scholarly journals Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Yaqi Li ◽  
Lei Liang ◽  
Weixing Dai ◽  
Guoxiang Cai ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Programed Cell Death ◽  
Infiltrating Lymphocytes

scholarly journals Clinicopathologic characteristics, tumor infiltrating lymphocytes and programed cell death ligand-1 expression in 162 endometrial carcinomas with deficient mismatch repair function

2019 ◽  
Vol 29 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Jesus A Chavez ◽  
Lai Wei ◽  
Adrian A Suarez ◽  
Anil V Parwani ◽  
Zaibo Li
Keyword(s):  
Cell Death ◽  
Mismatch Repair ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Clinicopathologic Characteristics ◽  
Younger Age ◽  
Significant Difference ◽  
Programed Cell Death ◽  
Infiltrating Lymphocytes ◽  
Deficient Mismatch Repair

ObjectiveEndometrial carcinoma (EC) with deficient mismatch repair (dMMR) protein has been reported to have increased tumor infiltrating lymphocytes (TILs) and programed cell death ligand-1 (PD-L1) expression. TILs and PD-L1 expression are compared between two main types of dMMR ECs (epigenetic dMMR due to MLH1 promoter methylation vs mutated dMMR due to genetic mutation).MethodsImmunohistochemistry for PD-L1 was performed in triplicate on tissue microarray sections. TILs were semi-quantitatively evaluated on whole-slide images of whole histologic sections. The clinicopathologic characteristics together with PD-L1 expression and TILs were analyzed between mutated and epigenetic dMMR ECs.ResultsOf the 162 dMMR ECs identified, 126 had epigenetic dMMR and 36 had mutated dMMR. Univariate analysis demonstrated mutated dMMR ECs showed younger age, less myometrium invasion of >50%, less lymphovascular invasion, and more TILs than epigenetic dMMR ECs. Multivariate analysis demonstrated significantly younger age and more TILs in mutated dMMR ECs than in epigenetic ECs. PD-L1 expression did not show any significant difference between these two groups. Seventeen (13.5%) patients with epigenetic dMMR EC had recurrence and 13 (10.3%) patients died of disease. In contrast, only one patient with mutated dMMR EC had recurrence (3%) and died of disease (3%).ConclusionECs with mutated dMMR demonstrated significantly increased TILs than ECs with epigenetic dMMR, suggesting a stronger immune reaction and potential response to immunotherapy in these tumors.

Prognostic Impact of Tumor-Infiltrating Lymphocytes in Primary and Metastatic Colorectal Cancer

2019 ◽  
Vol 62 (4) ◽  
pp. 498-508 ◽  
Author(s):  
Joseph C. Kong ◽  
Glen R. Guerra ◽  
Toan Pham ◽  
Catherine Mitchell ◽  
A. Craig Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Infiltrating Lymphocytes

scholarly journals Spatial analysis of tumor infiltrating lymphocytes based on deep learning using histopathology image to predict progression-free survival in colorectal cancer

2021 ◽  
Author(s):  
Hongming Xu ◽  
Yoon Jin Cha ◽  
Jean R. Clemenceau ◽  
Jinhwan Choi ◽  
Sung Hak Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Interobserver Agreement ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Kappa Coefficient ◽  
Prognostic Impact ◽  
Free Survival ◽  
Invasive Margin ◽  
Infiltrating Lymphocytes

AbstractPurposeThis study aimed to explore the prognostic impact of spatial distribution of tumor infiltrating lymphocytes (TILs) quantified by deep learning (DL) approaches based on digitalized whole slide images stained with hematoxylin and eosin in patients with colorectal cancer (CRC).MethodsThe prognostic impact of spatial distributions of TILs in patients with CRC was explored in the Yonsei cohort (n=180) and validated in the TCGA cohort (n=268). Concurrently, two experienced pathologists manually measured TILs at the most invasive margin as 0-3 by the Klintrup-Mäkinen (KM) grading method and compared to DL approaches. Interobserver agreement for TILs was measured using Cohen’s kappa coefficient.ResultsOn multivariate analysis of spatial TILs features derived by DL approaches and clinicopathological variables including tumor stage, Microsatellite instability, and KRAS mutations, TILs densities within 200 μm of the invasive margin (f_im200) was remained as the most significant prognostic factor for progression-free survival (PFS) (HR 0.004 [95% CI, 0.0001-0.1502], p=.002) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031, [95% CI 0.001-0.645], p=.024). Interobserver agreement of manual KM grading based on Cohen’s kappa coefficient was insignificant in the Yonsei (κ=.109) and the TCGA (κ=.121), respectively. The survival analysis based on KM grading showed statistically significant different PFS from the TCGA cohort, but not the Yonsei cohort.ConclusionsAutomatic quantification of TILs at the invasive margin based on DL approaches showed a prognostic utility to predict PFS, and could provide robust and reproducible TILs density measurement in patients with CRC.Data and Code AvailabilitySource code and data used for this study is available at the following link: https://github.com/hwanglab/TILs_Analysis

scholarly journals Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1261
Author(s):  
Nurul Fattin Che Rahim ◽  
Yazmin Hussin ◽  
Muhammad Nazirul Mubin Aziz ◽  
Nurul Elyani Mohamad ◽  
Swee Keong Yeap ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Curcuma Longa ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

scholarly journals Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1676-1688
Author(s):  
Rong Liao ◽  
Qi-Zhi Ma ◽  
Cong-Ya Zhou ◽  
Jun-Jun Li ◽  
Ning-Na Weng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Assessment of TRPV4 Channel and Its Role in Colorectal Cancer Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 629-638
Author(s):  
N. N. Bahari ◽  
S. Y. N. Jamaludin ◽  
A. H. Jahidin ◽  
M. N. Zahary ◽  
A. B. Mohd Hilmi
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Colorectal Cancer ◽  
Expression Levels ◽  
Pharmacological Modulation ◽  
Colorectal Cancer Cells ◽  
Ht 29

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.

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