EGFR-Targeted Antibody–Drug Conjugate to Different Aminobisphosphonates:Direct and Indirect Antitumor Effects on Colorectal Carcinoma Cells

Antibody––drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a “biological missile” that can destroy tumor cells while increasing the therapeutic index and decreasing toxicity. One of the most critical factors in ADC design is selecting a target antigen that is highly expressed on the surface of cancer cells. In this study, we conjugated Cetuximab (Cet), a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to aminobisphosphonates (N-BPs) such as ibandronate (IBA) or risedronate (RIS) or zoledronate (ZA). Cetuximab is administered to patients with metastatic colorectal carcinoma (mCRC) with a wild-type (WT) EGFR transduction pathway. Also, it is well established that N-BPs can trigger the antitumor activity of Vδ2 T cells in both in vitro and in vivo experimental models. The resulting ADCs were added in co-culture to assess the effect on CRC cell line proliferation and sensitivity to Vδ2 T antitumor lymphocytes in comparison with the native antibody. These assays have been performed both in conventional and 3D spheroid cultures. We found that all three ADCs can increase the inhibitory effect on cell proliferation of the WT-EGFR cell line Caco-2 while only Cet-RIS and Cet-ZA can increase the cytotoxicity mediated by Vδ2 T cells against both WT and EGFR-mutated CRC cell lines (Caco-2, DLD-1, and HCT-116). Also, the ADCs can trigger the cell proliferation of Vδ2 T cells present in peripheral blood and tumor specimens. Our findings indicate that anti-EGFR antibodies bound to N-BPs can improve the antitumor effects of the native antibody possibly increasing the therapeutic effect.</p

EGFR-Targeted Antibody–Drug Conjugate to Different Aminobisphosphonates:Direct and Indirect Antitumor Effects on Colorectal Carcinoma Cells

Antibody––drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a “biological missile” that can destroy tumor cells while increasing the therapeutic index and decreasing toxicity. One of the most critical factors in ADC design is selecting a target antigen that is highly expressed on the surface of cancer cells. In this study, we conjugated Cetuximab (Cet), a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to aminobisphosphonates (N-BPs) such as ibandronate (IBA) or risedronate (RIS) or zoledronate (ZA). Cetuximab is administered to patients with metastatic colorectal carcinoma (mCRC) with a wild-type (WT) EGFR transduction pathway. Also, it is well established that N-BPs can trigger the antitumor activity of Vδ2 T cells in both in vitro and in vivo experimental models. The resulting ADCs were added in co-culture to assess the effect on CRC cell line proliferation and sensitivity to Vδ2 T antitumor lymphocytes in comparison with the native antibody. These assays have been performed both in conventional and 3D spheroid cultures. We found that all three ADCs can increase the inhibitory effect on cell proliferation of the WT-EGFR cell line Caco-2 while only Cet-RIS and Cet-ZA can increase the cytotoxicity mediated by Vδ2 T cells against both WT and EGFR-mutated CRC cell lines (Caco-2, DLD-1, and HCT-116). Also, the ADCs can trigger the cell proliferation of Vδ2 T cells present in peripheral blood and tumor specimens. Our findings indicate that anti-EGFR antibodies bound to N-BPs can improve the antitumor effects of the native antibody possibly increasing the therapeutic effect.</p

Assessment of autologous serum skin test in chronic idiopathic urticaria

Background: In the vast majority of patients with chronic urticaria , the etiology is unknown. It has been noted that in one third of such patients it has an autoimmune base. Autologous serum skin test (ASST) is currently the best in vivo test for the detection of such patients. Our aim was to identify the prevalence of positive ASST among patients with chronic idiopathic urticaria (CIU) and to compare features of ASST + and ASST – groups. Methods: this study was done on 79 patients with CIU. Samples of 0.05ml of autologous serum and normal saline were separately injected intradermaly into the volar aspect of right and left forearm respectively. ASST Was deemed to be positive if a serum induced weal had a diameter bigger than a sailin induced response by < 1.5 mm was seen at 30min. Also we compare the clinical and laboratory parameters of ASST+ and ASST - groups.Results: Out of 79 patients with CIU, 39 patients (39%) had positive ASST and it was found that the frequency of attacks was higher in these patients (P=0.04). Conclusion: Significant percent of patients with CIU showed positive response to ASST which is most likely an autoimmune source for them. ASST can be used as a simple and cost - effective test for the detection of these patients, which has proven to be a therapeutic challenge to the treating physician

Quantitative Expression of SFN, lncRNA CCDC18-AS1, and lncRNA LINC01343 in Human Breast Cancer as the Regulator Biomarkers in a Novel ceRNA Network: Based on Bioinformatics and Experimental Analyses

Breast cancer (BC) is one of the leading cancers in the world, which has become an increasing serious problem. In this context, reports demonstrate that some long noncoding RNAs (lncRNAs) play significant regulatory roles in breast tumorigenesis and BC progression via various pathways and act as endogenous RNAs. Finding their dysregulation in cancer and evaluating their interaction with other molecules, such as short noncoding RNAs “microRNA (miRNAs)” as well as various genes, are the most important parts in cancer diagnostics. In this study, after performing GSEA and microarray analysis on the GSE71053 dataset, a new ceRNA network of CCDC18-AS1, LINC01343, hsa-miR4462, and SFN in BC was detected by bioinformatics analysis. Therefore, the expression of SFN, CCDC18-AS1, and LINC01343 was quantitatively measured in 24 BC and normal paired tissues using qRT-PCR. CCDC18-AS1, LINC01343, and SFN were expressed higher in BC than in the control (normal paired) tissues based on qRT-PCR data. Furthermore, a significant positive correlation was observed between CCDC18-AS1 and LINC01343 expression in the samples investigated in this study. The investigation of clinicopathological parameters showed that SFN was highly expressed in tumor size of <5 cm and in nonmenopausal ages, while CCDC18-AS1 and LINC01343 indicated a high expression in stages II-III and III of BC, respectively. The overall survival analysis displayed high and low survival in patients with high expression of SFN and CCDC18-AS1, respectively. The ROC curve analysis disclosed that SFN, CCDC18-AS1, and LINC01343 might be suggested as potential biological markers in BC patients. The high expression of CCDC18-AS1, LINC01343, and SFN in BC samples suggests their potential role in BC tumorigenesis and could be considered hallmarks for the diagnosis and prognosis of BC, although this will require further clinical investigations