Programmed cell death: Apoptosis and oncogenesis

doi:10.1016/0092-8674(91)90002-G

Cell

Volume 65, Issue 7, 28 June 1991, Pages 1097-1098

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Unravelling the role of long non-coding RNA - LINC01087 in breast cancer
2020, Non-coding RNA Research
Apoptosis is a ‘programmed fate’ of all cells participating in diverse physiological and pathological conditions. The role of critical regulators and their involvement in this complex multi-stage process of apoptosis weaved around non-coding RNAs (ncRNAs) is poorly deciphered in breast carcinoma (BC). Aberrant expression patterns of the ncRNAs and their interacting partners, either ncRNAs or coding RNAs or proteins at any point along these pathways, may lead to the malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Longest non-coding type of ncRNAs (lncRNAs) have been considered as critical factors for the development and progression of breast cancer. The aim of our study was to identify set of novel lncRNAs interacting with microRNAs (miRNAs) or proteins that were significantly dysregulated in breast cancer using RNA-Sequencing (RNA-Seq) technique in different samples acting as oncogenic drivers contributing to cancerous phenotype involved in post-transcriptional processing of RNAs. Four lncRNAs; LINC01087, lnc-CLSTN2-1:1, lnc-c7orf65–3:3 and LINC01559:2 were selected for further analysis. Gene expression analysis of over-expressed LINC01087 in vitro reduced both cell viability and apoptosis. We integrated miRNA and mRNA (hsa-miR-548 and AKT1) expression profiles with curated regulations with lncRNA (LINC01087) which has not been previously associated with any breast cancer type, using different computational tools. The network (lncRNA→ miRNA→ mRNA) is promising for the identification of carcinoma associated genes and apoptosis signaling path highlighting the potential roles of LINC01087, hsa-miR548n, AKT1 gene which may play crucial role in proliferation.
Synthesis, antiproliferative activity and mechanism of gallium(III)-thiosemicarbazone complexes as potential anti-breast cancer agents
2018, European Journal of Medicinal Chemistry
Five thiosemicarbazone ligands were synthesized and characterized by condensation with different aldehydes or ketones by 4-phenylthiosemicarbazone. The representative dichlorido[2-(Di-2-pyridinylmethylene)-Nphenylhydrazinecarbothioamide-N,N,S]-gallium(III) (Ga4) was characterized by X-ray single crystal diffraction, which was 1:1 ligand/Ga(III) complexes. The structure-activity relationship of these ligands and Ga (III) complexes have been investigated, and the results demonstrate that the formation of Ga (III) complexes have significant antiproliferative activity over the corresponding ligands. The anticancer mechanism of gallium (III) complexes has been studied in detail, which is typical agents that effect on the mitochondrial apoptotic pathway. The ability of gallium (III) complexes to inhibit the cell cycle does not enhanced with the increasing concentrations, whereas the ability to promote apoptosis is concentration-dependent.
Expression profile of biomarkers altered in papillary and anaplastic thyroid carcinoma: Contribution of Tunisian patients
2017, Bulletin du Cancer
The objective of this study was to compare the protein expression profile between well-differentiated (papillary) and undifferentiated (anaplastic) thyroid carcinoma in Tunisian patients.
This first Tunisian retrospective study concerned data of 38 thyroid cancer cases (19 papillary carcinoma PTC and 19 anaplastic carcinoma ATC) collected at Salah Azaiez Institute of Tunisia. Immunohistochemistry was used to evaluate tumor expression of different molecular markers (p53, Ki67, E-cadherin, cyclin D1, bcl2, S100 and Her-2). The molecular expression was correlated with the clinicopathological characteristics of the tumors.
There were 6 differentially expressed markers when comparing anaplastic thyroid carcinoma ATC with papillary thyroid carcinoma PTC. Expression of p53 and Ki67 were significantly increased in 16 and 18 ATC cases respectively, the Ki67 expression was lost in PTC. Cyclin D1, E-cadherin, bcl2 and S100 were overexpressed in PTC tumors; however, they were significantly decreased in ATC. The last marker, Her-2 was expressed in one case of PTC only.
Our results, similar with findings of other ethnic groups, showed alteration in expression of molecular markers associated with tumor dedifferentiation, indicating loss of cell cycle control with increased proliferative activity in ATC carcinoma. These data support the hypothesis that ATC may derive from dedifferentiation of preexisting PTC tumor.
L’objectif de cette étude était de comparer le profil d’expression protéique entre carcinomes thyroïdiens bien différenciés (papillaires) et indifférenciés (anaplasiques) chez des patients tunisiens.
Cette première étude rétrospective tunisienne a porté sur 38 cas de cancer de la thyroïde (19 carcinomes papillaires PTC et 19 carcinomes anaplasiques ATC) collectés à l’institut Salah Azaiez de Tunisie. On a utilisé l’immunohistochimie pour évaluer l’expression tumorale de différents marqueurs moléculaires (p53, Ki67, E-cadhérine, cycline D1, bcl2, S100 et Her-2). L’expression moléculaire a été corrélée aux caractéristiques clinicopathologiques des tumeurs.
Une différence de l’expression de 6 marqueurs moléculaires a été montrée lors de la comparaison du carcinome anaplasique ATC avec le carcinome papillaire PTC de la thyroïde. L’expression de p53 et Ki67 a été significativement augmentée respectivement dans 16 et 18 cas ATC, l’expression du Ki67 a été complètement perdue dans PTC. La cycline D1, la E-cadhérine, la bcl2 et la S100 ont été surexprimées dans les tumeurs PTC, mais elles ont été significativement diminuées dans l’ATC. Le dernier marqueur, Her-2, a été exprimé dans un seul cas de PTC.
Nos résultats, semblables aux résultats d’autres groupes ethniques, ont montré une altération de l’expression des marqueurs moléculaires associés à la dédifférenciation tumorale, ce qui indique une perte de contrôle du cycle cellulaire avec une activité proliférative accrue dans le carcinome ATC. Ces données sont en concordance avec l’hypothèse que l’ATC peut dériver de la dédifférenciation de tumeur PTC préexistante.
Comparison of apoptosis between adult worms of Schistosoma japonicum from susceptible (BALB/c mice) and less-susceptible (Wistar rats) hosts
2016, Gene
Citation Excerpt :
Currently, there are no effective vaccines available to prevent schistosomiasis (Beaumier et al., 2013), thus control of this disease is largely dependent on treatment with drugs, especially praziquantel (PZQ) (Thetiot-Laurent et al., 2013). Apoptosis, the most prominent form of programmed cell death among multicellular organisms, is executed by a genetically regulated process to maintain ontogenesis and homeostasis (Williams, 1991) and plays a major role in the elimination of unwanted or injured cells and the inhibition of the host inflammatory response (Voll et al., 1997). In schistosomes, previous genomic studies have identified similarities between schistosomes and higher organisms in regard to some apoptotic processes and molecules, although all factors involved in the apoptotic pathway of schistosomes have not yet been clearly identified (Berriman et al., 2009; Zhou et al., 2009).
Schistosomiasis remains a serious public health concern in China. BALB/c mice are susceptible to Schistosoma japonicum infection, whereas the Wistar rats are less susceptible. Apoptosis phenomenon was observed in 42 d adult worms of S. japonicum from both rats and mice at the morphologic, DNA, cellular, and gene levels by transmission electron microscopy (TEM), fluorometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis, fluorescein isothiocyanate-annexin-V/propidium iodide staining flow cytometry (FCM) analysis, and real-time PCR. The results showed that the apoptotic state in worms from two different susceptible hosts was diverse. Several classical hallmarks of apoptosis, including cell shrinkage, chromatin condensation and lunate marginalization, splitting of the nucleoli, nuclear shrinkage and apoptotic body formation were observed by TEM. TUNEL analysis showed that there were much more apoptosis spots in adult worms from rats than those from mice. Statistical analysis revealed that the degree of apoptosis and percentage of necrotic cells in adult worms from Wistar rats were significantly greater (P < 0.01) than those from BALB/c mice by flow cytometry. A total of 15 apoptosis-associated genes including the major components of an intrinsic cell-death pathway were identified from S. japonicum in this study, suggested that a similar apoptosis pathway might occur in S. japonicum. Real-time PCR analyses revealed that the expression levels of most of the tested apoptosis-associated genes, except CASP7, were significantly higher or at the similar level in adult worms from Wistar rats, as compared to those from BALB/c mice. The results obtained in this study collectively demonstrated that differential development of adult S. japonicum in less-susceptible rats and susceptible mice was significantly associated with apoptosis in the worm, and provided valuable information to guide further investigations of the mechanisms governing apoptosis and host interactions in schistosome infection.
Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma
2016, Journal of Controlled Release
Magnetic particles that can be precisely controlled under a magnetic field and transduce energy from the applied field open the way for innovative cancer treatment. Although these particles represent an area of active development for drug delivery and magnetic hyperthermia, the in vivo anti-tumor effect under a low-frequency magnetic field using magnetic particles has not yet been demonstrated. To-date, induced cancer cell death via the oscillation of nanoparticles under a low-frequency magnetic field has only been observed in vitro. In this report, we demonstrate the successful use of spin-vortex, disk-shaped permalloy magnetic particles in a low-frequency, rotating magnetic field for the in vitro and in vivo destruction of glioma cells. The internalized nanomagnets align themselves to the plane of the rotating magnetic field, creating a strong mechanical force which damages the cancer cell structure inducing programmed cell death. In vivo, the magnetic field treatment successfully reduces brain tumor size and increases the survival rate of mice bearing intracranial glioma xenografts, without adverse side effects. This study demonstrates a novel approach of controlling magnetic particles for treating malignant glioma that should be applicable to treat a wide range of cancers.
New Insight into the Development of the Respiratory Acini in Rabbits: Morphological, Electron Microscopic Studies, and TUNEL Assay
2019, Microscopy and Microanalysis

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Programmed cell death: Apoptosis and oncogenesis