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Abstract Background The second most common cancer in the world is breast cancer. Chemotherapy is used to treat breast cancer, but instances of multidrug resistance, targets that are not selective, and physicochemical issues raise doubts about its efficacy. So, the exploration of chemopreventive agents from efficient natural sources has been required. The chia and quinoa seeds have health-promoting activities that include cardio-protective, antidiabetic, and anticancer effects. Given the paramount importance of their oils and their potential bioactivities, this work aimed to assess the repressive effect of their oil nanocapsules against mammary tumors in rats. Rat models of chemically induced mammary tumors were gavaged with chia and quinoa nanocapsules for one month. The repressive effect of nanocapsules was studied by quantifying TNF-α, assessing the gene expression of proto-oncogenes (PIK3CA and MYC) using qRT-PCR, and analyzing the cell cycle in mammary tissue. Results The studies clarified that the inhibition of tumors in response to quinoa and chia nanocapsules was associated with a reduction in TNF-α levels, proliferation capability, and motivation for apoptosis. Furthermore, quinoa and chia nanocapsule management repressed the activation of the MYC and PIK3CA genes. As well as nanocapsules modulated the liver enzymes and kidney function alterations induced in mammary tumor animals. Meanwhile, both oils' nanocapsules do not have an impact on the liver and kidneys of healthy rats. Conclusions The findings indicate that quinoa and chia nanocapsules are safe and can reduce tumor growth, suggesting a potential natural therapeutic target for breast cancer treatment.

Neurofibromatosis type 1 is caused by a germline mutation in the NF1 gene encoding the tumor suppressor neurofibromin. Deficiency of this protein causes hyperactivation of Ras proto-oncogenes. This leads to the development of tumors. Ras proteins undergo prenylation, which is inhibited by inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Therefore, statins can be proposed as anticancer drugs in the complex treatment of neurofibromatosis type 1. Clinical studies have proven the effectiveness of statins in the treatment of sporadic malignant neoplasms, in the pathogenesis of which mutations in the NF1 gene play an important role. Various pathways of the influence of these drugs on the development of tumors are described, including the activation of autophagy, ferroptosis, suppression of proliferation, stimulation of antitumor immunity, and effects on the microenvironment of neoplasms. Data on the effect of statins on the development and progression of neurofibromas in patients with neurofibromatosis type 1 are not presented in the scientific literature. However, it was found that statins enhance the effect of anticancer drugs, the use of which in monotherapy against malignant neoplasms associated with neurofibromatosis is ineffective. In this regard, despite the inefficiency of statins in cognitive disorders in patients with neurofibromatosis type 1, the introduction of these drugs into clinical practice in combination with other drugs could provide a pleiotropic effect, affect various links in the pathogenesis of the disease.

Os mecanismos reguladores do ciclo celular e sua inter-relação com fatores de crescimento, oncogenes e anti-oncogenes têm se constituído nas áreas de maior avanço no estudo da biologia do câncer. Continuamente estão sendo descobertas novas proteínas envolvidas no complexo mecanismo que desencadeia as diferentes fases do ciclo celular, como também os seus mecanismos de ativação. A descoberta dessas proteínas e co-fatores que regulam as transições G1/S e G2/M e que atuam na replicação do material bem como o papel dos proto-oncogenes dentro do ciclo celular permitiu aumentar o conhecimento sobre as células ciclizantes como tarnbém, permitiu que estas pudessem ser detectadas mesmo sem a visualização de figuras mitóticas. O desenvolvimento de anticorpos monoclonais contra estas proteínas tornou viável o estudo, em larga escala, de taxas de proliferação celular em diferentes neoplaslas, uma vez que substâncias como Ki67, polimerase alfa e PCNA - Ciclina somente são expressas em células em proliferação. A detecção de células proliferativas permite, através de sua contagem, estimar as taxas do crescimento neoplásico com conseqüente repercussão no prognóstico da doença e na terapêutica do paciente. Neste artigo são revistos os mecanismos de controle do ciclo celular bem como os métodos de detecção de células proliferativas, enfatizando a aplicação de marcadores pela sua praticidade e confiabilidade.

In 1983, three of us reported in “Science” that umbilical-placental arteries and veins, obtained from normal pregnant women at term delivery, when exposed in vitro to low concentrations of Mg2+ went into vasospasm; the lower the Mg2+, the greater the contractile force developed. These blood vessels also demonstrated amplified contractile force development when challenged with circulating amines and peptides (e.g., norepinephrine, 5-HT, angiotensin II, etc.). We suggested that severe Mg deficiency during pregnancy could in part be responsible for spontaneous abortions, loss of fetuses, stillbirths, and developmental alterations in infants. Using short-term dietary Mg deficient animals, we have noted a great many molecular and biochemical alterations in ventricular, atrial and somatic vascular smooth muscle alterations including DNA methylation and histone changes leading us to speculate that Mg deficiency may represent a genotoxin promoting mutations and causing epigenetic changes. Over the last 35 years, we have new data on severely preeclamptic and gestational diabetic pregnant women that gives credence to our original hypothesis and demonstrates that recently- discovered developmental proteins, originally found 100 years ago in Drosophila fruit flies termed the “Notch pathway”, due to effects on its wings, appears to be important in development of the umbilical-placental blood vessels in pregnant women. Along with the developmental molecule, p53, these Notch proteins clearly alter the behavior of the umbilical-placental vessels. We believe these new findings probably help to explain many of the genetic-toxicity effects seen in women later in life who develop strokes and cardiovascular diseases. Notch alterations could also play an important role in babies born with cardiac defects.

Proto-oncogenes are the genes that have the potential to transform normal cells into cancer cells as a result of mutations. They usually contain encoding of proteins whose function is to inhibit cell differentiation, stimulate cell division, and prevent the death of cells. While the prognosis regarding proto-oncogene may occur at varying phases of cancer, the accuracy of the identification method is always questionable. The standard procedure for detecting these genes involves in-vitro experimentations but it proves to be very costly, time taking, and laborious. This problem is addressed by the use of computer-aided approaches established in studies encompassing methods in computational biology and bioinformatics. Early diagnosis of cancer is crucial for the full recovery of the patient. Proto-oncogene proteins are an important biomarker that helps identify the onset of a specific type of cancer. Keeping this in mind, this study proposes an efficient methodology for in-silico identification of proto-oncogenes. The predictor proposed in this study computes position and composition relevant statistical features incorporated into the pseudo-amino-acid composition (PseAAC) based on Chou’s 5-step rules. Subsequently, the study finds that the use of a random forest classifier performs the most accurate prediction of proto-oncogene proteins. The method was validated using the 10 folds cross-validation, Jackknife testing, Self-Consistency, and Independent set testing, giving 95.44%, 97.17%, 99.8%, and 96.41% accurate results, respectively. These results imply that the proposed model can play a key role in the early prognosis of cancer and aid scientists in the discovery of mechanisms against cancer.

Objective Weightlessness simulation due to the simulated microgravity has been shown to considerably affect behavior of tumor cells. It is aim of this study to evaluate characteristics of human breast cancer cells in this scaffold- free 3D culture model. Materials And Methods In this experimental study, the cells were exposed to simulated microgravity in a random- positioning machine (RPM) for five days. Morphology was observed under phase-contrast and confocal microscopy. Cytofilament staining was performed and changes in expression level of cytofilament genes, proliferation/differentiation genes, oncogenes and tumor suppressor genes were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), followed by western blot confirmation. Results After five days, distinct spheroid formation was observed. Rearrangement of the cytoskeleton into spherical shape was visible. VIM gene expression was significantly up-regulated for adherent cells and spheroids (3.3x and 3.6x respectively, P

Abstract Background The eukaryotic unicellular protist Plasmodiophora brassicae is an endocellular parasite of cruciferous plants. In host cortical cells, this protist develops a unicellular structure that is termed the plasmodium. The plasmodium is actually a multinucleated cell, which subsequently splits and forms resting spores. The mechanism for the growth of this endocellular parasite in host cell is unclear. Results Here, combining de novo genome sequence and transcriptome analysis of strain ZJ-1, we identified top five significant enriched KEGG pathways of differentially expressed genes (DEGs), namely translation, cell growth and death, cell communication, cell motility and cancers. We detected 171 proto-oncogenes from the genome of P. brassicae that were implicated in cancer-related pathways, of which 46 were differential expression genes. Three predicted proto-oncogenes (Pb-Raf1, Pb-Raf2, and Pb-MYB), which showed homology to the human proto-oncogenes Raf and MYB, were specifically activated during the plasmodial growth in host cortical cells, demonstrating their involvement in the multinucleate development stage of the unicellular protist organism. Gene networks involved in the tumorigenic-related signaling transduction pathways and the activation of 12 core genes were identified. Inhibition of phosphoinositol-3-kinase relieved the clubroot symptom and significantly suppressed the development process of plasmodia. Conclusions Proto-oncogene-related regulatory mechanisms play an important role in the plasmodial growth of P. brassicae.

Epithelial thyroid tumors are all from the thyrocytes, the follicular epithelial cells of the thyroid. If these cells do not replicate the normal mechanisms of growth, cell division, and apoptosis, and enter to the uncontrolled growth phase, thyroid tumors arise. Most of these tumors are benign, but some of them are slow-growing malignancies, and a small number of them are also highly-invasive cancers. Failure of the natural mechanisms, and creation a tumor can be due to genetic and epigenetic changes in proto-oncogenes and tumor suppressor genes. Understanding molecular pathology of epithelial thyroid tumors, and recognizing molecular changes of proto-oncogenes and tumor suppressor genes can explain their different clinical features, providing diagnostic and prognostic information, and discovering of the effective treatments. On the other hand, it can provide further research opportunities in the diagnosis, prognosis, and treatment areas. This review article targeted the molecular pathology of epithelial thyroid tumors.

Understanding genetic mechanisms and detection of biological markers of tumor growth forms an individual molecular phenotype oftransformed cells that characterizes stage of tumor, the ability to metastasize, hormonal sensitivity, chemotherapyefficiencyetc. Mutations in proto- and anti-oncogenes controlling mitotic activity of cells and their ability to DNA reparation are often found in tumor cells in patients with cancer. Defects of classical tumor suppressor genes (BRCA1/2, CHEK2, ATM, PALB2, NBS1, TP53, etc.) determine the hereditary predisposition to breast cancer caused by genomic instability and appearance of «chimeric» genes, aneuploidies and chromosomal aberrations. Breast cancer is a genetically heterogeneous disease with various molecular, biological and clinical features. Identificationof the molecular phenotype of breast carcinomas is an important prognostic factor of the disease, and it helps to individualize the therapeutic approach for patients.

Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.

Background: Cancer is a genetic disease and mainly arises due to a number of reasons include activation of oncogenes, malfunction of tumor suppressor genes or mutagenesis due to external factors. Methods: This article was written from the data collected from PubMed, Nature, Science Direct, Springer and Elsevier groups of journals. Results: Oncogenes are deregulated form of normal proto-oncogenes required for cell division, differentiation and regulation. The conversion of proto-oncogene to oncogene is caused due to translocation, rearrangement of chromosomes or mutation in gene due to addition, deletion, duplication or viral infection. These oncogenes are targeted by drugs or RNAi system to prevent proliferation of cancerous cells. There have been developed different techniques of molecular biology used to diagnose and treat cancer, including retroviral therapy, silencing of oncogenes and mutations in tumor suppressor genes. Conclusion: Among all the techniques used, RNAi, zinc finger nucleases and CRISPR hold a brighter future towards creating a Cancer Free World.

Recent studies on thyroid gland cancer development and progression have identified new classes of tumor markers, proto-oncogenes, tumor-suppressing genes, cell receptor genes, identified genetic tumor-predisposing polymorphism and some other significantly important segments of genome. The identification has been based mainly on revealing of DNA abnormal consequences, specific for occurrence of thyroid gland cancer and its progression.

The research work presents an analysis of literature review and results of investigations on the problems of etiology, pathogenesis, classification and peculiarities of clinical manifestations of chronic lymphocytic leukaemia. Special attention is paid to both contemporary conceptions of carcinogenesis, reflecting the role of proto-oncogenes activation, an-tioncogenes and apoptosis genes suppression in mechanisms of neoplasia development and «specific mechanisms» of oncogenic transformation induction of B-lymphocytes and the subsequent development of the stages of promotion, progression and marked clinical manifestations of formation. Possibility of further improvement of use of immune phe-notype character and oncomarkers in diagnostics of chronic lymphocytic leukaemia clinical variants and in evaluation of effectiveness of its therapy has been indicated in the article

The helical duplex architecture of DNA was discovered by Francis Crick and James Watson in 1951 and is well known and understood. However, nucleic acids can also adopt alternative structural conformations that are less familiar, although no less biologically relevant, such as the G-quadruplex. G-quadruplexes continue to be the subject of a rapidly expanding area of research, owing to their significant potential as therapeutic targets and their unique biophysical properties. This review begins by focusing on G-quadruplex structure, elucidating the intermolecular and intramolecular interactions underlying its formation and highlighting several substructural variants. A variety of methods used to characterize these structures are also outlined. The current state of G-quadruplex research is then addressed by proffering seven pertinent questions for discussion. This review concludes with an overview of possible directions for future research trajectories in this exciting and relevant field.

OBJETIVO: Comparar a expressão gênica (mRNA) e protéica dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos. MÉTODOS: Foi realizado um estudo do tipo caso-controle. O material foi coletado de 12 pacientes submetidas a histerectomia no Hospital de Clínicas de Porto Alegre. A expressão do mRNA específico para c-myc, c-fos, c-jun e beta-microglobulina foi avaliada pela técnica de RT-PCR, utilizando primers específicos para cada gene. A expressão protéica destes protooncogenes foi avaliada através de Western blot com anticorpos específicos. RESULTADOS: Não houve diferença significativa para expressão gênica desses protooncogenes entre miométrio normal e mioma (c-myc: 0,87 ± 0,08 vs 0,87 ± 0,08, p = 0,952; c-fos: 1,10 ± 0,17 vs 1,01 ± 0,11, p = 0,21; c-jun: 1,03 ± 0,12 vs 0,96 ± 0,09, p = 0,168, respectivamente). Não houve diferença significativa para expressão protéica desses protooncogenes entre miométrio normal e mioma (c-myc: 1,36 ± 0,48 vs 1,53 ± 0,29, p = 0,569; c-fos: 8,85 ± 5,5 vs 6,56 ± 4,22, p = 0,434; e c-jun: 6,47 ± 3,04 vs 5,42 ± 2,03, p = 0,266, respectivamente). CONCLUSÃO: A expressão gênica (transcrição) e a expressão protéica (tradução) dos protooncogenes c-myc, c-fos e c-jun em mioma e miométrio normal são semelhantes.Uterine myomas are common benign tumors of the female genital tract. The expression of growth factor signal transduction cascade components including the protooncogenes c-myc, c-fos, and c-jun seem to be involved in the development of myomas. PURPOSE: To compare the gene (mRNA) and protein expression of the protooncogenes c-fos, c-myc, and c-jun in human normal myometrium and leiomyoma. METHOD: A case-control study was performed. Samples were collected from 12 patients submitted to hysterectomy at the Hospital de Clínicas at Porto Alegre. The expression of the specific mRNA for c-myc, c-fos, c-jun, and beta-microglobulin was assessed through the RT-PCR technique, using specific primers to each gene. The protein expression of these protooncogenes was evaluated through the Western blot technique with specific antibodies. RESULTS: No statistically significant difference was observed in the gene expression for these protooncogenes between normal myometrium and leiomyoma (c-myc: 0,87 ± 0,08 vs 0,87 ± 0,08, p = 0,952; c-fos: 1,10 ± 0,17 vs 1,01 ± 0,11, p = 0,21; c-jun: 1,03 ± 0,12 vs 0,96 ± 0,09, p = 0,168, respectively). No statiscally significant difference was observed for the protein expression of these protooncogenes between normal myometrium and leiomyoma (c-myc: 1,36 ± 0,48 vs 1,53 ± 0,29, p = 0,569; c-fos: 8,85 ± 5,5 vs 6,56 ± 4,22, p = 0,434; e c-jun: 6,47 ± 3,04 vs 5,42 ± 2,03, p = 0,266, respectively). CONCLUSION: No difference was observed in the gene expression (transcription) nor in the protein expression (translation) of the protooncogenes c-myc, c-fos, and c-jun between leiomyoma and myometrium.

Costello syndrome (CS) is a rare genetic disorder, first described by Costello in 1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include facial dysmorphism, skin disorders, cognitive impairment, cardiac and musculoskeletal defects. There is an increased risk of malignancies in these patients, due to the proto-oncogene mutation, and also sudden death secondary to heart disease. We report a case with characteristic phenotype, highlighting the peculiar skin changes.