Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
Background This study aimed to investigate circular RNA‐mitochondrial tRNA translation optimization 1 (circ‐MTO1) expression in tumor tissue and its correlation with clinical characteristics and survival profiles, as well as its effect on cancer cell functions in prostate cancer. Methods A total of 298 primary prostate cancer patients were included. Reverse transcription‐quantitative polymerase chain reaction was conducted to evaluate circ‐MTO1 expression in tumor tissue and paired adjacent tissue. Disease‐free survival (DFS) and overall survival (OS) were recorded. In in vitro experiment, prostate cancer cells were transfected with circ‐MTO1 over‐expression and negative‐control over‐expression plasmids. Then cell proliferation, cell invasion and miR‐630 as well as miR‐17‐5p expressions in prostate cancer cells were detected. Results Circular RNA‐mitochondrial tRNA translation optimization 1 expression was downregulated in tumor tissue compared with paired adjacent tissue (P < .001) in patients with prostate cancer. Circ‐MTO1 high expression in tumor tissue was correlated with decreased pathological T stage (P = .001) as well as lower pathological N stage (P = .020). As for survival profiles, the DFS (P = .006) and OS (P = .018) were both longer in patients who had circ‐MTO1 high expression compared with patients who had circ‐MTO1 low expression. In addition, circ‐MTO1 high expression independently predicted favorable DFS and OS. Besides, further in vitro experiments illustrated that circ‐MTO1 inhibited proliferation (P < .05) and invasion (P < .05) as well as downregulated miR‐17‐5p expression in prostate cancer cells (P < .05). Conclusion Circ‐MTO1 correlates with decreased pathological T/N stage and favorable survival profiles, and it also inhibits cell proliferation, invasion as well as miR‐17‐5p expression in prostate cancer.
Abstract. Pancreatic cancer is one of the most frequently occurring malignancies worldwide and it is the fourth most common cause of cancer-associated mortality in Western countries. Thalidomide (THD) plays an important role in tumor therapy, as it is able to promote early stage apoptosis and inhibit the process of angiogenesis. The present study evaluated the ability of the combination of THD and gemcitabine (GEM) to inhibit the growth of the pancreatic cancer SW-1990 cell line in vitro and in vivo. Early apoptosis in the SW-1990 cells was detected by the Annexin V/propidium iodide double staining method, the level of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. In addition, the expression of vascular endothelial growth factor in transplanted tumor tissue was measured by RT-PCR, immunohistochemistry and western blot analysis. Cluster of differentiation 34 positivity was considered to indicate the microvessel density. Subsequent to treatment with THD and GEM alone or in combination, it was found that the expression of Bax was upregulated, while the expression of Bcl-2 was downregulated, and the growth of SW-1990 cells and transplanted tumors in nude mice was evidently inhibited. The administration of THD in combination with GEM may demonstrate a potent antitumor effect that increases with increasing dose. The mechanism behind the antitumor effect may be associated with the inhibition of tumor angiogenesis and induction of the apoptosis pathway.
On‐skin electronics have been widely used in fields, such as wearable healthcare and human–machine interfaces due to their excellent performances and wearable comfort. Among them, on‐skin sensors for collecting signals have been greatly developed, while the stimulators that provide tactile feedback are difficult to achieve in terms of flexibility and stretchability due to their rather complicated structures. Achieving on‐skin stimulators with superior performances and outstanding wearability requires major advances in materials, fabrication, and structure design. The on‐skin stimulator needs to be soft with a lightweight and thin structure so that it can be laminated onto the skin with conformal contact for accurate feedback. Three stimulation modes, namely electrotactile, thermal, mechanotactile, and vibrotactile stimulation, are investigated. Among them, electrotactile stimulation is the characteristics of high resolution and quick response. Thermal stimulation can provide a unique heat sensation without crosstalk with other stimuli. Mechanotactile and vibrotactile stimulation can bring comfortable feedback to skin, showing great potential in wearable applications. This paper summarizes the working principles, materials, structures, and applications of these on‐skin stimulators, and compares their advantages with conventional rigid devices. At the end of this paper, the challenging issues and future prospects in this field are discussed.
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