BackgroundAvenanthramides (AVN) are a relatively unstudied family of phytochemicals that could be novel chemotherapeutics. These compounds, found in oats, are non-toxic to healthy cells and have been shown to reduce viability of human colon and liver cancers in vitro. However, these studies do not elucidate a molecular mechanism for individual AVN. In this study we aim to see the effects of AVN on MDA-MB-231 breast cancer cells.MethodsAn MTT assay was used to determine cell viability. Staining and analysis with a flow cytometer was used to identify cell cycle progression and apoptosis. FloJo software was used to analyze the cytometric data. In all experiments, statistical significance was determined by a two-tailed t test.ResultsThis study demonstrates that AVN-A, B, and C individually reduce viability in the MDA-MB-231 breast cancer cell line. AVN-C has the most potent decrease in tumor cell viability, decreasing viable cells to below 25% at 400 µM when compared to control after 96 h. We demonstrate that treatment with AVN-C causes DNA fragmentation and accumulation of over 90% of cells into a sub G1 cell cycle population. Further, we conclude that AVN-C treated cells activate apoptosis because 97% of treated cells stain positive for annexin V while 91% have caspase-3/7 activity, a late marker of apoptosis.ConclusionsBreast cancer cells treated with AVN-C have a decrease in cell viability, an increase in the sub G1 population, and stain positive for both annexin V and caspase activity, indicating that AVN-C induces apoptosis in breast cancer cells. These compounds may be able to act as chemotherapeutics as demonstrated through future in vivo studies.

Triple-negative breast cancer is a highly aggressive subtype of breast cancer. Frequently, breast cancer cells modulate their calcium signaling pathways to optimize growth. Unique calcium pathways in breast cancer cells could serve as a way to target tumorigenic cells without affecting normal tissue. Resveratrol has previously been shown to activate calcium signaling pathways. We use cell viability, single-cell calcium microscopy, and RT-PCR assays to determine the activity and mechanism of three different 4′-esterified resveratrol derivatives. We demonstrate that two of the derivatives reduce cell viability more effectively than resveratrol in MDA-MB-231 human breast cancer cells. The derivatives also activate similar pro-apoptotic calcium signaling pathways. In particular, the pivalated and butyrated resveratrol derivatives are intriguing putative chemotherapeutics because they are more effective at decreasing cell viability in vitro and inhibiting the plasma membrane Ca2+-ATPase, a protein that is often modulated in breast cancer.

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Purpose To describe an atypical case of acanthamoeba keratitis with positive in vivo confocal microscopy in a non-contact lens user who presented with signs and symptoms suggestive of central toxic keratopathy. Observations The patient presented with bilateral, though sequential, decreased visual acuity with mild pain. Examination showed stromal haze with corneal flattening and thinning without epithelial defects. Optical coherence tonometry of the right eye revealed an inverse dome-shaped appearance of the opacity and in-vivo confocal imaging showed double-walled cysts consistent with acanthamoeba. Corneal haze, stromal loss, resolved and visual acuity improved over time. Conclusion and importance Acanthamoeba is a rare cause of infectious keratitis that is most often associated with contact lens wear in developed countries. Typically, it presents with a unilateral decrease in visual acuity, photophobia, watering, and pain that is out of proportion to slit lamp examination findings. However, many atypical presentations have been reported in the literature. Consequently, it may be misdiagnosed, especially early in the course of the disease. This delay in diagnosis can lead to progressive ulceration and visual impairment. In addition, cyst formation can make eradication with anti-amoebic treatment especially difficult. Central toxic keratopathy is a non-inflammatory clinical syndrome of unknown etiology that is most often associated with excimer laser ablation, though other associated causes have been reported. It is characterized by a central or paracentral opacity with corneal stromal loss and resultant hyperopic shift. The opacification and stromal loss mostly resolve over the course of months with an improvement in visual acuity. This report may help physicians broaden their differential and correctly diagnose atypical presentations of amoebic infection.

A 36-year-old man was referred back to our clinic after an uneventful laser in situ keratomileusis (LASIK) surgery 6 months previously, with a chief complaint of declining vision in the left eye for the last several months. His pertinent ocular history prior to the LASIK surgery was significant for episodic left eye irritation and inflammation of the superior part of the left cornea secondary to contact lens-induced keratopathy, according to his optometrist. This was a femtosecond-assisted LASIK surgery using the WaveLight FS200 femtosecond laser (Alcon) with the Allegretto EX500 excimer laser (Alcon) for attempted correction of −4.50 diopter (D) of myopia in both eyes under an 8.8 mm flap with a thickness of 100 μm. The uncorrected distance visual acuity (UDVA) was 20/15 in both eyes for the first 2 weeks; at the 1-month follow-up visit, a well-demarcated, wavelike plaque of coarse, thickened corneal epithelium along the superior aspect of the cornea was noted. The UDVA had declined to 20/30 in the left eye. The right eye remained clear with a UDVA of 20/15. The patient was treated for presumed interface inflammation with 1% topical prednisolone acetate for 3 weeks on a tapering regimen and it was noted that there was some improvement in the vision subjectively although the epithelial ridge involving the superior one third of the LASIK flap was present without any change. Over the course of the next 2 months, a progressive decline in vision was noted in the left eye. At no point did his right eye experience symptoms or visual decline. Four months postoperatively the UDVA had declined to 20/60 in the left eye. A linear epithelial ridge extending from limbus at 11 to 2 o'clock position was noted superiorly; staining showed the ridge involved the superior aspect of the flap. The patient was again given corticosteroid treatment, which would improve the symptom of irritation without any change in the visual acuity. Over the course of the next few months, a new wave of abnormal epithelium involving the inferior aspect of the limbus and the flap, encompassing the 2 o'clock position of the flap from the 4 to 6 o'clock positions, was also noted (Figure 1). JOURNAL/jcrs/04.03/02158034-202004000-00025/figure1/v/2023-08-19T002540Z/r/image-tiff Conjunctival staining using lissamine green and fluorescein dye showed staining of the well-demarcated epithelial ridge superiorly and inferiorly involving the flap encroaching the visual axis. On examination, the patient's corrected distance visual acuity was now 20/80 in the left eye. Figures 2, 3, and 4 show the tomographic, topographic, and optical coherence tomography (OCT) results at the 6-month follow-up post-LASIK surgery. JOURNAL/jcrs/04.03/02158034-202004000-00025/figure2/v/2023-08-19T002540Z/r/image-tiff JOURNAL/jcrs/04.03/02158034-202004000-00025/figure3/v/2023-08-19T002540Z/r/image-tiff JOURNAL/jcrs/04.03/02158034-202004000-00025/figure4/v/2023-08-19T002540Z/r/image-tiff Preoperatively the patient denied any ocular history but on further questioning at the 6-month follow-up visit, he provided information about the use of systemic isotretinoin (Accutane) for juvenile acne for 1 year at age 17 and potential exposure to chemicals during military service although he denied any specific ocular exposure. He is a barbeque enthusiast and brews his own alcohol but denies any thermal or direct injury to either eye. His mother had recently told him that he might have had battery acid exposure when he was very young, before age 10, but never required medical attention. What is the most likely diagnosis? What medical or surgical interventions would you recommend for this patient? What is the prognosis for this patient?