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Predicting the site of distant metastases in breast cancer
Статья научная
Background. Distant organ tumor dissemination is a major cause of breast cancer-related deaths. Breast cancer can metastasize to several organs, and the most frequent metastatic sites include the bones, lungs and liver. There is a question what factors can influence the direction of spread of tumor cells to a particular organ. Material and Methods. We summarized the data available in the world literature on methods for prediction of the localization of distant metastases in breast cancer patients. Results. We divided the factors associated with the localization of distant metastases into two main groups: clinicopathological parameters of breast cancer patients and molecular features of tumor microenvironment and tumor cells (primary tumor and circulating tumor cells) or its derivates - exosomes. From our point of view, the most powerful clinicopathological factor predicting the distant metastasis site is a molecular subtype of primary tumor. We can conclude that luminal (HR+/HER2-) tumors are often characterized by single metastases and bones are the most common metastatic site, while TNBC and HER2-enriched tumors often metastasize to multiple sites, most commonly brain and liver. However, several authors did not reveal these associations in their studies. It likely indicates the existence of other factors that significantly affect the organotropism of metastasis. Numerous studies demonstrate the association of different molecules expressed on tumor cells with organotropic metastasis. However, these data are very fragmentary and rather contradictory. Conclusion. The found associations are common to all participants of metastatic cascade, but remains unclear which factors are essential and crucial in determining the direction of metastasis.
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Статья научная
The aim of this study was to investigate the potential of compounds from the breadfruit tree (Artocarpus altilis) as anti-breast cancer agents using in silico techniques. Material and Methods. The methods used in this study include molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions to evaluate the interactions with Estrogen Receptor alpha (ERα). Results. Among the 22 compounds tested, Cycloaltisin-7 exhibited the most favorable binding affinity, with a free energy of -10.25 kcal/ mol and an inhibition constant of 30.89 nM. Additionally, Cyclocommunol and Cudraflavone B demonstrated significant binding interactions, with free energies of -9.61 kcal/mol and -9.53 kcal/mol, and inhibition constants of 90.82 nM and 103.50 nM, respectively. For comparison, the standard compound 4-Hydroxytamoxifen showed superior binding characteristics, with a free energy of -12.36 kcal/mol and an inhibition constant of 867.83 pM. ADMET predictions indicate that Cycloaltisin-7, Cyclocommunol, and Cudraflavone B meet essential drug-like criteria, suggesting their potential as viable candidates for further development as breast cancer therapeutics. Conclusion. These findings highlight Cycloaltisin-7 as a particularly promising compound, with Cyclocommunol and Cudraflavone B also showing considerable potential. This research provides valuable insights for the advancement of plant-based treatments for breast cancer. Supporting agencies: This study was funded by APBU 2024 Research Grant Universitas Islam Kalimantan MAB Banjarmasin, Indonesia.
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ABC-transporter family genes have been well studied and their involvement in the development of drug resistance has been assessed. The presence of aberrant conditions in these genes can affect the treatment and prognosis of the disease. Loss of heterozygosity (LOH) is one of these conditions; it is a common event in cancer development. Therefore, the aim of this study was to investigate the relationship between LOH in ABC transporter genes in breast cancer and response to chemotherapy and disease prognosis. Material and Methods. A total of 130 breast cancer patients were included in the study. Microarray analysis was performed on Affymetrix CytoScan™ HD Array high-density DNA chips to assess LOH status. Chromosome Analysis Suite 4.1 software (Affymetrix, USA) was used to process microarray results. Results. Forty-nine ABC transporter genes were evaluated for LOH. The frequency of LOH ranged from 6.9 % to 90 %. An association analysis identified two genes: ABCG5 and ABCG8, in which the presence of LOH was associated with a lack of objective response to neoadjuvant chemotherapy. The presence of LOH in the ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 and ABCC3 genes was associated with high rates of metastasis-free survival (log-rank test, p
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Predictors of local recurrence of renal cell cancer. Our experience
Статья научная
Risk factors for renal cell cancer (Rcc) recurrence, including its local form, include stage and high Fuhrman grading system score, regional lymph node involvement, microvascular invasion, tumor necrosis, positive surgical margin, and sarcomatoid or rhabdoid tumor differentiation. Objective. the study analyzes data from moscow Research oncological institute named by pa Herzen to determine the predictors of local recurrence of kidney cancer based on the data from surgically treated patients with local recurrent Rcc. material and methods. We analyzed retrospectively data from 87 patients who were divided into 2 groups: 1-st, patients with detected local recurrence of kidney cancer (n=43), and 2-nd, control group (n=44). the following predictors were evaluated: tumor size, tumor histotype, tumor stage, Fuhrman grading system, surgical margin status, tumor necrosis, sarcomatoid and rhabdoid changes, microvascular invasion, hemorrhage and invasion of collecting system components (css), renal capsule, and perirenal cellular tissue and primary treatment. Results. the risk of local recurrence was higher in the primary tumor, over 40 mm in diameter (oR=5.8, p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Primary liver cancer in the Republic of Sakha (Yakutia)
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Territorial and ethnic features of the prevalence of primary liver cancer in the republic of Sakha have been studied. The republic has been shown to be a high-risk area for primary liver cancer, which is the 2-nd most common form of cancer in males and the 3-rd most common form of cancer in females among all digestive system malignancies. The standard liver cancer incidence rates are 5 times higher than the average incidence rates in Russia. Primary liver cancer is more oftern registered in the age group of 70 years and more. Incidence rates are mainly raised due to indigenous and rural populations. The liver cancer incidence rates show a tendency to stabilization all over the republic.
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Probiotics Against Pathogenic Bacteria and Cancer
Статья обзорная
This review focuses on the role of probiotics as alternative prevention and treatment of cancer. In this regard, we discuss the alternative cancer biotherapeutic drugs including live or dead probiotics and their metabolites, such as short chain fatty acids, inhibitory compounds of protein, polysaccharide, nucleic acid and ferrichrome in vitro, in vivo and clinical studies. We also summarize the available data on the relationship between the development of cervical, breast and colorectal cancers, and microbiome, as well as data about the potential of probiotics as an alternative approach to cancer prevention and treatment. Material and Methods. A literature search was conducted using the Pubmed and eLibrary databases. Of 140 publications, the review included 57 studies.
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Статья научная
Purpose. to evaluate prostate specific antigen density (psad) as a predictor of overall (os) and cancer-specific survival (css) in patients with prostate cancer (pc) who have undergone combined hormonal-radiation therapy. material and methods. in order to assess the prognostic significance of psad we retrospectively analyzed outcomes of 714 pca patients who received combined hormonal-radiation therapy at the a.m. granov Russian scientific center of Radiology and surgical technologies, ministry of Healthcare of Russia, between January 1996 and december 2016. since the prognosis and management differ according to the extent of tumor involvement, patients were categorized into localized (n=272), locally advanced (n=231) and metastatic (n=211) pc groups. We equentially applied Roc-analysis, Kaplan-meier product limit estimator and cox proportional hazards model to assess the prognostic relevance and establish threshold values of psad that had a significant impact on survival rates. results. in the localized pc group, psad threshold values of 0.34 ng/ml/cc and 0.36 ng/ml/cc were associated with a decrease in os and css, respectively. patients with “low” psad had significantly better os and css survival rates in both uni- and multivariate analyses. in locally advanced pc group, psad threshold values were 0.28 ng/ml/cc and 0.63 ng/ml/cc for os and css, respectively. However, exceeding the specified values, in the locally advanced pc group, was not accompanied by a statistically significant decrease in survival rates. Finally, in the metastatic pc group, established psad threshold values were 2.25 ng/ml/cc and 2.30 ng/ml/cc for os and css, respectively. according to the results of univariate analysis, patients with “low” psa tend to demonstrate statistically significant better os and css rates. the results of multivariate analysis, however, failed to prove psad as an independent prognostic factor within the metastatic pc cohort. conclusion. psa density is a reliable tool for assessing survival rates in patients with localized pc who have undergone combined hormonal-radiation therapy.
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Psychological rehabilitation and life quality assessment for patients with thyroid cancer
Статья научная
Life quality values of thyroid cancer patients are characterized by reduction in psychological vector in early postoperative period and greatly in social vector. The detected damages are completely resolved within 6 months. Compensation of physical characteristics of life quality occurs more completely. High level of personal anxiety having preferably psychical and neurovascular character is observed in patients of the studied group. Comprehensive systematic psycho-therapeutic correction in early postoperative period taking account individual characteristics of the patients significantly increases the treatment efficacy. A high social-labor adaptation of the studied group patients has been found.
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Статья научная
The purpose of the study was to generalize information regarding the molecular and biological mechanisms involved in the resistance to endocrine therapy with aromatase inhibitors in patients with luminal breast cancer. material and methods. the literature search was conducted using medline, cochrane library, elibrary and pubmed databases. results. the review highlights the results of international studies on molecular and biological characteristics of breast tumors and their relationship with the effectiveness of hormone therapy. particular attention was paid to the description of modern studies on RoR1 and Bmi-1 proteins and their contribution to the development of tumor resistance to treatment. conclusion. the analysis of the world literature confirms the relevance of studying the molecular and genetic characteristics of tumor tissue in patients with luminal breast cancer. the data obtained were compared to the clinical course and response to hormone therapy in order to standardize them for implementation in everyday practice as the “gold standard of diagnosis”.
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Radical prostatectomy and robotic radiosurgery as treatment options for localized prostate cancer
Статья научная
Purpose: to compare immediate, short-term and long-term treatment outcomes after radical prostatectomy and robotic radiosurgery in patients with localized prostate cancer. Material and Methods. The study included 2 groups of patients. Group I patients (n=80) underwent radical surgery (nerve-sparing prostatectomy). Group II patients (n=102) underwent KiberKnife stereotactic robotic radiotherapy. Results. Immediate treatment outcomes after both radical prostatectomy and robotic radiosurgery did not demonstrate increased number of postoperative complications and severe radiation-induced injuries. The PSA level decreased and reached a nadir PSA level immediately after radical prostatectomy. After stereotactic radiation therapy, the PSA level decreased gradually every three months, reaching a nadir within a year. In the group of patients receiving CyberKnife treatment, changes in the prostate volume affected the quality of urination, which was confirmed by the assessment of the volume of residual urine. When comparing the quality of urination in treatment groups using the IPSS scale, the values were comparable. No differences in the 1-year disease-free survival rates between groups were found. However, 60 months later, disease free survival rate was higher by 8.2 % in patients treated with radiosurgery than in patients who underwent radical prostatectomy (p function show_abstract() { $('#abstract1').hide(); $('#abstract2').show(); $('#abstract_expand').hide(); }
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Статья научная
PCR clamping/wild-type blocking PCR with non-extendable locked nucleic acid (LNA) oligonucleotides is used for sensitive detection of somatic mutations in tumors. Various versions of the technique use different DNA polymerases and LNA oligonucleotides with and without additional phosphorothioate modifications. Here we studied requirements for successful PCR clamping with LNA oligonucleotides and Taq DNA polymerase for analysis of mutations in KRAS and bRAF genes by means of real-time PCR and Sanger sequencing. We found that addition of phosphorothioate linkages at the 5’-end of LNA oligonucleotide to protect from 5’-exonuclease activity of Taq DNA polymerase did not improve clamping. For most target sequences, efficient clamping was observed at melting temperature of LNA oligonucleotide 20-25°C above annealing/extension temperature of the PCR with a 2-step protocol. Under such conditions, simple and sensitive detection of mutations in KRAS and bRAF genes was feasible using real-time PCR with TaqMan probes or Sanger sequencing.
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Short-term results of surgical treatment of non-organic retroperitoneal tumors
Статья научная
Comparative analysis of short-term results of combined operations and isolated removal of non-organic retroperitoneal tumors has been carried out. The study included 97 patients with malignant primary and recurrent tumors adjacent to surrounding organs. A total of 106 operations were performed, 56 of them were combined operations (52 patients were operated on), and isolated tumor removal was performed in 50 cases (45 patients were operated on). It has been found that the hemorrhage volume and surgery duration are significantly increased during the combined operations resulting in the increase in the rate of postoperative complications, however, these differences are not significant.
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Single vein resection in surgery for pancreatic ductal carcinoma as a criterion of resectability
Статья научная
Background. pancreatic ductal carcinoma (pdc) with involvement of the superior mesenteric vein (smV) or/and portal vein (pV) remains a discussible subject. We have evaluated vein invasion as a criterion of borderline resectability and long-term outcome. material and methods. in our center, 68 patients underwent either 65 standard pancreatoduodenal resections or 3 pancreatoduodenectomies for pdc. Resection of smV/pV was performed in 18 cases (26.5 %). three patients received neoadjuvant chemotherapy (Nact), and adjuvant chemotherapy (act) was assigned to 37 patients (54.4 %). Results. morbidity (42.0 vs 50.0 %, р=0.590) and mortality rates (4.0 vs 16.7 %, р=0.111) had no significant differences in groups of standard and angioplasty operations respectively. act was completed in 10 (16.7 %) patients only. there was true vein invasion in 12 of 18 patients with vein resection. рN+ (р=0.012) and angioplasty by itself (р
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Study of dendritic cell migration using CELL-IQ analysis system
Статья научная
Dendritic cells (DCs) belong to specialized pool of antigen-presenting cells with high functional plasticity and manifest with immunostimulatory or immunosuppressive potential depending on sequence and combination of microenvironment stimuli, which determine their differentiation, maturation and activation. The use of antitumor DCs vaccines is based on the ability of DCs specifically activated in vitro migrate for antigen presentation to T-lymphocytes. We studied the components of the tumor microenvironment that are capable of inhibiting DCs migration. The study of the mobility of DCs in Cell-IQ experimental analytical system showed the presence of an inverse correlation of high strength between the average trajectory speed and the level of immunosuppressive factors (ISFs) in supernatants of cultured skin melanoma cells (TgFβ1, IL-10, IL-18, VEgF-A, EgF, FgF, HgF, sFASL (p
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Study of the effect of lomustin on HER2-positive breast cancer in FVB/N her-2 transgenic mice
Статья научная
Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p
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Статья научная
Introduction. Treatment of local RCC recurrence is a serious surgical and therapeutic problem. There is no single standard strategy for the treatment of locally recurrent RCC.
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Статья научная
Introduction. Identification of persons with a high oncological risk to squamous cell carcinoma of the head and neck region is an urgent problem for the early diagnosis of this disease. The activity of circulating proteasomes can be a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the upper respiratory and gastrointestinal tracts. The aim of the study is to investigate the chymotrypsin-like and caspase-like activities of circulating serum proteasomes depending on the localization of precancerous and neoplastic diseases of the larynx and oral cavity. Material and Methods. The study population consisted of 35 patients with histologically verified HNSCC (T1-3N0-3M0), 15 patients with chronic hyperplastic laryngitis (CHL) and oral leukoplakia, and 10 healthy volunteers who did not have chronic upper respiratory tract diseases in the acute stage. The median age of the patients was 53 ± 5.3 years. Results. An increase in the studied proteasome activities was found in the blood serum of patients with malignant tumors as compared with patients with chronic hyperplastic diseases associated with precancerous changes, as well as in the larynx and oral cavity cancers groups as compared with healthy donors. At the same time, depending on the localization of the pathological process, it was shown that only the chymotrypsin-like activity of the circulating pool of proteasomes significantly differs both in the groups of oral cancer leukoplakia, and in the groups of laryngeal cancer chronic hyperplastic laryngitis with dysplastic epithelial lesions. In addition, differences were found between chymotrypsin-like and caspase-like activities of circulating serum proteasomes in patients with chronic hyperplastic laryngitis with oral dysplasia and leukoplakia. Conclusion. The results obtained indicate that the determination of the CTP activity of the circulating pool of proteasomes can be used as a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the larynx and oral cavity.
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Статья научная
Introduction. The purpose of this study was to evaluate the feasibility of using 99mTc-Tg SPECT in the detection and staging of malignant lymphoma. materials and methods. Fifteen patients with newly diagnosed malignant lymphoma underwent 99mTc-Tg SPECT. Six patients had Hodgkin’s lymphoma and 9 patients had aggressive forms of non-Hodgkin’s lymphoma (NHL) : diffuse large b-cell lymphoma (7 cases), b-cell follicular lymphoma (1 case), and lymphoma from b cells in the marginal zone (1 case). Stage IIA was diagnosed in 5 patients, stage IIb in 1, stage IIIA in 1, stage IVA in 4 and stage IVb in 4 patients. results. Pathological 99mTc-Tg uptake in lymph nodes was observed in 14 (93 %) of the 15 patients. In one patient, the enlarged submandibular lymph node (16 mm in size) detected by CT was not visualized by 99mTc-Tg SPECT. This false-negative result was likely to be associated with increased accumulation of 99mTc-Tg in the oropharyngeal region. There were difficulties in the visualization of paratracheal, para-aortic and paracardial lymph nodes. These difficulties were associated with a high blood background activity, which persisted even 4 hours after intravenous injection of 99mTc-Tg. Software-based SPECT and CT image fusion allowed visualization of these lymph nodes. The pathological 99mTc-Tg accumulation in axillary, supraclavicular, infraclavicular and cervical lymph nodes was observed most often. Extranodal involvement was seen in 9 patients. 99mTc-Tg SPECT identified extranodal hypermetabolic lesions in 7 (78 %) of these patients. In one patient, hypermetabolic lesion in the lung detected by 99mTc-Tg SPECT was not detected on CT image. CT identified bone marrow involvement in the pelvic and scapula in 1 patient. The use of 99mTc-Tg SPECT allowed the visualization of hypermetabolic bone tissue lesions in this patient (Figure 4). In addition, in a patient with intact bone tissue on CT, 99mTc-Tg SPECT detected hypermetabolic lesions in the iliac bone. Conclusion. 99mTc-1-Thio-D-glucose demonstrated increased uptake in nodal and extranodal sites of lymphoma. The results indicate that SPECT with 99mTc-1-Thio-D-glucose is a feasible and useful tool in the detection and staging malignant lymphoma.
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The aim of the study was to identify differences in the immune system parameters between metastatic melanoma patients who responded and did not respond to dendritic cell vaccination. Material and Methods. The study group included 20 patients with stage III-IV metastatic melanoma, who received vaccine therapy with dendritic cells (DC) in a prophylactic mode. The control groups included 13 patients who had symptoms of disease progression at the time of starting vaccine therapy, and 5 healthy donors. The DC-vaccine was prepared in the form of a suspension of the patient's autologous dendritic cells loaded with tumor antigens in vitro . A single dose had 2 million dendritic cells in 1 ml of phosphate buffer solution, which was administered intradermally in the nearest site to the regional lymphatic collectors. The immune system status was assessed before starting vaccination. The immune system status was evaluated according to the indexes of 25 peripheral blood cell populations using multicolor flow cytometry and integral characteristic in the form of the visual image generated by the visualization method of multidimensional data (NovoSpark, Canada). Results. The immune status in patients with metastatic melanoma at the start of DC-vaccination differed and was associated with the effectiveness of subsequent vaccine therapy. The response to vaccination was observed in patients whose immune system status was similar to that of healthy individuals. Low efficacy of DC-vaccine therapy was shown in patients whose immune system status corresponded to that of patients with disease progression. Alterations of the immune system in patients with metastatic melanoma were registered both at the level of individual immunological parameters and at the level of visualized integral characteristics. The integral characteristics of the immune system associated with the patient's immunocompromised status can be considered as a criterion for stratification of patients with metastatic melanoma for the effective DC-vaccine therapy. Conclusion. The effectiveness of vaccine therapy with dendritic cells in patients with metastatic melanoma is associated with the immune system state before starting this therapy.
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