Experimental oncology最新文献

Advances implemented in the complex treatment of distal rectal cancer led to a decrease in the number of loco-regional recurrences to 5-10%, but high rates of distant metastases remain at up to 30%. They lead to disappointing long-term oncological results, which requires the search for improvement of each of the stages of complex treatment. As a consequence of the questionable effectiveness of adjuvant polychemotherapy for distal rectal cancer, the question of the possibility of transferring drug treatment from an adjuvant to a neoadjuvant regimen is reasonably raised. The presented options for full neoadjuvant therapy have been developed and tested in leading oncology centers and are based on National Comprehensive Cancer Network Version 1.2022 recommendations. It is premature to make categorical conclusions regarding the recommendation of one or another variant of their implementation. Our preliminary clinical results confirmed the need for an additional stage of restaging in the second option, after 16 weeks of polychemotherapy before chemoradiation, in order to exclude the generalization of the disease. Therefore, there is a need for a prospective, controlled intercentre study to answer some unresolved questions.

Multiple primary malignant tumors are characterized by independent occurrence and development of two or more malignant neoplasms in the same patient. We present an extremely rare case of synchronous double primary malignancies, hairy cell leukemia and hepatocellular carcinoma with lethal outcome. Diagnosis of hepatocellular carcinoma was difficult due to the presence of lymphoproliferative disease, which complicated the visualization of the process using ultrasonography. Carcinomatous emboli of hepatocellular carcinoma in small pulmonary arteries without the formation of metastatic foci have led to clinical manifestations typical of pulmonary embolism, pulmonary hypertension and severe respiratory failure. In lymphoproliferative diseases it is necessary to take into account the possibility of the development of another malignant neoplasm, which can be "buried" by tumor infiltration.

Background: Odontogenic cysts and tumors exhibit different degrees of aggressiveness in their biological behavior. There has been evidence that the presence of myofibroblasts (MFs) at the invasion front promotes tumor invasion. Our study is based on the fact that MFs are important in the biological behavior of odontogenic cysts and tumors.

Aim: To assess immunohistochemically expression of alpha-smooth muscle actin (α-SMA) of MFs in odontogenic cysts and tumors and correlate this expression to their biological behavior.

Materials and methods: The archival tissues collected for 1.5 years were obtained from the Department of Oral Pathology & Microbiology, People's Dental Academy, Bhopal (India). A total of 40 cases consisting of 10 cases each of odontogenic keratocysts, radicular cysts, dentigerous cysts and ameloblastomas formed the study group. An immunohistochemical analysis of α-SMA expression and localization was carried out.

Results: Mean MF counts were the highest in odontogenic keratocysts which was followed by ameloblastomas, entigerous cysts and radicular cysts. Weak α-SMA-expression was found in 50% of cases, moderate in 22.5% of cases, and intense - in 10% cases. MFs were arranged in the spindle, focal, or network patterns in 35; 27.5 and 20% of cases, respectively.

Conclusion: The analysis revealed that the MFs were distinctly heterogeneous in distribution and pattern of arrangement. This provided persuasive evidence that stroma of these lesions harbor MFs as reflected by α-SMA immunopositive cells.

Background: Identification of epitopes recognized by leukemic B cells could provide insights into the molecular mechanisms of B cell transformation in chronic lymphocytic leukemia (CLL). The aim of this paper was to compare nucleotide sequences of immunoglobulin heavy chain variable region (IGHV) genes in CLL with known sequences directed against antigens of different origins available in public databases.

Materials and methods: Analysis was performed in the groups of 412 unselected CLL patients with productive IGHV gene using polymerase chain reaction followed by direct sequencing.

Results: Homology between CLL Ig sequences and antibodies directed against autoantigens was found in 12 patients (2.9%), homology between CLL Ig sequences and antiviral antibodies - in 35 patients (8.5%). Most of these sequences belonged to stereotypical clusters. Among the sequences that have homology to antiviral antibodies, the most prevalent were cases homologous with antibodies against HIV (14 cases, 3.4%) and SARS-CoV-2 antigens (10 cases, 2.4%). None of the patients in our cohort was HIV-infected and the study was conducted before the emergence of SARS-CoV-2 virus.

Conclusions: Suggestions could be made about the possible impact of past infection of SARS-CoV-2 virus on the pathogenesis of CLL. In particular, an increase in the proportion of CLL cases with the expression of some stereotyped BCR and/or an increase of CLL risk in the long-term period after SARS-CoV-2 virus infection is not excluded. This assumption needs to be verified by epidemiological data.

Radical trachelectomy combined with pelvic lymphadenectomy (PLND) has been used to treat early stage cervical cancer patients who wish to preserve their fertility. But vaginal, abdominal, laparoscopic, and robotic approaches used for radical trachelectomy with pelvic PLND cause peritoneal damage, which could result in periadnexal adhesion. Here, we propose the neoadjuvant platinum based chemotherapy (NACT) with the vaginal radical trachelectomy with retroperitoneal PLND as a fertility-preserving option for early stage cervical cancer patients. VRT with retroperitoneal PLND was performed in three women with FIGO 2018 stage IB2 and IIA1 cervical cancers. In all three patients, complete response was achieved without causing any intraoperative and severe postoperative complications. NACT for fertility sparing treatment is an innovative approach, which is potentially quite interesting for many young women affected by cervical cancer with the tumor size >2 cm. Vaginal radical trachelectomy with retroperitoneal PLND can be safely performed and peritoneal damage, which can cause periadnexal adhesion, could be avoided. We consider that this surgical approach and NACT may be a good treatment option for women with cervical cancer who wish to preserve their fertility.

The real threat of emergency situations in Ukraine dictates the need to take into account the experience of previous radiation accidents, during which a significant part of the population was exposed to low-dose radiation. In such a case clinical manifestations of irradiation were mostly absent, while the danger of stochastic (carcinogenic) effects remained. Therefore, at present, the strategy of radiation protection of the population should be aimed at revising and choosing effective and low-toxic anti-radiation means. The main criterion for the development of stochastic consequences of exposure is radiation-induced genome instability, which is a promoter of carcinogenesis. The use of radiomitigators, which are able to weaken the harmful effect of ionizing radiation on critical highly radiosensitive systems of the human body, is promising. Our research showed the radiomitigative effect of inosine in cultured human T-lymphocytes on the genetic level with the significant decrease in the frequency of gamma-induced chromosome aberrations. The results experimentally justified an expediency of use of radiomitigators in the conditions of an emergency situation to minimize the occurrence and development of stochastic effects in population.

The aim of the study was to examine the prognostic value of immunobiological markers (tumor-infiltrating lymphocytes (TILs) and their subpopulations) in residual tumor after neoadjuvant chemotherapy (NACT) completion in patients with triple negative (TNBC) and luminal B HER2-neu negative breast cancer (LBBC).

Materials and methods: The analysis of the treatment results of 59 patients with TNBC and 56 patients with LBBC with stage IIB-IIIB who received NACT was performed. The levels of TILs and their subpopulations (FOXP3+, CD4+, CD8+) in patients at the time of diagnosis in core-needle biopsy material and in residual tumor in postoperative material were studied by immunohistochemical method.

Results: The risk of recurrence in patients with LBBC who received NACT before surgery is associated mainly with 4 factors: FOXP3+ lymphocytes, Ki-67 index in residual tumor, the number of affected axillary lymph nodes after NACT and viable residual tumor volume. Analysis of the treatment outcome in patients with TNBC revealed that the lack of pathologic complete response (pCR) after NACT increases the risk of disease recurrence by 2.9 times, hazard ratio (HR) = 2.9 (95% confidence interval (CI) 1.4-6.1; p = 0.005) compared with patients in which pCR was achieved after NACT. It was also found that the presence of residual tumor in patients with TNBC after NACT increases the risk of death from this disease by 2.7 times (95% CI 1.0-7.1; p = 0.05). Increased intratumoral and stromal CD8+ lymphocyte counts in the residual tumor after NACT significantly reduces the risk of death from TNBC, HR = 0.6 (95% CI 0.5-0.9; p = 0.01) and HR = 0.6 (95% CI 0.4-0.9; p = 0.008), respectively. Increase in intratumoral CD4+ lymphocytes in residual tumor in the non-pCR group reduces by half the risk of death from TNBC, HR = 0.5 (95% CI 0.3-1.0; p = 0.05).

Conclusion: The results of our study indicate a favorable prognostic value of TILS in residual tumor in TNBC. It is also reasonable to include the determination of the level of FOXP3+ lymphocytes in the residual tumor in the standard algorithms for stratification of risk groups.

Background: The combination of chemo- and radiotherapy used as main treatment of locally advanced cervical cancer (CC) may lead to side effects in healthy cells, which undermine the effectiveness of treatment and quality of life. The assessment of damage level in healthy radiosensitive cells from the tumor environment before the treatment is important in order to predict and prevent remote side effects of radiation.

Aim: To study the oxidative metabolism and genetic disorders in peripheral blood lymphocytes (PBL) of primary CC patients in order to evaluate the possibilities of predicting radiation complications based on the molecular and biological properties of PBL.

Materials and methods: Peripheral blood samples were collected from 13 primary CC patients T1-4N0-1M0-1, and PBL were routinely isolated. The oxidative metabolism (mitochondrial trans-membrane potential, superoxide anion radical (О2•) generation, reactive oxygen species (ROS) production in PBL as well as the level of SH-groups in plasma and pro/antioxidant ratio in hemolysates were examined. The development of genetic instability was determined by estimation of DNA double-strand breaks (DNA-DSB), frequency and spectrum of chromosome aberrations and apoptosis.

Results: The marked increase in the intensity of О2• generation in PBL (1.5-fold), depletion of SH-groups content (1.6-fold) and a shift in the pro-antioxidant balance (1.4-fold) towards its prooxidant component were observed in the blood of primary CC patients as compared to healthy individuals. These oxidative stress related events were accompanied by an increase in the level of DNA-DSB (2.1-fold), apoptosis (3.5-fold) and frequency of cells with chromosome aberrations (3.9-fold). On the contrary, significant decrease in mitochondrial trans-membrane potential (2.0-fold) and ROS generation in PBL (4.0-fold) were detected.

Conclusion: Preliminary data indicate a violation of redox processes regulation, a shift in the pro-antioxidant balance towards its pro-oxidant component, accompanied by an increase in the level of DNA damage, development of genetic instability and apoptotic death of blood lymphocytes in primary CC patients.

Background: Acute myeloid leukemia (AML) is a highly heterogeneous disease accompanied by the arrest of myeloid cell lineage differenti-ation due to accumulation of genetic abnormalities and clonal proliferation of myeloid blasts. Finding the differentially expressed molecules and studying their function within AML subgroups may help to improve diagnosis and prognosis with the aim of developing selected therapies for AML subsets. The aim of this study was to reveal the profile of CD150 cell surface expression on bone marrow (BM) cells of AML patients.

Materials and methods: The study was performed on samples of BM aspirates from 55 patients with primarily diagnosed AML. Flow cytometry analysis was applied for the evaluation of immunophenotype profile and CD150 cell surface expression on BM cells from AML patients.

Results: Four AML subtypes (M1, M2, M3 and M5) were identified. The CD150 expression was found in 14 (25.5%) cases predominantly of AML M3 subtype. CD150 expression was detected on 43.2-83.8% of leukemia cells in AML M3. The frequency of CD150 positive cases of non-M3 AML subtypes was low: all AML M1 cases were CD150-negative, while only 1 (10.0%) of 10 patients with AML M2 and 6 (19.4%) of 31 patients with AML M5 were CD150 positive. The median percentage of CD150 positive leukemia cells and the index of mean fluorescence intensity in AML M3 cases were significantly higher than in non-M3 AML cases (p < 0.05). The CD150 expression was significantly associated with CD11c, CD11b, CD14, CD34, CD36, CD56 and HLA-DR negative expression and CD33, CD38, CD117 positive expression among the examined cohort of patients with AML M3.

Conclusions: High level of CD150 expression is a unique feature of AML M3 subtype and may serve as additional phenotype marker for the identification of blast cells with impaired maturation at the promyelocyte stage and the development of AML M3. At the same time, the revealed negative association of CD150 expression with poor prognostic factor CD56 in AML M3 subtype also allows us to suggest potential prognostic value of CD150 examination in AML patients.

Background: The anticancer effects of phytohormones of cytokinin nature are similar to those of medicinal mushrooms, which are able to synthesize cytokinins in large amounts.

Aim: To determine the antiproliferative effect of crude extracts and cytokinin fractions from the mycelial biomass of seven fungi species on colon cancer cells in vitro.

Materials and methods: Cytokinin content in mycelial biomass of Ganoderma lucidum, Lentinula edodes, Trametes versicolor, Pleurotus ostreatus, Morchella esculenta, Hericium coralloides, and Fomitopsis officinalis was determined by high performance liquid chromatography mass spectrometry. The antiproliferative effect of the mushroom extracts on the human colon adenocarcinoma Colo 205 cells was assessed by MTT-test.

Results: The content of cytokinins (trans-zeatin, zeatin riboside, isopentenyladenosine, isopentenyladenine and zeatin-O-glucoside) was determined in the mycelial biomass of the medicinal macromycetes. Zeatin-type hormones prevailed in all species, though trans-zeatin was the most abundant in H. coralloides and M. esculenta. In P. ostreatus, only zeatin-O-glucoside was detected. The lowest IC50 was found for both the cytokinin fraction (0.21 μg/ml) and the crude extract (0.17 μg/ml) from mycelial biomass of H. coralloides. F. officinalis also demonstrated high antiproliferative effect against Colo 205 cells: IC50 was 0.9 μg/ml for the crude extract and almost twice lower for the cytokinin fraction. In the studied concentration range (0.016-2 μg/ml), the crude extracts from G. lucidum and M. esculenta and the cytokinin fraction from L. edodes did not reach IC50 values.

Conclusions: The present study showed that crude extracts and/or cytokinin fractions of several medicinal Basidiomycetes species are capable to inhibit proliferation of colon cancer cells in vitro. Crude extract cytotoxicity of H. coralloides, P. ostreatus and T. versicolor was higher than that of cytokinin fraction while antiproliferative effect of cytokinin fraction from F. officinalis was higher than that in its crude extract.