Abstract: Chronic lymphoproliferative disorder of natural killer cells (CLPDNK) is a rare heterogenous indolent disorder comprising a persistent peripheral blood cell count of more than ≥2 × 109/L natural killer cells for over 6 months. We report an unusual case of cutaneous neural infiltration as a manifestation of CLPDNK. A 52-year-old woman with a background of CLPDNK was referred to dermatology with a painful rash primarily affecting her back. Skin biopsies revealed a neurotropic atypical lymphoid infiltration. Results of immunohistochemistry studies showed CD8, CD56, granzyme B, perforin positivity, and CD3 negativity in keeping with an atypical neurotropic lymphoid infiltrate consistent with cutaneous involvement by the patient's known CLPDNK. Cutaneous lesions and peripheral neuropathy in patients with CLPDNK have been reported; however, the involvement of cutaneous peripheral nerves as described in our case has not been reported before. Correspondence: Sarah Ní Mhaolcatha, Department of Pathology, Cork University Hospital, Cork, Ireland (e-mail: Sarah.Nimhaolcatha@hse.ie). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2EN8WXf
Κυριακή 28 Οκτωβρίου 2018
Syringotropic Lichen Planus: A Potential Histopathologic Mimicker of Syringotropic Mycosis Fungoides
Abstract: Perieccrine inflammation may be observed in several different dermatoses, but true permeation of the secretory coil by lymphocytes (lymphocytic syringotropism) is a rather uncommon finding, usually observed in mycosis fungoides (MF—syringotropic MF). Rare cases of syringotropic lichen striatus and lymphocytic autoimmune hidradenitis showing a similar pattern have been described as well. We describe an exceptional case of lichen planus (LP) characterized by marked lymphocytic syringotropism with focal hyperplasia of the eccrine epithelium. Histopathology was characterized by the combination of features of conventional LP, prominent permeation of the secretory portion of the eccrine glands by reactive lymphocytes, and focal involvement of a hair follicle. Syringotropic LP may be regarded as a histologic mimicker of syringotropic MF, thus representing a potential diagnostic pitfall. Correspondence: Lorenzo Cerroni, MD, Department of Dermatology, Medical University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria (e-mail: lorenzo.cerroni@medunigraz.at). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2EPrard
https://ift.tt/2EPrard
Monitoring Melanoma Using Circulating Free DNA
Abstract
Genetic material derived from tumours is constantly shed into the circulation of cancer patients both in the form of circulating free nucleic acids and within circulating cells or extracellular vesicles. Monitoring cancer-specific genomic alterations, particularly mutant allele frequencies, in circulating nucleic acids allows for a non-invasive liquid biopsy for detecting residual disease and response to therapy. The advent of molecular targeted treatments and immunotherapies with increasing effectiveness requires corresponding effective molecular biology methods for the detection of biomarkers such as circulating nucleic acid to monitor and ultimately personalise therapy. The use of polymerase chain reaction (PCR)-based methods, such as droplet digital PCR, allows for a very sensitive analysis of circulating tumour DNA, but typically only a limited number of gene mutations can be detected in parallel. In contrast, next-generation sequencing allows for parallel analysis of multiple mutations in many genes. The development of targeted next-generation sequencing cancer gene panels optimised for the detection of circulating free DNA now provides both the flexibility of multiple mutation analysis coupled with a sensitivity that approaches or even matches droplet digital PCR. In this review, we discuss the advantages and disadvantages of these current molecular technologies in conjunction with how this field is evolving in the context of melanoma diagnosis, prognosis, and monitoring of response to therapy.
https://ift.tt/2RlTu5M
No evidence of adverse fertility and pregnancy outcomes in patients with unrecognised and untreated multiple endocrine neoplasia type 1
Clinical Endocrinology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2O8qH2t
Tumor suppressor miR-145-5p sensitizes prolactinoma to bromocriptine by downregulating TPT1
Abstract
Purpose
Prolactinoma is the most commonly seen secretory tumor of pituitary glands, which accounts for approximately up to 40% of total pituitary adenomas. Due to its high drug resistance, dopamine agonist, such as bromocriptine, has limited effect on the treatment of patients with prolactinoma. Recent discoveries have revealed that multiple miRNAs were involved in regulating drug resistance. In this research, we explored the relationship between miR-145-5p expression as well as bromocriptine sensitivity both in vitro and in vivo.
Methods
To study the role of miR-145-5p in drug resistance of prolactinoma, the expression levels of miR-145-5p in bromocriptine-resistant prolactinoma cell line MMQ/BRC and its parental cell line MMQ cells, 24 bromocriptine-resistant as well as eight sensitive clinical samples were measured by qRT-PCR. Moreover, CCK8, flow cytometry and immunofluorescence were performed to identify the biological characteristics of MMQ/BRC and MMQ. TPT1 was predicted as a direct target gene of miR-145-5p by bioinformatic methods. In addition, qRT-PCR, western blot and immunohistochemistry were used to detect the expression level of TPT1 in clinical specimens and cell lines. Xenograft mouse model was constructed to analyze whether miR-145-5p could reverse bromocriptine resistance in prolactinoma in vivo.
Results
In our study, bromocriptine-resistant prolactinoma clinical samples and cell line had decreased miR-145-5p levels and expressed high levels of TPT1 compared with their sensitive counterparts. Bioinformatic methods and our preliminary dual luciferase reporter assay were utilized to elucidate that TPT1 was a direct target gene of miR-145-5p. Furthermore, introducing miR-145-5p mimic into MMQ cells led to a decrease of IC50 along with upregulation of TPT1; nevertheless, transfecting the corresponding inhibitor into MMQ cells resulted in an upregulation of IC50 as well as reduction of TPT1.
Conclusions
Collectively, our findings elucidated the role of miR-145-5p as an important regulator of drug resistance in prolactinoma by controlling TPT1, and implicated the potential application of miR-145-5p in cancer therapy as well.
https://ift.tt/2zbtUc2
Scholar : New articles have been published for Journal of Natural History, Volume 52, Issue 35-36
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How transparent film applied on dermatologic imaging devices in order to prevent infections affects image quality?
Skin Research and Technology, EarlyView.
https://ift.tt/2RllCpH
Comparison of ceramide retention in the stratum corneum between dry skin and normal skin using animal model with fluorescent imaging method
Skin Research and Technology, EarlyView.
https://ift.tt/2PpU3hv
Sunscreen and facial skin care products in frontal fibrosing alopecia: a case control study
British Journal of Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2CO5mcy
Σάββατο 27 Οκτωβρίου 2018
Transparent reporting of experimental parameters in assays measuring phenotypic steps in metastasis
Abstract
Metastasis is key to cancer mortality. Understanding its biology is vital for developing strategies to prevent and treat metastasis. Phenotypic assays to either study metastasis or evaluate anti-metastatic drugs are widely used in preclinical research. This technical note discusses the adherence of reporting essential experimental and methodological parameters in chemotactic invasion assays in vitro and spontaneous metastasis assays in vivo. Following the analysis of 130 recent (< 5 years) research papers, several shortcomings in reporting were identified. Therefore, we strongly argue to increase experimental rigor which should result in a significant improvement with respect to reproducibility of preclinical metastasis research.
https://ift.tt/2AuKeqv
Associations among regorafenib concentrations, severe adverse reactions, and ABCG2 and OATP1B1 polymorphisms
Abstract
Purpose
The ability of predicting severe adverse reactions caused by regorafenib is important. We evaluated regorafenib concentrations for adverse reaction risks and assessed the relevance of laboratory values and gene polymorphisms.
Methods
A total of 28 Japanese cancer patients who were treated with regorafenib were evaluated for the steady state of serum regorafenib concentrations and adverse reactions for 28 days. In addition, we determined the association of regorafenib concentrations with ABCG2 and OATP1B1 polymorphisms, which are regorafenib transporters.
Results
Regorafenib concentrations were significantly higher in the group with Grade 2 or higher total bilirubin elevation and thrombocytopenia compared with the group with grades 0 or 1 [3.45 (2.18–7.31) vs. 1.76 (0.26–2.77) µg/mL, P = 0.01 and 3.45 (2.12–7.31) vs. 1.76 (0.26–2.77) µg/mL, P = 0.02, respectively]. A strong association was noted between serum regorafenib concentrations and total bilirubin levels, but the physical and genetic factors predicting regorafenib pharmacokinetics could not be clarified.
Conclusions
Regorafenib concentrations were associated with total bilirubin elevation and thrombocytopenia. Total serum bilirubin could be a useful marker when estimating regorafenib pharmacokinetics.
https://ift.tt/2yAsl8o
Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103)
Abstract
Purpose
The primary objective of this study was to determine the recommended dose of the vascular disrupting agent, BNC105P, in combination with gemcitabine and carboplatin in patients with ovarian cancer in first or second relapse with a minimum 4 month progression-free interval after last platinum.
Methods
Patients received carboplatin AUC4 on day 1 in combination with escalating doses of 800 or 1000 mg/m2 gemcitabine on days 1 and 8 and escalating doses of 12 or 16 mg/m2 BNC105P on days 2 and 9 every 21 days for a maximum for six cycles. Maintenance treatment with 16 mg/m2 BNC105P treatment continued for a maximum of six additional cycles. Patients were followed for safety and anti-tumor activity.
Results
Fifteen patients were enrolled in the study. Adverse events were most commonly of hematological origin. Dose-limiting toxicities (thrombocytopenia and neutropenia) occurred in two patients at the dose level of 800 mg/m2 gemcitabine, carboplatin AUC4 and 16 mg/m2 BNC105P. No dose-limiting toxicities were observed at a dose level of gemcitabine 1000 mg/m2, carboplatin AUC4 and BNC105P 12 mg/m2. BNC105P as a single agent was well tolerated at a dose of 16 mg/m2 in maintenance treatment. Ten patients (67%) achieved a complete or partial response according to CA125 and/or RECIST response criteria, four of 13 (31%) responded by RECIST alone. The median progression-free survival was 5.9 months.
Conclusions
We have established that BNC105P 12 mg/m2 with gemcitabine 1000 mg/m2 and carboplatin AUC4 is the recommended dose level and has an acceptable toxicity profile. Further exploration of BNC105P in the ovarian cancer setting is planned.
https://ift.tt/2CIDGWF
A case of an infant with extremely low birth weight and hypothyroidism associated with massive cutaneous infantile hemangioma
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2PXREaR
Cardiometabolic risk factors in preschool children with abdominal obesity from Medellín, Colombia
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2Aw3oMy
The prevalence and volumetry of pituitary cysts in children with growth hormone deficiency and idiopathic short stature
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
https://ift.tt/2PXRzE5
Dear Dr. Dermatoethicist: Exam of the Future or Exam of Future Cheating? Ethical Issues Surrounding the American Board of Dermatology’s New Certification Examination
Publication date: Available online 27 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Reid A. Waldman, Jane M. Grant-Kels
https://ift.tt/2StEowy
Non-cultured epidermal suspension grafting using suction blisters as donor tissue for vitiligo
Publication date: Available online 27 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Andrea Tovar-Garza, Jorge A. Hinojosa, Linda S. Hynan, Amit G. Pandya
https://ift.tt/2z4Z70I
Benign subungual epidermoid inclusions
Publication date: Available online 27 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Josette André, Eckart Haneke
https://ift.tt/2SlU9Fz
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