Multifunctional CaCO3@Cur@QTX125@HA nanoparticles for effectively inhibiting growth of colorectal cancer cells.

Colorectal cancer (CRC) is a major cause of cancer-related deaths in humans, and effective treatments are still needed in clinical practice. Despite significant developments in anticancer drugs and inhibitors, their poor stability, water solubility, and cellular membrane permeability limit their therapeutic efficacy. To address these issues, multifunctional CaCO3 nanoparticles loaded with Curcumin (Cur) and protein deacetylase (HDAC) inhibitor QTX125, and coated with hyaluronic acid (HA) (CaCO3@Cur@QTX125@HA), were prepared through a one-step gas diffusion strategy. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) showed that CaCO3@Cur@QTX125@HA nanoparticles have uniform spherical morphology and elemental distribution, with diameters around 450 nm and a Zeta potential of - 8.11 mV. The controlled release of Cur from the nanoparticles was observed over time periods of 48 h. Cellular uptake showed that CaCO3@Cur@QTX125@HA nanoparticles were efficiently taken up by cancer cells and significantly inhibited their growth. Importantly, CaCO3@Cur@QTX125@HA nanoparticles showed specific inhibitory effects on CRC cell growth. Encouragingly, CaCO3@Cur@QTX125@HA nanoparticles successfully internalized into CRC patient-derived organoid (PDO) models and induced apoptosis of tumor cells. The multifunctional CaCO3@Cur@QTX125@HA nanoparticles hold promise for the treatment of CRC.

Nanocarriers of Fe3O4 as a Novel Method for Delivery of the Antineoplastic Agent Doxorubicin Into HeLa Cells in vitro.

Here we report the synthesis and in vitro characterization of a redox-sensitive, magnetically inducible nanoparticle carrier system based on the doxorubicin (DOX) drug delivery model. Each quantal nanocarrier unit consists of a magnetite Fe3O4 nanoparticle core that is further encapsulated in self-assembled micelles of the redox-responsive polyethylene glycol derivative, DSPE-SS-mPEG. The nanocarrier system was prepared using a combination of ultrasonication and dialysis to produce the microenvironment sensitive delivery system. The final synthesized and DOX-loaded magnetic nanocarriers had an average size of ~150 nm when assembled with a 6.9% DOX payload. The release rate of DOX from these redox-responsive magnetic nanocarriers was shown to be accelerated in vitro when in the presence of glutathione (GSH). Furthermore, we demonstrated that more redox-responsive magnetic nanocarriers could be taken up by HeLa cells when a local magnetic field was applied. Once internalized within a cell, the micelles of the outer nanocarrier complex were broken down in the presence of higher concentrations of GSH, which accelerated the release of DOX. This produces a particle with dual operating characteristics that can be controlled via a specific cellular environment coupled with an exogenously applied signal in the form of a magnetic field triggering release.

Security and Radical Assessment in Open, Laparoscopic, Robotic Colorectal Cancer Surgery: A Comparative Study.

PURPOSE: This retrospective study was designed to assess the safety and effectiveness of open, laparoscopic, robotic colorectal cancer surgery. METHODS: Three hundred patients with colorectal cancer who underwent curative resection in the First Affiliated Hospital of Zhengzhou University between February 2014 and May 2016 were included. Patients were classified into open surgery group, laparoscopic surgery group, and robot-assisted group. RESULTS: The blood loss in laparoscopic surgery group was less than that in open surgery group, and the blood loss in robot-assisted group less was than the open surgery group. The number of lymph node dissection in robot-assisted group was significantly larger than that in the open group ( P < .05). The distance between the lower edge of the tumor group and the distal margin in robotic group was longer than that of the laparoscopic surgery group and the open group ( P < .05). Three (2.8%) cases of urinary retention occurred in the open surgery group, 4 (3.92%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group, while 2 (1.87%) cases of sexual dysfunction occurred in the open surgery group, 2 (1.96%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group. The urinary retention and sexual dysfunction rate did not differ between the 3 groups ( P > .05), but the minimally invasive group showed a certain advantage over the open group. CONCLUSION: Compared to the traditional open surgery, minimally invasive surgery (especially in robot-assisted group) has advantages such as less intraoperative bleeding, rapid postoperative recovery, and radical cure; open group, laparoscopic surgery group, and robot-assisted group have a similar incidence of postoperative complications, but reduction in the incidence of anastomotic leakage and intestinal obstruction. Robot-assisted group has the potential advantage for pelvic autonomic nerve protection.

MicroRNAs, long noncoding RNAs, and circular RNAs: potential tumor biomarkers and targets for colorectal cancer.

Noncoding RNAs (ncRNAs) can be divided into microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), pRNAs, and tRNAs. Traditionally, miRNAs exert their biological function mainly through the inhibition of translation via the induction of target RNA transcript degradation. lncRNAs and circRNAs were once considered to have no potential to code proteins. Here, we will review the current knowledge on ncRNAs in relation to their origins, characteristics, and functions. We will also review how ncRNAs work as competitive endogenous RNA, gene transcription and expression regulators, and RNA-binding protein sponges in colorectal cancer (CRC). Notably, except for the abovementioned mechanisms, recent advances revealed that lncRNAs can also act as the precursor of miRNAs, and a small portion of lncRNAs and circRNAs was verified to have the potential to code proteins, providing new evidence for the significance of ncRNAs in CRC tumorigenesis and development.

Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment.

Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.

Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas.

Human hypothalamic hamartoma (HH) is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. We hypothesized that neuronal gap junctions contribute to epileptogenesis through synchronous activity within the neuron networks in HH tissue. We studied surgically resected HH tissue with Western-blot analysis, immunohistochemistry, electron microscopy, biocytin microinjection of recorded HH neurons, and microelectrode patch clamp recordings with and without pharmacological blockade of gap junctions. Normal human hypothalamus tissue was used as a control. Western blots showed increased expression of both connexin-36 (Cx36) and connexin-43 (Cx43) in HH tissue compared with normal human mammillary body tissue. Immunohistochemistry demonstrated that Cx36 and Cx43 are expressed in HH tissue, but Cx36 was mainly expressed within neuron clusters while Cx43 was mainly expressed outside of neuron clusters. Gap-junction profiles were observed between small HH neurons with electron microscopy. Biocytin injection into single recorded small HH neurons showed labeling of adjacent neurons, which was not observed in the presence of a neuronal gap-junction blocker, mefloquine. Microelectrode field recordings from freshly resected HH slices demonstrated spontaneous ictal/interictal-like discharges in most slices. Bath-application of gap-junction blockers significantly reduced ictal/interictal-like discharges in a concentration-dependent manner, while not affecting the action-potential firing of small gamma-aminobutyric acid (GABA) neurons observed with whole-cell patch-clamp recordings from the same patient's HH tissue. These results suggest that neuronal gap junctions between small GABAergic HH neurons participate in the genesis of epileptic-like discharges. Blockade of gap junctions may be a new therapeutic strategy for controlling seizure activity in HH patients.

miR-411 regulated ITCH expression and promoted cell proliferation in human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third most common cause of cancer mortality in the world. In this study, we report that miR-411 expression is markedly upregulated in HCC cells and HCC tissues compared with normal control tissues and cells. Previous studies have shown that miR-411 plays a crucial role in a variety of biological processes in various human cancer cells. However, the specific function of miR-411 in HCC remains unclear. Ectopic expression of miR-411 promoted the proliferation and anchorage-independent growth of HCC cells, whereas inhibition of miR-411 reduced this effect. Bioinformatics analysis further revealed ITCH, a putative tumor suppressor as a potential target of miR-411. Data from luciferase reporter assays showed that miR-411 directly binds to the 3'-untranslated region (3'-UTR) of ITCH mRNA and repressed expression at both transcriptional and translational levels. In functional assays, miR-411 promoted HCC cell proliferation, which could be suppressed by miR-411-in. Taken together, our data provide convincing evidence that miR-411 functions as an onco-miRNA, which was associated with cell proliferation of HCC, and its oncogenic effect is mediated chiefly through direct suppression of ITCH expression.