Cancers, Vol. 13, Pages 4770: Alpha-Lipoic Acid Prevents Side Effects of Therapeutic Nanosilver without Compromising Cytotoxicity in Experimental Pancreatic Cancer

Cancers, Vol. 13, Pages 4770: Alpha-Lipoic Acid Prevents Side Effects of Therapeutic Nanosilver without Compromising Cytotoxicity in Experimental Pancreatic Cancer Cancers doi: 10.3390/cancers13194770 Authors: Xuefeng An Li Liu Michael Schaefer Bin Yan Christian Scholz Stefan Hillmer Kangtao Wang Yiqiao Luo Huihui Ji Jury Gladkich Ingrid Herr Silver nanoparticles (AgNPs) have attracted attention in cancer therapy and might support the treatment of pancreatic ductal adenocarcinoma (PDAC). Silver is in clinical use in wound dressings, catheters, stents and implants. However, the side effects of systemic AgNP treatment due to silver accumulation limit its therapeutic application. We evaluated whether the antioxidant and natural agent α-lipoic acid might prevent these side effects. We synthesized AgNPs using an Ionic-Pulser® Pro silver generator and determined the concentration by inductively coupled plasma–optical emission spectrometry. The effect of α-lipoic acid was examined in four PDAC and two nonmalignant cell lines by MTT, FACS analysis, TEM, xenotransplantation and immunohistochemistry. The viability of PDAC cells was nearly totally abolished by AgNP treatment, whereas nonmalignant cells largely resisted. α-Lipoic acid prevented AgNP-induced cytotoxicity in nonmalignant cells but not in PDAC cells, which might be due to the higher sensitivity of malignant cells to silver-induced cytotoxicity. α-Lipoic acid prot...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Aging (Albany NY). 2021 Oct 4;13(undefined). doi: 10.18632/aging.203589. Online ahead of print.ABSTRACTPancreatic carcinoma (PC) is a severe disease associated with high mortality. Although strategies for cancer therapy have made great progress, outcomes of pancreatic carcinoma patients remain extremely poor. Therefore, it is urgent to find novel biomarkers and therapeutic targets. To identify biomarkers for early diagnosis and therapy, three mRNA microarray datasets and two miRNA datasets were selected, and combinative analysis was performed by GEO2R. Functional and pathway enrichment analysis were performed using DAVID d...
Source: Aging - Category: Biomedical Science Authors: Source Type: research
Drug Discov Today. 2021 Sep 27:S1359-6446(21)00405-0. doi: 10.1016/j.drudis.2021.09.011. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is characterized by heightened autophagy and systemic immune dysfunction. Modest improvements in clinical outcomes have been demonstrated in completed clinical trials targeting autophagy with combination hydroxychloroquine (HCQ) and chemotherapy. Recent mechanistic insights into the role of autophagy-dependent immune evasion have prompted the need for more precise and druggable targets of autophagy inhibition. Sequestosome-1 (SQSTM-1) is a multidomain scaffold protei...
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Source Type: research
e Sebens Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at advanced stages and most anti-cancer therapies have failed to substantially improve prognosis of PDAC patients. As a result, PDAC is still one of the deadliest tumors. Tumor heterogeneity, manifesting at multiple levels, provides a conclusive explanation for divergent survival times and therapy responses of PDAC patients. Besides tumor cell heterogeneity, PDAC is characterized by a pronounced inflammatory stroma comprising various non-neoplastic cells such as myofibroblasts, endothelial cells and different leukocyte populations which enrich in th...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
CONCLUSION: Resistance development in neoadjuvant FOLFIRINOX organoids, recapitulating their primary tumor resistance, suggests continuation of FOLFIRINOX therapy as an adjuvant treatment may not be advantageous for these patients. Gene expression profiles of PDAC organoids identify targetable pathways involved in chemoresistance development upon neoadjuvant FOLFIRINOX treatment, thus opening up combination therapy possibilities.PMID:34580113 | DOI:10.1158/1078-0432.CCR-21-1681
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Source Type: research
Eiseler Even with all recent advances in cancer therapy, pancreatic cancer still has a dismal 5-year survival rate of less than 7%. The most prevalent tumor subtype is pancreatic ductal adenocarcinoma (PDAC). PDACs display an extensive crosstalk with their tumor microenvironment (TME), e.g., pancreatic stellate cells, but also immune cells to regulate tumor growth, immune evasion, and metastasis. In addition to crosstalk in the local TME, PDACs were shown to induce the formation of pre-metastatic niches in different organs. Recent advances have attributed many of these interactions to intercellular communication by sma...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In conclusion, we demonstrate not only that erlotinib has a distinct effect on tumor and normal cells but also that pancreatic ductal adenocarcinoma cells respond differently to drug treatment when cultured in a 3D microenvironment. This study highlights the importance of culture systems that can more accurately mimic the in vivo tumor physiology.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ate Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly regulated by differen...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Adv Exp Med Biol. 2021;1301:7-24. doi: 10.1007/978-3-030-62026-4_2.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a dismal 5-year survival rate of 5% and very limited efficacy of the current therapeutic regimens. The lethality of PDAC stems from asymptomatic early stage of the disease, its propensity to rapidly disseminate, as well as unusual, dense and highly active surrounding stroma. Fortunately, promising literature data suggests that exploiting newly contextualized type of cell death, termed "ferroptosis", has great potential for overcoming the major pro...
Source: Advances in Experimental Medicine and Biology - Category: Research Authors: Source Type: research
i Anti-cancer therapies promote clonal selection of resistant cells that evade treatment. Effective therapy must be stable against the evolution of resistance. A potential strategy based on concepts from evolutionary game theory is to impair intra-tumor cooperation using genetically modified cells in which genes coding for essential growth factors have been knocked out. Such engineered cells would spread by clonal selection, driving the collapse of intra-tumor cooperation and a consequent reduction in tumor growth. Here, I test this idea in vitro in four cancer types (neuroendocrine pancreatic cancer, mesothelioma, lun...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.PMID:34281873 | DOI:10.21873/anticanres.15205
Source: Cell Research - Category: Cytology Authors: Source Type: research
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