Статьи журнала - Сибирский онкологический журнал
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Статья научная
Цель исследования - оценить особенности взаимосвязи атипичных/гибридных форм EpCAM+CD45+ клеток в асцитической жидкости у больных новообразованиями яичников с уровнем онкомаркеров СА125, HE4 и степенью злокачественности опухоли. Материал и методы. В клиническое исследование NCT04817501 включены 48 больных с впервые диагностированными новообразованиями яичников, из которых 42 пациентки с впервые диагностированным раком яичников Ic-IV стадии по FIGO, а также 6 женщин с пограничными новообразованиями яичников (ПОЯ), в возрасте от 36 до 76 лет. Материалом для исследования служили образцы асцитической жидкости и венозной стабилизированной крови. Наличие атипичных/гибридных форм EpCAM+CD45+ клеток в асцитической жидкости определяли методом многоцветной проточной цитометрии. Уровень онкомаркеров СА125 и HE4 в сыворотке крови определяли методом ИФА. Результаты. Количество EpCAM+CD45+ клеток в асцитической жидкости больных серозной карциномой яичников составило 1,02 (0,30; 2,68) клеток/мкл, при этом в группе больных Low-grade серозной карциномы яичников (LGSC) их уровень составил 0,55 (0,03; 4,51) клеток/мкл, а в группе High-grade (HGSC) - 1,36 (0,41; 2,68) клеток/мкл. Показано, что количество EpCAM+CD45+ клеток в асцитической жидкости у больных с новообразованиями яичников имеет прямую корреляционную связь с уровнем CA125 и HE4 в сыворотке крови (R=0,60; р function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Early and long-term outcomes of liver resections: a single specialized center experience
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The purpose of the study was to evaluate the outcomes of a series of liver resections performed in a single regional specialized cancer center. Material and Methods. Eighty-nine patients underwent liver and/ or extrahepatic bile duct resections in the Penza Regional Oncology Hospital over the 8-year study period. Malignancies were observed in 81 patients. Extended liver resections (4 segments or more) were performed in 58 (65.2 %) cases. Results. Postsurgical morbidity and mortality rates were 31.5 % (28 of 89) and 6.7 % (6 of 89), respectively. Six of 10 patients with primary liver carcinomas were alive without evidence of disease progression at a follow-up time ranged from 1.0 to 76.7 months. Adjuvant chemotherapy (ACT) was the only predictor (HR=0.40; 95 % CI 0.16-0.98) of overall survival in patients with metastatic colorectal cancer (mCRC). The median survival time after liver resections for mCRC with or without ACT was 54.5 (95 % CI: 14.5-94.5) vs 21.8 months (95 % CI: 14.2-29.4), respectively. In mCRC patients with ACT, the 5-year overall survival rate was 44.8 ± 12.9 %. Conclusion. Primary hepatobiliary carcinomas and colorectal cancer liver metastases are the most common reasons for liver resections. A series of liver resections in a low-volume hospital is feasible with the achievement of good outcomes.
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Efficacy of overnight intubation in oral oncological surgeries a retrospective study
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Objective. In the post-operative period of maxillofacial oncological operations, tracheostomy is the most commonly used method for securing the airway. These untoward complications made practitioners choose alternative modalities like submental intubation, but literature support on alternatives to tracheostomy for oral oncologic cases is limited. The aim of this observational study is to ascertain whether the use of overnight intubation is a safer and cost-effective practice and if it can be considered an alternative to tracheostomy. material and methods. 30 patients, 23 males and 7 females in the age group of 34-80 years who underwent treatment for head and neck cancer with major intraoral resection and a unilateral or bilateral neck dissection were included in the study. The following variables were recorded: age, sex, site of tumour, type of neck dissection, use of mandibulotomy/ mandibulectomy, type of reconstruction, duration of stay in ICU, mean hospital stay and Mallampati classification. Postoperative complications, associated with the airway, if any, were recorded simultaneously. results. None of the 30 patients required re-intubation nor did they develop any respiratory distress post extubation. conclusion. The purpose of this study is to raise the conscience of every surgeon to cogitate his/her choice of procedure for his/her patients and advocate the use of overnight intubation, as it is a virtuous alternative to tracheostomy.
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Статья научная
The purpose of the study was to analyze the ability of five antitumor drugs from the pharmaceutical group of protein kinase inhibitors (gefitinib, imatinib, pazopanib, ponatinib and enzastaurin) to reactivate the expression of the epigenetically silenced GFP in HeLa TI cells, and to estimate the effect of epigenetically active drugs on: 1) acetylation and methylation of histones H3 and H4; 2) integral DNA methylation; 3) activity of HAT and HDAC1 enzymes; 4) expression levels of the genes encoding epigenetic regulation enzymes (DNMT1, DNMT3A, DNMT3B; SIRT1, HDAC1; SETD1A, SETD1B, SUV420H1, SUV420H2, SUV39H1, SUV39H2). Material and Methods. The epigenetic activity of antitumor drugs was determined using the HeLa TI test system, a population of HeLa cells with the retroviral vector containing the epigenetically silenced GFP. The level of integral DNA methylation was analyzed using MspI/HpaII methyl-sensitive restriction analysis. Histone modifications were analyzed by Western blotting with antibodies to acetylated and methylated histones H3 and H4. The total activity of HAT enzymes was analyzed using Histone Acetyltransferase Activity Assay Kit. Expression of the epigenetic enzyme genes was analyzed using real-time quantitative RT-PCR. Results. It was shown that only the enzyme inhibitor Cp protein kinase enzastaurin had the ability to reactivate the expression of epigenetically silenced GFP in the HeLa TI cells. We showed that under the action of enzastaurin, the level of integral DNA methylation and expression of DNMT3A and DNMT3B DNA methyltransferase genes decreased. It was also found that enzastaurin reduced the expression levels of histone deacetylases HDAC1 and SIRT1, but did not affect the activity and expression levels of histone acetylases, the level of histone methylation (H3K4me3, H3K9me3, H3K27me3, H4K20me3), and the level of expression of the histone methyltransferases (SUV39H1, SUV39H2, SUV420H1, SUV420H2, SETD1A и SETD1B). Conclusion. The data obtained are important for clarifying the mechanisms of action of 5 protein kinase inhibitors, in particular with respect to enzastaurin, the protein kinase Cp inhibitor, for which the ability to reactivate epigenetically silent genes due to the effect on DNA methylation and histone acetylation was demonstrated.
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Evaluation of biopsychosocial model for pain management in post-oral cancer therapy patients
Статья научная
Background. Approximately 50 % of cancer patients have pain in their daily lives, which is multifaceted sensation goes beyond basic biochemical signal of pain. Oral mucositis is one of the negative consequences with intense pain, discomfort, challenges in speaking and eating. These components collectively influence patient's total quality of life across mental, biological, social aspects. Biopsychosocial model (BPS) is an effective technique for understanding and addressing conceptualization and treatment of pain in cancer patients. The aim of this study is to assess efficacy of the BPS in managing post-cancer distress and potential to improve quality of life for individuals with cancer. Material and Methods. This study evaluated 30 cancer patients who completed radiotherapy and were referred from cancer hospital. The examination encompasses three distinct categories: biological, psychological, and social components. The biological aspect was documented based on mucosal lesions and VAS scores for individuals; followed by photo-biomodulation was given. Palliative care was provided in psychological aspect through implementation of exercise, meditation, music therapy. The social component encompasses community engagement, social activities, counseling services for family members. Patients were categorized into 3 groups - A, B, C. All three components were carefully evaluated and one-month follow-up was done.
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Evaluation of cell death after thermal ablation in patients with bone tumors
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Introduction. Bone tumors are heterogeneous group of skeletal neoplasms characterized by frequent recurrences, aggressive clinical course and low survival rates. The development of new treatment methods continues to pose pressing challenges. Radical intraoperative thermal ablation (RIT) using high-temperature exposure is emerging as a new and promising strategy for organ-preserving treatment. This study focuses on the effect of thermal ablation (TA) on tumors. Objective of the Study to assess the impact of TA (using the RIT method) on the viability of tumor cells. Material and Methods. The study included 8 patients with bone tumors. Tumors underwent TA at a temperature of 60 °C for 30 minutes ex vivo. Apoptosis was studied in tumor tissue samples before and after TA. Apoptosis was assessed using two methods: flow cytometry and the TUNEL assay. Results. The TA procedure developed by our scientific group represents a promising organ-preserving approach for treating malignant bone tumors. A temperature regime of 60 °C for 30 minutes was effective in initiating tumor cells death. This was confirmed by two independent methods – flow cytometry and TUNEL assay – which demonstrated a significant increase in the number of apoptotic cells immediately following the procedure and a notable rise in the number of cells exhibiting signs of late apoptosis one hour post thermal ablation. Therefore, the collected data confirm a pronounced antitumor effect immediately after implementing RIT. Conclusion. The findings confirm that RIT is a viable organ-preserving method for treating bone tumors, meriting further investigation to expand its application in clinical practice.
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Статья научная
Background. Esophageal cancer is the eighth most common cancer in the world. The antitumor effects of medicinal plants have been shown as a therapeutic strategy to treat esophageal cancer. This study aimed to evaluate in vitro effects of Cuscuta epithymum extract on the survival and apoptosis of esophageal cancer cell line. Material and Methods. Here, the hydroalcoholic Soxhlet extract of C. epithymum plant was prepared. The cell viability of esophageal cancer cell line KYSE-30 was evaluated by MTT assay after 24 h treatment with concentrations of 50, 100, 200, 400, 600, 800 and 1000 μg/ml of the extract. Then, the apoptotic effect of extract was evaluated by flow cytometry using Propidium Iodide (PI) staining and sub-G1 peak analysis, and Annexin V-FITC/PI staining in cells treated with concentrations of 125, 250, 500 and 750 μg/ml as well as morphological change of healthy cells to apoptotic and necrotic form.
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Expression Profiles of CYP1A1 and CYP1B1 Enzymes in Non-Small Cell Lung Cancer of Turkish Patients
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Background. The cytochrome P450 enzymes CYP1A1 and CYP1B1 are involved in the metabolism of carcinogens and have been linked to various cancers, including lung cancer, primarily through their overexpression in tumor tissues. Aim of study. This study describes the CYP1A1 and CYP1B1 expression profiles in lung adenocarcinoma (AC) and lung squamous cell carcinoma (SCC), and explores the possible associations with demographic and clinical features among Turkish patients. Material and Methods. This retrospective study analyzed clinical data from 40 patients with lung adenocarcinoma and lung squamous cell carcinoma. Tumor and adjacent healthy tissue samples were immunohistochemically stained to profile CYP1A1 and CYP1B1 expression. Associations between protein expression levels and patient characteristics were examined.
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Статья научная
Introduction. The esophagus cancer patients needs early diagnosis to achieve better prognosis. The delay barriers increase progression of diseases to higher stages. The aim of work was to identify and explore the barriers in diagnosis of esophagus cancer and chart the time duration in this process. Material and Methods. The study was conducted in Jinnah Hospital Lahore (JHL), a teaching care hospital of Allama Iqbal Medical College, during a period of one year from July 2019 to July 2020. There were 49.42 % female and 50.57 % male patients.
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Feasibility of simultaneous integrated boost for high-dose treatment of high-risk prostate cancer
Статья научная
Background. Radiation therapy for high-risk prostate cancer presents a challenge for cancer radiotherapists. The improvement of treatment outcomes is associated with radiation dose escalation and prophylactic irradiation of lymph nodes, therefore, the development of the new treatment schemes is needed. Simultaneous integrated boost technique based on the volumetric modulated arc therapy is the most efficient treatment option. Material and Methods. The anatomical data of 10 patients with high-risk prostate cancer was used for dosimetry-based treatment planning. Both simultaneous integrated boost and sequential boost technique were considered. The treatment planning goal was to deliver the equivalent dose of 96 Gy at 2 Gy per fraction (EQD2=96 Gy) (α/β=1.5 Gy) to the prostate, EQD2=62.5 Gy to the seminal vesicles and EQD2=50 Gy to lymph nodes avoiding damaging the organs at risk, mainly the bladder and rectum. The irradiation was based on volumetric modulated arc therapy with two partially coplanar arcs and two rotations at each arc. The obtained dose distributions were compared with respect to dose-volume histograms and equivalent uniform doses (EUD). Results. In the case of sequential boost, the minimal dose delivered to the prostate was equal to2cc95.9 ± 2.1 Gy, EUD=104.9 ± 1.7 Gy. The dose delivered to 2 cm3 ( D ) bladder was 97.4 ± 2.0 Gy. Normal tissue2cccomplication probability (NTCP) was 1.64 %. The dose delivered to 2 cm3 ( D ) rectum was 103.4 ± 9.2 Gyand NTCP was 27.4 %. In the case of simultaneous integrated boost, the minimal dose delivered to the prostate was equal to 90 . 4 ± 2 . 3 Gy, EUD= 103 . 9 ± 1 . 3 Gy. The bladder dose was as high as D 2cc = 96 . 1 ± 5 . 2 Gy, NTCP= 0 . 176 ± 0 . 132 %, the rectum dose - D 2cc = 81 . 1 ± 6 . 0 Gy, NTCP= 2 . 34 ± 1 . 92 %. Conclusion. Volumetric modulated arc therapy along with simultaneous integrated boost have shown the feasibility of simultaneous irradiation of the prostate, seminal vesicles and lymph nodes up to the prescribed dose values without significant over irradiation of the organs at risk (OARs). Dose values in the tumor as high as EUD= 103 . 9 ± 1 . 3 Gy along with prophylactic irradiation of lymph nodes may result in higher tumor control probability value and should be considered for clinical trials.
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Статья научная
Background. Subungual squamous cell carcinoma (SCC) of thumb is a rare disease. However, it is the most common malignancy affecting the nail bed. Early recognition is crucial and important for prompt diagnosis and effective treatment. Often this tumour needs to be treated surgically with wide local resection, which results in a defect in the thumb. If not handled appropriately, such defects render restriction in functionality of the involved thumb as well as a poor aesthetic outcome. In the worst-case scenario, it may result in a poor function of involved hand. Thus, reconstruction of the involved thumb is necessary. The main aim of reconstruction is to regain the hands’ function and preserved the thumbs’ sensation. Secondarily, to have an aesthetically pleasing hand. Our hands carry out delegate job and important duty for daily function. Especially, the thumb working together with the other fingers to carry out the hand function as one unit. Loss of thumb function affects the whole performance of the hand. Case descriptions. We report a case of recurrent subungual squamous cell carcinoma of thumb, which had wide local resection and subsequently underwent soft tissue coverage with an islanded first dorsal metacarpal artery (FDMA) perforator flap. One month after surgery, the patient was able to regain a good functional outcome of the hand. In this report, we discussed the procedures that had been done. Conclusion. The patient regained full functional hand after reconstruction with preserved sensation over distal thumb. The aesthetic outcome is satisfactory. The FDMA perforator flap is a very pliable and robust flap for reconstruction of distal thumb defect.
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Статья научная
Introduction. Radiation therapy (RT) has been widely used since the 1970s in the treatment of Hodgkin’s lymphoma. RT increases the risk of secondary malignancies and heart disease including coronary artery disease, noncoronary atherosclerotic valvular disease, valvular dysfunction, pericardial disease and radiation induced vasculopathy. Case Presentation. We describe a case of a patient with 4 secondary malignancies due to previous RT including parotid mucoepidermoid carcinoma, breast multicentric infiltrating ducta, thyroid papillary microcarcinoma with follicular pattern and lung adenocarcinoma that later presented with severe constrictive pericarditis, which led to an emergency pericardiectomy - all of these were complications of her previous radiotherapy. She received a prompt diagnosis and treatment. Discussion. Radiation-induced vascular disease (RIVD) occurs due to endothelial injury following RT; patients have up to 3-4 fold increase in risk of myocardial infarction due to CAD, therefore screening of CAD with a CT coronary angiography is recommended to begin 5 years after receiving RT in patients 45 and older and 10 years after RT in patients
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Статья научная
Introduction. Chemotherapy remains a cornerstone treatment for most non-Hodgkin lymphoma (NHL) patients, yet it is frequently associated with significant adverse effects that compromise their quality of life. Emerging evidence highlights that genetic factors, particularly single nucleotide polymorphisms (SNPs), play a critical role in determining individual variability in treatment responses and susceptibility to drug-related complications. Aim of this study: to identify SNPs associated with chemotherapy-induced adverse events in NHL through advanced bioinformatics approaches, enabling personalized therapeutic strategies to mitigate risks. Material abd Methods. This study leveraged the PharmGKB database to identify SNPs associated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. SNPs meeting inclusion criteria (Level of Evidence 1A-3, p<0.01) were prioritized for functional impact analysis using PolyPhen-2 scores. Data extraction and computational analysis utilized SNPnexus, HaploReg v4.2, Ensembl Genome Browser (GRCh37), and PharmGKB. The methodology employed a descriptive approach, relying exclusively on secondary data sources. Results. This study identified 11 SNPs that may be important for hematological toxicity, liver damage, and nausea risk. These genes are SLC22A16, GSTP1, NAT2, ATM, ABCB1, CYP2B6, XRCC1, ERCC1, MUTYH PIK3R2, and PNPLA3. In terms of priority and risk, the most significant variants were rs738409 (PNPLA3), rs12210538 (SLC22A16), rs2229109 (ABCB1), and rs56022120 (PIK3R2). The distribution of SNP alleles is more common in European populations than in Asians or Africans. Conclusion. For the first time, we found SNPs that indicate an increase in drug side effects. These SNPs rs738409, rs12210538, rs2229109 and rs56022120 increase the severity of NHL patients during chemotherapy. In order to ensure that these biomarkers can be used in clinical practice and to support the creation of precision medicine strategies, additional clinical validation is needed.
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Giant foam-like macrophages in advanced ovarian cancer
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Introduction. Ovarian cancer (OC) is the third most common gynecological cancer with the worst prognosis and highest mortality rate. The progression of OC can be accompanied by the detrimental functions of the components of the tumor microenvironment, including tumor-associated macrophages (TAMs). The purpose of the study to analyze distribution and morphological phenotype of TAMs in tumor tissue of patients with high-grade serous ovarian cancer (HGSOC). Material and Methods. Formalin fixed paraffin embedded tissue sections were obtained from ovarian cancer patients after tumor resection. The protein expression of general macrophage marker CD68 and M2-like markers CD206, CD163 and stabilin-1, belonging to scavenger receptors, was analysed by immunohistochemical staining in tumor tissue. Histological assessment of TAM distribution was performed by pathologist. Immunofluorescent analysis/confocal microscopy was applied to establish the co-expression of CD68 with the main macrophage scavenger receptors. Results. We were able to find giant CD68-positive macrophages with foamy cytoplasm in ovarian tumor tissue. The accumulation of these TAMs was specific only for patients with advanced stage (IIIC and IV stages). The presence of foam-like TAMs had a statistical tendency to be associated with ovarian cancer progression, including metastasis and recurrence. The distribution of stabilin-1-positive macrophages was matched to CD68 expression in almost all cases, as was shown by IHC. Confocal microscopy confirmed that stabilin-1 was expressed in at least 50 % of giant TAMs. IF analysis of tumor samples also demonstrated co-expression of other scavenger receptors, CD163 and CD36, in foam-like cells. Similar to IHC, in most samples the expression of CD206 in TAMs of foam-like morphology was limited. Conclusion. For the first time we demonstrated the accumulation of giant macrophages with fluffy foam cytoplasm in the tumor tissue of treated patients with advanced ovarian cancer. Such macrophages express diverse scavenger receptors (stabilin-1, CD163, CD36), thus indicating a high clearance activity of giant TAMs.
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Статья научная
Актуальность. Дефицит гомологичной рекомбинации (HRD) - это важный предиктивный маркер эффективности препаратов платины и ингибиторов поли (АДФ-рибоза)-полимеразы (PARP). Наследственные или соматические мутации генов BRCA1 или BRCA2 являются наиболее частой причиной HRD в карциномах яичника . Однако в некоторых случаях у носителей патогенных наследственных мутаций BRCA1/2 в опухоли сохраняется нормальная копия соответствующего гена и фенотип HRD не формируется. Цель исследования - описание морфологического и молекулярного портрета карциномы яичника высокой степени злокачественности у пациентки с наследственной мутацией BRCA2, не демонстрирующей дефицита гомологичной репарации ДНК. Описание клинического случая. Представлено наблюдение пациентки, 48 лет, с синхронными первично-множественными злокачественными новообразованиями: high-grade карциномой яичника и колоректальной аденокарциномой. У пациентки выявлен известный патогенный вариант BRCA2 c.658_659delGT [rs80359604]. Учитывая неопределенный гистологический вариант низкодифференцированной карциномы, а именно, отсутствие экспрессии маркеров серозной или эндометриоидной дифференцировки, а также высокую экспрессию HER2, выполнено дополнительное молекулярное исследование метастатических очагов в лимфатические узлы. Обнаружено, что в данной опухоли профиль хромосомной нестабильности не соответствует HRD и наблюдается делеция мутантного аллеля BRCA2, что исключает BRCA-подобный фенотип.
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Hereditary diffuse gastric cancer: genetic aspects and prophylactic total gastrectomy
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For patients with an identified germline E-cadherin-1 ( CDH1 ) mutation, prophylactic gastrectomy is the treatment of choice to eliminate the high risk of developing diffuse gastric cancer. The case report describes a rare case of hereditary diffuse gastric cancer (HDgC) associated with CDH1 gene mutation, which is reported in the Russian population for the first time. In 2013, a 28-year-old woman was referred to Clinical Oncogenetics Laboratory with a family history of gastric cancer. Molecular genetic analysis revealed CDH1 gene mutation. The lifetime risk of cancer in mutation positive members is more than 80. Histological examination of gastric biopsy specimens obtained during endoscopy revealed isolated signet ring cells in the lamina propria. Spleen-preserving D2-lymphodissection and total gastrectomy with Roux-en-Y reconstruction with a jejunal reservoir formation were performed at the Abdominal Oncology Surgery Department.
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IFN-индуцированные дендритные клетки у больных множественной миеломой
Статья научная
Проведено сравнительное исследование фенотипических и функциональных свойств дендритных клеток (ДК), генери- рованных in vitro в присутствии GM-CSF и IFN-α, у здоровых доноров (n=34) и больных множественной миеломой (n=12). Показано, что по своему составу (количеству зрелых/незрелых ДК и клеток промежуточной степени зрелости) популяция ДК больных в целом была сопоставима с ДК здоровых доноров. ДК больных множественной миеломой (ММ) не отличались от ДК доноров по уровню продукции IFN-γ и TNF-α. В то же время ДК больных характеризовались более низким содержанием активированных CD25+клеток в сочетании с повышенной продукцией IL-10, что, по-видимому, обусловливало ослабление их стимуляторной активности в СКЛ. Тем не менее ДК больных ММ сохраняли свою способность к запуску Th1-ответа, что проявлялось 5-кратным увеличением количества CD3+IFN-γ+ Т-клеток. Полученные данные аргументируют возмож- ность клинического применения ДК у больных ММ в качестве клеточных вакцин (особенно в сочетании с адъювантной цитокинотерапией) с целью повышения эффективности противоопухолевого иммунного ответа.
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