Clinical Prospects of Tumor-Associated Proteases and Their Tissue Inhibitors Investigation in Oncologic Patients

Герштейн, Е. С.; Кушлинский, Н. Е.

doi:10.15690/vramn.v68i5.659

Cited by 15 publications

(12 citation statements)

References 58 publications

(74 reference statements)

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“…The main role in the process of cleavage of structural proteins of ECM is played by the proteolytic enzymes of the matrix metalloproteinase (MMP) group, which are present both in the tumor and in the stromal cells. On the basis of currently accumulated scientific data, there is an impression that MMP are the major proteolytic enzymes that contribute to metastatic cancer cells [9,11,15]. Author Ganusevich I.I.…”

Section: Discussionmentioning

confidence: 99%

Expression of MMP-9 as a Prognostic Factor of Uterine Sarcoma

et al. 2018

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Uterine sarcoma is a highly aggressive mesenchymal neoplasm with an extremely unfavorable prognosis. Up today there are still relevant issues concerning search for clinical-morphological and biomolecular criteria for prognosis relapse-free survival of uterine sarcoma patients. It is well-known, the increase of the expression level of MMP-9 in primary tumor or metastatic foci correlates with a low differentiation of tumor cells, high ability for invasiveness, high metastatic activity, and shortened life expectancy. It’s still unknown, whether it is possible to consider the expression of MMP-9 in uterine sarcoma cells as a convincing prognostic factor. For many types of epithelial malignant neoplasms, high metastatic rate is associated with an increase level of MMP-9 both in plasma and in tumor tissue. The purpose of this study is to investigate the features of MMP-9 expression in uterine sarcoma cells for development of the model for individual prediction of the disease course. The study of the surgical material of selected 54 cases of uterine sarcoma of stage I-II (according to FIGO criteria) with a known prognosis of the disease, which were distributed depending on the morphological type done: leiomyosarcoma (LMS) – 18 cases, endometrial stromal sarcoma (ESS) - 22 cases, undifferentiated sarcoma (US) – 14 (according to the classification of tumors of the uterus of the WHO). For histological examination, pieces of tissue were cut from different parts of the tumor nodes – central, peripheral, parts of the adjacent intact tissue of myometrium (total of 6-8 bits). The tumor cell phenotype was determined using low molecular weight cytokeratins (Cytokeratin PAN, AE1 / AE3), smooth muscle actin (Smooth Muscle Actin, 1A4), myogenin (Myogenin (F5D)), CD 10 and vimentin (Vimentin, V9). The histochemical label was evaluated in two parameters: the degree of prevalence and intensity of coloration. To assess the color intensity, a qualitative scale was used: 0 – no reaction, 1+ – weak cytoplasmic coloration to 30.0% of tumor cells, 2+ – moderate reaction, 30.0 to 60.0% of stained cells, 3+ – pronounced cytoplasmic reaction in 60,0-100,0% of tumor cells. Statistical processing of the data was performed using the “STATISTICA 10.0” program package. The conducted study has showed, the negative (0) and weak (1+) expression of matrix metalloproteinase-9 were observed in the most part of ESS and only partially in US. Despite the stage of the disease, with such a status of MMP-9, there was observed no signs of relapsed disease. The moderate (2+) and high (3+) expression of MMP-9 was detected in 44.5 % of uterine sarcoma, in the most part in LMS patients. However, if in LMS cases the progressive disease was observed only in one third of them (4 of 12 cases), in case of ESS and US, in all the patients with such tumors status there was observed relapsed disease. Such a reaction may be indicative for invasive and metastatic potential of ESS and US and cause of the hematogenous metastases.

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Section: Discussionmentioning

confidence: 99%

Expression of MMP-9 as a Prognostic Factor of Uterine Sarcoma

et al. 2018

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“…Ассоциация повышенной экспрессии ММП опухолевыми и/ или стромальными клетками с ангиогенезом, инвазией и метастазированием продемонстрирована в экспериментальных исследованиях [13,44]. Гиперэкспрессия различных ММП и ТИМП выявлена в опухолях различного происхождения у 70-90% пациентов [1,18].…”

Section: ммп и их тканевые ингибиторы при раке почкиunclassified

Features of expression matrix metalloproteinases, their tissue inhibitors and renal cancer

Костылева¹,

Mushtenko²,

Колпаков³

et al. 2017

Lab. sluzh.

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A review of the literature is devoted to the role of the system of matrix metalloproteinases and their tissue inhibitors in renal carcinoma. Due to the absence of screening, diagnostic models for early diagnosis, as well as specific monitoring of relapse for renal tumors, the urgent task is the identification of new biomarkers of renal tumor. Recent studies demonstrate the prospects of using the system MMP/TIMP not only as a diagnostic but also a prognostic marker in some renal tumors, as well as to assess the effectiveness of targeting anticancer therapy.

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“…The ability of solid tumors to invade adjacent tissue and to metastasize depends on the uPA activated plasmin capable of digesting adjacent connective tissue and basement membranes (14). Overexpression of uPA in tumor tissues, as well as in serum, are well documented as prognostic markers of poor outcome in a wide range of malignancies (17). Yet, possible impact of uPA on the prognosis and outcome of an oral cancer was investigated only by a few laboratories.…”

Section: Plasminogen Activation System In Oral Cancersmentioning

confidence: 99%

Plasminogen activation system in oral cancer: Relevance in prognosis and therapy (Review)

Wyganowska‐Świątkowska

Jankun

2015

International Journal of Oncology

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Abstract.Research on carcinogenesis and progress in cancer treatment have reduced mortality of cancer patients. Mortality rates decreased by 1.5% per year from 2001 through 2010 for most types of cancer in men and women. However, oral cancer is still a significant global health problem since incidence and mortality rates are increasing. Oral cavity cancer is ranked the 8th in men and the 14th in women based on data collected between 2006 and 2010 by the National Institute of Health. Furthermore, an increasing incidence of head and neck neoplasms, particularly the tongue cancer among young adults has been reported recently. It is most likely due to increasing human papillomavirus (HPV) infection or the early start of tobacco and alcohol consumption. Treatment of oral cancer patients is mainly surgical and often leads to esthetic and functional deformities, with severe impact on the quality of life. Thus, novel form of treatments and selection of patients with high and low risk of mortality is of high priority for clinical studies. The expression of proteolytic enzymes in tumor and stromal tissues has been shown to have prognostic significance in many human cancers and inhibiting proteolysis can reduce tumor growth in many in vivo and in vitro models. Plasmin, with its activators and inhibitors are of great importance in many human malignances and collectively are called plasminogen activation system (PAS). In this comprehensive review we examine expression, possible prognostic markers and importance for therapy of the PAS members in oral cancer. Literature review suggests that overexpression of urokinase and its receptor are markers of poor outcome, thus, their inhibition can be explored in oral cancer therapy. Role of plasminogen activator inhibitor (PAI-1) is complex and depends on its concentration. Overexpression of PAI-1 favors angiogenesis, metastasis and poor prognosis, although when applied in very high concentrations it inhibits angiogenesis and tumor growth, the phenomenon is described as the PAI-1 paradox.

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Clinical Prospects of Tumor-Associated Proteases and Their Tissue Inhibitors Investigation in Oncologic Patients

Cited by 15 publications

References 58 publications

Expression of MMP-9 as a Prognostic Factor of Uterine Sarcoma

Expression of MMP-9 as a Prognostic Factor of Uterine Sarcoma

Features of expression matrix metalloproteinases, their tissue inhibitors and renal cancer

Plasminogen activation system in oral cancer: Relevance in prognosis and therapy (Review)

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