THE STUDY OF CIRCADIAN RHYTHMS IN OVARIAN CANCER RAT MODEL: IS THERE CONNECTION BETWEEN TUMOR DEVELOPMENT AND RHYTHMICITY DISRUPTION IN INTACT TISSUES?

2019 ◽  
Vol 65 (6) ◽  
pp. 889-897
Author(s):  
Galina Kireeva ◽  
Yekaterina Gubareva ◽  
Natalya Mityushkina ◽  
Andrey Panchenko ◽  
Mikhail Maydin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Circadian Rhythms ◽  
Tumor Cells ◽  
Clock Genes ◽  
Tumor Development ◽  
Tumor Model ◽  
Circadian Rhythmicity ◽  
Normal Tissues ◽  
Tumor Bearing

Considering emerging yet contradictory data on circadian rhythms disruption and its effects on tumor initiation and progression, we performed in vivo study to evaluate changes (if any) in clock genes expression in tumor compared to intact tissues as well as to see if tumor development affects normal tissues in tumor-bearing animals. The study was performed in 75 female Wistar rats, intraperitoneally transplanted ovarian cancer was used as a tumor model. Tumor-bearing rats had fragmented circadian rhythmicity of their locomotor activity compared to intact animals. No circadian rhythmicity in proliferation of tumor cells was detected. Precise proliferative rhythmicity was found in normal cells (intestinal epithelium) of intact rats, while significant disruption in such rhythmicity was observed in the same cells of tumor-bearing rats. Average clock genes (BMAL1, CLOCK, CRY1, PER2) expression rate was significantly reduced in tumor cells compared to intact tissues. The data from these experiments let us choosing 2 time points to perform chemotherapy in the following study where effects of chronochemotherapy will be evaluated.

scholarly journals Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53

2017 ◽  
Vol 44 (1) ◽  
pp. 255-266 ◽  
Author(s):  
Jinjin Liu ◽  
Jun Rao ◽  
Xuming Lou ◽  
Jian Zhai ◽  
Zhenhua Ni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Development ◽  
Tumor Model ◽  
Migration And Invasion ◽  
P53 Expression ◽  
Protein Levels ◽  
Normal Tissues ◽  
P53 Signaling

Background/Aims: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). Methods: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. Results: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. Conclusions: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.

Clinical Evaluation of Radio-Labelled Bleomycin for Tumor Detection

1978 ◽  
Vol 17 (06) ◽  
pp. 238-248
Author(s):  
H. Beekhuis ◽  
M.A.P.C. van de Poll ◽  
A. Versluis ◽  
H. Jurjens ◽  
M.G. Woldring ◽  
...  
Keyword(s):  
Clinical Evaluation ◽  
Acidic Solution ◽  
Tumor Detection ◽  
Neutral Solution ◽  
Normal Tissues ◽  
Patients With Cancer ◽  
Tumor Bearing

Investigations with bleomycin labelled with radionuclides other than 57Co in patients with cancer and in tumor-bearing animals are described. In patients 57Co-bleo appears to be a better tumor-seeking radiopharmaceutical than 111In-bleo, 99mTc-bleo or 197Hg-bleo. This can be explained by a higher stability in vivo and a better tumor-seeking property of 57Co-bleo and less disturbing activity in the cardiac pool and in bone and other normal tissues when assessing the scintigram.Results with 111In-bleo labelled in acidic solution are not essentially different from those with 111In-bleo labelled in neutral solution.Results of 197Hg-bleo are almost identical with those of 197HgCl2 regarding the tumor-seeking effect as well as the distribution in normal tissues and organs. Probably the complex of 197Hg to bleomycin is not stable in vivo. The superiority of 57Co-bleo over 99mTc-bleo, 197Hg-bleo and also over 67Cu-bleo is confirmed by experiments on tumor bearing animals.We may conclude that the indication for use of bleomycin as a tumor-seeking pharmaceutical labelled with 111In, 99mTc, 197Hg or 67Cu seems to be very limited.

scholarly journals Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takashi Nishina ◽  
Yutaka Deguchi ◽  
Daisuke Ohshima ◽  
Wakami Takeda ◽  
Masato Ohtsuka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Human Cancer ◽  
Tumor Development ◽  
Gene Signature ◽  
Free Survival ◽  
Expression Of Genes ◽  
Reporter Mice ◽  
Interleukin 11

AbstractInterleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

scholarly journals Early Detection and Dynamic Changes of Circulating Tumor Cells in Transgenic NeuN Transgenic (NTTg) Mice with Spontaneous Breast Tumor Development

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3294
Author(s):  
Wen-Sy Tsai ◽  
Tsung-Fu Hung ◽  
Jia-Yang Chen ◽  
Shu-Huan Huang ◽  
Ying-Chih Chang
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Breast Tumor ◽  
Early Stage ◽  
Tumor Development ◽  
P Value ◽  
Vascular Density ◽  
Dynamic Changes ◽  
Tumor Bearing ◽  
Development Methods

Background: This study used NeuN transgenic (NTTg) mice with spontaneous breast tumor development to evaluate the dynamic changes of circulating tumor cells (CTCs) prior to and during tumor development. Methods: In this longitudinal, clinically uninterrupted study, we collected 75 μL of peripheral blood at the age of 8, 12, 16, and 20 weeks in the first group of five mice, and at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability in the second group of four mice. Diluted blood samples were run through a modified mouse-CMx chip to isolate the CTCs. Results: The CTC counts of the first group of mice were low (1 ± 1.6) initially. The average CTC counts were 16 ± 9.5, 29.0 ± 18.2, and 70.0 ± 30.3 cells per 75 μL blood at the age of 32 weeks, the time of tumor palpability, and one week after tumor palpability, respectively. There was a significant positive correlation between an increase in CTC levels and tumor vascular density (p-value < 0.01). This correlation was stronger than that between CTC levels and tumor size (p-value = 0.076). The captured CTCs were implanted into a non-tumor-bearing NTTg mouse for xenografting, confirming their viability and tumorigenesis. Conclusion: Serial CTCs during an early stage of tumor progression were quantified and found to be positively correlated with the later tumor vascular density and size. Furthermore, the successful generation of CTC-derived xenografts indicates the tumorigenicity of this early onset CTC population.

Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo

2005 ◽  
Vol 13 (6) ◽  
pp. 337-343 ◽  
Author(s):  
Bhawna Gupta ◽  
Tatiana S. Levchenko ◽  
Dmitry A. Mongayt ◽  
Vladimir P. Torchilin
Keyword(s):  
Monoclonal Antibody ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Tumor Model ◽  
Subcutaneous Tumor ◽  
Brain Tumor Cells

Characterization of an intraperitoneal ovarian cancer xenograft model in nude rats using noninvasive microPET imaging

2007 ◽  
Vol 17 (2) ◽  
pp. 407-417 ◽  
Author(s):  
C. L. Zavaleta ◽  
W. T. Phillips ◽  
Y. C. Bradley ◽  
L. M. McMANUS ◽  
P. A. Jerabek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Nodes ◽  
Peritoneal Cavity ◽  
Imaging Modality ◽  
Xenograft Model ◽  
Tumor Model ◽  
Fdg Uptake ◽  
Tumor Bearing ◽  
Nude Rats ◽  
Biodistribution Data

MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose (18F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 μCi) of 18F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of 18F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of 18F-FDG throughout the peritoneal cavity of tumor rats (mean SUV = 4.64) compared with control rats (mean SUV = 1.03). Ascites gathered from tumor-bearing rats had increased 18F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. 18F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using 18F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model.

scholarly journals Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior

2017 ◽  
Vol 114 (4) ◽  
pp. 758-763 ◽  
Author(s):  
Kyoichi Hashimoto ◽  
Yosuke Yamada ◽  
Katsunori Semi ◽  
Masaki Yagi ◽  
Akito Tanaka ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Tumor Cells ◽  
Critical Role ◽  
Tumor Development ◽  
Cell Lineage ◽  
Genetic Rescue ◽  
Cellular Behavior ◽  
Cellular Context ◽  
Context Dependent

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.

scholarly journals Breast Tumor Cells Highly Resistant to Drugs Are Controlled Only by the Immune Response Induced in an Immunocompetent Mouse Model

2019 ◽  
Vol 18 ◽  
pp. 153473541984804 ◽  
Author(s):  
Paola Lasso ◽  
Mónica Llano Murcia ◽  
Tito Alejandro Sandoval ◽  
Claudia Urueña ◽  
Alfonso Barreto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
High Capacity ◽  
Cancer Cell Line ◽  
Tumor Model ◽  
Main Element ◽  
In Vivo Models

Background: The tumor cells responsible for metastasis are highly resistant to chemotherapy and have characteristics of stem cells, with a high capacity for self-regeneration and the use of detoxifying mechanisms that participate in drug resistance. In vivo models of highly resistant cells allow us to evaluate the real impact of the immune response in the control of cancer. Materials and Methods: A tumor population derived from the 4T1 breast cancer cell line that was stable in vitro and highly aggressive in vivo was obtained, characterized, and determined to exhibit cancer stem cell (CSC) phenotypes (CD44+, CD24+, ALDH+, Oct4+, Nanog+, Sox2+, and high self-renewal capacity). Orthotopic transplantation of these cells allowed us to evaluate their in vivo susceptibility to chemo and immune responses induced after vaccination. Results: The immune response induced after vaccination with tumor cells treated with doxorubicin decreased the formation of tumors and macrometastasis in this model, which allowed us to confirm the immune response relevance in the control of highly chemotherapy-resistant ALDH+ CSCs in an aggressive tumor model in immunocompetent animals. Conclusions: The antitumor immune response was the main element capable of controlling tumor progression as well as metastasis in a highly chemotherapy-resistant aggressive breast cancer model.

Effect of metallic nanoparticles on tumor growth: In vivo study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15650-e15650
Author(s):  
Elena Yu. Zlatnik ◽  
Elena I. Triandafilidi ◽  
Oksana V. Bykadorova ◽  
Oleg I. Kit ◽  
Galina V. Zhukova ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Ascitic Fluid ◽  
Metallic Nanoparticles ◽  
Fluid Volume ◽  
Control Group ◽  
Absolute Amount ◽  
Tumor Bearing ◽  
Sarcoma 37 ◽  
Zn Injection

e15650 Background: The aim of the study was to assess the effect of metallic nanoparticles on growth of transplanted ascitic tumor sarcoma 37 in mice. Methods: Nanoparticles (NP) of transition metals were experimentally developed and kindly provided us by Prof. V.B. Borodulin. Ultradispersed metallic powders (NP Cu, NP Zn, NP Fe) 30-100 nm sized were dispersed by ultrasound in 0.85% NaCl before use and daily administrated intraperitoneally to tumor-bearing mice with ascitic sarcoma 37. Injections of NP 500 µl (10 µg/ml) were performed for 4 days, and 4 days after the completion of the course mice were sacrificed. The control group received 0.85% NaCl. Ascitic fluid volume was measured and living cells were counted. Results: In all the tumor-bearing mice the progression of ascites was noted: it was maximal in controls, less in animals having received NP Fe and NP Cu, minimal – in mice after injection of NP Zn. The volume of the latter was 0.78±0.31 ml in comparison with control data: 1.79±0.66 ml (p < 0.05); it was also less than in mice after administration of NP Cu (2.16±0.68 ml) and NP Fe (3.3±1.3 ml). Similar difference was seen in the amount of tumor cells in ascitic fluid: (1.67±0.5)х106/ml after the injection of NP Zn and (27.7±2.86)х106/мл in the control group. Effect of NP Cu and NP Fe was less pronounced than of NP Zn though obvious in spite of the noted tendency of the increase of the ascitic fluid volume. The most significant changes were observed when absolute amount of living tumor cells was counted per one mouse – it was minimal after NP Zn administration (0.636±0.2)х106/ml and maximal in the control group (23.98±10.5)х106/ml), i.e. only 2.6% of tumor cells had survived after NP Zn injection. Conclusions: Our results demonstrate that metallic NP were able to produce antitumor in vivo without any supplements like laser or hyperthermia: the effect was likely to depend upon the metal and was the highest in NP Zn compared to NP Cu and Fe.

scholarly journals Candida Albicans Activated Splenocytes Promote Strong Immune Responses in a Murine Model of Breast Cancer

2021 ◽  
Author(s):  
Siavash Mashhouri ◽  
Erfan Yarahmadi ◽  
Seyyed Meysam Abtahi Froushani
Keyword(s):  
Breast Cancer ◽  
Candida Albicans ◽  
Immune Responses ◽  
Survival Curve ◽  
Tumor Development ◽  
Yeast Form ◽  
Tumor Bearing ◽  
4T1 Cells ◽  
Breast Cancer Growth

Background: The potential of Candida albicans to modulate antigen-presenting cells maturation has been documented in past studies. Dendritic cells are critical modulators in the orchestration of adaptive immune responses alongside myeloid subtypes, which play an important role in the presentation of antigens to T cells. The aim of this study was to evaluate the efficacy of splenocytes activated with the extract of heated 4T1 cells and the yeast form of C. albicans against breast cancer growth in vivo. Methods: 4T1 cells were subcutaneously injected into the left flanks of female BALB/c mice (n=40). At a time when palpable tumors had developed, experimental groups were immunized twice at one-week interim with either activated splenocytes with the extract of heated 4T1 or the killed preparation of yeast form of C. albicans or a combination of the two-One week after the second injection, one-half of animals (n=20) were euthanized to investigate the immune response profile. Results: Administration of activated splenocytes with the combination protocol caused a favorable survival curve and slower rates of tumor development compared to other tumor-bearing mice. Moreover, combination therapy significantly increased the secretion of IFN-γ, respiratory burst and nitric oxide production and conversely diminished the secretion of IL-4, IL-10 and TGF-β in the splenocyte population. Conclusion: Since the murine 4T1 cell line is similar to the final stage of human breast carcinoma, we postulate that activated splenocytes with the extract of heated 4T1 cells and yeast form of C. albicans can reduce tumor development in tumor-bearing mice.

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