Experimental oncology最新文献

Background: Radiation-induced dermatitis impairs the quality of life of cancer patients and may lead to the need of interrupting radiotherapy. The grade of dermatitis is subjectively assessed by the visual examination. There is an urgent need for both objective and quantitative methods for assessing the current grade of dermatitis and predicting its severity at an early stage of radiotherapy.

Aim: The aim of the study was to evaluate the advantages and limitations of infrared thermography for monitoring the current level of radiation-induced dermatitis and predicting its severity by quantitative analysis of the thermal field dynamics in the irradiated zone.

Materials and methods: 30 adult patients were examined by infrared thermography during the course of 2D conventional radiotherapy for malignant tumors of various types and localizations. Our approach for quantifying the thermal field caused by dermatitis alone was applied. A statistical (correlation and ROC) analysis was performed.

Results: Dermatitis of varying severity was observed in 100% of the patients studied. The dynamics in the intensity of the anomalous thermal fields in the irradiated zone correlated with the dynamics of dermatitis grades, excluding the case of a radiosensitive tumor (correlation coefficient 0.74÷0.84). It was found that the maximum toxicity (dermatitis grade ≥ 3) develops in patients who how significant hyperthermia in the area of interest (≥ 0.7 °C) at an early stage of radiotherapy. The ROC analysis demonstrated the "good quality" of the prognosis method (AUC = 0.871).

Conclusions: The non-invasive and cheap infrared thermography is a suitable tool for objective quantitative monitoring the current dermatitis grade during radiotherapy as well as predicting its severity for any tumor location.

Background: The development of human breast cancer (BC) is known to be closely related to disturbances in the mammary gland microbiota. Bacteria of the genus Bifidobacterium are an important component of normal breast microbiota and exert antitumor activity. The molecular-biological mechanisms of interaction between BC cells and microbiota members remain poorly studied yet. The aim of this study was to develop and optimize an experimental model system for the co-cultivation of BC cells with Bifidobacterium animalis in vitro.

Materials and methods: Human ВС cells of the MCF-7, T47D, and MDA-MB-231 lines, as well as live and heat-inactivated bacteria of Bifidobacterium animalis subsp. lactis (B. animalis) were used as research objects. The growth kinetics and viability of B. animalis in the presence of different ВС cell lines and without them were determined by both the turbidimetry method and seeding on an elective nutrient medium. Glucose consumption and lactate production by bifidobacteria were assessed by biochemical methods. The viability of BC cells was determined by a standard colorimetric method.

Results: The growth kinetics of B. animalis in the complete DMEM nutrient medium showed standard patterns. The indicators of glucose consumption and lactate production of B. animalis confirm its physiological metabolic activity under the growth conditions. The presence of BC cells in the model system did not affect the duration of the growth phases of the B. animalis cells' population but contributed to the increase in their counts. A significant decrease in the number of live BC cells of all studied lines was observed only after 48 h of co-cultivation with live B. animalis. To achieve similar suppression of the BC cell viability, 10-30-fold higher counts of heatinactivated bacteria were required compared to live ones.

Conclusions: The optimal conditions for co-cultivation of human BC cells and living B. animalis cells in vitro have been identified.

Background: In the last decades, the incidence of breast cancer (BCa) in young women has been increasing steadily. The quantitative indicators of expression of collagen, which play important role in stromal microenvironment, and their association with the age and survival rates of BCa patients have not been yet definitively clarified.

Aim: To investigate the relationship between the COL1A1 gene expression at the mRNA and protein levels in BCa tissue and the clinicopatological features and survival rates of BCa patients of different age groups.

Materials and methods: The study was conducted on the clinical material of 50 patients with stage I-III BCa. COL1A1 gene expression at the mRNA and protein levels in BCa tissue were studied using the real-time PCR and immunohistochemical methods, as well as the bioinformatic analysis (UALCAN and Kaplan - Meier Plotter databases).

Results: The bioinformatic analysis showed that BCa tissue is characterized by 6.0 times (p < 0.05) higher level of COL1A1 mRNA compared to normal breast tissue. The correlation of COL1A1 expression at the mRNA and protein levels with the molecular subtype of neoplasms was demonstrated. According to Kaplan - Meier Plotter database, a low level of expression of COL1A1 protein level in BCa tissue is associated with lower rates of relapse-free survival of patients. The ex vivo study of the clinical material revealed a decrease in COL1A1 protein expression in tumor tissue of young patients with BCa of T3 category (p < 0.0374), low differentiation grade (p < 0.0163) and basal molecular subtype (p < 0.0001). A correlation between the expression of COL1A1 at the mRNA and protein levels and the expression status of estrogen receptors (p < 0.0001) and progesterone receptors (p < 0.0040) was established. The relapse-free 3-year survival rate of young BCa patients is significantly lower in the presence of a low COL1A1 optical density index in the tumor tissue.

Conclusions: The identified relationship between COL1A1 expression and such indicators of BCa malignancy as tumor size, differentiation grade, molecular subtype, receptor status, and the recurrencefree survival of patients indicates the prospects of its use to predict the aggressiveness of the BCa course in young patients.

Background: In children, osteosarcoma (OS), Ewing's sarcoma (ES), and rhabdomyosarcoma (RMS) are the most common sarcomas. A link between the anti-programmed death ligand-1 PD-L1 and the tumor suppressor phosphatase and tensin homologue (PTEN) expression has been described in many tumors. The aim of this work is to determine clinicopathological relationships and the possible prognostic significance of PD-L1 and PTEN expression in rhabdomyosarcoma (RMS), Ewing's sarcoma (ES), and osteosarcoma (OS).

Materials and methods: Expression of PD-L1 and PTEN were examined by immunohistochemistry in 45 archival RMS, ES, and OS cases.

Results: The positive expression of PD-L1 was found in 16.7% and 31.6% of ES and OS, respectively. The negative PD-L1 was related to a substantially longer survival in ES cases (p = 0.045), but positive PD-L1 expression was significantly associated with the increased tumor stage and vascular invasion in the OS cases (p = 0.005 and p = 0.002), respectively. On the other hand, PTEN loss was strongly associated with deep tumor, high tumor grade, and recurrence in RMS (p = 0.002, p = 0.045, and p = 0.026, respectively). However, PTEN loss was significantly absent in ES as tumor grade increased (p = 0.031). It is noteworthy that tumor recurrence, the loss of PTEN, and positive PD-L1 were all considered predictive factors in OS patients (p = 0.045, p = 0.032, and p = 0.02, respectively).

Conclusions: In children, OS and ES have positive PD-L1 expression, which has an independent unfavorable prognostic effect and raises the possibility of using PD-L1 as a therapeutic target. OS, ES, and RMS prognosis are all predicted by PTEN loss.

To the Editor, Head and neck squamous cell carcinoma (HN- SCC) accounts for about 600,000 new cases globally every year and stands the sixth most common cancer, arising from the squamous epithelium. It is localized in the head and neck area involving oral cavity, pharynx, and larynx. Despite the rigorous therapy, the 5-year overall survival remains poor in HNSCC and has not changed appreciably in the last 30 years. The majority of patients develop resistance to chemotherapeutic agents, and cancer progression occurs. Cetuximab, which targets the epidermal growth factor receptor, and pembrolizumab, an anti-programmed-death ligand 1 antibody, are among few FDA-approved medications. Current therapies are poor and cause severe long-term toxicity, which has a long-term impact on the quality of life [1].......

The clinical case of a patient with multicentric breast cancer who underwent organ-sparing surgery after neoadjuvant chemo-radiation therapy is presented. An ipsilateral cancer recurrence was diagnosed 8 years after the first operation. The repeated organ-sparing surgery (lumpectomy) was done with a good cosmetic result and without disease progression during 1-year follow-up. The literature review shows that neoadjuvant systemic therapy accounting for molecular subtypes of cancer has radically changed breast cancer surgeries. The evolution of surgical approaches in stage I-II breast cancer patients consists in the de-escalation of surgery from mastectomy to organsparing or oncoplastic surgery, minimally directed surgery, and repeated breast-conserving surgery. De-escalation of surgical interventions in the area of the regional lymphatic collector consists in the transition from total axillary lymphatic dissection to sentinel lymph node biopsy or targeted removal of metastatic lymph nodes. The repeated breast-conserving surgery can be safely performed for ipsilateral recurrence in patients with all molecular subtypes of breast cancer.

Aim: To evaluate the effect of B. subtilis IMV B-7724 lectin on the functional activity of macrophages (Mph), natural killer (NK) cells and cytotoxic lymphocytes (CTL) of mice bearing Lewis lung carcinoma (LLC).

Materials and methods: The studies were performed on C57Bl/6J mice; LLC was used as an experimental transplantable tumor. The lectin from B. subtilis IMV B-7724 was administered to LLC-bearing mice subcutaneously at a dose of 1 mg/kg of body weight for 10 days. The immunological testing was performed on days 14, 21, and 28 after tumor grafting. The cytotoxic activity of Mph, NK, and CTL was estimated in MTT-assay; the content of the stable metabolites of nitric oxide (NO) was measured by a standard Griess reaction; the arginase activity (Arg) was determined based on the measurement of urea.

Results: The administration of the B. subtilis IMV B-7724 lectin to LLC-bearing mice exerted its antitumor and antimetastatic effects partially via a significant (p < 0.05) increase of Mph and NK activities after the completion of the treatment. In the group of animals injected with lectin, the NO/Arg ratio increased significantly, indicating the prevalence of Mph with proinflammatory and antitumor properties. The cytotoxic activity of Mph exceeded the indices of untreated mice and intact control by 1.8 times and 5.3 times respectively; of NK - by 2.8 and 1.3 times respectively. The effect of treatment on the CTL activity was less pronounced.

Conclusion: Antitumor and antimetastatic activity of the lectin from B. subtilis IMV B-7724 ensured the preservation of the cytotoxic activity of the main effectors of antitumor immunity (Mph, NK, and CTL) throughout LLC growth.

Background: Glioblastoma (GBM) is the most frequent primary malignant CNS tumor. Deficient mismatch repair (dMMR) is associated with better prognosis and is a biomarker for immunotherapy. Evaluation of MMR by immunohistochemistry (IHC) is accessible, cost effective, sensitive, and specific.

Aim: Our objective was to investigate MMR proteins in adult GBM patients.

Materials and methods: We retrospectively analyzed 68 GBM samples to evaluate the proficiency of MMR genes expression assessed by IHC. Clinicopathologic and molecular features were compared in proficient (pMMR) or dMMR.

Results: 10 (14.7%) samples showed dMMR, and the most frequent was MSH6 (100%) followed by MSH2, PMS2, and MLH1. We observed heterogeneous expression of dMMR in 5 GBMs. The median overall survival did not differ between pMMR (19.8 months; 0.2-30) and dMMR (16.9 months; 6.4-27.5) (p = 0.31). We observed a significantly higher overall survival associated with gross total resection compared to subtotal resection or biopsy (30.7 vs. 13.6 months, p = 0.02) and MGMT methylated status (29.6 vs. 19.8 months, p = 0.049). At the analysis time, 10 patients were still alive, all in the pMMR group.

Conclusions: Our data demonstrated dMMR phenotype assessed by IHC in an expressive portion of GBM patients, however without significant impact on overall survival.

This article briefly summarizes our long-term experience of research in the field of experimental and clinical radiation oncology unified by the key word "radiosensitivity". Consistently presented and interpreted here are the main results on biodosimetry of irradiation depending on doses and quality of ionizing radiation and determination of individual radiosensitivity of cancer patients. We justified the use of radiomitigators to reduce the frequency and severity of post-radiation complications in cancer patients, and for radiation protection of the general population. The radioprotective effect of the antioxidant inosine in the somatic cells of cancer patients in the range of low radiation doses was demonstrated. We established that in persons who are hypersensitive to irradiation, the reparative potential is reduced by about 60% compared to ones with normal indices of individual radiosensitivity. Cytogenetic predictors of radiosensitivity of healthy cells adjacent to the irradiated tumor have been determined. Unfortunately, they have not yet become a point of application for individual planning of irradiation courses and assessment of severity of post-radiation complications. The intensive development of selective radioprotectors that would selectively protect healthy tissues in the course of radiation therapy, reducing their radiosensitivity by activating reparation processes, is considered a priority direction of modern radiation oncology.

Background: Disseminated peritoneal leiomyomatosis (DPL) is an extremely rare benign disease characterized by widespread lesions of the abdominal cavity, pelvis, and retroperitoneal space with tumor nodules of varying size and number, which are benign neoplasms consisting of smooth muscle fibers in their histological structure.

Aim: To analyze clinical cases of DPL with a concise review of the current state of the DPL diagnosis and treatment.

Materials and methods: We analyzed 5 clinical cases of DPL of female patients aged 39-50 years (mean age 46.2 years) who underwent surgical treatment at the National Cancer Institute from 2010 to 2021. In all 5 patients, the diagnosis of DPL (8898/1) was verified according to pathological (using routine hematoxylin/eosin staining) and immunohistochemical (IHC) studies.

Results: All patients underwent surgical treatment with a laparotomy approach, the extent and radicality of which depended on the location and number of tumor lesions. At the time of follow-up, all 5 patients were alive and did not receive any special oncological treatment.

Conclusions: DPL is characterized by a variety of clinical manifestations from polyserositis to acute abdomen, depending on the location and size of the main tumor focus. IHC analysis is the criterion for the final diagnosis, and radical removal of all tumor foci provides the best therapeutic prognosis. The treatment should be carried out in highly specialized cancer centers where surgeons have gained sufficient experience in performing cytoreductive surgery.