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Exploring the molecular mechanisms behind the potentiation of chemotherapy effects by durvalumab in lung adenocarcinoma cell lines

ABSTRACT: Immune checkpoint inhibitors are increasingly used in combination with chemotherapy for treatment of non-small cell lung cancer, yet the success of combination therapies is relatively limited. Thus, more detailed insight regarding the tumour molecular markers that may affect the responsiveness of patients to therapy is required. Here, we set out to explore the proteome of two lung adenocarcinoma cell lines (HCC-44 and A549) treated with cisplatin, pemetrexed, durvalumab, and the corresponding mixtures to establish the differences in post-treatment protein expression that can serve as markers of chemosensitivity or resistance.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Lung Adenocarcinoma

SUBMITTER: Darja Lavogina

LAB HEAD: Darja Lavogina

PROVIDER: PXD040761 | Pride | 2023-05-12

REPOSITORIES: Pride

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			Action	DRS
	210903_14_Orbi3_MS_QC_G120_T150_Lav6gina_28_2ug_200pg_iRT.raw	Raw
	210903_16_Orbi3_MS_QC_G120_T150_Lav6gina_15_2ug_200pg_iRT.raw	Raw
	210903_18_Orbi3_MS_QC_G120_T150_Lav6gina_4_2ug_200pg_iRT.raw	Raw
	210903_20_Orbi3_MS_QC_G120_T150_Lav6gina_9_2ug_200pg_iRT.raw	Raw
	210903_22_Orbi3_MS_QC_G120_T150_Lav6gina_27_2ug_200pg_iRT.raw	Raw

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Project description:Pan-viral DNA array (PVDA) and high-throughput sequencing (HTS) are useful tools to identify novel virus of emerging diseases. However, both techniques have difficulties to identify viruses in clinical samples because of host genomic DNA (hgDNA) contamination. Both propidium monoazide (PMA) and ethidium bromide monoazide (EMA) have the capacity to bind free DNA but are cell membrane-impermeable and thus are unable to bind protected DNA and RNA such as viral genomic material. DNA modified by EMA or PMA is not amplifiable by polymerase. In order to assess the capacity of EMA or PMA to lower hgDNA, serum or lung tissue homogenates were spiked with porcine reproductive and respiratory virus (PRRSV) and were processed with different combination of treatment: with or without ultracentrifugation and incubation with or without different concentration of EMA or PMA. PVDA and HTS were used to evaluate the capacity of both techniques to detect the presence of PRRSV from each sample. Negative results were obtained by PVDA and low amount of PRRSV specific reads were obtained by HTS with untreated samples or samples treated only by ultracentrifugation. An increase capacity of PRRSV detection was observable by PVDA in EMA and PMA treated samples but PVDA best results were obtained following PMA treatment, with or without ultracentrifugation. HTS sensitivity was also improved by a treatment with EMA or PMA, but the number of reads was significantly higher in PMA treated samples. These results support the use of PMA as a treatment to increase sensitivity of PVDA and HTS. A non specific DNA probe is used as a negative hybridization control. Also, specifics probes targeting pUC19 plasmid DNA is used as a DNA array positive control as well as a localization control. Finally, there are 34 probes of 70 nucleotides spotted in duplicate were selected to target PRRSV conserved regions. A total of 80 different tests were done by DNA array in order to evaluate different treatments conditions with EMA or PMA, with or without ultracentrifugation. A total of 58 samples were tested on specific lung tissue homogenates spiked with different concentration of PRRSV and 12 samples were serum samples spiked with one concentration of PRRSV. Finally. A total of six samples

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Exploring the molecular mechanisms behind the potentiation of chemotherapy effects by durvalumab in lung adenocarcinoma cell lines

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