scholarly journals Abstract 3172: 1 Unsupervised cellular phenotypic hierarchy enables spatial intratumor heterogeneity characterization, recurrence-associated microdomains discovery, and harnesses network biology from hyperplexed in-situ fluorescence images of colorectal carcinoma

2021 ◽  
Author(s):  
Samantha Furman ◽  
Andrew Stern ◽  
Shikhar Uttam ◽  
Taylor D. Lansing ◽  
Pullara Filippo ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Network Biology ◽  
Intratumor Heterogeneity ◽  
Fluorescence Images

scholarly journals Unsupervised cellular phenotypic hierarchy enables spatial intratumor heterogeneity characterization, recurrence-associated microdomains discovery, and harnesses network biology from hyperplexed in-situ fluorescence images of colorectal carcinoma

2020 ◽  
Author(s):  
Samantha A. Furman ◽  
Andrew M. Stern ◽  
Shikhar Uttam ◽  
D. Lansing Taylor ◽  
Filippo Pullara ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Drug Targets ◽  
Spatial Configuration ◽  
Cell Types ◽  
Network Biology ◽  
Intratumor Heterogeneity ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Stem Cell Maintenance

AbstractLEAPH is an unsupervised machine learning algorithm for characterizing in situ phenotypic heterogeneity in tissue samples. LEAPH builds a phenotypic hierarchy of cell types, cell states and their spatial configurations. The recursive modeling steps involve determining cell types with low-ranked mixtures of factor analyzers and optimizing cell states with spatial regularization. We applied LEAPH to hyperplexed (51 biomarkers) immunofluorescence images of colorectal carcinoma primary tumors (N=213). LEAPH, combined with pointwise mutual information (PMI), enables the discovery of phenotypically distinct microdomains, composed of spatially configured computational phenotypes. LEAPH identified a subset of microdomains visualized as the spatial configuration of recurrence-specific signaling networks whose intracellular and intercellular interactions support cancer stem cell maintenance and immunosuppression in the evolving tumor microenvironment. The LEAPH framework, when combined with microdomain discovery and microdomain-specific network biology, has the potential to provide insights into pathophysiological mechanisms, identify novel drug targets and inform therapeutic strategies for individual patients.

scholarly journals Liquid Biopsy in Colorectal Carcinoma: Clinical Applications and Challenges

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1376 ◽  
Author(s):  
Drahomír Kolenčík ◽  
Stephanie N. Shishido ◽  
Pavel Pitule ◽  
Jeremy Mason ◽  
James Hicks ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Molecular Characterization ◽  
Liquid Biopsy ◽  
Intratumor Heterogeneity ◽  
Sample Collection ◽  
Potential Clinical Utility ◽  
Therapeutic Tools ◽  
Solid Tumor Tissue ◽  
Genomic Material

Colorectal carcinoma (CRC) is characterized by wide intratumor heterogeneity with general genomic instability and there is a need for improved diagnostic, prognostic, and therapeutic tools. The liquid biopsy provides a noninvasive route of sample collection for analysis of circulating tumor cells (CTCs) and genomic material, including cell-free DNA (cfDNA), as a complementary biopsy to the solid tumor tissue. The solid biopsy is critical for molecular characterization and diagnosis at the time of collection. The liquid biopsy has the advantage of longitudinal molecular characterization of the disease, which is crucial for precision medicine and patient-oriented treatment. In this review, we provide an overview of CRC and the different methodologies for the detection of CTCs and cfDNA, followed by a discussion on the potential clinical utility of the liquid biopsy in CRC patient care, and lastly, current challenges in the field.

Localization of Thymidine Phosphorylase Expression in Colorectal Carcinoma Tissues by in situ RT-PCR Assay

Oncology ◽  
2002 ◽  
Vol 62 (4) ◽  
pp. 327-332 ◽  
Author(s):  
Koshi Mimori ◽  
Ayumi Matsuyama ◽  
Keiji Yoshinaga ◽  
Keishi Yamashita ◽  
Takaaki Masuda ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Thymidine Phosphorylase ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Thymidine Phosphorylase Expression

scholarly journals Importance of Family History of Colorectal Carcinoma In Situ Versus Invasive Colorectal Cancer: A Nationwide Cohort Study

2021 ◽  
pp. 1-6
Author(s):  
Yu Tian ◽  
Elham Kharazmi ◽  
Hermann Brenner ◽  
Xing Xu ◽  
Kristina Sundquist ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Colorectal Carcinoma ◽  
Carcinoma In Situ ◽  
Cumulative Risk ◽  
First Degree Relatives ◽  
Younger Age ◽  
Increased Risk ◽  
History Of

Background: The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. Patients and Methods: We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. Results: The lifetime (0–79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5–1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6–1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1–3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3–2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Conclusions: Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.

scholarly journals Trafficking of Full-Length and N-Terminally Truncated Cathepsin B in Human Colorectal Carcinoma Cells

2021 ◽  
Vol 11 (24) ◽  
pp. 11936
Author(s):  
Tripti Tamhane ◽  
Robin W. Njenga ◽  
Roberta E. Burden ◽  
Heiko Büth ◽  
Gunhild M. Maelandsmo ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cathepsin B ◽  
Carcinoma Cells ◽  
Full Length ◽  
Adenocarcinoma In Situ ◽  
Tissue Samples ◽  
Mucosal Cells ◽  
Lysosomal Cysteine Protease

Cathepsin B is an endo-lysosomal cysteine protease. However, its increased expression and altered localization to the extracellular space, to mitochondria, or to the nucleus has been linked to tumor progression. In the present study, we show enhanced levels of cathepsin B in adenocarcinoma tissue in comparison to adjacent normal colon. Additionally, cathepsin B was observed in the nuclear compartment of mucosal cells in adenocarcinoma tissue samples and in the nuclei of the colorectal carcinoma cell line HCT116. Accordingly, a distinct 40-kDa form of cathepsin B was detected in HCT116 cells, which is proposed to represent a specific form lacking the signal peptide and parts of the propeptide. Trafficking studies with an EGFP-tagged N-terminally truncated form, mimicking the 40-kDa form, demonstrated accumulation in aggresome-like inclusion bodies, while EGFP-tagged full-length cathepsin B revealed regular sorting to endo-lysosomes. We conclude that the identity of nuclear cathepsin B in colorectal adenocarcinoma (in situ) and in carcinoma cells (in vitro) cannot be attributed to either full-length or 40-kDa N-terminally truncated cathepsin B forms. Hence, future studies are needed to demonstrate which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells, and whether redundant regulation of related cathepsin expression occurs.

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