Triplet-drug chemotherapy combined with anti-EGFR antibody as an effective therapy for patients with initially unresectable metastatic colorectal cancer: a meta-analysis.

The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable metastatic colorectal cancer (mCRC). A systematic literature search was performed in PubMed Publisher. Studies evaluating FOLFOXIRI combine with panitumumab or cetuximab as the therapy for initially unresectable mCRC were included. The primary outcome was objective response rate (ORR) and rate of R0 resections. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and grades 3 or 4 adverse events. R software (version 4.0.2) and RevMan (version 5.3) were used to analyze the extracted data. The studies included were published between 2010 and 2021, involving four single-arm phase II trials and two randomized phase II trials. A total of 6 studies with 282 patients were included. The data showed a significant benefit for the FOLFOXIRI + anti-EGFR antibody arm compared with FOLFOXIRI arm (RR 1.33; 95% CI, 1.13-1.58; I2 = 0%, P < 0.05). The pooled ORR and pooled rate of R0 resection in patients who receiving FOLFOXIRI + anti-EGFR antibody were 85% (95% CI, 0.78-0.91; I2 = 58%) and 42% (95% CI, 0.32-0.53; I2 = 62%), respectively. The range of median PFS between all the six studies was 9.5-15.5 months, with weighted pooled median PFS mean 11.7 months. The range of median OS between all the four studies was 24.7-37 months, with weighted pooled median PFS mean 31.9 months. The common grades 3 and 4 adverse events were diarrhea and neutropenia. Our findings show that triplet-drug chemotherapy (FOLFOXIRI) combined with anti-EGFR antibody (panitumumab or cetuximab) represents a very effective therapeutic combination associated with a significant ORR and R0 rection rate for patients with molecularly unselected and surgically unresectable metastatic CRC.

Long non-coding RNA (FALEC) promotes malignant behaviors of gastric cancer cells by regulating miR-203b/PIM3 axis.

Background: Existing research shows that long non-coding RNAs (lncRNAs) have important regulatory effects in gastric cancer (GC). In recent years, focally amplified lncRNA on chromosome 1 (FALEC) has been repeatedly reported to have carcinogenic effects in thyroid carcinoma, colorectal cancer, and endometrial cancer, etc. While the role and mechanism of FALEC during GC tumorigenesis remains unclear. Methods: The levels of FALEC, microRNA-203b (miR-203b), and Recombinant Pim-3 Oncogene (PIM3) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell autophagy, proliferation, apoptosis, migration, and invasion were estimated using western blot, transmission electron microscopy (TEM), cell counting kit-8 (CCK-8), flow cytometer, and Transwell assays. The interaction between miR-203b and FALEC or PIM3 was verified using a dual-luciferase reporter assay. Moreover, the involvement of miR-203b and PIM3 in the regulatory effects of FALEC on GC was determined with rescue experiments. Results: The results showed that FALEC and PIM3 were highly expressed, while miR-203b was lowly expressed, in GC. FALEC knockdown repressed GC cell proliferation, migration, and invasion, and promoted apoptosis and autophagy in vitro. Meanwhile, FALEC knockdown prevented growth and induced GC autophagy in vivo. This shows that FALEC upregulated PIM3 by sponging miR-203b in GC cells. Besides, FALEC induced the malignant behaviors of GC cells by regulating the miR-203b/PIM3 axis. Conclusions: The FALEC/miR-203b/PIM3 axis might be a promising therapeutic target for therapy in GC patients.

Salicylate •Phenanthroline copper (II) complex induces apoptosis in triple-negative breast cancer cells.

In this study, we investigated anti-tumor activity and associated molecular mechanism of action of Salicylate ●Phenanthroline Copper (II) Complex in triple-negative breast cancer. Salicylate ●Phenanthroline Copper (II) Complex inhibited the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20) and induced apoptosis in a concentration-dependent manner. The effect was more profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines. Western blot showed that the expression of the apoptosis-related protein Bcl-2, Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with Salicylate ●Phenanthroline Copper (II) Complex. In vivo, Salicylate ●Phenanthroline Copper (II) Complex administration significantly attenuated tumor growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and survivin were reduced as measured by immunohistochemical staining. These data suggest that Salicylate ●Phenanthroline Copper (II) Complex is a promising novel therapeutic drug for triple-negative breast cancer and warrants further study.

Effect of neoadjuvant chemotherapy in patients with triple-negative breast cancer: A meta-analysis.

The present meta-analysis aimed to evaluate the effect of neoadjuvant chemotherapy on pathological complete response (pCR) and survival rate in patients with triple-negative breast cancer (TNBC). Specific inclusion and exclusion criteria were used to conduct a search of the available databases, in order to find studies performed between January 2006 and January 2014. The bibliographies of the included studies were examined with the same criteria. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group framework was used to evaluate the included studies, and RevMan 5.1 and GRADEprofiler 3.6 were used to analyze the extracted data. A total of 19 studies with 6,180 patients were included. The meta-analysis revealed that the pCR rates in patients with TNBC were significantly higher than those in patients with non-TNBC. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly lower in the patients with TNBC compared with those with non-TNBC. Furthermore, these survival rates were significantly higher in the patients with TNBC who achieved a pCR compared with those in the patients who did not achieve a pCR. pCR rates were higher among the patients with TNBC with high Ki-67 expression than among those with low Ki-67 expression. The patients with TNBC exhibited lower survival rates compared with those with non-TNBC, but achieved higher pCR rates. Moreover, those patients achieving a pCR exhibited improved 5-year survival rates, suggesting that the pCR rate could be predictive of survival in patients with TNBC. In addition, high Ki-67 expression may predict the likelihood of a pCR. However, future multicenter randomized controlled trials are required to enhance the quantity and quality of the clinical evidence.

Platinum-based therapy for triple-negative breast cancer treatment: A meta-analysis.

The aim of the present study was to evaluate the effect of platinum-based therapy on the short-term efficacy and survival rate in patients with triple-negative breast cancer (TNBC). A search of available databases was conducted, based on specific inclusion and exclusion criteria, for trials conducted between January 2006 and January 2014. The bibliographies of the included studies were examined with the same criteria. Included studies were evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE), and extracted data were analyzed using RevMan 5.1 and GRADEprofiler 3.6. Eight studies with a total of 1,349 patients were included. The meta-analysis revealed that the pathological complete response rate and overall response rate in TNBC patients who were treated with a platinum-based regimen was significantly higher than that in those treated with a non-platinum-based regimen (49.2 and 64.3%, respectively). The disease-free survival rate and overall survival rate were not significantly different between TNBC patients treated with a platinum-based regimen and those treated with a non-platinum-based regiment (P>0.05). Platinum-based chemotherapy in TNBC patients resulted in improved short-term efficacy. Platinum-based regimens may therefore be more sensitive to TNBC patients. However, future multicenter randomized controlled trials are required to validate these findings and to determine whether platinum-based chemotherapy can extend the survival rate of TNBC patients.