Impact of ionizing radiation on cell-ECM mechanical crosstalk in breast cancer.

The stiffness of the extracellular matrix plays a crucial role in cell motility and spreading, influencing cell morphology through cytoskeleton organization and transmembrane proteins' expression. In this context, mechanical characterization of both cells and the extracellular matrix gains prominence for enhanced diagnostics and clinical decision-making. Here, we investigate the combined effect of mechanotransduction and ionizing radiations on altering cells' mechanical properties, analysing mammary cell lines (MCF10A and MDA-MB-231) after X-ray radiotherapy (2 and 10 Gy). We found that ionizing radiations sensitively affect adenocarcinoma cells cultured on substrates mimicking cancerous tissue stiffness (15 kPa), inducing an increased structuration of paxillin-rich focal adhesions and cytoskeleton: this process translates in the augmentation of tension at the actin filaments level, causing cellular stiffness and consequently affecting cytoplasmatic/nuclear morphologies. Deeper exploration of the intricate interplay between mechanical factors and radiation should provide novel strategies to orient clinical outcomes.

Interstitial lung disease was suspected, but biopsy revealed pulmonary lymphangitis carcinomatosa.

Introduction: Pulmonary lymphangitis carcinomatosa is a rare and severe manifestation of metastatic disease that causes pulmonary symptoms and radiologic patterns similar to interstitial lung diseases. Case presentation: We report a case of a 78-year-old woman who presented to our department with insidiously developed symptoms of fatigue, dry cough, and severe dyspnea for 3 months. Chest radiography showed bilateral interstitial changes. On suspicion of interstitial lung disease, bronchoscopy and transbronchial cryobiopsy were carried out. Surprisingly, histopathological investigation revealed pulmonary lymphangitis carcinomatosa originating from primary breast adenocarcinoma. Conclusion: To achieve an accurate diagnosis and prevent delay of initiation of proper treatment a thorough diagnostic approach is necessary. In case of doubt, biopsy should be performed to secure clarification. In this case report we discuss the diagnostic value of transbroncial cryobiopsy for this purpose.

Cladanthus scariosus Essential Oil and Its Principal Constituents with Cytotoxic Effects on Human Tumor Cell Lines.

Cladanthus is a small genus of the Asteraceae family comprising just five species that, apart from Cladanthus mixtus (L.) Chevall., has a large distribution in all the Mediterranean countries, mainly in the North Africa area. Several ethnopharmacological uses have been reported for species of this genus. Notably, Cladanthus scariosus (Ball) Oberpr. & Vogt is endemic to Morocco. Seeking to delve deeper into the phytochemistry and pharmacological aspects of this species, in this work, we investigated the essential oil (EO) obtained from the aerial parts of a locally sourced accession, hitherto unexplored, growing wild near Tizi n'Ticha, Morocco. The chemical composition of the EO, obtained by the hydrodistillation method, was evaluated by GC and GC-MS. The most abundant EO constituent was germacrene D (13.2%), the principal representative of the sesquiterpene hydrocarbons class (27.2%). However, the major class of constituents was monoterpene hydrocarbons (43.0%), with α-pinene (11.9%), sabinene (10.2%), p-cymene (8.5%), and α-phellandrene (5.2%) as the most abundant. The EO and its main constituents have been tested for their possible cytotoxic activity against three human tumor cell lines (MDA-MB 231, A375, and CaCo2) using the MTT assay, with corresponding IC50 values of 13.69, 13.21, and 22.71 µg/mL, respectively. Germacrene D and terpinen-4-ol were found to be the most active constituents with IC50 values between 3.21 and 9.53 µg/mL. The results demonstrate remarkable cytotoxic activity against the three human tumor cell lines studied, and in the future, further analyses could demonstrate the excellent potential of C. scariosus EO as an antitumor agent.

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines.

S-allyl-L-cysteine (SAC) is a sulfur compound present in fresh garlic. The reference literature describes its anticancer, antioxidant and neuroprotective effects. Breast cancer is infamously known as one of the most commonly diagnosed malignancies among women worldwide. Its morbidity and mortality make it reasonable to complete and expand knowledge on this cancer's characteristics. Hydrogen sulfide (H2S) and its naturally occurring donors are well-known investigation subjects for diverse therapeutic purposes. This study was conducted to investigate the SAC antiproliferative potential and effect on three enzymes involved in H2S metabolism: 3-mercaptopyruvate sulfurtransferase (MPST), cystathionine γ-lyase (CTH), and cystathionine ß-synthase (CBS). We chose the in vitro cellular model of human breast adenocarcinomas: MCF-7 and MDA-MB-231. The expression of enzymes after 2, 4, 6, 8, and 24 h incubation with 2.24 mM, 3.37 mM, and 4.50 mM SAC concentrations was examined. The number of living cells was determined by the MTS assay. Changes in cellular plasma membrane integrity were measured by the LDH test. Expression changes at the protein level were analyzed using Western blot. A significant decrease in viable cells was registered for MCF-7 cells after all incubation times upon 4.50 mM SAC exposure, and after 6 and 24 h only in MDA-MB-231 upon 4.50 mM SAC. In both cell lines, the MPST gene expression significantly increased after the 24 h incubation with 4.50 mM SAC. S-allyl-L-cysteine had opposite effects on changes in CTH and CBS expression in both cell lines. In our research model, we confirmed the antiproliferative potential of SAC and concluded that our studies provided current information about the increase in MPST gene expression mediated by S-allyl-L-cysteine in the adenocarcinoma in vitro cellular model for the MCF-7 and MDA-MB-231 cell lines. Further investigation of this in vitro model can bring useful information regarding sulfur enzyme metabolism of breast adenocarcinoma and regulating its activity and expression (gene silencing) in anticancer therapy.

Breast adenocarcinoma cells adhere stronger to brain pericytes than to endothelial cells.

Most of the malignancies detected within the brain parenchyma are of metastatic origin. As the brain lacks classical lymphatic circulation, the primary way for metastasis relies on hematogenous routes. Dissemination of metastatic cells to the brain implies attachment to the luminal surface of brain endothelial cells, transmigration through the vessel wall, and adhesion to the brain surface of the vasculature. During this process, tumor cells must interact with brain endothelial cells and later on with pericytes. Physical interaction between tumor cells and brain vascular cells might be crucial in the successful extravasation of metastatic cells through blood vessels and later in their survival within the brain environment. Therefore, we applied single-cell force spectroscopy to investigate the nanoscale adhesive properties of living breast adenocarcinoma cells to brain endothelial cells and pericytes. We found target cell type-dependent adhesion characteristics, i.e. increased adhesion of the tumor cells to pericytes in comparison to endothelial cells, which underlines the existence of metastatic potential-related nanomechanical differences relying partly on membrane tether dynamics. Varying adhesion strength of the tumor cells to different cell types of brain vessels presumably reflects the transitory adhesion to endothelial cells before extravasation and the long-lasting strong interaction with pericytes during survival and proliferation in the brain. Our results highlight the importance of specific mechanical interactions between tumor cells and host cells during metastasis formation.

Differences in nonoxidative sulfur metabolism between normal human breast MCF-12A and adenocarcinoma MCF-7 cell lines.

Recent studies have revealed the role of endogenous hydrogen sulfide (H2S) in the development of breast cancer. The capacity of cells to generate H2S and the activity and expression of the main enzymes (cystathionine beta synthase; CBS, cystathionase γ-lyase; CGL, 3-mercaptopyruvate sulfurtransferase; MPST and thiosulfate sulfurtransferase; TST) involved in H2S metabolism were analyzed using an in vitro model of a non-tumourigenic breast cell line (MCF-12A) and a human breast adenocarcinoma cell line (MCF-7). In both cell lines, MPST, CGL, and TST expression was confirmed at the mRNA (RT-PCR) and the protein (Western Blot) level, while CBS expression was detected only in MCF-7 cells. Elevated levels of GSH, sulfane sulfur and increased CBS and TST activity were presented in the MCF-7 compared to the MCF-12A cells. It appears that cysteine might be mainly a substrate for GSH synthesis in breast adenocarcinoma. Increased capacity of the cells to generate H2S was shown for MCF-12A compared to MCF-7 cell line. Results suggest an important function of CBS in H2S metabolism in breast adenocarcinoma. The presented work may contribute to further research on new therapeutic possibilities for breast cancer - one of the most frequently diagnosed types of cancer among women.

Association of Gene Polymorphisms with Breast Cancer Risk in the Kazakh Population.

OBJECTIVE: The research aim is analyzing and identify reliable genetic markers of breast cancer risk in the Kazakh population. METHODS: The databases were analyzed with the selection of polymorphisms associated with the development of breast cancer and further genotypic study of a group of women with a confirmed diagnosis of breast adenocarcinoma (group No. 1) and a group of relatively healthy women (group No. 2). RESULT: The research presents the results of a study on the frequency of certain single-nucleotide polymorphisms in patients with breast cancer in the Republic of Kazakhstan. The frequency of single-nucleotide polymorphisms rs4646, rs1065852, rs4244285, rs67376798, rs6504950, rs2229774, rs1800056, rs16942, rs4987047 is statistically significant compared to the control group of patients. These polymorphisms in the Kazakh population have a direct association with an increased risk of breast cancer in women and may be used as cancer indicators during the genetic screening of patients with a complicated family history. Single-nucleotide polymorphisms such as rs55886062, rs3918290, rs12721655, rs4987117, rs2229774, rs11203289, rs137852576, rs11571833, rs80359062 and rs11571746 were found in more than 40. Zero percent of patients with breast cancer may be used as markers for detecting patients at increased risk of breast malignancy in the Kazakh population without a history of poor family history. CONCLUSION: The usage of the data obtained in a set of state programs for early screening of patients will improve the rates of early breast tumor detection, form groups of patients with a high risk of disease development and improve the quality and expectancy of life.

Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response.

We developed recombinant variants of oncolytic vaccinia virus LIVP strain expressing interleukin-15 (IL-15) or its receptor subunit alpha (IL-15Rα) to stimulate IL-15-dependent immune cells. We evaluated their oncolytic activity either alone or in combination with each other in vitro and in vivo using the murine CT26 colon carcinoma and 4T1 breast carcinoma models. We demonstrated that the admixture of these recombinant variants could promote the generation of the IL-15/IL-15Rα complex. In vitro studies indicated that 4T1 breast cancer cells were more susceptible to the developed recombinant viruses. In vivo studies showed significant survival benefits and tumor regression in 4T1 breast cancer syngeneic mice that received a combination of LIVP-IL15-RFP with LIVP-IL15Ra-RFP. Histological analysis showed recruited lymphocytes at the tumor region, while no harmful effects to the liver or spleen of the animals were detected. Evaluating tumor-infiltrated lymphocytes represented profound activation of cytotoxic T cells and macrophages in mice receiving combination therapy. Thus, our experiments showed superior oncolytic effectiveness of simultaneous injection of LIVP-IL15-RFP and LIVP-IL15Ra-RFP in breast cancer-bearing mice. The combined therapy by these recombinant variants represents a potent and versatile approach for developing new immunotherapies for breast cancer.

Impact of REAC Regenerative Endogenous Bioelectrical Cell Reprogramming on MCF7 Breast Cancer Cells.

Human breast adenocarcinoma is a form of cancer which has the tendency to metastasize to other tissues, including bones, lungs, brain, and liver. Several chemotherapeutic drugs are used to treat breast tumors. Their combination is used to simultaneously target different mechanisms involved in cell replication. Radio electric asymmetric conveyer (REAC) technology is an innovative technology, used both in vitro and in vivo, to induce cell reprogramming and counteract senescence processes. Within this context, we treated MCF-7 cells with a regenerative (RGN) REAC treatment for a period ranging between 3 and 7 days. We then analyzed cell viability by trypan blue assays and gene and protein expression by real time-qPCR and confocal microscope, respectively. We also detected the levels of the main proteins involved in tumor progression, DKK1 and SFRP1, by ELISA and cell senescence by ß-galactosidase tests. Our results showed the ability of REAC RGN to counteract MCF-7 proliferation, probably inducing autophagy via the upregulation of Beclin-1 and LC3-I, and the modulation of specific tumorigenic biomarkers, such as DKK1 and SPFR1. Our results could suggest the application of the REAC RGN in future in vivo experiments, as an aid for the therapeutic strategies usually applied for breast cancer treatment.

Sulforaphane-Induced Cell Mitotic Delay and Inhibited Cell Proliferation via Regulating CDK5R1 Upregulation in Breast Cancer Cell Lines.

Our research has revealed that sulforaphane (SFN) has chemopreventive properties and could be used in chemotherapy treatments. Further investigation is needed to understand the mechanisms behind sulforaphane's (SFN) antitumor activity in breast adenocarcinoma, as observed in our studies. This research looked into the effects of SFN on mitosis delay and cell cycle progression in MDA-MB-231 and ZR-75-1 cells, two types of triple-negative breast cancer adenocarcinoma.The proliferation of the cancer cells after SFN exposure was evaluated using MTT assay, DNA content and cell cycle arrest induction by flow cytometry, and expressions of cdc25c, CDK1, cyclin B1 and CDK5R1 were assessed through qRT-PCR and Western blot analysis. SFN was found to inhibit the growth of cancer cells. The accumulation of G2/M-phase cells in SFN-treated cells was attributed to CDK5R1. The disruption of the CDC2/cyclin B1 complex suggested that SFN may have antitumor effects on established breast adenocarcinoma cells. Our findings suggest that, in addition to its chemopreventive properties, SFN could be used as an anticancer agent for breast cancer, as it was found to inhibit growth and induce apoptosis of cancer cells.

Visualization and Comparison of the Level of Apurinic/Apyrimidinic Endonuclease 1 in Live Normal/Cancerous and Neuron Cells with a Fluorescent Nanoprobe.

As a major apurinic/apyrimidinic endonuclease and a redox signaling protein in human cells, APE1 plays a crucial role in cellular function and survival. The relationship between alterations of APE1 expression and subcellular localization and the initiation, development and treatment of various cancers has received extensive attention. However, comparing the in-vivo activity of APE1 in normal and cancerous breast live cells remains challenging due to the low efficiency of commonly used liposome transfection methods in delivering DNA substrate probes into human normal breast epithelial cells (MCF-10A). In this work, we develop a DNA/RNA hybrid-based small magnetic fluorescent nanoprobe (25 ± 3 nm) that can be taken up by various live cells under magnetic transfection. The D0/R-nanoprobe demonstrates an outstanding specificity toward APE1 and strong resistance to the cellular background interference. Using this nanoprobe, we are not only able to visualize the intracellular activity of APE1 in breast ductal carcinoma (MCF-7) live cells, but also demonstrate the APE1 activity in MCF-10A live cells for the first time. The method is then extended to observe the changes in APE1 levels in highly metabolically active neuroendocrine cells under normal conditions and severe attacks by reactive oxygen species in real-time. The fluorescent nanoprobe provides a useful tool for studying the dynamic changes of intracellular APE1 in normal or cancerous live cells. It also displays the potential for visible and controllable release of miRNA drugs within live cells for therapeutic purposes.

Calpain-mediated Mechanoptosis in Breast Adenocarcinoma.

Calpains belong to a family of important calcium-dependent cysteine proteases. They are involved in intracellular processes including cytoskeleton disorganization and substrate proteolysis. They also enhance apoptosis and cell to cell adhesion. Calpains demonstrate also a mechanosensory function in neoplastic and malignant cells due to their implication in mechanoptosis. This is a specific type of apoptotic death induced by strong external mechanical stimuli. Anti-cytoskeleton rigidity inhibition strategies based on calpain induction lead to increased apoptosis of tumor transformed cells. Elevated intracellular calcium concentration mediated by specific receptors and channels activates calpains. In the current molecular review, we explored the role of calpains in calcium-dependent signa transduction pathways in breast adenocarcinoma in conjunction with novel agents that activate their important anti-tumor functions.

High Efficacy on the Death of Breast Cancer Cells Using SPMHT with Magnetite Cyclodextrins Nanobioconjugates.

In this study, we present the experimental results obtained in vitro on the human breast adenocarcinoma cell line (MCF-7) by applying superparamagnetic hyperthermia (SPMHT) using novel Fe3O4-PAA-(HP-γ-CDs) (PAA is polyacrylic acid and HP-γ-CDs is hydroxypropyl gamma-cyclodextrins) nanobioconjugates previously obtained by us. In the in vitro SPMHT experiments, we used concentrations of 1, 5 and 10 mg/mL of Fe3O4 ferrimagnetic nanoparticles from Fe3O4-PAA-(HP-γ-CDs) nanobioconjugates suspended in culture media containing 1 × 105 MCF-7 human breast adenocarcinoma cells. The harmonic alternating magnetic field used in the in vitro experiments that did not affect cell viability was found to be optimal in the range of 160-378 Gs and at a frequency of 312.2 kHz. The appropriate duration of the therapy was 30 min. After applying SPMHT with these nanobioconjugates under the above conditions, MCF-7 cancer cells died out in a very high percentage, of until 95.11%. Moreover, we studied the field up to which magnetic hyperthermia can be safely applied without cellular toxicity, and found a new upper biological limit H × f ~9.5 × 109 A/m⋅Hz (H is the amplitude and f is the frequency of the alternating magnetic field) to safely apply the magnetic field in vitro in the case of MCF-7 cells; the value was twice as high compared to the currently known value. This is a major advantage for magnetic hyperthermia in vitro and in vivo, because it allows one to achieve a therapy temperature of 43 °C safely in a much shorter time without affecting healthy cells. At the same time, using the new biological limit for a magnetic field, the concentration of magnetic nanoparticles in magnetic hyperthermia can be greatly reduced, obtaining the same hyperthermic effect, while at the same time, reducing cellular toxicity. This new limit of the magnetic field was tested by us in vitro with very good results, without the cell viability decreasing below ~90%.

Discovery of the mechanism of n-propylparaben-promoting the proliferation of human breast adenocarcinoma cells by activating human estrogen receptors via metabolomics analysis.

BACKGROUND: N-propylparaben (PP), a type of paraben, is commonly used as a preservative or antibacterial agent in daily chemicals, medicine, food, cosmetics, feed, and various industrial preservatives. Although PP promotes the growth of human breast adenocarcinoma (MCF-7) cells by activating the human estrogen receptor (ER), the mechanism responsible for this type of programmed cell proliferation is poorly understood. OBJECTIVE: To clarify the effect of PP on cell metabolic function and the potential molecular mechanism of PP induced MCF-7 cell proliferation from a new perspective. METHODS: To use high-resolution mass spectrometry-based metabolomics combined with bioinformatics analysis to analyze the molecular mechanism. RESULTS: The results illustrated that differential endogenous compounds related to the effects of PP on cell metabolic functions were detected. PP was found to promote glycolysis in MCF-7 cells and enhance the tricarboxylic acid cycle (TCA cycle) in mitochondria, thus improving the energy supply to these tumor cells for metabolic function and promotion of rapid proliferation. Moreover, we found that PP promoted cell proliferation by affecting the mitogen-activated protein kinase (MAPK) signaling pathway of MCF-7 cells. CONCLUSION: Our results revealed the molecular mechanism of low concentration PP promoting MCF-7 cell proliferation by activating ER.

Programmed Cell Death Protein 1 (PD-1) in Relation to PANoptosis: Immune Pharmacological Targets for Management of Breast Adenocarcinoma.

Programmed cell death protein 1 or Programmed death-1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) research have tremendously been taken into great consideration in the field of cancer immune pharmacology. Cancer immunotherapy has been convoyed by a capable outcome over the past few years. PD-1 and PD-L1 play a pivotal role in attenuating immune involvement, modulating the activity of T-cells, and promoting different types of programmed cell death. Participation of antigen-specific T cells and regulatory T cells and their acute mutations during cancer cell invasion and migration may lead to challenges for three programmed cell death methods, namely, pyroptosis, apoptosis, and necroptosis called "PANoptosis". This review aimed to explore the correlation between the PD-1/PD-L1 pathway in "PANoptosis" using available recently published literature with several schematic representations. Hopefully, the review will facilitate the biomedical scientist targeting cancer immune pharmacological aspect for the management of Breast Adenocarcinoma shortly.

A purified and lyophilized Pseudomonas aeruginosa derived pyocyanin induces promising apoptotic and necrotic activities against MCF-7 human breast adenocarcinoma.

BACKGROUND: Pyocyanin, a specific extracellular secondary metabolite pigment produced by Pseudomonas aeruginosa, exhibits redox activity and has toxic effects on mammalian cells, making it a new and potent alternative for treating cancer. Breast cancer (BC) treatment is now defied by acquired and de novo resistance to chemotherapy, radiation, or targeted therapies. Therefore, the anticancer activity of purified and characterized pyocyanin was examined against BC in our study. RESULTS: The maximum production of pyocyanin (53 µg/ml) was achieved by incubation of the highest pyocyanin-producing P. aeruginosa strain (P32) in pH-adjusted peptone water supplemented with 3% cetrimide under shaking conditions at 37 °C for 3 days. The high purity of the extracted pyocyanin was proven by HPLC against standard pyocyanin. The stability of pyocyanin was affected by the solvent in which it was stored. Therefore, the purified pyocyanin extract was lyophilized to increase its shelf-life up to one year. Using the MTT assay, we reported, for the first time, the cytotoxic effect of pyocyanin against human breast adenocarcinoma (MCF-7) with IC50 = 15 µg/ml while it recorded a safe concentration against human peripheral blood mononuclear cells (PBMCs). The anticancer potential of pyocyanin against MCF-7 was associated with its apoptotic and necrotic activities which were confirmed qualitatively and quantitively using confocal laser scanning microscopy, inverted microscopy, and flow cytometry. Caspase-3 measurements, using real-time PCR and western blot, revealed that pyocyanin exerted its apoptotic activity against MCF-7 through caspase-3 activation. CONCLUSION: Our work demonstrated that pyocyanin may be an ideal anticancer candidate, specific to cancer cells, for treating MCF-7 by its necrotic and caspase-3-dependent apoptotic activities.

The effect of dual-frequency sonication in the presence of thalidomide angiogenesis inhibitor and nanomicelles containing doxorubicin on inhibiting the growth and angiogenesis of breast adenocarcinoma in vivo.

This study aimed to evaluate the effect of dual-frequency sonication in the presence of thalidomide angiogenesis inhibitor and nanomicelles containing doxorubicin on inhibiting the growth and angiogenesis of breast adenocarcinoma in BALB/c female mice. Sixty mice carrying the tumor were divided into 12 groups: (A) control, (B) 28 kHz and 3 MHz sonication, (C) thalidomide, (D) thalidomide and 28 kHz, (E) thalidomide and 3 MHz, (F) thalidomide and dual-frequency sonication, (G) doxorubicin, (H) nanomicelles containing doxorubicin, (I) nanomicelles containing doxorubicin and dual-frequency sonication, (J) thalidomide and doxorubicin, (K) thalidomide and nanomicelles containing doxorubicin, and (L) thalidomide and nanomicelles containing doxorubicin and dual-frequency sonication. The delay in the tumor growth and angiogenesis percent were extracted. Pathological and immunohistochemical studies were performed to confirm the treatment. The findings of tumor growth retardation parameters and animal survival were significantly different in group L from all groups (P < 0.05). The highest rate of inhibition was in group L with a 46% inhibition. In group L, 100% of the animals survived until day 49. In groups F, C, G, B, and A, all the animals survived 45, 42, 39, 32, and 30 days, respectively. Pathological results showed a decrease in tumor grade in groups K and L. Histopathological results demonstrate a decrease in group L angiogenesis compared to group C. These findings were consistent with the results of color Doppler ultrasound imaging. Dual-frequency sonication in the presence of thalidomide and doxorubicin-containing nanomicelles inhibits tumor growth and angiogenesis.

Kinesin Eg5 Selective Inhibition by Newly Synthesized Molecules as an Alternative Approach to Counteract Breast Cancer Progression: An In Vitro Study.

Breast cancer (BC) is one of the most diagnosed cancers in women. Recently, a promising target for BC treatment was found in kinesin Eg5, a mitotic motor protein that allows bipolar spindle formation and cell replication. Thus, the aim of this work was to evaluate the effects of novel thiadiazoline-based Eg5 inhibitors, analogs of K858, in an in vitro model of BC (MCF7 cell line). Compounds 2 and 41 were selected for their better profile as they reduce MCF7 viability at lower concentrations and with minimal effect on non-tumoral cells with respect to K858. Compounds 2 and 41 counteract MCF7 migration by negatively modulating the NF-kB/MMP-9 pathway. The expression of HIF-1α and VEGF appeared also reduced by 2 and 41 administration, thus preventing the recruitment of the molecular cascade involved in angiogenesis promotion. In addition, 2 provokes an increased caspase-3 activation thus triggering the MCF7 apoptotic event, while 41 and K858 seem to induce the necrosis axis, as disclosed by the increased expression of PARP. These results allow us to argue that 2 and 41 are able to simultaneously intervene on pivotal molecular signaling involved in breast cancer progression, leading to the assumption that Eg5 inhibition can represent a valid approach to counteract BC progression.

Deep Learning Approaches for Detection of Breast Adenocarcinoma Causing Carcinogenic Mutations.

Genes are composed of DNA and each gene has a specific sequence. Recombination or replication within the gene base ends in a permanent change in the nucleotide collection in a DNA called mutation and some mutations can lead to cancer. Breast adenocarcinoma starts in secretary cells. Breast adenocarcinoma is the most common of all cancers that occur in women. According to a survey within the United States of America, there are more than 282,000 breast adenocarcinoma patients registered each 12 months, and most of them are women. Recognition of cancer in its early stages saves many lives. A proposed framework is developed for the early detection of breast adenocarcinoma using an ensemble learning technique with multiple deep learning algorithms, specifically: Long Short-Term Memory (LSTM), Gated Recurrent Units (GRU), and Bi-directional LSTM. There are 99 types of driver genes involved in breast adenocarcinoma. This study uses a dataset of 4127 samples including men and women taken from more than 12 cohorts of cancer detection institutes. The dataset encompasses a total of 6170 mutations that occur in 99 genes. On these gene sequences, different algorithms are applied for feature extraction. Three types of testing techniques including independent set testing, self-consistency testing, and a 10-fold cross-validation test is applied to validate and test the learning approaches. Subsequently, multiple deep learning approaches such as LSTM, GRU, and bi-directional LSTM algorithms are applied. Several evaluation metrics are enumerated for the validation of results including accuracy, sensitivity, specificity, Mathew's correlation coefficient, area under the curve, training loss, precision, recall, F1 score, and Cohen's kappa while the values obtained are 99.57, 99.50, 99.63, 0.99, 1.0, 0.2027, 99.57, 99.57, 99.57, and 99.14 respectively.

[Expression of HIV-1 Reverse Transcriptase in Murine Cancer Cells Increases Mitochondrial Respiration].

Changes in metabolic pathways are often associated with the development of a wide range of pathologies. Increased glycolysis under conditions of sufficient tissue oxygen supply and its dissociation from the Krebs cycle, known as aerobic glycolysis or the Warburg effect, is a hallmark of many malignant neoplasms. Identification of specific metabolic shifts can characterize the metabolic programming of individual types of tumor cells, the stage of their transformation, and predict their metastatic potential. Viral infection can also alter the metabolism of cells to support the process of viral replication. Infection with human immunodeficiency virus type 1 (HIV-1) is associated with an increased incidence of various cancers, and for some viral proteins a direct oncogenic effect was demonstrated. In particular, we showed that the expression of HIV-1 reverse transcriptase (RT) in 4T1 breast adenocarcinoma cells increases the tumorigenic and metastatic potential of cells in vitro and in vivo by a mechanism associated with the ability of RT to induce reactive oxygen species in cells (ROS). The aim of this work was to study the molecular mechanism of this process, namely the effect of HIV-1 RT on the key metabolic pathways associated with tumor progression: glycolysis and mitochondrial respiration. Expression of HIV-1 RT had no effect on the glycolysis process. At the same time, it led to an increase in mitochondrial respiration and the level of ATP synthesis in the cell, while not affecting the availability of the substrates, carbon donors for the Krebs cycle, which excludes the effect of RT on the metabolic enzymes of cells. Increased mitochondrial respiration was associated with restoration of the mitochondrial network despite the RT-induced reduction in mitochondrial mass. Increased mitochondrial respiration may increase cell motility, which explains their increased tumorigenicity and metastatic potential. These data are important for understanding the pathogenesis of HIV-1 infection, including the stimulation of the formation and spread of HIV-1 associated malignancies.