Anticancer research
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Anticancer research · Jul 2014
The angiopoietin-TIE2 pathway is a potential therapeutic target in urothelial carcinoma.
Angiopoietin/Tyrosine Kinase-2 (ANG/TIE2), Fibroblast Growth Factor-1 (FGFR1) and Vascular Endothelial Growth Factor Receptors (VEGFRs) promote growth of urothelial carcinoma (UC). We examined the pre-clinical activity of CEP-11981, a tyrosine kinase inhibitor of TIE2, FGFR1 and VEGFR-1-3, in UC. ⋯ CEP-11981 demonstrated a significant pre-clinical activity against human UC xenografts, which was attributable primarily to effects on TIE2 receptor.
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Anticancer research · Jul 2014
Synergistic antitumor effect of NVP-BEZ235 and sunitinib on docetaxel-resistant human castration-resistant prostate cancer cells.
According to recent studies, mTOR (mammalian target of rapamycin) inhibitor and tyrosine kinase inhibitor (TKI) can be used as combinational agents to enhance the antitumor effect or overcome resistance to one of the agents. In the present study, we investigated the synergistic interaction between NVP-BEZ235, a PI3K (phosphoinositide 3-kinase)/mTOR dual inhibitor, and sunitinib, a TKI, in castration-resistant prostate cancer (CRPC) cells with docetaxel resistance. Prostate cancer cells with different sensitivities to hormones and docetaxel levels were exposed to escalating doses of NVP-BEZ235 alone and in combination with sunitinib. ⋯ Combination therapy caused an induction of caspase-dependent apoptosis in docetaxel-resistant CRPC cells. Adding sunitinib did not produce any additional effect on the NVP-BEZ235-mediated inhibition of PI3K/AKT/mTOR phosphorylation. In conclusion, combining NVP-BEZ235, a dual PI3K/mTOR inhibitor, with sunitinib can synergistically potentiate the antitumor effect in CRPC cells after docetaxel failure though induction of caspase-dependent apoptosis.
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Anticancer research · Jul 2014
Comparison of colorectal cancer in differentially established liver metastasis models.
Metastasis is one of the main reasons for colorectal cancer (CRC)-related deaths due to the lack of effective therapeutics mainly for liver metastasis. In the present study, we established an orthotopic colorectal cancer mouse model using different transplantation protocols to determine the optimal conditions for CRC liver metastasis. ⋯ The model described herein will be effective in studying new therapeutic strategies against metastatic disease when used in conjunction with small animal MRI and optical imaging.
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Anticancer research · Jun 2014
The role of sentinel lymph node biopsy in patients with local recurrence or in-transit metastasis of melanoma.
From January 2003 to March 2010, a prospective study was undertaken at the National Cancer Research Institute of Genoa in 15 patients with melanoma who had local recurrence (LR) or a few (≤ 3) in-transit metastases and clinically-negative regional lymph nodes with the aim of defining: i) the feasibility of sentinel node re-staging (r-sN) of the regional nodal basin; ii) the prognostic value of sentinel node status, and iii) the potential benefit in terms of disease-free survival and overall survival in patients with an histologically-positive sentinel node undergoing therapeutic regional lymph node dissection. Preoperative lymphoscintigraphy was performed to identify the r-sN: the radiotracer was intra-dermally injected around the LR or in-transit metastasis. Moreover, 10 min prior to the operative procedure, 0.5 ml intradermal injection of Patent-Blue-V dye was given around each LR or in-transit metastasis site, so that r-sN identification was achieved by both visualization of the nodal blue dye staining and the information supplied by gamma-detection probe. ⋯ The interval between the diagnosis of primary melanoma and the onset of recurrence was longer, although not significantly, in patients with tumor-negative r-sN, a compared to tumor-positive r-sN (49 ± 47 months vs. 25 ± 19 months, p=0.342). There was a trend toward an improved 1-, 3-, and 5-year disease-free survival and overall survival in patients with tumor-negative r-sN a compared to tumor-positive r-sN. Hence, the r-sN proved to be a feasible and accurate staging procedure even in patients with a few localizations of LR or in-transit metastases (≤ 3). r-sN identified those with a more favorable prognosis, supporting an aggressive therapeutic approach in the natural history of their disease; moreover, an unnecessary regional lymph node dissection was safely avoided in 11 out of 15 73.3% patients because they had a tumor-negative r-sN.
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Anticancer research · May 2014
The impact of combined thoracoscopic and laparoscopic surgery on pulmonary complications after radical esophagectomy in patients with resectable esophageal cancer.
Pulmonary complications (PCs) after esophagectomy for patients with esophageal cancer have been correlated with prolonged hospital stays and in-hospital mortality. Previous studies have shown that minimally-invasive esophagectomy (MIE) is associated with a lower rate of PCs compared to conventional open surgery. Although PCs were reportedly associated with many factors, including surgical approaches, patients' demographics, and perioperative variables, the predictive factors for PCs including MIE, have not been fully evaluated. ⋯ The combination of thoracoscopic and laparoscopic MIE presents as an excellent surgical procedure for the reduction of PCs after esophagectomy.