Tamoxifen significantly reduces tumor recurrence in certain patients with early-stage estrogen receptor-positive breast cancer, but markers predictive of treatment failure have not been identified. Here, we generated gene expression profiles of hormone receptor-positive primary breast cancers in a set of 60 patients treated with adjuvant tamoxifen monotherapy. An expression signature predictive of disease-free survival was reduced to a two-gene ratio, HOXB13 versus IL17BR, which outperformed existing biomarkers. Ectopic expression of HOXB13 in MCF10A breast epithelial cells enhances motility and invasion in vitro, and its expression is increased in both preinvasive and invasive primary breast cancer. The HOXB13:IL17BR expression ratio may be useful for identifying patients appropriate for alternative therapeutic regimens in early-stage breast cancer.
The success of molecular targeted therapy in cancer may depend on the selection of appropriate tumor types whose survival depends on the drug target, so-called ''oncogene addiction.'' Preclinical approaches to defining drug-responsive subsets are needed if initial clinical trials are to be directed at the most susceptible patient population. Here, we show that gastric cancer cells with high-level stable chromosomal amplification of the growth factor receptor MET are extraordinarily susceptible to the selective inhibitor PHA-665752. Although MET activation has primarily been linked with tumor cell migration and invasiveness, the amplified wild-type MET in these cells is constitutively activated, and its continued signaling is required for cell survival. Treatment with PHA-665752 triggers massive apoptosis in 5 of 5 gastric cancer cell lines with MET amplification but in 0 of 12 without increased gene copy numbers (P ؍ 0.00016). MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors.gene amplification ͉ molecular marker ͉ oncogene addiction ͉ targeted therapy
In a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brca1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driven by loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in human breast cancers, the identification of a dominant somatic genetic lesion in the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist in BRCA1-initiated human breast cancer. (Cancer Res 2006; 66(7): 3452-5)
Prompt diagnosis of EGPA by the ophthalmologist can decrease patient morbidity and mortality. This requires knowledge of likely ophthalmic EGPA presentations, as well as recommended workups and treatment.
Despite papers reporting equivalent success rates between external and endonasal dacryocystorhinostomy, more American Society of Ophthalmic Plastic and Reconstructive Surgery members perform greater numbers of external dacryocystorhinostomy, prefer external dacryocystorhinostomy, and report a higher success rate with this approach.
The influence of social media is rapidly growing and can be strategically harnessed by oculoplastic surgeons to educate both patients and healthcare providers, collaborate with colleagues, and for referrals and marketing. Supplemental Digital Content is available in the text. Purpose: To determine the impact of social media content from oculoplastic surgeon-held accounts on public engagement. Methods: This study analyzed successful Instagram accounts (defined by >500 followers as of May 2019) held by American Society of Ophthalmic Plastic Reconstruction Surgery members. Each account’s 20 most and 20 least successful posts (based on number of likes) were characterized by the post’s subject, location, media type, and tag usage. Posts were then analyzed using a web-based application that calculates the engagement level of Instagram users with the selected post. Results: A total of 4,812 posts were analyzed from 37 Instagram accounts. Of these American Society of Ophthalmic Plastic Reconstruction Surgery members, the majority were men (67.6%, n = 25) in private practice solely (70.3%, n = 26). Numerous post characteristics, like content and media type, impacted success in a statistically significant manner; for example, public engagement rose when featuring the posting doctor, especially when smiling and wearing a white coat. Meanwhile, posts featuring an office procedure had a negative effect. Formatting was also found to contribute to success. For example, photographs were preferred over videos, while multiple images were best presented sequentially as a carousel (with the viewer swiping through the series) rather than in a large collage. Use of tags (hashtags, accounts, and locations) were associated with increased engagement. Conclusions: Social media is an important communication and marketing tool, especially in esthetic fields like oculoplastics. Guidelines for success are presented in this study; content, location, subject, media type, and tags statistically significantly impact public engagement.
Background Congenital ptosis is a drooping of one or both eyelids at birth, o en due to poor development of the levator palpebrae superioris muscle. This can result in amblyopia, astigmatism, and ocular torticollis and therefore may necessitate surgical intervention in early childhood if visual development is compromised. Patients may have varied levels of levator function. Those with moderate to good function may elect to first attempt ptosis repair with external levator advancement or mullerectomy/Fasanella-Servat procedures. For those with poor function, those procedures are less likely to be e ective, so they may undergo frontalis sling surgery, in which the tarsal plate is coupled to the frontalis muscle, so that movement of the brow and forehead result in movement of the eyelid. The optimal material to use in this surgery is unknown. Objectives To evaluate the comparative e ectiveness and safety of various materials used in frontalis sling surgery for congenital ptosis. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register)
A 15-month-old boy with left congenital proptosis presented to the emergency department with melena. Upper GI endoscopy and magnetic resonance angiography revealed vascular lesions, consistent with gastrointestinal tract manifestations of blue rubber bleb nevus syndrome. MRI revealed vascular malformations in both orbits, with mass effect on the left side. The patient was started on a trial of the antiangiogenic agent sirolimus (also known as rapamycin), and after 6 months of treatment showed clinical improvement in proptosis supported by radiologic evidence of regression in the larger, left orbital mass, with stability of the smaller, right orbital mass. There are 11 published cases of orbital blue rubber bleb nevus syndrome in the English literature. To our knowledge, this is the first reported case of successful, long-term treatment with sirolimus causing a reduction in the size of an orbital vascular malformation.
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