The Prognostic Value of Preoperative Systemic Inflammatory Response Index (SIRI) in Patients With High-Grade Glioma and the Establishment of a Nomogram.

BACKGROUND: The predictive value of systemic inflammatory response index (SIRI) was confirmed in some malignant tumors. However, few studies investigated the prognostic value of SIRI in high-grade gliomas. This study aimed to evaluate the prognostic relationship of preoperative SIRI in high-grade gliomas and established a nomogram accordingly. METHODS: Data of operable high-grade glioma patients were analyzed. Kaplan-Meier, log-rank test, cox regression and propensity score matching (PSM) analysis were used to analyze survival. ROC curve and area under the curve (AUC) were used to compare the ability of preoperative SIRI, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) to predict prognosis. A nomogram based on the results was established. The consistency index (C-index) was calculated and a calibration curve was drawn.The prediction effect of the nomogram and WHO grade was compared by AUC. RESULTS: A total of 105 patients were included. Kaplan-Meier survival analysis showed that the overall survival (OS) of grade III gliomas patients with lower preoperative SIRI (SIRI<1.26) was significantly prolonged (p=0.037), and grade IV gliomas patients with lower preoperative SIRI had a tendency to obtain longer OS (p = 0.107). Cox regression showed preoperative SIRI was an independent prognostic factor for grade IV and grade III glioma, however, in IDH mutant-type IV gliomas, patients with lower SIRI only showed a tendency to obtain better OS. Similar results were obtained in PSM. The prognostic value of SIRI were better than PLR and MLR by ROC analysis. And in grade IV gliomas, the predictive value of SIRI was better than NLR. The nomogram established based on preoperative SIRI, age, extent of resection, number of gliomas, MGMT methylation status and histological types (only in grade III gliomas) could predict the prognosis more accurately. CONCLUSION: SIRI was valuable for prognosis prediction in high-grade glioma. The nomogram covering SIRI could more accurately predict the survival rate in operable high-grade glioma patients.

Efficacy of Neoadjuvant Single or Dual Anti-HER-2 Therapy Combined with Chemotherapy in Patients with HER-2-Positive Breast Cancer: A Single-Center Retrospective Study.

BACKGROUND: Studies have shown that neoadjuvant anti-HER-2 therapy and chemotherapy can increase pathologic complete response (pCR) rate in HER-2-positive breast cancer patients and improve prognosis. However, data from Chinese patients are limited. Therefore, we conducted a single-center retrospective study to evaluate the effects of neoadjuvant single or dual anti-HER-2 therapy and chemotherapy in Chinese HER-2-positive breast cancer patients and to explore the prognostic indicators of pCR and progression-free survival (PFS). METHODS: We included patients with HER-2-positive breast cancer treated with neoadjuvant anti-HER-2 therapy and chemotherapy at the First Affiliated Hospital of Chongqing Medical University in China from January 2016 to July 2020. We analyzed the relationship between patient characteristics and the pCR rate or PFS. RESULTS: Forty-seven patients with HER-2-positive breast cancer receiving neoadjuvant anti-HER-2 therapy and chemotherapy were included. Univariate analysis suggested that compared with patients receiving neoadjuvant single anti-HER-2 therapy, patients receiving neoadjuvant dual anti-HER-2 therapy tended to have a higher pCR rate and better PFS. Patients who achieved pCR also tended to have longer PFS. Multivariate analysis indicated that patients with greater systemic inflammation response index (SIRI) reduction (>0.54) during neoadjuvant treatment (NAT) and patients with a lower T stage were more likely to achieve pCR. Patients aged ≤60 years with lower Ki-67 had longer PFS. CONCLUSION: Greater SIRI reduction during NAT was an independent influencing factor for pCR. Patients receiving neoadjuvant dual anti-HER-2 therapy and chemotherapy tended to have higher pCR rates and longer PFS. Patients who achieved pCR also tended to have longer PFS.

The Prognostic Value of the Prognostic Nutritional Index in Operable High-Grade Glioma Patients and the Establishment of a Nomogram.

BACKGROUND: Studies confirmed the predictive value of the prognostic nutrition index (PNI) in many malignant tumors. However, it did not reach a consensus in glioma. Therefore, this study investigated the prognostic value of preoperative PNI in operable high-grade glioma and established a nomogram. METHODS: Clinical data of high-grade glioma patients were retrospectively analyzed. The primary endpoint was overall survival (OS). Survival analysis was conducted by the Kaplan-Meier method, log-rank test, and Cox regression analysis. A nomogram was established. The prediction effect of the nomogram covering PNI was verified by area under the curve (AUC). RESULTS: A total of 91 operable high-grade glioma patients were included. Kaplan-Meier analysis showed that among grade IV gliomas (n = 55), patients with higher PNI (>44) showed a trend of OS benefit (p = 0.138). In grade III glioma (n = 36), patients with higher PNI (>47) had longer OS (p = 0.023). However, the intersecting Kaplan-Meier curve suggested that there may be some confounding factors. Cox regression analysis showed that higher PNI was an independent prognostic factor for grade IV glioma (HR = 0.388, p = 0.040). In grade III glioma, there was no statistically relationship between PNI levels and prognosis. When evaluating the prognostic ability of PNI alone by ROC, the AUC in grade III and IV gliomas was low, indicating that PNI alone had poor predictive power for OS. Interestingly, we found that the nomogram including preoperative PNI, age, extent of resection, number of gliomas, and MGMT methylation status could predict the prognosis of patients with grade IV glioma well. CONCLUSION: The PNI level before surgery was an independent prognostic factor for patients with grade IV glioma. The nomogram covering PNI in patients with grade IV glioma also proved the value of PNI. However, the value of PNI in grade III glioma needs to be further evaluated. More prospective studies are needed to verify this conclusion.

miR-21a in exosomes from Lewis lung carcinoma cells accelerates tumor growth through targeting PDCD4 to enhance expansion of myeloid-derived suppressor cells.

In patients with lung cancer, myeloid-derived suppressor cells (MDSCs) have been reported to be significantly increased. Tumor-derived exosomes (TDEs) from various cancers played a critical role in MDSC induction. However, studies on the molecular mechanism underlying MDSC expansion induced by exosomes from lung cancer cells are still limited. In this study, we demonstrated that LLC-Exo accelerated tumor growth along with a significant accumulation of MDSCs in mouse tumor model. miRNA profiling showed that miR-21a was enriched in LLC-Exo. The depletion of miR-21a in LLC-Exo leads to the loss of their ability to induce MDSC expansion. Further results showed that miR-21a of LLC-Exo induced MDSC expansion via downregulation of the programmed cell death protein 4 (PDCD4) protein. The results of gain-and loss-of-function experiments validated that PDCD4 function as a critical inhibitor to negatively regulate expansion of MDSCs via inhibition Il-6 production in bone marrow cells. In addition, our data showed that exosomes derived from human lung cancer cell lines expressing miR-21a, also induced expansion of MDSCs in human CD14+ monocytes in vitro. Overall, our results demonstrated that miR-21a enriched in lung carcinoma cell-derived exosomes could promote functional expansion of MDSCs through targeting PDCD4.

Intracranial radiotherapy with or without immune checkpoint inhibition for brain metastases: a systematic review and meta-analysis.

BACKGROUND: With the development of immunotherapy in recent years, the prognosis of patients is expected to improve due to immune checkpoint inhibition (ICI) combined with radiotherapy (RT). However, studies on combination therapy (ICI + intracranial RT) have reported inconsistent results, and it is unclear whether the combination has increased toxicity. By analyzing the latest relevant literature, we performed a meta-analysis to further clarify the effectiveness and safety of intracranial RT combined with ICI in patients with brain metastases (BMs). METHODS: We searched PubMed, Embase and the Cochrane Library for published studies that compared the efficacy and safety of intracranial RT combined with ICI versus intracranial RT alone in the treatment of BMs. Overall survival (OS), local brain failure (LBF), distant brain failure (DBF), and radiation necrosis (RN) were pooled with the use of the hazard ratio (HR) or odds ratio (OR). RESULTS: A total of 26 retrospective observation cohort studies were included, and over 1,500 patients who received ICI and intracranial RT were evaluated. Compared with intracranial RT alone, RT combined with ICI significantly improved OS in patients with BMs [HR =0.55, 95% confidence interval (CI): 0.48-0.64, P<0.001 when OS was defined from the date of diagnosis of BMs; HR =0.45, 95% CI: 0.39-0.52, P<0.001 when OS was defined from the date of RT], though the risk of RN was similar to that of RT alone (HR =1.27, 95% CI: 0.58-2.79, P=0.55). However, significant improvement in LBF and DBF was not obtained with RT combined with ICI (1-year LBF: OR =1.71, 95% CI: 0.38-7.67, P=0.48; LBF: HR =0.49, 95% CI: 0.28-0.87, P=0.01; 1-year DBF: OR =1.05, 95% CI: 0.47-2.33, P=0.90). CONCLUSIONS: ICI combined with intracranial RT confers a significant OS benefit for patients with BMs without significantly increasing treatment-related toxicity, but further research regarding the specific details of combined treatment application is needed to improve the survival and quality of life of patients with BMs.

The efficacy and safety of immune checkpoint inhibitors combined with antiangiogenic drugs in renal cell carcinomas: a systematic review and meta-analysis.

BACKGROUND: The treatment of solid malignant tumors using immune checkpoint inhibitors (ICIs) combined with antiangiogenic drugs, has gradually become an active field of clinical research. However, the results are inconsistent. Therefore, we designed this meta-analysis to evaluate the efficacy and safety of ICIs combined with antiangiogenic drugs in patients with solid malignant tumors. We found that the focus of combination therapy studies was on renal cell carcinomas (RCC). METHODS: We searched PubMed, Embase, and the Cochrane Library to summarize the hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and the odds ratio (OR) for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) of grade 3 or higher. RESULTS: A total of 6 studies were included. We found that patients who received antiangiogenic drugs combined with ICIs had better OS [HR =0.74, 95% confidence interval (CI): 0.60-0.89], PFS (HR =0.79, 95% CI: 0.70-0.89), ORR (OR =2.34, 95% CI: 1.35-4.04) and DCR (OR =1.52, 95% CI: 1.21-1.91) than those without ICIs. There was no significant difference in the incidence of grade 3 or higher AEs (OR =0.76, 95% CI: 0.52-1.11). Subgroup analyses showed that combination therapy resulted in a lower risk of death in patients with PD-L1 expression ≥1% or <1%, and better PFS in patients with RCCs who were of different ages, different genders, and different International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores (favorable/intermediate/poor). CONCLUSIONS: The results of this meta-analysis suggest that ICIs combined with antiangiogenic drugs can provide more clinical benefits to patients with solid malignant tumors without significantly increasing side effects. More clinical trials are needed to validate these findings further.

[Protective effect of meloxicam against acute radiation-induced brain injury in rats].

UNLABELLED: OBJECTIVE To observe the protective effect of meloxicam against acute radiation-induced brain injury in rats. METHODS: Fifty-four SD rats were randomly divided into blank control group, radiation group (20 Gy) and therapy group (20 Gy radiation followed by 10 mg/kg meloxicam treatment). The whole brain of SD rats in the radiation and therapy groups were vertically irradiated by 6 MeV electron beam at a dose of 20 Gy. One, 3 and 7 days after irradiation, the morphological changes of hippocampal neurons were observed using HE staining, and the expressions of cyclooxygenase-2 (COX-2) mRNA and protein were detected by RT-PCR and immunohistochemistry, respectively. RESULTS: Compared with the blank control group, the radiation group showed that the neuron swelling and vascular endothelial cell edema as well as space enlargement around the capillaries. Both neuron swelling and vascular endothelial cell injury in the therapy group were slighter than those in the radiation group. Compared with the blank control group, the levels of COX-2 mRNA and protein in the radiation and therapy groups increased obviously one day after irradiation (P<0.05), and compared with the radiation group, the levels decreased obviously in the therapy group (P<0.05); 3 and 7 days after irradiation, the levels of COX-2 mRNA and protein among the 3 groups had no statistical differences (P>0.05). CONCLUSION: The early use of meloxicam can reduce the brain injury induced by radiation. Its protective effect may be related to the relief of vascular endothelial cell injury and the decreased expression of COX-2.

[Therapeutic effects of C-erbB-2 and C-raf-1 gene combined with antisense oligodeoxynucleotide on the human ovarian carcinoma transplanted subcutaneously in nude mice].

BACKGROUND & OBJECTIVE: Although many positive studies were reported on single C-erbB-2 or C-raf-1 antisense oligodeoxynucleo- tide (ASODN) in cancer treatment, these studies were usually limited in single gene or in cell level and were not appropriate according to the multiple genes hypotheses of tumorigenesis. This study was designed to investigate the effects of C-erbB-2 and C-raf-1 combined with ASODN on the treatment of ovarian carcinoma xenograft in nude mice. METHODS: The model of xenografts derived from ovarian epithelial cancer SKOV3 cells was established in Balb/C nude mice, then they were randomly divided into a negative control group and 6 experimental groups [intraperitoneal injection of (1)liposome-C-erbB-2-ASODN, (2)liposome- C-raf-1-ASODN, (3)liposome-C-erbB-2-ASODN, (4)liposome-C-raf-1-ASODN, (5)whole-dose combined ASODN, (6)half-dose combined ASODN. The weight of nude mice and tumor volume were measured. The tumor growth inhibitory rates and the tumor volume decreased rates were calculated. RESULTS: C-erbB-2 and C-raf-1 combined with ASODN exhibited potent tumor growth inhibition. The tumor volume inhibitory rates were 72.5% and 78.4%; the tumor weight inhibitory rates were 70.7% and 75.3%; the tumor volume decreased rates were 29.7% and 41.6% for whole-dose combined group and half-dose combined group post-experiment, respectively. Of the 7 groups, there was no significant difference on nude mice weight post-experiment and therefore the toxicity was endurable. CONCLUSION: C-erbB-2 and C-raf-1 combined with ASODN showed potent tumor growth inhibition in vivo.

[Inhibition effects of c-erbB-2 and c-raf-1 antisense oligodeoxynucleotides combined transfection on the human ovarian carcinoma transplanted subcutaneously in nude mice].

OBJECTIVE: To investigate the inhibition effects of c-erbB-2 and c-raf-1 antisense oligodeoxynucleotides (ASODN) combined transfection on the human ovarian epithelial cancer transplanted subcutaneously in nude mice. METHODS: There were 7 groups: normal control group, c-erbB-2 sense observed group, c-raf-1 sense observed group, c-erbB-2 antisense observed group, c-raf-1 antisense observed group, whole dose combined group, half dose combined group. Human ovarian epithelial cancer cells SKOV3 were treated by different oligodeoxynucleotides, then transplanted subcutaneously in nude mice, respectively. The changes of tumor volume were observed and the tumor growth inhibitory rate was calculated. RESULTS: There was no difference between sense observed group and normal control group. There was a larger growth inhibitory rate in whole -dose combined group and half -dose combined group, the first time that can be detected was 13.7 days and 15.2 days, and the maximum tumor growth inhibitory rates were 61.1% and 71.3%, respectively. CONCLUSIONS: The results suggested that ASODN combined transfection can inhibit the tumorigenesis of ovarian epithelial cancer cells in nude mice, it may be a more useful gene therapy for the ovarian epithelial carcinoma.