The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.
Abstract Low-grade inflammation is part of the pathogenesis of osteoarthritis (OA) from its earliest stages and contributes to the acceleration of the degenerative process. Innate immunity has a leading role in it. Activation of the innate immune response is initiated by stimulation of the receptors on the cell membrane to recognize the secreted PAMPs (pathogen-associated molecular patterns). However, PAMPs can also be activated by endogenous damage-related molecular patterns (DAMPs). The group of DAMPs also includes toll-like receptors (TLRs).The disruption of matrix homeostasis in the course of OA is an example of activation of these receptors in chronic damage. The complement system is a key element of the innate immune system. It is one of the serum enzyme systems whose function is to opsonize antigens. The complement receptors on the surface of the cell membranes adhere to the targets for phagocytosis. The C3R fraction activates the complement cascade itself, as well as the oxygen metabolism of the cell, which is essential for the phagocytosis. The cartilage damage products released during joint damage are a separate class of potent complement modulators. Complement fractions bind to complement receptors on the surface of the chondrocyte and the synoviocyte cell membranes by TLR. The complement system is involved in many processes in the course of osteoarthritis: chondrocyte degeneration, ECM degradation, low-grade inflammation in the osteoarthritis, cell lysis, unbalanced bone remodeling, osteophyte formation, and neoangiogenesis. Whether drug control of complement activation may be a future therapeutic strategy in the treatment of OA and prevent its progression is a subject of future studies.
A total of 111 fresh brain biopsies from patients with primary brain tumors were examined for JC polyomavirus sequences from the Large T antigen encoding region (LT) and the viral non-coding control region (NCCR). SYBR Green and TaqMan real-time polymerase chain reaction assays were used. In the glioblastoma group of 39 patients 48.7% were positive for LT sequences. Among the astrocytoma group (19 patients) and the oligodendroglioma group (12 patients) 31.6% and 33.3% were also positive. The prevalence of LT genomic sequences among the other groups was as follows: in 2 out of 3 oligoastrocytomas; in 3 out 5 gangliogliomas; in 2 out of 5 meduloblastomas; in 1 out 3 pineocytomas; and in none of the tested 5 ependimomas. All positive samples had a late threshold cycle that varied from 36 to 49, indicative of very low starting viral number. Only 21 of all the 111 samples were positive for NCCR. Low copy number in range of 10-1,000 was present. Notably, only 8 of all NCCR positive specimens were also LT positive. It might be suggested that the disproportion between the results for LT and NCCR is either due to clonally integrated LT fragments, with loss of genetic material, or changes in the NCCR. The latter would alter the productive course of the infection and may establish a premise for continuous interaction of viral regulatory proteins with cell molecules that are responsible for the control of the cell cycle. This may lead subsequently to malignant transformation.
Objectives: Aim of the study was to assess the therapeutic efficacy and safety of upadacitinib in Rheumatoid arthritis patients with moderate to high disease activity in real-world clinical practice and to identify predictors of therapeutic success. Materials and methods: A retrospective single-center study was performed in RA patients treated with upadacitinib 15 mg daily. Demographic and clinical indicators were analyzed. The effectiveness and safety of the medication were evaluated over a six-month period. Disease activity was assessed with index-based scores. The primary endpoint was defined as low disease activity over a six-month treatment period with upadacitinib 15 mg/day (DAS28CRP ≤ 3.2, CDAI ≤ 10 and SDAI ≤ 11). Results: 41 patients were included, mean age 56.56 years (± 13.4), with long-standing RA (8 years ± 5.8), mostly female (80.5%). 19.5% of them were obese (BMI ≥ 30 kg/m2), 80.5% had osteoarthritis and 58.5% - hypertensive disease. Erosive arthritis was observed in 41.5% of patients and 61% had functional class III motor deficit. "Bio-naïve" were 58.5%, the rest had previous experience with biologic therapy. Upadacitinib was used as monotherapy in 90% of patients and in combination with Methotrexate in 10%. There was a significant reduction in the painful and swollen joint counts, VAS and CRP six months after starting treatment with upadacitinib. Low disease activity was achieved by a significant proportion of patients (DAS28CRP-70.7%, CDAI-60.5% and SDAI 63.2%). Therapeutic outcome was not determined by demographics, clinical factors, comorbidities, or prior biologic treatment. Increase in liver enzymes (n=3), decrease in hemoglobin levels (n=2), and urinary tract infection (n=2) were the adverse events recorded over the six-month treatment period. One patient died from COVID-19. Conclusion: A significant proportion of RA patients on treatment with upadacitinib 15 mg was able to achieve the therapeutic target in real clinical settings. No predictors of therapeutic efficacy were found. The registered side effects do not differ from the safety profile of the medication.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.