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  1. 1
    رسالة جامعية

    المؤلفون: Abad i Lázaro, Aina

    المساهمون: University/Department: Universitat de Barcelona. Facultat de Física

    مرشدي الرسالة: Martínez Fraiz, Elena, Samitier i Martí, Josep

    المصدر: TDX (Tesis Doctorals en Xarxa)

    الوصف: Programa de Doctorat en Biomedicina / Tesi realitzada a l'Institut de Bioenginyeria de Catalunya (IBEC)

    الوصف (مترجم): [eng] The standard in vitro model of the small intestine in the field of drug development still consists in a monolayer of cancer-derived cells seeded on a hard substrate. Despite the huge advances that this model has provided, it does not faithfully recapitulate the complexity of the native tissue. Recently, the long-term culture of primary intestinal epithelial cells has been achieved through intestinal organoids, self-organizing 3D structures retrieving many of the features of the native tissue. Yet, they still have some limitations: (i) they are closed structures whose apical side is difficult to access, (ii) to grow, they require to be embedded in a highly heterogeneous matrix where well-controlled gradients of biochemical factors cannot be established, (iii) despite recapitulating the native cell compartmentalization, they do not retrieve the dimensionality of the tissue and (iv) they do not include the stromal compartment (mainly fibroblasts), proven to be key to maintain the intestinal stem cell niche. Therefore, the general objective of this thesis is to contribute to the development of complex in vitro models of intestinal epithelium focusing on the incorporation of the input of the stroma. In the first section of this thesis, we successfully adapted an in-house developed photolithography-based technique to fabricate poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels with crypt-like cavities. Although the nature of the chemical reaction used yielded partially-crosslinked polymer trapped in the cavities, the fabricated hydrogels could be functionalized with collagen I and organoid-derived epithelial monolayers could be formed on top. In the second section of this thesis, we have developed an in vitro model that allows the culture of organoid-derived cells on hydrogels with villus-like architecture under gradients of the ISC niche. The fabricated hydrogels showed native tissue-like elasticity and microstructures resembling those of the native villi. The mesh size of the hydrogels allowed the diffusion of the factors of the ISC niche through the hydrogel, which formed stable gradients along the villus vertical axis. An in silico model of protein diffusion through the hydrogel was developed to predict the profiles of the gradients of the factors of the ISC niche. Organoid-derived single cells seeded on collagen I-functionalized hydrogels formed complete monolayers. Only under gradients of the ISC niche factors, as opposed to uniform concentrations, the monolayers displayed native-like cell compartmentalization. Finally, organoid-derived cells cultured under gradients that promote more the proliferation showed faster growth dynamics but also a depletion of the proliferative pool. Altogether, these findings demonstrate that our villus-like 3D intestinal epithelial model retrieves native-like cell compartmentalization under appropriate gradients of ISC niche factors. The in vitro model presented here could be used to systematically screen gradients of factors, of particular interest those secreted by fibroblasts, and study the cellular response. In the third section of this thesis, we aimed to study if intestinal fibroblasts have a physical role in epithelial cell migration under non-pathological conditions. Through the coculture of fibroblasts with intestinal organoids, we found that the paracrine signalling from the fibroblasts induced a cystic morphology in the organoids, whereas their physical presence triggered their expansion into 2D monolayers. This physical effect of fibroblasts leading the expansion of epithelial cells was also observed in a 2D engineered coculture in vitro model. Organoid-derived monolayers exposed to a cell-free space (gap) migrated directionally towards the gap and fully closed it. During this process, fibroblasts were found to also migrate but towards the monolayers, align perpendicularly to the migration front and produce equally oriented ECM proteins that might be used for epithelial cells to migrate directionally. Under only the paracrine signalling from fibroblasts, epithelial monolayers did not migrate that efficiently nor fully closed the gaps. Under no fibroblast input, epithelial cells migrated randomly and could not recover their integrity. All in all, we could demonstrate that fibroblasts are indispensable for epithelial integrity restoration under non-pathological conditions in a 2D coculture in vitro model. Given the physical role of fibroblasts on the epithelial tissue, in the fourth section of this thesis we aimed to develop an in vitro model that incorporated a lamina propria mimicking compartment, together with the epithelial tissue, all the while recapturing the native architecture. To do so, we employed an in-house developed 3D printing technology to fabricate flat and villus-like gelatine methacryloyl (GelMA)-PEGDA hydrogels. First, using flat hydrogels, embedded fibroblasts were shown to be viable, have proliferation capacity and spread over the hydrogel surface. Organoid-derived epithelial cells seeded on top could only grow and form monolayers when fibroblasts were embedded within the GelMA-PEGDA hydrogels. In villus-like hydrogels, fibroblasts not only migrated to and spread on the surface, but they preferentially located at the tips of the villus-like microstructures. Organoid-derived single cells seeded on top of grew mainly at the tips and bases of the hydrogels. In these cocultures, fibroblasts migrated to the regions where epithelial cells were growing, mainly the tips and the bases of the hydrogels. Finally, fibroblasts cocultured with epithelial cells had their nuclei more elongated than when cultured alone, indicating a physical communication between the two cell types. Overall, we developed an in vitro model that mimics the native tissue architecture and encompasses not only the epithelium but also the mesenchymal compartment. Through this platform, we have unveiled a bidirectional communication between epithelial cells and fibroblasts.
    [cat] Avui dia, el model in vitro estàndard de l'intestí prim al camp del desenvolupament de fàrmacs encara consisteix en una monocapa de cèl·lules cancerígenes sembrades sobre un substrat dur. Tot i els grans avenços que aquest model ha suposat, no recapitula de manera fidedigna la complexitat del teixit. Recentment s’ha posat apunt el cultiu d’organoids intestinals, estructures tridimensionals autoorganitzades que recapitulen moltes de les característiques del teixit nadiu. Tot i això, presenten diverses limitacions: (i) en ser estructures tancades, l'accés a la part apical és complicat; (ii) per créixer, necessiten estar dins una matriu altament heterogènia que dificulta poder establir gradients de factors bioquímics ben controlats; (ii) malgrat recapitular l'organització cel·lular del teixit, no mimetitzen la seva arquitectura i (iv) no inclouen el compartiment “estromal” (principalment fibroblasts), tot i que s'hagi demostrat ser essencial en el manteniment del nínxol de cèl·lules mare. Al llarg d’aquesta tesi s’han desenvolupat diferents models que recapitulen moltes de les característiques mencionades més amunt. La primera secció d'aquesta tesi ha tingut per objectiu reproduir l’arquitectura del teixit intestinal. Per això, hem adaptat una tècnica desenvolupada al nostre laboratori que es basa en fotolitografia per fabricar hidrogels de diacrilat de polietilè glicol (PEGDA) amb cavitats similar a les criptes intestinals. En la segona part, ens hem centrat en crear un model que permetés establir gradients bioquímics de factors del nínxol de cèl·lules mare. En concret, hem desenvolupat un model in vitro que permet el cultiu de cèl·lules epitelials derivades d'organoids en hidrogels amb unes microestructures que reprodueixen les vellositats intestinals sota l’efecte de gradients bioquímics fisiològicament rellevants. En la tercera part, hem desenvolupat un model que permet el co-cultiu de cèl·lules epitelials derivades d’organoids amb fibroblasts primaris aïllats de l’intestí. A més, a través d’aquest model, hem pogut veure com els fibroblasts son essencials per a la migració de les cèl·lules epitelials en un context no patològic. En la quarta i última secció d’aquesta tesi, hem incorporat el compartiment estromal en un model que també reprodueix l’arquitectura del teixit, establint doncs un co-cultiu de cèl·lules epitelials i fibroblasts espacio-fisiològicament rellevant.

    وصف الملف: application/pdf

  2. 2
    مؤتمر

    المؤلفون: Sari, Rina Kartika1 (AUTHOR) rina.kartika@unissula.ac.id

    المصدر: AIP Conference Proceedings. 2024, Vol. 3127 Issue 1, p1-6. 6p.

    مستخلص: Background: Chemotherapy, despite its high effectiveness, has side effects in the oral cavity, specifically mucositis. Centella asiatica (gotu kola) and various other herbal ingredients have shown promise and efficacy in the healing of these oral wounds. Compounds such as asiaticoside, madecassoside, triterpenoid saponins, and asiatic acid found in Centella asiatica leaves serve as antioxidants and aid in the healing of soft tissues. The process of wound healing can be assessed through the rate of proliferation, with Ki67 serving as a widely accepted marker for this purpose. Purpose: The purpose of this study was to evaluate the effect of a 25% Centella asiatica extract spray gel on the healing of oral mucositis, as indicated by the expression of Ki67. Methods: Oral mucositis was induced in 32 male Wistar rats via intravenous injection of 5-fluorouracil (5FU) for thirteen days. The treatment group (n = 16) received a 25% Centella asiatica gel spray twice daily for six days, whereas the control group (n = 16) received a hyaluronic acid spray over the same duration. On the sixth day post-treatment, the rats were decapitated, and the tissue samples underwent immunohistochemistry analysis. Results: Oral mucositis initiation commenced on day 10 and became clinically apparent on day 13, manifesting as ulcers with yellow pseudomembranes and erythema on the labial mucosa and gingiva of the rats. The mean Ki67 expression in the treatment group was 3.2000±0.2033 (p = 0.000), while it stood at 1.7125±0.2726 (p = 0.000) in the control group. Conclusion: Based on the Ki67 proliferation index, the administration of Centella asiatica extract gel spray was found to promote cell proliferation more effectively than the hyaluronic acid gel spray during the healing process of oral mucositis caused by chemotherapy in rats. [ABSTRACT FROM AUTHOR]

  3. 3
    دورية أكاديمية

    المصدر: Quintessence International; May2024, Vol. 55 Issue 5, p392-398, 7p

    مستخلص: Secretory carcinoma is a malignant salivary gland tumor, which typically presents as an indolent painless mass within the parotid gland. Involvement of the minor gland is reported but less common. Secretory carcinoma was often misclassified as other salivary gland mimics, particularly acinic cell carcinoma, prior to 2010. It was first recognized as a molecularly distinct salivary gland tumor harboring the same fusion gene as well as histologic and cytogenetic features seen in juvenile breast cancer. Secretory carcinoma is generally managed in the same way as other low-grade salivary gland neoplasms and has a favorable prognosis; however, high-grade transformation requiring aggressive therapeutic interventions have been documented. Recent studies of biologic agents targeting products of this fusion gene offer the promise of a novel therapeutic option for treatment of this malignancy. Due to the limited number of reported cases, the spectrum of clinical behavior, best practices for management, and long-term treatment outcomes for secretory carcinoma remain unclear. A long-standing secretory carcinoma involving minor salivary glands of the mucobuccal fold, which was detected years after it was first noted by the patient, is reported. This case brings to light the importance of a thorough clinical exam during dental visits and reviews diagnostic differentiation of this malignancy from other mimics and discusses decision making for its management. [ABSTRACT FROM AUTHOR]

    : Copyright of Quintessence International is the property of Quintessence Publishing Company Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

  4. 4
    دورية أكاديمية

    المصدر: International Journal of Oral & Maxillofacial Implants; May/Jun2024, Vol. 39 Issue 3, p381-388, 8p

    مستخلص: Purpose: The structural and compositional similarities between dentin and alveolar bone form the basis for utilizing dentin for bone regeneration. Various authors have recommended using treated mineralized, partially demineralized, or demineralized dentin grafts instead of xenografts because of their comparable clinical and radiographic results and lower costs. The current study therefore compared the effect of untreated mineralized dentin grafts (UMDGs) versus xenografts in vertical and horizontal augmentation around dental implants that were immediately placed in the mandibular anterior region. Materials and Methods: A total of 56 patients who required immediate dental implant placement in the mandibular anterior region were randomly allocated to group I (study), where ground dentin was washed with normal saline and placed around the dental implants, or group II (control), where a xenograft was used. The primary implant stability was measured at the time of implant placement. Secondary implant stability, plaque index (PI), bleeding index (BI), probing depth (PD), and keratinized mucosa width (KMW) were assessed at baseline (time of definitive abutment and provisional crown placement) and then at 3, 6, and 12 months. Pain and the number of analgesics consumed were assessed daily during the first postoperative week. Marginal bone loss (MBL) and radiodensity were assessed radiographically. Results: There were no significant differences between the groups in terms of postoperative pain, the number of analgesic tablets consumed, peri-implant mucositis, or peri-implantitis. Both groups showed comparable results for the PI, BI, and PD. Moreover, there was no statistical difference between the groups with regard to primary implant stability and secondary implant stability at baseline and 12 months. Group I showed significantly lower secondary implant stability after loading at 3 and 6 months and significantly greater bone loss and lower bone density before exposure. KMW and MBL after exposure were significantly higher in group I at all time points. Conclusions: Although UMDGs showed similar clinical results to xenografts, including primary and secondary implant stability, they had higher resorption rates than xenografts. Therefore, treatment of the dentin graft is required. Thus, the authors do not recommend using UMDGs. [ABSTRACT FROM AUTHOR]

    : Copyright of International Journal of Oral & Maxillofacial Implants is the property of Quintessence Publishing Company Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

  5. 5
    دورية أكاديمية

    المؤلفون: Bhatavadekar, Neel, Padhye, Ninad

    المصدر: International Journal of Periodontics & Restorative Dentistry; May/Jun2024, Vol. 44 Issue 3, p339-346, 8p

    مستخلص: This study assessed the effects of buccal contour augmentation for periodontally compromised teeth with horizontal bone loss. A total of 30 subjects were divided into Group A or Group B (n = 15 subjects per group). Group A received open-flap debridement (OFD) with buccal contour augmentation using deproteinized bovine bone mineral (DBBM), jointly referred to as contour augmentation for periodontal defects (CAPD; test group). Group B received only OFD (control group). Bleeding on probing (BOP), clinical attachment level (CAL), probing depth (PD), gingival recession (GR), keratinized mucosa width (WKM), keratinized mucosa thickness (TKM), and labial cortical plate thickness were compared at baseline and 1 year. BOP, CAL, PD, and GR did not show significant differences. TKM increased by 1.76 mm for Group A but decreased by 1 mm for Group B. WKM increased from 2.86 ± 0.4 mm to 3.6 ± 0.71 mm (P < .001) and from 2.93 ± 0.32 mm to 3 ± 0.7 mm (P = 0.5) for Groups A and B, respectively, which showed statistical significance. Labial cortical plate thickness increased from 0.94 ± 0.3 mm to 1.95 ± 0.54 mm (P < .001) for Group A but decreased from 0.87 ± 0.45 mm to 0.68 ± 0.31 mm for Group B. Visual analog scale scores for pain perception showed no difference between the two groups. CAPD for periodontally compromised teeth improves WKM and TKM. Long-term analyses are needed to determine its benefits in daily clinical practice. [ABSTRACT FROM AUTHOR]

    : Copyright of International Journal of Periodontics & Restorative Dentistry is the property of Quintessence Publishing Company Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

  6. 6
    دورية أكاديمية

    المؤلفون: Chwa, Jason S.1,2 (AUTHOR) jchwa@usc.edu, Kim, Minjun3 (AUTHOR) mik075@health.ucsd.edu, Lee, Yesun3 (AUTHOR) yel040@health.ucsd.edu, Cheng, Wesley A.3 (AUTHOR) wesleycheng@health.ucsd.edu, Shin, Yunho2 (AUTHOR), Jumarang, Jaycee3 (AUTHOR) jjumarang@health.ucsd.edu, Bender, Jeffrey M.4 (AUTHOR) jebender@coh.org, Pannaraj, Pia S.3,5 (AUTHOR) ppannaraj@ucsd.edu

    المصدر: Viruses (1999-4915). Jun2024, Vol. 16 Issue 6, p852. 11p.

    مستخلص: Mucosal immunity may contribute to clearing SARS-CoV-2 infection prior to systemic infection, thereby allowing hosts to remain seronegative. We describe the meaningful detection of SARS-CoV-2-specific nasal mucosal antibodies in a group of exposed-household individuals that evaded systemic infection. Between June 2020 and February 2023, nasopharyngeal swab (NPS) and acute and convalescent blood were collected from individuals exposed to a SARS-CoV-2-confirmed household member. Nasal secretory IgA (SIgA) antibodies targeting the SARS-CoV-2 spike protein were measured using a modified ELISA. Of the 36 exposed individuals without SARS-CoV-2 detected by the RT-PCR of NPS specimens and seronegative for SARS-CoV-2-specific IgG at enrollment and convalescence, 13 (36.1%) had positive SARS-CoV-2-specific SIgA levels detected in the nasal mucosa at enrollment. These individuals had significantly higher nasal SIgA (median 0.52 AU/mL) compared with never-exposed, never-infected controls (0.001 AU/mL) and infected-family participants (0.0002 AU/mL) during the acute visit, respectively (both p < 0.001). The nasal SARS-CoV-2-specific SIgA decreased rapidly over two weeks in the exposed seronegative individuals compared to a rise in SIgA in infected-family members. The nasal SARS-CoV-2-specific SIgA may have a protective role in preventing systemic infection. [ABSTRACT FROM AUTHOR]

  7. 7
    دورية أكاديمية

    المؤلفون: Kuo, Cheng‐Hao1,2 (AUTHOR), Wu, Li‐Ling3,4,5 (AUTHOR), Chen, Hsiao‐Ping6,7 (AUTHOR), Yu, Jun8 (AUTHOR), Wu, Chun‐Ying2,4,5,6,7 (AUTHOR) dr.wu.taiwan@gmail.com

    المصدر: Journal of Gastroenterology & Hepatology. Jul2024, Vol. 39 Issue 7, p1247-1255. 9p.

    مستخلص: The development of alcohol‐associated diseases is multifactorial, mechanism of which involves metabolic alteration, dysregulated immune response, and a perturbed intestinal host‐environment interface. Emerging evidence has pinpointed the critical role of the intestinal host–microbiota interaction in alcohol‐induced injuries, suggesting its contribution to disease initiation and development. To maintain homeostasis in the gut, the intestinal mucosa serves as the first‐line defense against exogenous factors in the gastrointestinal tract, including dietary contents and the commensal microbiota. The gut‐epithelial barrier comprises a physical barrier lined with a single layer of intestinal epithelial cells and a chemical barrier with mucus trapping host regulatory factors and gut commensal bacteria. In this article, we review recent studies pertaining to the disrupted gut‐epithelial barrier upon alcohol exposure and examine how alcohol and its metabolism can affect the regulatory ability of intestinal epithelium. [ABSTRACT FROM AUTHOR]

  8. 8
    دورية أكاديمية

    المصدر: Surgical Endoscopy & Other Interventional Techniques. Jul2024, Vol. 38 Issue 7, p3716-3727. 12p.

    مستخلص: Background: Post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) is an uncommon complication after colorectal endoscopic submucosal dissection (ESD). This study aimed to explore the risk factors of PEECS for superficial colorectal lesions based on the latest and consistent diagnostic criteria and to establish a predictive nomogram model. Methods: This retrospective analysis included patients with superficial colorectal lesions who underwent endoscopic submucosal dissection (ESD) between June 2008 and December 2021 in our center. The independent risk factors of PEECS for superficial colorectal lesions were identified using least absolute shrinkage and selection operator (LASSO) logistic regression analysis, as well as univariate analysis and multivariate logistic regression, and derived predictive nomogram model was constructed. Results: Among the 555 patients with superficial colorectal lesions enrolled, PEECS occurred in 45 (8.1%) patients. Multivariate logistic regression revealed that female sex (OR 3.94, P < 0.001), age > 50 years (OR 4.28, P = 0.02), injury to muscle layer (OR 10.38, P < 0.001), non-lifting sign (OR 2.20, P = 0.04) and inadequate bowel preparation (OR 5.61, P < 0.001) were independent risk factors of PEECS for superficial colorectal lesions. A predictive nomogram model was constructed based on the above five predictors. For this model, the area under the receiver operating characteristic (ROC) curve was 0.855, the calibration curve exhibited good consistency between the prediction and the actual observation, and the C-index was confirmed as 0.843 by bootstrap method. Conclusion: Female sex, age > 50 years, injury to muscle layer, non-lifting sign and inadequate bowel preparation were independent risk factors of PEECS for superficial colorectal lesions. The proposed nomogram could accurately predict the risk of PEECS for superficial colorectal lesions. [ABSTRACT FROM AUTHOR]

  9. 9
    دورية أكاديمية

    المؤلفون: Shigenobu, Takao1 (AUTHOR) ta00-shigenobu@hosp.city.yokohama.lg.jp, Suzuki, Takahiro1 (AUTHOR), Hayashi, Hiroyuki2 (AUTHOR), Yoshizu, Akira1 (AUTHOR)

    المصدر: World Journal of Surgical Oncology. 6/20/2024, Vol. 22 Issue 1, p1-6. 6p.

    مستخلص: Background: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and is known to be associated with Sjögren's syndrome (SjS). SjS is rarely accompanied by serositis. Here, we describe the first case of postoperative cardiac tamponade and acute pleuritis in a patient with thymic MALT lymphoma associated with SjS. Case presentation: A 33-year-old woman with SjS presented with an anterior mediastinal mass on chest computed tomography, which was performed for further examination of the condition. Suspecting a thymic MALT lymphoma or thymic epithelial tumor, total thymectomy was performed. The mediastinal mass was histopathologically diagnosed as a thymic MALT lymphoma. The patient was discharged with a good postoperative course but visited the hospital 30 days after surgery for dyspnea. Cardiac tamponade was observed and drainage was performed. Four days after pericardial drainage, chest radiography revealed massive left pleural effusion, and thoracic drainage was performed. The patient was diagnosed with serositis associated with SjS and treated with methylprednisolone, which relieved cardiac tamponade and pleuritis. Conclusions: Surgical invasion of thymic MALT lymphomas associated with SjS may cause serositis. Postoperative follow-up should be conducted, considering the possibility of cardiac tamponade or acute pleuritis due to serositis as postoperative complications. [ABSTRACT FROM AUTHOR]

  10. 10
    دورية أكاديمية

    المؤلفون: Covarrubias, Alejandra A.1,2,3,4 (AUTHOR) alejandra.covarrubias@ucn.cl, Reyna-Jeldes, Mauricio1,2,3,5 (AUTHOR) mauricio.reynajeldes@oncology.ox.ac.uk, Pedroso-Santana, Seidy2,6 (AUTHOR) cdemerga@ucn.cl, Marín, Sabrina2,6 (AUTHOR), Madero-Mendoza, Carolina7 (AUTHOR) caromadero16@gmail.com, Demergasso, Cecilia2,6 (AUTHOR), Coddou, Claudio1,2,3 (AUTHOR) ccoddou@ucn.cl

    المصدر: International Journal of Molecular Sciences. Jun2024, Vol. 25 Issue 12, p6723. 17p.

    مصطلحات موضوعية: *ANOIKIS, *GASTRIC mucosa, *APOPTOSIS, *ARSENIC, *EXTRACELLULAR matrix, *NANOPARTICLES

    مصطلحات جغرافية: CHILE

    مستخلص: Arsenic compounds have been used as therapeutic alternatives for several diseases including cancer. In the following work, we obtained arsenic nanoparticles (AsNPs) produced by an anaerobic bacterium from the Salar de Ascotán, in northern Chile, and evaluated their effects on the human oral squamous carcinoma cell line OECM-1. Resazurin reduction assays were carried out on these cells using 1–100 µM of AsNPs, finding a concentration-dependent reduction in cell viability that was not observed for the non-tumoral gastric mucosa-derived cell line GES-1. To establish if these effects were associated with apoptosis induction, markers like Bcl2, Bax, and cleaved caspase 3 were analyzed via Western blot, executor caspases 3/7 via luminometry, and DNA fragmentation was analyzed by TUNEL assay, using 100 µM cisplatin as a positive control. OECM-1 cells treated with AsNPs showed an induction of both extrinsic and intrinsic apoptotic pathways, which can be explained by a significant decrease in P-Akt/Akt and P-ERK/ERK relative protein ratios, and an increase in both PTEN and p53 mRNA levels and Bit-1 relative protein levels. These results suggest a prospective mechanism of action for AsNPs that involves a potential interaction with extracellular matrix (ECM) components that reduces cell attachment and subsequently triggers anoikis, an anchorage-dependent type of apoptosis. [ABSTRACT FROM AUTHOR]