Cancer dormancy emerges when tumor cells cease to proliferate but remain alive in a quiescent state. Recent evidence suggests that cancer cells can stay dormant in a patient’s body for years before returning to a proliferative state, leading to cancer relapse. The lack of a system to efficiently identify and study dormant cancer cells is currently limiting further diagnostic and treatment developments to prevent cancer relapse. Herein, we present a novel encapsulation platform to identify and study dormancy-capable cancer cells in a quiescent state by inhibiting proliferation through physical confinement. The platform involves the encapsulation of cells within a stiff silica-PEG hydrogel produced by a sol–gel technique. Cells are immobilized in a nondegradable microenvironment where proliferation and movement are inhibited due to physical confinement of the gel. The platform was tested using non-cancerous cell lines HFF, HUVEC, Jurkat, MEF, and MCF-10A, and cancer cell lines LnCAP, MCF-7, MCF10DCIS.com , MDA-MB-468, and OVCAR-5. Viability and metabolic activity measurements showed that MCF-7, LnCAP, and MCF10DCIS.COM cells remained metabolically active for up to 3 weeks while non-cancerous lines and the rest of the cancer cell lines did not survive after a few days. Ki-67 immunofluorescent staining confirmed that surviving MCF-7 cells underwent cell cycle arrest as early as 48 hours after encapsulation. Furthermore, following extraction and recovery, these cells resumed proliferation, indicating that the induced cell cycle arrest was reversible. These results conclude that physically inhibiting proliferation via the silica-PEG hydrogel system can be used to identify cells that can enter a quiescent state, setting the groundwork for this platform to be explored as a cancer cell dormancy model.
The financial costs of laryngeal cancer treatment are a notable burden on healthcare budgets. In this study, we assess whether CO2 laser surgery is cheaper than radiotherapy or laryngofissure and cordectomy in the treatment of T1-2, N0, M0 glottic squamous cell carcinoma. 56 patients with a mean age of 65.88 years (SD = 10.04), 53 men and 3 women, with T1-2, N0, M0 glottic squamous cell carcinoma were retrospectively analysed. We conducted a comparative analysis of costs associated with three treatments: carbon dioxide laser cordectomy (n = 21), radiotherapy (n = 20), and laryngofissure cordectomy (n = 15). Complications of the radiotherapy and surgical treatments, need for tracheotomy and its permanence, length of hospital stay, occupation and ability to work and economic costs of treatments were recorded. Cost-minimisation and cost-effectiveness analysis were obtained. The cost of transoral laser cordectomy (2,289.79 euro) is statistically significantly lower than that of radiotherapy (4,804.72 euro) or laryngofissure cordectomy (13,229.75 euro) (p < 0.001). Transoral carbon dioxide laser surgery is the best option in terms of cost-effectiveness for the treatment of T1-2, N0, M0 glottic cancer.
The principal cause of cancer deaths is the residual disease, which eventually results in metastases. Certain metastases are induced by disseminated dormancy-capable single cancer cells that can reside within the body undetected for months to years. Awakening of the dormant cells starts a cascade resulting in the patient's demise. Despite its established clinical significance, dormancy research and its clinical translation have been hindered by lack of in vitro models that can identify, isolate, and analyze dormancycapable cells. We have previously shown that immobilization of cells in a stiff microenvironment induces dormancy in dormancy-capable cell lines. In this communication, we present a novel biomaterial and an in vitro immobilization method to isolate, analyze, and efficiently recover dormancy-capable cancer cells. MCF-7, MDA-MB-231, and MDA-MB-468 cells were individually coated with agarose using a microfluidic flowfocusing device. Coated cells were then immobilized in a rigid and porous silica gel. Dormancy induction by this process was validated by decreased Ki-67 expression, increased p38/ERK activity ratio, and reduced expression of CDK-2, cyclins D1, and E1.We showed that we can reliably and repeatedly induce dormancy in dormancy-capable MCF-7 cells and enhance the dormancy-capable sub-population in MDA-MB-231 cells.As expected, dormancy-resistant MDA-MB-468 cells did not survive immobilization.The dormant cells could be awakened on demand, by digesting the agarose gel in situ, and efficiently recovered by magnetically separating the silica gel, making the cells available for downstream analysis and testing. The awakened cells were shown to regain motility immediately, proliferating, and migrating normally.
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