Minimal dosing of leukocyte targeting TRAIL decreases triple-negative breast cancer metastasis following tumor resection

Abstract

Surgical removal of the primary tumor is a common practice in breast cancer treatment. However, postsurgical metastasis poses an immense setback in cancer therapy. Considering that 90% of cancer-related deaths are due to metastasis, antimetastatic therapeutic strategies that can target disseminating tumor cells in the circulation before they can form secondary tumors hold preclinical and clinical potential for cancer patients. Our current work uses a liposomal formulation functionalized with the adhesion receptor E-selectin and the apoptosis-inducing ligand TNF (tumor necrosis factor)–related apoptosis-inducing ligand (TRAIL) to reduce metastasis following tumor resection in an aggressive triple-negative breast cancer (TNBC) mouse model. We demonstrate that minimal administration of E-selectin–TRAIL liposomes can target metastasis in a TNBC model, with primary tumor resection to mimic clinical settings. Our study indicates that TRAIL liposomes, alone or in combination with existing clinically approved therapies, may neutralize distant metastasis of a broad range of tumor types systemically.

F-18 fluorodeoxyglucose positron emission computed tomography in the diagnosis of pleural metastases from breast carcinoma

“…Moreover, up to 50% of the remaining group of cases will eventually develop metastatic disease which distinctly decreases the survival time and deteriorates the quality of life. [6][7][8][9][10][11] The most common metastatic targets of breast cancer are lungs, bones and liver. Almost 60% of the patients with advanced breast cancer suffer lung and bone metastasis.…”

“…[1][2][3][4][5] It is also of capital importance for physicians considering that distant organ dissemination may be present at the time of diagnosis and even the early-stage disease is predisposed to develop metastases. 2,6 Surgical resection of primary tumor is the principal practice of treatment for non-metastasizing breast cancers whereas locally advanced disease and distant metastases necessitate chemotherapy, hormonal therapy or radiotherapy following evaluation on a case-by-case basis. 7,8 Pleural metastasis of breast cancer mostly present as pleural nodularity or thickening frequently with an accompanying malignant pleural effusion.…”

“…3,4 Median survival is regarded as 15 months at most following the accumulation of pleural effusion secondary to breast cancer metastasis. 6 As in any other malignancies, a newly diagnosed breast cancer indicates appropriate staging to constitute an accurate treatment algorithm. This study aimed to reveal the efficiency of PET/CT in exposing the pleural invasion of metastatic breast cancers.…”

A simplified method for the efficient purification and refolding of recombinant human TRAIL

“…To test the bioactivity of the recombinant trimeric TRAIL, human colon cancer cells COLO 205, which we have found to be highly sensitive to TRAIL-induced apoptosis, were treated with the purified rhTRAIL and commercial TRAIL as a positive control for 2 hr at the specified concentrations (Figure 4). [7][8][9] Cell viability was then analyzed with Annexin V/PI assay to quantify the viable percentage. Cancer cell apoptosis-inducing activity was observed even at 5 ng/ml (Figure 4).…”

“…5 Consequently, novel approaches to increase the bioactivity of recombinant TRAIL, such as means to deliver TRAIL to target cancer cells with minimal loss of activity before reaching its target, are currently being developed. 2,[6][7][8][9][10] Expressed by various types of immune cells, TRAIL is a type II transmembrane protein with the receptor binding domain extending outside the cells. 1 Proteolytical cleavage of TRAIL from the cell surface yields the soluble extracellular portion composed of amino acids 114-281.…”