Compared to preoperative plasma levels post-operative urokinase-type plasminogen activator-1 levels are persistently elevated for 6 weeks after minimally invasive colorectal resection

Abstract

Background: Urokinase-type plasminogen activator-1 (uPA) is a serine protease that converts plasminogen to plasmin after binding to uPA receptor (uPAR). Plasmin catalyzes the regeneration of basement membrane, extracellular matrix, and other tissues. uPA alone and with plasmin leads to activation of angiogenic growth factors that impact tumor cell proliferation, adhesion, and migration. uPA over expression has been noted in colorectal cancer (CRC) and high tissue levels have been correlated with prognosis. uPA/uPAR promotes immune cell activation in healing surgical wounds and may alter perioperative uPA plasma levels.Postoperative (postop) plasma levels, if elevated, may impact the early growth of residual metastases. The impact of minimally invasive colorectal resection (MICR) surgery for CRC on plasma uPA levels is unknown. This study's aim was to measure plasma uPA levels during the first postop month.Methods: CRC patients undergoing MICR who enrolled in an Institutional Review Board (IRB) approved data/plasma bank for whom adequate plasma was available were included in the study. Patients who had chemotherapy or radiotherapy within 4 weeks, those who received blood transfusions perioperatively and immunosuppressed patients were excluded. Clinical and pathological data were prospectively collected as were blood samples preoperatively, postop day (POD) 1, 3 and at least 1 late time point between POD 7-41.Plasma was isolated and stored at −80 ℃. Late samples were bundled into 7-day blocks and considered as single time points. Total uPA levels (ng/mL) were analyzed in duplicate via enzyme-linked immunosorbent assay (ELISA) and results reported as mean ± standard deviation (SD). The Wilcoxon paired t-test was used for analysis.Results: Ninety-three patients undergoing MICR for CRC [colonic 68%; rectal 32%; average age 65.6 years, laparoscopic 63%, hand-assisted minimally invasive surgery (MIS) 37%] who met criteria were studied. Cancer stage breakdown was; stage I, 30%, stage II, 29%, stage III, 34%, stage IV, 7%. The median preoperative (preop) uPA plasma level (ng/mL) was 529.8 [95% confidence interval (CI): 462.8, 601.1] (n=93). Significant elevations in median levels vs. preop were present during

Units of fibrinolytic system in mice with urokinase gene knockout in presence of growing B16/F10 melanoma

“…В настоящее время известно, что урокиназа (uPA) секретируется во многих злокачественных клетках, включая рак поджелудочной железы, молочной железы, колоректальный рак и ее экспрессия часто коррелирует с прогнозом течения заболевания [4,16]. Биологическая роль этой протеиназысвязаться с рецептором uPAR, чтобы стимулировать протеолитический каскад и превратить неактивные South Russian Journal of Cancer 2024.…”

“…uPA обнаруживают на поверхности опухолевых клеток, а его сверхэкспрессия на конечной стадии трансформации злокачественных клеток, способствует процессам метастазирования [3]. Активация фибринолитической системы и образование плазмина стимулирует металлопротеиназы, ангиогенные факторы роста, что разрушает физический барьер на пути миграции опухолевых клеток и стимулирует рост опухоли [4].…”

Effect of different analgesic treatments on the pulmonary function in elderly hip fracture patients: A prospective study

“…Measurement of serum levels of CRP and IL-6 can serve as indicators to assess the extent of stress and inflammatory response in the body. [ 30 , 31 ] These biomarkers provide valuable information about the physiological impact of trauma and surgery on the patient’s overall condition.…”

Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator

“…In-depth reviews have been compiled for many of these new approaches, and thus, we have provided a broader overview. Given the recent prior reviews on uPAR-modifying treatments [ 189 , 190 , 191 , 192 , 193 , 194 ], we have provided an overview of these approaches together with a more in-depth review of the virus-derived immune-modulating serpin, Serp-1 ( Table 2 ).…”

“…The negative prognostic value with uPAR stromal expression in multiple cancer types, including colon, breast, and pancreatic cancers, clearly highlights the therapeutic potential of aiming at stromal TME as an adjuvant anti-angiogenic, anticancer treatment [ 191 , 192 , 193 , 194 ]. uPAR’s role in the tumor stromal microenvironment, overexpression in non-homeostatic tissue, high expression in aggressive cancer subtypes of poor prognosis, along with the lack of obvious cancer phenotypes when uPAR is deficient, all suggest uPAR as a candidate in anti-tumor cytotoxic therapy.…”