Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles

In the paper

“Micro-RNAs are small non-coding RNAs discovered in 1993 that play crucial roles in cancer, including in cell viability, proliferation, invasion, metastasis, tumor suppressors, and oncogenes [83,84], allowing them to be used in cancer diagnosis and treatment [85,86].”

What the sources say

• ?Not checked — no full text of the sourcecites [83] Slack, 2006, Oncomirs—MicroRNAs with a role in cancer, Nat. Rev. Cancer source
• ?Not checked — no full text of the sourcecites [84] Lee, 1993, The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14, Cell source
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [85] Schetter, 2012, The role of microRNAs in colorectal cancer, Cancer J. sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [86] Cekaite, 2016, MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer, Oncotarget sourceExperimental — accuracy not yet measured

In the paper

“Further post-antimitotic response can arrest the cell cycle at the G2/M phase [51] and cause apoptotic cell death [52].”

What the sources say

• Partly supported

  The Discussion reports G2 arrest after treatment with microtubule-disrupting agents, supporting the arrest portion attributed to this source. But it explicitly describes that arrest as premitotic—before some cells ever reach mitosis—not as a post-antimitotic response. The apoptosis clause has a separate citation and is not assessed here. (LLM, conf=0.86)

  cites [51] Blajeski, 2002, G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells, J. Clin. Investig. sourceExperimental — accuracy not yet measured
• Supported

  The Results section reports G2/M arrest after treatment with the microtubule inhibitor SP-6-27 in ovarian cancer cells. The Discussion reports that SP-6-27 also induced apoptotic cell death, supporting the cited sentence’s qualified claim that an antimitotic response can produce both outcomes. (LLM, conf=0.89)

  cites [52] Kulshrestha, 2017, Microtubule inhibitor, SP-6-27 inhibits angiogenesis and induces apoptosis in ovarian cancer cells, Oncotarget source

In the paper

“Among others, MALAT1 increases tumor formation in many cancers, including gastric, gallbladder, and lung cancer in vivo [77,78,79,80].”

What the sources say

• Partly supported

  The 'Association of MALAT1 with cancers' section reports that high MALAT1 expression promotes gastric-cancer development and describes its role in non-small-cell lung cancer progression. The 'Signaling pathways involving MALAT1' section describes it as oncogenic in gallbladder carcinoma. These passages support a cancer-promoting role, but do not establish increased tumor formation in vivo in the three named cancers. (LLM, conf=0.85)

  cites [77] Zhao, 2018, MALAT1: A long non-coding RNA highly associated with human cancers, Oncol. Lett. sourceExperimental — accuracy not yet measured
• Partly supported

  The gastric-cancer expression results and Discussion (page unavailable) report elevated MALAT1 in gastric tumors and an association with peritoneal metastasis. They do not show that MALAT1 increases tumor formation in vivo: the paper's in-vivo tumor-growth experiments tested HOTAIR, not MALAT1. The copy also does not establish in-vivo tumor formation by MALAT1 in gallbladder or lung cancer. (LLM, conf=0.87)

  cites [78] Okugawa, 2014, Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis, Carcinogenesis sourceExperimental — accuracy not yet measured
• Supported

  This paper supports the gallbladder-cancer part of the multi-cited sentence. In “Effects of MALAT1 knockdown on SGC-996 and NOZ cell proliferation,” it reports significantly inhibited tumor growth in mice given MALAT1-depleted gallbladder cancer cells compared with controls. No page number is provided in our copy. (LLM, conf=0.92)

  cites [79] Wu, 2014, MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway, Cancer Biol. Ther. source
• Supported

  The Results section reports that MALAT1 was required for effective lung tumor-nodule formation in mice: A549 cells lacking MALAT1 formed significantly fewer nodules than wild-type cells. In this multiply cited sentence, this paper supports the lung-cancer in vivo example. (LLM, conf=0.91)

  cites [80] Gutschner, 2013, The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells, Cancer Res. source

In the paper

“The expression levels of the studied lncRNAs were evaluated using GAPDH, which is widely used as an internal control for serum lncRNAs in numerous studies [98,99] according to the manufacturer’s protocol.”

What the sources say

• Partly supported

  The Materials and Methods section (Serum lncRNAs assay; page not provided) says this study used GAPDH as an internal control for serum lncRNAs. It does not say that GAPDH is widely used for that purpose in numerous studies. (LLM, conf=0.85)

  cites [98] Shaker, 2017, Association of rs6983267 at 8q24, HULC rs7763881 polymorphisms and serum lncRNAs CCAT2 and HULC with colorectal cancer in Egyptian patients, Sci. Rep. sourceExperimental — accuracy not yet measured
• Partly supported

  The RNA extraction and qRT-PCR section says the authors normalized serum and tissue lncRNA expression using GAPDH as the reference. This supports GAPDH’s use as an internal control in this study, but the cited paper does not establish that it is widely used for serum lncRNAs in numerous studies. (LLM, conf=0.82)

  cites [99] Duan, 2016, Identification of a serum circulating lncRNA panel for the diagnosis and recurrence prediction of bladder cancer, Oncotarget sourceExperimental — accuracy not yet measured

In the paper

“The FE-SEM images (Figure 2A) show the 3D dendritic mesoporous structure of MSNs with a spherical shape that is uniform in size.”

In the paper

“For MSNsPCOL, the size slightly decreased to 391 ± 3.9 nm but was an insignificant difference.”

In the paper

“The results of the DTG thermograms in Figure 4B are consistent with STA, providing clear data that confirm the degradation.”

In the paper

“Two new peaks at 1639 cm−1, and an intensive peak centered at 3355 cm−1 were presented in MSNsPCOL, corresponding to shifted peaks at 1542 and 3629 cm−1 for COL.”

In the paper

“In MSNsP, a peak at 63 °C showed moisture, and another at 500 °C was attributed to organic decomposition.”

In the paper

“Additional modification with organic phosphonate groups changed the elemental content, resulting in the presence of new elements, including 0.24 wt% P, 7.40 wt% C, and 0.95 wt% Na, as seen for MSNsP, confirming the modification.”

In the paper

“Additional coating resulted in several new peaks, with bands at 698 and 946 cm−1 attributed to chitosan, glycine, or folic acid.”

In the paper

“As their surface was functionalized with phosphonate groups in MSNsP, we observed a new band at 953 cm−1 and a broad peak from 3000 to 3600 cm−1, reflecting phosphonate groups [39].”

What the sources say

• ?Not checked — no full text of the sourcecites [39] Menon, 2016, Cytotoxic Effects of Phosphonate-Functionalized Mesoporous Silica Nanoparticles, ACS Appl. Mater. Interfaces source

In the paper

“The highest weight loss was recorded for MSNsPCOL/CG-FA, which was the result of decomposition of the coating complex (calculated to be 33.4 wt%), which confirms successful fabrication of the coating.”

In the paper

“As expected, MSNsP had negative zeta values compared to MSNs associated with phosphonate groups.”

In the paper

“Higher cytotoxicity was recorded for HCT116 cells than PC3 and HepG2 cells, with 1000 µg/mL MSN and MSNsP treatment of HCT116 cells resulting in 85.9 ± 6.0% and 77.4 ± 4.7% inhibition, respectively.”

In the paper

“MSNs had a very low positive value (<+2 mV) in acidic media and very negative in alkaline medium (−55 mV).”

In the paper

“MSNsPCOL exhibited negative values at various pH values, probably due to the low COL content in particles.”

In the paper

“MSNsPCOL/CG-FA significantly inhibited all tested cancer cells lines than COL ranking in this order: HCT116 > HepG2 > PC3.”

In the paper

“MSNsPCOL/CG-FA had a maximum inhibition effect with 0.3 ± 0.05-fold change, followed by COL (0.46 ± 0.05-fold change), MSNsPCOL (1.5 ± 0.15-fold change), and 5-FU (10.06 ± 0.57-fold change) compared to positive control cells (~160-fold change).”

In the paper

“After 24 h, MSNsPCOL/CG-FA resulted in the maximum accumulation of cells at G2/M (14.8%), followed by 5-FU (12.4%), MSNsPCOL (11.2%), and COL (8.7%), with the lowest accumulation for MSNs (4.9%), MSNsP (4.8%), and untreated control (4.76%).”

In the paper

“Figure 5 presents the dependence of cell inhibition on concentration, time, cell line, and MSNs, with significant differences at p < 0.5.”

In the paper

“MSNsPCOL/CG-FA inhibited 4% after 72 h, compared to 60% for COL, which indicates negligible effects.”

In the paper

“PD-1 reached 10.3 ± 0.2 and 11.2 ± 0.5 with free COL and 5-FU, respectively.”

In the paper

“Figure 11E shows the suppression of PD-1 checkpoint with significant changes compared control cells; the maximum inhibition level was reached at 9.8 ± 0.3 ng/mL and 10 ± 0.3 ng/mL for MSNsPCOL/CG-FA and MSNsPCOL, respectively, compared to 14 ± 0.5 ng/mL with positive control cells.”

In the paper

“Notably, MSNsPCOL/CG-FA had a gradual inhibitory effect compared to carriers; it had lower inhibition at 24 h and increased after 72 h, with a maximum inhibition of 80% when treated at 200 μg/mL.”

In the paper

“A maximum inhibition of Ang-2 recorded for MSNsPCOL/CG-FA (174.0 ± 0.75 ng/mL) > MSNsPCOL (175.7 ± 1.0 ng/mL) > 5-FU (182.3 ± 1.15 ng/mL) > COL (188.6 ± 1 ng/mL) compared to positive control cells (213.3 ± 3.0 ng/mL).”

In the paper

“Clear differences were confirmed by IC50 calculations, as MSNsPCOL/CG-FA had lower values than MSNsPCOL and COL and reached 19.7 μg/mL after 24 h, 17.4 μg/mL after 48 h, and 17.0 μg/mL after 72 h.”

In the paper

“The cell-killing was cell line-, concentration-, time-, and delivery method-dependent.”

In the paper

“The modulation of pro-apoptotic proteins is shared with apoptosis; treating cells with MSNsPCOL/CG-FA promoted Bax and inhibited Bcl-2 protein.”

In the paper

“Castedo et al. [15] proposed that the mitotic cell death catastrophe results from a combination of deficient cell-cycle checkpoints and cellular damage.”

What the sources say

• ?Not checked — no full text of the sourcecites [15] Castedo, 2004, Cell death by mitotic catastrophe: A molecular definition, Oncogene source

In the paper

“Qi et al. provided evidence that, by arresting cell cycle progression in the presence of antimitotic drugs, mitotic spindles are disrupted, and cancer cells directly undergo apoptosis via the mitotic catastrophe [16].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [16] Qi, 2018, Anti-mitotic chemotherapeutics promote apoptosis through TL1A-activated death receptor 3 in cancer cells, Cell Res. source

In the paper

“Therefore, it is considered a new potential target for cancer immunotherapy [19,21].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [19] Silva, 2016, The PD-1:PD-L1 immune inhibitory checkpoint in Helicobacter pylori infection and gastric cancer: A comprehensive review and future perspectives, Porto Biomed. J. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [21] Berntsson, 2018, Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis, Oncoimmunology source

In the paper

“This observation indicates successful preparation, in agreement with previous results [26,27,37,38].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [26] AbouAitah, 2018, Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action, Oncotarget source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [27] Shahein, 2019, Targeted anticancer potential against glioma cells of thymoquinone delivered by mesoporous silica core-shell nanoformulations with pH-dependent release, Int. J. Nanomed. source
• ?Not checked — no full text of the sourcecites [37] AbouAitah, K., Farghali, A., Swiderska-Sroda, A., Lojkowski, W., Razin, A., and Khedr, M.K. (2016). Mesoporous silica materials in drug delivery system: pH/glutathione-responsive release of poorly water-soluble pro-drug quercetin from two and three-dimensional pore-structure nanoparticles. J. Nanomed. Nanotechnol., 7. source
• Not checked yetcites [38] AbouAitah, K.E., Farghali, A., Swiderska-Sroda, A., Lojkowski, W., Razin, A., and Khedr, M.K. (2016). pH-controlled release system for curcumin based on functionalized dendritic mesoporous silica nanoparticles. J. Nanomed. Nanotechnol., 7.

In the paper

“FA was employed as the main targeting ligand, which is known for its binding potential to folate receptors, which are over-expressed on many cancers and facilitate the endocytosis pathway [26,34,35,36].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [26] AbouAitah, 2018, Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action, Oncotarget source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [34] Javaid, 2018, Advances in targeting the folate receptor in the treatment/imaging of cancers, Chem. Sci. source
• ?Not checked — no full text of the sourcecites [35] Sabharanjak, 2004, Folate receptor endocytosis and trafficking, Adv. Drug Deliv. Rev. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [36] Zwicke, 2012, Utilizing the folate receptor for active targeting of cancer nanotherapeutics, Nano Rev. source

In the paper

“Glycine was employed as a source of amino groups that require for cancer growth [33].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [33] Lukey, 2017, Targeting amino acid metabolism for cancer therapy, Drug Discov. Today source

In the paper

“This observation is expected because both chitosan and glycine are composed of amino groups, which is important for confirmation of the coating process.”

In the paper

“We propose two reasons for this finding: Low loading and entrapment in pores.”

In the paper

“MSNs have been investigated as a drug delivery carrier for several drugs and biomolecules [27,31,32].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [27] Shahein, 2019, Targeted anticancer potential against glioma cells of thymoquinone delivered by mesoporous silica core-shell nanoformulations with pH-dependent release, Int. J. Nanomed. source
• ?Not checked — no full text of the sourcecites [31] Chang, 2013, Bioresponsive Controlled Drug Release Based on Mesoporous Silica Nanoparticles Coated with Reductively Sheddable Polymer Shell, Chem. Mater. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [32] Castillo, 2019, Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: An update, Expert Opin. Drug Deliv. source

In the paper

“Despite the promising anticancer effects of COL, a few COL drug delivery systems (DDSs) have been tested to improve its therapeutic efficiency through cancer-targeting [28,29].”

What the sources say

• ?Not checked — no full text of the sourcecites [28] Cauda, 2010, Colchicine-loaded lipid bilayer-coated 50 nm mesoporous nanoparticles efficiently induce microtubule depolymerization upon cell uptake, Nano Lett. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [29] Muvaffak, 2004, Prolonged cytotoxic effect of colchicine released from biodegradable microspheres, J. Biomed. Mater. Res. Part B Appl. Biomater. source

In the paper

“and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.”

In the paper

“An explanation may be the coating used for most of the particles with a smaller size compared to particles with a larger size, leading to an increase in their average size in the sample.”

In the paper

“However, recent studies have revealed the intrinsic expression of PD-1 in many cancers, along with immune T cells [20,21].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [20] Yao, 2018, Cancer Cell-Intrinsic PD-1 and Implications in Combinatorial Immunotherapy, Front. Immunol. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [21] Berntsson, 2018, Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis, Oncoimmunology source

In the paper

“Recently, antimitotic agents such as COL were reported to have a regulatory effect on most immune cell types, leading to the development of effective cancer immunotherapies [17].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [17] Fong, A., Durkin, A., and Lee, H. (2019). The Potential of Combining Tubulin-Targeting Anticancer Therapeutics and Immune Therapy. Int. J. Mol. Sci., 20. source

In the paper

“PD-1 is an inducible immune modulatory receptor expressed on surface-activated T cells, and its ligand PD-L1 is expressed on cancer cells [18].”

What the sources say

• Not checked yetcites [18] Fourcade, 2010, Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients, J. Exp. Med. source

In the paper

“Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL”

In the paper

“Gupta and Dudani [13] proposed that the mechanism of action for antimitotic drugs, such as COL, includes blockade of cell growth at metaphase upon the binding of antimitotic drugs to tubulin (for COL through the colchicine binding site) due to cell-cycle arrest (e.g., at G2/M).”

What the sources say

• ?Not checked — no full text of the sourcecites [13] Gupta, 1989, Mechanism of action of antimitotic drugs: A new hypothesis based on the role of cellular calcium, Med. Hypotheses source

In the paper

“Therefore, cancer-targeting delivery systems with different nano-platforms have gained attention [25,26,27].”

What the sources say

• ?Not checked — no full text of the sourcecites [25] Banerjee, 2017, Strategies for targeted drug delivery in treatment of colon cancer: Current trends and future perspectives, Drug Discov. Today source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [26] AbouAitah, 2018, Folic acid-conjugated mesoporous silica particles as nanocarriers of natural prodrugs for cancer targeting and antioxidant action, Oncotarget source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [27] Shahein, 2019, Targeted anticancer potential against glioma cells of thymoquinone delivered by mesoporous silica core-shell nanoformulations with pH-dependent release, Int. J. Nanomed. source

In the paper

“Recently, the regulatory action by which antimitotic drugs inhibit PD-1 over-expression on the surface of T-cells was highlighted, and that PD-1 is strongly inhibited in the presence of the COL-binding site (CBS) of tubulin [23].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [23] Franchini, 2019, Microtubule-Driven Stress Granule Dynamics Regulate Inhibitory Immune Checkpoint Expression in T Cells, Cell Rep. source

In the paper

“Binding PD-1 to PD-L1 leads to prevent from the immune antitumor effects by T cells against cancer cells [19].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [19] Silva, 2016, The PD-1:PD-L1 immune inhibitory checkpoint in Helicobacter pylori infection and gastric cancer: A comprehensive review and future perspectives, Porto Biomed. J. source

In the paper

“It was reported that free COL decreased mitochondrial membrane potential in HT-29 colon cells, which led to intrinsic apoptotic cell death [6].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [6] Huang, 2015, Colchicine induces apoptosis in HT29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways, Mol. Med. Rep. source

In the paper

“This, because of the vasculature of tumors, is often leaky, leading to accumulating nanoparticles in the bloodstream compared to normal tissue [45].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [45] Tran, 2017, Cancer nanomedicine: A review of recent success in drug delivery, Clin. Transl. Med. source

In the paper

“Concerning the anti-apoptotic effect of CD44 expression in colon cancer, Lakshman et al. previously reported that it prevents the apoptosis killing pathway because it promotes cell transformation into a malignant phenotype with the help of other anti-apoptotic factors in the tumor microenvironment [75].”

What the sources say

• ?Not checked — no full text of the sourcecites [75] Lakshman, 2004, CD44 promotes resistance to apoptosis in human colon cancer cells, Exp. Mol. Pathol. source

In the paper

“The enhanced antimitotic effects block cancer cell growth due to the binding of COL to tubulin in cells, leading to cell death.”

In the paper

“The results create an opportunity to develop a new approach of PD-1 inhibitors through further ongoing research.”

In the paper

“However, mir-205 has also been reported to be downregulated in colon cancer [88].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [88] Orang, 2014, Diagnostic and prognostic value of miR-205 in colorectal cancer, Asian Pac. J. Cancer Prev. source

In the paper

“As a result, cells cannot enter mitosis prior to repairing their DNA damage, resulting in apoptosis or death after their division [53] through various molecular signaling pathways [54,55].”

What the sources say

• ?Not checked — no full text of the sourcecites [53] Cuddihy, 2003, Cell-cycle responses to DNA damage in G2, Int. Rev. Cytol. source
• ?Not checked — no full text of the sourcecites [54] Johnstone, 2002, Apoptosis: A Link between Cancer Genetics and Chemotherapy, Cell source
• ?Not checked — no full text of the sourcecites [55] Hengartner, 2000, The biochemistry of apoptosis, Nature source

In the paper

“In a previous study of colon cancer cells, Park et al. reported that knockdown of CD44 leads to inhibition of cell proliferation and induction of apoptosis [71].”

What the sources say

• Not checked yetcites [71] Park, 2012, shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells, Oncol. Rep.

In the paper

“We propose that the action for MSNsPCOL/CG-FA is the release of COL molecules into cells after folate receptor–folic acid interaction; the COL binds to tubulin in cells through colchicine binding sites, destabilizing tubulin [50], and further interferes with microtubule dynamics.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [50] Lu, 2012, An overview of tubulin inhibitors that interact with the colchicine binding site, Pharm. Res. source

In the paper

“In a study by Schmittnaegel et al., inhibition of Ang-2 together with vascular endothelial growth factor A (VEGFA) enhanced the antitumor immunity, allowing PD-1 checkpoint inhibition [89].”

What the sources say

• ?Not checked — no full text of the sourcecites [89] Schmittnaegel, M., Rigamonti, N., Kadioglu, E., Cassara, A., Wyser Rmili, C., Kiialainen, A., Kienast, Y., Mueller, H.J., Ooi, C.H., and Laoui, D. (2017). Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci. Transl. Med., 9. source

In the paper

“However, the anticancer effect of free COL or enhanced delivery route is in response to inherited antimitotic effects from COL.”

In the paper

“Therefore, either MSNs or MSNsP is a promising nanocarrier for COL delivery.”

In the paper

“They mentioned that cancer cells uptake more MSNs than normal cells, and MSNs are more cytotoxic for cancer cells compared normal cells.”

What the sources say

• ?Not checked — no full text of the sourcecites [39] Menon, 2016, Cytotoxic Effects of Phosphonate-Functionalized Mesoporous Silica Nanoparticles, ACS Appl. Mater. Interfaces source

In the paper

“Thus, mir-205 may be a potential tumor marker and therapeutic target [87].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [87] Jing, 2018, Expression levels of miR-205 and miR-506 in colon cancer tissues and their relationships with clinicopathological features, Oncol. Lett. source

In the paper

“This finding agrees with previously published data for MCF-7 cells and BJ cells treated with MSNs and phosphonate-functionalized MSNs [39].”

What the sources say

• ?Not checked — no full text of the sourcecites [39] Menon, 2016, Cytotoxic Effects of Phosphonate-Functionalized Mesoporous Silica Nanoparticles, ACS Appl. Mater. Interfaces source

In the paper

“It was shown that expression levels of folate receptors vary depending on type of cancer and the colorectal cancers show higher level than liver and prostate cancers [47].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [47] Cheung, 2016, Targeting folate receptor alpha for cancer treatment, Oncotarget source

In the paper

“The G2/M checkpoint inhibitor class of drugs leads to DNA damage, preventing cells from passing mitosis and stopping their proliferation.”

What the sources say

• ?Not checked — no full text of the sourcecites [53] Cuddihy, 2003, Cell-cycle responses to DNA damage in G2, Int. Rev. Cytol. source

In the paper

“Several reports have demonstrated that COL can arrest at G2/M in different cancer cells [7,56].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [7] Zhang, 2016, High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor, Oncotarget source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [56] Kim, 2013, The colchicine derivative CT20126 shows a novel microtubule-modulating activity with apoptosis, Exp. Mol. Med. source

In the paper

“The reason for this is that the anticancer effect is in response to COL release from nanoformulations because it is controlled by a coating that needs some time for degradation.”

In the paper

“In recent years, emerging indications are that lncRNAs, non-protein coding transcripts longer than 200 nucleotides, are responsible for a broad spectrum of biological impacts with gene regulation and other functions in many diseases [76,77].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [76] Ponting, 2009, Evolution and Functions of Long Noncoding RNAs, Cell source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [77] Zhao, 2018, MALAT1: A long non-coding RNA highly associated with human cancers, Oncol. Lett. source

In the paper

“Although many approved therapies are efficient in cancer (e.g., nivolumab and pembrolizumab), they have many limitations, including side effects, toxicity, internal response changes in the immune system, and expense [94,95].”

What the sources say

• ?Not checked — no full text of the sourcecites [94] Ottaviano, 2019, Recent success and limitations of immune checkpoint inhibitors for cancer: A lesson from melanoma, Virchows Arch. Int. J. Pathol. source
• Not checked yetcites [95] Seidel, 2018, Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations, Front. Oncol. source

In the paper

“In addition, Kim et al. indicated that Ang-2 maybe play a crucial role as an oncogene in colorectal carcinogenesis, supporting tumor progression as a prognostic marker [90].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [90] Kim, 2017, Oncogenic function of angiopoietin-2 in vitro and its modulation of tumor progression in colorectal carcinoma, Oncol. Lett. source

In the paper

“CD44 is well-recognized as a robust marker (via overexpression) of colon cancer initiation because it promotes cell adhesion, maintains cell–matrix interactions [73], and induces anti-apoptotic properties [71,74].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [73] Sahlberg, S.H., Spiegelberg, D., Glimelius, B., Stenerlow, B., and Nestor, M. (2014). Evaluation of cancer stem cell markers CD133, CD44, CD24: Association with AKT isoforms and radiation resistance in colon cancer cells. PLoS ONE, 9. source
• Not checked yetcites [71] Park, 2012, shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells, Oncol. Rep.
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [74] Schneider, M., Huber, J., Hadaschik, B., Siegers, G.M., Fiebig, H.H., and Schuler, J. (2012). Characterization of colon cancer cells: A functional approach characterizing CD133 as a potential stem cell marker. BMC Cancer, 12. source

In the paper

“Therefore, it is considered as a new potential for cancer therapy [19] and efficient treatments [92].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [19] Silva, 2016, The PD-1:PD-L1 immune inhibitory checkpoint in Helicobacter pylori infection and gastric cancer: A comprehensive review and future perspectives, Porto Biomed. J. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [92] Khalil, 2016, The future of cancer treatment: Immunomodulation, CARs and combination immunotherapy. Nature reviews, Clin. Oncol. source

In the paper

“Recent studies have revealed the intrinsic expression of PD-1 in many cancers, along with T immune cells [20,21].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [20] Yao, 2018, Cancer Cell-Intrinsic PD-1 and Implications in Combinatorial Immunotherapy, Front. Immunol. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [21] Berntsson, 2018, Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis, Oncoimmunology source

In the paper

“From the observations, the proposed delivery route has an enhanced anticancer effect with a longer duration to 72 h.”

In the paper

“PD-1 immune checkpoint inhibitors act by blocking the PD-1 protein and activate the immune system to treat many tumors [22,93].”

What the sources say

• ?Not checked — no full text of the sourcecites [22] Syn, 2017, De-novo and acquired resistance to immune checkpoint targeting, Lancet Oncol. source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [93] Webb, 2018, Immune checkpoint inhibitors in cancer therapy, J. Biomed. Res. source

In the paper

“Jing et al. showed that the expression of mir-205 is upregulated in plasma from colon cancer patients, permitting the occurrence and development of the cancer.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [87] Jing, 2018, Expression levels of miR-205 and miR-506 in colon cancer tissues and their relationships with clinicopathological features, Oncol. Lett. source

In the paper

“In addition, genetic regulation and immunotherapeutic effects have a role.”

In the paper

“In a next step, it releases COL into cancer cells, which can bind to the tubulin forming the microtubules in the cellular skeleton, resulting in tubulin inhibition.”

In the paper

“The assay was performed as instructed in the kit.”

In the paper

“We propose that the anticancer mechanism is mainly apoptosis cell death, with the contribution of genetic regulation and immunotherapy effects.”

In the paper

“Apoptosis (intrinsic) was found to be the main mechanism of action occurring as a consequence of the strong antimitotic effects.”

In the paper

“Measurements were made in triplicate.”

• Also stated in: § 3.2. Methods · plain

  “Finally, measurements were made in triplicate.”

In the paper

“For the estimation of in vitro cytotoxic potency, the 3-4,5-dimethylthiazol-Z-yl-2,5-diphenyltetrazolium bromide (MTT) assay was conducted according to Mosmann [96].”

What the sources say

• ?Not checked — no full text of the sourcecites [96] Mosmann, 1983, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Methods source

In the paper

“The reactions were performed in triplicate on a Rotor-Gene 3000 RT-PCR system.”

In the paper

“Measurements were made in triplicate.”

In the paper

“The observations provide strong evidence of the intrinsic apoptosis mechanism due to enhanced cytochrome c triggering and reduce the mitochondrial membrane potential, in agreement with the literature.”

In the paper

“The assay was performed in triplicate, and data are expressed as mean ± SD.”