scholarly journals The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic

2019 ◽  
Author(s):  
Zhaoduan Liang ◽  
Lili Qin ◽  
Lei Chen ◽  
Wenhui Li ◽  
Chao Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Regression ◽  
Individual Treatment ◽  
Cytotoxic Lymphocyte ◽  
Oncogenic Mutations ◽  
Incidence And Mortality ◽  
High Incidence ◽  
The Common ◽  
High Binding Affinity

ABSTRACTColorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world, as the result of the traditional treatments. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to individual treatment, resulting from the unique neoantigens. Many shared oncogenic mutations are detected, but whether the common neoantigens can be identified in CRC is unknown. Using the somatic mutations data from 321 CRC patients combined with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and presentation score (>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens were proved to be naturally processed and presented on constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) to secrete IFN-γ. However, only 2 out of 25 common neoantigens were simultaneously presented and immunogenic. Moreover, using cell-sorting technology combined with single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens with presentation and immunogenicity could be found in CRC, which would be developed as the universal targets for CRC immunotherapy.

scholarly journals MiR-103 Assumes Signifying Capacity in Prostate Cancer Diagnosis

2020 ◽  
Author(s):  
Sheng Li ◽  
Xiaolan Ruan ◽  
Tongzu Liu
Keyword(s):  
Prostate Cancer ◽  
Roc Analysis ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Node Metastasis ◽  
Incidence And Mortality ◽  
High Incidence ◽  
The Common ◽  
Proliferation And Invasion

Abstract Background: Prostate cancer is one of the common cancers among males with high incidence and mortality. MiR-103 has been reported to be involved in several human cancers. In our study, we aimed to explore the diagnostic value of miR-103 in PCa.Methods: In this study, qRT-PCR was performed to investigate the expression levels of miR-103 in serum specimens collected from 141 PCa patients and 77 healthy volunteers. MTT and cell invasion assay were performed to detect the effects of miR-103 on the proliferation and invasion of PCa cells. The diagnostic value of miR-103 in PCa was evaluated by ROC curve.Results: The results showed that serum miR-103 levels were higher in PCa patients than that in healthy group (P<0.001). And the expression of miR-103 was significantly associated with PSA (P=0.007), differentiation (P=0.009), and lymph node metastasis (P=0.037). Cell experiments in vitro demonstrated that miR-103 could promote PCa cell line proliferation and invasion. In addition, ROC analysis suggested that miR-103 could discriminate between PCa patients and healthy individuals at the cut-off value of 0.970. The AUC was 0.885, with the sensitivity of 97.2% and specificity of 81.8%.Conclusions: The increased miR-103 levels can promote proliferation and invasion of PCa cells. Serum miR-103 is significantly associated with tumor progression, which may be a novel biomarker for PCa diagnosis.

scholarly journals MicroRNA, Diabetes Mellitus and Colorectal Cancer

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 530
Author(s):  
Hsiuying Wang
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
The Body ◽  
Incidence And Mortality ◽  
The Common ◽  
Regulation Of Cell Cycle ◽  
The Relationship ◽  
Development Regulation ◽  
Inhibit Cell Proliferation ◽  
Improve Glucose Tolerance

Diabetes mellitus (DM) is an endocrinological disorder that is due to either the pancreas not producing enough insulin, or the body does not respond appropriately to insulin. There are many complications of DM such as retinopathy, nephropathy, and peripheral neuropathy. In addition to these complications, DM was reported to be associated with different cancers. In this review, we discuss the association between DM and colorectal cancer (CRC). CRC is the third most commonly diagnosed cancer worldwide that mostly affects older people, however, its incidence and mortality are rising among young people. We discuss the relationship between DM and CRC based on their common microRNA (miRNA) biomarkers. miRNAs are non-coding RNAs playing important functions in cell differentiation, development, regulation of cell cycle, and apoptosis. miRNAs can inhibit cell proliferation and induce apoptosis in CRC cells. miRNAs also can improve glucose tolerance and insulin sensitivity. Therefore, investigating the common miRNA biomarkers of both DM and CRC can shed a light on how these two diseases are correlated and more understanding of the link between these two diseases can help the prevention of both DM and CRC.

scholarly journals Clinical Validation Results of an Innovative Non-Invasive Device for Colorectal Cancer Preventive Screening through Fecal Exhalation Analysis

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1471
Author(s):  
Giulia Zonta ◽  
Cesare Malagù ◽  
Sandro Gherardi ◽  
Alessio Giberti ◽  
Alessandro Pezzoli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Low Cost ◽  
Occult Blood ◽  
Machine Learning Techniques ◽  
Fecal Occult Blood ◽  
Clinical Validation ◽  
Non Invasive ◽  
Fecal Occult ◽  
Incidence And Mortality

Screening is recommended to reduce both incidence and mortality of colorectal cancer. Currently, many countries employ fecal occult blood test (FOBT). In Emilia-Romagna (Italy), since 2005, FOBT immunochemical version (FIT) is performed every two years on people aged between 50 and 69 years. A colonoscopy is then carried out on those who are FIT positive. However, FIT shows approximately 65% false positives (non-tumoral bleedings), leading to many negative colonoscopies. The use of an economic and easy-to-use method to check FOBT-positives will improve screening effectiveness, reducing costs to the national health service. This work illustrates the results of a three-year clinical validation protocol (started in 2016) of a patented device composed of a core of nanostructured gas sensors. This device was designed to identify CRC presence by fecal volatile compounds, with a non-invasive, in vitro and low-cost analysis. Feces are, in fact, affected by tumor-volatile biomarkers, produced by cellular peroxidation and metabolic alterations. The protocol consisted in the analysis of fecal samples of FIT-positive subjects, using colonoscopy as a gold standard. A total of 398 samples were analyzed with machine learning techniques, leading to a sensitivity and specificity of 84.1% and 82.4%, respectively, and a positive predictive value of 72% (25–35% for FIT).

scholarly journals An Immunometabolic Shift Modulates Cytotoxic Lymphocyte Activation During Melanoma Progression in TRPA1 Channel Null Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Maria Fernanda Forni ◽  
Omar Alberto Domínguez-Amorocho ◽  
Leonardo Vinícius Monteiro de Assis ◽  
Gabriela Sarti Kinker ◽  
Maria Nathalia Moraes ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Progression ◽  
Cd8 T Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Cytotoxic Lymphocyte ◽  
Melanoma Tumor ◽  
Incidence And Mortality

Melanoma skin cancer is extremely aggressive with increasing incidence and mortality. Among the emerging therapeutic targets in the treatment of cancer, the family of transient receptor potential channels (TRPs) has been reported as a possible pharmacological target. Specifically, the ankyrin subfamily, representing TRPA1 channels, can act as a pro-inflammatory hub. These channels have already been implicated in the control of intracellular metabolism in several cell models, but little is known about their role in immune cells, and how it could affect tumor progression in a process known as immune surveillance. Here, we investigated the participation of the TRPA1 channel in the immune response against melanoma tumor progression in a mouse model. Using Trpa1+/+ and Trpa1-/- animals, we evaluated tumor progression using murine B16-F10 cells and assessed isolated CD8+ T cells for respiratory and cytotoxic functions. Tumor growth was significantly reduced in Trpa1-/- animals. We observed an increase in the frequency of circulating lymphocytes. Using a dataset of CD8+ T cells isolated from metastatic melanoma patients, we found that TRPA1 reduction correlates with several immunological pathways. Naïve CD8+ T cells from Trpa1+/+ and Trpa1-/- animals showed different mitochondrial respiration and glycolysis profiles. However, under CD3/CD28 costimulatory conditions, the absence of TRPA1 led to an even more extensive metabolic shift, probably linked to a greater in vitro killling ability of Trpa1-/- CD8+ T cells. Therefore, these data demonstrate an unprecedented role of TRPA1 channel in the metabolism control of the immune system cells during carcinogenesis.

scholarly journals Importance of Screening Colonoscopy for Colorectal Cancer among Inflammatory Bowel Disease Patients in Qatar

2020 ◽  
Vol 5 (4) ◽  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Colorectal Adenocarcinoma ◽  
Screening Colonoscopy ◽  
International Guidelines ◽  
Incidence And Mortality ◽  
High Incidence ◽  
High Incidence Rate ◽  
Inflammatory Bowel

Since 1920, inflammatory bowel disease (IBD) has been linked to increased incidence and mortality from colorectal adenocarcinoma (CRC). Several studies have found that screening colonoscopy reduced CRC mortality and improved survival in IBD patients. However, there are little or no data about the prevalence of CRC/Dysplasia in Qatar detected by screening colonoscopy and weather the Qatar gastroenterologists adhere to the international guidelines. Thus, the focus of the present study was to examine the rate of CRC and dysplasia in IBD patients who underwent a screening colonoscopy. The sample consisted of 153 patients who were diagnosed and treated for IBD. The results of the study showed high incidence rate of CRC/Dysplasia among IBD patients and it was also found that the gastroenterologists in Qatar did not strictly adhere to the international guidelines in relation to the time of first screening colonoscopy of IBD patients.

scholarly journals Radiolabelled Aptamers for Theranostic Treatment of Cancer

2018 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Umair Khalid ◽  
Chris Vi ◽  
Justin Henri ◽  
Joanna Macdonald ◽  
Peter Eu ◽  
...  
Keyword(s):  
Binding Affinity ◽  
High Specificity ◽  
Cancer Diagnostics ◽  
Molecular Biomarker ◽  
Specificity And Sensitivity ◽  
Number Of Patients ◽  
Incidence And Mortality ◽  
High Incidence ◽  
High Binding Affinity ◽  
As Toxicity

Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a large number of patients will also present with micrometastasis tumours which are often missed, as conventional medical imaging modalities are unable to detect micrometastases due to the lack of specificity and sensitivity. Recent advances in radiochemistry and the development of nucleic acid based targeting molecules, have led to the development of novel agents for use in cancer diagnostics. Monoclonal antibodies may also be used, however, they have inherent issues, such as toxicity, cost, unspecified binding and their clinical use can be controversial. Aptamers are a class of single-stranded RNA or DNA ligands with high specificity, binding affinity and selectivity for a target, which makes them promising for molecular biomarker imaging. Aptamers are presented as being a superior choice over antibodies because of high binding affinity and pH stability, amongst other factors. A number of aptamers directed to cancer cell markers (breast, lung, colon, glioblastoma, melanoma) have been radiolabelled and characterised to date. Further work is ongoing to develop these for clinical applications.

scholarly journals β-Adrenergic Receptor Inhibitor and Oncolytic Herpesvirus Combination Therapy Shows Enhanced Antitumoral and Antiangiogenic Effects on Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiali Hu ◽  
Cuiyu Chen ◽  
Ruitao Lu ◽  
Yu Zhang ◽  
Yang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Oncolytic Virus ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Tumor Regression ◽  
Oncolytic Viruses ◽  
Cell Viability Assay ◽  
Viability Assay

Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, despite the development of novel OVs with improved efficacy and tumor selectivity, their limited efficacy as monotherapeutic agents remains a significant challenge. This study extended our previously observed combination effects of propranolol, a nonselective β-blocker, and the T1012G oncolytic virus into colorectal cancer models. A cell viability assay showed that cotreatment could induce synergistic killing effects on human and murine colorectal cell lines. Moreover, cotreatment caused sustained tumor regression compared with T1012G monotherapy or propranolol monotherapy in human HCT116 and murine MC38 tumor models. The propranolol activity was not via a direct effect on viral replication in vitro or in vivo. Western blotting showed that cotreatment significantly enhanced the expression of cleaved caspase-3 in HCT116 and MC38 cells compared with the propranolol or T1012G alone. In addition, propranolol or T1012G treatment induced a 35.06% ± 0.53% or 35.49% ± 2.68% reduction in VEGF secretion in HUVECs (p &lt; 0.01/p &lt; 0.01). Cotreatment further inhibited VEGF secretion compared with the monotherapies (compared with propranolol treatment: 75.06% ± 1.50% decrease, compared with T1012G treatment: 74.91% ± 0.68%; p＜0.001, p &lt; 0.001). Consistent with the in vitro results, in vivo data showed that cotreatment could reduce Ki67 and enhance cleaved caspase 3 and CD31 expression in human HCT116 and murine MC38 xenografts. In summary, β-blockers could improve the therapeutic potential of OVs by enhancing oncolytic virus-mediated killing of colorectal cancer cells and colorectal tumors.

scholarly journals Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

2021 ◽  
Vol 22 (4) ◽  
pp. 1907
Author(s):  
Myriam González ◽  
María Ovejero-Sánchez ◽  
Alba Vicente-Blázquez ◽  
Raquel Álvarez ◽  
Ana B. Herrero ◽  
...  
Keyword(s):  
Water Solubility ◽  
Aqueous Solubility ◽  
Carcinoma Cells ◽  
Mitotic Catastrophe ◽  
Multi Drug Resistance ◽  
Cervix Carcinoma ◽  
Microtubule Network ◽  
Incidence And Mortality ◽  
High Incidence

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.

scholarly journals Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Yingying Shi ◽  
You Wang ◽  
Huangang Jiang ◽  
Xuehua Sun ◽  
Hui Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mitochondrial Dysfunction ◽  
Histone Acetylation ◽  
Complex I ◽  
Tumor Regression ◽  
Aerobic Glycolysis ◽  
Metabolic Reprogramming ◽  
Retrograde Signaling ◽  
Neoadjuvant Radiotherapy

AbstractMitochondrial retrograde signaling (mito-RTG) triggered by mitochondrial dysfunction plays a potential role in regulating tumor metabolic reprogramming and cellular sensitivity to radiation. Our previous studies showed phos-pyruvate dehydrogenase (p-PDH) and PDK1, which involved in aerobic glycolysis, were positively correlated with radioresistance, but how they initiate and work in the mito-RTG pathway is still unknown. Our further genomics analysis revealed that complex I components were widely downregulated in mitochondrial dysfunction model. In the present study, high expression of p-PDH was found in the complex I deficient cells and induced radioresistance. Mechanistically, complex I defects led to a decreased PDH both in cytoplasm and nucleus through [Ca2+]m-PDP1-PDH axis, and decreased PDH in nucleus promote DNA damage repair (DDR) response via reducing histone acetylation. Meanwhile, NDUFS1 (an important component of the complex I) overexpression could enhance the complex I activity, reverse glycolysis and resensitize cancer cells to radiation in vivo and in vitro. Furthermore, low NDUFS1 and PDH expression were validated to be correlated with poor tumor regression grading (TRG) in local advanced colorectal cancer (CRC) patients underwent neoadjuvant radiotherapy. Here, we propose that the [Ca2+]m-PDP1-PDH-histone acetylation retrograde signaling activated by mitochondrial complex I defects contribute to cancer cell radioresistance, which provides new insight in the understanding of the mito-RTG. For the first time, we reveal that NDUFS1 could be served as a promising predictor of radiosensitivity and modification of complex I function may improve clinical benefits of radiotherapy in CRC.

scholarly journals IT-141, a Polymer Micelle Encapsulating SN-38, Induces Tumor Regression in Multiple Colorectal Cancer Models

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Adam Carie ◽  
Jonathan Rios-Doria ◽  
Tara Costich ◽  
Brian Burke ◽  
Richard Slama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Anticancer Agents ◽  
Tumor Regression ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Analysis ◽  
Polymer Micelle ◽  
Drug Delivery Vehicles ◽  
Cancer Models

Polymer micelles are promising drug delivery vehicles for the delivery of anticancer agents to tumors. Often, anticancer drugs display potent cytotoxic effects towards cancer cells but are too hydrophobic to be administered in the clinic as a free drug. To address this problem, a polymer micelle was designed using a triblock copolymer (ITP-101) that enables hydrophobic drugs to be encapsulated. An SN-38 encapsulated micelle, IT-141, was prepared that exhibited potent in vitro cytotoxicity against a wide array of cancer cell lines. In a mouse model, pharmacokinetic analysis revealed that IT-141 had a much longer circulation time, plasma exposure, and tumor exposure compared to irinotecan. IT-141 was also superior to irinotecan in terms of antitumor activity, exhibiting greater tumor inhibition in HT-29 and HCT116 colorectal cancer xenograft models at half the dose of irinotecan. The antitumor effect of IT-141 was dose-dependent and caused complete growth inhibition and tumor regression at well-tolerated doses. Varying the specific concentration of SN-38 within the IT-141 micelle had no detectible effect on this antitumor activity, indicating no differences in activity between different IT-141 formulations. In summary, IT-141 is a potent micelle-based chemotherapy that holds promise for the treatment of colorectal cancer.

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