Author Correction: A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens
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3D printing of micro-nano devices and their applications
In recent years, the utilization of 3D printing technology in micro and nano device manufacturing has garnered significant attention. Advancements in 3D printing have enabled achieving sub-micron level precision. Unlike conventional micro-machining techniques, 3D printing offers versatility in material selection, such as polymers. 3D printing technology has been gradually applied to the general field of microelectronic devices such as sensors, actuators and flexible electronics due to its adaptability and efficacy in microgeometric design and manufacturing processes. Furthermore, 3D printing technology has also been instrumental in the fabrication of microfluidic devices, both through direct and indirect processes. This paper provides an overview of the evolving landscape of 3D printing technology, delineating the essential materials and processes involved in fabricating microelectronic and microfluidic devices in recent times. Additionally, it synthesizes the diverse applications of these technologies across different domains.
Targeting of TAMs: can we be more clever than cancer cells?
With increasing incidence and geography, cancer is one of the leading causes of death, reduced quality of life and disability worldwide. Principal progress in the development of new anticancer therapies, in improving the efficiency of immunotherapeutic tools, and in the personification of conventional therapies needs to consider cancer-specific and patient-specific programming of innate immunity. Intratumoral TAMs and their precursors, resident macrophages and monocytes, are principal regulators of tumor progression and therapy resistance. Our review summarizes the accumulated evidence for the subpopulations of TAMs and their increasing number of biomarkers, indicating their predictive value for the clinical parameters of carcinogenesis and therapy resistance, with a focus on solid cancers of non-infectious etiology. We present the state-of-the-art knowledge about the tumor-supporting functions of TAMs at all stages of tumor progression and highlight biomarkers, recently identified by single-cell and spatial analytical methods, that discriminate between tumor-promoting and tumor-inhibiting TAMs, where both subtypes express a combination of prototype M1 and M2 genes. Our review focuses on novel mechanisms involved in the crosstalk among epigenetic, signaling, transcriptional and metabolic pathways in TAMs. Particular attention has been given to the recently identified link between cancer cell metabolism and the epigenetic programming of TAMs by histone lactylation, which can be responsible for the unlimited protumoral programming of TAMs. Finally, we explain how TAMs interfere with currently used anticancer therapeutics and summarize the most advanced data from clinical trials, which we divide into four categories: inhibition of TAM survival and differentiation, inhibition of monocyte/TAM recruitment into tumors, functional reprogramming of TAMs, and genetic enhancement of macrophages.
Implantation of engineered adipocytes suppresses tumor progression in cancer models
Tumors exhibit an increased ability to obtain and metabolize nutrients. Here, we implant engineered adipocytes that outcompete tumors for nutrients and show that they can substantially reduce cancer progression, a technology termed adipose manipulation transplantation (AMT). Adipocytes engineered to use increased amounts of glucose and fatty acids by upregulating UCP1 were placed alongside cancer cells or xenografts, leading to significant cancer suppression. Transplanting modulated adipose organoids in pancreatic or breast cancer genetic mouse models suppressed their growth and decreased angiogenesis and hypoxia. Co-culturing patient-derived engineered adipocytes with tumor organoids from dissected human breast cancers significantly suppressed cancer progression and proliferation. In addition, cancer growth was impaired by inducing engineered adipose organoids to outcompete tumors using tetracycline or placing them in an integrated cell-scaffold delivery platform and implanting them next to the tumor. Finally, we show that upregulating UPP1 in adipose organoids can outcompete a uridine-dependent pancreatic ductal adenocarcinoma for uridine and suppress its growth, demonstrating the potential customization of AMT.
Artificial intelligence-enabled microfluidic cytometer using gravity-driven slug flow for rapid CD4+ T cell quantification in whole blood
The quantification of immune cell subpopulations in blood is important for the diagnosis, prognosis and management of various diseases and medical conditions. Flow cytometry is currently the gold standard technique for cell quantification; however, it is laborious, time-consuming and relies on bulky/expensive instrumentation, limiting its use to laboratories in high-resource settings. Microfluidic cytometers offering enhanced portability have been developed that are capable of rapid cell quantification; however, these platforms involve tedious sample preparation and processing protocols and/or require the use of specialized/expensive instrumentation for flow control and cell detection. Here, we report an artificial intelligence-enabled microfluidic cytometer for rapid CD4+ T cell quantification in whole blood requiring minimal sample preparation and instrumentation. CD4+ T cells in blood are labeled with anti-CD4 antibody-coated microbeads, which are driven through a microfluidic chip via gravity-driven slug flow, enabling pump-free operation. A video of the sample flowing in the chip is recorded using a microscope camera, which is analyzed using a convolutional neural network-based model that is trained to detect bead-labeled cells in the blood flow. The functionality of this platform was evaluated by analyzing fingerprick blood samples obtained from healthy donors, which revealed its ability to quantify CD4+ T cells with similar accuracy as flow cytometry (<10% deviation between both methods) while being at least 4× faster, less expensive, and simpler to operate. We envision that this platform can be readily modified to quantify other cell subpopulations in blood by using beads coated with different antibodies, making it a promising tool for performing cell count measurements outside of laboratories and in low-resource settings.
Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies
Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic and epigenetic alterations. Enhancer reprogramming has emerged as a pivotal driver of carcinogenesis, with cancer cells often relying on aberrant transcriptional programs. The advent of high-throughput sequencing technologies has provided critical insights into enhancer reprogramming events and their role in malignancy. While targeting enhancers presents a promising therapeutic strategy, significant challenges remain. These include the off-target effects of enhancer-targeting technologies, the complexity and redundancy of enhancer networks, and the dynamic nature of enhancer reprogramming, which may contribute to therapeutic resistance. This review comprehensively encapsulates the structural attributes of enhancers, delineates the mechanisms underlying their dysregulation in malignant transformation, and evaluates the therapeutic opportunities and limitations associated with targeting enhancers in cancer.
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