Статьи журнала - Сибирский онкологический журнал
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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 inflammatory status and lymph node metastases in non-small cell lung cancer
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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
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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
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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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Treatment of cervical esophageal carcinoma: systematic review and meta-analysis
Статья научная
Objectives. Up to date managing a cervical esophageal carcinoma (CEC) has remained a controversial challenge. The choice of treatment is still uncertain. In the present review we attempted to assess eligibility of surgery in treatment of CEC. Material and Methods. We have enquired particular publication databases and the enquiries yielded 24 contributions matching study selection criteria such as (1) original articles published from 2000 to 2022, (2) primary tumor localization in the cervical esophagus, (3) squamous cell carcinoma,(4) available characteristics of studied groups (age, sex, T, N, M, stage), (5) detailed description of curative procedures (radiation therapy, chemotherapy, surgery), (6) information about overall survival. These publications represented two arms of 14 surgical and 17 non-surgical subgroups to analyze. Individual patient data and parameter estimates have been renewed on the basis of original Kaplan-Meier curves plotted. Results. The analysis revealed a highly heterogeneous (I2=83.76 %; 95 % CI, 71.40-92.16) random effects model. Including a surgical option into treatment of CEC did not affect 3-year overall survival (р=0.665); 46.4 % (95% CI, 37.4-55.6) vs 43.7 % (95 % CI, 35.3-51.6), respectively. Possibilities of surgical and non-surgical modalities employment were discussed. Conclusion. In treatment of CEC CRT and surgery are non-inferior to each other. These modalities are evenly associated with posterior side effects and complications, which adversely affect functional outcomes and survival. The choice of a treatment mode may depend on tumor response to induction therapy. The latter demands further investigations.
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Treatment of early cervical cancer: survival, complications and economical aspects
Статья научная
The paper presents recent data on current methods of combined modality treatment of cervical cancer patients, comparative effectiveness of different regimes of neo-and adjuvant chemotherapy and cost-effective analysis.
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Treatment results for stage IV gastric cancer patients
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Treatment results for stage IV gastric cancer patients treated at the Southern-Kazakhstan Regional Oncological Clinic during the period from 2003 to 2007 have been presented. One hundred patients underwent palliative surgery, 49 (49 %) of them underwent cytoreductive subtotal distal gastric resection, 31 (31 %) cytoreductive gastrectomy and 20 (20 %) cytoreductive proximal gastric resection. Postoperative lethality was 13 %. Sixty-one patients (61 %) received systemic polychemotherapy following surgery. The 3-year survival rate was 3,3 and 3,8 times higher after distal subtotal resection than after gastrectomy and proximal resection, respectively. The 5-year survival rate was 6,1 % after cytoreductive distal subtotal gastric resection. Patients who underwent cytoreductive distal subtotal gastric resection received up to 4 cycles of systemic chemotherapy.
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Ultrasound-guided interventional procedures - effective method of tumor morphological verification
Статья научная
From 2001 to 2006, 767 ultrasound-guided interventional procedures were performed, out of them there were 43 (5,6 %) with curative intent. Multi-functional digital ultrasound scan (HP Image Point NX) with the kit of multi-frequency sensors was used for making biopsies. All interventional procedures were done using mechanical needles with 14G in diameter. Specimens for pathomorphological examination were obtained in 68,2-97,5 % of cases.
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Venous thromboembolism in cancer patients in postoperative period
Статья научная
The modern methods of antithrombotic prevention and treatment were shown to result in 6,7-fold reduction in the incidence of postoperative thrombotic complications (p0,5). The 2-year survival rate was lower by 29,5 % for cancer patients with postoperative venous thromboembolism than for patients without complications.
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Virtual surgical planning in soft tissue reconstruction for oral cancer
Статья научная
Introduction. Reconstruction of soft tissue defects after radical surgeries in cancer patients is important for early surgical rehabilitation and improving quality of life. Our study presents technologies for virtual surgical planning (VSP) of soft tissue defect reconstruction in patients with squamous cell carcinoma of the oral cavity. Case presentation. We described VSP in a report of a 54-year-old patient with locally advanced buccal mucosa cancer after extensive radical resection and reported the results. VSP was used to construct a 3D model from CT images, which was used to accurately assess the margin of radical surgical resection, as well as to develop individually based reconstruction of soft tissue defects. Next, we reported a series of cases of patients with oral cancer of various locations, who, after radical surgery, underwent reconstruction with using of VSP (n=7) or conventional reconstruction (n=10). A comparative analysis of intra and postoperative results was carried out.
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Аберрантное метилирование промоторных участков генов - основное эпигенетическое изменение, характеризующее колоректальные неопластические образования. В настоящей работе был исследован количественный уровень метилирования 42 CpG-сайтов промоторных участков генов MGMT, APC и CDH13 в опухолях толстой кишки по отношению к уровню метилирования прилежащей условно нормальной ткани 25 пациентов. С помощью метода пиросеквенирования выявлено повышение уровня метилирования промоторных участков генов MGMT, APC и CDH13 в опухолевых образцах от 3 до 5 раз. В этих же образцах опухолей проведен скрининг активирующих SNP-мутаций в онкогенах KRAS (40 %), NRAS (0 %) и BRAF (0 %). Наличие SNP-мутаций в гене KRAS сопровождалось гиперметилированием одного или более промоторов исследованных генов. Доказана ассоциация этого эпигенетического показателя с метастазированием опухоли. Полученные данные об увеличении метилирования промоторных участков генов-онкосупрессоров могут быть использованы в качестве чувствительных прогностических маркеров прогрессирования и метастазирования колоректального рака.
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Статья научная
Найдены параметры линейно-квадратичной модели для нейтронной терапии. На этой основе проведено сравнение значений однократных терапевтических доз в нейтронной терапии, рассчитанных по модели время - доза - фракционирование и по линейноквадратичной модели. Установлено, что результаты расчета хорошо согласуются между собой. Также проведено сравнение степени расхождения результатов расчета по модели время - доза - фракционирование и по линейно-квадратичной модели в нейтронной и гамма-терапии. Показано, что применение линейно-квадратичной модели, разработанной для нейтронной терапии, способно обеспечить адекватный контроль за лучевыми реакциями облучаемых тканей.
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Статья научная
Цель. Изучение уровня адипокинов сыворотки крови, экспрессии AdipoR1, AdipoR2 и sOb-R у больных раком ободочной кишки в зависимости от клинико-морфологических параметров и наличия метаболического синдрома (МС). Материал и методы. В исследование включен 31 больной раком ободочной кишки I-III стадий с МС и без метаболических нарушений. Сывороточный уровень лептина, адипонектина, AdipoR1, AdipoR2 и растворимой формы рецептора лептина оценивался с помощью ELISA. Результаты и заключение. Частота МС у больных раком ободочной кишки составила 71 %. Выявлены взаимосвязи уровня лептина сыворотки крови с полом и стадией заболевания. Показана тенденция к повышению лептина у больных с МС. Уровень sOb-R был выше у больных без МС. Уровень AdipoR1 и AdipoR2 был значимо выше у больных раком ободочной кишки женского пола. Имелась тенденция к повышению рецепторов адипонектина у больных раком ободочной кишки с наличием МС.
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