Assessment of proteasome concentration and chymotrypsin-like activity in plasma of patients with newly diagnosed multiple myeloma

Ołdziej, Agnieszka Ewa; Bołkuń, Łukasz; Galar, Marzenna; Kalita, Joanna; Ostrowska, H; Romaniuk, Wioletta; Kłoczko, Janusz

doi:10.1016/j.leukres.2014.05.008

Cited by 21 publications

(16 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First of all, the study confirmed some significantly greater differences in the study proteasome parameters of MM patients compared to healthy volunteers, which are consistent with those obtained by others, including a studies concerning patients with solid tumours and haematological malignancies [6, 7, 10–12, 20]. Unfortunately, the source of an elevated proteasome level remains unclear.…”

Section: Discussionsupporting

confidence: 90%

“…In this context, recent studies have considered the assessment of proteasomal system to be useful in diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases [6, 7]. Proteasomes are important nonlysosomal multisubunit proteolytic complexes, whose elementary function consists in the degradation of damaged and short half-life proteins.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

High chymotrypsin-like activity in the plasma of patients with newly diagnosed multiple myeloma treated with bortezomib is predictive of a better response and longer PFS

et al. 2018

Self Cite

View full text Add to dashboard Cite

Proteasome inhibitors (PIs) such as bortezomib constitute an important part of the modern standard therapy for multiple myeloma (MM). In this study, we set out to assess whether proteasome concentration and chymotrypsin-like (ChT-L) activity could serve as potential biomarkers defining the likelihood of response to treatment with bortezomib, in order to identify patients who are more likely to respond to treatment with PI. We analysed proteasome concentration and ChT-L activity in the plasma of 78 patients with newly diagnosed MM during treatment with or without proteasome inhibitors. Values of all the studied parameters in the group of responders decreased sharply from the initial levels already after the third cycle of chemotherapy and remained significantly lower until the end of treatment. On the other hand, in the group of non-responders, there was an increase in the measured proteasome parameters already after the third cycle, and they remained high during the next cycles of therapy. We also showed that high baseline proteasome ChT-L activity values might prognosticate longer progression-free survival (PFS) in patients treated with PI. Our findings demonstrate that measuring plasma proteasome ChT-L activity can be used as a powerful biomarker for predicting clinical response to treatment and PFS in patients with newly diagnosed MM.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

High chymotrypsin-like activity in the plasma of patients with newly diagnosed multiple myeloma treated with bortezomib is predictive of a better response and longer PFS

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further work to validate the data of the present study for patients with prostate cancer will be required. Secondly, proteasomal chymotrypsin-like activity is not a specific marker for prostate cancer; it is likely to be increased in various types of carcinoma (36)(37)(38). Therefore, elevated chymotrypsin-like activity cannot independently indicate the occurrence of prostate cancer; however, it may improve the accuracy of prostate cancer diagnosis when used in conjunction with increased PSA level, thus decreasing the chances of over-diagnosis and over-treatment for patients with suspected prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Potential use of chymotrypsin-like proteasomal activity as a biomarker for prostate cancer

et al. 2018

View full text Add to dashboard Cite

Abstract. Although it is the most widely used biomarker for prostate cancer, the use of prostate specific antigen (PSA) is controversial due to its limitations in specificity and sensitivity. The proteasome is a complex associated with cell proliferation and apoptosis, and the abnormity of these processes may lead to tumor occurrence. Previous studies have reported that proteasomal activity is associated with cancer progression and can be used in risk stratification. The purpose of the present study was thus to investigate the feasibility of proteasome activity as a biomarker for prostate cancer. Proteasome activity in vitro and in vivo was detected, along with the expression of the substrate proteins NF-κB inhibitor-α (IκB-α), Bcl-2-associated X (Bax) and p27. Chymotrypsin-like proteasomal activity was elevated by 70% in vitro and 23% in vivo, and the expression levels of the proteasome substrate proteins IκB-α, Bax and p27 were decreased in prostate cancer cells and prostate tumor xenografts compared with normal mouse prostate tissue. In conclusion, proteasomal chymotrypsin-like activity maybe a potential biomarker for prostate cancer, and may be suitable to supplement PSA in clinical application for prostate cancer diagnosis. IntroductionProstate cancer is the most commonly diagnosed malignancy in men in western countries (1). As the second most common cause for cancer-associated mortality among men, prostate cancer caused ~27,540 deaths in the United States (2015) (2).In addition, the incidence and mortality for prostate cancer have been evidently increasing in Asia, including in China, in recent years (3).Although novel therapies for prostate cancer with proven survival benefits have been developed relatively recently (4,5), the overall increase in survival rate has been negligible. A major clinical challenge in prostate cancer is the insufficient power of the currently available diagnostic tests. Since the introduction of serum prostate specific antigen (PSA) screening >30 years ago, prostate cancer diagnosis and management have been guided by this biomarker; it remains the most commonly used tumor marker for prostate cancer diagnosis, postoperative monitoring and prognosis evaluation. PSA is a protein secreted by the epithelial cells of the prostate; an increase in serum PSA is often identified in prostate cancer patients (6,7). However, PSA is susceptible to various confounding factors, including benign prostatic hyperplasia, prostatitis and urethral surgery, which may influence the clinical reliability (8,9). The deficiencies of PSA, including the lack of specificity and sensitivity, may lead to false-positive or false-negative results. In view of this, identifying a biomarker with an improved diagnostic and prognostic potential for prostate cancer assessment may be of great significance.Refinements to PSA measurements have been proposed, including early PSA, benign PSA, free PSA, dynamic PSA parameters (including PSA velocity and PSA doubling time), PSA density (PSA to prostate volume ratio) and age-sp...

show abstract

“…Under conditions of rapid cell turnover and growth rate, proteasomes are returned into circulation. In this context, the proteasomal system could offer a new approach to diagnosis, prognosis and monitoring of anticancer treatment [2,3].…”

mentioning

confidence: 99%

“…More recently, A Oldziej et al have demonstrated that plasma proteasome concentration and Proteasome chymotrypsin-Like (ChT-L) activity could be useful markers of MM disease activity. Pretreatment values of proteasome ChT-L activity but not proteasome concentration could also serve as diagnostic and prognostic factors of progression free survival [3]. Further studies are necessary to understand the role of plasma proteasome ChT-L activity in the prognosis of multiple myeloma and the prediction of therapeutic response, especially in patients treated with bortezomib, as it can identify patients likely to benefit most from the use of proteasome inhibition.…”

mentioning

confidence: 99%

Proteasome Activity as New Approach to the Management of Multiple Myeloma

Bouacha¹

2014

J Hematol Thrombo

View full text Add to dashboard Cite

Assessment of proteasome concentration and chymotrypsin-like activity in plasma of patients with newly diagnosed multiple myeloma

Cited by 21 publications

References 39 publications

High chymotrypsin-like activity in the plasma of patients with newly diagnosed multiple myeloma treated with bortezomib is predictive of a better response and longer PFS

High chymotrypsin-like activity in the plasma of patients with newly diagnosed multiple myeloma treated with bortezomib is predictive of a better response and longer PFS

Potential use of chymotrypsin-like proteasomal activity as a biomarker for prostate cancer

Proteasome Activity as New Approach to the Management of Multiple Myeloma

Contact Info

Product

Resources

About