patients. It showed persistent antitumor activity, prolonged overall survival, and tolerable safety profile.
EUROPEAN JOURNAL OF CANCER
(2023)
Editorial Material
Microbiology
Agustina Taglialegna
Summary: In this study, Sharafutdinov et al. report the identification of a single nucleotide polymorphism in the gene encoding the HtrA protease of Helicobacter pylori that is linked to gastric cancer.
NATURE REVIEWS MICROBIOLOGY
(2023)
Review
Immunology
Wei-Jian Mei, Mi Mi, Jing Qian, Nan Xiao, Ying Yuan, Pei-Rong Ding
Summary: Colorectal cancers with high microsatellite instability and deficient mismatch repair have different characteristics compared to normal CRC, but the testing rates for MSI and MMR remain low in clinical practice. Insufficient testing fails to identify patients with these types of CRC who could benefit from immunotherapy. Understanding the importance of MMR/MSI status in the clinical characteristics and prognosis of CRC may help improve testing rates and guide the development of more effective therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Bruno Cavadas, Marina Leite, Nicole Pedro, Ana C. Magalhaes, Joana Melo, Marcelo Correia, Valdemar Maximo, Rui Camacho, Nuno A. Fonseca, Ceu Figueiredo, Luisa Pereira
Summary: The continuous characterization of genome-wide diversity in population and case-cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. The results showed that African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted.
Article
Oncology
Joana Figueiredo, Rui M. Ferreira, Han Xu, Margarida Goncalves, Andre Barros-Carvalho, Janine Cravo, Andre F. Maia, Patricia Carneiro, Ceu Figueiredo, Michael L. Smith, Dimitrije Stamenovic, Eurico Morais-de-Sa, Raquel Seruca
Summary: Research has shown that mutations in E-cadherin lead to abnormal interactions of cells with specific ECM components, resulting in increased traction forces and activation of Integrin beta 1, which promotes cell scattering and invasion. This crosstalk between E-cadherin and Integrin beta 1 is validated in Drosophila models and human gastric carcinomas, where low E-cadherin and high Integrin beta 1 levels are associated with increased tumour grade and poor survival. Integrin beta 1 is identified as a key mediator of invasion in carcinomas with E-cadherin impairment and a biomarker of poor prognosis in gastric cancer.
Article
Microbiology
Joana Melo, Vanessa Pinto, Tania Fernandes, Ana R. Malheiro, Hugo Osorio, Ceu Figueiredo, Marina Leite
Summary: The study presents a time- and cost-efficient protocol for the isolation of H. pylori OMVs from a chemically defined culture medium, yielding highly pure OMVs from cultures of different H. pylori strains and growth periods. Analysis of the proteome of OMVs revealed differentially expressed proteins, including VacA, suggesting the reliability of the protocol.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ana Freitas, Miguel Aroso, Antonio Barros, Miriam Fernandez, Eduardo Conde-Sousa, Marina Leite, Eva Daniela Carvalho, Cristina C. Ribeiro, Rita Ferreira, Ana Paula Pego, Rui Vitorino, Maria Gomez-Lazaro
Summary: The extracellular matrix in the brains of Parkinson's disease patients shows increased oxalate content and oxidative modifications, affecting microglial survival, morphology, and cytoskeletal tension. Thorough investigation into these modifications may lead to new therapies for Parkinson's disease.
Review
Microbiology
Claudia Sousa, Rute Ferreira, Nuno F. Azevedo, Monica Oleastro, Joana Azeredo, Ceu Figueiredo, Luis D. R. Melo
Summary: H. pylori infection treatment faces challenges due to antibiotic resistance, leading to the development of alternative strategies like probiotics, antimicrobial peptides, and photodynamic therapy. Human vaccine development remains a major challenge, while natural products show potential against H. pylori, requiring further clinical studies.
CRITICAL REVIEWS IN MICROBIOLOGY
(2022)
Article
Oncology
Tessa Suzanne van Schooten, Sarah Derks, Elena Jimenez-Marti, Fatima Carneiro, Ceu Figueiredo, Erika Ruiz, Maria Alsina, Cristina Molero, Marcelo Garrido, Arnoldo Riquelme, Carmelo Caballero, Eva Lezcano, Juan Manuel O'Connor, Federico Esteso, Judith Farres, Jose Manuel Mas, Florian Lordick, Jeannette Vogt, Antonella Cardone, Charis Girvalaki, Andres Cervantes, Tania Fleitas
Summary: The LEGACy study is a multi-institutional research project aimed at filling the knowledge gap on gastric cancer in European and Latin American countries. It will generate novel knowledge on tumor biology characteristics by integrating epidemiological, multi-omics, and clinical data, and develop and validate cost-effective clinical decision-making methods.
Article
Oncology
Patricia Dias Carvalho, Flavia Martins, Susana Mendonca, Andreia Ribeiro, Ana Luisa Machado, Joana Carvalho, Maria Jose Oliveira, Sergia Velho
Summary: This study reveals the role of mutant KRAS in modulating cell fate through autonomous and nonautonomous signaling mechanisms in colorectal cancer cells. Mutant KRAS autonomously controls processes such as proliferation and cell-cell aggregation, while cancer cell invasion depends on the cooperation between fibroblast-derived HGF and mutant KRAS regulation of C-MET expression.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Rute Ferreira, Claudia Sousa, Raquel F. S. Goncalves, Ana Cristina Pinheiro, Monica Oleastro, Jeroen Wagemans, Rob Lavigne, Ceu Figueiredo, Joana Azeredo, Luis D. R. Melo
Summary: This study successfully isolated a new bacteriophage, named HPy1R, which has potential therapeutic value against Helicobacter pylori infections. HPy1R is a podovirus with a genome length of 31,162 bp and exhibits stability and adaptability to the gastric tract environment. It is capable of suppressing H. pylori population levels for up to 24 hours post-infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Carolina Pinto da Costa, Patricia Vieira, Melissa Mendes-Rocha, Joana Pereira-Marques, Rui Manuel Ferreira, Ceu Figueiredo
Summary: The relationship between the microbiome and colorectal cancer has been extensively studied, but little is known about the microbial community in intestinal tumor tissues. This systematic review compiled evidence on the relationship between tissue-associated microbiota and colorectal cancer and identified several bacterial groups that are strongly associated with the disease.
Article
Cell Biology
Patricia Dias Carvalho, Flavia Martins, Joana Carvalho, Maria Jose Oliveira, Sergia Velho
Summary: Understanding how external stimuli modulate mutant KRAS signaling is crucial for uncovering resistance mechanisms and therapeutic targets in mutant KRAS patients. This study found that factors secreted by rhTGF beta 1-activated fibroblasts triggered cell-specific proteome alterations in mutant KRAS colorectal cancer cell lines. Mutant KRAS was shown to govern a significant portion of these alterations, while a substantial portion was controlled by fibroblast-secreted factors. The study highlights the context-dependent nature of KRAS signaling and emphasizes the importance of considering the tumor microenvironment in KRAS-related effects.
Article
Immunology
Rui M. Ferreira, Joana Figueiredo, Ines Pinto-Ribeiro, Irene Gullo, Dionyssios N. Sgouras, Laura Carreto, Patricia Castro, Manuel A. Santos, Fatima Carneiro, Raquel Seruca, Ceu Figueiredo
Summary: Helicobacter pylori infection induces overexpression of laminin gamma 2 in gastric cancer cells, promoting cell invasion and resistance to apoptosis through modulation of Src, JNK, and AKT activity. Laminin gamma 2 and its downstream effectors could be potential therapeutic targets, and H. pylori eradication may delay the onset and progression of gastric cancer.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Luis Moreira, Nuno M. Guimaraes, Sara Pereira, Rita S. Santos, Joana A. Loureiro, Rui M. Ferreira, Ceu Figueiredo, Maria C. Pereira, Nuno F. Azevedo
Summary: Liposomes loaded with nucleic acid mimics (NAMs)-modified oligonucleotides (LipoNAMs) were evaluated for delivering antisense oligonucleotides (ASOs) in Escherichia coli. Different surface modifications, such as methoxyPEG coating and conjugation of antibodies, were tested to improve delivery efficiency and selectivity. Antibody coupling to PEGylated liposomes significantly enhanced the delivery of ASOs in E. coli, providing potential alternative routes for the treatment of bacterial infections.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Oncology
Ana Raquel Bastos, Joana Pereira-Marques, Rui Manuel Ferreira, Ceu Figueiredo
Summary: Pancreatic cancer has a poor prognosis and lacks effective strategies for prevention, diagnosis, and treatment. The human microbiome has been found to influence pancreatic cancer development and treatment response. This review discusses the potential of using the microbiome for diagnostic and therapeutic interventions in pancreatic cancer.
Article
Gastroenterology & Hepatology
Miguel S. Marques, Ana C. Costa, Hugo Osorio, Marta L. Pinto, Sandra Relvas, Mario Dinis-Ribeiro, Fatima Carneiro, Marina Leite, Ceu Figueiredo
Summary: Helicobacter pylori infects approximately half of the world's population and is a major risk factor for peptic ulcer disease and gastric cancer. It disrupts epithelial integrity by targeting the junctional adhesion molecule-A (JAM-A) and uses a unique strategy to do so. This study identified PqqE (HP1012) as the virulence factor responsible for cleaving JAM-A, providing new insights into the pathogenesis of this infection.
