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Genesis (New York, N.Y. : 2000) Nov 2023
Topics: Animals; Urochordata; Gene Expression Regulation; Gene Expression Regulation, Developmental
PubMed: 38009987
DOI: 10.1002/dvg.23572 -
Cell Communication and Signaling : CCS Aug 2023Breast cancer exhibits the highest global incidence among all tumor types. Regardless of the type of breast cancer, metastasis is a crucial cause of poor prognosis.... (Review)
Review
Breast cancer exhibits the highest global incidence among all tumor types. Regardless of the type of breast cancer, metastasis is a crucial cause of poor prognosis. Anoikis, a form of apoptosis initiated by cell detachment from the native environment, is an outside-in process commencing with the disruption of cytosolic connectors such as integrin-ECM and cadherin-cell. This disruption subsequently leads to intracellular cytoskeletal and signaling pathway alterations, ultimately activating caspases and initiating programmed cell death. Development of an anoikis-resistant phenotype is a critical initial step in tumor metastasis. Breast cancer employs a series of stromal alterations to suppress anoikis in cancer cells. Comprehensive investigation of anoikis resistance mechanisms can inform strategies for preventing and regressing metastatic breast cancer. The present review first outlines the physiological mechanisms of anoikis, elucidating the alterations in signaling pathways, cytoskeleton, and protein targets that transpire from the outside in upon adhesion loss in normal breast cells. The specific anoikis resistance mechanisms induced by pathological changes in various spatial structures during breast cancer development are also discussed. Additionally, the genetic loci of targets altered in the development of anoikis resistance in breast cancer, are summarized. Finally, the micro-RNAs and targeted drugs reported in the literature concerning anoikis are compiled, with keratocin being the most functionally comprehensive. Video Abstract.
Topics: Humans; Anoikis; Signal Transduction; Neoplasms; Integrins; Cytoskeleton; Cell Line, Tumor
PubMed: 37537585
DOI: 10.1186/s12964-023-01183-4 -
BMB Reports Feb 2024Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on...
Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin β1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer. [BMB Reports 2024; 57(2): 104-109].
Topics: Female; Humans; Anoikis; Gefitinib; HeLa Cells; Uterine Cervical Neoplasms; Apoptosis; Antineoplastic Agents; Cell Line, Tumor
PubMed: 38303562
DOI: 10.5483/BMBRep.2023-0225 -
Indian Journal of Ophthalmology Jul 2023In LASIK (laser in situ keratomileusis), a hinged corneal flap is made, which enables the flap to be lifted and the excimer laser to be applied to the stromal bed. If...
BACKGROUND
In LASIK (laser in situ keratomileusis), a hinged corneal flap is made, which enables the flap to be lifted and the excimer laser to be applied to the stromal bed. If the hinge of the corneal flap detaches from the cornea, the flap is called a free cap. A free cap is a rare intra-operative complication of LASIK most commonly associated with the use of a microkeratome on corneas with flat keratometry, which predisposes to a small flap diameter. Free caps are preventable and treatable. Rarely does the complication lead to a severe or permanent decrease in visual acuity.
PURPOSE
As free caps are avoidable, prevention is critical. Our video gives some tips and tricks on how to avoid a free flap and also focuses on how to manage a cut through a free flap.
SYNOPSIS
If a free cap is created, the surgeon must decide whether to continue with excimer laser ablation or to abort the procedure. When to abort: If the stromal bed is irregular, the flap is replaced without applying laser ablation. Without ablation, generally, there is no change in refractive error or significant loss of visual acuity. When to continue: If the stromal bed is regular and the cap is of normal thickness, the surgeon may proceed with ablation. To prevent desiccation, the free cap should be handled with caution and should be placed on a drop of balanced salt solution. The free cap should be placed epithelial facing up, along with a bandage contact lens. The endothelial cell pump mechanism typically allows the cap to re-adhere tightly.
HIGHLIGHTS
Risk factors for a free cap are generally anatomic or mechanical. Especially in flat corneas, an appropriate ring and stop size should be chosen looking at the nomogram on the basis of the keratometry values. Deep orbits and deep-seated eyes should be looked for as PRK is a better option in such cases. Inadequate suction should be dealt with a lot of care, and once this is done, the vacuum should be stopped. Re-docking of the microkeratome with suction can be done again. Prior testing of the microkeratome and a good verbal anesthesia are a few more such important points to be pondered upon. This video gives us such tips and is a comprehensive video for a novice surgeon performing microkeratome LASIK.
VIDEO LINK
https://youtu.be/piU9nK6rbm4.
Topics: Humans; Free Tissue Flaps; Myopia; Cornea; Keratomileusis, Laser In Situ; Photorefractive Keratectomy; Lasers, Excimer; Corneal Stroma
PubMed: 37417158
DOI: 10.4103/IJO.IJO_756_23 -
Advanced Science (Weinheim,... Sep 2023When circulating tumor cells (CTCs) travel in circulation, they can be killed by detachment-induced anoikis and fluidic shear stress (SS)-mediated apoptosis. Circulatory...
When circulating tumor cells (CTCs) travel in circulation, they can be killed by detachment-induced anoikis and fluidic shear stress (SS)-mediated apoptosis. Circulatory treatment, which can make CTCs detached but also generate SS, can increase metastasis of cancer cells. To identify SS-specific mechanosensors without detachment impacts, a microfluidic circulatory system is used to generate arteriosus SS and compare transcriptome profiles of circulating lung cancer cells with suspended cells. Half of the cancer cells can survive SS damage and show higher invasion ability. Mesotrypsin (PRSS3), protease-activated receptor 2 (PAR2), and the subunit of activating protein 1, Fos-related antigen 1 (FOSL1), are upregulated by SS, and their high expression is responsible for promoting invasion and metastasis. SS triggers PRSS3 to cleave the N-terminal inhibitory domain of PAR2 within 2 h. As a G protein-coupled receptor, PAR2 further activates the Gα protein to turn on the Src-ERK/p38/JNK-FRA1/cJUN axis to promote the expression of epithelial-mesenchymal transition markers, and also PRSS3, which facilitates metastasis. Enriched PRSS3, PAR2, and FOSL1 in human tumor samples and their correlations with worse outcomes reveal their clinical significance. PAR2 may serve as an SS-specific mechanosensor cleavable by PRSS3 in circulation, which provides new insights for targeting metastasis-initiating CTCs.
Topics: Humans; Cell Line, Tumor; Lung Neoplasms; Neoplastic Cells, Circulating; Receptor, PAR-2; Receptors, G-Protein-Coupled; Trypsin
PubMed: 37395651
DOI: 10.1002/advs.202301059 -
Advanced Science (Weinheim,... Oct 2023Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-β (Aβ) is a pathological hallmark. However, Aβ peptide...
Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-β (Aβ) is a pathological hallmark. However, Aβ peptide is also observed in the intestinal tissues of AD patients and animal models. In this study, it is reported that Aβ monomers can target and disintegrate microbial amyloids of FapC and CsgA formed by opportunistic gut pathogens, Pseudomonas aeruginosa and Escherichia coli, explaining a potential role of Aβ in the gut-brain axis. Employing a zebrafish-based transparent in vivo system and whole-mount live-imaging, Aβ is observed to diffuse into the vasculature and subsequently localize with FapC or CsgA fibrils that were injected into the tail muscles of the fish. FapC aggregates, produced after Aβ treatment (Faβ), present selective toxicity to SH-SY5Y neuronal cells while the intestinal Caco-2 cells are shown to phagocytose Faβ in a non-toxic cellular process. After remodeling by Aβ, microbial fibrils lose their native function of cell adhesion with intestinal Caco-2 cells and Aβ dissolves and detaches the microbial fibrils already attached to the cell membrane. Taken together, this study strongly indicates an anti-biofilm role for Aβ monomers that can help aid in the future development of selective anti-Alzheimer's and anti-infective medicine.
Topics: Animals; Humans; Alzheimer Disease; Caco-2 Cells; Zebrafish; Neuroblastoma; Amyloid beta-Peptides; Amyloid; Escherichia coli; Biofilms
PubMed: 37594661
DOI: 10.1002/advs.202301423 -
Graefe's Archive For Clinical and... Mar 2024Proliferative vitreoretinopathy (PVR) remains the main cause of failure in retinal detachment (RD) surgery and a demanding challenge for vitreoretinal surgeons. Despite... (Review)
Review
Proliferative vitreoretinopathy (PVR) remains the main cause of failure in retinal detachment (RD) surgery and a demanding challenge for vitreoretinal surgeons. Despite the large improvements in surgical techniques and a better understanding of PVR pathogenesis in the last years, satisfactory anatomical and visual outcomes have not been provided yet. For this reason, several different adjunctive pharmacological agents have been investigated in combination with surgery. In this review, we analyze the current and emerging adjunctive treatment options for the management of PVR and we discuss their possible clinical application and beneficial role in this subgroup of patients.
Topics: Humans; Vitreoretinopathy, Proliferative; Ophthalmologists; Retinal Detachment; Surgeons
PubMed: 37843566
DOI: 10.1007/s00417-023-06264-1 -
Nature Communications Oct 2023Crystal dissolution, which is a fundamental process in both natural and technological settings, has been predominately viewed as a process of ion-by-ion detachment into...
Crystal dissolution, which is a fundamental process in both natural and technological settings, has been predominately viewed as a process of ion-by-ion detachment into a surrounding solvent. Here we report a mechanism of dissolution by particle detachment (DPD) that dominates in mesocrystals formed via crystallization by particle attachment (CPA). Using liquid phase electron microscopy to directly observe dissolution of hematite crystals - both compact rhombohedra and mesocrystals of coaligned nanoparticles - we find that the mesocrystals evolve into branched structures, which disintegrate as individual sub-particles detach. The resulting dissolution rates far exceed those for equivalent masses of compact single crystals. Applying a numerical generalization of the Gibbs-Thomson effect, we show that the physical drivers of DPD are curvature and strain inherently tied to the original CPA process. Based on the generality of the model, we anticipate that DPD is widespread for both natural minerals and synthetic crystals formed via CPA.
PubMed: 37813861
DOI: 10.1038/s41467-023-41443-y -
ACS Nanoscience Au Aug 2023Developing new techniques to prepare free-standing tubular scaffolds has always been a challenge in the field of regenerative medicine. Here, we report a new and simple...
Developing new techniques to prepare free-standing tubular scaffolds has always been a challenge in the field of regenerative medicine. Here, we report a new and simple way to prepare free-standing collagen constructs with rolled-up architecture by self-assembling nanofibers on porous alumina (AlO) textiles modified with different silanes, carbon or gold. Following self-assembly and cross-linking with glutaraldehyde, collagen nanofibers spontaneously rolled up on the modified AlO textiles and detached. The resulting collagen constructs had an inner diameter of approximately 2 to 4 mm in a rolled-up state and could be easily detached from the underlying textiles. Mechanical testing of wet collagen scaffolds following detachment yielded mean values of 3.5 ± 1.9 MPa for the tensile strength, 41.0 ± 20.8 MPa for the Young's modulus and 8.1 ± 3.7% for the elongation at break. No roll-up was observed on AlO textiles without any modification, where collagen did not assemble into fibers, either. Blends of collagen and chitosan were also found to roll into fibrous constructs on silanized AlO textiles, while fibrinogen nanofibers or blends of collagen and elastin did not yield such structures. Based on these differences, we hypothesize that textile surface charge and protein charge, in combination with the porous architecture of protein nanofibers and differences in mechanical strain, are key factors in inducing a scaffold roll-up. Further studies are required to develop the observed roll-up effect into a reproducible biofabrication process that can enable the controlled production of free-standing collagen-based tubes for soft tissue engineering.
PubMed: 37601922
DOI: 10.1021/acsnanoscienceau.3c00008