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Colorectal cancer (CRC) is the third most frequent malignancy worldwide. Coffee is the second most consumed drink in the globe and suggested to decrease the CRC risk. Here, we explored whether coffee, decaffeinated coffee, or caffeine impact on the development of colorectal carcinogenesis induced by the direct carcinogen N-methyl-N-nitro-N-nitrosoguanidine (MNNG) in rats. To this end, sixty-four young male Wistar rats were divided into eight groups of eight animals each. We analyzed the frequency of dysplastic crypts and expression of metallothionein as a biomarker of the cancer risk, as well the expression of phosphorylated H2A histone family/member X (γH2AX) for DNA damage and cyclooxygenase-2 (COX-2) for inflammatory response. We also studied the oxidative stress profile in hepatic and colonic frozen samples (malondialdehyde [MDA], glutathione [GSH], and α-tocopherol). We found that coffee but neither decaffeinated coffee nor caffeine decreased the development of dysplastic crypts in MNNG-exposed rats. All treatments reduced DNA damage intensity in colonocytes. Only decaffeinated coffee increased the numbers of metallothionein positive crypts in comparison with coffee-treated rats. Coffee and caffeine inhibited COX-2 expression in the colon. Both decaffeinated coffee and caffeine decreased hepatic α-tocopherol levels. We suggest that coffee may have other compounds that elicit greater chemoprotective effects than caffeine reducing the CRC risk. [ABSTRACT FROM AUTHOR]

Laryngeal squamous cell carcinoma (LSCC) is a very aggressive cancer, considered to be a subtype of the head and neck squamous cell carcinoma (HNSCC). Despite significant advances in the understanding and treatment of cancer, prognosis of patients with LSCC has not improved recently. In the present study, we sought to understand better the genetic mechanisms underlying LSCC development. Thirty-two tumor samples were collected from patients undergoing surgical resection of LSCC. The samples were submitted to whole-genome cDNA microarray analysis aiming to identify genetic targets in LSCC. We also employed bioinformatic approaches to expand our findings using the TCGA database and further performed functional assays, using human HNSCC cell lines, to evaluate viability, cell proliferation, and cell migration after silencing of selected genes. Eight members of the homeobox gene family (HOX) were identified to be overexpressed in LSCC samples when compared to normal larynx tissue. Quantitative RT-PCR analysis validated the overexpression of HOX gene family members in LSCC. Receiver operating characteristic (ROC) statistical method curve showed that the expression level of seven members of HOX gene family can distinguish tumor from nontumor tissue. Correlation analysis of clinical and gene expression data revealed that HOXC8 and HOXD11 genes were associated with the differentiation degree of tumors and regional lymph node metastases, respectively. Additionally, siRNA assays confirmed that HOXC8, HOXD10, and HOXD11 genes might be critical for cell colony proliferation and cell migration. According to our findings, several members of the HOX genes were overexpressed in LSCC samples and seem to be required in biological processes involved in tumor development. This suggests that HOX genes might play a critical role in the physiopathology of LSCC tumors. [ABSTRACT FROM AUTHOR]

Purpose: Physical exercise has been shown to be protective against colon carcinogenesis. Physical exercise, however, covers a wide range of modalities, from which different effects on the human body have been reported. We sought to clarify whether aerobic and resistance trainings would differently affect the development of early carcinogenic events in the colon. Methods: Male BALB/c, C57/BL6, and interleukin 10 knockout (IL-10~ , on C57/BL6 background) mice were exposed to the carcinogen A-methyl-A'-nitro-A-nitrosoguanidine. BALB/c mice were subjected to either aerobic (swimming) or resistance trainings (climbing a ladder with load attached to the tail). C57/BL6 and IL-10- _ mice only swam. Results: In BALB/c carcinogen-exposed mice, aerobic and resistance trainings decreased serum creatine kinase levels (P< 0.001). Although aerobic and resistance trainings reduced the generation of lipid thiobarbituric reactive species (P< 0.01 and P< 0.001), only aerobic exercises enhanced serum glutathione levels aside from carcinogenic exposure (P < 0.05). Carcinogen-exposed and aerobic-trained mice developed 36% less colon preneoplastic lesions than its control group (P < 0.05). Aerobic training reduced colonic subepithelial cyclooxygenase-2 expression in carcinogen-exposed mice (P < 0.001). Interestingly, in this same group, colonic IL-10 expression was upregulated sevenfold (P < 0.001). Current findings were confirmed in C57/BL6 carcinogen-exposed mice, in which aerobic training promoted antipreneoplastic effects (P < 0.05). Knocking IL-10 out o f C57/BL6 mice abrogated antipreneoplastic effects of aerobic training on the colon tissue (.P > 0.05). Conclusions: IL-10 is a pivotal element for antipreneoplastic effects of aerobic training on the colon. [ABSTRACT FROM AUTHOR]

Platelet-derived growth factor (PDGF) and signaling via its receptors plays a crucial role in tumor cell proliferation and thus may represent an attractive target besides VEGF/EGFR-based antibody therapies. In this study we analyzed the influence of PDGF in colorectal cancer. PDGF was expressed intensively in early and even more intensively in late stage primary CRCs. Like VEGF, PDGF enhanced human colon cancer proliferation, and increased oxidative glycolytic activity, and activated HIF1α and c-Myc in vitro. PDGF activated the PI3K/Akt/mTOR pathway while leaving MAPK signaling untouched. Further dissection showed that inhibition of Akt strongly impeded cancer cell growth while inhibition of PI3K did not. MAPK analysis suggested an inhibitory crosstalk between both pathways, thus explaining the different effects of the Akt and PI3K inhibitors on cancer cell proliferation. PDGF stimulates colon cancer cell proliferation, and prevents inhibitor induced apoptosis, resulting in tumor growth. Therefore inhibition of PDGF signaling seems to be a promising target in colorectal cancer therapy. However, due to the multifaceted nature of the intracellular PDGF signaling, careful intervention strategies are needed when looking into specific signaling pathways like PI3K/Akt/mTOR and MAPK.

Glycans are emerging as important regulators of T cell function but remain poorly characterized across the functionally distinct populations that exist in vivo . Here, we couple single-cell analysis technologies with soluble lectins and chemical probes to interrogate glycosylation patterns on major T cell populations across multiple mouse and human tissues. Our analysis focused on terminal glycan epitopes with immunomodulatory functions, including sialoglycan ligands for Siglecs. We demonstrate that glycosylation patterns are diverse across the resting murine T cell repertoire and dynamically remodelled in response to antigen-specific stimulation. Surprisingly, we find that human T cell populations do not share the same glycoprofiles or glycan remodelling dynamics as their murine counterparts. We show that these differences can be explained by divergent regulation of glycan biosynthesis pathways between the species. These results highlight fundamental glycophysiological differences between mouse and human T cells and reveal features that are critical to consider for glycan-targeted therapies.

Colon cancer is one of the most common tumors worldwide, with increasing incidence in developing countries. Patients treated with fluoxetine (FLX) have a reduced incidence of colon cancer, although there still remains great controversy about the nature of its effects. Here we explore the latest achievements related to FLX treatment and colon cancer. Moreover, we discuss new ideas about the mechanisms of the effects of FLX treatment in colon cancer. This leads to the hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase through a control of the tumor-related energy generation machinery. We believe that the potential of FLX to act against tumor metabolism warrants further investigation.