cGAS-STING at the crossroads in cancer therapy.

DNA is highly immunogenic, both exogenous and endogenous DNA can activate the pathogen-associated molecular pattern (PAMP) and danger-associated molecular pattern (DAMP), respectively, and hence activate the evolutionarily conserved cGAS-STING pathway for inflammatory responses. The cGAS-STING signaling pathway plays a very important role in the pathogenesis and progression of neoplastic diseases. For cancer therapy, there are some discrepancies on whether cGAS-STING should be inhibited or activated. Deregulated cGAS-STING signaling pathway might be the origin and pathogenesis of tumor, understanding and modulating cGAS-STING signaling holds great promise for cancer therapy. In this review article, we discuss the molecular mechanisms underlying cGAS-STING deregulation, highlighting the tumor inhibiting and promoting roles and challenges with cGAS-STING agonists in the context of cancer therapies.

Targeting ROR1 inhibits glucocorticoid-induced gastric cancer growth.

Glucocorticoids are commonly used in clinic but are also a double-edged sword. While treating tumors, they are reported to promote tumor growth and metastasis. To explore the role and elucidate the mechanism of dexamethasone in promoting tumor growth and metastasis, we detected the levels of cortisol and adrenocorticotropic hormone (ACTH) in peripheral blood of patients with gastric cancer, and immunohistochemical staining was used to detect the expression of ROR1 in the surgically resected gastric cancer samples. The levels of cortisol and ACTH in peripheral blood of patients with stage III and IV gastric cancer were higher than those of patients with stage I/II gastric cancer. Dexamethasone up-regulated the ROR1 level on gastric cancer cell lines in a concentration-dependent manner. Gastric cancer specimen with high ROR1 had higher rates of relapse and metastasis than gastric adenocarcinomas expressing low levels of ROR1.Gastric cancer patients with high expression of ROR1 had a short survival time. ROR1 was expressed by gastric cancer cell lines, but not on normal gastric epithelial cell line. Suppressing ROR1 in gastric cancer cell lines impaired their invasion, migration, scratch healing and clone formation ability in vitro and slowed down the tumor growth of MKN-45 cells in immunodeficient mice in vivo. Collectively, our study indicated that dexamethasone up-regulated ROR1 levels on gastric cancer cells. ROR1 participated in and mediated the role of dexamethasone in promoting gastric tumor growth, and blocking ROR1 can prevent the tumor growth.

Clinicopathological Analysis and Prognostic Assessment of TCN1 in Patients with Gastric Cancer.

BACKGROUND: Stomach cancer is the fourth most common type of cancer worldwide. TCN1 mainly encodes the vitamin B12 transporter, transcobalamin. TCN1 is a marker of gastrointestinal tumor progression, but the impact of TCN1 on survival is unclear. MATERIAL/METHODS: Gastrointestinal tumor records were reviewed and analyzed, clinicopathological data were summarized, immunohistochemical detection of TCN1 was performed again, and the protein expression in tumor tissue, non-tumor tissue, and lymph nodes was semi-quantitatively analyzed. Patients were followed up for 5 years to determine the 5-year survival rates. RESULTS: The strong immune reactivity of the TCN1 protein was significantly correlated with tumor invasion depth, regional lymph nodes, and a tumor diameter of >5 cm (Z = -2.531 and P = .016; Z = 3.785 and P < .001; Z = 2.541 and P = .049). Kaplan-Meier survival analysis showed that the total survival time of patients in the low-expression TCN1 group was significantly longer than that in the high-expression TCN1 group (P = .001; Table 2 and Figure 5). The mean survival time of all patients was 49.774 months (95% CI: 47.871-51.676; Table 4) and the 5-year overall survival rates were 73.3, 50.8, and 34.0%, respectively. Multivariate analysis revealed that regional lymph nodes (HR = 1.253; 95% CI: 1.031-1.747, P = .012), TCN1 immune expression status (HR = 2.707; 95% CI: 1.068-1.886, P = .016), and pTNM staging (HR = 2.293; 95% CI: 1.583-3.321; P = .001) were independent risk factors for poor survival. CONCLUSION: The high expression of TCN1 in gastric tumor tissues was found to be associated with the clinicopathological factors of patients, and the high expression of TCN1 was shown to indicate a poor clinical prognosis.

Mg-Mg-bonded compounds with N,N'-dipp-substituted phenanthrene-diamido and o-phenylene-diamino ligands.

Two Mg-Mg-bonded compounds were synthesized by using the ligands N,N'-bis(dipp)-phenanthrene-9,10-diimine (L2) and N,N'-bis(dipp)-o-phenylenediamine (H2L3; dipp = 2,6-diisopropylphenyl). These new Mg(i) species were characterized by X-ray diffraction, NMR, UV-Vis and fluorescence spectroscopy, and DFT computations. Their reactions with unsaturated organic molecules were examined.

Clinical observation on treatment of clearing the Governor Vessel and refreshing the mind needling in neural development and remediation of children with cerebral palsy.

OBJECTIVE: To investigate the effects of clearing the Governor Vessel and refreshing the mind needling in neural development and remediation of children with cerebral palsy. METHODS: A total of 200 cases of children with cerebral palsy were randomly assigned to the treatment group (100 patients) and the control group (100 patients). The treatment group was given the combined therapy of acupuncture and rehabilitation training, and the chosen acupoints were 13 points of the Governor Vessel, Shenshu (BL 23), Taixi (KI 3), Yanglingquan (GB 34), Zusanli (ST 36) and Sanyinjiao (SP 6), and points of refreshing the mind were also selected, which included puncturing Shenting (GV 24) toward Qianding (GV 21), puncturing Qianding (GV 21) toward Baihui (GV 20), puncturing Baihui (GV 20) toward Naohu (GV 17) and Sishencong (Ex-HN 1). The control group was only treated with rehabilitation training. A contrastive analysis of the therapeutic effect between acupuncture combined with rehabilitation training and rehabilitation training alone was made after a treatment course of 3 months. The Gross Motor Function Measure (GMFM) and Beijing Gesell Developmental Scale were adopted to assess the neural development and rehabilitation outcomes of the two groups. In addition, skull CT/MRI was adopted to evaluate the plerosis of injured cerebral nerve after treatment. RESULTS: The total effective rate in treatment group was 87% (87/100), significantly higher than the 55% (55/100) in the control group. The children's development quotient (DQ) tested by Gesell Developmental Scale and scores tested by GMFM in the treatment group were obviously higher than those in the control group (P<0.01). The improving and curing rates presented by skull CT/MRI in the treatment group were higher than those in the control group (P<0.01). CONCLUSIONS: Clearing the Governor Vessel and refreshing the mind needling could accelerate the recovery of injured brain nerve and the reconstruction of brain function. The acupuncture therapy could ameliorate both the motor development and cognitive development. On the other hand, the forward curative effect of acupuncture combined with rehabilitation training was significantly better than the rehabilitation training alone.

[Effect of acupuncture-moxibustion combined with nerve growth factor on compensation of cerebral function in the children of cerebral palsy].

OBJECTIVE: To investigate the compensation of cerebral function in acupuncture for rehabilitation of cerebral palsy. METHODS: One hundred children of cerebral palsy were randomly divided into a treatment group and a control group, 50 cases in each group. The treatment group were treated with scalp acupuncture at the Motor Area, Foot Motor Sensory Area and Equilibrium Area, body acupuncture at Binao (LI 14), Fengchi (GB 20), Huantiao (GB 30), etc. and injection of nerve growth factor into Zusanli (ST 36), in combination with rehabilitation training; the control group were treated only with rehabilitation training. Their clinical therapeutic effects and recoveries of brain lesion detected by CT, SEPCT were investigated. RESULTS: The total effective rate was 84.0% in the treatment group better than 52.0% of the control group. After treatment, the development quotient (DQ) in the treatment group was higher than the control group (P<0.01). CONCLUSION: Acupuncture can promote compensation of cerebral function in the children of cerebral palsy.

[Effects of acupuncture on quality of life in children with spastic cerebral palsy].

OBJECTIVE: To investigate the effect of acupuncture in children with spastic cerebral palsy (SCP). METHODS: One hundred SCP children, 2 to 7 years old, were randomly assigned to two groups equally. The control group was treated with rehabilitation training using Bobath and Vojta physical training methods and the acupuncture group treated also with the same training but with acupuncture conducted additionally. The therapeutic course was 3-12 months arranged according to the state of illness. RESULTS: The total effective rate, development quotient (DQ), improvement rate of brain hypogenesis and atrophy showed by skull CT, and recovery rate of cerebral emission computed tomography (ECT) were all higher in the acupuncture group than those in the control group (all P < 0.01). CONCLUSION: Acupuncture obviously promotes the compensation of cerebral function and shows a favorable effect in improving quality of life of the children with SCP.