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de Melo LRS, Dos Santos Pereira J, Melo MS, Andrade LA, Bezerra-Santos M, Lima CA, Dos Santos AD. Spatial and temporal dynamic of colorectal cancer mortality in Brazil: A nationwide population-based study of four decades (1980-2021). Cancer Epidemiol 2025; 95:102766. [PMID: 39923291 DOI: 10.1016/j.canep.2025.102766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 01/19/2025] [Accepted: 02/04/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Regardless of being preventable through screening strategies and prompt diagnosis, deaths from colorectal cancer (CRC) still represent a serious public health concern in Brazil, with more than 20 thousand deaths annually. Herein, we aimed to assess the temporal trends and spatiotemporal patterns of CRC mortality in all Brazilian states. METHODS An ecological study using temporal and spatial analysis techniques on deaths due to CRC as the underlying cause in Brazil from 1980 to 2021 was conducted. Death certificate and population data were provided by the Department of Informatics of the Unified Health System (DATASUS) and by the Brazilian Institute of Geography and Statistics (IBGE), respectively. RESULTS A total of 395,782 deaths from CRC were recorded in this period and most of them were in female (205,479; 51.92 %), ≥ 65 years old (233,059; 58.89 %), diagnosed with malignant neoplasm of the colon (212,277; 53.63 %), with 1-7 years of education (157.564; 39.81 %), married (192.276; 48.58 %), hospital as place of death (331.393; 83.73 %) and white (212.666; 65.07 %). Moreover, there was an increasing temporal trend in the Northeast region (APC: 2.6; p < 0.05), men (APC: 1.5; p < 0.05) and 45-64 years old (APC: 1.2; p < 0.05). Also, the spatial analysis showed positive spatial autocorrelation in all periods, with the South and Southeast regions presenting the highest concentration of high-risk clusters CRC deaths. Nevertheless, high-risk clusters were also observed in capitals and municipalities in metropolitan regions in the Northeast region. CONCLUSIONS In general, a temporal and spatial expansion of CRC mortality has been observed in Brazil over the last few decades.
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Affiliation(s)
- Luís Ricardo Santos de Melo
- Nursing Graduate Program, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Center for Research in Public Health, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
| | - Júlio Dos Santos Pereira
- Center for Research in Public Health, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Department of Pharmacy, Federal University of Sergipe, Lagarto, Sergipe, Brazil
| | - Matheus Santos Melo
- Center for Research in Public Health, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Department of Health and Environmental Surveillance, Ministry of Health, Distrito Federal, Brasília, Brazil
| | - Lucas Almeida Andrade
- Center for Research in Public Health, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Health Sciences Graduate Program, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil
| | - Márcio Bezerra-Santos
- Center for Research in Public Health, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Health Sciences Graduate Program, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Health Sciences Graduate Program, Federal University of Alagoas, Maceió, Alagoas, Brazil; Medical and Nursing Science Complex Federal University of Alagoas, Maceió, Alagoas, Brazil
| | - Carlos Anselmo Lima
- University Hospital, Federal University of Sergipe, Aracaju, Sergipe, Brazil; Aracaju Cancer Registry, Aracaju, Sergipe, Brazil
| | - Allan Dantas Dos Santos
- Nursing Graduate Program, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Center for Research in Public Health, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; Department of Nursing, Federal University of Sergipe, Lagarto, Sergipe, Brazil
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Kwan ASH, Uwishema O, Mshaymesh S, Choudhary K, Salem FK, Sengar AS, Patel RP, Kazan Z, Wellington J. Advances in the diagnosis of colorectal cancer: the application of molecular biomarkers and imaging techniques: a literature review. Ann Med Surg (Lond) 2025; 87:192-203. [PMID: 40109625 PMCID: PMC11918703 DOI: 10.1097/ms9.0000000000002830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 11/22/2024] [Indexed: 03/22/2025] Open
Abstract
Background Following neoplasms of the lung and breast, colorectal cancer (CRC) is the third most frequent malignancy globally. Screening for CRC at the age of 50 years is strongly encouraged for prompt earlier diagnosis owing to prognoses being greatly correlated with time of detection and cancer staging. Aim This review aimed to elucidate the most recent advancements in the detection of CRC, with an emphasis on the latest innovations in diagnostic molecular biomarkers in conjunction with radiological imaging alongside stool-based tests for CRC screening. Methods A comprehensive review of the literature was performed, focusing on specific terms in different electronic databases, including that of PubMed/MEDLINE. Keywords pertaining to "colorectal cancer," "diagnosis," "screening," "imaging," and "biomarkers," among others, were employed in the search strategy. Articles screened and evaluated were deemed relevant to the study aim and were presented in the medium of the English language. Results There have been several innovations in the diagnostics and identification of CRC. These generally comprise molecular biomarkers, currently being studied for suitability in disease detection. Examples of these include genetic, epigenetic, and protein biomarkers. Concurrently, recent developments in CRC diagnostics highlight the advancements made in radiological imaging that offer precise insights on tumor biology in addition to morphological information. Combining these with statistical methodologies will increase the sensitivity and specificity of CRC diagnostics. However, putting these strategies into reality is hampered by several issues. Conclusion Progress in diagnostic technology alongside the identification of a few prognostic predictive molecular biomarkers suggested great promise for prompt detection and management of CRC. This clearly necessitates further efforts to learn more in this specific sector.
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Affiliation(s)
- Alicia Su Huey Kwan
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Department of Medicine for Older People, Southampton General Hospital, Southampton, United Kingdom
| | - Olivier Uwishema
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
| | - Sarah Mshaymesh
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Department of Natural Sciences, Faculty of Sciences, Haigazian University, Beirut, Lebanon
| | - Karan Choudhary
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Medical School, Department of General Medicine, MGM Medical College, Aurangabad, India
| | - Fatma K Salem
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Biochemistry Department, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt
| | - Aman Singh Sengar
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Medical School, Department of General Medicine, Yerevan State Medical University after Mkhitar Heratsi, Yerevan, Armenia
| | - Raj Pravin Patel
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Department of General Surgery, Manohar Waman Desai General Hospital, Mumbai, India
| | - Zeinab Kazan
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Jack Wellington
- Department of Research and Education, Oli Health Magazine Organization, Research and Education, Kigali, Rwanda
- Department of Neurosurgery, Leeds Teaching Hospitals NHS Foundation Trust, Leeds, United Kingdom
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Choi S, Kang M, Kim JW, Kim JW, Jeon JH, Oh HK, Lee HW, Cho JY, Kim DW, Cho S, Kim JH, Kim K, Kang SB, Jheon S, Lee KW. Long-term clinical outcomes after the second metastasectomy in patients with resected metastatic colorectal cancer. Curr Probl Cancer 2024; 53:101151. [PMID: 39442487 DOI: 10.1016/j.currproblcancer.2024.101151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 10/25/2024]
Abstract
PURPOSE Primary tumor resection and metastasectomy are curative for metastatic colorectal cancer. However, there is still a paucity of data regarding the clinical outcomes and risk factors after disease recurrence and second metastasectomy. MATERIALS AND METHODS We retrospectively evaluated the clinical outcomes of patients who underwent the second metastasectomy. In addition, risk factors for the outcomes were analyzed. RESULTS A total of 94 patients (39 females and 55 males) received a second metastasectomy after the recurrence. Recurrent sites included the lung (47 patients), liver (36 patients), both lung and liver (four patients), and non-lung/non-liver (seven patients). Among them, 89 (94.7 %) patients achieved R0 resection, while three (3.2 %) and two (2.1 %) patients achieved R1 and R2 resections, respectively. The 5-year disease-free survival (DFS) and overall survival (OS) were 42.8±5.3 % and 67.2±4.9 %, respectively. Multivariable analysis for DFS identified that primary rectal cancer (hazard ratio [HR] 0.45, P=0.033) and disease-free interval after the first metastasectomy of ≥12 months (HR 0.39, P=0.002) were good predictive factors; in contrast, non-lung/non-liver metastasis (HR 3.32, P=0.020) was a poor predictive factor. Multivariable analysis for OS showed that age ≥70 years (HR 3.27, P=0.011), non-lung/non-liver metastasis (HR 4.04, P=0.024), and lesion number ≥2 (HR 2.25, P=0.023) were poor prognostic factors. CONCLUSION Patients who underwent a second metastasectomy had a long-term disease-free state and good OS. Our data suggest that a second metastasectomy should be considered if a patient has a limited number of metastases confined to the liver and/or lung and long DFS after the first metastasectomy.
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Affiliation(s)
- Songji Choi
- Department of Genomic Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Minsu Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Ji-Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jae Hyun Jeon
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Heung-Kwon Oh
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Duck-Woo Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sukki Cho
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Kwhanmien Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sung-Bum Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Sanghoon Jheon
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
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Fialková V, Ďúranová H, Borotová P, Klongová L, Grabacka M, Speváková I. Natural Stilbenes: Their Role in Colorectal Cancer Prevention, DNA Methylation, and Therapy. Nutr Cancer 2024; 76:760-788. [PMID: 38950568 DOI: 10.1080/01635581.2024.2364391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/29/2024] [Accepted: 05/31/2024] [Indexed: 07/03/2024]
Abstract
The resistance of colorectal cancer (CRC) to conventional therapeutic modalities, such as radiation therapy and chemotherapy, along with the associated side effects, significantly limits effective anticancer strategies. Numerous epigenetic investigations have unveiled that naturally occurring stilbenes can modify or reverse abnormal epigenetic alterations, particularly aberrant DNA methylation status, offering potential avenues for preventing or treating CRC. By modulating the activity of the DNA methylation machinery components, phytochemicals may influence the various stages of CRC carcinogenesis through multiple molecular mechanisms. Several epigenetic studies, especially preclinical research, have highlighted the effective DNA methylation modulatory effects of stilbenes with minimal adverse effects on organisms, particularly in combination therapies for CRC. However, the available preclinical and clinical data regarding the effects of commonly encountered stilbenes against CRC are currently limited. Therefore, additional epigenetic research is warranted to explore the preventive potential of these phytochemicals in CRC development and to validate their therapeutic application in the prevention and treatment of CRC. This review aims to provide an overview of selected bioactive stilbenes as potential chemopreventive agents for CRC with a focus on their modulatory mechanisms of action, especially in targeting alterations in DNA methylation machinery in CRC.
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Affiliation(s)
- Veronika Fialková
- AgroBioTech Research Centre, Slovak University of Agriculture, Nitra, Slovakia
| | - Hana Ďúranová
- AgroBioTech Research Centre, Slovak University of Agriculture, Nitra, Slovakia
| | - Petra Borotová
- AgroBioTech Research Centre, Slovak University of Agriculture, Nitra, Slovakia
| | - Lucia Klongová
- AgroBioTech Research Centre, Slovak University of Agriculture, Nitra, Slovakia
| | - Maja Grabacka
- Department of Biotechnology and General Technology of Foods, Faculty of Food Technology, University of Agriculture, Cracow, Poland
| | - Ivana Speváková
- AgroBioTech Research Centre, Slovak University of Agriculture, Nitra, Slovakia
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Perné MG, Sitar-Tăut AV, Orășan OH, Negrean V, Vlad CV, Alexescu TG, Milaciu MV, Ciumărnean L, Togănel RD, Petre GE, Șimon I, Crăciun A. The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma. Int J Mol Sci 2024; 25:4997. [PMID: 38732222 PMCID: PMC11084444 DOI: 10.3390/ijms25094997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 04/22/2024] [Accepted: 05/01/2024] [Indexed: 05/13/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.
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Affiliation(s)
- Mirela-Georgiana Perné
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Adela-Viviana Sitar-Tăut
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Olga Hilda Orășan
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Vasile Negrean
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Călin Vasile Vlad
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Teodora-Gabriela Alexescu
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Mircea Vasile Milaciu
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Lorena Ciumărnean
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Răzvan Dan Togănel
- 6th Department–Surgery, 4th Surgery Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Gabriel Emil Petre
- 6th Department–Surgery, 4th Surgery Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Ioan Șimon
- 6th Department–Surgery, 4th Surgery Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Alexandra Crăciun
- 2nd Department–Molecular Sciences, Discipline of Medical Biochemistry, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Pasteur Street, Nr. 6, 400349 Cluj-Napoca, Romania
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Freitas RB, Rodrigues MJLF, Pimenta S, Belsley M, Correia JH, Maciel MJ. Highly-selective optical filter for NADH fluorescence detection in multiphoton microscopy. BIOMEDICAL OPTICS EXPRESS 2024; 15:3317-3328. [PMID: 38855678 PMCID: PMC11161364 DOI: 10.1364/boe.506777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 01/11/2024] [Accepted: 01/11/2024] [Indexed: 06/11/2024]
Abstract
Colorectal cancer (CRC) is a pressing global health concern, emphasizing the need for early detection tools. In this study an optical filter for precise detection of nicotinamide adenine dinucleotide (NADH) fluorescence via two-photon excitation fluorescence (TPEF) was developed. Fabricated with silicon dioxide and titanium dioxide thin films in a Fabry-Perot structure, the filter achieved a peak transmittance of about 95% at 483 nm, with a 12 nm full-width at half maximum. TPEF measurements using a tailored setup and NADH liquid phantoms underscored the filter's significance in selectively capturing NADH fluorescence while mitigating interference from other fluorophores. This work marks a substantial stride towards integrating multiphoton microscopy into conventional colonoscopy, enabling non-invasive, objective optical biopsy for colorectal tissue analysis. Further refinements of the experimental setup are imperative to advance tissue differentiation and enhance CRC diagnosis.
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Affiliation(s)
- R. B. Freitas
- CMEMS-UMinho, University of Minho, 4800-058, Guimarães, Portugal
| | - M. J. L. F. Rodrigues
- Centre of Physics of Minho and Porto Universities (CF-UM-UP), Laboratory for Materials and Emergent Technologies (LAPMET), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - S. Pimenta
- CMEMS-UMinho, University of Minho, 4800-058, Guimarães, Portugal
- LABBELS – Associate Laboratory, Braga/Guimarães, Portugal
| | - M. Belsley
- Centre of Physics of Minho and Porto Universities (CF-UM-UP), Laboratory for Materials and Emergent Technologies (LAPMET), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - J. H. Correia
- CMEMS-UMinho, University of Minho, 4800-058, Guimarães, Portugal
- LABBELS – Associate Laboratory, Braga/Guimarães, Portugal
| | - M. J. Maciel
- CMEMS-UMinho, University of Minho, 4800-058, Guimarães, Portugal
- LABBELS – Associate Laboratory, Braga/Guimarães, Portugal
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7
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Rio-Vilariño A, Cenigaonandia-Campillo A, García-Bautista A, Mateos-Gómez PA, Schlaepfer MI, Del Puerto-Nevado L, Aguilera O, García-García L, Galeano C, de Miguel I, Serrano-López J, Baños N, Fernández-Aceñero MJ, Lacal JC, Medico E, García-Foncillas J, Cebrián A. Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells. Br J Cancer 2024; 130:1402-1413. [PMID: 38467828 PMCID: PMC11014903 DOI: 10.1038/s41416-024-02649-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 02/28/2024] [Accepted: 03/01/2024] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA's role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer. METHODS We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance. We assessed cetuximab efficacy using CCK8 proliferation assays and cell cycle analysis. Additionally, we examined the effects of AURKA inhibition with alisertib and created a dominant-negative YAP1 Ser397 mutant to assess its impact on cancer stem cell features. RESULTS The RAS/RAF wild-type CRC models exhibiting primary resistance to cetuximab prominently displayed elevated YAP1 phosphorylation at Ser397 primarily mediated by AURKA. AURKA-induced YAP1 phosphorylation was identified as a key trigger for cancer stem cell reprogramming. Consequently, we found that AURKA inhibition had the capacity to effectively restore cetuximab sensitivity and concurrently suppress the cancer stem cell phenotype. CONCLUSIONS AURKA inhibition holds promise as a therapeutic approach to overcome cetuximab resistance in RAS/RAF wild-type colorectal cancer, offering a potential means to counter the development of cancer stem cell phenotypes associated with cetuximab resistance.
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Affiliation(s)
- Anxo Rio-Vilariño
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Aiora Cenigaonandia-Campillo
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Ana García-Bautista
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Pedro A Mateos-Gómez
- Biochemistry and Molecular Biology Unit, Department of System Biology, School of Medicine and Health Sciences, University of Alcalá. Alcalá de Henares, Madrid, Spain
| | - Marina I Schlaepfer
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Laura Del Puerto-Nevado
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Oscar Aguilera
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Laura García-García
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain
| | - Carlos Galeano
- Pathology Department, IIS-Fundación Jiménez Diaz-UAM, Madrid, Spain
| | - Irene de Miguel
- Biochemistry and Molecular Biology Unit, Department of System Biology, School of Medicine and Health Sciences, University of Alcalá. Alcalá de Henares, Madrid, Spain
| | | | - Natalia Baños
- Preclinical program START Madrid-FJD, Hospital Fundación Jiménez Díaz-UAM, Madrid, Spain
| | - María Jesús Fernández-Aceñero
- Department of Pathology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Juan Carlos Lacal
- Instituto de Investigaciones Biomédicas, CSIC/UAM, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital La Paz, IDIPAZ, Madrid, Spain
| | - Enzo Medico
- Department of Oncology, Università degli Studi di Torino, Candiolo (TO), Italy
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy
| | - Jesús García-Foncillas
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain.
| | - Arancha Cebrián
- Translational Oncology Division, Oncohealth Institute, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Fundación Jiménez University Hospital (IIS-FJD, UAM), Madrid, Spain.
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Zhang S, Xu R, Hu M, Choueiry F, Jin N, Li J, Mo X, Zhu J. Distinct plasma molecular profiles between early-onset and late-onset colorectal cancer patients revealed by metabolic and lipidomic analyses. J Pharm Biomed Anal 2024; 241:115978. [PMID: 38237540 PMCID: PMC11181242 DOI: 10.1016/j.jpba.2024.115978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/24/2023] [Accepted: 01/09/2024] [Indexed: 02/21/2024]
Abstract
Colorectal cancer (CRC) incidence in younger adults has been steadily rising, warranting an in-depth investigation into the distinctions between early-onset CRC (EOCRC, < 50 years) and late-onset CRC (LOCRC, ≥ 50 years). Despite extensive study of clinical, pathological, and molecular traits, differentiating EOCRC from LOCRC and identifying potential biomarkers remain elusive. We analyzed plasma samples from healthy individuals, EOCRC, and LOCRC patients using liquid-chromatography mass spectrometry (LC/MS)-based metabolomics and lipidomics. Distinct polar metabolite and lipid profiles with significant metabolites altered in CRC group (e.g., choline and DG 40:4) were identified. Notably, EOCRC exhibited distinct polar metabolomic and differential lipidomic profiles compared to LOCRC, with polar metabolites like aminoadipate and uridine contributing significantly to the difference, and originating from pathways such as lysine biosynthesis and nucleotide metabolism. Furthermore, gene set enrichment analysis (GSEA) using independent TCGA gene expression data identified pathways significantly enriched in either EOCRC or LOCRC. Integrating gene expression and metabolomics data revealed numerous associations differentiating EOCRC and LOCRC. Our multi-omics integration underscores critical molecular distinctions, offers insights into the EOCRC development mechanisms and potential plasma biomarkers for diagnosis.
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Affiliation(s)
- Shiqi Zhang
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Rui Xu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Ming Hu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Fouad Choueiry
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Ning Jin
- Medical Oncology, The Ohio State University, Columbus, OH 43210, USA
| | - Jieli Li
- Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
| | - Xiaokui Mo
- Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA
| | - Jiangjiang Zhu
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA; James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
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9
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Görgec B, Verpalen IM, Sijberden JP, Abu Hilal M, Bipat S, Verhoef C, Swijnenburg RJ, Besselink MG, Stoker J. Added Value of Liver MRI in Patients Eligible for Surgical Resection or Ablation of Colorectal Liver Metastases Based on CT: A Systematic Review and Meta-Analysis. ANNALS OF SURGERY OPEN 2024; 5:e401. [PMID: 38883954 PMCID: PMC11175892 DOI: 10.1097/as9.0000000000000401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 02/19/2024] [Indexed: 06/18/2024] Open
Abstract
Background Abdominal computed tomography (CT) is the standard imaging modality for detection and staging in patients with colorectal liver metastases (CRLM). Although liver magnetic resonance imaging (MRI) is superior to CT in detecting small lesions, guidelines are ambiguous regarding the added value of an additional liver MRI in the surgical workup of patients with CRLM. Therefore, this systematic review and meta-analysis aimed to evaluate the clinical added value of liver MRI in patients eligible for resection or ablation of CRLM based on CT. Methods A systematic search was performed in the PubMed, Embase, and Cochrane Library databases through June 23, 2023. Studies investigating the impact of additional MRI on local treatment plan following CT in patients with CRLM were included. Risk of bias was assessed using the QUADAS-2 tool. The pooled weighted proportions for the primary outcome were calculated using random effect meta-analysis. Results Overall, 11 studies with 1440 patients were included, of whom 468 patients (32.5%) were assessed for change in local treatment plan. Contrast-enhanced liver MRI was used in 10 studies, including gadoxetic acid in 9 studies. Liver MRI with diffusion-weighted imaging was used in 8 studies. Pooling of data found a 24.12% (95% confidence interval, 15.58%-32.65%) change in the local treatment plan based on the added findings of liver MRI following CT. Sensitivity analysis including 5 studies (268 patients) focusing on monophasic portal venous CT followed by gadoxetic acid-enhanced liver MRI with diffusion-weighted imaging showed a change of local treatment plan of 17.88% (95% confidence interval, 5.14%-30.62%). Conclusions This systematic review and meta-analysis found that liver MRI changed the preinterventional local treatment plan in approximately one-fifth of patients eligible for surgical resection or ablation of CRLM based on CT. These findings suggest a clinically relevant added value of routine liver MRI in the preinterventional workup of CRLM, which should be confirmed by large prospective studies.
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Affiliation(s)
- Burak Görgec
- From the Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
| | - Inez M. Verpalen
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
| | - Jasper P. Sijberden
- From the Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Mohammad Abu Hilal
- Department of Surgery, Poliambulanza Foundation Hospital, Brescia, Italy
| | - Shandra Bipat
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Rutger-Jan Swijnenburg
- From the Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Marc G. Besselink
- From the Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Jaap Stoker
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, The Netherlands
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10
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Kopetskyi V, Antoniv M, Yarema R, Maksymovskyi V, Chetverikova-Ovchinnik V, Kryzhevskyi V, Volodko N, Gushchin V, Nikiforchin A. Building an Efficient Peritoneal Surface Malignancies Program Despite the Lower-Middle-Income Barriers: Ukraine Experience. JCO Glob Oncol 2024; 10:e2300432. [PMID: 38330272 DOI: 10.1200/go.23.00432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 11/26/2023] [Accepted: 12/04/2023] [Indexed: 02/10/2024] Open
Abstract
PURPOSE Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) programs are often limited to centers in developed countries because of extensive requirements. We aimed to analyze efficacy and challenges of CRS/HIPEC centers in lower-middle-income settings in the Ukraine example. METHODS A multicenter descriptive study was conducted using data sets (2008-2022) from Kyiv, Lviv, and Odesa centers. Patients with appendiceal neoplasm (AN); colorectal cancer (CRC); malignant peritoneal mesothelioma (MPM); and epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) treated with CRS ± HIPEC were included. Overall survival (OS) was analyzed for N ≥ 20 cohorts using the Kaplan-Meier method. RESULTS We included 596 patients. At Kyiv and Lviv centers, 37 and 28 patients with AN had completeness of cytoreduction (CC-0/1) rates of 84% and 71%, respectively. Thirty-day major morbidity stood at 24% and 18%, respectively. Median OS was not reached (NR) at both centers. Nineteen patients with CRC from Kyiv, 11 from Lviv, and 156 from Odesa had CC-0/1 rates of 84%, 91%, and 86%, respectively. Thirty-day major complications occurred in 16%, 18%, and 8%, respectively. Median OS in the Odesa cohort was 35 (95% CI, 32 to 38) months. Among 15 Kyiv, five Lviv, and six Odesa patients with MPM, CC-0/1 rates were 67%, 80%, and 100%, respectively, while major complications occurred in 13%, 0%, and 17%, respectively. OS was not analyzed because of small MPM cohorts. At Kyiv, Lviv, and Odesa centers, 91, 40, and 89 patients, respectively, had primary EOC. CC-0/1 rates were 79%, 100%, and 80%, and 30-day major morbidity rates were 23%, 5%, and 6%, respectively. Median OS was NR, 71 (95% CI, 32 to 110), and 67 (95% CI, 61 to 73) months, respectively. CONCLUSION CRS/HIPEC programs in lower-middle-income environment can achieve safety and survival that meet global standards. Our discussion highlights common obstacles in such settings and proposes effective overcoming strategies.
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Affiliation(s)
- Viacheslav Kopetskyi
- Department of Hepatopancreatobiliary Surgery, National Cancer Institute, Kyiv, Ukraine
| | - Marta Antoniv
- Department of Surgery, Ordensklinikum Linz, Linz, Austria
| | - Roman Yarema
- Department of Oncology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | | | | | - Vitalii Kryzhevskyi
- Department of Hepatopancreatobiliary Surgery, National Cancer Institute, Kyiv, Ukraine
| | - Nataliya Volodko
- Department of Oncology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
| | - Vadim Gushchin
- Department of Surgical Oncology, Mercy Medical Center, Baltimore, MD
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11
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Fernández Montes A, Alonso Orduña V, Asensio Martínez E, Rodríguez Salas N, Torres E, Cacho Lavín D, Rodríguez Alonso RM, Falcó E, Oliva JC, Cirera L, García Gómez J, Pericay C. The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer. Oncologist 2023; 28:e902-e909. [PMID: 37141400 PMCID: PMC10546812 DOI: 10.1093/oncolo/oyad117] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/17/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.
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Affiliation(s)
- Ana Fernández Montes
- Servicio de Oncología Médica, Complexo Hospitalario Universitario de Ourense, Calle Ramón Puga Noguerol, Ourense, Spain
| | - Vicente Alonso Orduña
- Servicio de Oncología Médica, Hospital Universitario Miguel Servet, Instituto de Investigacion Sanitaria de Aragon, Paseo Isabel la Católica, Zaragoza, Spain
| | - Elena Asensio Martínez
- Servicio de Oncología Médica, Hospital General Universitario de Elche, Carrer Almazara, Elche, Alicante, Spain
| | - Nuria Rodríguez Salas
- Servicio de Oncología Médica, Hospital Universitario La Paz, Paseo de la Castellana, Madrid, Spain
| | - Esperanza Torres
- UGC intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria and Instituto de Investigación Biomédica de Málaga (IBIMA), Campus de Teatinos, Málaga, Spain
| | - Diego Cacho Lavín
- Servicio de Oncología Médica, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
| | - Rosa María Rodríguez Alonso
- Servicio de Oncología Médica, Hospital Universitario Reina Sofía-Córdoba, Avenida Menéndez Pidal, Córdoba, Spain
| | - Esther Falcó
- Servicio de Oncología Médica, Hospital de Son Llàtzer, Carretera de Manacor, Palma de-Mallorca, Illes Balears, Spain
| | - Joan Carles Oliva
- Institut d’Investigació I Innovació I3PT, Fundació Parc Taulí, Plaça Taulí, Sabadell, Barcelona, Spain
| | - Lluis Cirera
- Servicio de Oncología Médica, Hospital Universitario Mútua Terrassa, Plaça del Doctor Robert, Terrassa, Barcelona, Spain
| | - Jesus García Gómez
- Servicio de Oncología Médica, Complexo Hospitalario Universitario de Ourense, Calle Ramón Puga Noguerol, Ourense, Spain
| | - Carles Pericay
- Servicio de Oncología Médica, Hospital Universitari Parc Taulí, Plaça Taulí, Sabadell, Barcelona, Spain
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12
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Rather TB, Parveiz I, Bhat GA, Rashid G, Wani RA, Khan IY, Mudassar S. Evaluation of Forkhead BOX M1 (FOXM1) gene expression in colorectal cancer. Clin Exp Med 2023; 23:2385-2405. [PMID: 36318377 DOI: 10.1007/s10238-022-00929-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/15/2022] [Indexed: 11/05/2022]
Abstract
Forkhead Box M1 (FOXM1)-a key cell cycle regulator is a member of the Forkhead transcription factor family. It plays a key role in embryogenesis and cell proliferation and has been strongly linked to various solid tumors. We sought to understand the regulation of FOXM1 in colorectal cancer (CRC), as well as if and to what extent other clinicopathological characteristics are associated with FOXM1. The investigation comprised 98 CRC samples and normal tissues (controls). All colon cancer patients had a colonoscopy and targeted biopsy. All rectal cancer patients had a CT and MRI. Real-time PCR, Immunohistochemistry, and Western blotting were used to evaluate FOXM1 expression, and the findings were analyzed using SPSS (v.26). FOXM1 mRNA and protein expression were substantially upregulated in tumor tissues, with the majority of these proteins localized in nucleo-cytoplasm. Elevated protein levels of FOXM1 were strongly correlated with lower education level, larger tumor size, lymph node status, lymphovascular invasion (LVI), perineural invasion (PNI), lymph node metastasis (LNM), tumor invasion depth (subserosal and serosal invasion), late stage (III and IV), localization (nucleo-cytoplasmic), intensity (strong) and recurrence. Based on survival analysis, FOXM1 overexpression and nucleo-cytoplasmic localization were associated with shorter disease-free survival while stage and PNI were linked to poorer overall and disease-free survival. According to the results of the Cox regression analysis, stage and PNI were significant predictors of prognosis in CRC patients. FOXM1 expression was elevated in CRC and was linked to reduced disease-free survival. These findings support prior reports and hence FOXM1 can be an important prognostic marker for CRC and a promising therapeutic target. Additionally, we found a link between poor disease-free survival and FOXM1's nucleo-cytoplasmic localization. However, since the sample size of this study was small, further research is needed to validate our findings.
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Affiliation(s)
- Tahseen Bilal Rather
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
| | - Ishrat Parveiz
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
| | - Gulzar A Bhat
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
| | - Gowhar Rashid
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India
- Department of Medical Lab Technology, Amity Medical School, Amity university, Haryana, India
| | - Rauf A Wani
- Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, India
| | - Ishrat Younas Khan
- Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, India
| | - Syed Mudassar
- Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India.
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13
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Wu YJ, Huang ST, Chang YH, Lin SY, Lin WL, Chen YJ, Chien ST. SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer. Curr Issues Mol Biol 2023; 45:8013-8026. [PMID: 37886949 PMCID: PMC10605852 DOI: 10.3390/cimb45100506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/28/2023] [Accepted: 09/29/2023] [Indexed: 10/28/2023] Open
Abstract
Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.
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Affiliation(s)
- Yueh-Jung Wu
- Division of Colorectal Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Siang-Ting Huang
- Cancer Center, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Ya-Hui Chang
- Cancer Center, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Shih-Yi Lin
- Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Weng-Ling Lin
- Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
| | - Ying-Jung Chen
- Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Shang-Tao Chien
- Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung 802, Taiwan
- Department of Nursing, Fooyin University, Kaohsiung 831, Taiwan
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14
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Tanomrat R, Naktubtim C, Aimvijarn P, Suwannalert P. N-acetylcysteine improves the inhibitory effect of Quercetin-rich onion extract on HT-29 and HCT-116 colorectal cancer migration and invasion through iNOS suppression. Int J Med Sci 2023; 20:1123-1134. [PMID: 37575276 PMCID: PMC10416724 DOI: 10.7150/ijms.86573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 07/11/2023] [Indexed: 08/15/2023] Open
Abstract
As colorectal cancer (CRC) usually presents at an advanced stage, it responds poorly to traditional surgery and chemoradiotherapy. Reactive oxygen species (ROSs) are a critical factor in cancer progression. Quercetin, a bioflavonoid derived from onion peel extract, provides great anti-oxidant and anti-cancer potential. Therefore, quercetin in combination with N-Acetylcysteine (NAC), a well-known anti-oxidant and adjuvant agent in cancer-chemotherapeutic drugs, was considered as a way of increasing treatment efficacy. Thus, this study aimed to evaluate the improvement effect of quercetin in combination with NAC in human CRC (HT-29 and HCT-116) cell progression, migration and invasion. Firstly, the effects of quercetin, NAC, and the combination of quercetin and NAC on cellular oxidants and glutathione levels were evaluated. Cell viability, anti-migrative activity and invasive activity were determined by MTT, wound healing, and Matrigel invasion tests, respectively. Then, the proteins involved in cell migration, invasion, and cellular oxidants were investigated. Moreover, the gene expression and overall survival were further validated by the GEPIA2 database. The results reveal that the combination was most effective in decreasing cellular oxidants and increasing glutathione levels, while there was a significant decrease in cancer cell migration and invasion involved in the suppression of iNOS, ICAM-1, and MMP-2 proteins. Furthermore, bioinformatic analysis verified that iNOS, ICAM-1, and MMP-2 were highly expressed in CRC tissue and also associated with a poor prognosis. This study demonstrated that Quercetin has higher efficacy when used in combination with NAC, representing a potential combination agent for anti-cancer drug development.
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Affiliation(s)
- Rataya Tanomrat
- Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Chonnapat Naktubtim
- Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
- Pathobiology Information and Learning Center, Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
| | - Parichaya Aimvijarn
- Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
- Department of Pathology, Faculty of Medicine, Kasetsart University, Bangkok 10900, Thailand
| | - Prasit Suwannalert
- Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
- Pathobiology Information and Learning Center, Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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15
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Fülöp AC, Serac G, Gurzu S. Detection of Hepatic Metastasis in Colorectal Cancer: A Comparative Case Report of 18F-FDG PET-CT and Diffusion-Weighted MRI with a b Value of 1000. J Belg Soc Radiol 2023; 107:52. [PMID: 37457674 PMCID: PMC10348067 DOI: 10.5334/jbsr.3186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 06/19/2023] [Indexed: 07/18/2023] Open
Abstract
Detection of hepatic metastasis from colorectal cancer remains a clinical challenge. In this case report, we present a 66-year-old male patient with a rectal carcinoma who underwent 18F-FDG PET-CT for staging, which revealed one hepatic metastasis. Abdominal magnetic resonance imaging (MRI) with diffusion-weighted sequence with a b value of 1000 was performed, which identified a second metastasis of the liver. Teaching Point This case report illustrates that, in some patients, diffusion-weighted MRI with a b value of 1000 might be a more sensitive technique for detecting small hepatic metastases than 18F-FDG PET-CT.
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Affiliation(s)
- Andrei-Cristian Fülöp
- Department of Radiology and Imaging, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
| | - Gabriel Serac
- Department of Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
| | - Simona Gurzu
- Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Romania
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16
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Fuad Hetta D, Abdelfatah Mohamed M, Elmorabaa HA, Ahmed MI, Elgalaly NA, Kamal SM. Efficacy of perioperative duloxetine as a part of multimodal analgesia in laparoscopic colorectal cancer surgeries. BMC Anesthesiol 2023; 23:166. [PMID: 37194004 DOI: 10.1186/s12871-023-02119-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 04/30/2023] [Indexed: 05/18/2023] Open
Abstract
BACKGROUND Although laparoscopic surgery provides earlier recovery, less morbidity and hospital stay, however, severe pain is still a problem after it. Duloxetine has been recently used in postoperative pain management. We tested perioperative duloxetine to evaluate its effect on patients undergoing laparoscopic colorectal cancer surgery. METHODS Sixty patients were enrolled in this study divided into two equal groups; duloxetine group each patient received an oral duloxetine capsule (60 mg) 1st dose at night before surgery, the 2nd dose 1 h preoperative, and the 3rd dose 24 h postoperative. Placebo group received placebo capsules at the same times. The cumulative morphine consumption in 48 h, postoperative VAS score, quality of recovery (QoR-40 score), sedation, and adverse effects were evaluated. RESULTS Duloxetine group had lower VAS scores compared to placebo group, (3 ± 0.69) VS. (4.17 ± 0.83), (2.5 ± 0.6) VS. (4.3 ± 0.9), (2.2 ± 0.7) VS. (3.9 ± 0.6), (1.6 ± 0.7) VS. (3.6 ± 0.8), (1.1 ± 0.8) VS. (3.7 ± 0.7), (0.7 ± 0.7) VS. (3.5 ± 0.8), (0.6 ± 0.7) VS. (3.5 ± 0.8) respectively, P ˂0.01. The cumulative morphine consumption was significantly reduced in the Duloxetine group compared to the placebo group (4.6 ± 2.9 vs. 11.3 ± 1.7 mg), P < 0.01. The total QoR-40 score for duloxetine group was (180.8 ± 4.5) vs. (156 ± 5.9) in placebo group (P < 0.01). Patients in Duloxetine group were more sedated in all the 48 h postoperatively in comparison to placebo group. CONCLUSIONS Perioperative duloxetine had reduced postoperative pain, decreased opioid consumption, and improved the quality of recovery in patients undergoing laparoscopic colorectal surgery.
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Affiliation(s)
- Diab Fuad Hetta
- Anesthesia and intensive care and pain management department, South Egypt Cancer Institiue, Assiut University, Assiut, Egypt
| | - Montaser Abdelfatah Mohamed
- Anesthesia and intensive care and pain management department, South Egypt Cancer Institiue, Assiut University, Assiut, Egypt
| | - Hany Ahmed Elmorabaa
- Anaesthesia, Intensive care and pain management department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mirna Ismail Ahmed
- Anesthesia and intensive care and pain management department, South Egypt Cancer Institiue, Assiut University, Assiut, Egypt
| | - Nourhan Alaa Elgalaly
- Anesthesia and intensive care and pain management department, South Egypt Cancer Institiue, Assiut University, Assiut, Egypt
| | - Shereen Mamdouh Kamal
- Anesthesia and intensive care and pain management department, South Egypt Cancer Institiue, Assiut University, Assiut, Egypt.
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17
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Carconi C, Cerreti M, Roberto M, Arrivi G, D'Ambrosio G, De Felice F, Di Civita MA, Iafrate F, Lucatelli P, Magliocca FM, Picchetto A, Picone V, Catalano C, Cortesi E, Tombolini V, Mazzuca F, Tomao S. The Management of Oligometastatic Disease in Colorectal Cancer: Present Strategies and Future Perspectives. Crit Rev Oncol Hematol 2023; 186:103990. [PMID: 37061075 DOI: 10.1016/j.critrevonc.2023.103990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 03/29/2023] [Accepted: 04/11/2023] [Indexed: 04/17/2023] Open
Abstract
Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.
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Affiliation(s)
- Catia Carconi
- Sant'Andrea University Hospital, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy
| | - Micaela Cerreti
- Sant'Andrea University Hospital, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy
| | - Michela Roberto
- UOC Oncologia A, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy.
| | - Giulia Arrivi
- Oncology Unit, Sant' Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Giancarlo D'Ambrosio
- Department of General Surgery, Surgical Specialties and Organ Transplantation, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Francesca De Felice
- Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy
| | - Mattia Alberto Di Civita
- UOC Oncologia A, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Franco Iafrate
- Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Pierleone Lucatelli
- Vascular and Interventional radiology Unit, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Fabio Massimo Magliocca
- Vascular and Interventional radiology Unit, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Andrea Picchetto
- Emergency Department, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Vincenzo Picone
- UOC Oncologia B, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Carlo Catalano
- Vascular and Interventional radiology Unit, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Enrico Cortesi
- UOC Oncologia B, Department of radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy
| | - Vincenzo Tombolini
- Department of Radiotherapy, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy
| | - Federica Mazzuca
- Oncology Unit, Sant' Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Silverio Tomao
- Oncology Unit, Sant' Andrea University Hospital, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
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18
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Basu B, Karmakar S, Basu M, Ghosh MK. USP7 imparts partial EMT state in colorectal cancer by stabilizing the RNA helicase DDX3X and augmenting Wnt/β-catenin signaling. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119446. [PMID: 36791810 DOI: 10.1016/j.bbamcr.2023.119446] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 02/08/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023]
Abstract
Epithelial mesenchymal transition (EMT) is a fundamental and highly regulated process that is normally observed during embryonic development and tissue repair but is deregulated during advanced cancer. Classically, through the process of EMT, cancer cells gradually transition from a predominantly epithelial phenotype to a more invasive mesenchymal phenotype. Increasing studies have, however, brought into light the existence of unique intermediary states in EMT, often referred to as partial EMT states. Through our studies we have found the deubiquitinase USP7 to be strongly associated with the development of such a partial EMT state in colon cancer cells, characterized by the acquisition of mesenchymal characteristics but without the reduction in epithelial markers. We found USP7 to be overexpressed in colon adenocarcinomas and to be closely associated with advancing tumor stage. We found that functional inhibition or knockdown of USP7 is associated with a marked reduction in mesenchymal markers and in overall migration potential of cancer cells. Starting off with a proteomics-based approach we were able to identify and later on verify the DEAD box RNA helicase DDX3X to be an interacting partner of USP7. We then went on to show that USP7, through the stabilization of DDX3X, augments Wnt/β-catenin signaling, which has previously been shown to be greatly associated with colorectal cancer cell invasiveness. Our results indicate USP7 as a novel key player in establishing a partial mesenchymal phenotype in colorectal cancer.
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Affiliation(s)
- Bhaskar Basu
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Subhajit Karmakar
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Malini Basu
- Department of Microbiology, Dhruba Chand Halder College, Dakshin Barasat, South 24 Parganas PIN-743372, India
| | - Mrinal K Ghosh
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata-700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
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19
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Plekhanov AA, Sirotkina MA, Gubarkova EV, Kiseleva EB, Sovetsky AA, Karabut MM, Zagainov VE, Kuznetsov SS, Maslennikova AV, Zagaynova EV, Zaitsev VY, Gladkova ND. Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography. Front Oncol 2023; 13:1121838. [PMID: 37064146 PMCID: PMC10100073 DOI: 10.3389/fonc.2023.1121838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young’s modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer – low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors.
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Affiliation(s)
- Anton A. Plekhanov
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
- *Correspondence: Anton A. Plekhanov,
| | - Marina A. Sirotkina
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Ekaterina V. Gubarkova
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Elena B. Kiseleva
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Alexander A. Sovetsky
- Laboratory of Wave Methods for Studying Structurally Inhomogeneous Media, Institute of Applied Physics Russian Academy of Sciences, Nizhny Novgorod, Russia
| | - Maria M. Karabut
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Vladimir E. Zagainov
- Department of Faculty Surgery and Transplantation, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
- Department of Pathology, Nizhny Novgorod Regional Oncologic Hospital, Nizhny Novgorod, Russia
| | - Sergey S. Kuznetsov
- Department of Pathology, Nizhny Novgorod Regional Oncologic Hospital, Nizhny Novgorod, Russia
| | - Anna V. Maslennikova
- Department of Oncology, Radiation Therapy and Radiation Diagnostics, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - Elena V. Zagaynova
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
- Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia
| | - Vladimir Y. Zaitsev
- Laboratory of Wave Methods for Studying Structurally Inhomogeneous Media, Institute of Applied Physics Russian Academy of Sciences, Nizhny Novgorod, Russia
| | - Natalia D. Gladkova
- Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia
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20
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Miao Z, Zhao X, Li X. [18F]FDG PET/CT versus [18F]FDG PET/MRI for the diagnosis of colorectal liver metastasis: A systematic review and meta-analysis. Front Oncol 2023; 13:1114059. [PMID: 36860315 PMCID: PMC9969139 DOI: 10.3389/fonc.2023.1114059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 01/31/2023] [Indexed: 02/16/2023] Open
Abstract
Purpose The purpose of our meta-analysis and systematic review was to compare the diagnostic performance of [18F]FDG PET/CT and [18F]FDG PET/MRI in colorectal liver metastasis. Methods We searched PubMed, Embase, and Web of Science for eligible articles until November 2022. Studies focusing on the diagnostic value of [18F]FDG PET/CT or PET/MRI for colorectal liver metastasis were included. Using a bivariate random-effect model, the pooled sensitivity and specificity for [18F]FDG PET/CT and [18F]FDG PET/MRI were reported as estimates with 95% confidence intervals (CIs). Heterogeneity among pooled studies was assessed using the I2 statistic. The Quality Assessment of Diagnostic Performance Studies (QUADAS-2) method was used to evaluate the quality of the studies that were included. Results There were a total of 2743 publications identified in the initial search, finally, a total of 21 studies comprising 1036 patients were included. The pooled sensitivity, specificity, and AUC of [18F]FDG PET/CT in were 0.86 (95% CI: 0.76-0.92), 0.89 (95% CI: 0.83-0.94), and 0.92(95% CI: 0.90-0.94). [18F]FDG PET/MRI were 0.84 (95% CI: 0.77-0.89), 1.00 (95% CI: 0.32-1.00), and 0.89(95% CI: 0.86-0.92), respectively. Conclusion [18F]FDG PET/CT shows similar performance compared to [18F]FDG PET/MRI in detecting colorectal liver metastasis. However, pathological results were not obtained for all patients in the included studies and PET/MRI results were derived from studies with small sample sizes. There is a need for additional, larger prospective studies on this issue. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier (CRD42023390949).
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Affiliation(s)
- Zhi Miao
- Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China,School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, China,*Correspondence: Zhi Miao,
| | - Xiaomeng Zhao
- Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China,School of Chemical Engineering and Technology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, China
| | - Xuanwen Li
- Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Japan
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21
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Zhang H, Zhao G, Zhu G, Ye J. Identification of lymph node metastasis-related genes and patterns of immune infiltration in colon adenocarcinoma. Front Oncol 2023; 12:907464. [PMID: 36727052 PMCID: PMC9884978 DOI: 10.3389/fonc.2022.907464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 12/30/2022] [Indexed: 01/18/2023] Open
Abstract
Backgrounds Colon adenocarcinoma(COAD) is one of the most common tumors of the digestive tract. Lymph node metastasis (LNM) is a well-established prognostic factor for COAD. The mechanism of COAD lymph node metastasis in immunology remains unknown. The identification of LNM-related biomarkers of COAD could help in its treatment. Thus, the current study was aimed to identify key genes and construct a prognostic signature. Methods Gene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes were calculated by using R software. GO functional and KEGG pathway enrichment analysis were processed. The CIBERSORT algorithm was used to assess immune cell infiltration. STRING database was used to screen key genes and constructed a protein-protein interaction network (PPI network). The LASSO-Cox regression analysis was performed based on the components of the PPI network. The correlation analysis between LNM-related signature and immune infiltrating cells was then investigated. TISIDB was used to explore the correlation between the abundance of immunomodulators and the expression of the inquired gene. Results In total, 394 differentially expressed genes were identified. After constructing and analyzing the PPI network, 180 genes were entered into the LASSO-Cox regression model, constructing a gene signature. Five genes(PMCH, LRP2, NAT1, NKAIN4, and CD1B) were identified as LNM-related genes of clinical value. Correlation analysis revealed that LRP2 and T follicular helper cells (R=0.34, P=0.0019) and NKAIN4 and T follicular helper cells (R=0.23, P=0.041) had significant correlations. Immunologic analysis revealed that LRP2 and NKAIN4 are potential coregulators of immune checkpoints in COAD. Conclusion In general, this study revealed the key genes related to lymph node metastasis and prognostic signature. Several potential mechanisms and therapeutic and prognostic targets of lymph node metastasis were also demonstrated in COAD.
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Affiliation(s)
- Haoxiang Zhang
- Department of Gastrointestinal Surgery 2 Section, Institute of Abdominal Surgery, Key Laboratory of Accurate Diagnosis and Treatment of Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China,Department of Gastrointestinal Surgery 2 Section, National Regional Medical Center, Fujian Medical University, Fuzhou, China
| | - Guibin Zhao
- Department of Gastrointestinal Surgery, Mindong Hospital Affiliated to Fujian Medical University, Fuan, China
| | - Guangwei Zhu
- Department of Gastrointestinal Surgery 2 Section, Institute of Abdominal Surgery, Key Laboratory of Accurate Diagnosis and Treatment of Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China,Department of Gastrointestinal Surgery 2 Section, National Regional Medical Center, Fujian Medical University, Fuzhou, China,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuan, China
| | - Jianxin Ye
- Department of Gastrointestinal Surgery 2 Section, Institute of Abdominal Surgery, Key Laboratory of Accurate Diagnosis and Treatment of Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China,Department of Gastrointestinal Surgery 2 Section, National Regional Medical Center, Fujian Medical University, Fuzhou, China,*Correspondence: Jianxin Ye,
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22
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Kdimati S, Bürtin F, Linnebacher M, Mullins CS. Patient-Derived Organoids for In Vivo Validation of In Vitro Data. Methods Mol Biol 2023; 2589:111-126. [PMID: 36255621 DOI: 10.1007/978-1-0716-2788-4_8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Patient-derived organoids are promising tumor models for functional validation of next-generation sequencing-based therapy recommendations. In times of rapidly advancing precision oncology approaches in everyday clinical processes, reliable and valid tumor models are required. Tumor organoids consist of tumor "stem" cells, differentiated (epithelial) tumor, and stroma cells. The cellular architecture and interactions closely mimic the original patient tumor. These organoids can be implanted into immunodeficient mice, generating patient-derived organoid-derived xenografts, thus enabling in vitro to in vivo transfer. Most importantly, the high clinical relevance of PDO models is maintained in this conversion. This protocol describes in detail the methods and techniques as well as the materials necessary to generate in vitro PDO and in vivo PDO-derived xenograft models. The elaborate process description starts with the processing of freshly obtained tumor tissue. The proceedings include tissue processing, organoid culturing, PDO implantation into immunodeficient mice, tumor explantation, and finally tumor preservation. All these proceedings are described in this timely chronological order. This protocol will enable researchers to generate PDO models from freshly received tumor tissue and generate PDO-derived xenografts. Models generated according to these methods are suitable for a very broad research spectrum.
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Affiliation(s)
- Said Kdimati
- Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
| | - Florian Bürtin
- Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
| | - Michael Linnebacher
- Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock, Germany
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23
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Tabari A, Chan SM, Omar OMF, Iqbal SI, Gee MS, Daye D. Role of Machine Learning in Precision Oncology: Applications in Gastrointestinal Cancers. Cancers (Basel) 2022; 15:cancers15010063. [PMID: 36612061 PMCID: PMC9817513 DOI: 10.3390/cancers15010063] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/14/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022] Open
Abstract
Gastrointestinal (GI) cancers, consisting of a wide spectrum of pathologies, have become a prominent health issue globally. Despite medical imaging playing a crucial role in the clinical workflow of cancers, standard evaluation of different imaging modalities may provide limited information. Accurate tumor detection, characterization, and monitoring remain a challenge. Progress in quantitative imaging analysis techniques resulted in "radiomics", a promising methodical tool that helps to personalize diagnosis and treatment optimization. Radiomics, a sub-field of computer vision analysis, is a bourgeoning area of interest, especially in this era of precision medicine. In the field of oncology, radiomics has been described as a tool to aid in the diagnosis, classification, and categorization of malignancies and to predict outcomes using various endpoints. In addition, machine learning is a technique for analyzing and predicting by learning from sample data, finding patterns in it, and applying it to new data. Machine learning has been increasingly applied in this field, where it is being studied in image diagnosis. This review assesses the current landscape of radiomics and methodological processes in GI cancers (including gastric, colorectal, liver, pancreatic, neuroendocrine, GI stromal, and rectal cancers). We explain in a stepwise fashion the process from data acquisition and curation to segmentation and feature extraction. Furthermore, the applications of radiomics for diagnosis, staging, assessment of tumor prognosis and treatment response according to different GI cancer types are explored. Finally, we discussed the existing challenges and limitations of radiomics in abdominal cancers and investigate future opportunities.
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Affiliation(s)
- Azadeh Tabari
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
- Correspondence:
| | - Shin Mei Chan
- Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06510, USA
| | - Omar Mustafa Fathy Omar
- Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
| | - Shams I. Iqbal
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Michael S. Gee
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
| | - Dania Daye
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
- Harvard Medical School, Boston, MA 02115, USA
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24
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Perlo D, Berton L, Delpiano A, Menchini F, Tibaldi S, Grosso M, Fonio P. Exploiting Liver CT scans in Colorectal Carcinoma genomics mutation classification. 2022 IEEE INTERNATIONAL CONFERENCE ON BIG DATA (BIG DATA) 2022:4425-4433. [DOI: 10.1109/bigdata55660.2022.10020613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Affiliation(s)
- Daniele Perlo
- Luxembourg Institute of Health, Fondazione Ricerca Molinette Onlus
| | - Luca Berton
- Fondazione Ricerca Molinette Onlus,Turin,Italy
| | | | | | | | | | - Paolo Fonio
- University of Turin,Dept. of Radiology,Turin,Italy
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25
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Tharwat M, Sakr NA, El-Sappagh S, Soliman H, Kwak KS, Elmogy M. Colon Cancer Diagnosis Based on Machine Learning and Deep Learning: Modalities and Analysis Techniques. SENSORS (BASEL, SWITZERLAND) 2022; 22:9250. [PMID: 36501951 PMCID: PMC9739266 DOI: 10.3390/s22239250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 11/24/2022] [Indexed: 06/17/2023]
Abstract
The treatment and diagnosis of colon cancer are considered to be social and economic challenges due to the high mortality rates. Every year, around the world, almost half a million people contract cancer, including colon cancer. Determining the grade of colon cancer mainly depends on analyzing the gland's structure by tissue region, which has led to the existence of various tests for screening that can be utilized to investigate polyp images and colorectal cancer. This article presents a comprehensive survey on the diagnosis of colon cancer. This covers many aspects related to colon cancer, such as its symptoms and grades as well as the available imaging modalities (particularly, histopathology images used for analysis) in addition to common diagnosis systems. Furthermore, the most widely used datasets and performance evaluation metrics are discussed. We provide a comprehensive review of the current studies on colon cancer, classified into deep-learning (DL) and machine-learning (ML) techniques, and we identify their main strengths and limitations. These techniques provide extensive support for identifying the early stages of cancer that lead to early treatment of the disease and produce a lower mortality rate compared with the rate produced after symptoms develop. In addition, these methods can help to prevent colorectal cancer from progressing through the removal of pre-malignant polyps, which can be achieved using screening tests to make the disease easier to diagnose. Finally, the existing challenges and future research directions that open the way for future work in this field are presented.
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Affiliation(s)
- Mai Tharwat
- Information Technology Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt
| | - Nehal A. Sakr
- Information Technology Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt
| | - Shaker El-Sappagh
- Information Systems Department, Faculty of Computers and Artificial Intelligence, Benha University, Benha 13512, Egypt
- Faculty of Computer Science and Engineering, Galala University, Suez 435611, Egypt
| | - Hassan Soliman
- Information Technology Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt
| | - Kyung-Sup Kwak
- Department of Information and Communication Engineering, Inha University, Incheon 22212, Republic of Korea
| | - Mohammed Elmogy
- Information Technology Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt
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Mao Q, Zhou MT, Zhao ZP, Liu N, Yang L, Zhang XM. Role of radiomics in the diagnosis and treatment of gastrointestinal cancer. World J Gastroenterol 2022; 28:6002-6016. [PMID: 36405385 PMCID: PMC9669820 DOI: 10.3748/wjg.v28.i42.6002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/24/2022] [Accepted: 10/27/2022] [Indexed: 11/10/2022] Open
Abstract
Gastrointestinal cancer (GIC) has high morbidity and mortality as one of the main causes of cancer death. Preoperative risk stratification is critical to guide patient management, but traditional imaging studies have difficulty predicting its biological behavior. The emerging field of radiomics allows the conversion of potential pathophysiological information in existing medical images that cannot be visually recognized into high-dimensional quantitative image features. Tumor lesion characterization, therapeutic response evaluation, and survival prediction can be achieved by analyzing the relationships between these features and clinical and genetic data. In recent years, the clinical application of radiomics to GIC has increased dramatically. In this editorial, we describe the latest progress in the application of radiomics to GIC and discuss the value of its potential clinical applications, as well as its limitations and future directions.
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Affiliation(s)
- Qi Mao
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Mao-Ting Zhou
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Zhang-Ping Zhao
- Department of Radiology, Panzhihua Central Hospital, Panzhihua 617000, Sichuan Province, China
| | - Ning Liu
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Lin Yang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiao-Ming Zhang
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
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Zhang W, Han X, Yang L, Song Y, Xie L, Gai W, Wang Y, Shi Y. Safety, pharmacokinetics and efficacy of SCT200, an anti-EGFR monoclonal antibody in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer: a phase I dose-escalation and dose-expansion study. BMC Cancer 2022; 22:1104. [PMID: 36307775 PMCID: PMC9617324 DOI: 10.1186/s12885-022-10147-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/26/2022] [Indexed: 12/02/2022] Open
Abstract
Background An over-expression of the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer and is associated with aggressive disease and poor prognosis. SCT200 is a newly developed recombinant, fully humanized, anti-EGFR monoclonal antibody. This study aimed to evaluate its safety, tolerability, pharmacokinetics (PK), and efficacy in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer (mCRC). Methods This phase I study comprising dose-escalation phase and dose-expansion phase. SCT200 was administrated intravenously to groups of three to six patients. An every 3-week dosing cycle (0.5–15.0 mg/kg) and multiple dosing schedule were evaluated. Blood samples were collected at preset intervals for PK assessment, radiological imaging was used for efficacy assessment, and continuous safety monitoring was performed in each group during the study. Results From December 16, 2014 to December 31, 2018, fifty-six patients with wild-type KRAS/NRAS/BRAF mCRC receiving ≥ 1 dose of SCT200 were evaluated. Among them, 44.6% (25/56) of the patients failed at least two prior lines of chemotherapy. No dose-limiting toxicities occurred in any group. All of the patients experienced treatment-emergent adverse events (TEAEs). 96.4% (54/56) of patients experienced treatment-related adverse events (TRAEs), and 26.8% (15/56) of patients with Grade ≥ 3 TRAEs. No serious TRAEs were observed. The most common TRAEs were dermotoxicity and hypomagnesemia. PK analysis showed non-linear PK in the range of 0.5 - 8.0 mg/kg of single dose SCT200, the clearance decreased, and the elimination half-life (T1/2) prolonged following dose increase. In the multiple-dose period, the clearance decreased, peak concentration increased, and T1/2 prolonged during prolonged drug administration, and a steady state was reached after five consecutive dose of 6.0 mg/kg quaque week (QW). The objective response rate (ORR) was 30.4% (17/56, 95% confidence interval [CI], 18.8%–44.1%). The ORR in the dose-expansion group (6.0 mg/kg QW) was 48.0% (12/25, 95% CI, 27.8%–68.7%), the median progression-free survival was 5.2 months (95%CI, 3.6–5.5), and the median overall survival was 20.2 months (95%CI, 12.1-not reached). Conclusions SCT200 showed favorable safety, PK profile, and preliminary efficacy for patients with wild-type KRAS/NRAS/BRAF mCRC. Trial registration This study was registered with ClinicalTrials.gov (NCT02211443). Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-10147-9.
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Xu W, Liu S, Chen Z, Wu F, Cao W, Tian Y, Xiong H. Bichromatic Imaging with Hemicyanine Fluorophores Enables Simultaneous Visualization of Non-alcoholic Fatty Liver Disease and Metastatic Intestinal Cancer. Anal Chem 2022; 94:13556-13565. [PMID: 36124440 DOI: 10.1021/acs.analchem.2c03100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Simultaneous detection of different diseases via a single fluorophore is challenging. We herein report a bichromatic fluorophore named Cy-914 for the simultaneous diagnosis of non-alcoholic fatty liver disease (NAFLD) and metastatic intestinal cancer by leveraging its NIR-I/NIR-II dual-color imaging capability. Cy-914 with a pKa of 6.98 exhibits high sensitivity to pH and viscosity, showing turn-on NIR-I fluorescence at 795 nm in an acidic tumor microenvironment, meanwhile displaying intense NIR-II fluorescence at 914/1030 nm under neutral to slightly basic viscous conditions. Notably, Cy-914 could sensitively and noninvasively monitor viscosity variations in the progression of NAFLD. More importantly, it was able to simultaneously visualize NAFLD (ex/em = 808/1000-1700 nm) and intestinal metastases (ex/em = 570/810-875 nm) in two independent channels without spectral cross interference after topical spraying, further improving fluorescence-guided surgery of tiny metastases less than 3 mm. This strategy may provide an understanding for developing multi-color fluorophores for multi-disease diagnosis.
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Affiliation(s)
- Weijia Xu
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Senyao Liu
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Zhaoming Chen
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Fapu Wu
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Wenwen Cao
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Yang Tian
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
| | - Hu Xiong
- Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
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Zhang J, Wu Y, Mu J, Xin D, Wang L, Fan Y, Zhang S, Xu Y. Glycosyltransferase-related long non-coding RNA signature predicts the prognosis of colon adenocarcinoma. Front Oncol 2022; 12:954226. [PMID: 36203430 PMCID: PMC9530784 DOI: 10.3389/fonc.2022.954226] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 08/23/2022] [Indexed: 11/29/2022] Open
Abstract
Purpose Colon adenocarcinoma (COAD) is the most common type of colorectal cancer (CRC) and is associated with poor prognosis. Emerging evidence has demonstrated that glycosylation by long noncoding RNAs (lncRNAs) was associated with COAD progression. To date, however, the prognostic values of glycosyltransferase (GT)-related lncRNAs in COAD are still largely unknown. Methods We obtained the expression matrix of mRNAs and lncRNAs in COAD from The Cancer Genome Atlas (TCGA) database. Then, the univariate Cox regression analysis was conducted to identify 33 prognostic GT-related lncRNAs. Subsequently, LASSO and multivariate Cox regression analysis were performed, and 7 of 33 GT-related lncRNAs were selected to conduct a risk model. Gene set enrichment analysis (GSEA) was used to analyze gene signaling pathway enrichment of the risk model. ImmuCellAI, an online tool for estimating the abundance of immune cells, and correlation analysis were used to explore the tumor-infiltrating immune cells in COAD. Finally, the expression levels of seven lncRNAs were detected in colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results A total of 1,140 GT-related lncRNAs were identified, and 7 COAD-specific GT-related lncRNAs (LINC02381, MIR210HG, AC009237.14, AC105219.1, ZEB1-AS1, AC002310.1, and AC020558.2) were selected to conduct a risk model. Patients were divided into high- and low-risk groups based on the median of risk score. The prognosis of the high-risk group was worse than that of the low-risk group, indicating the good reliability and specificity of our risk model. Additionally, a nomogram based on the risk score and clinical traits was built to help clinical decisions. GSEA showed that the risk model was significantly enriched in metabolism-related pathways. Immune infiltration analysis revealed that five types of immune cells were significantly different between groups, and two types of immune cells were negatively correlated with the risk score. Besides, we found that the expression levels of these seven lncRNAs in tumor cells were significantly higher than those in normal cells, which verified the feasibility of the risk model. Conclusion The efficient risk model based on seven GT-related lncRNAs has prognostic potential for COAD, which may be novel biomarkers and therapeutic targets for COAD patients.
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Affiliation(s)
- Jiawei Zhang
- Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yinan Wu
- Zhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, China
| | - Jiayi Mu
- Zhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dijia Xin
- Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Luyao Wang
- Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yili Fan
- Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Suzhan Zhang
- Zhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- *Correspondence: Suzhan Zhang, ; Yang Xu,
| | - Yang Xu
- Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China
- *Correspondence: Suzhan Zhang, ; Yang Xu,
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Qin Y, Zhu LH, Zhao W, Wang JJ, Wang H. Review of Radiomics- and Dosiomics-based Predicting Models for Rectal Cancer. Front Oncol 2022; 12:913683. [PMID: 36016617 PMCID: PMC9395725 DOI: 10.3389/fonc.2022.913683] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 06/23/2022] [Indexed: 12/20/2022] Open
Abstract
By breaking the traditional medical image analysis framework, precision medicine-radiomics has attracted much attention in the past decade. The use of various mathematical algorithms offers radiomics the ability to extract vast amounts of detailed features from medical images for quantitative analysis and analyzes the confidential information related to the tumor in the image, which can establish valuable disease diagnosis and prognosis models to support personalized clinical decisions. This article summarizes the application of radiomics and dosiomics in radiation oncology. We focus on the application of radiomics in locally advanced rectal cancer and also summarize the latest research progress of dosiomics in radiation tumors to provide ideas for the treatment of future related diseases, especially 125I CT-guided radioactive seed implant brachytherapy.
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Affiliation(s)
- Yun Qin
- School of Physics, Beihang University, Beijing, China
| | - Li-Hua Zhu
- School of Physics, Beihang University, Beijing, China
| | - Wei Zhao
- School of Physics, Beihang University, Beijing, China
| | - Jun-Jie Wang
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, China
| | - Hao Wang
- Department of Radiation Oncology, Peking University Third Hospital, Beijing, China
- Cancer Center, Peking University Third Hospital, Beijing, China
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Noninvasive urinary protein signatures associated with colorectal cancer diagnosis and metastasis. Nat Commun 2022; 13:2757. [PMID: 35589723 PMCID: PMC9119985 DOI: 10.1038/s41467-022-30391-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 04/25/2022] [Indexed: 12/24/2022] Open
Abstract
Currently, imaging, fecal immunochemical tests (FITs) and serum carcinoembryonic antigen (CEA) tests are not adequate for the early detection and evaluation of metastasis and recurrence in colorectal cancer (CRC). To comprehensively identify and validate more accurate noninvasive biomarkers in urine, we implement a staged discovery-verification-validation pipeline in 657 urine and 993 tissue samples from healthy controls and CRC patients with a distinct metastatic risk. The generated diagnostic signature combined with the FIT test reveals a significantly increased sensitivity (+21.2% in the training set, +43.7% in the validation set) compared to FIT alone. Moreover, the generated metastatic signature for risk stratification correctly predicts over 50% of CEA-negative metastatic patients. The tissue validation shows that elevated urinary protein biomarkers reflect their alterations in tissue. Here, we show promising urinary protein signatures and provide potential interventional targets to reliably detect CRC, although further multi-center external validation is needed to generalize the findings. More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.
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Khan AA, Mannan V, Pervaiz MA, Akram A, Momin ES, Sanusi M, Kashyap T, Elshaikh AO. The Role of Glucosamine and Chondroitin Sulfate in the Prevention of Colorectal Cancer: A Systematic Review. Cureus 2022; 14:e25401. [PMID: 35774674 PMCID: PMC9236665 DOI: 10.7759/cureus.25401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/25/2022] [Indexed: 12/24/2022] Open
Abstract
Currently, colorectal cancer is the third most common cancer in the world. Recently, glucosamine and chondroitin have gained popularity for their beneficial effects on cancer. They have already been recognized for their therapeutic role in osteoarthritis. This systematic review aims to analyze the relationship between the combined consumption of glucosamine and chondroitin and the prevention of colorectal cancer. Three databases: PubMed, Google Scholar, and Science Direct, were searched to collect relevant articles. After screening full-text articles, seven studies were included in the systematic review. The review found a supportive association between glucosamine and chondroitin and the decreased incidence of colorectal cancer. Through an anti-inflammatory effect on the cell signaling pathway, the supplementation caused a reduction in colorectal cancer occurrence. The dose, frequency of usage of the supplement, and weight of individuals, along with the use of non-steroidal anti-inflammatory drugs, also affected the efficacy. To further assess this relationship, it is necessary to conduct double-blind, randomized controls trials for the supplements in cancer prevention and further explore their safety and efficacy with different ethnicities, drugs, doses, and weight individuals.
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Affiliation(s)
- Asma A Khan
- College of Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Vij Mannan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Muhammad Ahad Pervaiz
- Urology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aqsa Akram
- Internal Medicine, Dallah Hospital, Riyadh, SAU.,Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Elina S Momin
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.,Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand Municipal Medical College, Ahmedabad, IND
| | - Muhammad Sanusi
- Internal Medicine, Cardiology, Shenyang Medical College, Shenyang, CHN.,Internal Medicine, Cardiology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Tejasvi Kashyap
- General Practice, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Abeer O Elshaikh
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Cheng YX, Liu XY, Kang B, Tao W, Wei ZQ, Peng D. Comparison of surgical and oncologic outcomes in very elderly patients (≥ 80 years old) and elderly (65-79 years old) colorectal cancer patients: a propensity score matching. BMC Gastroenterol 2022; 22:205. [PMID: 35468733 PMCID: PMC9036748 DOI: 10.1186/s12876-022-02277-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 04/05/2022] [Indexed: 12/14/2022] Open
Abstract
Purpose The purpose of this study was to investigate the short-term outcomes and prognosis of elderly and very elderly colorectal cancer (CRC) patients after primary CRC surgery using propensity score matching (PSM). Methods This study retrospectively collected the medical records of CRC patients ≥ 65 years old undergoing primary CRC surgery from Jan 2011 to Jan 2020. Short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared between very elderly CRC patients (≥ 80 years old) and elderly CRC patients (65–79 years old). Results A total of 2084 patients were enrolled for analysis. After PSM, 331 very elderly patients were matched to 331 elderly patients. In terms of short-term outcomes, the very elderly patients had longer postoperative hospital stays (p = 0.007) after PSM. In terms of OS, it was found that age (p < 0.01, HR = 1.878, 95% CI 1.488–2.371), tumor stage (p < 0.01, HR = 1.865, 95% CI 1.603–2.170), overall complications (p < 0.01, HR = 1.514, 95% CI 1.224–1.872) and major complications (p = 0.001, HR = 2.012, 95% CI 1.319–3.069) were independent prognostic factors. For DFS, age (p < 0.01, HR = 1.816, 95% CI 1.579–2.088), tumor stage (p < 0.01, HR = 1.816, 95% CI 1.579–2.088), overall complications (p = 0.002, HR = 1.379, 95% CI 1.128–1.685) and major complications (p = 0.002, HR = 1.902, 95% CI 1.259–2.874) were found to be independent prognostic factors. Moreover, elderly patients had a better OS and DFS than very elderly patients. Conclusion Very elderly patients had a poorer prognosis than elderly patients after primary CRC surgery. Surgeons should be cautious when treating very elderly CRC patients.
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Affiliation(s)
- Yu-Xi Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing, Medical University, Chongqing, 400016, China
| | - Xiao-Yu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing, Medical University, Chongqing, 400016, China
| | - Bing Kang
- Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Wei Tao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing, Medical University, Chongqing, 400016, China
| | - Zheng-Qiang Wei
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing, Medical University, Chongqing, 400016, China
| | - Dong Peng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing, Medical University, Chongqing, 400016, China.
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Langko JM, Atmaja MHS, Laraswati B. Transverse Colorectal Carcinoma Imaging: A Case Report. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Colorectal cancer (CRC) is a type of malignancy in the digestive system. Colorectal cancer can be found anywhere along the large intestine from the cecum to the rectum. However, transverse colorectal cancer is a rare case and is only found in 6.8% of total colorectal cancers. A 64-year-old male patient with complaints of weakness, changes in the pattern of defecation, namely dark brown bowel movements for approximately +/- 8 months, anemia, and an increase in serum CEA. The results of the initial examination with plain abdominal radiographs did not reveal any abnormalities, only normal gas shadows mixed with fecal material were found that were prominent in the right to left hypochondrium region. After further examination, the patient was found to have stage 4 transverse colorectal cancer. The diagnosis of transverse colorectal carcinoma (CRC) was established based on fluoroscopy findings which showed filling abnormalities and colonic lumen irregularities in the medial 1/3 of the transverse colon forming an apple core image with the narrowest diameter + /- 3 mm along +/- 6 cm, shouldering sign (+), and on CT abdomen with contrast, an intraluminal malignant mass was found (Staging AJCC 8th ed 2018 T4aN2aM0). The diagnosis of CRC was confirmed by the results of resection and histopathological examination which found well-differentiated adenocarcinoma of the colon.
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Arabahmadi M, Farahbakhsh R, Rezazadeh J. Deep Learning for Smart Healthcare-A Survey on Brain Tumor Detection from Medical Imaging. SENSORS (BASEL, SWITZERLAND) 2022; 22:1960. [PMID: 35271115 PMCID: PMC8915095 DOI: 10.3390/s22051960] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/18/2022] [Accepted: 02/28/2022] [Indexed: 12/13/2022]
Abstract
Advances in technology have been able to affect all aspects of human life. For example, the use of technology in medicine has made significant contributions to human society. In this article, we focus on technology assistance for one of the most common and deadly diseases to exist, which is brain tumors. Every year, many people die due to brain tumors; based on "braintumor" website estimation in the U.S., about 700,000 people have primary brain tumors, and about 85,000 people are added to this estimation every year. To solve this problem, artificial intelligence has come to the aid of medicine and humans. Magnetic resonance imaging (MRI) is the most common method to diagnose brain tumors. Additionally, MRI is commonly used in medical imaging and image processing to diagnose dissimilarity in different parts of the body. In this study, we conducted a comprehensive review on the existing efforts for applying different types of deep learning methods on the MRI data and determined the existing challenges in the domain followed by potential future directions. One of the branches of deep learning that has been very successful in processing medical images is CNN. Therefore, in this survey, various architectures of CNN were reviewed with a focus on the processing of medical images, especially brain MRI images.
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Affiliation(s)
| | - Reza Farahbakhsh
- Institut Polytechnique de Paris, Telecom SudParis, 91000 Evry, France;
| | - Javad Rezazadeh
- North Tehran Branch, Azad University, Tehran 1667914161, Iran;
- Kent Institute Australia, Sydney, NSW 2000, Australia
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Gurba A, Taciak P, Sacharczuk M, Młynarczuk-Biały I, Bujalska-Zadrożny M, Fichna J. Gold (III) Derivatives in Colon Cancer Treatment. Int J Mol Sci 2022; 23:724. [PMID: 35054907 PMCID: PMC8775370 DOI: 10.3390/ijms23020724] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/03/2022] [Accepted: 01/04/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.
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Affiliation(s)
- Agata Gurba
- Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.T.); (M.S.); (M.B.-Z.)
| | - Przemysław Taciak
- Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.T.); (M.S.); (M.B.-Z.)
| | - Mariusz Sacharczuk
- Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.T.); (M.S.); (M.B.-Z.)
- Department of Genomics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland
| | - Izabela Młynarczuk-Biały
- Department for Histology and Embryology, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland;
| | - Magdalena Bujalska-Zadrożny
- Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland; (P.T.); (M.S.); (M.B.-Z.)
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland;
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Small Particle DEBIRI TACE as Salvage Therapy in Patients with Liver Dominant Colorectal Cancer Metastasis: Retrospective Analysis of Safety and Outcomes. Curr Oncol 2022; 29:209-220. [PMID: 35049694 PMCID: PMC8774320 DOI: 10.3390/curroncol29010020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 12/22/2022] Open
Abstract
The aim of this study was to examine the safety and efficacy of 40 µm and 75 µm calibrated irinotecan-eluting beads (DEBIRI-TACE) for the treatment of colorectal cancer metastases. We conducted a retrospective review of 36 patients with unresectable liver metastases from colorectal cancer who were treated with DEBIRI-TACE between 2017 to 2020. Patients who received at least one session of DEBIRI were included in our analysis. A total of 105 DEBIRI sessions were completed. 86% of patients (n = 31) underwent one round of treatment, 14% of patients (n = 5) underwent two distinct rounds of treatment. The majority of patients were discharged the next day (92%, n = 33 patients) with no 30-day post-DEBIRI mortality. Five high-grade adverse events occurred, including longer stay for pain management (n = 2), postembolization syndrome requiring readmission (n = 2), and liver abscess (n = 1). The average survival from diagnosis of metastatic disease was 33.3 months (range 11–95, median 28). Nine of 36 patients are still alive (December 2020) and have an average follow-up time of 36.8 months from T0 (range 12–63, median 39). Small particle DEBIRI is safe and well-tolerated in the salvage setting, with outcomes comparable to that of larger bead sizes.
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Chen SH, Miles K, Taylor SA, Ganeshan B, Rodriquez M, Fraioli F, Wan S, Afaq A, Shortman R, Walls D, Hoy L, Endozo R, Bhargava A, Hanson M, Huang J, Raouf S, Francis D, Siddiqi S, Arulampalam T, Sizer B, Machesney M, Reay-Jones N, Dindyal S, Ng T, Groves AM. FDG-PET/CT in colorectal cancer: potential for vascular-metabolic imaging to provide markers of prognosis. Eur J Nucl Med Mol Imaging 2021; 49:371-384. [PMID: 33837843 PMCID: PMC8712298 DOI: 10.1007/s00259-021-05318-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 03/13/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. METHODS This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. RESULTS A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon - high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441-8.333), p = 0.006; M0rectum - high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901-10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162-5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants. CONCLUSION Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility.
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Affiliation(s)
- Shih-hsin Chen
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
- Department of Nuclear Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Kenneth Miles
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
| | - Stuart A. Taylor
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
- Centre for Medical Imaging, University College London, London, UK
| | - Balaji Ganeshan
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
| | - Manuel Rodriquez
- University College London Hospitals (UCLH) NHS Foundation Trust, Surgery and Cancer Board, Imaging Division, University College Hospital (UCH), London, UK
- Department of Research Pathology, Cancer Institute, UCL, London, UK
| | - Francesco Fraioli
- University College London Hospitals (UCLH) NHS Foundation Trust, Surgery and Cancer Board, Imaging Division, University College Hospital (UCH), London, UK
| | - Simon Wan
- University College London Hospitals (UCLH) NHS Foundation Trust, Surgery and Cancer Board, Imaging Division, University College Hospital (UCH), London, UK
| | - Asim Afaq
- University College London Hospitals (UCLH) NHS Foundation Trust, Surgery and Cancer Board, Imaging Division, University College Hospital (UCH), London, UK
- University of Iowa, Carver College of Medicine, Iowa City, USA
| | - Robert Shortman
- Department of Nuclear Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Darren Walls
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
| | - Luke Hoy
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
| | - Raymond Endozo
- University College London Hospitals (UCLH) NHS Foundation Trust, Surgery and Cancer Board, Imaging Division, University College Hospital (UCH), London, UK
| | - Aman Bhargava
- Institute of Health Barts and London Medical School, Queen Mary University of London (QMUL), London, UK
| | - Matthew Hanson
- Barking, Havering and Redbridge University Hospitals NHS Trust, Division of Cancer and Clinical Support, Queens and King George Hospitals, Essex, UK
| | - Joseph Huang
- Barking, Havering and Redbridge University Hospitals NHS Trust, Division of Cancer and Clinical Support, Queens and King George Hospitals, Essex, UK
| | - Sherif Raouf
- Barking, Havering and Redbridge University Hospitals NHS Trust, Division of Cancer and Clinical Support, Queens and King George Hospitals, Essex, UK
- Radiotherapy Department, Barts Cancer Centre, St Bartholomew’s Hospital, West Smithfield, London, UK
| | - Daren Francis
- Royal Free London NHS Foundation Trust, Department of Colorectal Surgery, Barnet and Chase Farm Hospitals, London, UK
| | - Shahab Siddiqi
- Mid Essex Hospital Services NHS Trust, Department of Lower GI Surgery and Coloproctology, Broomfield Hospital, Essex, UK
| | - Tan Arulampalam
- East Suffolk and North Essex NHS Foundation Trust, Department of Surgery & Department of Clinical Oncology, Colchester General Hospital, Essex, UK
| | - Bruce Sizer
- East Suffolk and North Essex NHS Foundation Trust, Department of Surgery & Department of Clinical Oncology, Colchester General Hospital, Essex, UK
| | - Michael Machesney
- Barts Health NHS Trust, Cancer Clinical Board, Colorectal Surgery, Whipps Cross Hospital, London, UK
| | - Nicholas Reay-Jones
- East and North Hertfordshire NHS Trust, Colorectal Surgery, Queen Elizabeth II Hospital, Hertfordshire, UK
| | - Sanjay Dindyal
- East and North Hertfordshire NHS Trust, Colorectal Surgery, Lister Hospital, Hertfordshire, UK
| | - Tony Ng
- School of Cancer & Pharmaceutical Sciences, Kings College London (KCL), London, UK
| | - Ashley M Groves
- Division of Medicine, Research Department of Imaging, University College London (UCL), London, UK
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Chen W, Di Z, Chen Z, Nan K, Gu J, Ge F, Liu J, Zhang H, Miao C. NBPF4 mitigates progression in colorectal cancer through the regulation of EZH2-associated ETFA. J Cell Mol Med 2021; 25:9038-9050. [PMID: 34405537 PMCID: PMC8435418 DOI: 10.1111/jcmm.16867] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 07/30/2021] [Accepted: 08/05/2021] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of death worldwide, and hence, there is a need to elucidate the molecular mechanisms contributing to the progression of CRC. In this study, we aimed at assessing the role of long non‐coding RNA NBPF4 on the tumorigenesis of CRC. Silencing or overexpression experiments were performed on HCT116 and SW260 in vitro models. BALB/c athymic female nude mice aged 5–6 weeks were used as in vivo models. To assess the relationship between NBPF4 and its regulatory RNA pull‐down assay, RNA immunoprecipitation, luciferase activity, Western blotting and qRT‐PCR were employed. Initially, we identified that NBPF4 was downregulated in CRC tissues and cell lines. Furthermore, we observed that NBPF4 decreased tumorigenesis in both in vitro and in vivo models. Additionally, we identified that ETFA was highly expressed in CRCs and was negatively associated with NBPF4. Subsequently, we identified that EZH2, a transcriptional factor, activated ETFA by enhancing the methylation of its promoter, and EZH2 was also highly regulated in CRCs. Using COAD and READ databases, we confirmed that EZH2 and ETFA were positively correlated. Furthermore, we identified NBPF4 and EZH2 were targets for ZFP36, which bound and positively regulated NBPF4. This prevented NBPF4 from binding to its negative regulator miR‐17‐3p. Our results demonstrated that NBPF4 downregulated EZH2 and stabilized itself by binding to ZFP36, thus escaping from inhibition by miR‐17‐3p, which allowed mitigation of CRC through inhibition of ETFA.
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Affiliation(s)
- Wankun Chen
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.,Fudan Zhangjiang Institute, Shanghai, China
| | - Zhou Di
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaoyuan Chen
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ke Nan
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiahui Gu
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Feng Ge
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jinlong Liu
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hao Zhang
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Changhong Miao
- Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.,Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
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Zhang P, Liu G, Lu L. N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients. Front Cell Dev Biol 2021; 9:703629. [PMID: 34336856 PMCID: PMC8321625 DOI: 10.3389/fcell.2021.703629] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 06/21/2021] [Indexed: 12/12/2022] Open
Abstract
Background Colon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown. Materials and Methods The m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status. Results We identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group. Conclusion In this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.
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Affiliation(s)
- Peiling Zhang
- Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Guolong Liu
- Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Lin Lu
- Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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Balkrishnan R, Desai RP, Narayan A, Camacho FT, Flausino LE, Chammas R. Associations between initiating antihypertensive regimens on stage I-III colorectal cancer outcomes: A Medicare SEER cohort analysis. Cancer Med 2021; 10:5347-5357. [PMID: 34184420 PMCID: PMC8335848 DOI: 10.1002/cam4.4088] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 05/24/2021] [Accepted: 06/04/2021] [Indexed: 12/15/2022] Open
Abstract
Purpose Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. Patients and Methods This study was a non‐interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End‐Results (SEER)‐Medicare database. The association between AH drug utilization on AJCC stage I–III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. Results The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer‐specific mortality (HR: 0.79, 95% CI: 0.75–0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80–0.87), beta‐blockers (HR: 0.87, 95% CI: 0.84–0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80–0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer‐specific mortality (HR: 0.94, 95% CI: 0.90–0.98). Conclusion Further research needs to be performed, but AH medications may present a promising, low‐cost pathway to supporting CRC treatment for stage I–III cancers.
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Affiliation(s)
- Rajesh Balkrishnan
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Raj P Desai
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Aditya Narayan
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Fabian T Camacho
- Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Lucas E Flausino
- Universidade de São Paulo Instituto do Câncer do Estado de São Paulo, Sao Paulo, Brazil
| | - Roger Chammas
- Center for Translational Research in Onc, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, Brazil
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Shroff N, Bhargava P. Metastatic Cecal Adenocarcinoma presenting as acute appendicitis. Radiol Case Rep 2021; 16:2129-2132. [PMID: 34158906 PMCID: PMC8203588 DOI: 10.1016/j.radcr.2021.04.077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 04/30/2021] [Indexed: 12/29/2022] Open
Abstract
This case report details the findings of metastatic colon cancer in an older male patient who initially presented with signs and symptoms of acute appendicitis. The patient underwent routine CT (Computed Tomography) imaging for diagnostic evaluation of appendicitis. Subsequently, the patient was found to have findings consistent with acute appendicitis secondary to obstruction from a cecal mass with evidence of hepatic and pulmonary metastases. This case report demonstrates the radiological findings of acute appendicitis secondary to metastatic colorectal disease and highlights the importance of considering underlying malignancy in cases of appendicitis occurring in older individuals.
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Affiliation(s)
- Neel Shroff
- Department of Radiology, University of Texas Medical Branch, Galveston, TX, 77555
| | - Peeyush Bhargava
- Department of Radiology, University of Texas Medical Branch, Galveston, TX, 77555
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Cheng YX, Tao W, Zhang H, Peng D, Wei ZQ. Does liver cirrhosis affect the surgical outcome of primary colorectal cancer surgery? A meta-analysis. World J Surg Oncol 2021; 19:167. [PMID: 34107967 PMCID: PMC8191032 DOI: 10.1186/s12957-021-02267-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/18/2021] [Indexed: 12/16/2022] Open
Abstract
PURPOSE The purpose of this meta-analysis was to evaluate the effect of liver cirrhosis (LC) on the short-term and long-term surgical outcomes of colorectal cancer (CRC). METHODS The PubMed, Embase, and Cochrane Library databases were searched from inception to March 23, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of enrolled studies, and RevMan 5.3 was used for data analysis in this meta-analysis. The registration ID of this current meta-analysis on PROSPERO is CRD42021238042. RESULTS In total, five studies with 2485 patients were included in this meta-analysis. For the baseline information, no significant differences in age, sex, tumor location, or tumor T staging were noted. Regarding short-term outcomes, the cirrhotic group had more major complications (OR=5.15, 95% CI=1.62 to 16.37, p=0.005), a higher re-operation rate (OR=2.04, 95% CI=1.07 to 3.88, p=0.03), and a higher short-term mortality rate (OR=2.85, 95% CI=1.93 to 4.20, p<0.00001) than the non-cirrhotic group. However, no significant differences in minor complications (OR=1.54, 95% CI=0.78 to 3.02, p=0.21) or the rate of intensive care unit (ICU) admission (OR=0.76, 95% CI=0.10 to 5.99, p=0.80) were noted between the two groups. Moreover, the non-cirrhotic group exhibited a longer survival time than the cirrhotic group (HR=2.96, 95% CI=2.28 to 3.85, p<0.00001). CONCLUSION Preexisting LC was associated with an increased postoperative major complication rate, a higher rate of re-operation, a higher short-term mortality rate, and poor overall survival following CRC surgery.
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Affiliation(s)
- Yu-Xi Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Wei Tao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Hua Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Dong Peng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
| | - Zheng-Qiang Wei
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
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Zhu Y, Xiong H, Chen Y, Liu Z, Jiang Z, Huang R, Gao F, Zhang Q, Wang M, Jin Y, Qiao T, Ma T, Hu H, Wang X, Tang Q, Wang G. Comparison of natural orifice specimen extraction surgery and conventional laparoscopic-assisted resection in the treatment effects of low rectal cancer. Sci Rep 2021; 11:9338. [PMID: 33927293 PMCID: PMC8085046 DOI: 10.1038/s41598-021-88790-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 04/14/2021] [Indexed: 02/07/2023] Open
Abstract
Natural orifice specimen extraction surgery (NOSES) is an intra-abdominal procedure that does not require an auxiliary incision to take a surgical sample from the abdominal wall through the natural orifice, but there are few systematic clinical studies on it. The aim of this study was to demonstrate the safety and feasibility of NOSES. We retrospectively analyzed the clinical data and follow-up of 165 patients with low rectal cancer who underwent NOSES or conventional laparoscopic surgery at our center from January 2013 to June 2015. From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (49.3 ± 55.8 ml vs. 75.1 ± 57.3 ml, p = 0.02), shorter postoperative gastrointestinal recovery (42.3 ± 15.5 h vs. 50.1 ± 17.0 h, p = 0.01), less postoperative analgesic use (35.6% vs. 57.6%, p = 0.02), lower postoperative pain scores, lower rate of postoperative complications (6.8% vs. 25.4%, p = 0.01), better satisfaction of the image and cosmesis of the abdominal wall postoperatively, and higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups. Overall, NOSES is a safe and reliable minimally invasive surgical technique for patients with low rectal cancer.
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Affiliation(s)
- Yihao Zhu
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Huan Xiong
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Yinggang Chen
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Rui Huang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Feng Gao
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Qian Zhang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.,Department of Colorectal Surgery, Zhejiang Cancer Hospital (Affiliated Cancer Hospital of the Chinese Academy of Sciences), Hangzhou, 310022, China
| | - Meng Wang
- Department of Colorectal Surgery, Zhejiang Cancer Hospital (Affiliated Cancer Hospital of the Chinese Academy of Sciences), Hangzhou, 310022, China
| | - Yinghu Jin
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Tianyu Qiao
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Tianyi Ma
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Hanqing Hu
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Xishan Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.,Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Qingchao Tang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
| | - Guiyu Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. .,Department of Colorectal Surgery, Zhejiang Cancer Hospital (Affiliated Cancer Hospital of the Chinese Academy of Sciences), Hangzhou, 310022, China.
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Georgieva M, Gospodinova Z, Keremidarska-Markova M, Kamenska T, Gencheva G, Krasteva N. PEGylated Nanographene Oxide in Combination with Near-Infrared Laser Irradiation as a Smart Nanocarrier in Colon Cancer Targeted Therapy. Pharmaceutics 2021; 13:pharmaceutics13030424. [PMID: 33809878 PMCID: PMC8004270 DOI: 10.3390/pharmaceutics13030424] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/18/2021] [Accepted: 03/19/2021] [Indexed: 02/07/2023] Open
Abstract
Anti-cancer therapies that integrate smart nanomaterials are the focus of cancer research in recent years. Here, we present our results with PEGylated nanographene oxide particles (nGO-PEG) and have studied their combined effect with near-infrared (NIR) irradiation on low and high invasive colorectal carcinoma cells. The aim is to develop nGO-PEG as a smart nanocarrier for colon cancer-targeted therapy. For this purpose, nGO-PEG nanoparticles' size, zeta potential, surface morphology, dispersion stability, aggregation, and sterility were determined and compared with pristine nGO nanoparticles (NPs). Our results show that PEGylation increased the particle sizes from 256.7 nm (pristine nGO) to 324.6 nm (nGO-PEG), the zeta potential from -32.9 to -21.6 mV, and wrinkled the surface of the nanosheets. Furthermore, nGO-PEG exhibited higher absorbance in the NIR region, as compared to unmodified nGO. PEGylated nGO demonstrated enhanced stability in aqueous solution, improved dispensability in the culture medium, containing 10% fetal bovine serum (FBS) and amended biocompatibility. A strong synergic effect of nGO-PEG activated with NIR irradiation for 5 min (1.5 W/cm-2 laser) was observed on cell growth inhibition of low invasive colon cancer cells (HT29) and their wound closure ability while the effect of NIR on cellular morphology was relatively weak. Our results show that PEGylation of nGO combined with NIR irradiation holds the potential for a biocompatible smart nanocarrier in colon cancer cells with enhanced physicochemical properties and higher biological compatibility. For that reason, further optimization of the irradiation process and detailed screening of nGO-PEG in combination with NIR and chemotherapeutics on the fate of the colon cancer cells is a prerequisite for highly efficient combined nanothermal and photothermal therapy for colon cancer.
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Affiliation(s)
- Milena Georgieva
- Institute of Molecular Biology “R. Tsanev”, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria
- Correspondence: (M.G.); (N.K.); Tel.: +359-896833604 (M.G.); +359-889577074 (N.K.)
| | - Zlatina Gospodinova
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (Z.G.); (M.K.-M.); (T.K.)
- Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria
| | - Milena Keremidarska-Markova
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (Z.G.); (M.K.-M.); (T.K.)
- Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tsankov Blvd, 1164 Sofia, Bulgaria
| | - Trayana Kamenska
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (Z.G.); (M.K.-M.); (T.K.)
| | - Galina Gencheva
- Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1 James Bourchier Blvd., 1164 Sofia, Bulgaria;
| | - Natalia Krasteva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (Z.G.); (M.K.-M.); (T.K.)
- Correspondence: (M.G.); (N.K.); Tel.: +359-896833604 (M.G.); +359-889577074 (N.K.)
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Pillay S, Terreblanche O, Devar J, Wadee A. Unusual case of colorectal carcinoma with sarcoid-like mediastinal adenopathy and near-fatal DPD deficiency. SOUTH AFRICAN JOURNAL OF ONCOLOGY 2021. [DOI: 10.4102/sajo.v5i0.160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Liu H, Liu X, Li Y, Zhou X, Tan X, Niu B, Cheng N, Liu H. Novel Peptide Inhibitors of β-Catenin Effectively Suppress the Tumorigenesis of Colorectal Cancer. Int J Pept Res Ther 2021. [DOI: 10.1007/s10989-020-10080-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Tsili AC, Alexiou G, Naka C, Argyropoulou MI. Imaging of colorectal cancer liver metastases using contrast-enhanced US, multidetector CT, MRI, and FDG PET/CT: a meta-analysis. Acta Radiol 2021; 62:302-312. [PMID: 32506935 DOI: 10.1177/0284185120925481] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Imaging of colorectal cancer liver metastases (CRCLMs) has improved in recent years. Therefore, the role of current imaging techniques needs to be defined. PURPOSE To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS), multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the detection of CRCLMs. MATERIAL AND METHODS PubMed database was searched for articles published during 2000-2019. Inclusion criteria were as follows: diagnosis/suspicion of CRCLMs; CEUS, MDCT, MRI, or FDG PET/CT performed for the detection of CRCLMs; prospective study design; histopathologic examination, intraoperative findings and/or follow-up used as reference standard; and data for calculating sensitivity and specificity reported. RESULTS Twelve prospective studies were assessed, including 536 patients with CRCLMs (n = 1335). On a per-lesion basis, the sensitivity of CEUS, MDCT, MRI, and FDG PET/CT was 86%, 84%, 89%, and 62%, respectively. MRI had the highest sensitivity on a per-lesion analysis. CEUS and MDCT had comparable sensitivities. On a per-patient basis, the sensitivity and specificity of CEUS, MDCT, MRI, and FDG PET/CT was 80% and 97%, 87% and 95%, 87% and 94%, and 96% and 97%, respectively. The per-patient sensitivities for MRI and MDCT were similar. The sensitivity for MRI was higher than that for CEUS, MDCT, and FDG PET/CT for lesions <10 mm and lesions at least 10 mm in size. Hepatospecific contrast agent did not improve diagnostic performances. CONCLUSION MRI is the preferred imaging modality for evaluating CRCLMs. Both MDCT and CEUS can be used as alternatives.
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Affiliation(s)
- Athina C Tsili
- Department of Clinical Radiology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - George Alexiou
- Department of Neurosurgery, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Christina Naka
- Department of Clinical Radiology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Maria I Argyropoulou
- Department of Clinical Radiology, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
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van Amerongen MJ, Vos AM, van der Woude W, Nagtegaal ID, de Wilt JHW, Fütterer JJ, Hermans JJ. Does perfusion computed tomography correlate to pathology in colorectal liver metastases? PLoS One 2021; 16:e0245764. [PMID: 33497385 PMCID: PMC7837475 DOI: 10.1371/journal.pone.0245764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 01/08/2021] [Indexed: 11/18/2022] Open
Abstract
Introduction Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM. Material and methods Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation. Results Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21–54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48–79) and 30 ml/min/100ml (95% CI 22–38). Mean PI was 68% (95% CI 62–73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found. Conclusion In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM.
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Affiliation(s)
- M. J. van Amerongen
- Department of Radiology and Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
- * E-mail:
| | - A. M. Vos
- Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - W. van der Woude
- Department of Radiology and Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - I. D. Nagtegaal
- Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - J. H. W. de Wilt
- Department of Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - J. J. Fütterer
- Department of Radiology and Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - J. J. Hermans
- Department of Radiology and Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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Reidy E, Leonard NA, Treacy O, Ryan AE. A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance. Cancers (Basel) 2021; 13:E227. [PMID: 33435170 PMCID: PMC7827038 DOI: 10.3390/cancers13020227] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/05/2021] [Accepted: 01/07/2021] [Indexed: 12/12/2022] Open
Abstract
Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.
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Affiliation(s)
- Eileen Reidy
- Lambe Institute for Translational research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 V4AY Galway, Ireland; (E.R.); (N.A.L.); (O.T.)
- Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W2TY Galway, Ireland
- Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W5P7 Galway, Ireland
- CÚRAM, SFI Research Centre for Medical Devices, NUI Galway, H91 W2TY Galway, Ireland
| | - Niamh A. Leonard
- Lambe Institute for Translational research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 V4AY Galway, Ireland; (E.R.); (N.A.L.); (O.T.)
- Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W2TY Galway, Ireland
- Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W5P7 Galway, Ireland
| | - Oliver Treacy
- Lambe Institute for Translational research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 V4AY Galway, Ireland; (E.R.); (N.A.L.); (O.T.)
- Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W2TY Galway, Ireland
- Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W5P7 Galway, Ireland
| | - Aideen E. Ryan
- Lambe Institute for Translational research, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 V4AY Galway, Ireland; (E.R.); (N.A.L.); (O.T.)
- Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W2TY Galway, Ireland
- Discipline of Pharmacology and Therapeutics, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, H91 W5P7 Galway, Ireland
- CÚRAM, SFI Research Centre for Medical Devices, NUI Galway, H91 W2TY Galway, Ireland
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