Anti-angiogenesis in colorectal cancer therapy.

The morbidity of colorectal cancer (CRC) has risen to third place among malignant tumors worldwide. In addition, CRC is a common cancer in China whose incidence increases annually. Angiogenesis plays an important role in the development of tumors because it can bring the nutrients that cancer cells need and take away metabolic waste. Various mechanisms are involved in the formation of neovascularization, and vascular endothelial growth factor is a key mediator. Meanwhile, angiogenesis inhibitors and drug resistance (DR) are challenges to consider when formulating treatment strategies for patients with different conditions. Thus, this review will discuss the molecules, signaling pathways, microenvironment, treatment, and DR of angiogenesis in CRC.

HOXD11 upregulates JAM-A and exerts oncogenic properties via NF-κB signaling pathway in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a tumor with high incidence and poor prognosis in developing countries. Junctional adhesion molecule A (JAM-A, also known as F11R) affects numerous biological processes, which is a vital regulator of the development of malignant tumors. However, its exact role and underlying mechanism in ESCC remain obscure. Our present study demonstrated that JAM-A was upregulated in ESCC tissues and cell lines by RNA sequencing and immunohistochemistry (IHC). JAM-A knockdown significantly suppressed the proliferation of the ESCC cells, induced cell cycle arrest at the G1 and promoted apoptosis, and suppressed the ability of invasion and migration in vivo and in vitro. Mechanistically, JAM-A may activate the NF-κB signaling pathway to regulate malignant behavior of ESCC. Further research showed that Homeobox D11 (HOXD11) could directly regulate JAM-A transcription by binding to specific sequences of JAM-A promoter region, thereby activating NF-κB signaling pathway to regulate malignant behavior of ESCC. Functional experiments indicated that HOXD11 could exert an oncogenic role in ESCC. Collectively, our findings support the hypothesis that the HOXD11/JAM-A/NF-κB signal axis plays a role in regulating malignant behavior in ESCC patients, highlighting its potential therapeutic value for ESCC.

Diagnostic pitfalls: a case of prostate cancer and rectal cancer accompanied by prostate cancer invasion of the rectum.

INTRODUCTION: Case of double primary cancer of the prostate and rectum is rare, prostate cancer involving the postoperative intestinal anastomotic mucosal tissue is even rarer. CASE PRESENTATION: We report a case of rectal cancer discovered 1 year after a diagnosis of prostate cancer and a tumour in the postoperative anastomotic intestinal mucosal tissue involving prostatic adenocarcinoma at 1 year after the diagnosis of rectal cancer. Due to the poor differentiation of both prostate and rectal cancers, there are some pitfalls in the diagnosis of intestinal mucosal lesions at an anastomosis. The lack of an accurate diagnosis of a tumour in anastomosis intestinal mucosal tissue will affect treatment and patient survival. CONCLUSIONS: The pathologists should have a detailed understanding of the patient's medical history and carefully observe the histopathological morphology and, if necessary, immunohistochemistry or other techniques should be used to assist in the pathological diagnosis and avoid both misdiagnosis and missed diagnosis.

Preparation and performance characteristics of spider venom peptide nanocapsules.

BACKGROUND: ω-hexatoxin-Hvn1b is an insecticidal toxin produced by the Tasmanian funnel-web spider (Hadronyche venenata), that can be exploited for development of novel bioinsecticides. Due to its larger size and low membrane permeability, this toxin usually has a slower mode of action compared to conventional small molecule insecticides. Nanoscale materials have unique optical, electrical, mechanical and biological properties, and show great application prospects for pesticide delivery. RESULTS: The physical and chemical properties of nanocapsules were characterized using transmission electron microscopy, laser particle size analysis, Fourier transform infrared spectroscopy, contact angle testing and with a fluorescence spectrophotometer. The results indicated that the nanocapsules were spherical, with an average particle size of 197.70 nm, the encapsulation efficiency rate was 75.82% and the Zeta potential was -32.90 mV. Penetration experiments showed that the nanocapsules could promote protein passage through the intestinal tract of Spodoptera litura and reach the body fluid. Then we expressed ω-hexatoxin-Hvn1b by prokaryotic expression. Bioassay results showed that the oral toxicity of ω-hexatoxin-Hvn1b nanocapsules to S. litura was higher than that of the ω-hexatoxin-Hvn1b. CONCLUSION: In this paper, we reported a construction method of spider venom peptide nanocapsules based on polylactic-co-glycolic acid by multiple emulsion for delivery of protein to improve the insecticidal effect and oral activity of ω-hexatoxin-Hv1a. © 2022 Society of Chemical Industry.

PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma.

BACKGROUND: Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer. METHODS: We examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration. RESULTS: Both Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells. CONCLUSIONS: PTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.

Brachytherapy Using Elastin-Like Polypeptides with (131)I Inhibit Tumor Growth in Rabbits with VX2 Liver Tumor.

BACKGROUND: Brachytherapy is a targeted type of radiotherapy utilized in the treatment of cancers. Elastin-like polypeptides are a unique class of genetically engineered peptide polymers that have several attractive properties for brachytherapy. AIMS: To explore the feasibility and application of brachytherapy for VX2 liver tumor using elastin-like polypeptides with (131)I so as to provide reliable experimental evidence for a new promising treatment of liver cancer. METHODS: Elastin-like polypeptide as carrier was labeled with (131)I using the iodogen method. Ten eligible rabbits with VX2 liver tumor were randomly divided into the treatment group (n = 5) and control group (n = 5). The treatment group received brachytherapy using elastin-like polypeptide with (131)I, and in the control group, elastin-like polypeptide was injected into the VX2 liver tumor as a control. Periodic biochemical and imaging surveillances were required to assess treatment efficacy. RESULTS: The stability of elastin-like polypeptide with (131)I in vitro was maintained at over 96.8 % for 96 h. Biochemistry and imaging indicated brachytherapy using elastin-like polypeptide with (131)I for liver tumor can improve liver function and inhibit tumor growth (P < 0.05). CONCLUSIONS: Elastin-like polypeptide can be an ideal carrier of (131)I and have high labeling efficiency, radiochemical purity and stability. Brachytherapy using elastin-like polypeptide with (131)I for liver tumor is a useful therapy that possesses high antitumor efficacy advantages.

A feasibility study of a thermally sensitive elastin-like polypeptide for submucosal injection application in endoscopic resection in 3 animal models.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) can successfully resect large lesions en bloc by using a submucosal injection solution, but the cost of currently available submucosal injection solutions is not satisfactory. The authors' aim was to evaluate the feasibility and effectiveness of a thermally sensitive elastin-like polypeptide (ELP) used as submucosal injection solution in ESD. METHODS: We conducted an ex vivo study to determine the optimal concentration of ELPs in rabbits, an in vivo study to evaluate the effectiveness of mucosal elevation in rats, and a large animal study to confirm the feasibility of preclinical application by using conventional clinical procedure in pigs. RESULTS: ELP (500 µM) was proved to be the optimal injectable submucosal injection solution and elevated mucosa more efficiently than any control. The same concentration of ELP exhibited an equivalent effectiveness of mucosal elevation, the retention of the elevation, and minimal bleeding with sodium hyaluronate. The ESD procedure time with 500 µM ELP in a preclinical study with pigs was significantly shorter than with any other concentration of ELP and normal saline solution. CONCLUSIONS: Use of ELP as submucosal injection solution was feasible, with higher and longer-lasting elevation and fewer adverse events.