scholarly journals Mathematical Modeling of Locoregional Recurrence Caused by Premalignant Lesions Formed Before Initial Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Mitsuaki Takaki ◽  
Hiroshi Haeno
Keyword(s):  
Mathematical Model ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Locoregional Recurrence ◽  
Branching Processes ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Premalignant Lesions ◽  
Cancer Type ◽  
Normal Cells

Locoregional recurrence after surgery is a major unresolved issue in cancer treatment. Premalignant lesions are considered a cause of cancer recurrence. A study showed that premalignant lesions surrounding the primary tumor drove a high local cancer recurrence rate after surgery in head and neck cancer. Based on the multistage theory of carcinogenesis, cells harboring an intermediate number of mutations are not cancer cells yet but have a higher risk of becoming cancer than normal cells. This study constructed a mathematical model for cancer initiation and recurrence by combining the Moran and branching processes in which cells require two specific mutations to become malignant. There are three populations in this model: (i) normal cells with no mutation, (ii) premalignant cells with one mutation, and (iii) cancer cells with two mutations. The total number of healthy tissue is kept constant to represent homeostasis, and there is a rare chance of mutation every time a cell divides. If a cancer cell with two mutations arises, the cancer population proliferates, violating the homeostatic balance of the tissue. Once the number of cancer cells reaches a certain size, we conduct computational resection and remove the cancer cell population, keeping the ratio of normal and premalignant cells in the tissue unchanged. After surgery, we considered tissue dynamics and eventually observed the second appearance of cancer cells as recurrence. Consequently, we computationally revealed the conditions where the time to recurrence became short by parameter sensitivity analysis. Particularly, when the premalignant cells’ fitness is higher than normal cells, the proportion of premalignant cells becomes large after the surgical resection. Moreover, the mathematical model was fitted to clinical data on disease-free survival of 1,087 patients in 23 cancer types from the TCGA database. Finally, parameter values of tissue dynamics are estimated for each cancer type, where the likelihood of recurrence can be elucidated. Thus, our approach provides insights into the concept to identify the patients likely to experience recurrence as early as possible.

Small Molecular Leads Differentially Active Against HER2 Positive and Triple Negative Breast Cancer Cell Lines

2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cancer Type

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.

scholarly journals Links between Inflammation and Postoperative Cancer Recurrence

2021 ◽  
Vol 10 (2) ◽  
pp. 228
Author(s):  
Tomonari Kinoshita ◽  
Taichiro Goto
Keyword(s):  
Clinical Practice ◽  
Cancer Cells ◽  
Cancer Recurrence ◽  
Complete Resection ◽  
The Body ◽  
Cancer Development ◽  
Clinical Settings ◽  
Cancer Type ◽  
Clinical Indicators ◽  
The Status

Despite complete resection, cancer recurrence frequently occurs in clinical practice. This indicates that cancer cells had already metastasized from their organ of origin at the time of resection or had circulated throughout the body via the lymphatic and vascular systems. To obtain this potential for metastasis, cancer cells must undergo essential and intrinsic processes that are supported by the tumor microenvironment. Cancer-associated inflammation may be engaged in cancer development, progression, and metastasis. Despite numerous reports detailing the interplays between cancer and its microenvironment via the inflammatory network, the status of cancer-associated inflammation remains difficult to recognize in clinical settings. In the current paper, we reviewed clinical reports on the relevance between inflammation and cancer recurrence after surgical resection, focusing on inflammatory indicators and cancer recurrence predictors according to cancer type and clinical indicators.

scholarly journals LncRNA NEAT1 Silenced miR-133b Promotes Migration and Invasion of Breast Cancer Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3616 ◽  
Author(s):  
Xinping Li ◽  
Siwei Deng ◽  
Xinyao Pang ◽  
Yixiao Song ◽  
Shiyu Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cancer Type ◽  
Lncrna Neat1

Breast cancer, the most prevalent cancer type among women worldwide, remains incurable once metastatic. Long noncoding RNA (lncRNA) and microRNA (miRNA) play important roles in breast cancer by regulating specific genes or proteins. In this study, we found miR-133b was silenced in breast cancer cell lines and in breast cancer tissues, which predicted poor prognosis in breast cancer patients. We also confirmed that lncRNA NEAT1 was up-regulated in breast cancer and inhibited the expression of miR-133b, and identified the mitochondrial protein translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) that serves as the target of miR-133b. Both miR-133b knockdown and TIMM17A overexpression in breast cancer cells promoted cell migration and invasion both in vitro and in vivo. In summary, our findings reveal that miR-133b plays a critical role in breast cancer cell metastasis by targeting TIMM17A. These findings may provide new insights into novel molecular therapeutic targets for breast cancer.

scholarly journals Mathematical Model and Numerical Simulation for Electric Field Induced Cancer Cell Migration

2020 ◽  
Vol 26 (1) ◽  
pp. 4
Author(s):  
Antonino Amoddeo
Keyword(s):  
Mathematical Model ◽  
Electric Field ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Applied Electric Field ◽  
Nerve Fibers ◽  
Plasminogen Activation ◽  
Cell Dynamics ◽  
Plasminogen Activation System ◽  
Activation System

A mathematical model describing the interaction of cancer cells with the urokinase plasminogen activation system is represented by a system of partial differential equations, in which cancer cell dynamics accounts for diffusion, chemotaxis, and haptotaxis contributions. The mutual relations between nerve fibers and tumors have been recently investigated, in particular, the role of nerves in the development of tumors, as well neurogenesis induced by cancer cells. Such mechanisms are mediated by neurotransmitters released by neurons as a consequence of electrical stimuli flowing along the nerves, and therefore electric fields can be present inside biological tissues, in particular, inside tumors. Considering cancer cells as negatively charged particles immersed in the correct biological environment and subjected to an external electric field, the effect of the latter on cancer cell dynamics is still unknown. Here, we implement a mathematical model that accounts for the interaction of cancer cells with the urokinase plasminogen activation system subjected to a uniform applied electric field, simulating the first stage of cancer cell dynamics in a three-dimensional axial symmetric domain. The obtained numerical results predict that cancer cells can be moved along a preferred direction by an applied electric field, suggesting new and interesting strategies in cancer therapy.

scholarly journals Pulsed Magnetic Fields Cause hes1 and hsa-Circ-0068530 Expression Changes in Gastric Cancer Cell Line and Human Normal Fibroblast Cell Line

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Fereshteh Mansoury ◽  
Soheila Abdi ◽  
Nahid Babaei ◽  
Maliheh Entezari ◽  
Abbas Doosti ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Magnetic Flux ◽  
Cancer Cells ◽  
Cell Line ◽  
Electromagnetic Fields ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Normal Cells

Background: In recent years, the relationship between cancer cells and electromagnetic radiation has received much attention. Objectives: The present study aimed to evaluate the effects of different intensities of electromagnetic fields on gastric cancer cell lines (AGS). Methods: After preparing AGS and Hu02 (normal) cell lines, they were exposed to magnetic flux densities of 0.25, 0.5, 1, and 2 millitesla (mT) for 18 h. The cell viability was studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of hes1 and hsa-circ-0068530 RNAs were studied by the quantitative Real-time-PCR technique. Results: The inhibition of gastric cancer cell line growth was observed under the influence of electromagnetic fields at different intensities. However, they did not affect the viability of normal cells. A sharp increase in the expression of hes1 and hsa-circ-0068530 genes was observed in normal cells exposed to 2 mT electromagnetic fields. Conclusions: In general, it can be concluded that the effect of electromagnetic fields on gastric cancer cells depends on their intensity. Magnetic flux densities of 0.25 and 0.5 mT had anti-cancer effects and magnetic flux density of 2 mT showed carcinogenic effects.

scholarly journals Overview on the Side Effects of Doxorubicin

2020 ◽  
Author(s):  
Chittipolu Ajaykumar
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Cytotoxic Effect ◽  
Molecular Mechanisms ◽  
Current Understanding ◽  
Preventive Strategies ◽  
Normal Cells ◽  
Dna Strand

Doxorubicin is an anthracycline antibiotic extracted from the bacterium Streptomyces peucetius. Its cytotoxic effect produced by intercalating with DNA causing breakdown of DNA strand which causes cancer cell apoptosis. Despite being an effective anticancer agent it causes several crucial side effects like carditoxicity, neuropathy, hepatotoxicity, nephrotoxicity, alopecia, typhlitis, myelosuppression, neutropenia, anaemia, thrombocytopenia, nausea, and diarrhoea were caused mainly due to the inability to distinguish between cancer cells and normal cells. This chapter mainly focuses on doxorubicin’s side effects, current understanding of the molecular mechanisms, and management and preventive strategies of doxorubicin’s cardiotoxicity during the treatment of various type of cancer.

Targeting Y397 FAK scaffolding compared with FAK kinase inhibition: Efficacy and specificity for tumor cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13547-e13547 ◽  
Author(s):  
Vita Golubovskaya ◽  
Baotran Ho ◽  
Adam Stright ◽  
Maria Zajac-Kaye ◽  
Steven N. Hochwald ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Kinase Domain ◽  
Normal Cells ◽  
Atp Binding Site ◽  
Survival Signaling ◽  
Student’S T

e13547 Background: Focal Adhesion Kinase is a non-receptor kinase which is highly overexpressed and activated or autophosphorylated in many types of tumors and plays a major role in survival signaling and metastasis. Recently, our group developed a highly specific allosteric scaffolding FAK autophosphorylation inhibitor, Y15, that blocked FAK Y397 autophosphorylation, decreased cancer cell viability, and significantly decreased breast, neuroblastoma, pancreatic and glioblastoma tumor growth. In addition, Y15 was not toxic in mice. In this study, we compared side by side efficacy of Y15 with two other FAK inhibitors in clinical trials, Pfizer PF-04554878 and Glaxo GSK-2256098. Methods: MTT, clonogenicity and Western blotting assays were used to detect the effect of FAK inhibitors on different cancer and normal cells. Student’s t-test was used for statistical analysis and p<0.05 was considered significant. Results: We tested different cancer cell lines: kidney 293T, colon SW620 and LoVo; lung A549; glioblastoma U251 and U87; breast: BT474, MDA-231, MDA-361, MDA-453, MDA-468 and T47D and pancreatic PANC-1 cancer cells with different doses of Y15, PF and GSK inhibitors by MTT assay and found that Y15 was the most effective at decreasing cancer cell viability in most cancer cell lines, with higher efficacy than PF and much higher efficacy than GSK inhibitor. The same was observed for clonogenicity assay. In addition, we found that Y15 did not significantly affect viability of normal colon (CCD-112) cells, while viability of these cells with PF and GSK decreased to 54% and 57% at a 2 microM dose, respectively, from 100% in untreated cells. In addition, Y15 significantly decreased Y397-FAK, Y418-Src, phospho- Ser 473-AKT and phospho-ERK1/2, while PF had less effect and GSK only a minimal effect in four different cancer cell lines: U251, A549, 293T and Lovo at 10 microM and 100 microM doses, showing high potency of the FAK Y397 scaffolding inhibitor. Conclusions: These data show that Y15, which inhibits the Y397 site of FAK, is more potent against cancer cells and less toxic to normal cells than FAK inhibitors that target the conserved ATP-binding site in the kinase domain.

scholarly journals Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs)

2016 ◽  
Vol 113 (42) ◽  
pp. E6447-E6456 ◽  
Author(s):  
Thomas J. Bartosh ◽  
Mujib Ullah ◽  
Suzanne Zeitouni ◽  
Joshua Beaver ◽  
Darwin J. Prockop
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Kinase Inhibitor ◽  
Cancer Recurrence ◽  
Primary Treatment ◽  
Molecular Signature ◽  
Cellular Interactions ◽  
The Impact

Patients with breast cancer often develop malignant regrowth of residual drug-resistant dormant tumor cells years after primary treatment, a process defined as cancer relapse. Deciphering the causal basis of tumor dormancy therefore has obvious therapeutic significance. Because cancer cell behavior is strongly influenced by stromal cells, particularly the mesenchymal stem/stromal cells (MSCs) that are actively recruited into tumor-associated stroma, we assessed the impact of MSCs on breast cancer cell (BCC) dormancy. Using 3D cocultures to mimic the cellular interactions of an emerging tumor niche, we observed that MSCs sequentially surrounded the BCCs, promoted formation of cancer spheroids, and then were internalized/degraded through a process resembling the well-documented yet ill-defined clinical phenomenon of cancer cell cannibalism. This suspected feeding behavior was less appreciable in the presence of a rho kinase inhibitor and in 2D monolayer cocultures. Notably, cannibalism of MSCs enhanced survival of BCCs deprived of nutrients but suppressed their tumorigenicity, together suggesting the cancer cells entered dormancy. Transcriptome profiles revealed that the resulting BCCs acquired a unique molecular signature enriched in prosurvival factors and tumor suppressors, as well as inflammatory mediators that demarcate the secretome of senescent cells, also referred to as the senescence-associated secretory phenotype. Overall, our results provide intriguing evidence that cancer cells under duress enter dormancy after cannibalizing MSCs. Importantly, our practical 3D coculture model could provide a valuable tool to understand the antitumor activity of MSCs and cell cannibalism further, and therefore open new therapeutic avenues for the prevention of cancer recurrence.

scholarly journals Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells

Open Biology ◽  
2017 ◽  
Vol 7 (3) ◽  
pp. 160338 ◽  
Author(s):  
Christine A. Armstrong ◽  
Kazunori Tomita
Keyword(s):  
Transcriptional Regulation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Current Knowledge ◽  
Model Systems ◽  
Cancer Treatments ◽  
Normal Cells ◽  
Telomere Homeostasis ◽  
Multiple Levels

Aberrant activation of telomerase occurs in 85–90% of all cancers and underpins the ability of cancer cells to bypass their proliferative limit, rendering them immortal. The activity of telomerase is tightly controlled at multiple levels, from transcriptional regulation of the telomerase components to holoenzyme biogenesis and recruitment to the telomere, and finally activation and processivity. However, studies using cancer cell lines and other model systems have begun to reveal features of telomeres and telomerase that are unique to cancer. This review summarizes our current knowledge on the mechanisms of telomerase recruitment and activation using insights from studies in mammals and budding and fission yeasts. Finally, we discuss the differences in telomere homeostasis between normal cells and cancer cells, which may provide a foundation for telomere/telomerase targeted cancer treatments.

scholarly journals Terrein Inhibits Aggressive Phenotype of A549 Human Lung Cancer Cell through Suppression of HIF-1α

2021 ◽  
Vol 18 (11) ◽  
Author(s):  
Paiwan BUACHAN ◽  
Maneekarn NAMSA-AID ◽  
Wanlaya TANECHPONGTAMB
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Specific Effect ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Normal Cells ◽  
Aggressive Phenotype

Terrein is a fungal metabolite that has already been reported with anticancer properties. However, the effect on the aggressive phenotype of cancer cells has not been elucidated yet.  In the present study, the cytotoxicity of terrein was first determined against lung cancer cells (A549) model and compared with several normal cell lines (Vero, L6, and H9C2 cells). The data demonstrated that terrein had a specific effect on A549 cells relative to normal cells with high selectivity index values. Then, the hypoxic model that recognized to induce aggressive abilities was established in A549 cells by cobalt chloride (CoCl2) stimulation. With this model, terrein could reduce HIF-1α, a marker of hypoxia, and inhibit both migration and invasion of which the effect on invasion is more explicit. Our results demonstrated that terrein has a potential new role as the anti-aggressive phenotype by inhibiting cancer cell migration and invasion through HIF-1α reduction. HIGHLIGHTS Terrein, a secondary bioactive metabolite extracted from Aspergillus terreus, demonstrates anticancer effect on lung cancer cells with less cytotoxic on normal cells CoCl2 treatment was successfully used for creating hypoxic model which resulting in HIF-1a augmentation and aggressive abilities enhancement in lung cancer cells Terrein could reduce HIF-1a expression and invasive ability of lung cancer cells demonstrated the potential role as anti-metastatic agent for lung cancer GRAPHICAL ABSTRACT

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