Therapeutic potential of fractalkine: a novel approach to metastatic colon cancer

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

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Faculty Opinions recommendation of CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1137898.594995 ◽

2008 ◽

Author(s):

Avri Ben-Ze'ev

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Cancer Cells ◽

Metastatic Colon Cancer ◽

Colon Cancer Cells ◽

Cd133 Expression

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Faculty Opinions recommendation of Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically unresectable metastatic colon cancer and an intact asymptomatic colon cancer: definitive analysis of NSABP trial C-10.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717954590.793463270 ◽

2012 ◽

Author(s):

Yiqian Nancy You ◽

Brian Keith Bednarski

Keyword(s):

Colon Cancer ◽

Primary Tumor ◽

Metastatic Colon Cancer

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Faculty Opinions recommendation of A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727453501.793539415 ◽

2017 ◽

Author(s):

Mariann Bienz

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Metastatic Colon Cancer ◽

Distinct Role

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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 ◽

10.3390/molecules26051261 ◽

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.

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Metastasectomy for Stage IVA Colon Cancer: Does the Type of Treating Institution Make a Difference?

The American Surgeon ◽

10.1177/00031348211023389 ◽

2021 ◽

pp. 000313482110233

Author(s):

Shinho T. Kang ◽

Ryan Moran ◽

Lala Hussain ◽

Hamza Guend ◽

Erik M. Dunki-Jacobs ◽

...

Keyword(s):

Colon Cancer ◽

Liver Metastasis ◽

Complex Disease ◽

Academic Research ◽

Disease Process ◽

Tumor Location ◽

Colon Resection ◽

Academic Community ◽

Metastatic Colon Cancer ◽

Isolated Liver

Treatment of metastatic colon cancer has evolved over time. More evidence has been emerging in recent years supporting metastasectomy in selected patients. We sought to elucidate whether the type of institution—community, comprehensive community, academic/research, and integrated cancer network—would have an effect on patient outcome, specifically those colon cancer patients with isolated liver metastasis. This retrospective cohort study queried the National Cancer Database (NCDB) from 2010 to 2014 for patients who were 18 years of age or older with stage IVA colon cancer with isolated liver metastasis. We then performed uni- and multivariate analyses comparing patients based on such factors as age, tumor characteristics, primary tumor location, rate of chemotherapy, and type of treating institution. Patients who came from regions of higher income, receiving chemotherapy, and presenting to an academic/research hospital were more likely to undergo metastasectomy. Median survival was longest at academic/community hospitals at 22.4 months, 6 to 7 months longer than the other three types of institutions. Factors positively affecting survival included receiving chemotherapy, presenting to an academic/research institution, and undergoing metastasectomy, all at P < .05. In our study, the rate of metastasectomy was more than double at academic/research institutions for those with stage IVA colon cancer with isolated liver metastasis. Prior studies have quoted a mere 4.1% synchronous colon resection and metastasectomy. Our findings suggest that we should maintain multidisciplinary approach to this complex disease process and that perhaps it is time for us to consider regionalization of care in treating metastatic colon cancer.

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