Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone-receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and crosstalk between ER and other growth factor signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. METHODS: Using immunohistochemical techniques, we focused on the expression and phosphorylation of hormone receptors themselves and examined the phosphorylation of ER-α Ser118 and ER-α Ser167 and the expression of ER-α, ER-β1, ER-βcx/β2, progesterone receptor (PR), PRA, and PRB in the primary breast carcinomas of 75 patients with metastatic breast cancer who received first-line treatment with endocrine therapy after relapse. RESULTS: Phosphorylation of ER-α Ser118, but not Ser167, was positively associated with overexpression of HER2, and HER2-positive tumors showed resistance to endocrine therapy. The present study has shown for the first time that phosphorylation of ER-α Ser167, but not Ser118, and expression of PRA and PRB, as well as ER-α and PR in primary breast tumors are predictive of response to endocrine therapy, whereas expression of ER-β1 and ER-βcx/β2 did not affect response to the therapy. In addition, patients with either high phosphorylation of ER-α Ser167, or high expression of ER-α, PR, PRA, or PRB had a significantly longer survival after relapse. CONCLUSION: These data suggest that phosphorylation of ER-α Ser167 is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in metastatic breast cancer

Pets as Sentinels of Human Exposure to Neurotoxic Metals

The idea that animals may be used as sentinels of environmental hazards pending over humans and the associated public health implications is not a new one. Nowadays pets are being used as bioindicators for the effects of environmental contaminants in human populations. This is of paramount importance due to the large increase in the worldwide distribution of synthetic chemicals, particularly in the built environment. Companion animals share the habitat with humans being simultaneously exposed to and suffering the same disease spectrum as their masters. Moreover, their shorter latency periods (due to briefer lifespans) enable them to act as early warning systems, allowing timely public health interventions. The rise on ethical constraints on the use of animals and, consequently, on the sampling they can be subjected to has led to the preferential use of noninvasive matrices, and in this case we are looking into hair. This chapter focuses in three non-essential metals: mercury, lead, and cadmium, due to their ubiquitous presence in the built environment and their ability of affecting the mammal nervous system. There is a fairly short amount of studies reporting the concentrations of these metals in pets’ hair, particularly for cats. These studies are characterized, and the metal concentrations corresponding to different parameters (e.g., age, sex, diet, rearing) are described in order to provide the reader with a general vision on the use of this noninvasive matrix on the studies conducted since the last two decades of the twentieth century.publishe

Comorbid conditions in lichen planopilaris: A retrospective data analysis of 334 patients.

BackgroundLichen planopilaris (LPP) is a rare, cicatricial, lymphocyte-mediated alopecia that is thought to have an autoimmune pathogenesis and possibly related to other autoimmune diseases. However, data are limited and studies that examine comorbid conditions are lacking.ObjectivesWe sought to determine the prevalence of systemic comorbid conditions, nutritional deficiencies, psychological problems, and skin cancers in patients with LPP.MethodsWe identified 334 patients with LPP who were seen in the Department of Dermatology at the Cleveland Clinic Foundation between 2000 and 2016. Patients with LPP were compared with 78 control patients with a diagnosis of seborrheic dermatitis.ResultsThere were more female patients with LPP compared with the controls (93.1% vs. 79.5%; p < .001) but the average age did not differ (54.77 ± 12.83 vs. 52.19 ± 15.37; p = .12). Conditions positively associated with LPP were Hashimoto's thyroiditis (6.3% vs. 0%; p = .023), hypothyroidism (24.3% vs. 12.8%; p = .028), and hirsutism (11.4% vs. 1.3%; p = .006). Negatively associated conditions were allergic rhinitis (15% vs. 24.4%; p = .046), diabetes mellitus type II (11.7% vs. 21.8%; p = .019), hyperlipidemia (38.6% vs. 52.6%; p = .024), vitamin D deficiency (50% vs. 65.4%; p = .014), depression (15.6% vs. 28.9%; p = .018), and sleep problems (7.5% vs. 29.5%; p < .001).ConclusionsOur study further emphasizes that dermatologists should screen patients with LPP for autoimmune disorders that are associated with LPP and complete a full metabolic workup to avoid missing other abnormalities. The importance of atopy, autoimmune disorders, endocrine disorders, nutritional deficiencies, psychological problems, and skin cancers in patients with scarring alopecia should be better understood

Mohs surgery for the treatment of lentigo maligna and lentigo maligna melanoma - a systematic review.

BackgroundThe role of Mohs micrographic surgery (MMS) in the treatment of lentigo maligna (LM), and lentigo maligna melanoma (LMM) has been controversial. The use of frozen sections is commonly cited as a suboptimal way to distinguish atypical melanocytes, resulting in traditional wide-local excision techniques as the mainstay of therapy.ObjectiveTo compare the success of MMS as a treatment option for LM and LMM with that of traditional surgical and nonsurgical therapies by analyzing the published recurrence rates of these lesions after MMS procedures.Methods and materialsPubMed database was used to find relevant articles with search terms related to MMS, LM, and LMM.ResultsThe search strategy resulted in 27 articles that fulfilled the inclusion criteria. All studies considered; MMS provided a 1.35% recurrence rate with follow-up times ranging from 1 month to 5 years. Specifically, studies employing classical MMS and MMS with rush sections provided recurrence rates of 1.17% and 2.4%, respectively.ConclusionMMS is one of the most successful treatment options for LM and LMM, with published evidence of improved recurrence rates when compared to other forms of therapy. Additional clinical trials are needed to further delineate the role of MMS in the treatment algorithm for these conditions

Feature characterization of scarring and non-scarring types of alopecia by multiphoton microscopy.

ObjectivesNon-invasive visualization of hair follicles is important for proper diagnosis and management of alopecia; however, histological assessment remains the gold standard. Laser imaging technologies have made possible noninvasive in vivo evaluation of skin and hair follicle. The aim of this study was to evaluate the ability of multiphoton microscopy (MPM) to non-invasively identify morphological features that can distinguish scarring from non-scarring alopecia.MethodsMPM images were obtained from areas on the scalp affected by alopecia. Investigators blinded to the diagnosis analyzed hair follicle and shaft sizes. Patients were recruited and imaged at the UC Irvine Health Medical Center and the University of California, Irvine Beckman Laser Institute. Patients with androgenetic alopecia (AGA) and alopecia areata (AA), and scarring alopecia, in particular frontal fibrosing alopecia (FFA) were recruited and imaged from July 2016 to July 2017.ResultsWe imaged 5 normal scalp subjects and 12 patients affected by non-scarring (7 subjects) and scarring (5 subjects) alopecia. In normal and non-scarring alopecia patients, MPM identified presence of sebaceous glands associated with hair follicles. MPM images of scarring alopecia were characterized by the presence of inflammatory cells surrounding hair follicles. Measurements of hair follicle diameter sizes were found to be significantly smaller in scarring alopecia patients compared to normal (P < 0.001) and compared to non-scarring alopecia patients (P = 0.046); non-scarring hair follicles were also significantly smaller than normal hair follicles (P = 0.043).ConclusionsThis study shows that MPM imaging can non-invasively identify morphological features that distinguish scarring from non-scarring alopecia. Further studies are needed to validate this technique and evaluate its potential to be used as an aid for guiding treatment. Lasers Surg. Med. 51:95-103, 2019. © 2018 Wiley Periodicals, Inc

Feature characterization of scarring and non-scarring types of alopecia by multiphoton microscopy.

ObjectivesNon-invasive visualization of hair follicles is important for proper diagnosis and management of alopecia; however, histological assessment remains the gold standard. Laser imaging technologies have made possible noninvasive in vivo evaluation of skin and hair follicle. The aim of this study was to evaluate the ability of multiphoton microscopy (MPM) to non-invasively identify morphological features that can distinguish scarring from non-scarring alopecia.MethodsMPM images were obtained from areas on the scalp affected by alopecia. Investigators blinded to the diagnosis analyzed hair follicle and shaft sizes. Patients were recruited and imaged at the UC Irvine Health Medical Center and the University of California, Irvine Beckman Laser Institute. Patients with androgenetic alopecia (AGA) and alopecia areata (AA), and scarring alopecia, in particular frontal fibrosing alopecia (FFA) were recruited and imaged from July 2016 to July 2017.ResultsWe imaged 5 normal scalp subjects and 12 patients affected by non-scarring (7 subjects) and scarring (5 subjects) alopecia. In normal and non-scarring alopecia patients, MPM identified presence of sebaceous glands associated with hair follicles. MPM images of scarring alopecia were characterized by the presence of inflammatory cells surrounding hair follicles. Measurements of hair follicle diameter sizes were found to be significantly smaller in scarring alopecia patients compared to normal (P < 0.001) and compared to non-scarring alopecia patients (P = 0.046); non-scarring hair follicles were also significantly smaller than normal hair follicles (P = 0.043).ConclusionsThis study shows that MPM imaging can non-invasively identify morphological features that distinguish scarring from non-scarring alopecia. Further studies are needed to validate this technique and evaluate its potential to be used as an aid for guiding treatment. Lasers Surg. Med. 51:95-103, 2019. © 2018 Wiley Periodicals, Inc