Photosensitizing metal-organic framework nanoparticles combined with tumor-sensitization strategies can enhance the phototherapeutic effect upon medullary thyroid carcinoma.

Photodynamic therapy (PDT) utilizing metal-organic frameworks (MOFs) has developed as a new and efficacious treatment for malignant tumors located on the surface of the human body. In order to achieve more effective PDT treatment outcomes, the traditional method has been to increase the intensity of the laser irradiation, but this approach can easily lead to tissue burns. In this study, we developed a new type of nanoparticle, F68-PKI@PCN224, aims to achieve effective PDT upon medullary thyroid carcinoma (MTC) which is an uncommon form of thyroid cancer that originates in the parafollicular cells of the thyroid and the therapeutic outlook for patients with MTC remains unsatisfactory.

Incidence of renal cell carcinoma after solid organ transplantation: a systematic review and meta-analysis.

Background: The incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell carcinoma (RCC) after liver, kidney, heart and lung transplantation, respectively, and suggest that transplant patients can be screened early for tumors to avoid risk.

Methods: PubMed, Embase and the Cochrane Library from their inception until August 16,2023.

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway.

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells.

A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma.

New strategies for molecular-targeted drug therapy for advanced hepatocellular carcinoma (HCC) ignore the contribution of the nutritional status of patients and nutritional support to improve physical status and immunity. We aimed to elucidate the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of HCC, and to explore the importance of a SNM as adjuvant therapy for HCC. Compared with a lipid emulsion (commonly used nutritional supplement for HCC patients), the SNM could not induce metabolic abnormalities in HCC cells (Warburg effect), and did not affect expression of metabolic abnormality-related factors in HCC cells.

Knockdown of TANK-Binding Kinase 1 Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular-Targeted Drugs.

The protein kinase, TANK-binding kinase 1 (TBK1), not only regulates various biological processes but also functions as an important regulator of human oncogenesis. However, the detailed function and molecular mechanisms of TBK1 in hepatocellular carcinoma (HCC), especially the resistance of HCC cells to molecular-targeted drugs, are almost unknown. In the present work, the role of TBK1 in regulating the sensitivity of HCC cells to molecular-targeted drugs was measured by multiple assays.

A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs.

The transcription factor, sterol regulatory element binding protein 1 (SREBP-1), plays important roles in modulating the proliferation, metastasis, or resistance to antitumor agents by promoting cellular lipid metabolism and related cellular glucose-uptake/Warburg Effect. However, the underlying mechanism of SREBP-1 regulating the proliferation or drug-resistance in lung squamous cell carcinoma (LUSC) and the therapeutic strategies targeted to SREBP-1 in LUSC remain unclear. In this study, SREBP-1 was highly expressed in LUSC tissues, compared with the paired non-tumor tissues (the para-tumor tissues).

The Disassociation of the A20/HSP90 Complex Downregulation of HSP90 Restores the Effect of A20 Enhancing the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents.

NF-κB (nuclear factor κB) is a regulator of hepatocellular cancer (HCC)-related inflammation and enhances HCC cells' resistance to antitumor therapies by promoting cell survival and anti-apoptosis processes. In the present work, we demonstrate that A20, a dominant-negative regulator of NF-κB, forms a complex with HSP90 (heat-shock protein 90) and causes the disassociation of the A20/HSP90 complex downregulation of HSP90. This process restores the antitumor activation of A20.

Novel Nanocrystal Injection of Insoluble Drug Anlotinib and Its Antitumor Effects on Hepatocellular Carcinoma.

The molecularly targeted agent anlotinib offers a novel therapeutic strategy against advanced hepatocellular carcinoma (HCC). With this study, we aimed to solve the technical problem of anlotinib being insoluble in injectable solutions; we also aimed to assess the antitumor activity of anlotinib on hepatocellular carcinoma cells. We prepared an anlotinib nanocrystal injection by wet grinding, and we optimized the prescription process using a transmission electron microscope (TEM) and a laser particle size analyzer (LPSA).

A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma.

BAY-876 is an effective antagonist of the Glucose transporter type 1 (GLUT1) receptor, a mediator of aerobic glycolysis, a biological process considered a hallmark of hepatocellular carcinoma (HCC) together with cell proliferation, drug-resistance, and metastasis. However, the clinical application of BAY-876 has faced many challenges. In the presence study, we describe the formulation of a novel microcrystalline BAY-876 formulation.

Hsa-miR-4277 Decelerates the Metabolism or Clearance of Sorafenib in HCC Cells and Enhances the Sensitivity of HCC Cells to Sorafenib by Targeting .

Increasing evidence has shown that the metabolism and clearance of molecular targeted agents, such as sorafenib, plays an important role in mediating the resistance of HCC cells to these agents. Metabolism of sorafenib is performed by oxidative metabolism, which is initially mediated by CYP3A4. Thus, targeting CYP3A4 is a promising approach to enhance the sensitivity of HCC cells to chemotherapeutic agents.

DNA methyltransferase mediates the hypermethylation of the microRNA 34a promoter and enhances the resistance of patient-derived pancreatic cancer cells to molecular targeting agents.

DNA methyltransferase (DNMT) participates in the transformation or progression of human cancers by mediating the hypermethylation of cancer suppressors. However, the regulatory role of DNMT in pancreatic cancer cells remains poorly understood. In the present study, we demonstrated that DNMT1 repressed the expression of microRNA 34a (miR-34a) and enhanced the activation of the Notch pathway by mediating the hypermethylation of the miR-34a promoter.

Quantitative examination of the inhibitory activation of molecular targeting agents in hepatocellular carcinoma patient-derived cell invasion via a novel in vivo tumor model.

Background: The outcomes for patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib are far from satisfactory because of treatment resistance to sorafenib. However, the exact mechanism of resistance to sorafenib remains unclear and it is valuable to establish a novel mouse model to quantitatively analyze the inhibition rates of sorafenib on the invasive growth of HCC cells in the liver.

Methods: HCC tissue microblocks derived from patients were cultured and mixed with hydrogel drops.

Effect of the hyaluronic acid-poloxamer hydrogel on skin-wound healing: in vitro and in vivo studies.

Background: Recent research into skin injury and wound healing has focused mainly on post-trauma hemostasis, infection prevention, dermal regeneration and angiogenesis. However, less attention has been paid to air permeability and moisture loss prevention which also play important roles in injury healing.

Methods: In the present work, we prepared a hyaluronic acid-poloxamer (HA-POL) hydrogel and tested the therapeutic effect of the hydrogel on skin-wound healing.

A Novel Noninvasive Program for Staging Liver Fibrosis in Untreated Patients With Chronic Hepatitis B.

Objectives: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications.

Methods: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB.

ETS-1 induces Sorafenib-resistance in hepatocellular carcinoma cells via regulating transcription factor activity of PXR.

Transcription factor E26 transformation specific sequence 1 (ETS-1) is a primary regulator in the metastasis of human cancer cells, especially hepatocellular carcinoma (HCC) cells; and it would affect the prognosis of HCC patients who received chemotherapies. However, the regulatory role of ETS-1 in the resistance of HCC cells to molecular-targeting agent remains poorly understood. In the present work, we demonstrate that high ETS-1 expression correlates with poor prognosis of advanced HCC patients received Sorafenib treatment.

Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial-mesenchymal transition (EMT), and also participate in the induction of multi-drug resistance (MDR). In the present study, we demonstrated the discovery of a novel inhibitor for Notch activating/cleaving enzyme ADAM-17, named ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins.

Which is the best combination of TACE and Sorafenib for advanced hepatocellular carcinoma treatment? A systematic review and network meta-analysis.

The aim of this study was to assess the comparative efficacy and safety of combination therapy with transarterial chemoembolization (TACE) and Sorafenib for patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and identify the best combination of TACE and Sorafenib. We searched databases for publications prior to May 2018. The prespecified efficacy outcomes were the objective response rate, overall survival rate, and time to progression.

Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma.

Background: Kinase inhibitor sorafenib is the most widely used drug for advanced HCC clinical treatment nowadays. However, sorafenib administration is only effective for a small portion of HCC patients, and the majority develop sorafenib-resistance during treatment. Thus, it is urgent to discover the endogenous mechanism and identify new pharmaceutical targets of sorafenib-resistance.

Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents.

Background: The rapid development of multi-drug resistance (MDR) process has hindered the effectiveness of advanced hepatocellular carcinoma (HCC) treatments. Notch-1 pathway, which mediates the stress-response, promotes cell survival, EMT (epithelial-mesenchymal transition) process and induces anti-apoptosis in cancer cells, would be a potential target for overcoming MDR process. This study investigated the potential application of rhamnetin, a specific inhibitor of Notch-1 pathway, in anti-tumor drug sensitization of HCC treatment.

MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells.

MicroRNA-153 (miR-153) is considered to be a tumor regulator. Silencing of miR-153 expression induced apoptosis in breast cancer cells. Data on mechanism suggest that up-regulation of miR- 153 level promotes cell proliferation via the down regulation of the expression of PTEN or FOXO1, which attenuates the proliferation of cancerous cells.

Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity.

Addition of immunoregulation factor to an oncolytic adenovirus being constructed is a developmental step in tumor gene therapy; however, cytokine IL-15 has not been frequently used as a potential cancer therapy agent. Here, we constructed an E2F-1 promoter oncolytic adenovirus based on type 5 adenovirus, which induces viral replication and proliferation in targeted tumor cells. We inserted the IL-15 gene into the E3 region of the model and found that human IL-15 expressing oncolytic adenovirus (Ad-E2F/IL15) shows a more intense antitumor effect than simple oncolytic viruses (Ad-E2F) do.

Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced killer cells enhances the antitumor effects in an orthotopic rectal cancer model.

Due to the anatomical structure of the rectum, the treatment of rectal cancer remains challenging. Ad-E2F, an oncolytic adenovirus containing the E2F-1 promoter, can selectively replicate within and kill cancer cells derived from solid tumors. Thus, this virus provides a novel approach for the treatment of rectal cancer.

An engineered three-dimensional gastric tumor culture model for evaluating the antitumor activity of immune cells in vitro.

Monolayer tumor culture models have been used for evaluating the antitumor activity of immune cells in vitro. However, their value in this research is limited. We used human gastric cancer cells (BGC823) and collagen hydrogel as a matrix to establish an engineered three-dimensional (3-D) tumor culture model in vitro.

[Establishment of a nude mouse model of orthotopic engineered gastric tumor and its in vivo fluorescence imaging].

Objective: To establish a nude mouse model of orthotopic engineered gastric tumor for in vivo fluorescence imaging studies.

Methods: An engineered gastric tumor was constructed in vitro using collagen as the scaffold and the human gastric cancer cell line BGC823-EGFP cells expressing enhanced green fluorescence protein (EGFP) as the seed cells. The engineered tumor was then implanted into the stomach of nude mice, and the tumor growth was observed with in vivo fluorescence imaging.

Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging.

Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic, however, the distribution of immune cells injected into a tumor-bearing body is unclear. In this study, we investigated the tumor-targeting capacity of cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes (CTLs) in a human gastric carcinoma orthotopic mouse model using a near-infrared fluorescence imaging system. CIK cells and tumor-specific CTLs were prepared with the near-infrared fluorescent dye DiR.