Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.

Cancer is a commonly lethal disease that causes many deaths every year around the world. Many strategies have been applied to treat cancer, such as surgery, radiation, and chemotherapy, but all of these therapeutic approaches are limited. Nanotechnology could provide a tremendous platform to boost the efficacy of therapeutic systems from the bench to clinical applications. The current trend of using nanomaterials for therapeutic applications is limited to drug delivery and external stimuli-responsive systems. However, several nanomaterials can reduce the growth of aggressive tumors through their self-therapeutic properties. In this review, we discuss the self-therapeutic nanomaterials that can kill cancer cells without the need for any external stimulation (heat, light, radiation, or a magnetic field) or the loading of any extra therapeutic compounds. These nanomaterials can produce reactive oxygen species, act as deoxygenating agents, or produce free radicals at tumor sites. Self-therapeutic peptide-based and other organic nanomaterials that are used to inhibit multidrug resistance (MDR) proteins, e.g., poly glycoprotein (p-gp), are also discussed. This review discusses the possible mechanisms of action of self-therapeutic nanomaterials for cancer inhibition, highlighting critical and future aspects.

Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell‒cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles.

Background: The hallucinogenic tryptamine analog 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) causes social problems worldwide. There are several studies on the metabolism; however, not more studies were found in the literature on acute toxicity. Aims: To report the acute toxicity of 5-MeO-MiPT in mice, followed by quantitative toxicological analysis of blood and organs, hystotoxico-logical and immunohistochemical analysis of tissues and cells. Study design: Animal experiment Methods: In vivo experiments were performed using CD1 adult female mice (n=26). Animals were caged in 4 groups randomly. First group was a control (n=3). Second group was vehicle control (n=3) and injected 150 mu L of blank solution (50% dimethyl sulfoxide in saline /0.9% of NaCl). While for acute toxicity experiments, 5-MeO-MiPT was added to a blank solution in order to obtain a dose of 0.27 mg/kg in 150 mu L injection (n=10) and the last group were injected 2.7 mg/kg 5-MeO-MiPT in a 150 mu L injection (n=10). Quantitative toxicological analysis, hystotoxicological and immunohistochemical analysis were performed. Results: In the toxicological analysis, 5-MeO-MiPT was found negative in biological samples which were control, vehicle control, and 0.27 mg/kg dose mice groups. 5-MeO-MiPT was found 2.7-13.4 ng/mL in blood, 11-29 ng/g in kidney, 15.2-108.3 ng/g in liver, and 1.5-40.6 ng/g in the brain in 2,7 mg/kg injected group. In a low dose of the 5-MeO-MiPT liver section, compared with normal tissues, the difference in staining was statistically significant (p<0.0001). In high-dose of 5-MeO-MiPT, H-score showed that the increase in the number of Caspase-3 positive cells was significant compared to the control (p<0.05). In high-dose of 5-MeO-MiPT, intense Caspase-3 immunoreactivity was observed and the increase in the number of Caspase-3 positive cells compared to the control was statistically significant (p<0.05). In brain section, the statistics of the results obtained from the H-score showed that the increase in the number of Caspase-3 positive cells was significant compared to the control (p=0.0183). In vehicle control liver section, there were few Caspase-8 positive cells characterized by a light brown appearance (p=0.0117). In the high-dose 5-MeO-MiPT group, the numbers of positive cells at low and high doses of 5-MeO-MiPT group were statistically significant compared to the control (p<0.05). In the high-dose 5-MeO-MiPT group, Caspase-8 immunoreactivity was detected in the glomerular structures. Compared to control, the increase in Caspase-8 immunoreactivity was found to be statistically significant (p<0.05). Conclusion: Low-dose 5-MeO-MiPT did not cause any serious histopathological effects on the liver, kidney, and brain. High doses induce apoptotic cell death through caspase activity.

Lynch Syndrome (LS) provides the perfect context to understand DNA mismatch repair deficient carcinogenesis, which is characterized by neoplastic lesions with high rates of shared neoantigens eliciting adaptive immunity through T cell receptor (TCR) recognition. However, the TCR landscape in LS carriers remains unexplored. Here, we perform TCR sequencing of 277 blood samples from LS cancer survivors, previvors, and controls, as well as matching colorectal cancers and pre-cancers. We show that up to 41% of the most expanded TCRβs from colorectal neoplasms are detectable in the blood of LS carriers, while showing minimal expansion in controls. In addition, we develop and validate a classification model that distinguishes LS carriers from controls using circulating TCRβs signatures associated with LS independent of thecancer history and with cancer-free LS previvors. Together, our findings characterize circulating and tissue TCRβs associated with LS, thus representing a step toward identifying blood-based TCR biomarkers for immune surveillance.

Aim: The low-density lipoprotein receptor gene (LDLR) family plays a fundamental role in many malignancies and may have a putative cancer-boosting function. In our study, we have attempted to comparatively investigate the differential gene expressions of LDLR family in normal prostate epithelial cell line (RWPE-1), prostate cancer cell line (DU145 cell line), prostate cancer stem cells (DU145 CSCs) and non-CSCs (DU145 non-CSCs, bulk population). Materials and Methods: Cancer stem cells in DU-145 prostate cancer cell line were isolated by flow cytometry according to CD133 and CD44 cell surface properties. Whole transcriptome sequencing data was comprehensively analyzed for each group. The protein-protein interaction network was determined using the STRING protein database. Results: Our data showed that the expression levels of LRP1, LRP3, LRP8 and LRP11 were increased in the DU145 CSCs relative to the normal prostate epithelial cell line. Conclusion: Overall, our data suggest that the LRP functions and/or the expression in prostate cancer may ultimately change the invasive phenotype of the CSCs.