Phosphorylation of Ser78 of Hsp27 correlated with HER-2/neu status and lymph node positivity in breast cancer

<p>Abstract</p> <p>Background</p> <p>Abnormal amplification/expression of HER-2/<it>neu </it>oncogene has been causally linked with tumorigenesis and metastasis in breast cancer and associated with shortened overall survival of patients. Recently, heat shock protein 27 (Hsp27) was reported to be highly expressed in HER-2/<it>neu </it>positive tumors and cell lines. However, putative functional links between phosphorylation of Hsp27 with HER-2/<it>neu </it>status and other clinicopathological features remain to be elucidated.</p> <p>Results</p> <p>Comparative phosphoproteomic studies of HER-2/<it>neu </it>positive and -negative breast tumors revealed that Hsp27, one of the identified phosphoproteins, was highly phosphorylated in HER-2/<it>neu </it>positive tumors. The extent of Hsp27 phosphorylation at its Ser¹⁵, Ser⁷⁸and Ser⁸²residues were further evaluated with site-specific antibodies in tumor samples by tissue lysate array- and tissue microarray-based analyses, and in the BT474 breast cancer cell line treated with heregulin α1 (HRG α1) or the p38 MAPK inhibitor, SB203580. The tissue lysate array study indicated that only the level of pSer⁷⁸in HER-2/<it>neu </it>positive tumors was more than 2-fold that in HER-2/<it>neu </it>negative tumors. Treatment of BT474 cells with HRG α1 and SB203580 indicated that Ser⁷⁸phosphorylation was mainly regulated by the HER-2/<it>neu</it>-p38 MAPK pathway. Immunohistochemical staining of sections from a tissue microarray with 97 breast tumors showed that positive staining of pSer⁷⁸significantly correlated with HER-2/<it>neu </it>(<it>p </it>= 0.004) and lymph node positivity (<it>p </it>= 0.026).</p> <p>Conclusion</p> <p>This investigation demonstrated the significant correlation of enhanced phosphorylation of the Ser⁷⁸residue of Hsp27 with HER-2/<it>neu </it>and lymph node positivity in breast cancer.</p

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support

The instances of U.N. missions activities in selected conflicts

<p><b>Copyright information:</b></p><p>Taken from "Phosphorylation of Serof Hsp27 correlated with HER-2/status and lymph node positivity in breast cancer"</p><p>http://www.molecular-cancer.com/content/6/1/52</p><p>Molecular Cancer 2007;6():52-52.</p><p>Published online 14 Aug 2007</p><p>PMCID:PMC1976621.</p><p></p>SDS-PAGE and transferred onto PVDF membranes. After blocking, the membranes were incubated with the respective primary antibodies (anti-Hsp27, anti-pSer, anti-pSerand anti-pSer), followed by hybridization to HRP-conjugated secondary antibody. The chemiluminescent signals emitted were captured with the MULTI-GENIUS Bio-Imaging System and signal intensities were analyzed using the GeneTools software (Syngene). The relative phosphorylation levels of pSer, pSerand pSerpresented (histograms, right) are the respective ratios of signal intensity probed with phosphorylation site-specific antibody to signal intensity probed with anti-Hsp27, for each of the three pSer residues. Data with ± SD (standard deviation) are expressed as the average of triplicate experiments. *< 0.05 (Student -test)

Phosphorylation of Serof Hsp27 correlated with HER-2/status and lymph node positivity in breast cancer-3

<p><b>Copyright information:</b></p><p>Taken from "Phosphorylation of Serof Hsp27 correlated with HER-2/status and lymph node positivity in breast cancer"</p><p>http://www.molecular-cancer.com/content/6/1/52</p><p>Molecular Cancer 2007;6():52-52.</p><p>Published online 14 Aug 2007</p><p>PMCID:PMC1976621.</p><p></p>) or SB 203580 for 10 hours (B) and total cell lysates were extracted using M-PER reagent (Pierce). Equal amounts of proteins (20 μg) were separated by SDS-PAGE and transferred onto PVDF membrane. The membranes were blocked for 1 hour, followed by being probed with the respective primary antibodies (anti-Hsp27, anti-pSer, anti-pSerand anti-pSer), and HRP-conjugated secondary antibody. The signals were captured and their intensities were detected as described in Figure 2. The phosphorylation levels of pSer, pSerand pSerwere expressed as the ratios of intensity probed with phosphorylation site-specific antibody to the intensity probed with anti-Hsp27. Data with ± SD represents the average of triplicate experiments. C: control; SB: inhibitor SB203580. For the control of HRG-treated cells, untreated cells were cultured for 10 and 30 min and equal amounts of cellular proteins from both time intervals were mixed and used as control. For the control of inhibitor-treated cells, cells were treated with DMSO for 10 hours and cellular proteins were used as the control. *< 0.05 (student -test

Sampling circulating tumor cells for clinical benefits: how frequent?

10.1186/s13045-015-0174-9Journal of Hematology and Oncology817

Clinical and laboratory findings of SARS in Singapore.

INTRODUCTION: Singapore was one of 29 countries worldwide affected by severe acute respiratory syndrome (SARS) in 2003. MATERIALS AND METHODS: There were 238 cases identified during the outbreak. We performed a retrospective analysis of the clinical and laboratory data of 234 patients admitted to Tan Tock Seng Hospital and Singapore General Hospital. RESULTS: The mean age of patients was 21 years, 31.6% of patients were males and 41.8% were healthcare workers. At presentation, the common symptoms were fever, myalgia, cough and headache; rhinorrhoea was uncommon. On admission, 21% had leukopenia, 18% had thrombocytopaenia, 29% had hyponatraemia, 31% had hypokalaemia, 21% had transaminitis. Polymerase chain reaction (PCR) testing of respiratory and stool samples provided the best yield at the end of the first week of illness. Thirty-two patients were initially not recognised as probable SARS and were reclassified when the serology test results were available. The chief reasons for not identifying these patients early were persistently normal chest X-rays (68.8%), very mild presentation (43.8%) and the presence of a concomitant illness (12.5%). Overall, 12% of the patients were probable SARS with atypical presentations. Overall mortality was 11.8%. CONCLUSION: Patients infected with the SARS coronavirus had a wide clinical presentation with non-specific symptoms

Overexpression of CC3/TIP30 is associated with HER-2/neu status in breast cancer

10.1007/s00432-005-0674-zJournal of Cancer Research and Clinical Oncology1319603-608JCRO