Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumatoid arthritis: Text mining of the Japanese postmarketing adverse event-reporting database

<p><b>Objective:</b> To search for signs and symptoms before serious infection (SI) occurs in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients.</p> <p><b>Methods:</b> Individual case safety reports, including structured (age, sex, adverse event [AE]) and unstructured (clinical narratives) data, were analyzed by automated text mining from a Japanese post-marketing AE-reporting database (16 April 2008–10 April 2015) assuming the following: treated in Japan; TCZ RA treatment; ≥1 SI; unable to exclude causality between TCZ and SIs.</p> <p><b>Results:</b> The database included 7653 RA patients; 1221 reports met four criteria, encompassing 1591 SIs. Frequent SIs were pneumonia (15.9%), cellulitis (9.9%), and sepsis (5.0%). Reports for 782 patients included SI onset date; 60.7% of patients had signs/symptoms ≤28 days before SI diagnosis, 32.7% had signs/symptoms with date unidentified, 1.7% were asymptomatic, and 4.9% had unknown signs/symptoms. The most frequent signs/symptoms were for skin (swelling and pain) and respiratory (cough and pyrexia) infections. Among 68 patients who had normal laboratory results for C-reactive protein, body temperature, and white blood cell count, 94.1% had signs or symptoms of infection.</p> <p><b>Conclusion:</b> This study identified prodromal signs and symptoms of SIs in RA patients receiving TCZ. Data mining clinical narratives from post-marketing AE databases may be beneficial in characterizing SIs.</p

Immunoblot analysis of phosphorylated estrogen receptor (ER)-α Ser118 and ER-α Ser167

<p><b>Copyright information:</b></p><p>Taken from "Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer"</p><p>Breast Cancer Research 2005;7(5):R753-R764.</p><p>Published online 27 Jul 2005</p><p>PMCID:PMC1242143.</p><p>Copyright © 2005 Yamashita et al.; licensee BioMed Central Ltd.</p> Transfected COS-7 cells were grown in serum- and estrogen-deprived conditions and treated with vehicle (medium) (lane 1), 17β-estradiol (E) (lane 2), epidermal growth factor (EGF) (lane 3), or Eand EGF (lane 4) for 30 min. Equal amounts of total protein from whole cell lysates were blotted for either anti-ER-α-phosphoserine (α-pS118 and α-pS167) and anti-ER-α (α-ER-α) antibodies. T47D cells were grown in serum- and estrogen-deprived conditions and treated with vehicle (medium) (lane 1), 17β-estradiol (E) for 10 min (lane 2) and 30 min (lane 3), EGF for 10 min (lane 4) and 30 min (lane 5), or Eand EGF for 10 min (lane 6) and 30 min (lane 7). Equal amounts of total protein from whole cell lysates were blotted for either anti-ER-α-phosphoserine (α-pS118 and α-pS167) and anti-ER-α (α-ER-α) antibodies

Representative immunohistochemical staining of estrogen receptor (ER)-α Ser118, and ER-α Ser167 in normal breast epithelium and invasive ductal carcinoma

<p><b>Copyright information:</b></p><p>Taken from "Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer"</p><p>Breast Cancer Research 2005;7(5):R753-R764.</p><p>Published online 27 Jul 2005</p><p>PMCID:PMC1242143.</p><p>Copyright © 2005 Yamashita et al.; licensee BioMed Central Ltd.</p> Phosphorylation of ER-α Ser118 in normal breast epithelium and invasive ductal carcinoma: negative (b) and positive (c) nuclear staining was observed in carcinoma cells. Phosphorylation of ER-α Ser167 in normal breast epithelium and invasive ductal carcinoma: negative (e) and positive (f) nuclear staining was observed in carcinoma cells (magnification, 400×)