C-Terminal-PEDF Reduces IC50 Doses and Chemoresistant Population of CD133 and BCRP1-Positve Cancer Stem Like Cells

Abstract

We report on two patients, successfully treated by the combination therapy of gemcitabine and 24-h intravenous infusion of cisplatin, who were initially diagnosed with node-positive advanced urothelial cancer. Each patient had a very good clinical response and underwent curative radical surgery after gemcitabine/cisplatin chemotherapy. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. As a pilot study, we have used the regimen of gemcitabine plus 24-h continuous infusion of cisplatin, instead of bolus injection, for the treatment of 20 patients with node-positive or metastatic urothelial cancer. The clinical response rate in this regimen was 75% (complete response 7/20; 35%, partial response 8/20; 40%). The median overall survival was 665 days. As for the adverse effects, the incidences of severe neutropenia and thrombocytopenia (grade 3-4) were 20% and 15%, which might be less toxic than conventional gemcitabine plus cisplatin therapy. The 24-h infusion of cisplatin combined with gemcitabine can be highly recommended as neoadjuvant chemotherapy for locally advanced urothelial cancer.

Moonlight role of PEDF in breast cancer: self-renewal inhibition in breast cancer stem cells

“…We postulated that this is the reason for the resistance observed in some treatments. Similar differences in resistance have also been observed in other colon and breast cancer cell lines [9,33] and even in other more aggressive types of tumours such as a glioblastoma C6 cell line [40,53]. In our hands, the nal percentage of resistant cells after maximum physiological doses of docetaxel treatment is also higher in LT+ positive cells than in the rest.…”

“…A signi cant difference is shown between treated cells and controls, with PEDF or derived peptides, but the protocol followed in this experiment should be standardized to obtain a better result. The molecular subtype used in this work could be in uencing the observed effects, however, the same results have been obtained in cell lines of other types of tumours [33,40]. Also we observe differences in the level of expression of proteins that participate in the PEDF signalling pathway justifying the differences between cell lines in the different experiments while maintaining the nal effect and the extractable conclusions.…”

“…This has a potential application in clinical cancer therapies by the co-administration with chemotherapy to improve relapse-cancer treatment. This is the case for CTE-PEDF, which decreases drug resistance [33,40,41]. The co-administration with chemotherapy would lead to a less resistant population because TICs would have lost their stemness characteristics, as we discuss in the following paragraphs.…”

Moonlighting Role of PEDF in Breast Cancer

“…We postulated that this is the reason for the resistance observed in some treatments. Similar differences in resistance have also been observed in other colon and breast cancer cell lines[6] and even in other more aggressive type of tumours as a glioblastoma C6 cell line [37]. The final percentage of resistant cells after maximum physiological doses of Docetaxel treatment is also higher in LT+ positive cells than in the rest.…”

“…We demonstrate that PEDF (and derivatives) have a moonlighting role in breast cancer development and relapse, and it has a potential application in clinical cancer therapies by the co-administration with chemotherapy for relapse cancer treatment. This is the case of CTE-PEDF, that decreases drug resistance [37,38]. The co-administration with chemotherapy would lead to a less resistant population because TICs would have changed and lost their stemness characteristics, as we discuss in the following sections.…”