RNA disruption indicates CHOP therapy efficacy in canine lymphoma

Parissenti, Amadeo M.; Pritzker, Laura B.; Guo, Baoqing; Narendrula, Rashmi; Wang, Shirly Xiaohui; Lin, Lin Laura; Pei, Jingchun; Skowronski, Karolina; Bienzle, Dorothee; Woods, J. Paul; Pritzker, Kenneth P.H.; Coomber, Brenda L.

doi:10.1186/s12917-019-2189-x

Cited by 5 publications

(11 citation statements)

References 37 publications

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“…This makes flow cytometric assessment of DNA content in tumours of cancer patients untenable. In contrast, the RDA is not limited to investigations involving disaggregated cells, as evidenced by our previous works with tumour biopsies from human breast cancer patients 21 , 23 and canine lymphoma patients 22 .…”

Section: Discussionmentioning

confidence: 99%

“…In 2010, we observed that chemotherapy treatment can strongly reduce tumour RNA integrity, inducing the formation of abnormal high-molecular-weight RNA species 19 . We later termed this phenomenon "RNA disruption", due to the ability of chemotherapy treatment to disrupt the normal RNA banding pattern [20][21][22] . High RNA disruption in human breast cancer patients and canine lymphoma patients was found to be strongly associated with clinical response to treatment and improved disease-free survival after treatment [20][21][22] .…”

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confidence: 99%

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RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells

Butler

Pascheto

Lizzi

et al. 2023

Sci Rep

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We have previously shown that neoadjuvant chemotherapy can induce the degradation of tumour ribosomal RNA (rRNA) in patients with advanced breast cancer, a phenomenon we termed “RNA disruption”. Extensive tumour RNA disruption during chemotherapy was associated with a post-treatment pathological complete response and improved disease-free survival. The RNA disruption assay (RDA), which quantifies this phenomenon, is now being evaluated for its clinical utility in a large multinational clinical trial. However, it remains unclear if RNA disruption (i) is manifested across many tumour and non-tumour cell types, (ii) can occur in response to cell stress, and (iii) is associated with tumour cell death. In this study, we show that RNA disruption is induced by several mechanistically distinct chemotherapy agents and report that this phenomenon is observed in response to oxidative stress, endoplasmic reticulum (ER) stress, protein translation inhibition and nutrient/growth factor limitation. We further show that RNA disruption is dose- and time-dependent, and occurs in both tumourigenic and non-tumourigenic cell types. Northern blotting experiments suggest that the rRNA fragments generated during RNA disruption stem (at least in part) from the 28S rRNA. Moreover, we demonstrate that RNA disruption is reproducibly associated with three robust biomarkers of cell death: strongly reduced cell numbers, lost cell replicative capacity, and the generation of cells with a subG1 DNA content. Thus, our findings indicate that RNA disruption is a widespread phenomenon exhibited in mammalian cells under stress, and that high RNA disruption is associated with the onset of cell death.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells

Butler

Pascheto

Lizzi

et al. 2023

Sci Rep

Self Cite

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“…There are two studies recently published involving molecular markers for prediction. Parissenti by et al 33 revealed that RNA disruption in affected lymph nodes can be associated with good response to CHOP chemotherapy. Other study evaluated the miRNAs concentration in plasma and identify 8 miRNAs had differential expression in the non-remission group compared to dogs that completed CHOP in complete response 23 .…”

Section: Discussionmentioning

confidence: 99%

Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas

Garnica

Lesbon

Ávila

et al. 2020

Sci Rep

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Lymphoma is the most common type of canine hematological malignancy where the multicentric (cMCL) form accounts for 75% of all cases. The standard treatment is the CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone, where the majority of dogs achieve complete/partial response; however, it is very important to predict non-responsive cases to improve treatment and to develop new targeted therapies. Here we evaluate a liquid biopsy approach based on serum Small Extracellular Vesicles enriched for exosomes (SEVs) to predict cMCL chemotherapy response. Nineteen dogs at the end of the 19-week chemotherapy protocol (8 Complete Response and 11 Progressive Disease) were evaluated for serum SEVs size, concentration and screened for 95 oncomirs. PD patients had higher SEVs concentration at the diagnosis than CR patients (P = 0.034). The ROC curve was significant for SEVs concentration to predict the response to CHOP (AUC = 0.8011, P = 0.0287). A potential molecular signature based on oncomirs from SEVs (caf-miR-205, caf-miR-222, caf-mir-20a and caf-miR-93) is proposed. To the best of our knowledge, this is the first study demonstrating the potential of a liquid biopsy based on SEVs and their miRNAs content to predict the outcome of chemotherapy for canine multicentric lymphomas.

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“…In addition, evaluation of therapeutic response based only in clinical signs and lymph node measurement can result in misdiagnosis of complete remission (MARCONATO et al, 2016;CUNNINGHAM;IYENGAR;SHARMA, 2017;PARISSENTI et al, 2019), corroborating the need of more quantitative markers to help evaluate therapeutic response and improve lymphoma treatment.…”

Section: Oncomirs Screening Revealed Potential Markers For Clinical R...mentioning

confidence: 99%

“…There are two studies recently published involving molecular markers for prediction. Parissenti by et al 2019 revealed that RNA disruption in affected lymph nodes can be associated with good response to CHOP chemotherapy (PARISSENTI et al, 2019). Other study evaluated the miRNAs concentration in plasma and identify 8 miRNAs had differential expression in the non-remission group compared to dogs that completed CHOP in complete remission (CRAIG et al, 2019).…”

Section: Oncomirs Screening Revealed Potential Markers For Clinical R...mentioning

confidence: 99%

Vesículas extracelulares pequenas como marcador preditivo em cães com linfoma multicêntrico

Garnica¹

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I know you try to do your best." "I would like to thank my co-supervisor professor Juliano Coelho da Silveira for this opportunity and to introduced myself to amazing but also crazy extracellular vesicle's world. You are inspiration for me. Thank you for chats, for your patience and also for trust in me." "I also would like to thank professor Ricardo de Francisco Strefezzi for your support in pathology, for trust in our work and help since the beginning. Thank you very much!" "I would like to thank professor Andrigo Barboza de Nardi for be our first collaborator. You were fundamental for this project. Thank you very much!" "I would like to thank professor David Argyle for collaborate with us and open the doors to me. I really enjoyed my time in Scotland. Thank you very much to trust in my work." "I would like to thank doctor Lisa Pang to be my supervisor at Roslin Institute. You are brilliant and I learned too much from you. Thank you for trust in our work, for your patience and dedication. It was a very special time". "I also would like to thank our collaborators doctors Adriana Nishiya and Aline Zoppa for the opportunity of collaboration". "I would like to thank my mother for everything, for your love and cuddle. You teach the most important things. I love you mom. Thank you for always help me." "I would like to thank my fiancé Bruno Camargo de Moraes for always be patient with and hear me (it is not easy) haha. I love you so much. Thank you for staying with me in bad and moments and in all important moments of my life. You inspire me." "I would like to thank my brothers of heart Arina Lázaro Rochetti, Jéssika Cristina Chagas Lesbon and Juan Lesbon for help me every and stay with me. I am very grateful for our friendship. I am also very grateful for our dinners on Wednesday's nights. Very delicious and gourmet." "I would like to thank my family in Scotland Amanda, JV and Alana for our good times together. It was a pleasure to stay with you. Thank you very much guys, you are awesome! I miss you all." "I would like to thank Ana Clara for teach me everything about EVs. Thank you for your friendship, for be patient.

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RNA disruption indicates CHOP therapy efficacy in canine lymphoma

Cited by 5 publications

References 37 publications

RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells

RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells

Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas

Vesículas extracelulares pequenas como marcador preditivo em cães com linfoma multicêntrico

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