scholarly journals Colon Cancer Biomarkers: Implications for Personalized Medicine

2020 ◽  
Vol 10 (4) ◽  
pp. 167
Author(s):  
Kenneth P.H. Pritzker
Keyword(s):  
Colon Cancer ◽  
Personalized Medicine ◽  
Site Selection ◽  
Clinical Utility ◽  
Strong Association ◽  
Quality Analysis ◽  
Science Data ◽  
High Quality ◽  
Colon Cancers ◽  
Genomic Probes

The heterogeneity of colon cancers and their reactions presents both a challenge and promise for personalized medicine. The challenge is to develop effective biologically personalized therapeutics guided by predictive and prognostic biomarkers. Presently, there are several classes of candidate biomarkers, including genomic probes, inhibitory RNAs, assays for immunity dysfunction and, not to be forgotten, specific histopathologic and histochemical features. To develop effective therapeutics, candidate biomarkers must be qualified and validated in comparable independent cohorts, no small undertaking. This process and subsequent deployment in clinical practice involves not only the strong association of the biomarker with the treatment but also careful attention to the prosaic aspects of representative tumor site selection, obtaining a fully adequate sample which is preserved and prepared to optimize high quality analysis. In the future, the clinical utility of biomarker analytical results will benefit from associated clinical and basic science data with the assistance of artificial intelligence techniques. By application of an individualized, selected suite of biomarkers, comprehensively interpreted, individualized, more effective and less toxic therapy for colon cancer will be enabled, thereby fulfilling the promise of personalized medicine.

Image Quality Analysis of X-ray Grating Interferometer Using Integrating-bucket Method

2020 ◽  
Vol 64 (2) ◽  
pp. 20503-1-20503-5
Author(s):  
Faiz Wali ◽  
Shenghao Wang ◽  
Ji Li ◽  
Jianheng Huang ◽  
Yaohu Lei ◽  
...  
Keyword(s):  
Image Quality ◽  
Phase Contrast ◽  
Quality Analysis ◽  
Phase Contrast Imaging ◽  
Phase Image ◽  
Contrast Imaging ◽  
High Quality ◽  
Image Quality Analysis ◽  
X Ray ◽  
Grating Interferometer

Abstract Grating-based x-ray phase-contrast imaging has the potential to enhance image quality and provide inner structure details non-destructively. In this work, using grating-based x-ray phase-contrast imaging system and employing integrating-bucket method, the quantitative expressions of signal-to-noise ratios due to photon statistics and mechanical error are analyzed in detail. Photon statistical noise and mechanical error are the main sources affecting the image noise in x-ray grating interferometry. Integrating-bucket method is a new phase extraction method translated to x-ray grating interferometry; hence, its image quality analysis would be of great importance to get high-quality phase image. The authors’ conclusions provide an alternate method to get high-quality refraction signal using grating interferometer, and hence increases applicability of grating interferometry in preclinical and clinical usage.

scholarly journals Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323363
Author(s):  
Ester Pagano ◽  
Joshua E Elias ◽  
Georg Schneditz ◽  
Svetlana Saveljeva ◽  
Lorraine M Holland ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumour Growth ◽  
Tumour Microenvironment ◽  
Tube Formation ◽  
Tissue Remodelling ◽  
Colon Cancers ◽  
Inflammatory Bowel ◽  
Ion Pumping ◽  
G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

scholarly journals Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer

2020 ◽  
Author(s):  
Sebastian Dwertmann Rico ◽  
Doris Höflmayer ◽  
Franziska Büscheck ◽  
David Dum ◽  
Andreas M. Luebke ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mismatch Repair ◽  
Cancer Progression ◽  
Strong Association ◽  
Tumor Location ◽  
Colorectal Cancers ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency ◽  
Cancer Aggressiveness ◽  
Rectal Cancers

AbstractMucin 5AC (MUC5AC) is a secreted gel-forming mucin expressed by several epithelia. In the colon, MUC5AC is expressed in scattered normal epithelial cells but can be abundant in colorectal cancers. To clarify the relationship of MUC5AC expression with parameters of tumor aggressiveness and mismatch repair deficiency (dMMR) in colorectal cancer, a tissue microarray containing 1812 colorectal cancers was analyzed by immunohistochemistry. MUC5AC expression was found in 261 (15.7%) of 1,667 analyzable colorectal cancers. MUC5AC expression strongly depended on the tumor location and gradually decreased from proximal (27.4% of cecum cancers) to distal (10.6% of rectal cancers; p < 0.0001). MUC5AC expression was also strongly linked to dMMR. dMMR was found in 21.3% of 169 cancers with MUC5AC positivity but in only 4.6% of 1051 cancers without detectable MUC5AC expression (p < 0.0001). A multivariate analysis showed that dMMR status and tumor localization predicted MUC5AC expression independently (p < 0.0001 each). MUC5AC expression was unrelated to pT and pN status. This also applied to the subgroups of 1136 proficient MMR (pMMR) and of 84 dMMR cancers. The results of our study show a strong association of MUC5AC expression with proximal and dMMR colorectal cancers. However, MUC5AC expression is unrelated to colon cancer aggressiveness.

Abstract 13721: The Monitoring of rSO2 Value During CPR is Useful for High-Quality CPR

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yoshihito Ogawa ◽  
Tadahiko Shiozaki ◽  
Tomoya Hirose ◽  
Mitsuo Ohnishi ◽  
Goro Tajima ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Chest Compression ◽  
Clinical Utility ◽  
Spontaneous Circulation ◽  
Regional Cerebral Oxygen Saturation ◽  
High Quality ◽  
Specificity And Sensitivity ◽  
Single Center Study ◽  
Manual Chest Compression ◽  
Hospital Cardiac Arrest

[Background] Recently, the patients with out-of-hospital cardiac arrest are increasing. It is very important to do chest compression continuously for the return of spontaneous circulation (ROSC). But we can not but stop chest compression during checking pulse every few minutes. We reported that Regional cerebral Oxygen Saturation (rSO2) value was not elevated by manual chest compression and mechanical chest compression increased a little rSO2 value on CPR without ROSC and rSO2 value became a good parameter of ROSC in single center study. [Purpose] The purpose of this study is to evaluate clinical utility of rSO2 value during CPR in multicenter study. [Method] Retrospectively, we considered the rSO2 value of the out-of -hospital cardiac arrest patients from December 2012 to December 2014 in multicenter. During CPR, rSO2 were recorded continuously from the forehead of the patients by TOS-OR (Japan). CPR for patients with OHCA was performed according to the JRC-guidelines 2010. [Result] 252 patients with OHCA were included in this study. The rSO2 value on arrival, during CPR and ROSC were 44.4±8.9%, 45.4±9.7%, 58.6±9.2%. In ROSC, with rSO2 cutoff value of 52.7%, the specificity and sensitivity were 80% and 79%, respectively. The negative predict value was 99.2%, respectively. It means little possible to ROSC, if the rSO2 value is less than 52.7%. So, it may be possible to reduce the frequency of checking pulse during CPR. [Conclusion] The monitoring of rSO2 value could reduce the frequency of checking pulse during CPR and do chest compression continuously.

scholarly journals Age-related inequalities in colon cancer treatment persist over time: a population-based analysis

2018 ◽  
Vol 73 (1) ◽  
pp. 34-41 ◽  
Author(s):  
Louise Hayes ◽  
Lynne Forrest ◽  
Jean Adams ◽  
Mira Hidajat ◽  
Yoav Ben-Shlomo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Treatment ◽  
Treatment Decision ◽  
Population Based ◽  
Surgical Patients ◽  
Area Deprivation ◽  
Treatment Decision Making ◽  
Colon Cancers ◽  
Age Related ◽  
Over Time

BackgroundOlder people experience poorer outcomes from colon cancer. We examined if treatment for colon cancer was related to age and if inequalities changed over time.MethodsData from the UK population-based Northern and Yorkshire Cancer Registry on 31 910 incident colon cancers (ICD10 C18) diagnosed between 1999–2010 were obtained. Likelihood of receipt of: (1) cancer-directed surgery, (2) chemotherapy in surgical patients, (3) chemotherapy in non-surgical patients by age, adjusting for sex, area deprivation, cancer stage, comorbidity and period of diagnosis, was examined.ResultsAge-related inequalities in treatment exist after adjustment for confounding factors. Patients aged 60– 69, 70–79 and 80+ years were significantly less likely to receive surgery than those aged <60 years (multivariable ORs (95% CI) 0.84(0.74 to 0.95), 0.54(0.48 to 0.61) and 0.19(0.17 to 0.21), respectively). Age-related differences in receipt of surgery and adjuvant chemotherapy (but not chemotherapy in non-surgical patients) narrowed over time for the ’younger old’ (aged <80 years) but did not diminish for the oldest patients.ConclusionsAge inequality in treatment of colon cancer remains after adjustment for confounders, suggesting age remains a major factor in treatment decisions. Research is needed to better understand the cancer treatment decision-making process, and how to influence this, for older patients.

scholarly journals Alteration in the immune microenvironment based on APC status in MSS/pMMR colon cancer data retrieved from TCGA

2020 ◽  
Author(s):  
Haishan Lin ◽  
Hongchao Zhen ◽  
Kun Shan ◽  
Xiaoting Ma ◽  
Bangwei Cao
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Enrichment Analysis ◽  
Tumor Immunotherapy ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Cancer Data ◽  
T Cell Infiltration ◽  
Colon Cancers ◽  
Tumor Immune Microenvironment

Abstract Immunotherapy is currently the most advanced anti-tumor treatment approach. The efficacy of anti-tumor immunotherapy is closely related to the tumor immune microenvironment, including immune cells, infiltration of immune factors, and expression of immune checkpoints. At present, the biomarkers for predicting the efficacy of colon cancer immunotherapy do not cover all colon cancer patients suitable for immunotherapy. In this study, TCGA database was used to identify tumor genotypes suitable for anti-tumor immunotherapy. We found that some of the MSS/pMMR populations, that were initially considered unsuitable for immunotherapy, might actually be suitable. In APC-wt/MSS colon cancer, the expression of PD-1, PD-L1, CTLA4 and CYT（GZMA and PRF1）were increased. Based on calculations done by ESTIMATE and CIBERSORT algorithms, the ImmunoScore and the proportion of CT8+ T cell infiltration is increased in these patients. Enrichment analysis was done to screen signaling pathways involved in immune response, extracellular matrix, and cell adhesion. Tumors from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. Based on the results, we found that some colon cancers of APC-wt/MSS are classified by Tumor Immune Microenvironment types (TIMTs) TMIT I. So that we speculate that APC-wt/MSS colon cancer patients could benefit from anti-tumor immunotherapy.

scholarly journals Lemongrass Extract Possesses Potent Anticancer Activity Against Human Colon Cancers, Inhibits Tumorigenesis, Enhances Efficacy of FOLFOX, and Reduces Its Adverse Effects

2019 ◽  
Vol 18 ◽  
pp. 153473541988915 ◽  
Author(s):  
Ivan Ruvinov ◽  
Christopher Nguyen ◽  
Benjamin Scaria ◽  
Caleb Vegh ◽  
Ola Zaitoon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Human Colon ◽  
Dependent Manner ◽  
Anticancer Efficacy ◽  
Colon Cancers ◽  
Induced Apoptosis

Current chemotherapeutics for metastatic colorectal cancers have limited success and are extremely toxic due to nonselective targeting. Some natural extracts have been traditionally taken and have shown anticancer activity. These extracts have multiple phytochemicals that can target different pathways selectively in cancer cells. We have shown previously that lemongrass ( Cymbopogon citratus) extract is effective at inducing cell death in human lymphomas. However, the efficacy of lemongrass extract on human colorectal cancer has not been investigated. Furthermore, its interactions with current chemotherapies for colon cancer is unknown. In this article, we report the anticancer effects of ethanolic lemongrass extract in colorectal cancer models, and importantly, its interactions with FOLFOX and Taxol. Lemongrass extract induced apoptosis in colon cancer cells in a time and dose-dependent manner without harming healthy cells in vitro. Oral administration of lemongrass extract was well tolerated and effective at inhibiting colon cancer xenograft growth in mice. It enhanced the anticancer efficacy of FOLFOX and, interestingly, inhibited FOLFOX-related weight loss in animals given the combination treatment. Furthermore, feeding lemongrass extract to APCmin/+ transgenic mice led to the reduction of intestinal tumors, indicating its preventative potential. Therefore, this natural extract has potential to be developed as a supplemental treatment for colorectal cancer.

scholarly journals High Throughput, High Quality Analysis in the Electron Microscope

2013 ◽  
Vol 19 (S2) ◽  
pp. 1312-1313
Author(s):  
A. Hyde ◽  
J. Goulden ◽  
N. Rowlands ◽  
S. Ubhi
Keyword(s):  
Electron Microscope ◽  
High Throughput ◽  
Quality Analysis ◽  
High Quality

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

scholarly journals Automated high-throughput analysis of B cell spreading on immobilized antibodies with whole slide imaging

2015 ◽  
Vol 1 (1) ◽  
pp. 224-227 ◽  
Author(s):  
Veit Wiesmann ◽  
Dorothea Reimer ◽  
Daniela Franz ◽  
Hanna Hüttmayer ◽  
Dirk Mielenz ◽  
...  
Keyword(s):  
Image Processing ◽  
B Cells ◽  
Quality Analysis ◽  
Imaging Data ◽  
Whole Slide Imaging ◽  
High Quality ◽  
High Throughput Analysis ◽  
Fluorescent Cell ◽  
Immobilized Antibodies ◽  
Automated Image Processing

AbstractAutomated image processing methods enable objective, reproducible and high quality analysis of fluorescent cell images in a reasonable amount of time. Therefore, we propose the application of image processing pipelines based on established segmentation algorithms which can handle massive amounts of whole slide imaging data of multiple fluorescent labeled cells. After automated parameter adaption the segmentation pipelines provide high quality cell delineations revealing significant differences in the spreading of B cells: LPS-activated B cells spread significantly less on anti CD19 mAb than on anti BCR mAb and both processes could be inhibited by the F-actin destabilizing drug Cytochalasin D. Moreover, anti CD19 mAb induce a more symmetrical spreading than anti BCR mAb as reflected by the higher cell circularity.

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