THE ROLE OF THE UROKINASE SYSTEM IN LYMPHOGENOUS METASTASIS OF COLORECTAL CANCER

The aim of this work was to study the role and relationship of the levels of the components of the urokinase system with lymphogenous metastasis in patients with colorectal cancer.Materials and methods: the study was carried out on the basis of the Medical Scientific and Educational Center of the Moscow State University named after M.V. Lomonosov from 2019 to 2021. The study included healthy donors (control group) and patients with a verified diagnosis of stage I-III colorectal cancer in accordance with the inclusion criteria; all patients underwent surgical resection of the primary tumor with lymphadenectomy of the appropriate level. All patients underwent determination of the level of uPA and uPAR in blood serum before surgery. We also analyzed the clinical and demographic data of the patients, as well as the pathomorphological characteristics of the tumor.Results. The study included 7 healthy donors and 49 patients with stage I-III colorectal cancer. The average level of serum urokinase in the control group was 2.7±1.04 ng / ml, in the study group – 4, 15±1.9 ng / ml (p = 0.071), the level of the urokinase receptor in the control and study groups was 1.36 ±0.8 ng / ml vs 3.22±2.06 ng / ml (p = 0.05). The average level of serum urokinase in patients without and with lesions of lymph nodes was 3.4±1.4 ng / ml and 4.4±2.3 ng / ml (p = 0.068).Conclusion. There is a tendency to an increase in the level of components of the urokinase system in the peripheral blood in patients with colon neoplasms in the preoperative period, depending on the presence of metastatic lesions of regional lymph nodes, which indicates the need for further research in this area.

Puncture biopsy of bifurcation lymph nodes in the diagnosis of lung cancer

Clinical, radiological and pathological data of a number of authors testify to the frequent defeat of the lymph nodes of the mediastinum with cancer metastases (MN Goryunova, 1951; Ya. G. Dillon, 1947; BK Osipov, 1959, etc.). Anatomical works of Ruvier (1932), DA Zhdanov (1947) and others testify to broad afferent connections of bifurcation lymph nodes in normal conditions with the organs of the chest cavity. These factors create the possibility of lymphogenous metastasis of cancer of the lung and esophagus in the mediastinal lymph nodes, in particular, in the bifurcation.

Regional lymph nodes and hematogenous metastasis of cancer

Aim. Morphological study of the microvasculature of regional lymph nodes in relation to the cancer of the lymph nodes as possible additional or alternative metastasis pathways. Methods. The lymph nodes of 150 cancer patients (1263 nodes in total), regional to cancer of various localization, were studied. Histological sections staining with hematoxylin and eosin by Van-Giesons method, pyronine by Brachets method, toluidine blue and picro-Mallory were prepared. An immunohistochemical study was performed using monoclonal antibodies to pan-cytokeratins, CD31, type IV collagen, CD3, CD20, and CD68. The area of metastases to the lymph nodes was determined by using a morphometric grid and used to identify the four study groups. In addition, the immunomorphological reactions of the lymph nodes were taken into account in each group. Results. It was identified that the microvasculature of the lymph nodes can be involved in the metastatic process along with the lymphatic pathways. At the same time, there is a decrease in vascular wall function and violation of the rheological properties of blood, accompanied by the deposition of intra- and extravascular fibrin. Hematogenous metastasis is largely influenced by the state of lymph node sinuses, in which blood is found, and in some observations by the expression of CD31 (a marker of blood endothelium). Hematogenous dissemination of cancer often begins after the appearance of lymph node metastases. The greater the anatomical extent of lymph node metastases, the more often tumor cells are present in the blood vessels. In addition, an isolated lesion of the microvasculature with the presence of tumor cells in the extranodal vessels without metastases in the lymph node itself was revealed. It was observed that the invasion of tumor cells into the microvasculature depended on the immunomorphological reactions of the lymph nodes. Conclusion. The microvasculature of regional lymph nodes can be both an additional and an alternative lymphogenous metastasis pathway of cancer; at the same time, vascular invasion is accompanied by microcirculation disorders and depends on the volume of metastases and the immunomorphological reactions of the lymph nodes.

Post-Surgery Subcutaneous Seeding of Laryngeal Squamous Cell Carcinoma: A Rare Case

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant head and neck cancer, with a 40% recurrence rate in the first 3 years after radical treatment. Recurrence of LSCC mostly comprises lymphogenous metastasis, hematogenic metastasis, and locoregional recurrence, while LSCC seeding is rarest: there are only 4 cases reported in PubMed, and none of them is one of subcutaneous seeding. We report a case with post-surgery subcutaneous seeding of LSCC. The final biopsy demonstrated that the subcutaneous seeding of the LSCC was 2 cm away from the primary lesion, with no recurrent foci observed in the larynx and tracheostoma and little relation to the primary lesion. Thus, we drew the conclusion that LSCC surgeries should stick to the principle of the non-tumor technique to prevent subcutaneous seeding.

The significance of clinical and hormonal-metabolic parameters in the preoperative prediction of the risk of lymphogenous metastasis in patients with stage I endometrial cancer

In patients with moderately differentiated endometrial cancer with less than half myometrial invasion, there are no specific indications for performing or not performing lymphadenectomy. Given the high prevalence of metabolic syndrome (MS) among patients with endometrial cancer (up to 62%) and a large proportion of G2 tumors in combination with MS, the anthropometric and hormonal-metabolic parameters were considered for predicting the risk of lymphogenous metastasis. To build a model of preoperative prognosis of lymphogenous metastasis, the method of logistic regression was used. Data on 53 patients with stage I endometrial cancer was analyzed. All patients underwent total laparoscopic hysterectomy with bilateral salpingo-ovariectomy and pelvic lymphadenectomy. Positive lymph nodes were found in the surgical specimen of six patients. The additional risk parameters for lymphogenous metastasis were revealed in patients with stage I endometrial cancer, namely: leptin level (AUC = 0.957), visfatin level (AUC = 0.918), body mass index (AUC = 0.911), patient age (AUC = 0.828), and HDL cholesterol (AUC = 0.699). In addition to traditional risk factors (the depth of invasion and tumor differentiation grade), the model of preoperative prediction of the risk of lymphogenous metastasis for patients with intermediate- risk stage I endometrial cancer included the following parameters: age, body mass index, HDL cholesterol, level of adipose hormones leptin and visfatin in blood plasma.. The sensitivity and specificity of the model were 83.3% and 97.9%, respectively.

Innovative Radiopharmaceuticals for Cancer Diagnosis and Treatment

The presented material summarizes the experience of Cancer Research Institute and Tomsk Polytechnical University team in the development of original radiopharmaceuticals (RP) for nuclear medicine. The first such unique for world nuclear medicine RP was a Thallium­199. The Thallium­199 is successfully used for breast cancer diagnosis and its lymphogenous metastasis, as well as to visualize cancer of the larynx and laryngopharynx, their relapses and for differential diagnosis of inflammatory and tumor processes of the musculoskeletal system. The great practical importance for nuclear medicine has the organization of a waste­free production of sorption and extraction generators of Technetium­-99m at the IRT­T TPU nuclear research reactor, as well as the creation of a fully automated 99mTc module operating on a waste­ free technology. The development of the 99mTc­Alotech for targeting imaging of sentinel lymph nodes (SLN) has also great importance for clinical oncology. The main advantage of 99mTc­Glucoscin is that metabolic tumor imaging with the innovative RP use can be performed using a conventional gamma camera, which significantly reduces the cost of the diagnostic procedure. The present and promising developments of the research teams of the Tomsk Scientific Research Center and the Tomsk Polytechnic University are closely related to theranostics — the use of RPs obtained on the basis of same target compound labeled with different isotopes intended for the diagnosis or therapy of oncological diseases.

Consecutive Observation of Dynamic Metastases of Human Ovarian Carcinoma to Grading Lymph Nodes in Mouse Model

Background：Lymphogenous metastasis, one of the most common dissemination routes for ovarian carcinoma, predicts a poor prognosis and relates to most cancer-related death. Now there were no effective therapy and control methods for ovarian carcinoma. Hence, it is necessary to build an animal model of lymph node metastasis in ovarian cancer to seek for the tools to find effective treatments. Our purpose of this study was to investigate the tumor cell dissemination of ovarian carcinoma to the gradient lymph nodes of nude mice and its possible mechanism.Methods: The mice models of VEGF-D over-expressed were built, and the tumor growth and sentinel lymph nodes were evaluated weekly, while the visible lymph nodes and tumor masses were excised for histological examination using HE examination. Then Evan’s Blue was conducted to observe the unveil lymphatic network. Subsequently, immunohistochemistry (IHC) was performed to check the protein expression of relative genes. Meanwhile, microvessel counting was performed within the tumor tissues and measured using computer assisted morphometric analysis.Results: The over-expression of VEGF-D promoted the tumor growth of ovarian carcinoma, facilitated the hyperplasia of tumor lymphatic and increased the intratumoral lymphatic vessel density. Besides, the up-regulation of VEGF-D induced the expression of MMP-2, which might be the underlying mechanism of the lymph metastasis in ovarian cancer.Conclusion: It was a step-by-step progression from the inoculation of cancer cells to the proliferation of the primary tumors, and then to the lymphatic metastases, in which VEGF-D and MMP-2 played vital roles.

The Dynamic Metastases of Human Ovarian Carcinoma to Grading Lymph Nodes in Mouse Model

Background：Lymphogenous metastasis, one of the most common dissemination routes for ovarian carcinoma, predicts a poor prognosis and relates to most cancer-related death. Now there were no effective therapy and control methods for ovarian carcinoma. Hence, it is necessary to build an animal model of lymph node metastasis in ovarian cancer to seek for the tools to find effective treatments. Our purpose of this study was to investigate the tumor cell dissemination of ovarian carcinoma to the gradient lymph nodes of nude mice and its possible mechanism. Methods: The mice models of VEGF-D over-expressed were built and the tumor growth and sentinel lymph nodes were evaluated weekly, while the visible lymph nodes and tumor masses were excised for histological examination using HE examination. Then Evan’s Blue was conducted to observe the unveil lymphatic network. Subsequently, immunohistochemistry was performed to check the expression of relative genes. Meanwhile, microvessel counting was performed within the tumor tissues and measured using computer assisted morphometric analysis.Results: The over-expression of VEGF-D promoted the tumor growth of ovarian carcinoma, facilitated the hyperplasia of tumor lymphatic and increased the intratumoral lymphatic vessel density. Besides, the up-regulation of VEGF-D induced the expression of MMP-2, which might be the underlying mechanism for the lymph metastasis in ovarian cancer. Conclusion: It was a step-by-step progression from the inoculation of cancer cells, to the proliferation of the primary tumors, and then to the lymphatic metastases, in which VEGF-D and MMP-2 played vital roles.

Consecutive Observation of Dynamic Metastases of Human Ovarian Carcinoma to Grading Lymph Nodes in Mouse Model

Background：Lymphogenous metastasis, one of the most common dissemination routes for ovarian carcinoma, predicts a poor prognosis and relates to most cancer-related death. Now there were no effective therapy and control methods for ovarian carcinoma. Hence, it is necessary to build an animal model of lymph node metastasis in ovarian cancer to seek for the tools to find effective treatments. Our purpose of this study was to investigate the tumor cell dissemination of ovarian carcinoma to the gradient lymph nodes of nude mice and its possible mechanism. Methods: The mice models of VEGF-D over-expressed were built and the tumor growth and sentinel lymph nodes were evaluated weekly, while the visible lymph nodes and tumor masses were excised for histological examination using HE examination. Then Evan’s Blue was conducted to observe the unveil lymphatic network. Subsequently, immunohistochemistry was performed to check the expression of relative genes. Meanwhile, microvessel counting was performed within the tumor tissues and measured using computer assisted morphometric analysis.Results: The over-expression of VEGF-D promoted the tumor growth of ovarian carcinoma, facilitated the hyperplasia of tumor lymphatic and increased the intratumoral lymphatic vessel density. Besides, the up-regulation of VEGF-D induced the expression of MMP-2, which might be the underlying mechanism for the lymph metastasis in ovarian cancer. Conclusion: it was a step-by-step progression from the inoculation of cancer cells, to the proliferation of the primary tumors, and then to the lymphatic metastases, in which VEGF-D and MMP-2 played vital roles.