1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD), a diamantane derivative, was previously noted as an anticancer compound through anticancer drug screening with NCI‑60 human tumor cells. Irinotecan (CPT‑11), a semisynthetic derivative of camptothecin, is clinically active in the treatment of colorectal cancer, with no cross‑resistance. The current study conducted a pharmacokinetic evaluation of DPD, an essential component of drug discovery. Subsequent pathway analysis of microarray gene expression data indicated that the anticancer mechanisms of DPD were associated with cell cycle progression and apoptosis. The combined effect of DPD and CPT‑11 with regard to the mechanisms of apoptosis‑related pathways in COLO 205 cells, and the antitumor effects in colon cancer xenograft mice, were investigated. The plasma concentration and pharmacokinetic parameters of DPD in male albino rats were analyzed following a single dose of DPD by injection. The protein expression of active caspase‑3, procaspase‑3 and poly ADP‑ribose polymerase (PARP) in COLO 205 cells treated with DPD and CPT‑11, alone or combined, was evaluated by western blotting. A trypan blue dye exclusion assay revealed that, whilst DPD alone demonstrated good antitumor effects, this effect was potentiated when combined with CPT‑11. Combined treatment with DPD and CPT‑11 upregulated the expression of cleaved PARP, procaspase‑3, caspase‑3 and active caspase‑3 in COLO 205 cells. In the colon cancer xenograft model, compared with the control (vehicle‑treated) mice, the sizes of the tumors were significantly lower in mice treated with DPD and CPT‑11, alone or in combination. Thus, DPD may be a potential therapeutic agent for the treatment of colorectal cancer via upregulating apoptosis‑related pathways.
Oral squamous cell carcinoma (OSCC) is an aggressive tumor that has a poor prognosis, with high levels of local invasion and lymph node metastasis. Vascular endothelial growth factor A (VEGF-A) plays essential roles in OSCC tumor angiogenesis and metastasis. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is implicated in various inflammatory conditions and pathological processes, including oral cancer. The existing evidence has failed to confirm any correlation between MCP-1 or VEGF-A expression and OSCC angiogenesis. In this study, high expression levels of MCP-1 and VEGF-A were positively correlated with disease stage in patients with OSCC. In oral cancer cells, MCP-1 increased VEGF-A expression and subsequently promoted angiogenesis; miR-29c mimic reversed MCP-1 activity. We also found that MCP-1 modulated VEGF-A expression and angiogenesis through CCR2/ILK/MEK1/2 signaling. Ex vivo results of the chick embryo chorioallantoic membrane (CAM) assay revealed the angiogenic qualities of MCP-1, with increased numbers of visible blood vessel branches. Our data suggest that MCP-1 is a new molecular therapeutic target for the inhibition of angiogenesis and metastasis in OSCC.
Abstract Obesity is associated with a higher incidence of thyroid cancer. Adiponectin is one of the most abundant adipokines with pleiotropic roles in metabolism and in the development and progression of cancer. This study aimed to investigate the possible association between the expression of adiponectin receptors (AdipoR1 and AdipoR2) and clinicopathological variables in papillary thyroid cancer. We found that levels of AdipoR1 and AdipoR2 were commonly increased in thyroid cancer compared with adjacent normal thyroid tissues. Thyroid cancer cells expressed AdipoR1 and AdipoR2, which were attenuated by histone deacetylase inhibitor trichostatin A. We determined the expression of AdipoR1 and AdipoR2 by immunohistochemical staining in primary tumor samples and metastatic lymph nodes. AdipoR1 was expressed in 27% of primary tumors and AdipoR2 in 47%. AdipoR1 expression correlated with AdipoR2 expression in primary tumors and in metastatic lymph nodes. Tumor AdipoR1 expression was associated with larger tumor size, whereas negative AdipoR2 expression was significantly associated with extrathyroidal invasion and multicentricity. Patients in the high AMES risk group had negative tumor expression of AdipoR1 and AdipoR2. Collectively, altered expression of adiponectin receptors in thyroid cancer supports a potential role in the pathogenesis of thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5752. doi:1538-7445.AM2012-5752
We aimed to investigate global variations in incidence and mortality and their associations to possible risk factors for prompt cancer prevention and control.
Cellular retinoic acid binding protein 1 (CRABP1) participates in the regulation of retinoid signaling. Previous studies showed conflicting results regarding the role of CRABP1 in tumor biology, including protumorigenic and tumor-suppressive effects in different types of cancer. Our bioinformatics analyses suggested that CRABP1 expression was downregulated in thyroid cancer. Ectopic expression of CRABP1 in thyroid cancer cells suppressed migratory and invasive activity without affecting cell growth or cell cycle distribution. In transformed normal thyroid follicular epithelial cells, silencing of CRABP1 expression increased invasiveness. Additionally, CRABP1 overexpression was associated with downregulation of the mesenchymal phenotype. Kinase phosphorylation profiling indicated that CRABP1 overexpression was accompanied by a decrease in phosphorylation of epidermal growth factor (EGF) receptor and downstream phosphorylation of Akt, STAT3, and FAK, which were reversed by exogenous EGF treatment. Immunohistochemical analysis of our tissue microarrays revealed an inverse association between CRABP1 expression and disease stage of differentiated thyroid cancer. Taken together, our results suggest that CRABP1 expression is aberrantly lost in thyroid cancer, and this downregulation promotes the epithelial-mesenchymal transition at least partly through modulating EGF receptor signaling.
A 66-year-old man initially underwent appendectomy and cytoreductive surgery for a low-grade appendiceal mucinous neoplasm with pseudomyxoma peritonei. One and a half years later, multiple disseminated lesions developed in rectus abdominis muscle and peritoneal cavity. Biopsy showed histopathological transformation to sarcomatoid carcinoma. This case illustrates that evolution of low-grade pseudomyxoma peritonei to high-grade carcinoma truly develops in some patients. The development of this dedifferentiation appears associated with aggressive behavior and poor clinical outcome.
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