Experimental oncology最新文献

Colorectal carcinoma (CRC) is the third most frequent neoplasm worldwide and the second leading cause of mortality. Neuroendocrine peptides such as glucagon, bombesin, somatostatin, cholecystokinin, and gastrin as well as growth factors such as platelet-derived growth factor, epidermal growth factor, insulin-like growth factor, and fibroblast growth factor have been postulated as being involved in carcinogenesis. The fact that these neuroendocrine peptides are involved in the development of CRC through the activation of growth factors that stimulate a series of molecular pathways that activate oncogenic signaling mechanisms is emphasized in this review. Peptides such as CCK1, serotonin, and bombesin have been found to be over-expressed in human tumor tissues. Meanwhile, the expression of peptides such as GLP2 has been seen mainly in murine models. The information contained in this review provides a better understanding of the role these peptides play in the pathogenesis of CRC for basic and clinical science studies.

Background: Skeletal muscle wasting is a common phenotypic feature of several types of cancer, and it is associated with functional impairment, respiratory complications, and fatigue. However, equivocal evidence remains regarding the impact of cancer-induced muscle wasting on the different fiber types.

Aim: The aim of this study was to investigate the impact of urothelial carcinoma induced in mice on the histomorphometric features and collagen deposition in different skeletal muscles.

Materials and methods: Thirteen ICR (CD1) male mice were randomly assigned into two groups: exposed to 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for 12 weeks, plus 8 weeks of tap water (BBN, n = 8) or with access to tap water for 20 weeks (CONT, n = 5). Tibialis anterior, soleus, and diaphragm muscles were collected from all animals. For cross-sectional area and myonuclear domain analysis, muscle sections were stained with hematoxylin and eosin, and for collagen deposition assessment, muscle sections were stained with picrosirius red.

Results: All animals from the BBN group developed urothelial preneoplastic and neoplastic lesions, and the tibialis anterior from these animals presented a reduced cross-sectional area (p < 0.001), with a decreased proportion of fibers with a higher cross-sectional area, increased collagen deposition (p = 0.017), and higher myonuclear domain (p = 0.031). BBN mice also showed a higher myonuclear domain in the diaphragm (p = 0.015).

Conclusion: Urothelial carcinoma induced muscle wasting of the tibialis anterior, expressed by a decreased cross-sectional area, higher infiltration of fibrotic tissue, and increased myonuclear domain, which also increased in the diaphragm, suggesting that fast glycolytic muscle fibers are more susceptible to be affected by cancer development.

Background: Lung cancer (LC) is one of the most common malignant neoplasms in men around the world, which poses a number of important challenges for scientists.

Aim: To analyze the histogenesis, features of the histological structure, and growth of LC.

Materials and methods: The surgical material of 81 patients with LC was studied. Histological preparations were stained with hematoxylin and eosin (H&E) using the Papanicolaou method. Immunohistochemical reactions with monoclonals (Ki67, PCNA) were conducted.

Results: In histological preparations of all LC types (squamous, adenocarcinoma, and small cell), along with solid growth, tumor growth in the alveoli was determined, which started from the basal membrane and grew toward the alveolus center, as evidenced by the morphological features of growth, tumor spread, and development of necrosis in the center.

Conclusion: In all the studied histological preparations of LC, tumor growth in the alveoli is noted, which is confirmed by structural and cellular signs and the nature of tumor decay in the alveolus center, which corresponds to the general patterns of development of malignant epithelial tumors.

A case of recurrent lentigo maligna in a 45-year-old woman is presented. The disease relapsed several times following the surgical excision of the lesion. An alternative treatment with imiquimod 5% cream was then used. After 4 years of follow-upfrom the last surgery, this treatment achieved total clearance of the lesion. The problems of lentigo maligna diagnosis and treatment are discussed.

The changes in the quantitative parameters and spatial structure of collagen are considered a key diagnostic and prognostic factor associated with the development of many malignant neoplasms, including breast cancer (BCa). The aim of the work was to develop and test an algorithm for the assessment of collagen organization parameters as informative attributes associated with BCa for developing technology of machine learning and building an intelligent system of cancer diagnostics.

Materials and methods: Tumor tissue samples of 5 patients with breast fibroadenomas and 20 patients with stage I-II BCa were studied. Collagen was identified histochemically by Mallory method. Photomicrographs of the studied preparations were obtained using a digital microscopy complex AxioScope A1. Morphometric studies were performed using the software CurveAlign v. 4.0. beta and ImageJ.

Results: The algorithm for determining the quantitative characteristics and spatial organization of the collagen matrix in tumor tissue samples has been developed and tested. We showed that collagen fibers in the BCa tissue are characterized by significantly lower values of length (p < 0.001) and width (p < 0.001) as well as higher values of straightness (p < 0.001) and angle (p < 0.05) compared to these in the fibroadenoma tissue. No significant difference was found in the density of collagen fibers in the tissue of benign and malignant neoplasms of the mammary gland.

Conclusion: The algorithm allows assessing a wide range of parameters of collagen fibers in tumor tissue, including their spatial orientation and mutual arrangement, parametric characteristics and density of the three-dimensional fibrillar network.

The work describes a case of rare neonatal systemic juvenile xanthogranuloma with an initial damage of the scalp, limbs, back and abdomen, multiple damages of the parenchyma of both lungs, spleen and liver with the development of a severe form of congenital cholestatic hepatitis. The diagnosis was established on the basis of histopathological and immunohistochemical examination of the skin nodules. The child on the background of therapy under the Langerhans cell histiocytosis III program achieved a partial response, which was manifested by a reduction of granulomatous formations on the skin, elimination of liver failure, but retained hepatosplenomegaly, specific lesions of the lung parenchyma, liver, and left kidney. Against the background of cytostatic therapy, the patient developed secondary pancytopenia, perianal ulcerative-necrotic dermatitis with lesions on buttocks, stomatitis, protein-energy deficiency, acute liver failure. coagulopathy, disseminated intravascular coagulation syndrome, acute renal failure, respiratory failure of III degree, cardiovascular insufficiency of III degree, pulmonary edema, cerebral edema, cerebral coma of II-III degree, enterocolitis, intestinal paresis. Despite multicomponent intensive care, the child's condition progressively deteriorated, and the patient died. The aspects of differential diagnosis of neonatal systemic juvenile xanthogranuloma are discussed.

Aim: Given the invaluable success of immune checkpoint inhibitors for tumor immunotherapy, in this study, the effect of programmed cell death 1 (PD-1) and T cell immunoglobulin-3 (TIM-3) blocking was investigated to induce apoptosis of leukemic cells by exhausted CD8⁺ T cells in patients with chronic lymphocytic leukemia (CLL).

Materials and methods: Peripheral blood CD8⁺ T cells were positively isolated from 16 CLL patients using magnetic beads separation method. Isolated CD8⁺ T cells were treated with either blocking anti-PD-1, anti-TIM-3 and isotype-matched control antibodies and then co-cultured with CLL leukemic cells as target. The percentage of apoptotic leukemic cells and the expression of apoptosis-related genes were evaluated by flow cytometry and real-time polymerase chain reaction methods, respectively. Interferon gamma and tumor necrosis factor alpha concentration was also measured by ELISA.

Results: Flow cytometric analysis of apoptotic leukemic cells indicated that the blockade of PD-1 and TIM-3 did not significantly enhance the apoptosis of CLL cells by CD8+ T cells, which then were confirmed by analysis of BAX, BCL2 and CASP3 gene expression, which was similar in blocked and control groups. No significant difference was found between blocked and control groups in terms of interferon gamma and tumor necrosis factor alpha production by CD8+ T cells.

Conclusion: We concluded that the blockade of PD-1 and TIM-3 is not an effective strategy to restore the function of CD8+ T cells in CLL patients at the early clinical stages of the disease. Further in vitro and in vivo studies are needed to more address the application of immune checkpoint blockade in CLL patients.

Aim: To investigate the neurofunctional parameters in breast cancer (BC) patients with paclitaxel-induced peripheral neuropathy (PIPN) and to clarify the feasibility of using alpha-lipoic acid (ALA) in combination with the acetylcholinesterase inhibitor ipidacrine hydrochloride (IPD) for its prevention.

Materials and methods: 100 BC patients (T1-4N0-3M0-1) prescribed for polychemotherapy (PCT) by the AT (paclitaxel, doxorubicin) or ET (paclitaxel, epirubicin) regimens in the neoadjuvant, adjuvant or palliative modes, were enrolled. The patients were randomized into two groups (n = 50 per group): group I treated by PCT only; group II treated with PCT plus the studied PIPN prevention scheme (ALA in combination with IPD). An electroneuromyography (ENMG) of the sensory (superficial peroneal and sural) nerves was performed before PCT, and after the 3 and 6 PCT cycles.

Results: According to ENMG data, the electrophysiological disturbances in the sensory nerves were manifested in the form of axonal sensory peripheral neuropathy of a symmetrical nature, which was reflected in a decrease in the amplitude of the action potential (AP) of the studied nerves. The AP reduction in sensory nerves was dominant, in contrast to the nerve conduction velocity, which in most patients remained within the reference values, thus evidencing on axonal degeneration rather than demyelination as an underlying cause of PIPN. The ENMG testing of the sensory nerve in the groups of BC patients treated by PCT with paclitaxel with or without PIPN prevention treatment established that the use of ALA in combination with IPD significantly improved AP amplitude, duration and area of ​​the response to the stimulation of the superficial peroneal and sural nerves after 3 and 6 PCT cycles.

Conclusion: The use of ALA in combination with IPD significantly reduced the severity of damage to the superficial peroneal and sural nerves caused by PCT with paclitaxel and could be recommended for PIPN prevention.

Synovial sarcoma is an aggressive soft tissue sarcoma, which most often occurs in the limbs near the joints. It accounts for 5-10% of all soft tissue sarcomas. It extremely rarely affects the pelvis. So far, only 4 cases of primary involvement of the adnexa have been described. We present a case of a 77-year-old female patient diagnosed with a rapidly growing pelvic formation, subsequently diagnosed as monophasic synovial sarcoma of the ovary. Synovial sarcoma derived from the adnexa is a rare disease that is virtually unknown. The diagnosis is complex, and there is a poor prognosis.

Background: Hormonal therapy is one of the main methods of comprehensive treatment of patients with locally advanced breast cancer (BC). Despite the intensive search for molecules associated with the aggressiveness of the tumor process, currently there are no reliable markers predicting response to neoadjuvant hormonal therapy (NHT).

Aim: To investigate the correlation between miR-125b-2, -155, -221, -320a expression in tumor tissue and HER2/neu status and response to tamoxifen treatment in BC patients.

Materials and methods: Expression levels of miR-125b-2, -155, -221, and -320a were analyzed in biopsy samples of 50 BC patients using a real-time polymerase chain reaction.

Results: We found that levels of miR-125b-2, -155, -221, and -320a were 1.72, 1.65, 1.85, and 2.89 times higher in BC biopsy samples expressing estrogen/progesterone receptors and HER2/neu compared with HER2/neu-negative luminal tumors. Patients with a luminal BC showing higher levels of miR-125b-2 and miR-320a expression before therapy demonstrated better response to NHT with tamoxifen. A strong correlation was calculated for miR-221 expression and response to NHT (r = 0.61).

Conclusions: The high levels of miR-125b-2, -155, -221, and -320a in tumor tissue are associated with the HER2/neu-positive status of luminal BC subtypes. Tumor samples of patients showing the low response to NHT with tamoxifen are characterized by lower expression of miR-125b-2 and -320a. Hence, miR-125b-2 and -320a could be considered as putative predictive biomarkers associated with tamoxifen sensitivity of hormone-dependent BC.