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South Russian Journal of Cancer

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Vol 3, No 4 (2022)
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https://doi.org/10.37748/2686-9039-2022-3-4

ORIGINAL ARTICLES

6-13 500
Abstract

Purpose of the study. Improvement of surgical treatment outcomes in patients with advanced cancer of the tongue and the mouth floor providing radical surgery with preservation of the organ functions.

Materials and methods. Two patients with advanced cancer of the tongue and the mouth floor with metastases to lymph nodes in the neck (St.4 (IVA, рT4a N2b M0), clinical group 2, were operated on according to our special technique. The surgery was performed under endotracheal anesthesia. After cervical lymph node dissection, the tongue and the mouth floor tissues were resected intraorally. The incisions were made through their entire thickness along healthy tissues. Smears were taken from the dissected tissues for intraoperative pathology consultation control for the presence of cancer cells. The tissues of the mouth floor affected by the tumor were completely removed without going beyond the hyoglossus muscle, since the lingual and hypoglossal nerves go along its outer surface. This allowed radical tumor removal with preservation of the tongue functions.

Results. Patients operated on according to our special technique have been observed for more than 9 months without continued tumor growth and recurrences tumor with preservation of the tongue and the mouth floor functions.

Conclusion. In such patients, ablastics principles are combined with the preservation of the tongue functions. This can be achieved because after removal of the tongue tumor, resection of the mouth floor is performed without going beyond the hyoglossus muscle not affected by the tumor, since the lingual and hypoglossal nerves go along its outer surface. Complying with ablastics, it preserves the tongue functions: chewing, swallowing, articulate speech, taste perception.

14-25 467
Abstract

Purpose of the study. Testing of new chemotherapeutic agents in translational and biology medicine needs studies on immortalized cell lines. However, such models do not always have the biological properties of a tumor in situ, in contrast to primary cell cultures. Primary cultures of lung cancer cells have biological, morphological and molecular characteristics close or identical to tumor cells in vivo. Obtaining collections of primary lung cancer cell lines is an important task in creating various models for preclinical studies.

Materials and methods. The materials are represented by postoperative tumor samples obtained from 25 patients with newly diagnosed lung cancer without prior treatment. The following methods were used to obtain primary cultures: enzymatic dissociation in Hanks' solution with the addition of 300 units/ml collagenase I (Thermo Fisher Scientific, USA), enzymatic dissociation using the Brain Tumor Dissoсiation Kit (Miltenyi Biotec, Germany) and 150 units/ml. ml of collagenase I, as well as the method of explants. The following methods were used to remove fibroblasts: the use of the FibrOut™ system (CHI Scientific, USA), magnetic separation of fibroblasts using Anti-Fibroblast MicroBeads (Miltenyi Biotec, Germany), and cold trypsinization.

Results. We have obtained 15 primary lung cancer cell cultures that have passed the zero order passage. In this work, the method of enzymatic dissociation turned out to be the most effective. Incubation of lung tumor samples with collagenase for 1 hour preserves the viability and adhesiveness of the cells. The explant method did not show its effectiveness for long-term cultivation, there was no migration of tumor cells to plastic. Magnetic separation, as a method of removing stromal components of fibroblasts, showed the greatest efficiency, while maintaining the viability of tumor cells.

Conclusion. The obtained primary cell cultures of lung cancer can be used for many tasks of experimental oncology: studies of the biological characteristics of lung cancer, development of preclinical models for the studies on new chemotherapeutic drugs. 

26-39 486
Abstract

Purpose of the study. Was to analyze changes in pathophysiological parameters of transplantable tumor growth and functional activity of the hypothalamic-pituitary-thyroid axis (HPT) in rats of both sexes with Guerin's carcinoma in presence of induced hypothyroidism.

Materials and methods. The dynamics of tumor growth and average life span were assessed in white alley rats of both sexes with Guerins carcinoma transplanted subcutaneously on the background of thyreostatic induced hypothyroidism. RIA (radioimmune assay) and ELISA (enzyme-linked immunosorbent assay) methods were used to determine levels of thyroid hormones in the blood and thyroid and tumor samples, and thyrotropin-releasing hormone (TRH) in the hypothalamus, as well as TSH in the pituitary gland. The experiment included 2 control groups: animals of both sexes with hypothyroidism (control group 1, number of rodents = 15) and animals with subcutaneously transplanted Guerin's carcinoma without hypothyroidism (control group 2, number of rodents = 15).

Results. Hypothyroidism in female rats inhibited the tumor growth and improved median survival by 1.8 times (p < 0.05). No such effect was observed in males of the main group. Levels of regulatory peptides of the hypothalamus and pituitary gland declined in females of the main group, while levels of TSH in the pituitary gland in males increased, despite a decrease in TRH by 3.5 times. TSH levels decreased in the thyroid and blood of animals of both sexes; however, a decrease in levels of total and free circulating thyroxine (T4 and FT4) by 1.6 times and by 2.8 times was found in the tumor, respectively; samples of Guerin's carcinoma in males of the main group remained saturated with T4 and FT4 as well as and in control group rodents without induced hypothyroidism.

Conclusions. The gender differences in the pathophysiology of the tumor development in presence of hypothyroidism, as well as changes in the functional activity of the HPT axis in experimental animals revealed in this study can probably be associated with sex hormones, which requires further study of the hypothalamic-pituitary-gonadal (HPG) axis and steroid hormones in peripheral organs and tumor samples. 

40-48 356
Abstract

Purpose of the study. An analysis of changes in the expression of the VEGF neoangiogenic factor in the tumor tissue of patients with squamous cell carcinoma of the oral mucosa receiving targeted therapy with cetuximab and chemotherapy.

Patients and methods. We performed an immunohistochemical study of tumor samples obtained from 60 patients with squamous cell carcinoma of the oral mucosa T3-4N0-1M0. The main group comprised 30 patients who received therapy with cisplatin and fluoruracil plus cetuximab. The control group included 30 patients receiving standard chemotherapy without targeted therapy. Each group was divided into two subgroups with different treatment efficacy: patients sensitive to treatment (n = 17 in the group with cetuximab and n = 12 in the group without cetuximab) and resistant to treatment (n = 13 in the group with targeted therapy and n = 18 in the group with standard chemotherapy).

Results. Quantification of the VEGF expression demonstrated minimal numbers of vessels stained positively for this marker in the field of view in patients of the main group sensitive to chemotherapy and cetuximab. The value was 5.3 times lower than initial values, and 4.3 times lower than in the subgroup of patients resistant to the treatment (the data were statistically significant, р = 0.0132 and р = 0.0455, respectively). In the control group, patients who were sensitive to the treatment showed 1.4 times lower values than initially (р = 0.921), and patients who were resistant to the treatment had 1.1 times lower values than initial values (р = 0.936). The data were not statistically significant.

Conclusions. The study showed that the number of microvessels in patients resistant to chemotherapy and cetuximab was 4.3 times higher than in patients with effective targeted therapy (р = 0.0455). The differences in the control group were not statistically significant.

49-57 434
Abstract

Purpose of the study. To study the expression of immunophenotypic marker molecules on B-lymphocytes of patients with chronic lymphocytic leukemia at the stages of immunochemotherapy while monitoring minimal residual disease.

Patients and methods. 20 patients with CLL were examined, who in the period 2019–2022 underwent 6 courses of immunochemotherapy (ICT) in the RB/FCR mode at the National Medical Research Centre for Oncology, Rostov-on-Don. Before, after 3, 6 courses of ICT, bone marrow immunophenotyping was performed by flow cytometry. The data is evaluated in Statistica 13.0.

Results. Before treatment, 3 groups of patients were identified depending on the expression of prognostic markers (CD38, ZAP‑70, CD11c, CD25, FMC7). I (2 people) – without expression of CD38, ZAP‑70, CD11c, CD25, FMC7 on tumor B-lymphocytes. II (14 people) – with variable expression of CD25, CD38 (0.4–47.6 % and 0.0–57.5 %, respectively), lack of expression of ZAP‑70, CD11c, FMC7. III (4 people)– with high expression of CD38 (57.5–69.2 %), ZAP‑70 (36.6–48.3 %), CD11c (20.0–96.5 %), CD25 (64.9–92.7 %), FMC7 (13.6–88.6 %). After the 3rd course of ICT, the minimum residual disease (MRD): 0 % in group I, 0.48 ±  0.13 % in group II, 33.5 ± 7.84 % in group III. After the 6th course of ICT MRD: 0 % in group I, 0.42 ± 0.09 % in group II, 33.2 ± 8.07 % in group III. The expression of immunophenotypic markers in groups II and III remained unchanged after 3, 6 courses of ICT. According to the criteria for assessing the response to therapy (IWCLL, 2018), patients of groups I, II after the 6th course of ICT have complete remission, 3 patients of group III have partial remission, 1 patient has stabilization of the process. Preliminary data have been obtained indicating that the absence or increased expression of CD38, CD25, ZAP‑70, CD11c, FMC7 on B-lymphocytes of CLL patients before treatment may predetermine the hematological response to therapy according to RB/FCR regimens.

Conclusion. Initially, increased expression of all prognostic antigens simultaneously: CD38, CD25, ZAP‑70, CD11c, FMC7 on the tumor population of B-lymphocytes in patients with CLL is associated with an unsatisfactory response to treatment, which seems promising from the point of view of studying the effect of the analyzed marker molecules on achieving a hematological response at the stages of immunochemotherapy.

58-66 387
Abstract

Purpose of the study. To study the features of the local distribution of populations of immune system cells in patients with non-invasive muscular bladder cancer of various degrees of malignancy.

Materials and methods. The study included 51 patients with newly diagnosed non-muscle-invasive bladder cancer (papillary urothelial carcinoma) who received complex treatment and follow-up after 9 months at the oncourological department of the National Medical Research Center of Oncology. Patients were divided into two groups: group 1 – with a tumor of low malignant potential (Low grade – LG), n = 31; group 2 – with a tumor of high malignant potential (High grade – HG), n = 20. After 6–9 months, 24 patients were diagnosed with a relapse of the disease – in 48,4 % in patients of group 1 (n = 15) and in 45 % – in group 2 (n = 9). In cell suspensions obtained from the primary and recurrent tumors, as well as the perifocal zone, the relative number of populations of immunocompetent cells was estimated using flow cytometry. A comparison was made of the content of individual populations of lymphocytes in the tumor tissue, the perifocal zone of primary and recurrent lesions of various degrees of malignancy. Statistical processing was performed using Statistica 13.0.

Results. The development of a recurrent tumor of low malignant potential is accompanied by the involvement of cells of innate immunity (NK- and NKT-lymphocytes) into its microenvironment, which is associated with an imbalance in the number of main cells of adaptive immunity – a fairly pronounced decrease in the tumor of T-lymphocytes of the helper-inductor type was noted with a constant content cytotoxic T-lymphocytes, as well as the multidirectional nature of changes in DP- (decrease) and DN-lymphocytes (increase). A feature of the development of a recurrent tumor of high malignant potential is that it is accompanied by the involvement of innate immunity cells (NK- and NKT-lymphocytes) into its microenvironment, as well as multidirectional changes in DP- (decrease) and DN-lymphocytes (increase).

Conclusion. Studies of the population composition of tumors and their perifocal tissues of NMIBC revealed a number of features that are reflected in the redistribution of cytolytic cells, the formation of immunosuppressive conditions, which are reflected both in the manifestation of the biological properties of tumor cells and in changes in the cellular composition of bladder tissues involved in the process. development and progression of cancer. 

CLINICAL CASE REPORT

67-73 528
Abstract

Today, lung cancer (LC) occupies a special place in the oncological general morbidity among the male population both in Russia and in foreign countries. Despite modern diagnostic capabilities provided for modern physicians, steadily frequent cases of triggering and exclusion are more common in patients older than 60–65 years. Surgery is the main treatment for early-stage non-small cell lung cancer (NSCLC), but as the disease progresses, unfortunately, its effectiveness decreases. The strategy of diagnosing and treating patients with one NSCLC has been developed and worked out for a long time and does not cause any difficulties, but in the presence of two or more tumors, especially when they are located in both lungs, the correct choice of therapy is determined by many additional factors. This article describes the rare use of extended bronchoplastic upper lobectomy as a surgical component of the complex treatment of a patient with bilateral synchronous NSCLC. Based on our own observational data, it can be claimed that the use of modern therapeutic principles in combination with surgical intervention allows achieving satisfactory long-term results in the treatment of patients with primary multiple NSCLC.

The interest of the presented observation is based on the fact that it contains a description of a rare and unique application of sequential extended bronchoplastic upper lobectomy as a surgical component of the complex treatment of a patient with bilateral synchronous NSCLC, which we have not found analogues in the literature. We have shown that the consistent use of modern therapeutic modalities makes it possible to achieve satisfactory long-term results in the treatment of a locally advanced disease. 



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ISSN 2686-9039 (Online)