Small‐cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 (
SLIT2
) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. In addition, the expression of the SLIT2 receptor, roundabout guidance receptor 1 (
ROBO1
), is upregulated. We find a positive association between
SLIT2
expression and the Yes1 associated transcriptional regulator (
YAP1
)‐expressing SCLC subtype (SCLC‐Y), which shows a better prognosis. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, we show that
SLIT2
overexpression or the deletion of
ROBO1
restricts tumor growth
in vitro
and
in vivo
. Mechanistic studies revealed significant inhibition of myeloid‐derived suppressor cells (MDSCs) and M2‐like tumor‐associated macrophages (TAMs) in the SCLC tumors. In addition, SLIT2 enhances M1‐like and phagocytic macrophages. Molecular analysis showed that
ROBO1
knockout or
SLIT2
overexpression suppresses the transforming growth factor beta 1 (TGF‐β1)/β‐catenin signaling pathway in both tumor cells and macrophages. Overall, we find that SLIT2 and ROBO1 have contrasting effects on SCLC tumors. SLIT2 suppresses, whereas ROBO1 promotes, SCLC growth by regulating the Tgf‐β1/glycogen synthase kinase‐3 beta (GSK3)/β‐catenin signaling pathway in tumor cells and TAMs. These studies indicate that SLIT2 could be used as a novel therapeutic agent against aggressive SCLC.
As the number of arteriosclerotic diseases continues to increase, much improvement is still needed with treatments for cardiovascular diseases. This is mainly due to the limitations of currently existing treatment options, including the limited number of donor organs available or the long-term durability of the artificial organs. Therefore, tissue engineering has attracted significant attention as a tissue regeneration therapy in this area. Porous scaffolds are one of the effective methods for tissue engineering. However, it could be better, and its effectiveness varies depending on the tissue application. This paper will address the challenges presented by various materials and their combinations. We will also describe some of the latest methods for tissue engineering.
Cardiovascular diseases remain the leading cause of mortality worldwide. Although new therapies are actively being developed and used for cardiovascular pathologies, these attempts have not significantly decreased mortality rates. Regenerative medicine has made enormous progress and set promising approaches over the past half-century. However, since autologous (donor-derived) vascular grafts are lacking, an alternative prosthesis must be constructed for cardiovascular disease patients. In vascular tissue manufacturing and regenerative medicine, scientists seek to improve this significant clinical challenge using bio-fabrication techniques combining additive manufacturing, biomaterials science, and advanced cellular biology. In the last few decades, many improvements and changes in various approaches have helped develop bioengineered concepts that reflect native blood vessels’ structure and function. However, numerous challenges must be overcome to clinically translate the next generation of tissue-engineered vascular transplants. This review provides update on the cell sources, scaffold essential for cardiovascular tissue engineering, and tissue engineering approaches as prospective options for curative therapy for blood vessel disease.
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