Serum Untargeted UHPLC-HRMS-Based Lipidomics to Discover the Potential Biomarker of Colorectal Advanced Adenoma DOI Creative Commons
Yifan Zhu, Lisheng Wang,

Yanying Nong

et al.

Cancer Management and Research, Journal Year: 2021, Volume and Issue: Volume 13, P. 8865 - 8878

Published: Nov. 1, 2021

As a key precancerous lesion, colorectal advanced adenoma (CAA) is closely related to the occurrence and development of cancer (CRC). Effective identification CAA-related biomarkers can prevent CRC morbidity mortality. Lipids, as an important endogenous substance, have been proved be involved in CRC. Lipidomics technique that studies lipid metabolism diseases. However, there are no lipidomics based on large serum samples explore diagnostic for CAA.An integrated profile from 50 normal (NR) 46 CAA subjects was performed using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Lipidomic data were acquired negative positive ionization modes, respectively. Differential lipids selected by univariate multivariate statistics analyses. A receiver operator characteristic curve (ROC) analysis conducted evaluate differential lipids.A total 53 obtained combining statistical analyses (P < 0.05 VIP > 1). In addition, 12 showed good (AUC 0.90) discrimination NR operating analysis. Of them, PC 44:5 35:6e presented outstanding = 1.00, (95% CI, 1.00-1.00)). Moreover, triglyceride (TAG) had highest proportion (37.74%) major dysregulated CAA.This first study profiled explored with ability contribute early prevention Twelve effectively discriminate between serve potential markers CAA. An obvious perturbation TAG could formation.

Language: Английский

Immune Checkpoint Inhibitors in Cancer Therapy DOI Creative Commons
Yavar Shiravand, Faezeh Khodadadi, Seyyed Mohammad Amin Kashani

et al.

Current Oncology, Journal Year: 2022, Volume and Issue: 29(5), P. 3044 - 3060

Published: April 24, 2022

The discovery of immune checkpoint proteins such as PD-1/PDL-1 and CTLA-4 represents a significant breakthrough in the field cancer immunotherapy. Therefore, humanized monoclonal antibodies, targeting these have been utilized successfully patients with metastatic melanoma, renal cell carcinoma, head neck cancers non-small lung cancer. US FDA has approved three different categories inhibitors (ICIs) PD-1 (Nivolumab, Pembrolizumab, Cemiplimab), PDL-1 (Atezolimumab, Durvalumab Avelumab), inhibitor (Ipilimumab). Unfortunately, not all respond favourably to drugs, highlighting role biomarkers Tumour mutation burden (TMB), expression, microbiome, hypoxia, interferon-γ, ECM predicting responses ICIs-based current study aims review literature updates on ICIs therapy.

Language: Английский

Citations

756
Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability DOI Creative Commons
Julien Taı̈eb, Olivier Bouché, Thierry André

et al.

JAMA Oncology, Journal Year: 2023, Volume and Issue: 9(10), P. 1356 - 1356

Published: Aug. 3, 2023

Only 1 randomized clinical trial has shown the superiority of immune checkpoint inhibitors in patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC) first-line setting.To determine whether avelumab (an anti-programmed cell death ligand antibody) improves progression-free survival (PFS) compared standard second-line chemotherapy dMMR/MSI mCRC.The SAMCO-PRODIGE 54 is a national open-label phase 2 that was conducted from April 24, 2018, to 29, 2021, at 49 French sites. Patients mCRC who experienced progression while receiving therapy were included analysis.Patients receive or every weeks until progression, unacceptable toxic effects, patient refusal.The primary end point PFS according RECIST (Response Evaluation Criteria Solid Tumours), version 1.1, evaluated by investigators and confirmed dMMR MSI status received least dose treatment (modified intention-to-treat [mITT] population).A total 122 enrolled mITT population. Median age 66 (IQR, 56-76) years, 65 (53.3%) women, 100 (82.0%) had right-sided tumor, 52 (42.6%) BRAF V600E-mutated tumors. There no difference tumor characteristics between groups. No new safety concerns either group detected, fewer treatment-related adverse events grade 3 than (20 [31.7%] vs 34 [53.1%]; P = .02). After median follow-up 33.3 (95% CI, 28.3-34.8) months, superior without targeted agents respect (15 [24.6%] 5 [8.2%] among progression; .03). Rates rates 12 months 31.2% 20.1%-42.9%) 19.4% 10.6%-30.2%) control groups, respectively, 27.4% 16.8%-39.0%) 9.1% 3.2%-18.8%) 18 months. Objective response similar both groups (18 [29.5%] 16 [26.2%]; .45). Among disease control, (75.7%) 9 (19.1%) ongoing months.The showed, mCRC, better duration over treatment, favorable profile.ClinicalTrials.gov Identifier: NCT03186326.

Language: Английский

Citations

22
NAT10 mediated mRNA acetylation modification patterns associated with colon cancer progression and microsatellite status DOI Creative Commons
Hailin Zhang,

Wenqing Shan,

Zhenwei Yang

et al.

Epigenetics, Journal Year: 2023, Volume and Issue: 18(1)

Published: March 12, 2023

N4-acetylcytidine (ac4C) is one type of RNA modification found in eukaryotes. acetylation modifications are gradually expanding oncology. However, the role colorectal cancer and its association with microsatellite status remain unclear. Using public databases vitro experiments, we verified expression biological function NAT10, as key enzyme, cancer. The results showed that NAT10 was highly expressed cancer, significantly promoted cell proliferation. also involved several aspects homoeostasis such ion transport, calcium-dependent phospholipid binding, stability. positively correlated immune infiltration We further constructed a risk regression model for mRNA using acetylation-related differential genes. tumour infiltration, instability (MSI) proportion, mutation burden, patient response to immunotherapy were scores. For first time, our study level elevated correlates patients. Based on findings, may be new target treatment.

Language: Английский

Citations

19
Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer – possible implications for immunotherapy DOI Creative Commons
Sofia Edin, Björn Gylling, Xingru Li

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 130(1), P. 143 - 150

Published: Dec. 1, 2023

Abstract Background The immune response has important clinical value in colorectal cancer (CRC) both prognosis and to immunotherapy. This study aims explore tumour cell infiltration relation clinically well-established molecular markers of CRC. Methods Multiplex immunohistochemistry multispectral imaging was used evaluate cytotoxic T cells (CD8 + ), Th1 (T-bet regulatory (FoxP3 B (CD20 macrophages (CD68 ) a cohort 257 CRC patients. Results We found the expected association between higher immune-cell microsatellite instability. Also, whereas BRAF -mutated tumours displayed increased compared wild-type tumours, opposite seen for KRAS differences that were most prominent cells. opposing relationships mutations with validated an independent 608 A positive prognostic importance as well CRCs cohorts. Conclusion combined evaluation MSI status, mutational (cytotoxic cells) may provide insights immunotherapy

Language: Английский

Citations

15
A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability DOI Creative Commons

Mathilde Moreau,

Emily Alouani,

Clémence Flecchia

et al.

European Journal of Cancer, Journal Year: 2024, Volume and Issue: 202, P. 114033 - 114033

Published: March 21, 2024

One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared CT other advanced dMMR/MSI-H digestive tumors.

Language: Английский

Citations

5
Recent updates in the therapeutic uses of Pembrolizumab: a brief narrative review DOI
Vítor Silva, Cristiano Matos

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: 26(10), P. 2431 - 2443

Published: April 24, 2024

Language: Английский

Citations

5
Role of the cGAS-STING pathway in regulating the tumor-immune microenvironment in dMMR/MSI colorectal cancer DOI

Akinao Kaneta,

Shotaro Nakajima, Hirokazu Okayama

et al.

Cancer Immunology Immunotherapy, Journal Year: 2022, Volume and Issue: 71(11), P. 2765 - 2776

Published: April 16, 2022

Language: Английский

Citations

20
WRN helicase and mismatch repair complexes independently and synergistically disrupt cruciform DNA structures DOI Creative Commons

Valentina Mengoli,

Ilaria Ceppi, Aurore Sanchez

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 42(3)

Published: Dec. 21, 2022

Abstract The Werner Syndrome helicase, WRN, is a promising therapeutic target in cancers with microsatellite instability (MSI). Long‐term MSI leads to the expansion of TA nucleotide repeats proposed form cruciform DNA structures, which turn cause breaks and cell lethality upon WRN downregulation. Here we employed biochemical assays show that helicase can efficiently directly unfold thereby preventing their cleavage by SLX1‐SLX4 structure‐specific endonuclease. are particularly prone explaining why these sequences preferentially broken cells We further demonstrate activity mismatch repair (MMR) complexes MutSα (MSH2‐MSH6), MutSβ (MSH2‐MSH3), MutLα (MLH1‐PMS2) similarly decreases level cruciforms, although mechanism different from WRN. When combined, exhibited higher than additive effects vitro processing, suggesting MMR proteins may cooperate. Our data explain how defects genome expanded repeats, provide mechanistic basis for recently discovered synthetic‐lethal interaction applications precision cancer therapy.

Language: Английский

Citations

20
Current Strategy to Treat Immunogenic Gastrointestinal Cancers: Perspectives for a New Era DOI Creative Commons
Keitaro Shimozaki, Izuma Nakayama, Toru Hirota

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(7), P. 1049 - 1049

Published: March 30, 2023

Since pembrolizumab, an anti-programmed death-1 (PD-1) antibody, showed a dramatic response to immunogenic cancers with microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) in the pilot clinical trial KEYNOTE-016, subsequent studies have confirmed durable responses of anti-PD-1 inhibitors for MSI-H/dMMR solid tumors. As immunotherapy is described as “game changer,” therapeutic landscape tumors including gastrointestinal has changed considerably last decade. An MSI/MMR status been established predictive biomarker immune checkpoint blockades, playing indispensable role practice patients Immunotherapy also now investigated locally advanced cancers. Despite this great success, few populations do not respond immunotherapy, possibly due existence intrinsic or acquired resistance mechanisms. Clarifying underlying mechanisms remains future task, whereas attempts overcome and improve efficacy are currently ongoing. Herein, we review recent trials special attention together basic/translational findings, which provide their rationale, discuss perspectives further development treatment field.

Language: Английский

Citations

13
Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome DOI Creative Commons
Ana María Bolívar, Fahriye Düzağaç, Krishna M. Sinha

et al.

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 93, P. 101204 - 101204

Published: July 19, 2023

Language: Английский

Citations

12