Mitotic Activity Of Tumor Cells Research Articles

A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber

Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber mesh (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHN™Z and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHN™Z+rutin, significantly reduced sphere size compared to untreated and LHN™Z-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHN™Z+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHN™Z alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHN™Z+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin (IL)-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHN™Z+rutin is a promising biocompatible model for the local treatment of GB.

Dendritic Cell-Derived Artificial Microvesicles Inhibit RLS40 Lymphosarcoma Growth in Mice via Stimulation of Th1/Th17 Immune Response.

Cell-free antitumor vaccines represent a promising approach to immunotherapy of cancer. Here, we compare the antitumor potential of cell-free vaccines based on microvesicles derived from dendritic cells (DCs) with DC- and cationic-liposome-based vaccines using a murine model of drug-resistant lymphosarcoma RLS40 in vivo. The vaccines were the following: microvesicle vaccines-cytochalasin B-induced membrane vesicles (CIMVs) obtained from DCs loaded with total tumor RNA using cholesterol/spermine-containing cationic liposomes L or mannosylated liposomes ML; DC vaccines-murine DCs loaded with total tumor-derived RNA using the same liposomes; and liposomal vaccines-lipoplexes of total tumor-derived RNA with liposomes L or ML. Being non-hepatotoxic, CIMV- and DC-based vaccines administered subcutaneously exhibited comparable potential to stimulate highly efficient antitumor CTLs in vivo, whereas liposomal vaccines were 25% weaker CTL inducers. Nevertheless, the antitumor efficiencies of the different types of the vaccines were similar: sizes of tumor nodes and the number of liver metastases were significantly decreased, regardless of the vaccine type. Notably, the booster vaccination did not improve the overall antitumor efficacy of the vaccines under the study. CIMV- and DC- based vaccines more efficiently than liposome-based ones decreased mitotic activity of tumor cells and induced their apoptosis, stimulated accumulation of neutrophil inflammatory infiltration in tumor tissue, and had a more pronounced immunomodulatory activity toward the spleen and thymus. Administration of CIMV-, DC-, and liposome-based vaccines resulted in activation of Th1/Th17 cells as well as the induction of positive immune checkpoint 4-1BBL and downregulation of suppressive immune checkpoints in a raw PD-1 &gt;&gt;&gt; TIGIT &gt; CTLA4 &gt; TIM3. We demonstrated that cell-free CIMV-based vaccines exhibited superior antitumor and antimetastatic activity in a tumor model in vivo. The obtained results can be considered as the basis for developing novel strategies for oncoimmunotherapy.

Evaluation of fractionated and repeated sonodynamic therapy by using dual frequency for murine model of breast adenocarcinoma.

BackgroundSonodynamic therapy (SDT) is a new approach for cancer treatment. Repair by reoxygenation induces cell damage in all treatment which uses photo- and sonosensitizers. In this study, the in vivo antitumor effect of dual-frequency sonication is investigated at low-level intensity and hematoporphyrin (Hp). It is used for the treatment of spontaneous breast adenocarcinoma of Balb/c mice with a variety of dose repetition and fractionation regimes.MethodsEighty tumor-bearing mice were divided into eight groups, the control group (A); the sham group (B); the injection of Hp alone group (C); 30-min dual-frequency sonication with Hp injection in one repetition at the first day group (D); two repetitions at the first and sixth days group (E); three repetitions at the first, sixth, and twelfth days group (F); four repetitions at the first, sixth, twelfth, and eighteenth days (30 min/repetition) group (G); and the fractional treatment group treated by dual-frequency sonication and Hp injection at the first, third, sixth, and ninth days (7.5 min/fraction) (H). For each group, the tumor growth delay was calculated during 30 days after treatment. These tumors were studied histopathologically.ResultsThe results show that the treatment with ultrasound dose repetition in two, three, and four times (E, F, and G groups) were effective in delaying tumor growth compared with one-time sonication (D group) (p < 0.05). Also, the ultrasound dose fractionation is more effective in decreasing the tumor growth rate compared with the ultrasound dose repetition in four repeats and in one repeat from the 12th to the 30th day (p < 0.05). Histopathological studies indicated that the mitotic activity of tumor cells was reduced following treatment with four fraction and four repetition protocols.ConclusionThe ultrasound dose fractionation and repetition technique with dual-frequency sonication can have a useful therapeutic effect in sonodynamic therapy with the possibility of use in future clinical applications.

Neuroendocrine tumors of the vagina

The paper covers the most important topographic-anatomic and histological characteristics of the vagina, gives general information on the epidemiology of primary vaginal cancer (VC), on the rules of its staging, describes the frequently encountered morphological types of this tumor, and indicates the properties and features of the course of neuroendocrine tumors (NETs), including the most common manifestations of carcinoid syndrome and the symptoms of tumor hypersecretion of a number of biologically active substances. It also indicates the most common sites of NETs, the rules of their classification according to the grade and mitotic activity of tumor cells, as well as major methods for biochemical and radiological diagnosis. The immunohistochemical NET markers that can diagnose VC, their physiological role, sensitivity, and specificity, as well as the possibility of determining them in the body’s biological environments in order to increase physicians’ awareness are described in detail and the main aspects of tumor immunohistochemical staining are denoted. The role of circulating tumor cells as a promising method to specify the extent of NETs is defined. The paper gives epidemiological information on the development of vaginal NET and summarizes the available data by their clinical course and treatment results. It provides current guidelines on the required treatment volume and specifies the role of surgical intervention and the necessary volume if the intervention is expedient. It sets forth the up-to-date guidelines for chemotherapy for small cell tumors, as well as VC, which includes the specific features of managing patients with tumor recurrences depending on the time of their development.

Correction of Drug-Induced Hepatotoxicity with New Triterpene Derivatives in Transplanted RLS Lymphoma

The hepatoprotective effects of new triterpene derivatives, betulin 3β,28-di-O-nicotinate (of3) and 3,20-dioximino-29-norlup-28-ic acid methyl ester (of15), were studied in CBA/Lac mice with transplanted RLS lymphoma receiving polychemotherapy and without it. Injection of of3 and of15 agents to animals with tumors receiving polychemotherapy reduced the severity of toxic involvement of the liver, reduced mitotic activity of tumor cells in the primary node in animals receiving and not polychemotherapy, and produced a moderate antitumor effect. These effects were more pronounced for of15 agent. In addition, injection of agents of3 and of5 to animals with transplanted RLS lymphoma reduced the intensity of alterations associated with the total systems and local effects of the neoplastic process.

Proliferation of Walker 256 Carcinosarcoma Cells: Effect of Whole-Body Hyperthermia and Antitumor Agents

We studied the main biological characteristics of spontaneous growth of Walker 256 carcinosarcoma and under conditions of antitumor therapy. A combination of whole-body hyperthermia and cytostatic treatment (cyclophosphamide and melatonin) produced maximum suppression of the tumor growth, inhibition of mitotic activity of tumor cells, and stimulation of their necrotic and apoptotic death. The maximum decrease in mitotic activity of tumor cells was observed after combined exposure to whole-body hyperthermia and both cytostatic preparations; enhancement of apoptotic cell death and the decrease in the tumor node weight were also most pronounced under these conditions and practically no body weight loss was recorded in this case.

Role Of Lymphatic Polychemotherapy And Ehf Therapy In Treatment Of Colorectal Cancer Complicated By Carcinomatosis Of Abdominal Cavity

Aim: to improve treatment results of colorectal cancer, complicated carcinomatosis of abdominal cavity, by associated using of endolymphatic chemotherapy (ELCT) and local extremely high frequency (EHF) therapy.Materials and methods: I-group – 21 people (33.3%) performed colostomy, then neoadjuvant systemic chemotherapy by the scheme FOLFOX-4. It was held two cycles, after two cycles their were received cytoreductive surgery;II group – 26 people (41,3%) received cytoreductive operations with early postoperative intra-abdominal chemotherapy by oxaliplatin (200 mg/m(2) at day 1 and 5-FU 650 mg/m(2) from days 1 to 4.III group – 16 people (25,4%) also performed colostomy, then used 2 courses of ELCT with local EHF therapy and all patients were received cytoreductive operations. ELCT was carried out injecting oxaliplatin-100 mg/m(2) a day during 12 hours and then 5 – FU in doze of 600 mg/m2 a day during 72 hours by the instrumentality of the dozer and LV-200 mg/m(2) (2-h intravenous infusion). During ELCT patients received local EHF therapy in abdominal cavity for an hour.Results: After chemotherapy the partial regress of tumor observed in 1st group in 4,8 % and in 3rd –37,5 %, stabilization of process noted in 28,6 and 50% cases, progressing –66,7 and 12,5% cases correspondingly to groups. Histomorphologic study of malignant foci after ELCT+EHF therapy showed reduction of specific area of parenchyma cancer cell from 57 till 39% simultaneous growth of stroma from 40 till 58% and in necrosis area – from 1,8 till 2,5%. Mitotic activity of tumor cells in the 1st group decreased (average in 22 un.), but in 3rd group it decreased until 11 units. Analysis of life span showed that in 1st group of patients 2-year survival rate was 66,7%. In 2nd group of patients 2-year survival rate was 42,3%. Сonclusion: ELCH+EHF-therapy has high clinic efficacy and promotes to decrease terms of progression of tumor process, increases life span from 0 till 24% and quality of life of the patients. ELCH+EHF-therapy brings to reduction of specific area of parenchyma in cancer cells from 57 till 39% with simultaneous growth of stroma area from 40 till 58% and necrosis area – from 1,8 till 2,5%. ELCT+EHF-therapy lowers mitotic activity of tumor cells, activates apoptosis, hemodynamic and metabolic rates.

Expression of different proteoglycans in human breast tumors

The composition of proteoglycans and their changes during malignant transformation are important factors influencing adhesive properties and mitotic activity of tumor cells. In this study, expression level of different proteoglycans (decorin, syndecan-1, lumican, glypican-1, and aggrecan) in tumors and normal human breast tissue was investigated. Multiplex RT-PCR data revealed different expression changes for different proteoglycans in human breast tumors--syndecan expression was activated compared to almost no expression in normal breast tissue, expression of decorin and lumican decreased 2-5- and 2-3-fold, respectively, and aggrecan transcription seems to be unaffected. A change of expression level of decorin correlated with expression of D-glucuronyl-C5-epimerase, a key enzyme responsible for the biosynthesis of idurone-containing glycosaminoglycans, possessing antimitotic activity. The results suggest that changes in decorin, lumican, and syndecan-1 expression in tumor tissue could induce a distortion of proteoglycan composition and mitotic activity of cells in human breast tumor.

Epitalon and colon carcinogenesis in rats: Proliferative activity and apoptosis in colon tumors and mucosa

The effect of the synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on proliferative activity in colon tumors, and in mucosal epithelial cells adjacent to and located far from tumors was studied in rats. To evaluate the effect of Epitalon on different stages of carcinogenesis, different treatment regimens were used: during the tumor initiation stage, during the tumor-promotion stage, or during the entire process of tumor development. Eighty 2-month-old male LIO rats were exposed weekly to five subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg body weight. Rats were divided into four groups. Control rats (group 1) received saline at a dose of 0.1 ml during the entire experiment. Rats in group 2 were treated with Epitalon at a dose of 1 micro g, five times a week, for 6 months, from the first injection of DMH till the end of the experiment. Rats in group 3 were treated with Epitalon after termination of the carcinogen injections. Rats in group 4 were treated with Epitalon only during the period of DMH exposure (for the first 5 weeks of the experiment). DMH induced proliferation of the secretory epithelium, and this phenomenon was accompanied by a decrease in the size of the stromal area and the area of lymph infiltration in colon tumors and in the colon mucosa adjacent to the tumors (group 1). Epitalon attenuated this effect, especially when the treatment was continued throughout the experiment (group 2). It increased the stromal areas, as well as that of lymphoid infiltration in the colon mucosa adjacent to the tumors. The intensity of lymphoid infiltration was activated in both the colon mucosa adjacent to a tumor and in the tumor. Mitotic activity of tumor cells was significantly inhibited by Epitalon when the treatment was given throughout the experiment (group 2). In parallel, a high level of apoptosis was seen in the same group. Thus, the strongest inhibitory effect of Epitalon on carcinogenesis in the colon mucosa was manifested when the treatment was continued throughout the experiment.

Methodologic aspects of a standardized evaluation of mitotic activity in tumor tissues

Although estimation of mitotic activity is generally a recognized clinical practice in the diagnosis and grading of tumors, there are several methodologic aspects that merit special consideration. Our results, in relation to those of others, lead to the following conclusions: 1. The values attained by calculating the mitotic activity of tumor cells in paraffin-embedded tumor tissue are lower than those obtained in vivo. The results cannot always be interpreted clinically due to the complexity of some of the factors associated with it which require special attention. That the method still has clinical relevance and value in spite of the associated problems may be due to the fact that tumor tissues generally undergo long periods of hypoxia before being fixed for histomorphological analyses--a condition which by itself is a decisive factor in the reduction of mitotic activity--so that additional changes in some individual factors from case to case do not make much difference to the estimated or calculated value. 2. Mitotic activity should be calculated in areas of tumor sections where there are numerous mitotic tumor cells. Additionally, only cells with nuclei showing lysed nuclear membranes and identifiable single chromosomes at higher magnification ought to be considered in the calculation. Apoptotic and pyknotic elements should not be calculated. 3. The specification of the final magnification (e.g., x 400) is not a sufficient basis for comparison of optical conditions for the mitotic estimation, since the visual fields of standard light microscopes may differ up to 2.6-fold. A temporary streamlining of the standard may be the application of a 0.159 mm2 visual field (x 40 objective, x 10 ocular by visual field value 18). As an intermediate goal, mitosis should be calculated in percentages of the tumor cells or areas of the total tumor tissue. 4. The interspecific reproducibility of the quantified mitosis makes it reliable for clinical application. It compares well with cytometric and morphometric methods in assessment of tumor cells and is of higher clinical relevance than the conventional histomorphological tumor grading systems.

Regression of Sarcoma-180 after cis-Dichlorodiammineplatinum (II) : A Fine Structural Study

Sarcoma-180, a transplantable tumor in Swiss White mice regresses completely after a single intraperitoneal injection of cis-Dichlorodiammineplatinum (II). Fine structural studies before and after cis (Pt (NH3)2C12) treatment show certain morphological changes indicative of possible mechanisms involved in the tumor regression. The mitotic activity of tumor cells is inhibited soon after platinum injection possibly due to its interaction with DNA. Appearance of plasma cells (Fig. 1) and lymphocytes within the tumor mass after a 4-6 days period of platinum treatment indicates a possible enhancement of the immune system. The plasma cells display a well developed RER and a typical nuclear morphology. Further studies on spleen of both treated and control animals show an increase in the number of plasma cells after about 5 days of platinum treatment (Fig. 2).The increase in the lymphocytes and the plasma cells indicates an immune system at the cellular level as these antibody producing cells directly come in contact with the Sarcoma-180 cells. Also the double diffusion method on agar plates indicates the enhanced humoral antibody production against Sarcoma-180 as opposed to the controls.

Effect of periodic administration of antitumor sera on mitotic activity of tumor cells

Effect of periodic administration of antitumor sera on mitotic activity of tumor cells

Duration of the inhibiting influence of antironidase serum and its ?-globulin fraction on the mitotic activity of tumor cells

Duration of the inhibiting influence of antironidase serum and its ?-globulin fraction on the mitotic activity of tumor cells