- Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study. [Journal Article]
- PMPLoS Med 2018; 15(9):e1002651
- CONCLUSIONS: In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
- EGF ligand fused to truncated Pseudomonas aeruginosa exotoxin A specifically targets and inhibits EGFR‑positive cancer cells. [Journal Article]
- OROncol Rep 2018 Sep 06
- Cancer cells have been known to overexpress the epidermal growth factor receptor (EGFR) and hence relevant multiple‑targeted therapies have been developed, with a recent clinical application of the a...
Cancer cells have been known to overexpress the epidermal growth factor receptor (EGFR) and hence relevant multiple‑targeted therapies have been developed, with a recent clinical application of the antibody‑mediated inhibition of the EGFR. However, this strategy is not useful in cancer cells with mutations in KRAS; a GTPase downstream of EGFR which constitutively activates the pathway without EGF stimulation. Furthermore, mutations in EGFR also reduce the binding of monoclonal antibodies and thereby render them ineffective. In the present study, we designed a chimeric EGF protein fused to the truncated N‑terminal domain fragment of Pseudomonas aeruginosa exotoxin A (EGF‑ETA), which has ADP‑ribosylation activity and induces apoptosis. The EGF‑ETA protein was expressed in E. coli as a His‑tagged fusion. Our results showed that EGF‑ETA significantly inhibited the proliferation of EGFR‑positive A431 epidermoid carcinoma (IC50 27 ng/ml) and HN5 head and neck squamous cell carcinoma (IC50 36 ng/ml) cells. However, its effect on cancer cells with little or no EGFR expression was limited (A549‑IC50 1,000 ng/ml; MCF‑7‑IC50 >10,000 ng/ml). Compared to cetuximab, EGF‑ETA was highly potent in its killing capacity of HN5 cancer cells at 1,000 ng/ml, while cetuximab had little effect at 1,000 ng/ml. Furthermore, EGF‑ETA was just as potent in HCT116 (KRAS G13D) and SW480 (KRAS G12V) colon cancer cell lines harbouring KRAS hyperactivating mutations when compared to KRAS wild‑type HT29 colon cancer cells. Finally, co‑incubation of EGF‑ETA with an anti‑EGF antibody abrogated its effect on the EGFR‑positive A431 cells. Our results show that the chimeric EGF‑ETA toxin is extremely effective against EGFR‑positive cancers and raises the potential to further develop this chimera for use in targeting EGFR‑positive tumours resistant to monoclonal antibodies.
- Epigenetic roles of PIWI‑interacting RNAs (piRNAs) in cancer metastasis (Review). [Journal Article]
- OROncol Rep 2018 Sep 06
- P‑element‑induced wimpy testis (PIWI)‑interacting RNAs (piRNAs) are epigenetic‑related short ncRNAs that participate in chromatin regulation, transposon silencing, and modification of specific gene s...
P‑element‑induced wimpy testis (PIWI)‑interacting RNAs (piRNAs) are epigenetic‑related short ncRNAs that participate in chromatin regulation, transposon silencing, and modification of specific gene sites. These epigenetic factors or alterations are also involved in the growth of a variety of human cancers, including lung, breast, and colon cancer. Accumulating evidence has revealed that tumor metastasis and invasion involve genetic and epigenetic factors. Cancer metastasis is characterized by epigenetic alterations including DNA methylation and histone modification. Changes in DNA methylation, H3K9me3 heterochromatin and transposable elements have been detected in several cancers. piRNAs may function in gene silencing and gene modification upstream or downstream of oncogenes in cancer cell lines or cancer tissues. In addition to piRNAs, PIWI proteins can be used as biomarkers for prognosis, diagnosis and clinical evaluation and may be factors in cancer metastasis. Here, we elucidated the possible mechanisms by which piRNAs regulate cancer metastasis, including but not restricted to influencing DNA and histone methylation and transposable elements.
- RASSF1A suppresses colorectal tumor cell growth through p53-dependent p21WAF1 activation. [Journal Article]
- JGJ Gastroenterol Hepatol 2018 Sep 18
- CONCLUSIONS: RASSF1A suppresses colonic tumor growth through the activation of the p53-p21WAF1 pathway. This finding supports that RASSF1A could be a valuable marker for the assessment of colorectal cancer development and progression.
- Changes in spatio-temporal localization of tripeptidyl peptidase II (TPPII) in murine colon adenocarcinoma cells during aggresome formation: a microscopy study based on a novel fluorescent proteasome inhibitor. [Journal Article]
- HHHistol Histopathol 2018 Sep 18; :18042
- Extralysosomal proteolysis is a multistep process involving the Ubiquitin- Proteasome System (UPS) and supplementary peptidases. Tripeptidyl peptidase II (TPPII) is the most extensively characterized...
Extralysosomal proteolysis is a multistep process involving the Ubiquitin- Proteasome System (UPS) and supplementary peptidases. Tripeptidyl peptidase II (TPPII) is the most extensively characterized enzyme, supplementing and sometimes substituting for proteasomal functions. In response to proteasome inhibition, polyubiquitinated proteins acting as proteasome substrates aggregate with proteasomes and form aggresomes. Several proteasome inhibitors are used as anti-cancer drugs. Thus, in our study, we used a novel fluorescent-tagged proteasome inhibitor BSc2118 to induce aggresome formation in C26 murine colon adenocarcinoma cells. It allowed us to obtain effective, inhibitor-based, proteasome staining in vivo. This method has been validated by standard post-fixed indirect immunostaining and also allowed co-immunodetection of TPPII and polyubiquitinated proteins under laser scanning confocal microscopy. We found that in the absence of the inhibitor, TPPII is diffusely dispersed within the cytoplasm of C26 cells. The proteasome and ubiquitin-rich perinuclear region failed to display enhanced TPPII staining. However, when proteasome function was impaired by the inhibitor, TPPII associated more closely with both the proteasome and polyubiquitinated proteins via TPPII recruitment to the perinuclear region and subsequently into emerging aggresomal structures. Furthermore, we have demonstrated the dynamic recruitment of TPPII into the developing aggresome: TPPII in the early aggresome was dispersed within the central part but subsequently aggregated on the surface of this structure. In the mature aggresome of C26 cells TPPII formed a spherical mantle, which surrounded the round core containing proteasomes and polyubiquitinated proteins. Our morphological data indicate that TPPII displays spatial localization with proteasomes especially upon proteasome inhibition in aggresomes of C26 cells.
- Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon Cancer. [Journal Article]
- MIMol Imaging Biol 2018 Sep 17
- CONCLUSIONS: USMI (semi)quantitative parameters provide earlier assessment of the response to therapy compared to tumor volume, permit early prediction of non-responders, and correlate well with ex-vivo angiogenesis biomarkers.
- Identification of 16,25-O-diacetyl-cucurbitane F and 25-O-acetyl-23,24-dihydrocucurbitacin F as novel anti-cancer chemicals. [Journal Article]
- RSR Soc Open Sci 2018; 5(8):180723
- Seven new cucurbitane glucosides, hemslepensides J-P (1-7), and two known compounds, 16,25-O-diacetyl-cucurbitane F (8) and 25-O-acetyl-23,24-dihydrocucurbitacin F (9), were isolated from the tubers ...
Seven new cucurbitane glucosides, hemslepensides J-P (1-7), and two known compounds, 16,25-O-diacetyl-cucurbitane F (8) and 25-O-acetyl-23,24-dihydrocucurbitacin F (9), were isolated from the tubers of Hemsleya pengxianensis var. jinfushanensis. The structures of 1-7 were elucidated using infrared absorption spectroscopy, nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry. The treatment of HT29 cells, human colon cancer cells, with compounds 8 and 9 inhibited cell proliferation. Further study demonstrated that compounds 8 and 9 induced F-actin aggregation, G2/M phase cell cycle arrest and cell apoptosis in HT29 cells. In summary, the present study enriched the chemical composition research of H. pengxianensis, and suggested that the compounds 8/9 treatment may be a potentially useful therapeutic option for colon cancer.
- In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice. [Journal Article]
- JCJ Clin Med 2018 Sep 15; 7(9)
- Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its pos...
Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive (through inhibition of human angiotensin-converting enzyme; ACE) properties. The phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame-Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). In this study, all biological methods were performed at the level of in vitro studies. The results showed that TB-EO exerted remarked cytotoxic properties against human cervical carcinoma cells, colon cancer cells, and lung adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values of 7.22, 9.30, and 8.62 µg/mL, respectively, in comparison with that of standard anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 µg/mL, respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy human fetal lung fibroblast cells with an IC50 value of 118.34 µg/mL compared with that of cisplatin (IC50 = 10.08 µg/mL). TB-EO, its main component geraniol, TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed pronounced inhibitory properties against the replication of HSV-2 with the half-maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 µg/mL, respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26 and 108.25, respectively. TB-EO and geraniol at a concentration of 15 µg/mL showed prominent inhibitory activities against ACE with % of inhibition 95.4% and 92.2%, respectively, compared with that of standard inhibitor captopril (99.8%; 15 µg/mL). Molecular docking studies were performed to unveil the mechanism of action of geraniol as well as structural parameters necessary for anti-HSV-2 activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is the first report on the chemical composition of Egyptian TB-EO along with the above-mentioned biological activities. Our results may be considered as novel findings in the course of a search for new and active anticancer, anti-HSV-2 and antihypertensive agents, and expand the medicinal value of this plant and its phytochemicals in clinical practice.
- Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer. [Journal Article]
- CCancers (Basel) 2018 Sep 14; 10(9)
- Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colo...
Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E. Invasive canine tumors harbor prominent fibroblast proliferation and overactivated stroma. Both groups have recurrent TP53 mutations. We observed three invasion patterns in canine tumors: collective, crypt-like and epithelial⁻mesenchymal transition (EMT). We detected enriched Helicobacter bilis and Alistipes finegoldii in proliferative and crypt-like tumors, but depleted mucosa-microbes in the EMT tumor. Second, guided by our canine findings, we classified 79% of 478 human colon cancers from The Cancer Genome Atlas into four subtypes: primarily proliferative, or with collective, crypt-like or EMT invasion features. Their molecular characteristics match those of canine tumors. We showed that consensus molecular subtype 4 (mesenchymal) of human CRC should be further divided into EMT and crypt-like subtypes, which differ in TGF-β activation and mucosa-microbe content. Our canine tumors share the same pathogenic pathway as human CRCs. Dog-human integration identifies three CRC invasion patterns and improves CRC subtyping.
New Search Next
- Genome-wide methylation analysis identifies novel prognostic methylation markers in colon adenocarcinoma. [Journal Article]
- BPBiomed Pharmacother 2018 Sep 14; 108:288-296
- Previous studies have indicated that abnormal methylation is a critical and early event in the pathogenesis of most types of human cancer, which contributes to tumorigenesis. However, there has been ...
Previous studies have indicated that abnormal methylation is a critical and early event in the pathogenesis of most types of human cancer, which contributes to tumorigenesis. However, there has been little focus on the potential of DNA methylation patterns as predictive markers for the prognosis of colon adenocarcinoma (COAD). In the present study, a genome-wide comparative analysis of DNA methylation profiles was performed between 315 COAD samples and 38 matched tumor-adjacent normal tissue samples. A total of 675 differentially methylated regions (DMRs) associated with 630 genes were identified, including 654 hypermethylated regions (UMRs) and 21 hypomethylated regions, which were capable of distinguishing COAD samples from non-malignant tissue samples. Although most of the DMRs appeared to be located within the gene body or promoter regions, UMRs were mostly located within CpG islands. Functional analysis suggested that genes associated with DMRs were enriched in many of the core cancer-signaling pathways known to be important in COAD biology. A survival analysis was also performed, which identified 7 DMRs as potential candidate markers with the ability to classify patients into high and low-risk groups with significantly different overall survival. The present study provides a better understanding of the molecular mechanisms underlying COAD, and demonstrates the utility of aberrant DNA methylation in the prognosis of COAD.