CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?

Cyclin-dependent kinase inhibitor 1A (Cip1/Waf1/CDKN1A/p21) is a well-established protein, primarily recognised for its pivotal role in the cell cycle, where it induces cell cycle arrest by inhibiting the activity of cyclin-dependent kinases (CDKs). Over the years, extensive research has shed light on various additional mechanisms involving CDKN1A/p21, implicating it in processes such as apoptosis, DNA damage response (DDR), and the regulation of stem cell fate. Interestingly, p21 can function either as an oncogene or as a tumour suppressor in these contexts. Complicating matters further, the expression of CDKN1A/p21 is elevated in certain tumour types while downregulated in others. In this comprehensive review, we provide an overview of the multifaceted functions of CDKN1A/p21, present clinical data pertaining to cancer patients, and delve into potential strategies for targeting CDKN1A/p21 as a therapeutic approach to cancer. Manipulating CDKN1A/p21 shows great promise for therapy given its involvement in multiple cancer hallmarks, such as sustained cell proliferation, the renewal of cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cell migration, and resistance to chemotherapy. Given the dual role of CDKN1A/p21 in these processes, a more in-depth understanding of its specific mechanisms of action and its regulatory network is imperative to establishing successful therapeutic interventions.

Explantation of a sutureless scleral fixated Carlevale intraocular lens due to calcification: a clinical and laboratory report.

BACKGROUND: Hydrophilic intraocular lens opacification is a rare complication due to calcification. With current new surgical techniques, including lamellar endothelial keratoplasty and vitrectomies, this irreversible complication is becoming more common. In this case study, we present clinical and laboratory features of a case of Carlevale hydrophilic acrylic IOL calcification. CASE PRESENTATION: Observational case report of a single incident case. An 83-year-old man was referred to our ophthalmic department complaining of right eye vision blurring for six months. Slit-lamp biomicroscopy revealed IOL opacification. Deposits of calcium phosphate were found both on the IOL's surface and inside it, according to thorough investigation using optical, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) spectrometry. CONCLUSIONS: To the best of our knowledge, this is the first case to describe the laboratory evidence of Carlevale hydrophilic IOL calcification, suggesting possible explanation mechanisms based on underlying pathology and surgical technique. It reminds us that these findings suggest that physicians should be aware of possible hydrophilic IOL calcification.

Anterior Chamber Dislocation of Dexamethasone Implant in the Presence of Carlevale Sutureless Scleral Fixation Intraocular Lens.

Dexamethasone intravitreal implant (Ozurdex®; Allergan, Inc., CA, USA) has been proved to be effective in a variety of clinical settings including cases of pseudophakic cystoid macular edema. Uncommonly, this implant can migrate from the vitreous cavity and into the anterior chamber, especially in vitrectomized eyes with lens capsule defects. We report herein a rare case of anterior chamber migration and illustrate the passageway of the dexamethasone intravitreal implant through a new type of scleral fixated lens, the Carlevale IOL (Soleko-Italy). A 78-year-old woman was left aphakic following a complicated right eye hypermature cataract surgery with posterior capsule rupture and zonular dehiscence. Shortly thereafter, she underwent a planned combined pars plana vitrectomy with the placement of a Carlevale sutureless scleral fixated intraocular lens for the treatment of her aphakia. Due to a subsequent persistent cystoid macular edema that was unresponsive to topical treatment and sub-tenon corticosteroids, an intravitreal dexamethasone implant was injected. Eleven days after implantation, the patient presented with a floating implant in the anterior chamber and corneal edema. Following an immediate surgical removal, corneal edema resolved and visual acuity improved. One year later, results remain stable without macular edema recurrence. Anterior chamber migration of the Ozurdex implant is a potential complication in vitrectomized eyes, even when new types which are larger and specially designed for scleral fixation intraocular lenses are utilized. Corneal complications can be reversible following an immediate removal of the implant.

Agreement between swept-source optical biometry and Scheimpflug-based tomography in eyes with previous myopic refractive surgery.

PURPOSE: The purpose of the study is to evaluate the comparability of corneal power measurements, anterior chamber depth (ACD), and white-to-white (WTW) distance between a high-resolution Scheimpflug-based tomography (Pentacam HR; Oculus GmbH, Wetzlar, Germany) and a swept-source optical biometry, IOL Master 700; Carl Zeiss Meditec AG, Jena, Germany) in patients having undergone a myopic refractive surgery. METHODS: This prospective, interinstrument reliability analysis included 31 individuals with a previous myopic laser refractive correction. Standard keratometry and total keratometry (TK) of the flattest and steepest axis of the IOL Master 700 were compared with standard keratometry (simulated keratometry [SimK]), true net power (TNP), equivalent keratometer readings (EKR), and total corneal refractive power of the Pentacam. The Bland-Altman analysis evaluated the agreement between the measurements of both devices. A paired t-test was performed to compare the mean values of the variables obtained by the two devices. RESULTS: Mean age of the participants was 31.87 ± 13.17 years. Ten patients (32.3%) had undergone laser in situ keratomileusis surgery, and 21 (67.7%) had undergone photorefractive keratectomy surgery. The two devices generated statistically significant differences in almost all the comparisons between their corneal keratometry values, ACD, and WTW. The two devices agreed in some of the flat axis values and more specifically on SimK1 and K1, EKR K1 along 1 mm-zone and K1, as well as on the comparison between the EKR keratometry values along 1, 2, and 3 mm-zone with their corresponding TKs. CONCLUSION: IOL Master 700 and Pentacam HR do not show good concordance and cannot be used interchangeably when measuring keratometry values in postrefractive eyes, rendering the IOL power calculation in postrefractive eyes really challenging.

Agreement in anterior segment measurements between swept-source and Scheimpflug-based optical biometries in keratoconic eyes: a pilot study.

Background: Cataract surgery in keratoconic patients is challenging because of the corneal distortion, which can lead to inaccurate keratometry readings. This study is a comparison of the accuracy of keratometry readings by two types of devices in a tertiary hospital. Purpose: To evaluate the comparability of corneal power measurements, anterior chamber depth (ACD), and white-to-white (WTW) distance between Scheimpflug-based tomography (Pentacam AXL; OCULUS GmbH, Wetzlar, Germany) and swept-source optical biometry (IOLMaster 700; Carl Zeiss Meditec AG, Jena, Germany) in patients with keratoconus. Methods: This pilot, prospective, interinstrument reliability study included 30 keratoconic eyes of 15 individuals who had not undergone any kind of corneal surgery. Standard K and total refractive power (TK®) of the flattest and steepest axes of the IOLMaster 700 were compared with the standard keratometry (SimK), true net power (TNP), equivalent keratometer readings (EKR), and total corneal refractive power (TCRP) of the Pentacam. The Bland-Altman analysis was used to evaluate the agreement between the measurements of both devices. The paired-samples t-test and the Wilcoxon signed-rank test were performed to compare the mean values of the variables obtained with the devices. Results: The K1 value of the IOLMaster 700 was significantly higher from EKR K1 along the 3-mm (mean difference: 0.79 diopters, p = 0.01), 4-mm (mean difference: 1.01 D, p = 0.01), and 4.5-mm zones (mean difference: 1.20 D, p = 0.01) and TNP K1 along the 3-mm (mean difference: 0.88 D, p < 0.001) and 4-mm zones (mean difference: 0.97 D, p < 0.001). The TK1 value was significantly higher from EKR K1 along the 2-mm (mean difference: 0.42 D, p = 0.04), 3-mm (mean difference: 0.83 D, p = 0.003), 4-mm (mean difference: 1.05 D, p = 0.004), and 4.5-mm zones (mean difference: 1.24 D, p = 0.005) and TNP K1 along the 3-mm (mean difference: 0.92 D, p < 0.001) and 4-mm zones (mean difference: 1.01 D, p < 0.001). The K2 value of the IOLMaster 700 was significantly higher from TK2 (mean difference: 0.11 D, p = 0.04) and all the corresponding variables of the Pentacam device. The TK2 value was significantly higher from all the corresponding variables of the Pentacam device. The Pentacam also yielded significantly lower values for the WTW distance (mean difference: 0.31 mm, p < 0.001) and no significant difference in terms of ACD values (p = 0.9). Conclusion: The IOLMaster measured significantly greater keratometry readings in the steep axis for all the variables studied. The keratometry and WTW measurements of the investigated devices cannot be used interchangeably in keratoconus.