We firstly identified 48 kDa molecular form of the unconventional myosin 1c (p48/Myo1C), and isol... more We firstly identified 48 kDa molecular form of the unconventional myosin 1c (p48/Myo1C), and isolated it from blood serum of the multiple sclerosis patients (Myronovkij et al., 2015). The amount of p48/Myo1C in human blood serum correlated with some autoimmune, hematooncological and neurodegenerative diseases and, thus, may serve as a potential molecular biomarker. The biological function(s) of this protein in human blood remains unknown. Earlier, we used the monodisperse magnetic poly (glycidyl methacrylate)(mag-PGMA-NH2 ) microspheres with immobilized 48/Myo1C and Western-blot analysis that allowed us to identify IgM and IgG immunoglobulins presenting an affinity to this protein (Zasońska et al., 2018). Here, we used mass-spectrometry followed by the Western blotting in order to identify other blood serum proteins with affinity to the 48/Myo1C. The obtained data demonstrate that 48/Myo1C binds to component 3 of the complement and the anti-thrombin III proteins. A combination of the magnetic micro-particle-based affinity chromatography with the MALDI-TOF mass-spectrometry and an in silico analysis gave an opportunity to identify the partners of interaction of 48/Myo1C with other proteins, in particular, participating in complement and coagulation cascades.
Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical... more Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical challenges facing the global health system today. The possibility to identify the group of persons in the cohort of people under 50 years old, who are sensitive to the COVID-disease by non-invasive methods, is a very perspective approach for estimating the epidemiological state of the human population. The study aimed to identify the features of people's faces with COVID-19 that the most correlate with disease severity could serve as one of these approaches. For this aim, 525 photos of patients' faces with different outcomes of COVID-19 disease were analyzed using the Dlib face recognition convolutional neural network pre-trained for face recognition. Face descriptor vectors were obtained using the convolutional neural network. Facial features were found that predict a person's sensitivity to the SARS-CoV-2 virus (disease severity), and the contribution of each of the featur...
Annals of the Russian academy of medical sciences, 2020
The coronavirus disease 2019 (COVID-19) has rapidly swept the world. Patients with cancer could b... more The coronavirus disease 2019 (COVID-19) has rapidly swept the world. Patients with cancer could be at particular risk of COVID-19, since they are often immunosuppressed by their therapy. Assessing the risk-benefit ratio of potentially immunosuppressive treatment for patients with cancer with insufficient knowledge of this new disease and balancing individual and community benefits poses acute ethical dilemmas for oncologists. Researchers provided the first guidelines for cancer patients treatment. Individual treatment plans should be adjusted to minimise routine visits, procedures and tests. Patients should be categorised into different priorities for receiving active cancer therapy during the pandemic. Oncologists should consider changing intravenous treatments to subcutaneous or oral routes, as well as suspending radiation therapy or using hypofractionation. In case of developing COVID-19 patients with cancer should be treated in the respiratory or intensive care units rather than...
Aim: comparative analysis of plasmin, plasminogen (PG), urokinase PG activator (uPA) and its rece... more Aim: comparative analysis of plasmin, plasminogen (PG), urokinase PG activator (uPA) and its receptor (uPAR) in tissues of malignant tumors and intact skin of С57ВЬ/6 mice of both genders in В16/F10 melanoma reproduced in chronic neurogenic pain (CNP). Methods: The study was performed on 130 mice and В16/ F10 melanoma cell line. Levels of uPA-antigen (uPA-AG) and uPA-activity (uPA-act), uPAR, PG, PAP (plasmin-a2-antiplasmin complex) were determined by ELISA. Statistics: the Statistica 10 program. Results. CNP-induced depletion of the content and activity of uPA was maintained in the skin and tumors after melanoma transplantation. Elevation of uPAR in females under the influence of CNP after the transplantation normalized at the terminal stage only; decreased levels of uPAR in males were maintained during the whole experiment. Elevation of PAP in females with CNP was maintained in the skin and tumors after the transplantation, and in males it was less marked. CNP affected the time of...
In 50 patients with gastric cancer, a neuroendocrine component was screened using immunohistochem... more In 50 patients with gastric cancer, a neuroendocrine component was screened using immunohistochemical studies with antibodies to chromogenic and synaptophysin in the surgical material, as well as a somatostatin receptor status researcher (SSTR). The neuroendocrine component in various proportions was found in 62% of observers. In 2 neuroendocrine carcinomas, expression of type 2 SSTR was observed at the level of “2+”, and only one adeno-neuroendocrine carcinoma produced the same expression. In carcinomas with and without neuroendocrine component, the expression of various types of SSTR was detected in 61.8% of observers in both neuroendocrine and exocrine structures. In the group of highly differentiated neuroendocrine tumors, 100% of the observers detected the expression of at least one of the 5 types of somatostatin receptors, and in 95% - at the «3+» level. The data obtained do not allow making statistically significant conclusions about the dependence of the expression of SSTR o...
Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor w... more Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor with nearly 100 % rate of recurrence and unfavorable prognosis. The aim of the present review is to analyze recent studies and experimental results (Scopus, Web of Science, PubMed) concerning somatic mutations in glioblastoma, aberrant regulation of gene expression of signal pathways including EGFR, TGFß, etc. and markers for GBM progression. Particularly the molecular subtypes of glioblastoma and NGS results are considered in this review.
Risk factors, p53, bcl-2, Topo2α, E-cadgerin, androgen receptor's expression, estrodiol, estr... more Risk factors, p53, bcl-2, Topo2α, E-cadgerin, androgen receptor's expression, estrodiol, estron, testosterone, progesterone, prolactin, estrogen methabolitis, sex-steroid connecting globulin, growth factors: VEGF, EGF, TGFß1, IGF1, IGF2, plasmin, plasminogen, u-PA, t-PA, PAI-1 levels in the tumor and perifocal tissue, population and subpopulation structure of the lymphocytes in peripheral blood, tumor and perifocal tissue, ploidy and cell cycle estimating among the 850 patients with different biologic breast cancer subtypes were tested. «Statistica 7.0» and MedCalc (version 9.3.5.0) were used for the statistical analysis. The results showed that it was impossible to analyze breast cancer only as a biological subtype according to the typical IGC. It was needed to use and other external and internal factors, determine biologic tumor behavior in complex with menstrual state of a woman. Only such way allowed developing the preventive services according tumor biological characteristi...
We analyzed literature data and our results of preoperative radiotherapy for 179 patients with re... more We analyzed literature data and our results of preoperative radiotherapy for 179 patients with resectable rectal cancer T2-4N0-2M0. The purpose of the study was to analyze the complete clinical response to chemoradiotherapy for rectal cancer. The results showed the advantages of monitoring patients with complete clinical response before total mesorectumectomy: no complications and deaths after surgery; absence of a syndrome of low anterior resection of the rectum and dysfunction of the pelvic organs; low intestinal stoma rates; similar overall survival of patients. The problems associated with the “Watch and Wait” tactics were: absence of standardized criteria for including patients in the protocol and absence of the standard protocol of treatment; no reliable criteria for the complete clinical response; high recurrence rates. Thus the “Watch and Wait” approach could be applied during a clinical study at a reference center with a multidisciplinary medical team; otherwise, total meso...
Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 canc... more Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 cancer were analyzed. 52 patients received a short-term course of the large-fraction radiation therapy and 67 patients received a prolonged course of chemoradiation therapy. The results demonstrated that the prolonged course reduced clinical signs of the disease twice as much as the short course, it reduced the tumor size and increased the distance to the anorectal line (p
Most of melanomas of the gallbladder are metastatic lesions of cutaneous melanoma. Primary melano... more Most of melanomas of the gallbladder are metastatic lesions of cutaneous melanoma. Primary melanomas of the gallbladder are described as single, polypoid, intraluminal masses emanating from the mucous membrane. The most important characteristic is the absence of melanoma damage to the skin. If it is not possible to localize primary melanoma a multidisciplinary approach to diagnostic search comes to the fore. Predicting for primary melanoma of the gallbladder is a difficult task due to the small number of cases and the absence of long-term follow-up for this category of patients.
Repeated development of a metachronous tumor in the esophagus resected because of cancer is usual... more Repeated development of a metachronous tumor in the esophagus resected because of cancer is usually observed in later periods. The period of time between the plasticity of the esophagus and the appearance of tumor can reach several tens of years. Optimal for patients with cancer of their own esophagus after esophagoplasty is early and radical surgical treatment with an individual approach to choosing surgical tactics to achieve the possible high quality of life.
The important role of the thyroid axis in the body's response to various endogenous and exoge... more The important role of the thyroid axis in the body's response to various endogenous and exogenous factors is beyond doubt. The data on the effect of tumor growth on the functional activity of the thyroid gland are inconsistent. A modifying effect of chronic neurogenic pain on the biological aggressiveness of transplantable B16/F10 melanoma requires studying the main mechanisms of action. The aim of the study was to analyze the effect of chronic neurogenic pain on the functional activity of the thyroid gland in the dynamics of B16/F10 melanoma growth in male mice. Methods. The comparison group included animals with standard subcutaneous transplantation of B16/F10 melanoma; the main group - mice with B16/F10 melanoma transplanted 2 weeks after the generation of the chronic neurogenic pain model. Levels of total and free forms of thyroid hormones and TSH were determined in thyroid cytosolic fractions by standard ELISA methods. Results. Chronic neurogenic pain increases the levels o...
The purpose of the study was to evaluate anorectal function with high-resolution anorectal manome... more The purpose of the study was to evaluate anorectal function with high-resolution anorectal manometry in patients receiving combination treatment for rectal cancer. Material and methods. We analyzed literature data (PubMed, Scopus, eLIBRARY databases) and our treatment outcomes in 50 rectal cancer patients receiving combination or surgical treatment at Rostov Research Institute of Oncology. Results. The mean anal resting pressure was 1.8 times lower, and the maximal anal squeeze pressure was 1.5 times lower in patients after combination treatment, compared to surgical treatment (p<0.05). 3 months after combination treatment with prolonged radiotherapy, contractile properties of the internal sphincter were decreased in 83.3%, of the external sphincter - in 26.7% of patients. Fatigue rate of external sphincter muscles was increased in 17 (56.7%) patients of this group. We observed a correlation between some anorectal manometry data and the LARS score: in both groups, patients with t...
The development of the tumor process involves the involvement of various functional elements of i... more The development of the tumor process involves the involvement of various functional elements of innate and adaptive immunity. A special role in the reorganization of tissues, changes and evolution of the properties of cancer cells is given to cytokines, the study of the role of which in these processes with various types of neoplasms and, in particular, with nonmetastatic gastric cancer is an urgent task. The aim of the work was to determine the characteristics of the cytokine status in the tissues of patients with non-metastatic gastric cancer. Materials and methods. In the extracts of tumor tissue, perifocal zone, omentum, peritoneum of patients with gastric cancer without metatstases (T3-4aN0-3M0, n = 20, 58.9 ± 9.7 years), the concentration of IL-1P, IL-2, IL -6, IL-8, IL-18, TNF-a, IL-10 and IL-1RA in tumor tissue, the perifocal zone, as well as in the omentum and peritoneum. Results and discussion. In the tumor tissue, an increase in the content of IL-1P, IL-8 and a decrease i...
e21583 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deat... more e21583 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world, and metastasis is the most common cause of death in lung cancer patients. Musashi-2 (MSI2) is a member of RNA-binding protein family and regulates mRNA translation of numerous intracellular targets, and influences multiple biological processes, including maintenance of stem cell identity. Previously we reported that MSI2 is upregulated in the metastasis-competent NSCLC murine and human cell lines, drives NSCLC metastasis, and is progressively elevated in lung cancer patient samples. This study assessed MSI2 as potential clinical biomarker in NSCLC. Methods: The current study included 40 patients with NSCLC, of whom 15 presented with stage II and III respectively (37,5% each), and 10 patients (25%) had stage IV. All patients received treatment in accordance with the NCCN guidelines, and did not participate in clinical trials. All patient samples were obtained before treatm...
We firstly identified 48 kDa molecular form of the unconventional myosin 1c (p48/Myo1C), and isol... more We firstly identified 48 kDa molecular form of the unconventional myosin 1c (p48/Myo1C), and isolated it from blood serum of the multiple sclerosis patients (Myronovkij et al., 2015). The amount of p48/Myo1C in human blood serum correlated with some autoimmune, hematooncological and neurodegenerative diseases and, thus, may serve as a potential molecular biomarker. The biological function(s) of this protein in human blood remains unknown. Earlier, we used the monodisperse magnetic poly (glycidyl methacrylate)(mag-PGMA-NH2 ) microspheres with immobilized 48/Myo1C and Western-blot analysis that allowed us to identify IgM and IgG immunoglobulins presenting an affinity to this protein (Zasońska et al., 2018). Here, we used mass-spectrometry followed by the Western blotting in order to identify other blood serum proteins with affinity to the 48/Myo1C. The obtained data demonstrate that 48/Myo1C binds to component 3 of the complement and the anti-thrombin III proteins. A combination of the magnetic micro-particle-based affinity chromatography with the MALDI-TOF mass-spectrometry and an in silico analysis gave an opportunity to identify the partners of interaction of 48/Myo1C with other proteins, in particular, participating in complement and coagulation cascades.
Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical... more Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical challenges facing the global health system today. The possibility to identify the group of persons in the cohort of people under 50 years old, who are sensitive to the COVID-disease by non-invasive methods, is a very perspective approach for estimating the epidemiological state of the human population. The study aimed to identify the features of people's faces with COVID-19 that the most correlate with disease severity could serve as one of these approaches. For this aim, 525 photos of patients' faces with different outcomes of COVID-19 disease were analyzed using the Dlib face recognition convolutional neural network pre-trained for face recognition. Face descriptor vectors were obtained using the convolutional neural network. Facial features were found that predict a person's sensitivity to the SARS-CoV-2 virus (disease severity), and the contribution of each of the featur...
Annals of the Russian academy of medical sciences, 2020
The coronavirus disease 2019 (COVID-19) has rapidly swept the world. Patients with cancer could b... more The coronavirus disease 2019 (COVID-19) has rapidly swept the world. Patients with cancer could be at particular risk of COVID-19, since they are often immunosuppressed by their therapy. Assessing the risk-benefit ratio of potentially immunosuppressive treatment for patients with cancer with insufficient knowledge of this new disease and balancing individual and community benefits poses acute ethical dilemmas for oncologists. Researchers provided the first guidelines for cancer patients treatment. Individual treatment plans should be adjusted to minimise routine visits, procedures and tests. Patients should be categorised into different priorities for receiving active cancer therapy during the pandemic. Oncologists should consider changing intravenous treatments to subcutaneous or oral routes, as well as suspending radiation therapy or using hypofractionation. In case of developing COVID-19 patients with cancer should be treated in the respiratory or intensive care units rather than...
Aim: comparative analysis of plasmin, plasminogen (PG), urokinase PG activator (uPA) and its rece... more Aim: comparative analysis of plasmin, plasminogen (PG), urokinase PG activator (uPA) and its receptor (uPAR) in tissues of malignant tumors and intact skin of С57ВЬ/6 mice of both genders in В16/F10 melanoma reproduced in chronic neurogenic pain (CNP). Methods: The study was performed on 130 mice and В16/ F10 melanoma cell line. Levels of uPA-antigen (uPA-AG) and uPA-activity (uPA-act), uPAR, PG, PAP (plasmin-a2-antiplasmin complex) were determined by ELISA. Statistics: the Statistica 10 program. Results. CNP-induced depletion of the content and activity of uPA was maintained in the skin and tumors after melanoma transplantation. Elevation of uPAR in females under the influence of CNP after the transplantation normalized at the terminal stage only; decreased levels of uPAR in males were maintained during the whole experiment. Elevation of PAP in females with CNP was maintained in the skin and tumors after the transplantation, and in males it was less marked. CNP affected the time of...
In 50 patients with gastric cancer, a neuroendocrine component was screened using immunohistochem... more In 50 patients with gastric cancer, a neuroendocrine component was screened using immunohistochemical studies with antibodies to chromogenic and synaptophysin in the surgical material, as well as a somatostatin receptor status researcher (SSTR). The neuroendocrine component in various proportions was found in 62% of observers. In 2 neuroendocrine carcinomas, expression of type 2 SSTR was observed at the level of “2+”, and only one adeno-neuroendocrine carcinoma produced the same expression. In carcinomas with and without neuroendocrine component, the expression of various types of SSTR was detected in 61.8% of observers in both neuroendocrine and exocrine structures. In the group of highly differentiated neuroendocrine tumors, 100% of the observers detected the expression of at least one of the 5 types of somatostatin receptors, and in 95% - at the «3+» level. The data obtained do not allow making statistically significant conclusions about the dependence of the expression of SSTR o...
Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor w... more Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor with nearly 100 % rate of recurrence and unfavorable prognosis. The aim of the present review is to analyze recent studies and experimental results (Scopus, Web of Science, PubMed) concerning somatic mutations in glioblastoma, aberrant regulation of gene expression of signal pathways including EGFR, TGFß, etc. and markers for GBM progression. Particularly the molecular subtypes of glioblastoma and NGS results are considered in this review.
Risk factors, p53, bcl-2, Topo2α, E-cadgerin, androgen receptor's expression, estrodiol, estr... more Risk factors, p53, bcl-2, Topo2α, E-cadgerin, androgen receptor's expression, estrodiol, estron, testosterone, progesterone, prolactin, estrogen methabolitis, sex-steroid connecting globulin, growth factors: VEGF, EGF, TGFß1, IGF1, IGF2, plasmin, plasminogen, u-PA, t-PA, PAI-1 levels in the tumor and perifocal tissue, population and subpopulation structure of the lymphocytes in peripheral blood, tumor and perifocal tissue, ploidy and cell cycle estimating among the 850 patients with different biologic breast cancer subtypes were tested. «Statistica 7.0» and MedCalc (version 9.3.5.0) were used for the statistical analysis. The results showed that it was impossible to analyze breast cancer only as a biological subtype according to the typical IGC. It was needed to use and other external and internal factors, determine biologic tumor behavior in complex with menstrual state of a woman. Only such way allowed developing the preventive services according tumor biological characteristi...
We analyzed literature data and our results of preoperative radiotherapy for 179 patients with re... more We analyzed literature data and our results of preoperative radiotherapy for 179 patients with resectable rectal cancer T2-4N0-2M0. The purpose of the study was to analyze the complete clinical response to chemoradiotherapy for rectal cancer. The results showed the advantages of monitoring patients with complete clinical response before total mesorectumectomy: no complications and deaths after surgery; absence of a syndrome of low anterior resection of the rectum and dysfunction of the pelvic organs; low intestinal stoma rates; similar overall survival of patients. The problems associated with the “Watch and Wait” tactics were: absence of standardized criteria for including patients in the protocol and absence of the standard protocol of treatment; no reliable criteria for the complete clinical response; high recurrence rates. Thus the “Watch and Wait” approach could be applied during a clinical study at a reference center with a multidisciplinary medical team; otherwise, total meso...
Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 canc... more Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 cancer were analyzed. 52 patients received a short-term course of the large-fraction radiation therapy and 67 patients received a prolonged course of chemoradiation therapy. The results demonstrated that the prolonged course reduced clinical signs of the disease twice as much as the short course, it reduced the tumor size and increased the distance to the anorectal line (p
Most of melanomas of the gallbladder are metastatic lesions of cutaneous melanoma. Primary melano... more Most of melanomas of the gallbladder are metastatic lesions of cutaneous melanoma. Primary melanomas of the gallbladder are described as single, polypoid, intraluminal masses emanating from the mucous membrane. The most important characteristic is the absence of melanoma damage to the skin. If it is not possible to localize primary melanoma a multidisciplinary approach to diagnostic search comes to the fore. Predicting for primary melanoma of the gallbladder is a difficult task due to the small number of cases and the absence of long-term follow-up for this category of patients.
Repeated development of a metachronous tumor in the esophagus resected because of cancer is usual... more Repeated development of a metachronous tumor in the esophagus resected because of cancer is usually observed in later periods. The period of time between the plasticity of the esophagus and the appearance of tumor can reach several tens of years. Optimal for patients with cancer of their own esophagus after esophagoplasty is early and radical surgical treatment with an individual approach to choosing surgical tactics to achieve the possible high quality of life.
The important role of the thyroid axis in the body's response to various endogenous and exoge... more The important role of the thyroid axis in the body's response to various endogenous and exogenous factors is beyond doubt. The data on the effect of tumor growth on the functional activity of the thyroid gland are inconsistent. A modifying effect of chronic neurogenic pain on the biological aggressiveness of transplantable B16/F10 melanoma requires studying the main mechanisms of action. The aim of the study was to analyze the effect of chronic neurogenic pain on the functional activity of the thyroid gland in the dynamics of B16/F10 melanoma growth in male mice. Methods. The comparison group included animals with standard subcutaneous transplantation of B16/F10 melanoma; the main group - mice with B16/F10 melanoma transplanted 2 weeks after the generation of the chronic neurogenic pain model. Levels of total and free forms of thyroid hormones and TSH were determined in thyroid cytosolic fractions by standard ELISA methods. Results. Chronic neurogenic pain increases the levels o...
The purpose of the study was to evaluate anorectal function with high-resolution anorectal manome... more The purpose of the study was to evaluate anorectal function with high-resolution anorectal manometry in patients receiving combination treatment for rectal cancer. Material and methods. We analyzed literature data (PubMed, Scopus, eLIBRARY databases) and our treatment outcomes in 50 rectal cancer patients receiving combination or surgical treatment at Rostov Research Institute of Oncology. Results. The mean anal resting pressure was 1.8 times lower, and the maximal anal squeeze pressure was 1.5 times lower in patients after combination treatment, compared to surgical treatment (p<0.05). 3 months after combination treatment with prolonged radiotherapy, contractile properties of the internal sphincter were decreased in 83.3%, of the external sphincter - in 26.7% of patients. Fatigue rate of external sphincter muscles was increased in 17 (56.7%) patients of this group. We observed a correlation between some anorectal manometry data and the LARS score: in both groups, patients with t...
The development of the tumor process involves the involvement of various functional elements of i... more The development of the tumor process involves the involvement of various functional elements of innate and adaptive immunity. A special role in the reorganization of tissues, changes and evolution of the properties of cancer cells is given to cytokines, the study of the role of which in these processes with various types of neoplasms and, in particular, with nonmetastatic gastric cancer is an urgent task. The aim of the work was to determine the characteristics of the cytokine status in the tissues of patients with non-metastatic gastric cancer. Materials and methods. In the extracts of tumor tissue, perifocal zone, omentum, peritoneum of patients with gastric cancer without metatstases (T3-4aN0-3M0, n = 20, 58.9 ± 9.7 years), the concentration of IL-1P, IL-2, IL -6, IL-8, IL-18, TNF-a, IL-10 and IL-1RA in tumor tissue, the perifocal zone, as well as in the omentum and peritoneum. Results and discussion. In the tumor tissue, an increase in the content of IL-1P, IL-8 and a decrease i...
e21583 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deat... more e21583 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world, and metastasis is the most common cause of death in lung cancer patients. Musashi-2 (MSI2) is a member of RNA-binding protein family and regulates mRNA translation of numerous intracellular targets, and influences multiple biological processes, including maintenance of stem cell identity. Previously we reported that MSI2 is upregulated in the metastasis-competent NSCLC murine and human cell lines, drives NSCLC metastasis, and is progressively elevated in lung cancer patient samples. This study assessed MSI2 as potential clinical biomarker in NSCLC. Methods: The current study included 40 patients with NSCLC, of whom 15 presented with stage II and III respectively (37,5% each), and 10 patients (25%) had stage IV. All patients received treatment in accordance with the NCCN guidelines, and did not participate in clinical trials. All patient samples were obtained before treatm...
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