A Tumor Homing Peptide-Linked Arsenic Compound Inhibits Pancreatic Cancer Growth and Enhances the Inhibitory Effect of Gemcitabine.

Arsenic trioxide (ATO) has been shown to inhibit pancreatic cancer (PC) cell growth and to promote the inhibitory effects of gemcitabine (Gem) on PC . However, the high toxicity of ATO associated with the required high doses and indiscriminate targeting has limited its clinical application. This study aimed to determine whether coupling arsenic to a tumor homing peptide would increase the inhibitory potency against PC cells.

Inhibition of P21-activated kinases 1 and 4 synergistically suppresses the growth of pancreatic cancer by stimulating anti-tumour immunity.

Background: Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal types of cancer, and KRAS oncogene occurs in over 90% of cases. P21-activated kinases (PAK), containing six members (PAK1 to 6), function downstream of KRAS. PAK1 and PAK4 play important roles in carcinogenesis, but their combinational effect remains unknown.

CXCL5 knockdown attenuated gemcitabine resistance of pancreatic cancer through regulation of cancer cells and tumour stroma.

Chemoresistance is one of the major causes to the poor prognosis of pancreatic cancer (PC). Gemcitabine alone and gemcitabine-based therapies are mostly used for the treatment of PC. Gemcitabine resistance becomes the focus of chemotherapy.

A novel PAK4 inhibitor suppresses pancreatic cancer growth and enhances the inhibitory effect of gemcitabine.

Over 95% of Pancreatic ductal adenocarcinomas (PDA) carry mutations in the oncogene KRas which has been proven to be a difficult drug target. P21-activated kinase 4 (PAK4), acts downstream of KRas, and is overexpressed in PDA contributing to its growth and chemoresistance, and thus becomes an attractive therapeutic target. We have developed a new PAK4 inhibitor, PAKib and tested its effect on pancreatic cancer (PC) cell growth in vitro and in a syngeneic mouse model of PC.

Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway.

The anti-cancer effects of cannabinoids including CBD (Cannabidiol) and THC ((-)-trans-∆9-tetrahydrocannabinol) have been reported in the case of pancreatic cancer (PC). The connection of these cannabinoids to oncogenes that mutate in more than 90% of PC, and their effects on PD-L1, a key target of immune checkpoint blockade, have not been thoroughly investigated. Using cell lines and mouse models of PC, the effects of CBD and THC on cancer growth, the interaction between PC cells and a stromal cell, namely pancreatic stellate cells (PSCs), and the mechanism(s) involved were determined by cell-based assays and mouse study in vivo.

Inhibition of PAK1 suppresses pancreatic cancer by stimulation of anti-tumour immunity through down-regulation of PD-L1.

Immunotherapies have not yielded significant clinical benefits for pancreatic ductal adenocarcinoma (PDA) because of the existence of an immunosuppressive tumour microenvironment (TME) characterized by a desmoplastic stroma containing infiltrated immune cells and activated pancreatic stellate cells (PSCs). This study aims to investigate the involvement of PAK1 in anti-tumour immunity. In PDA patients, low PAK1 expression, low activation of PSC and high CD8 T cell/PAK1 ratios correlated with longer overall survival.

Depletion of p21-activated kinase 1 up-regulates the immune system of APC mice and inhibits intestinal tumorigenesis.

Background: P21-activated kinase 1 (PAK1) stimulates growth and metastasis of colorectal cancer (CRC) through activation of multiple signalling pathways. Up-regulation of CRC stem cell markers by PAK1 also contributes to the resistance of CRC to 5-fluorouracil. The aim of this study was to investigate the effect of PAK1 depletion and inhibition on the immune system and on intestinal tumour formation in APC mice.

Recombinant C-terminal fragments of the gastrin-releasing peptide precursor are bioactive.

C-terminal fragments from the precursor for gastrin-releasing peptide (GRP) have been detected in several human tumour types. We have previously demonstrated that recombinant human proGRP42-98 is biologically active. To investigate the regions responsible, proGRP42-98 was cleaved with thrombin, and the fragments purified by HPLC.

C-terminal fragments of the gastrin-releasing peptide precursor stimulate cell proliferation via a novel receptor.

There are many precedents for the production from a single precursor of multiple peptides, with independent receptors and different bioactivities. Gastrin-releasing peptide (GRP) is initially synthesized as amino acids 1-27 of a 125-residue precursor, proGRP, and is subsequently cleaved and amidated to form GRP18-27. We investigated the hypothesis that C-terminal proGRP peptides are also biologically active.

Synthesis, expression and biological activity of the prohormone for gastrin releasing peptide (ProGRP).

Gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on endocrine and exocrine secretions and metabolism. The prohormone for GRP (ProGRP, 125 amino acids) is processed to the amidated, biologically active end products GRP(1-27) and GRP(18-27). Amidated forms of GRP are putative autocrine or paracrine growth factors in a number of cancers including colorectal cancer.

Stimulation of proliferation and migration of a colorectal cancer cell line by amidated and glycine-extended gastrin-releasing peptide via the same receptor.

Although amidated forms of gastrin-releasing peptide (GRP) have been identified as autocrine growth factors in small cell lung cancer, their role in the development and progression of colorectal carcinoma is less clear. In addition, the biological activity of non-amidated gastrin-releasing peptide has not been investigated in colorectal carcinoma cells. We therefore investigated the effect of bombesin (a homologue of gastrin-releasing peptide) on proliferation, migration and inositol phosphate production in the human colorectal carcinoma cell line DLD-1, and determined the ability of gastrin-releasing peptide receptor antagonists to inhibit these effects.

Developmental expression and biological activity of gastrin-releasing peptide and its receptors in the kidney.

Mammalian gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on metabolism, release of regulatory peptides, gastrointestinal and pancreatic secretions, and behavior. GRP is a potent mitogen for a number of tumor types, including colon and lung. Although GRP is known to stimulate the growth of renal tumors, little is known of its synthesis, distribution, and receptors in the developing and mature kidney.