Thyroid lymphoepithelial nodule

Thyroid benign lymphoepithelial lesions are rare in adults, reported as associated with thyroiditis or adjacent to tumours. Here we report a unique case of a thyroid solid nodule with benign lymphoepithelial morphology. A 56-year-old woman presented with a thyroid nodule increasing in size. Thyroid function was normal. On the surgical resection specimen, in addition to a 2-cm follicular adenoma, there was, at distance, a 0.5-cm solid nodule with lymphoepithelial morphology, without Hassal’s corpuscles or calcifications. On immunohistochemistry, the epithelial component was cytokeratin 5/6 positive and very focally cytokeratin 7 positive, the immunophenotype of the lymphoid tissue confirming the benign nature. The diagnosis of thyroid benign lymphoepithelial nodule was proposed. In conclusion, recognition of thyroid solid benign lymphoepithelial nodules is important since they can be misdiagnosed with other thyroid micronodule types including carcinoma, primary or metastatic

miR-9 Acts as an OncomiR in Prostate Cancer through Multiple Pathways That Drive Tumour Progression and Metastasis

Identification of dysregulated microRNAs (miRNAs) in prostate cancer is critical not only for diagnosis, but also differentiation between the aggressive and indolent forms of the disease. miR-9 was identified as an oncomiR through both miRNA panel RT-qPCR as well as high-throughput sequencing analysis of the human P69 prostate cell line as compared to its highly tumorigenic and metastatic subline M12, and found to be consistently upregulated in other prostate cell lines including DU-145 and PC3. While miR-9 has been characterized as dysregulated either as an oncomiR or tumour suppressor in a variety of other cancers including breast, ovarian, and nasopharyngeal carcinomas, it has not been previously evaluated and proven as an oncomiR in prostate cancer. miR-9 was confirmed an oncomiR when found to be overexpressed in tumour tissue as compared to adjacent benign glandular epithelium through laser-capture microdissection of radical prostatectomy biopsies. Inhibition of miR-9 resulted in reduced migratory and invasive potential of the M12 cell line, and reduced tumour growth and metastases in male athymic nude mice. Analysis showed that miR-9 targets e-cadherin and suppressor of cytokine signalling 5 (SOCS5), but not NF-ĸB mRNA. Expression of these proteins was shown to be affected by modulation in expression of miR-9

Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis

MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was confirmed in human prostate tumor samples as compared to adjacent benign glandular epithelium collected through laser capture microdissection from radical prostatectomies. In fact, alterations in hsa-miR-125b expression appeared to be an early event in tumorigenesis. Reverse phase microarray proteomic analysis revealed ErbB2/3 and downstream members of the PI3K/AKT and MAPK/ERK pathways as well as PTEN to be protein targets differentially expressed in the M12 tumor cell compared to its parental p69 cell. Relevant luciferase+3’-UTR expression studies confirmed a direct interaction between hsa-miR-125b and ErbB2 and between hsa-miR-22 and PTEN. Restoration of hsa-miR-125b or inhibition of hsa-miR-22 expression via an antagomiR resulted in an alteration of M12 tumor cell behavior in vitro. Thus, the dual action of hsa-miR-125b as a tumor suppressor and hsa-miR-22 as an oncomiR contributed to prostate tumorigenesis by modulations in PI3K/AKT and MAPK/ERK signaling pathways, key pathways known to influence prostate cancer progression

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Correlation and prediction of solute transfer to chloroalkanes from both water and the gas phase

Article discussing research on the correlation and prediction of solute transfer to chloroalkanes from both water and the gas phase

Tumour growth and metastasis is reduced upon miR-9 inhibition.

<p>A: Subcutaneous injections into the flank of the respective cell lines into nude athymic mice. Tumour reduction was significantly reduced in mice injected with M12 cells transformed with miR-9 inhibitor (p <.0001). Results are reported as the average ratio of tumour volume to the final average M12 tumour volume. N = 5 mice for each treatment. B: Intraprostatic (IP) injection into nude athymic mice resulted in 0 metastatic lesions when miR-9 was inhibited, as compared to 7 lesions in the mouse injected with M12 cells alone.</p

Inhibition of miR-9 significantly reduces migratory and invasive potential, but has no effect on cell proliferation.

<p>M12 cells were stably transformed with scrambled control or miR-9 inhibitor, plated on a ThinCert transwell membrane (with basement membrane added for invasion assay) and assessed for (A) migratory (p < 0.0001), (B) invasive potential (p < 0.0001), and (C) proliferation. Data is the mean of 3 independent experiments, each performed in triplicate (A&B) or one representative of three independent experiments (C).</p

While protein levels of SOCS5 are increased upon miR-9 inhibition, messenger RNA levels are not significantly different.

<p>SOCS5 expression in the P69, M12, and M12 stably transformed with vector expressing miR-9 inhibitor. A: messenger RNA relative quantitation shows that mRNA levels are not significantly impacted by miR-9. mRNA is normalized to GAPDH and reported as relative to the M12 cell line; results are compiled data from three independent lysates, each performed in triplicate. Regardless of similar SOCS5 mRNA levels, (B) Western blot analysis and (C) quantitation show that miR-9 inhibition results in increased levels of SOCS5. Blot is representative of 6 independent experiments, Quantitation the average of 3 independent experiments normalized to β-Actin and reported as relative to the M12 cell line (p<0.05). (D) The proven SOCS5 mRNA:miR-9 hybrid [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159601#pone.0159601.ref021" target="_blank">21</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159601#pone.0159601.ref022" target="_blank">22</a>]. miR-9 is the top sequence, and hybridized below is the complementary region of the 3’-UTR of SOCS5. (E) SOCS5 expression is suppressed by miR-9. M12 cells were transiently transfected with a dual luciferase reporter construct containing a portion of the SOCS5 3’-UTR, with the wild type or mutated miR-9 binding seed region. Firefly luciferase expression is reported as normalized to renilla luciferase activity and relative to mutated seed region expression. Results are the mean of 2 independent experiments, each performed in triplicate. (p = .016).</p

miR-9 levels are upregulated in all prostate cancer cell line models.

<p>A: miR-9 levels were significantly upregulated in M12 cells as relative to the parental P69 line (p = .002). Data is the mean of 3 independent experiments, each performed in duplicate (F6) or triplicate (P69, M2182, M12). B: miR-9 levels in DU-145 and PC3 cells are upregulated as relative to P69 cells (p <.001). Data was normalized to RNU48 (dC_T) and expressed relative to P69 using the comparative C_T method. Data is the mean of three technical replicates. C: miR-9 expression is upregulated in 75% of positive patient tumours. miR-9 levels were measured in tumour and benign tissue separated from prostate biopsies using laser-captured microdissection (LCM). Data was normalized to RNU48 and expressed relative to the benign tissue using the comparative C_T method, and is the average of 3 technical replicates. miR-9 was undetected in both benign and tumour of the fifth patient, and thus was not included in the analysis.</p

messenger RNA and protein levels of CDH1 are increased upon miR-9 inhibition.

<p>A: RT-qPCR analysis shows that mRNA levels are impacted by miR-9, and miR-9 inhibition relieves mRNA and protein levels (p<0.03 for P69 and miR-9 inhibited lines vs. M12). mRNA is normalized to GAPDH and reported as relative to the M12 cell line using the comparative C_T method. Results are compiled data from two biological replicates, each performed in triplicate. B: Proven binding site for miR-9 in e-cadherin. Adapted from RNAHybrid [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159601#pone.0159601.ref021" target="_blank">21</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159601#pone.0159601.ref022" target="_blank">22</a>] analysis of CDH1 mRNA (NM_004360.3). miR-9 is the left sequence, and hybridized on the right is the complementary region of the 3’-UTR of CDH1. C: Western blot analysis and D: quantitation. Blot is representative of 5 independent experiments, Quantitation the average of 3 independent experiments normalized to β-Actin and reported as relative to the M12 cell line (p<0.05). (E) e-cadherin expression is suppressed by miR-9. M12 cells were transiently transfected with a firefly luciferase reporter construct containing a portion of the CDH1 3’-UTR, with the wild type or mutated miR-9 binding seed region along with a renilla luciferase plasmid. Firefly luciferase expression is reported as normalized to renilla luciferase activity and relative to mutated seed region expression. Results are the mean of 2 independent experiments, each performed in triplicate. (p <0.01). Western blot analysis shows that NF-kB levels do not change significantly between M12 or M12 cells stably transfected with miR-9 inhibitor. Blot (F) is representative of 3 independent experiments and quantitation (G) is from one representative experiment.</p