The effects of concentration and salinity on polymer adsorption isotherm at sandstone rock surface

Adsorption of hydrolyzed polyacrylamide (HPAM) polymers on sandstone rock surface was studied by static adsorption experiments. Total of 10 Runs of static experiments were conducted in test tubes by mixing the desired solution with crushed rock sample, at temperature of 25 °C, and salinity range from 0-4 wt%. The results are in conformity with Langmuir's isotherm. Ten different isotherms were generated at each Run. The initial polymer concentration was varied from 0.3-2.1 g/l. The effects of salinity have been studied by observation on Langmuir adsorption coefficients (Y and K). The results show that the adsorption coefficient (Y) was found to have linear relationship with salinity. The adsorption coefficient (K) was found to be related to salinity by a quadratic relationship

Anti‐cN‐1A autoantibodies are absent in juvenile dermatomyositis

Objectives: To assess anti‐cytosolic 5′‐nucleotidase 1A (cN‐1A/NTC51A) autoantibodies in children with juvenile dermatomyositis (JDM) and healthy controls, using three different methods of antibody detection, as well as verification of the results in an independent cohort. / Methods: Anti‐cN‐1A reactivity was assessed in 34 Dutch JDM patients and 20 healthy juvenile controls by a commercially available full‐length cN‐1A ELISA, a synthetic peptide ELISA and by immunoblotting using a lysate from cN‐1A expressing HEK‐293 cells. Sera from JDM patients with active disease and in remission were analysed. An independent British cohort of 110 JDM patients and 43 healthy juvenile controls was assessed by an in‐house full‐length cN‐1A ELISA. / Results: Anti‐cN‐1A reactivity was not present in JDM patients’ sera or in healthy controls when tested with the commercially available full‐length cN‐1A ELISA or by immunoblotting, both in active disease and in remission. Also, in the British JDM cohort anti‐cN‐1A reactivity was not detected. Three Dutch JDM patients tested weakly positive for one of the three synthetic cN‐1A peptides measured by ELISA. / Conclusion: JDM patients and young healthy individuals do not show anti‐cN‐1A reactivity as assessed by different antibody detection techniques

A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer

Positive results of phase I studies evaluating lenvatinib in solid tumors, including thyroid cancer, prompted a phase II trial in advanced medullary thyroid carcinoma (MTC)

Search for NTRK1 proto-oncogene rearrangements in human thyroid tumours originated after therapeutic radiation

Rearrangements of NTRK1 proto-oncogene were detected in ‘spontaneous’ papillary thyroid carcinomas with a frequency varying from 5 to 25% in different studies. These rearrangements result in the formation of chimaeric genes composed of the tyrosine kinase domain of NTRK1 fused to 5′ sequences of different genes. To investigate if the NTRK1 gene plays a role in radiation-induced thyroid carcinogenesis, we looked for the presence of NTRK1 -activating rearrangements in 32 human thyroid tumours (16 follicular adenomas, 14 papillary carcinomas and two lymph-node metastases of papillary thyroid carcinomas) from patients who had received external radiation, using the reverse transcription polymerase chain reaction, Southern blot and direct sequencing techniques. These data were compared with those obtained in a series of 28 ‘spontaneous’ benign and malignant thyroid tumours, collected from patients without a history of radiation exposure and four in vitro culture cell lines derived from ‘spontaneous’ thyroid cancers. Our results concerning the radiation-associated tumours showed that only rearrangements between NTRK1 and TPM3 genes (TRK oncogene) were detected in 2/14 papillary carcinomas and in one lymph-node metastasis of one of these papillary thyroid carcinomas. All the radiation-associated adenomas were negative. In the ‘spontaneous’ tumours, only one of the 14 papillary carcinomas and one of the four in vitro culture cell lines, derived from a papillary carcinoma, presented a NTRK1 rearrangement also with the TPM3 gene. Twenty-five of this series of radiation-associated tumours were previously studied for the ras and RET/PTC oncogenes. In conclusion, our data: (a) show that the overall frequency of NTRK1 rearrangements is similar between radiation-associated (2/31: 6%) and ‘spontaneous’ epithelial thyroid tumours (2/32: 6%). The frequency, if we consider exclusively the papillary carcinomas, is in both cases 12%; (b) show that the TRK oncogene plays a role in the development of a minority of radiation-associated papillary thyroid carcinomas but not in adenomas; and (c) confirm that RET/PTC rearrangements are the major genetic alteration associated with ionizing radiation-induced thyroid tumorigenesis. © 2000 Cancer Research Campaig

Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1−/− mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1−/− mouse embryos showed a significantly smaller total thyroid surface area (−40 to −60%) compared to wild type mice at all study time points (E9.5−E16.5). In both Hes1−/− and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1−/− mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1−/− thyroids revealed a significantly decreased labelling area for T4 (−78%) and calcitonin (−65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (−69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells

Detection of human parvovirus B19 in papillary thyroid carcinoma

To evaluate whether parvovirus B19, a common human pathogen, was also involved in papillary thyroid carcinoma (PTC), 112 paraffin-embedded thyroid specimens of benign nodules, papillary, medullary and follicular carcinomas, and normal controls were examined for B19 DNA and capsid protein by nested PCR, in situ hybridisation (ISH) and immunohistochemistry (IHC). The expression of the nuclear factor-κB (NF-κB) was investigated by IHC. The results showed B19 DNA commonly exists in human thyroid tissues; however, there were significant differences between PTC group and normal controls, and between PTC and nonneoplastic adjacent tissues (P<0.001). The presence of viral DNA in PTC neoplastic epithelium was confirmed by laser-capture microdissection and sequencing of nested PCR products. B19 capsid protein in PTC group was significantly higher than that of all the control groups and nonneoplastic adjacent tissues (P⩽0.001). Compared with control groups, the activation of NF-κB in PTC group was significantly increased (P⩽0.02), except for medullary carcinomas, and the activation of NF-κB was correlated with the viral protein presence (P=0.002). Moreover, NF-κB was colocalised with B19 DNA in the neoplastic epithelium of PTC by double staining of IHC and ISH. These results indicate for the first time a possible role of B19 in pathogenesis of PTC

Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

<p>Abstract</p> <p>Background</p> <p>The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC.</p> <p>Methods/design</p> <p>DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI<b>-</b>refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and pharmacokinetic analysis.</p> <p>Discussion</p> <p>The DECISION study has been designed to test whether sorafenib improves PFS in patients with locally advanced or metastatic RAI-refractory DTC.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00984282">NCT00984282</a>; EudraCT: 2009-012007-25.</p