Article
Surgery
Lakhdar Khellaf, Francois Quenet, Marta Jarlier, Hugo Gil, Marie-Helene Pissas, Sebastien Carrere, Emmanuelle Samalin, Thibault Mazard, Marc Ychou, Olivia Sgarbura, Frederic Bibeau
Summary: The desmoplastic growth pattern may serve as a useful marker for early identification of patients who may benefit from two-stage hepatectomy completion.
Article
Pharmacology & Pharmacy
Zeting Yuan, Chaolian Liu, Yuji Sun, Yue Li, Honglei Wu, Shuli Ma, Jing Shang, Yueping Zhan, Peihao Yin, Feng Gao
Summary: This study designed iRGD-modified nanoparticles to co-deliver mTHPC and BU, aiming to enhance the efficacy of photodynamic therapy (PDT) in colorectal cancer (CRC). The nanoparticles passively accumulated in tumor cells, with mTHPC inducing apoptosis and death under laser irradiation, while the sustained release of BU inhibited hypoxia and angiogenesis by targeting the SRC-3/HIF-1α pathway.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Gastroenterology & Hepatology
Dan Li, Amanda R. Doherty, Menaka Raju, Liyan Liu, Nan Ye Lei, Laura B. Amsden, Jeffrey K. Lee, Theodore R. Levin, Douglas A. Corley, Lisa J. Herrinton
Summary: This community-based, case-control study found a close association between serrated polyps (SPs) and the risk of colorectal cancer (CRC), especially large proximal serrated lesions or those with dysplasia. Close endoscopic surveillance of serrated polyps can help reduce the risk of CRC. Proximal unspecified SPs are also associated with an increased risk of CRC and should be managed as serrated lesions.
Article
Pathology
Janko T. Zujovic, Marko M. Stojanovic, Vesna M. Brzacki, Aleksandar D. Kujovic, Miodrag N. Dordevic, Snezana A. Jancic, Sanja M. Milenkovic, Velimir S. Milosevic
Summary: Stathmin1 expression is closely associated with neoangiogenesis in colorectal adenocarcinoma, with high expression being correlated with severe VEGF expression and high microvascular density index (mvdIDX). Based on Stathmin1 expression, patients at increased risk for metastatic disease can be differentiated.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Oncology
Xiang Li, Zitao Li, Caijuan Li, Xuemei Wang, Bin Jiang, Jiannan Wang, Zhen Zhang
Summary: The study aimed to investigate the impact of CXCR7 on proliferation, migration, and angiogenesis in colon cancer cells by altering its expression levels. Contrast-enhanced ultrasound technology was used to quantify tumor perfusion parameters in vivo to detect angiogenesis after changes in CXCR7 expression in colon cancer xenografts.
Review
Cell Biology
Simon G. Powell, Priyanka Sharma, Samuel Masterson, James Wyatt, Ilyas Arshad, Shakil Ahmed, Gendie Lash, Michael Cross, Dharani K. Hapangama
Summary: Deep endometriosis (DE) is the most severe subtype of endometriosis, characterized by lesions infiltrating adjacent tissue. Abnormal vascularization is implicated in DE lesion development, with higher microvessel density (MVD) and increased levels of vascular endothelial growth factor (VEGF-A) and its associated receptor (VEGFR-2) in DE lesions compared to other types of endometriotic lesions. Progestin therapy decreases MVD in DE lesions, suggesting potential therapeutic targets for DE management. This systematic review provides comprehensive evidence of the role of abnormal vascularization in DE pathogenesis.
Article
Cell Biology
Xin Zhang, Kexin Wang, Xingbo Feng, Jian Wang, Yali Chu, Chunmeng Jia, Qingsi He, Cheng Chen
Summary: The study revealed that HIF1 alpha R282 is methylated by PRMT3, which is essential for its stability and oncogenic function. Using MPG-peptide to inhibit HIF1 alpha expression offers a new therapeutic strategy for colorectal cancer resistant to anti-angiogenesis therapy.
CELL DEATH & DISEASE
(2021)
Article
Medicine, Research & Experimental
Zhiyuan Zheng, Ting Xu, Zhiyan Liu, Wenyue Tian, Zhi-Hong Jiang, Guo-Yuan Zhu, Ting Li, Jin Gao, Li-Ping Bai
Summary: The current study found that Cryptolepine possesses the potential to treat breast cancer by inhibiting HIF-1 activity and decreasing HIF-1α protein expression. It suppresses tumor growth by blocking HIF-1-mediated glycolysis and reducing ATP production. Mechanistically, Cryptolepine inhibits the phosphorylation of eIF4E to suppress HIF-1α mRNA translation.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Cell Biology
Yoichiro Okubo, Soji Toda, Shinya Sato, Emi Yoshioka, Kyoko Ono, Chie Hasegawa, Kota Washimi, Tomoyuki Yokose, Yohei Miyagi, Hiroyuki Iwasaki, Hiroyuki Hayashi
Summary: This study aimed to analyze the histological changes in patients who underwent thyroidectomy after lenvatinib therapy. Results showed that lenvatinib therapy may induce specific ischemic changes in thyroid cancer cells, and non-cancerous thyroid tissues may also show inflammatory cell infiltration and decreased microvessel density, possibly related to the side effect of hypothyroidism caused by lenvatinib.
Review
Biology
Fabio Grizzi, Mohamed A. A. A. Hegazi, Matteo Zanoni, Paolo Vota, Giovanni Toia, Maria Chiara Clementi, Cinzia Mazzieri, Maurizio Chiriva-Internati, Gianluigi Taverna
Summary: Angiogenesis plays a pivotal role in prostate cancer, but evaluating angiogenic activity remains challenging. This review discusses various angiogenic mechanisms in prostate cancer and their potential relevance for predictive and prognostic evaluations.
Article
Pathology
Jung-Soo Pyo, Kyueng-Whan Min, Il Hwan Oh, Dae Hyun Lim, Byoung Kwan Son
Summary: The aim of this study was to evaluate the clinicopathological significance and associated signaling pathways of p21-activated kinase 1 (PAK1) in colorectal cancer (CRC). The results showed that PAK1 expression was significantly correlated with metastatic lymph node ratio and low immunoscore, as well as high expression of HIF-1 alpha and pFOXO1 in CRC. PAK1 expression was also associated with worse prognosis in CRC patients.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Pharmacology & Pharmacy
Aranka Brockmueller, Sosmitha Girisa, Mahzad Motallebi, Ajaikumar B. Kunnumakkara, Mehdi Shakibaei
Summary: A study found that Calebin A (CA), a compound derived from turmeric, inhibits colorectal cancer (CRC) cell migration by modulating the NF-kappa B pathway through the inhibition of HIF-1 alpha. CA suppressed the proliferation and migration of CRC cells, reduced the expression of metastatic factors, and induced apoptosis through inhibition of HIF-1 alpha. This research has important implications for cancer therapy.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Nasim Kheshtchin, Jamshid Hadjati
Summary: Hypoxia, a common characteristic of solid tumors, contributes to different aspects of tumor progression and limits the efficacy of immunotherapies. Developing new immunotherapy strategies involving therapeutic targeting of HIF-1 molecules associated with hypoxia may enhance the clinical effectiveness of immunotherapy. Targeting hypoxia presents a potential opportunity to improve the clinical benefit of cancer immunotherapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Charles Muller, Akihiro Yamada, Sachie Ikegami, Haider Haider, Yuga Komaki, Fukiko Komaki, Dejan Micic, Atsushi Sakuraba
Summary: Serrated polyposis syndrome (SPS) is an underrecognized CRC predisposition syndrome with a higher risk of colorectal cancer, especially at the time of diagnosis. Early recognition, screening, and enhanced surveillance protocols are crucial in managing the elevated CRC risk in SPS patients.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Oncology
Marek Samec, Alena Liskova, Lenka Koklesova, Sandra Mersakova, Jan Strnadel, Karol Kajo, Martin Pec, Kevin Zhai, Karel Smejkal, Sepideh Mirzaei, Kiavash Hushmandi, Milad Ashrafizadeh, Luciano Saso, Aranka Brockmueller, Mehdi Shakibaei, Dietrich Busselberg, Peter Kubatka
Summary: This comprehensive review discusses the anticancer effects of plant phenolic compounds, known as flavonoids, through the targeting of HIF-1 and critical enzymes contributing to the Warburg effect. Flavonoids represent a promising avenue in cancer-related research by regulating glucose metabolism through HIF-1 activity. Further investigations are needed to elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.
Article
Immunology
Niko Kemi, Olli Ylitalo, Juha P. Vayrynen, Olli Helminen, Anna Junttila, Johanna Mrena, Jan Bohm, Joonas H. Kauppila
Summary: TLS density and maximal diameter are associated with prognosis in gastric cancer, with moderate reproducibility in their assessments.
Article
Oncology
Mehrdad Rakaee, Elio Adib, Biagio Ricciuti, Lynette M. Sholl, Weiwei Shi, Joao Alessi, Alessio Cortellini, Claudia A. M. Fulgenzi, Patrizia Viola, David J. Pinato, Sayed Hashemi, Idris Bahce, Ilias Houda, Ezgi B. Ulas, Teodora Radonic, Juha P. Vayrynen, Elin Richardsen, Simin Jamaly, Sigve Andersen, Tom Donnem, Mark M. Awad, David J. Kwiatkowski
Summary: This study developed a machine-learning-based approach to evaluate the association between tumor-infiltrating lymphocytes (TILs) and immune checkpoint inhibitor (ICI) therapy in lung cancer patients. The results showed that high levels of TILs were associated with ICI treatment response and could be used for patient selection and precision therapy guidance.
Article
Oncology
Topias Karjula, Hanna Elomaa, Anne Niskakangas, Olli Mustonen, Iiris Puro, Teijo Kuopio, Maarit Ahtiainen, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Juha P. Vayrynen, Fredrik Yannopoulos, Olli Helminen
Summary: The study found that CD3(+) and CD8(+) T-cell density and PD-1/PD-L1 expression have prognostic value in pulmonary metastases of colorectal cancer. T-cell infiltration is higher in pulmonary metastases compared to primary tumors. High CD3(+) and CD8(+) cell density are associated with better survival, while high PD-L1 expression is associated with favorable prognosis.
Article
Oncology
Meeri Kastinen, Paeivi Sirnio, Hanna Elomaa, Maarit Ahtiainen, Sara A. Vayrynen, Karl-Heinz Herzig, Sanna Merilainen, Raila Aro, Reetta Haivala, Tero Rautio, Juha Saarnio, Erkki-Ville Wirta, Olli Helminen, Toni T. Seppala, Teijo Kuopio, Jan Bohm, Anne Tuomisto, Jukka-Pekka Mecklin, Markus J. Makinen, Juha P. Vayrynen
Summary: This study analyzed data from 1413 patients with colorectal cancer and found associations between tumor necrosis percentage and tumor characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis. The results showed that high tumor necrosis percentage is associated with shorter colorectal cancer-specific survival, independent of other factors. Tumor necrosis is therefore considered an important prognostic factor in colorectal cancer.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Hanna Elomaa, Maarit Ahtiainen, Sara A. Vaeyrynen, Shuji Ogino, Jonathan A. Nowak, Mai Chan Lau, Olli Helminen, Erkki-Ville Wirta, Toni T. Seppaelae, Jan Boehm, Jukka-Pekka Mecklin, Teijo Kuopio, Juha P. Vaeyrynen
Summary: The expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised. This study found that PD-L1(+) macrophages and PD-1(+) T cells were associated with better clinical outcomes in colorectal cancer patients. These findings enhance the understanding of immune checkpoints in the tumor microenvironment and could contribute to the development of improved immunotherapies.
BRITISH JOURNAL OF CANCER
(2023)
Letter
Hematology
Tero Vuolio, Outi Kuittinen, Juha P. Vayrynen, Hanna-Riikka Teppo, Roosa E. I. Prusil, Maria Ramet, Hanne Kuitunen, Timo Paloneva, Milla E. L. Kuusisto
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Liisa Petainen, Juha P. Vayrynen, Pekka Ruusuvuori, Ilkka Polonen, Sami Ayramo, Teijo Kuopio
Summary: This study proposes an automated method for estimating tumor-stroma ratio (TSR) from histopathological images of colorectal cancer using convolutional neural networks. The models achieved high accuracy in classifying stroma, tumor, and other tissues, with the best model reaching 99.3% accuracy for tumor classification. The predicted TSR values showed moderate correlation with pathologist estimations (0.57).
Article
Pathology
Topias Karjula, Anne Niskakangas, Olli Mustonen, Iiris Puro, Hanna Elomaa, Maarit Ahtiainen, Teijo Kuopio, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Fredrik Yannopoulos, Olli Helminen, Juha P. Vayrynen
Summary: In this study, the prognostic effect of tertiary lymphoid structures (TLSs) on colorectal cancer (CRC) pulmonary metastases and primary tumors was analyzed. The density and diameter of TLSs showed no prognostic value in pulmonary metastases, but higher density and diameter were associated with lower mortality in primary tumors.
Article
Multidisciplinary Sciences
Pei-Chen Tsai, Tsung-Hua Lee, Kun-Chi Kuo, Fang-Yi Su, Tsung-Lu Michael Lee, Eliana Marostica, Tomotaka Ugai, Melissa Zhao, Mai Chan Lau, Juha P. Vayrynen, Marios Giannakis, Yasutoshi Takashima, Seyed Mousavi Kahaki, Kana Wu, Mingyang Song, Jeffrey A. Meyerhardt, Andrew T. Chan, Jung-Hsien Chiang, Jonathan Nowak, Shuji Ogino, Kun-Hsing Yu
Summary: The authors develop a machine learning-based platform, MOMA, to systematically identify and interpret the relationship between patients' histologic patterns, multi-omics, and clinical profiles. MOMA successfully predicts the overall survival, disease-free survival, and copy number alterations of colorectal cancer patients. Additionally, MOMA identifies interpretable pathology patterns predictive of gene expression profiles, microsatellite instability status, and clinically actionable genetic alterations.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jouni Harkonen, Petri Polonen, Ashik Jawahar Deen, Ilakya Selvarajan, Hanna-Riikka Teppo, Elitsa Y. Dimova, Thomas Kietzmann, Maarit Ahtiainen, Juha P. Vayrynen, Sara A. Vayrynen, Hanna Elomaa, Niko Tynkkynen, Tiia Eklund, Teijo Kuopio, Eva-Maria Talvitie, Pekka Taimen, Markku Kallajoki, Minna U. Kaikkonen, Merja Heinaniemi, Anna-Liisa Levonen
Summary: The NRF2 pathway is frequently activated in various cancer types, but a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and conducted a pan-cancer analysis of oncogenic NRF2 signaling using it. Our findings revealed an immunoevasive phenotype in squamous malignancies of the lung, head and neck area, cervix, and esophagus, where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression, and T cell and macrophage infiltration. These tumors have a molecular phenotype with amplification of SOX2/TP63, TP53 mutation, and CDKN2A loss, and are associated with upregulation of immunomodulatory genes NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1, and PD-L1. Our functional genomics analyses suggest that these genes are candidate NRF2 targets, indicating a direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands and increased expression of immunosuppressive ligands NAMPT, SPP1, and WNT5A involved in intercellular crosstalk. Moreover, the negative relationship between NRF2 and immune cells is explained by stromal populations of lung squamous cell carcinoma, indicating a potential effect across multiple squamous malignancies based on our molecular subtyping and deconvolution data.
Article
Oncology
Melissa Zhao, Mai Chan Lau, Koichiro Haruki, Juha P. Vayrynen, Carino Gurjao, Sara A. Vayrynen, Andressa Dias Costa, Jennifer Borowsky, Kenji Fujiyoshi, Kota Arima, Tsuyoshi Hamada, Jochen K. Lennerz, Charles S. Fuchs, Reiko Nishihara, Andrew T. Chan, Kimmie Ng, Xuehong Zhang, Jeffrey A. Meyerhardt, Mingyang Song, Molin Wang, Marios Giannakis, Jonathan A. Nowak, Kun-Hsing Yu, Tomotaka Ugai, Shuji Ogino
Summary: By using Bayesian additive regression trees (BART), a statistical learning technique, the study aimed to improve the prediction of prognosis for colorectal cancer by comprehensively analyzing patient-specific tumor characteristics. The BART risk model identified seven stable survival predictors and the risk stratifications based on model-predicted survival were statistically significant. BART demonstrated flexibility, interpretability, and comparable or superior performance to other machine-learning models, making it a valuable tool for prognostic stratifications in colorectal cancer patients.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Topias Karjula, Niko Kemi, Anne Niskakangas, Olli Mustonen, Iiris Puro, Vesa-Matti Pohjanen, Teijo Kuopio, Hanna Elomaa, Maarit Ahtiainen, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Juha P. Vayrynen, Fredrik Yannopoulos, Olli Helminen
Summary: The prognostic value of tumor budding and tumor-stroma ratio (TSR) in resected pulmonary metastases of colorectal carcinoma (CRC) was evaluated in this study. The results showed that tumor budding and TSR after metastasectomy were not statistically correlated with overall survival rates, indicating no prognostic value. Further studies are needed for confirmation.
Article
Respiratory System
Topias Karjula, Anne Niskakangas, Olli Mustonen, Iiris Puro, Juha P. Vayrynen, Olli Helminen, Fredrik Yannopoulos
Summary: A considerable proportion of intended pulmonary metastasectomies turn out as new incidental primary lung cancers. The study highlights the diagnostic importance of pulmonary metastasectomy and suggests segmentectomy as a primary procedure for patients with a long disease-free interval and a heavy smoking history.
JOURNAL OF THORACIC DISEASE
(2023)
Article
Immunology
Tomotaka Ugai, Takashi Shimizu, Hidetaka Kawamura, Satoko Ugai, Yasutoshi Takashima, Genki Usui, Juha P. Vayrynen, Kazuo Okadome, Koichiro Haruki, Naohiko Akimoto, Yohei Masugi, Annacarolina da Silva, Kosuke Mima, Xuehong Zhang, Andrew T. Chan, Molin Wang, Wendy S. Garrett, Gordon J. Freeman, Jeffrey A. Meyerhardt, Jonathan A. Nowak, Mingyang Song, Marios Giannakis, Shuji Ogino
Summary: This study aimed to investigate the relationship between F. nucleatum (bacteria) and CD274 (tumor immune checkpoint) in colorectal cancer. The results showed that the expression level of tumor CD274 was inversely associated with the amount of F. nucleatum. This suggests that different immunosuppressive mechanisms are utilized by different tumor subgroups.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Henna Karjalainen, Paivi Sirnio, Anne Tuomisto, Markus J. J. Makinen, Juha P. P. Vayrynen
Summary: The study aimed to compare the prognostic value of a B cell/plasma cell-based scoring system and T cell score in colorectal cancer. Immunohistochemistry was used to analyze the expression of CD20, CD138, CD3, and CD8 in 221 colorectal cancer patients. The results showed that a high T cell score was associated with longer cancer-specific survival and clinicopathological factors typical to less aggressive tumors, while the additional prognostic value of B cell/plasma cell quantification was not supported.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2023)