Growth Rate Of Cancer Cells Research Articles

Upregulation of EPSTI1/Drp1/AKT1 Signaling Pathways Using pDNA/Melittin Against Breast Cancer.

This study investigates the role of genes related to breast cancer in apoptosis control. A melittin nucleic acid sequence was synthesized and introduced into a pcDNA3.1(+) Mammalian Expression Plasmid. The cloning accuracy was assessed using PCR testing and enzyme digestion techniques. The vectors were transfected into cells using LipofectamineTM2000. The transfection efficacy of MCF-7 and 4T1 cells was evaluated using fluorescence and bright-field imaging. Pure melittin produced from bee venom had a notable hemolytic impact, with lower hemolytic activity levels than the positive control, Triton X-100. The growth rate of 4T1 and MCF-7 cancer cells was significantly inhibited. The apoptosis rates were 8.54%, 46.20%, and 78.82% for free pDNA, melittin, and pDNA-melittin, respectively. The C-pDNA/Melittin-treated group showed a statistically significant reduction in cancer factors compared to the control group. The treated tumors exhibited significant necrosis and late apoptosis, with a prevalence ranging from about 5% to 10% of the lesions. After exposure to pDNA-melittin, there was no significant increase in transcription levels of caspase-3, caspase-8, BCRA1, BAX, Drp1, AKT1, and EPSTI1 genes in the normal non-cancerous groups. The findings provide novel opportunities for the therapeutic targeting of malignancies via melittin and the stimulation of the EPSTI1/Drp1/AKT1 signaling cascades.

Research progress in endometriosis-associated ovarian cancer.

Endometriosis-associated ovarian cancer (EAOC) is a unique subtype of ovarian malignant tumor originating from endometriosis (EMS) malignant transformation, which has gradually become one of the hot topics in clinical and basic research in recent years. According to clinicopathological and epidemiological findings, precancerous lesions of ovarian clear cell carcinoma (OCCC) and ovarian endometrioid carcinoma (OEC) are considered as EMS. Given the large number of patients with endometriosis and its long time window for malignant transformation, sufficient attention should be paid to EAOC. At present, the pathogenesis of EAOC has not been clarified, no reliable biomarkers have been found in the diagnosis, and there is still a lack of basis and targets for stratified management and precise treatment in the treatment. At the same time, due to the long medical history of patients, the fast growth rate of cancer cells, and the possibility of eliminating the earliest endometriosis-associated ovarian cancer, it is difficult to find the corresponding histological evidence. As a result, few patients are finally diagnosed with EAOC, which increases the difficulty of in-depth study of EAOC. This article reviews the epidemiology, pathogenesis, risk factors, clinical diagnosis, new treatment strategies and prognosis of endometriosis-associated ovarian cancer, and prospects the future direction of basic research and clinical transformation, in order to achieve stratified management and personalized treatment of ovarian cancer patients.

ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair.

Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as a significant player in transcription and the DNA damage response pathway. Transcriptional effects induced by ARGLU1 occur via enhancement of promoter-proximal RNA polymerase II pausing, likely by inhibiting the interaction between JMJD6 and BRD4. When overexpressed, ARGLU1 increases the growth rate of cancer cells, while its knockdown leads to growth arrest. Significantly, overexpression of ARGLU1 increased cancer cell resistance to genotoxic drugs and promoted DNA damage repair. These results identify new roles for ARGLU1 in cancer cell survival and the DNA damage repair pathway, with potential clinical implications for chemotherapy resistance.

Abstract 4241: Development of stroma cells-rich oral cancer organoid for functional analysis of tumor microenvironment

Abstract Background: Tumor microenvironment (TME), composed of cancer cells, endothelial cells, fibroblast, immune cells, and etc, plays crucial roles in tumor progression and treatment resistance. Thus, it is extremely important to find its role involved in the interaction of TME. However, it is more difficult to examine the biological activities of those cells in vitro assay. The purpose of this study is to develop stroma cells-incorporating preclinical model, termed stroma cells-rich oral cancer organoid, for functional analysis of TME. Materials and Methods: We have first developed the stroma cells-rich oral cancer organoid by selecting the types of stroma cells such as endothelial cells, fibroblast, ratio of those cells, culture method, 3-D methods, culture media, and supplement of growth factors. Then, growth rate, morphology, radiosensitivity, and drug response were analyzed to investigate the effect of TME. Finally, the function of tumor-associated macrophage was determined using this organoid model. The growth rate of cancer cells and drug response were investigated using the organoid treated with supernatant of M1 and M2 macrophages polarized from THP-1 monocyte. Results: Oral cancer cells were co-cultured with endothelial cells (ECs) and mesenchymal stem cells (MSCs) in a particular ratio in 3D-culture, and the formed organoid became sphere. The vascular formation in the organoid was confirmed by immunofluorescent analysis. The organoid also showed higher tumorigenicity in nude mice when inoculated, compared to cancer cells alone or mixed cells with ECs and MSCs. Cell viability of luciferase-expressing tongue cancer cells (OSC-19-luc) in the organoid was assessed after treatment with cisplatin using the IVIS system showing that OSC-19-luc organoid was resistance to cisplatin compared to 3D-cultured OSC-19-luc alone or OSC-19-luc co-cultured with ECs/MSCs. The supernatant of M1 or M2 macrophage had no effect on cancer cell growth in the organoid. However, when the organoid was treated with cisplatin in the presence of M2 macrophage supernatant, the drug sensitivity was low compared to those of M1 suggesting that secretory factor from M2 macrophage may lead to drug resistance of oral cancer cells in the presence of TME. Conclusions: We have successfully established stroma cells-incorporating preclinical model that recreates the tumor microenvironment by co-culturing stromal cells. This will serve as a platform that can recapitulate the tumor biology and drug response profiles of cancer cells derived from individual oral cancer patients. This will also enable us to elucidate the role of other factors in TME and to identify novel targets for the treatment of chemo-resistant oral cancer. Citation Format: Ami Shimoda, Shizuka Shiiya, Haruka Yoshii, Kenji Mitsudo, Mitomu Kioi. Development of stroma cells-rich oral cancer organoid for functional analysis of tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4241.

WITHDRAWN: Towards robotic laboratory automation Plug & play: Survey and concept proposal on teaching-free robot integration with the LAPP digital twin

Establishment of drug testing of patient-derived cancer cells (PDCs) in physiologically relevant 3-dimensional (3D) culture is central for drug discovery and cancer research, as well as for functional precision medicine. Here, we describe the detailed protocol allowing the 3D drug testing of PDCs – or any type of cells of interest – in Matrigel in 384-well plate format using automation. We also provide an alternative protocol, which does not require supporting matrices. The cancer tissue is obtained directly from clinics (after surgery or biopsy) and processed into single cell suspension. Systematic drug sensitivity and resistance testing (DSRT) is carried out on the PDCs directly after cancer cell isolation from tissue or on cells expanded for a few passages. In the 3D-DSRT assay, the PDCs are plated in 384-well plates in Matrigel, grown as spheroids, and treated with compounds of interest for 72 h. The cell viability is directly measured using a luminescence-based assay. Alternatively, prior to the cell viability measurement, drug-treated cells can be directly subjected to automated high-content bright field imaging or stained for fluorescence (live) cell microscopy for further image analysis. This is followed by the quality control and data analysis. The 3D-DSRT can be performed within a 1–3-week timeframe of the clinical sampling of cancer tissue, depending on the amount of the obtained tissue, growth rate of cancer cells, and the number of drugs being tested. The 3D-DSRT method can be flexibly modified, e.g., to be carried out with or without supporting matrices with U-bottom 384-well plates when appropriate for the PDCs or other cell models used.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC)

BackgroundRecently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient‘s groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test.MethodsOn the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides.ResultsThe conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response.ConclusionsTherefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

MiR-199a and miR-199b facilitate diffuse gastric cancer progression by targeting Frizzled-6

Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify microRNAs (miRNAs) that can differentiate between early and advanced DGC in the gastric mucosa, miRNA expression profiling was performed using the NanoString nCounter method in human DGC tumors. Ectopic expression of miR-199a and miR-199b (miR-199a/b) in SNU601 human GC cells accelerated the growth rate, viability, and motility of cancer cells and increased the tumor volume and weight in a mouse xenograft model. To study their clinicopathological roles in patients with GC, miR-199a/b levels were measured in human GC tumor samples using in situ hybridization. High miR-199a/b expression level was associated with enhanced lymphovascular invasion, advanced T stage, and lymph-node metastasis. Using the 3′-untranslated region (UTR) luciferase assay, Frizzled-6 (FZD6) was confirmed to be a direct target of miR-199a/b in GC cells. siRNA-mediated depletion of FZD6 enhanced the motility of SNU601 cells, and addback of FZD6 restored cancer cell motility stimulated by miR-199a/b. In conclusion, miR-199a/b promotes DGC progression by targeting FZD6, implying that miR-199a/b can be used as prognostic and diagnostic biomarkers for the disease.

Mathematical Model of Leukemia Treatment with Chimeric Antigen Receptor (CAR) T Cell Therapy

Leukemia, a type of blood cancer that originates in the bone marrow, is characterized by the uncontrolled growth of abnormal blood cells, which disrupt the normal functioning of blood cells. Chimeric antigen receptor (CAR) T-cell treatment, a form of immunotherapy, utilizes genetically modified T cells to specifically target and eliminate cancer cells. This treatment has shown promising results for leukemia patients who are unresponsive to chemotherapy or other therapies, as well as those who experience relapses. In this study, we develop a mathematical model of leukemia that incorporates chimeric antigen receptor (CAR) T-cell therapy. The model takes into account the logistic intrinsic growth rate of leukemia cells, which gradually declines over time due to limited resources within the body. There are four compartments in this model: susceptible blood cells, infected blood cells, leukemia cells, and immune cells. We have analyzed the equilibrium points and their local stability, determined the basic reproduction number, and conducted a sensitivity analysis. Through numerical simulations, we observed that prior to treatment, the number of leukemia cells in the blood escalated rapidly towards endemic conditions. However, after receiving CAR T-cell therapy through external infusion, the leukemia cells either became extinct or took a significant amount of time to reach endemic levels in the blood. Sensitivity analysis revealed that the growth rate of cancer cells (r) and the death rate of immune cells (significantly contribute to the increase in the basic reproduction number (.

Anticancer Activity of Mineral-Supplemented Organically Cultivated Carrot on HT-29 Cells and Its Anti-Inflammatory Effect on Mice Splenocytes

Carrot (Daucus carota) is one of the world’s most significant root vegetables, with various bioactivities. This study aimed to investigate the anticancer activity and anti-inflammatory effects of natural dream cultivation carrot (NC). Natural dream cultivation is a cultivation method based on organic farming incorporating minerals. An MTT assay was used to evaluate the inhibitory rate of carrot samples on HT-29 human colon cancer cells, and qPCR was used to assess the mRNA expression of the cell cycle and apoptosis-related genes in the cancer cells. The nitrite oxide (NO) concentration was determined using the Griess method. The levels of inflammatory cytokines in LPS-induced mouse splenocytes were determined using an enzyme-linked immunosorbent assay, and the activity of NK cells was determined using LDH analysis. The results revealed that NC effectively inhibited cancer cell growth rate. Moreover, NC upregulated the mRNA expression of cell-cycle-arrest-related genes (p53 and p21) and apoptosis-related genes (Bim, Bad, Bax, Bak, caspase-9, and caspase-3) in cancer cells while downregulating the expression of anti-apoptotic genes, Bcl-2 and Bcl-xL. NC inhibited NO production and the release of inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, and IL-12) in LPS-induced mouse splenocytes. NC also demonstrated the ability to stimulate NK cell activation. This study explored the potential mechanisms underlying carrots’ anticancer and anti-inflammatory properties by investigating their inhibitory effects on cancer cells and regulating the inflammatory response. The innovative mineral-supplemented organic cultivation method, as explored in this study, opens new avenues for harnessing the potential of carrots as a functional food source with promising applications in cancer and inflammation management. This research not only provides insights into the bioactive potential of carrots but also contributes to the future development of novel dietary interventions and therapeutics.

Hypoxia Changes Energy Metabolism and Growth Rate in Non-Small Cell Lung Cancer Cells.

Hypoxia occurs in 80% of non-small cell lung carcinoma (NSCLC) cases, leading to treatment resistance. Hypoxia's effects on NSCLC energetics are not well-characterized. We evaluated changes in glucose uptake and lactate production in two NSCLC cell lines under hypoxia in conjunction with growth rate and cell cycle phase distribution. The cell lines A549 (p53 wt) and H358 (p53 null) were incubated under hypoxia (0.1% and 1% O2) or normoxia (20% O2). Glucose and lactate concentrations in supernatants were measured using luminescence assays. Growth kinetics were followed over seven days. Cell nuclei were stained with DAPI and nuclear DNA content was determined by flow cytometry to determine cell cycle phase. Gene expression under hypoxia was determined by RNA sequencing. Glucose uptake and lactate production under hypoxia were greater than under normoxia. They were also significantly greater in A549 compared to H358 cells. Faster energy metabolism in A549 cells was associated with a higher growth rate in comparison to H358 cells under both normoxia and hypoxia. In both cell lines, hypoxia significantly slowed down the growth rate compared to proliferation under normoxic conditions. Hypoxia led to redistribution of cells in the different cycle phases: cells in G1 increased and the G2 population decreased. Glucose uptake and lactate production increase under hypoxia in NSCLC cells indicated greater shunting of glucose into glycolysis rather than into oxidative phosphorylation compared to normoxia, making adenosine triphosphate (ATP) production less efficient. This may explain the redistribution of hypoxic cells in the G1 cell cycle phase and the time increase for cell doubling. Energy metabolism changes were more prominent in faster-growing A549 cells compared to slower-growing H358 cells, indicating possible roles for the p53 status and inherent growth rate of different cancer cells. In both cell lines, genes associated with cell motility, locomotion and migration were upregulated under chronic hypoxia, indicating a strong stimulus to escape hypoxic conditions.

The Effect of Resistance Training on P53 Gene Expression in Prostate Cancer Patients

Background and Objective: Prostate cancer is one of the most common cancers in men, which causes many deaths every year. P53 suppressor protein is one of the indicators the high level of which in the serum of cancer people is related to a decrease in the growth rate of cancer cells that prevents the development of cancer. There is evidence that exercise can alter p53 levels. This study aimed to investigate the effect of 8 weeks of resistance training on P53 gene expression in prostate cancer patients. Materials and Methods: The statistical population of this randomized clinical trial included men aged 50 to 65 years with prostate cancer. In total, 40 people were selected by convenience sampling and randomly divided into two groups. The first group was subjected to resistance training, and the second group was regarded as a control. The training protocol included a period of resistance training. The obtained data were analyzed in SPSS software (version 20) at a significance level of P≤0.05. Results: Based on the findings, before the intervention, the serum level of P53 was not statistically and significantly different between the two groups (P≤0.05). However, after 8 weeks of intervention, there was a significant difference before and after the intervention in the resistance training group in terms of the value of this variable (P=0.000); however, it showed no significant difference in the control group after 8 weeks (P≤0.05). Conclusion: According to the findings, resistance training increases the serum level of P53 suppressor protein in patients with prostate cancer, and as a result, control and help in the treatment of this cancer.

Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles.

Local and regional recurrence after surgical intervention is a significant problem in cancer management. The multistage theory of carcinogenesis precisely places the presence of histologically normal but mutated premalignant lesions surrounding the tumor - field cancerization, as a significant cause of cancer recurrence. The relationship between tissue dynamics, cancer initiation and cancer recurrence in multistage carcinogenesis is not well known. This study constructs a computational model for cancer initiation and recurrence by combining the Moran and branching processes in which cells requires 3 or more mutations to become malignant. In addition, a spatial structure-setting is included in the model to account for positional relativity in cell turnover towards malignant transformation. The model consists of a population of normal cells with no mutation; several populations of premalignant cells with varying number of mutations and a population of malignant cells. The model computes a stage of cancer detection and surgery to eliminate malignant cells but spares premalignant cells and then estimates the time for malignant cells to re-emerge. We report the cellular conditions that give rise to different patterns of cancer initiation and the conditions favoring a shorter cancer recurrence by analyzing premalignant cell types at the time of surgery. In addition, the model is fitted to disease-free clinical data of 8,957 patients in 27 different cancer types; From this fitting, we estimate the turnover rate per month, relative fitness of premalignant cells, growth rate and death rate of cancer cells in each cancer type. Our study provides insights into how to identify patients who are likely to have a shorter recurrence and where to target the therapeutic intervention.

The Identification of certain chemical disruptors of the estrogen receptor α: Structural and docking analyses

Due to the active role of estrogen receptor α (ERα) in certain breast cancer, finding possible ERα antagonists is important for lowering the growth rate of ERα-motivated breast cancer cells. Here, the current work was conducted to computationally find ERα inhibitors based on the use of certain docking methods. The three-dimensional (3D)-ERα structure was freely docked with the 3D structure of certain ligands, including milbemycin_A3_5-oxime (MA), Baloxavir marboxil (BM), tadalafil (TF), sesamol (SM), raspberry ketone (RK), guaiacol (GuC), proanthocyanidins (PAC), epicatechin (EC), and catechin (CC). The results of the protein-ligand based binding affinity values (kcal/mol) revealed the following; MA= -9.7, TF= -8.5, BM= -8.2, PAC= -8.1, CC= -7.5, EC= -7.2, RK= -6.1, SM= -5.7, and GuC= -4.8. According to the above-mentioned data, milbemycin_A3_5-oxime, tadalafil, Baloxavir marboxil, and proanthocyanidins show the highest binding affinity, which can further be studied in vitro and in vivo for their proposed activity. In addition, catechin, epicatechin, raspberry ketone, sesamol, and guaiacol can also further be investigated for their anti-ERα activity, in which some structural modification to the ligand molecules can be performed to increase their binding action, if they show low ERα-based blocking via in vitro and in vivo research.

SPRR3 Contributes to Aggressiveness of Pancreatic Cancer Cells via NF-κB Signaling Pathway.

Pancreatic cancer remains a deadly solid tumor with worst survival, and a better understanding of the mechanisms of carcinogenesis of pancreatic cancer is critical to promote the survival of patients with pancreatic cancer. qPCR and western blot assay were used to determine the expression of SPRR3 in pancreatic cancer. Anchorage-independent growth ability, BrdU labeling, Transwell assay, and in vivo experiment were used to examine the functions of SPRR3 in aggressiveness of pancreatic cancer. Luciferase reporter assay, nucleoplasmic-separation technique, qPCR, and western blot assay were used to investigate the mechanism of SPRR3 regulating aggressiveness of pancreatic cancer. Our results showed that SPRR3 was significantly increased in pancreatic cancer, which resulted in poor survival for patients with pancreatic cancer. Further analysis showed that overexpression of SPRR3 contributed to anchorage-independent growth ability, growth rate, and invasion ability of pancreatic cancer cells. While, knockdown of SPRR3 showed the reverse results. Mechanistically, overexpression of SPRR3 can promote the transcription of NF-κB pathway, nuclear accumulation of p65, and mRNA levels of NF-κB pathway downstream genes. But, knockdown of SPRR3 induced the reverse results. The above findings clarified the important roles of SPRR3 in the progression of pancreatic cancer through NF-κB pathway. And targeting SPRR3 might be an effective strategy to therapy pancreatic cancer.

Synthesis of Novel Kidney-Type Glutaminase Allosteric Inhibitors Targeting the Critical Lys-320 Residue.

Reversible allosteric inhibitors of kidney-type glutaminase (GLS1, KGA) showed incomplete inhibition of cancer cell proliferation and poor in vivo efficacy. Here, we investigate some irreversible inhibitors targeting the critical K320 residue responsible for GLS1 biological activity. The (trifluoromethoxy)phenylacetic acid motif was replaced by α,β-unsaturated carboxylic acids, and the resulting terminally substituted CB839 derivatives (e.g., GJ2 and GJ5) showed good stability in solid form at room temperature, and better liver microsome stability and in vivo pharmacokinetics than coumarin. Both compounds showed binding to the wild-type KGA, whose K D is 106-fold stronger than that of CB839, but only weak binding to the KGA K320A mutant and no inhibition of GDH proteins. Interestingly, GJ2 treatment significantly decreased the trypsin digestion of KGA, tumor cell clonal formation, and cancer cell growth rate. Taking these results together, targeting the critical K320 residue of GLS1 might be a new strategy to make a potent GLS1 allosteric inhibitor.

Inferring parameters of cancer evolution in chronic lymphocytic leukemia.

As a cancer develops, its cells accrue new mutations, resulting in a heterogeneous, complex genomic profile. We make use of this heterogeneity to derive simple, analytic estimates of parameters driving carcinogenesis and reconstruct the timeline of selective events following initiation of an individual cancer, where two longitudinal samples are available for sequencing. Using stochastic computer simulations of cancer growth, we show that we can accurately estimate mutation rate, time before and after a driver event occurred, and growth rates of both initiated cancer cells and subsequently appearing subclones. We demonstrate that in order to obtain accurate estimates of mutation rate and timing of events, observed mutation counts should be corrected to account for clonal mutations that occurred after the founding of the tumor, as well as sequencing coverage. Chronic lymphocytic leukemia (CLL), which often does not require treatment for years after diagnosis, presents an optimal system to study the untreated, natural evolution of cancer cell populations. When we apply our methodology to reconstruct the individual evolutionary histories of CLL patients, we find that the parental leukemic clone typically appears within the first fifteen years of life.

Some thoughts on the possible health effects of electric and magnetic fields and exposure guidelines.

Concerns about the possible health effects from exposure to weak electric and magnetic (EM) fields have been debated since the early 1960s. It is now well established that biological systems respond to exposure to weak EM fields at energy levels well below the current safety guidelines which result in modification of their functionality without significant changes in temperature. These observations are adding to the debate over what should be done to protect the users of cellular telecommunications systems. Experimental results showing both increases and decreases in cancer cell growth rates and concentration of reactive oxygen species for exposure to nano-Tesla magnetic fields at both radio frequencies (RF) and extra low frequencies (ELF) are cited in this paper. Some theoretical models on how variations in EM exposure can lead to different biological outcomes and how feedback and repair processes often mitigate potential health effects due to long-term exposure to low-level EM energy sources are presented. Of particular interest are the application of the radical pair mechanisms that affect polarization of electrons, and nuclear spins and the importance of time-delayed feedback loops and the timing of perturbations to oscillations in biological systems. These models help account for some of the apparently conflicting experimental results reported and suggest further investigation. These observations are discussed with particular emphasis on setting future safety guidelines for exposure to electromagnetic fields in cellular telecommunications systems. The papers cited are a very small fraction of those in the literature showing both biological effects and no effects from weak electric and magnetic fields.

Prediction of fluctuations in a chaotic cancer model using machine learning

Cancer is a group of diseases and the second leading cause of death according to World Health Organization. Mathematical and computational methods have been used to explore the cancer cells spread and the mechanism of their growth. We study a cancer model that exhibits both periodic and chaotic attractors. It describes the interactions among host, effector immune, and cancer cells. It is observed fluctuations in the population of cells. The fluctuation range can be associated with the appearance of tumour cells. In this work, we use machine learning algorithms for the prediction of fluctuations. We show that our machine learning classification is able to identify fluctuations that are associated with the growth rate of cancer cells.

Pervasive conditional selection of driver mutations and modular epistasis networks in cancer.

Cancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We develop a method (Coselens) to quantify conditional selection on the excess of nonsynonymous substitutions in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identify 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25%-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.

Impact of cancer cell growth rate on the quality of life of animals

It is widely known that cancer cells grow much more rapidly and cause pain, ultimately leading to a low quality of life for the patients in many different ways. How this effect can happen in the case of animals was tested using a simulation study on cancer in canines. Basic assumptions on differences in the growth of normal and cancer cells and pain, affecting the quality of growth and cell growth limits were set for the simulation. The results showed that cancer cells grow at least eight times faster than normal cells. The cancer cell growth was positively correlated with pain score. Thus, it was established that cancer induces pain. The pain score due to cancer was 4.8, representing moderate to severe pain, and that of the normal cell was 2.0, representing no pain. Since the pain was assumed to represent the quality of life in canines, it was concluded, cancer-induced pain leads to poor quality of life for canines under the simulation conditions. Some limitations of this study have also been stated.