Статьи журнала - Сибирский онкологический журнал
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Статья научная
Purpose. to evaluate prostate specific antigen density (psad) as a predictor of overall (os) and cancer-specific survival (css) in patients with prostate cancer (pc) who have undergone combined hormonal-radiation therapy. material and methods. in order to assess the prognostic significance of psad we retrospectively analyzed outcomes of 714 pca patients who received combined hormonal-radiation therapy at the a.m. granov Russian scientific center of Radiology and surgical technologies, ministry of Healthcare of Russia, between January 1996 and december 2016. since the prognosis and management differ according to the extent of tumor involvement, patients were categorized into localized (n=272), locally advanced (n=231) and metastatic (n=211) pc groups. We equentially applied Roc-analysis, Kaplan-meier product limit estimator and cox proportional hazards model to assess the prognostic relevance and establish threshold values of psad that had a significant impact on survival rates. results. in the localized pc group, psad threshold values of 0.34 ng/ml/cc and 0.36 ng/ml/cc were associated with a decrease in os and css, respectively. patients with “low” psad had significantly better os and css survival rates in both uni- and multivariate analyses. in locally advanced pc group, psad threshold values were 0.28 ng/ml/cc and 0.63 ng/ml/cc for os and css, respectively. However, exceeding the specified values, in the locally advanced pc group, was not accompanied by a statistically significant decrease in survival rates. Finally, in the metastatic pc group, established psad threshold values were 2.25 ng/ml/cc and 2.30 ng/ml/cc for os and css, respectively. according to the results of univariate analysis, patients with “low” psa tend to demonstrate statistically significant better os and css rates. the results of multivariate analysis, however, failed to prove psad as an independent prognostic factor within the metastatic pc cohort. conclusion. psa density is a reliable tool for assessing survival rates in patients with localized pc who have undergone combined hormonal-radiation therapy.
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Psychological rehabilitation and life quality assessment for patients with thyroid cancer
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Life quality values of thyroid cancer patients are characterized by reduction in psychological vector in early postoperative period and greatly in social vector. The detected damages are completely resolved within 6 months. Compensation of physical characteristics of life quality occurs more completely. High level of personal anxiety having preferably psychical and neurovascular character is observed in patients of the studied group. Comprehensive systematic psycho-therapeutic correction in early postoperative period taking account individual characteristics of the patients significantly increases the treatment efficacy. A high social-labor adaptation of the studied group patients has been found.
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Статья научная
The purpose of the study was to generalize information regarding the molecular and biological mechanisms involved in the resistance to endocrine therapy with aromatase inhibitors in patients with luminal breast cancer. material and methods. the literature search was conducted using medline, cochrane library, elibrary and pubmed databases. results. the review highlights the results of international studies on molecular and biological characteristics of breast tumors and their relationship with the effectiveness of hormone therapy. particular attention was paid to the description of modern studies on RoR1 and Bmi-1 proteins and their contribution to the development of tumor resistance to treatment. conclusion. the analysis of the world literature confirms the relevance of studying the molecular and genetic characteristics of tumor tissue in patients with luminal breast cancer. the data obtained were compared to the clinical course and response to hormone therapy in order to standardize them for implementation in everyday practice as the “gold standard of diagnosis”.
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Radical prostatectomy and robotic radiosurgery as treatment options for localized prostate cancer
Статья научная
Purpose: to compare immediate, short-term and long-term treatment outcomes after radical prostatectomy and robotic radiosurgery in patients with localized prostate cancer. Material and Methods. The study included 2 groups of patients. Group I patients (n=80) underwent radical surgery (nerve-sparing prostatectomy). Group II patients (n=102) underwent KiberKnife stereotactic robotic radiotherapy. Results. Immediate treatment outcomes after both radical prostatectomy and robotic radiosurgery did not demonstrate increased number of postoperative complications and severe radiation-induced injuries. The PSA level decreased and reached a nadir PSA level immediately after radical prostatectomy. After stereotactic radiation therapy, the PSA level decreased gradually every three months, reaching a nadir within a year. In the group of patients receiving CyberKnife treatment, changes in the prostate volume affected the quality of urination, which was confirmed by the assessment of the volume of residual urine. When comparing the quality of urination in treatment groups using the IPSS scale, the values were comparable. No differences in the 1-year disease-free survival rates between groups were found. However, 60 months later, disease free survival rate was higher by 8.2 % in patients treated with radiosurgery than in patients who underwent radical prostatectomy (p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Статья научная
PCR clamping/wild-type blocking PCR with non-extendable locked nucleic acid (LNA) oligonucleotides is used for sensitive detection of somatic mutations in tumors. Various versions of the technique use different DNA polymerases and LNA oligonucleotides with and without additional phosphorothioate modifications. Here we studied requirements for successful PCR clamping with LNA oligonucleotides and Taq DNA polymerase for analysis of mutations in KRAS and bRAF genes by means of real-time PCR and Sanger sequencing. We found that addition of phosphorothioate linkages at the 5’-end of LNA oligonucleotide to protect from 5’-exonuclease activity of Taq DNA polymerase did not improve clamping. For most target sequences, efficient clamping was observed at melting temperature of LNA oligonucleotide 20-25°C above annealing/extension temperature of the PCR with a 2-step protocol. Under such conditions, simple and sensitive detection of mutations in KRAS and bRAF genes was feasible using real-time PCR with TaqMan probes or Sanger sequencing.
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Short-term results of surgical treatment of non-organic retroperitoneal tumors
Статья научная
Comparative analysis of short-term results of combined operations and isolated removal of non-organic retroperitoneal tumors has been carried out. The study included 97 patients with malignant primary and recurrent tumors adjacent to surrounding organs. A total of 106 operations were performed, 56 of them were combined operations (52 patients were operated on), and isolated tumor removal was performed in 50 cases (45 patients were operated on). It has been found that the hemorrhage volume and surgery duration are significantly increased during the combined operations resulting in the increase in the rate of postoperative complications, however, these differences are not significant.
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Single vein resection in surgery for pancreatic ductal carcinoma as a criterion of resectability
Статья научная
Background. pancreatic ductal carcinoma (pdc) with involvement of the superior mesenteric vein (smV) or/and portal vein (pV) remains a discussible subject. We have evaluated vein invasion as a criterion of borderline resectability and long-term outcome. material and methods. in our center, 68 patients underwent either 65 standard pancreatoduodenal resections or 3 pancreatoduodenectomies for pdc. Resection of smV/pV was performed in 18 cases (26.5 %). three patients received neoadjuvant chemotherapy (Nact), and adjuvant chemotherapy (act) was assigned to 37 patients (54.4 %). Results. morbidity (42.0 vs 50.0 %, р=0.590) and mortality rates (4.0 vs 16.7 %, р=0.111) had no significant differences in groups of standard and angioplasty operations respectively. act was completed in 10 (16.7 %) patients only. there was true vein invasion in 12 of 18 patients with vein resection. рN+ (р=0.012) and angioplasty by itself (р
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Study of dendritic cell migration using CELL-IQ analysis system
Статья научная
Dendritic cells (DCs) belong to specialized pool of antigen-presenting cells with high functional plasticity and manifest with immunostimulatory or immunosuppressive potential depending on sequence and combination of microenvironment stimuli, which determine their differentiation, maturation and activation. The use of antitumor DCs vaccines is based on the ability of DCs specifically activated in vitro migrate for antigen presentation to T-lymphocytes. We studied the components of the tumor microenvironment that are capable of inhibiting DCs migration. The study of the mobility of DCs in Cell-IQ experimental analytical system showed the presence of an inverse correlation of high strength between the average trajectory speed and the level of immunosuppressive factors (ISFs) in supernatants of cultured skin melanoma cells (TgFβ1, IL-10, IL-18, VEgF-A, EgF, FgF, HgF, sFASL (p
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Study of the effect of lomustin on HER2-positive breast cancer in FVB/N her-2 transgenic mice
Статья научная
Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p
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Статья научная
Introduction. Identification of persons with a high oncological risk to squamous cell carcinoma of the head and neck region is an urgent problem for the early diagnosis of this disease. The activity of circulating proteasomes can be a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the upper respiratory and gastrointestinal tracts. The aim of the study is to investigate the chymotrypsin-like and caspase-like activities of circulating serum proteasomes depending on the localization of precancerous and neoplastic diseases of the larynx and oral cavity. Material and Methods. The study population consisted of 35 patients with histologically verified HNSCC (T1-3N0-3M0), 15 patients with chronic hyperplastic laryngitis (CHL) and oral leukoplakia, and 10 healthy volunteers who did not have chronic upper respiratory tract diseases in the acute stage. The median age of the patients was 53 ± 5.3 years. Results. An increase in the studied proteasome activities was found in the blood serum of patients with malignant tumors as compared with patients with chronic hyperplastic diseases associated with precancerous changes, as well as in the larynx and oral cavity cancers groups as compared with healthy donors. At the same time, depending on the localization of the pathological process, it was shown that only the chymotrypsin-like activity of the circulating pool of proteasomes significantly differs both in the groups of oral cancer leukoplakia, and in the groups of laryngeal cancer chronic hyperplastic laryngitis with dysplastic epithelial lesions. In addition, differences were found between chymotrypsin-like and caspase-like activities of circulating serum proteasomes in patients with chronic hyperplastic laryngitis with oral dysplasia and leukoplakia. Conclusion. The results obtained indicate that the determination of the CTP activity of the circulating pool of proteasomes can be used as a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the larynx and oral cavity.
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Статья научная
Introduction. The purpose of this study was to evaluate the feasibility of using 99mTc-Tg SPECT in the detection and staging of malignant lymphoma. materials and methods. Fifteen patients with newly diagnosed malignant lymphoma underwent 99mTc-Tg SPECT. Six patients had Hodgkin’s lymphoma and 9 patients had aggressive forms of non-Hodgkin’s lymphoma (NHL) : diffuse large b-cell lymphoma (7 cases), b-cell follicular lymphoma (1 case), and lymphoma from b cells in the marginal zone (1 case). Stage IIA was diagnosed in 5 patients, stage IIb in 1, stage IIIA in 1, stage IVA in 4 and stage IVb in 4 patients. results. Pathological 99mTc-Tg uptake in lymph nodes was observed in 14 (93 %) of the 15 patients. In one patient, the enlarged submandibular lymph node (16 mm in size) detected by CT was not visualized by 99mTc-Tg SPECT. This false-negative result was likely to be associated with increased accumulation of 99mTc-Tg in the oropharyngeal region. There were difficulties in the visualization of paratracheal, para-aortic and paracardial lymph nodes. These difficulties were associated with a high blood background activity, which persisted even 4 hours after intravenous injection of 99mTc-Tg. Software-based SPECT and CT image fusion allowed visualization of these lymph nodes. The pathological 99mTc-Tg accumulation in axillary, supraclavicular, infraclavicular and cervical lymph nodes was observed most often. Extranodal involvement was seen in 9 patients. 99mTc-Tg SPECT identified extranodal hypermetabolic lesions in 7 (78 %) of these patients. In one patient, hypermetabolic lesion in the lung detected by 99mTc-Tg SPECT was not detected on CT image. CT identified bone marrow involvement in the pelvic and scapula in 1 patient. The use of 99mTc-Tg SPECT allowed the visualization of hypermetabolic bone tissue lesions in this patient (Figure 4). In addition, in a patient with intact bone tissue on CT, 99mTc-Tg SPECT detected hypermetabolic lesions in the iliac bone. Conclusion. 99mTc-1-Thio-D-glucose demonstrated increased uptake in nodal and extranodal sites of lymphoma. The results indicate that SPECT with 99mTc-1-Thio-D-glucose is a feasible and useful tool in the detection and staging malignant lymphoma.
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Статья научная
The aim of the study was to identify differences in the immune system parameters between metastatic melanoma patients who responded and did not respond to dendritic cell vaccination. Material and Methods. The study group included 20 patients with stage III-IV metastatic melanoma, who received vaccine therapy with dendritic cells (DC) in a prophylactic mode. The control groups included 13 patients who had symptoms of disease progression at the time of starting vaccine therapy, and 5 healthy donors. The DC-vaccine was prepared in the form of a suspension of the patient's autologous dendritic cells loaded with tumor antigens in vitro . A single dose had 2 million dendritic cells in 1 ml of phosphate buffer solution, which was administered intradermally in the nearest site to the regional lymphatic collectors. The immune system status was assessed before starting vaccination. The immune system status was evaluated according to the indexes of 25 peripheral blood cell populations using multicolor flow cytometry and integral characteristic in the form of the visual image generated by the visualization method of multidimensional data (NovoSpark, Canada). Results. The immune status in patients with metastatic melanoma at the start of DC-vaccination differed and was associated with the effectiveness of subsequent vaccine therapy. The response to vaccination was observed in patients whose immune system status was similar to that of healthy individuals. Low efficacy of DC-vaccine therapy was shown in patients whose immune system status corresponded to that of patients with disease progression. Alterations of the immune system in patients with metastatic melanoma were registered both at the level of individual immunological parameters and at the level of visualized integral characteristics. The integral characteristics of the immune system associated with the patient's immunocompromised status can be considered as a criterion for stratification of patients with metastatic melanoma for the effective DC-vaccine therapy. Conclusion. The effectiveness of vaccine therapy with dendritic cells in patients with metastatic melanoma is associated with the immune system state before starting this therapy.
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The impact of cancer diagnosis on employment status in a working population
Статья научная
The aim of this study was to investigate the status of return to work and the influencing factors in patients with common cancers referring to three medical centers during the years 2020 to 2022. Material and Methods. In the present study (a retrospective cohort), all patients who visited three medical centers during the years 2020-2022 and were diagnosed with common cancers (non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, gastrointestinal cancers and sarcoma), were included in the study. Work ability index (WAI) was assessed based on selected questions from the WAI questionnaire. Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety, and Multidimensional Fatigue Inventory (MFI-20) was used to assess the level of fatigue. Then, the data obtained from individuals who returned to work were compared with those who did not return.
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The inflammatory status and lymph node metastases in non-small cell lung cancer
Статья научная
Introduction. The development of inflammation is characterized by changes in blood hematology parameters and indices. Various inflammatory parameters are used to assess the inflammatory status (iS) during cancer treatment. Recent studies have revealed a relationship between tumor progression and the presence of chronic inflammation. Consequently, there have been many attempts to predict the risk of tumor recurrence and distant metastases, as well as patient's survival assessing the various inflammatory markers. The relationship between iS parameters and lymph node metastasis remains poorly understood in non-small cell lung cancer (NSCLC). Material and Methods. The prospective study included 35 patients with NSCLC (T1-4N0-2M0). Seventeen patients received 2-3 cycles of neoadjuvant chemotherapy (NAC). A leukocyte formula was determined in the peripheral blood and inflammatory indices, such as neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), lymphocytes to monocytes ratio (LMR) and systemic immuno-inflammatory index (Sii) were calculated. in addition, the concentrations of fibrinogen, C-reactive protein (CRP) and cortisol were evaluated. Results. NAC alone did not significantly change the parameters of patients' iS. Lymph node metastases were associated with changes in parameters indicating the enhanced iS. in the group of patients who did not receive NAC, lymph node metastasis was associated with fibrinogen blood levels (cut-off value 5.35 g/L), PLR index value (cut-off value 7.18) and cortisol blood concentration (cut-off value 414 nmol/mL). The confidence level was x2=10.118; р=0.018. in the group of patients who received NAC, lymph node metastasis was associated with the leukocyte count (cut-off value 7.1*109/L), PLR index value (cut-off value is 7.18) and CRP blood concentration (cut-off value is 8.5 mg/L). The confidence level was x2=8.193; р=0.042. Conclusion. Risk of lymph node metastasis in NSCLC is associated with iS. Parameters of iS can be used to predict the risk of lymph node metastases.
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Статья научная
Localized and metastatic tumors are known to lead to the formation of circulating tumor cell (CTC) clusters in the blood. Currently, there is a heightened interest in the study of molecular and biological characteristics of CTCs. Recent studies have shown the presence of different populations of CTCs in the blood of cancer patients. Some cells are cancer stem cells, some tumor cells undergo epithelial-mesenchymal transition (EMT), and most CTCs do not have features of either stem cells or EMT. The aim of the study was to evaluate the five-year metastasis-free survival rate in patients with invasive breast carcinoma, depending on the presence of various populations of circulating tumor cells in the blood before treatment. Material and Methods. A prospective study included 47 patients with newly diagnosed invasive breast cancer (T1-4N0-3M0), who were treated at Cancer Research institute, Tomsk National Research Medical Center. The patients aged 31 to 69 years. The presence of different populations of CTCs in the blood of patients before treatment was determined by multicolor flow cytometry on the BD FACS Canto system, using different fluorochrome-labeled monoclonal antibodies to EpCam, CD45, CD44, CD24, and N-cadherin. Five-year metastasis-free survival was evaluated by the Kaplan-Meier method. The differences were considered significant at p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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The role of EZH2 and ARID1A in the diagnosis of flat urothelial lesions with atypia
Статья научная
Background. Diagnosis of urothelial carcinoma in situ is of great importance because it has prognostic and therapeutic value. We aim to determine the utility of EZH2 and ARiD1A as a new tool in the diagnosis of carcinoma in situ. Material and Methods. This retrospective cross-sectional study included Twenty-four specimens of flat urothelial lesions, twenty specimens of CiS, and 10 of normal adjacent urothelium that was taken by cystoscopic resection biopsy procedure. immunohistochemical expression of EZH2 and ARiD1A. were evaluated in all studied cases. Results. All normal urothelium specimens showed high nuclear staining for ARiD1A and negative nuclear staining for EZH2. High EZH2 expression was observed in 80 % of CiS specimens compared to 20 % of flat urothelial lesions with atypia (p=0.001 ), while high ARiD1A expression was observed in 70.8 % of flat urothelial lesions with atypia compared to 25 % of CiS specimens (p=0.001). EZH2 was more accurate and specific in the diagnosis of carcinoma in situ. Conclusion. EZH2 and ARiD1A are promising diagnostic markers for urothelial CiS. EZH2 is more accurate and specific than ARiD1A in the diagnosis of carcinoma in situ versus other flat urothelial lesions.
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The role of liquid biopsy in the diagnosis of glioblastoma progression
Статья научная
Purpose: to summarize available data on the diagnostic value of various circulating biomarkers for the detection of glioblastoma recurrence. material and methods. a literature search was conducted using pubmed exocarta and silVa databases. results. glioblastoma multiforme (gBm) is the most common glioma in adults with an unfavorable prognosis. treatment of tumor recurrence can improve the survival of patients. Neuroimaging is the standard method of diagnosing brain tumor recurrence. However, a neuroimaging method to clearly distinguish between pseudo progression and tumor progression has not been found to date. current molecular tumor profiling relies heavily on tissue resection or biopsy. tissue profiling has several disadvantages in the central nervous system’s tumors, including the challenge associated with invasive biopsy, the heterogeneous nature of many malignancies where a small biopsy can under represent the mutational profile. liquid biopsy is a promising method in diagnosing malignant tumors. Blood collection is a simple, minimally invasive procedure, but cerebrospinal fluid allows tumor markers to be detected more confidently. However, collection of cerebrospinal fluid is a complex and invasive procedure that can be accompanied by serious complications. conclusion. Biological fluid markers such as circulating tumor cells, extracellular vesicles, cell-free dNa and cell-free RNa allow for the detection of gmB, determination of molecular genetic features of cancer during response to therapy, and early detection of gBm recurrence.
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The spectrum of BRCA1 gene mutations in early onset breast cancer patients from Russia
Статья научная
Aim of the study. Aim of the study was to estimate the occurrence of pathogenic mutations in the BRCA1 gene in Russian breast cancer patients. material and methods. Complete coding sequence of the BRCA1 gene of 445 early onset breast cancer patients (under 40 years) from Novosibirsk region (Russia) were analyzed by targeted Next generation Sequencing (NgS) using Ion Torrent platform. results. Forty (9%) carriers of various pathogenic mutations were revealed. Thirty five (7,9%) patients carried 5382insC mutation, described earlier as a founder mutation for Slavic population. Five (1.1%) patients carried various pathogenic mutations, namely C61g, 462delCC, E143x, 4153delA, and IVS18+1g>T. besides, 29 genetic variants with no clinical significance or with unknown clinical significance were detected in BRCA1 gene among 445 early-onset breast cancer patients. Conclusions. Data on the frequency of genetic variations in the BRCA1 gene among early-onset breast cancer patients in the Novosibirsk Region (Russia) were obtained. Proportion of the 5382insC mutation is 87.5% of all pathogenic mutations in the BRCA1 gene found in patients.
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Transcriptomic analysis of melanoma cells extracted from different sites of the primary tumor
Статья научная
Introduction. Intratumor heterogeneity is a characteristic feature for most malignant tumors, including cutaneous melanoma. This property represents one of the main obstacles for effective targeted therapy, due to the different sensitivity to chemotherapeutic agents on various tumor cells subclones. Treatment of malignant tumors requires an individual approach to choose the most appropriate treatment regimen. The purpose of the study was to evaluate differences in melanoma tissue samples obtained from different parts of one patient’s primary tumor at the transcriptomic level. Material and Methods. Melanoma cell cultures obtained from both central and peripheral parts of the primary tumor of two patients were used in the study. Results. Subclones from different parts of the first patient’s tumor were similar, whereas the second patient demonstrated significant differences at the transcriptomic level (in 2953 transcripts out of 48226). In the cells of the central zone of the second patient’s tumor, an increase in mRNA of the genes encoding proteins associated with tumor-specific immune response, as well as ABC-family transport proteins and cytokine signaling molecules, were noted. In the cells from the peripheral area of the same tumor, a more intensive transcription of genes encoding extracellular matrix and inflammatory response proteins was observed. Taken all round, the differences between the subclones of the second patient’s cells were relevant to some signaling cascades playing a leading role in oncogenesis (MAPK, PI3K-Akt-mTOR, VEGFA-VEGFR2, etc.). Conclusion. The study allowed evaluation of differences between cancer cells within a tumor at the transcriptional level in order to search for further approaches to personalized melanoma therapy.
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