18F 一FD G PE T 显像在分化型甲状腺癌患者随访中的应用

分化型甲状腺癌（Differentiated thyroid carcinoma,DTC）在其病程演变过程中,分化程度较低的复发或转移灶摄^131I能力降低而对^18F-脱氧葡萄糖（Fluoredeoxyglucose,FDG）摄取增多。因此,依赖于^131I和FDG显像的两种不同机制,正电子发射型断层成像（Positron Emission Tomography,PET）探测非功能性DTC复发或转移灶兼具定位诊断、敏感性及特异性都高的优点。因此。DTE患者随访期间,对甲状腺球蛋白阳性（Thyroglobulin positive,TG＋）（在促甲状腺激素刺激作用下TG〉10μg／L或在促甲状腺激素被抑制作用下TG〉2μg／L）或TG阴性（TG negative,TG-）但TsAb〉200U／mL,且131I-诊断剂量全身显像阴性（Diagnostic whole—body scanning negative,dWBS-）的高危患者（Ⅲ期或Ⅳ期患者）是进行^18F—FDG PET显像的指征。同机融合显像设备PET／CT、PET／MRI具有更高的敏感性和分辨率,为病灶的定性和定位,提供更准确的信息。     

Dependency of the remnant 131I-NaI biokinetics on the administered activity in patients with differentiated thyroid cancer

PurposeTo study the dependency of the effective half-life on the administered activity and the correlation between the time-integrated activity and the remnant uptake at 2d and 7d in patients treated for DTC with 1.11 GBq, 3.7 GBq or 5.55 GBq of ¹³¹I-NaI.MethodsNinety-two patients undergoing total thyroidectomy and lymph node removal were included. If cancer had not spread to lymph nodes, patients received 1.11 GBq of ¹³¹I-NaI when the lesion maximal diameter was smaller than 4 cm, and 3.7 GBq for bigger sizes. If cancer had spread to lymph nodes patients received 5.55 GBq. There were 30, 49 and 13 patients respectively treated with 1.11 GBq(Group 1), 3.7 GBq(Group 2) and 5.55 GBq(Group 3). Two SPECT/CT scans were performed at 2d and 7d after radioiodine administration for each patient to determine the thyroid remnant activities and effective half-lives of the radioiodine.ResultsStatistical analysis showed significant differences (p < 0.05) in the effective half-life among patients treated with 1.11 GBq, 3.7 GBq and 5.55 GBq. A high positive correlation (ρ > 0.95) was found between the time-integrated activity and the remnant activity at 2d for the three groups of patients.ConclusionsThere were significant differences in the effective half-life of the radioiodine in remnants of patients treated with activities of 1.11 GBq, 3.7 GBq or 5.55 GBq. The high positive linear correlation found between the time-integrated activity and the remnant activity at 2d for the three groups of patients indicate that the time-integrated activity could be estimated from one time-point.     

An evaluation of the value of first thyroglobulin determination in the diagnostics of metastases immediately following differentiated thyroid carcinoma surgery

INTRODUCTION: Evaluation of the differential value of the first thyroglobulin (Tg) concentration, measured after thyroidectomy (Tx) but before thyroid remnant ablation, in patients with differentiated thyroid carcinoma (DTC) as a marker of either metastases or residual cancer (M). MATERIAL AND METHODS: Data from 517 patients with DTC after Tx, with follow-up > 1.5 year were analysed retrospectively. Patients in whom either the course of the disease was unclear or interference in the Tg test was possible (a-TgAb [+], Tg recovery < 80%) were excluded from the study. Finally, the data from 247 patients were evaluated (age: 14-79 years; 223 women, 24 men). The results of TSH, thyroid radioiodine uptake (T(up24)), thyroid remnant volume (V) and Tg in patients with diagnosed M (group M1; n = 35) were compared with the same parameters in patients with remission > 1.5 year (group M0; n = 212). The area under the ROC curve was calculated. The clinical decision limit of Tg level to be suggestive of metastases was determined by means of efficiency curve. RESULTS: Groups M0 and M1 did not differ from each other with respect to TSH concentration (median 49.7 mIU/l vs 44.3; p = 0.16) or thyroid remnant volume (1.4 vs 1.1 ml; p = 0.79). However, they did differ with respect to T(up24) (7.6 vs 3.2%; p = 0.01) and Tg (4.5 vs 96.7 ng/ml; p = 0.000000). Area under ROC for Tg was 0.78 +/- 0.05 (mean +/- s.e.m.). The decision limit of Tg for suspected M was determined at 38.1 ng/ml, Tg sensitivity was 0.57 (95%CI 0.39-0.74) and specificity 0.96 (95%CI 0.92-0.98). CONCLUSIONS: First thyroglobulin concentration, determined after thyroidectomy but before other treatment, is higher in patients with metastatic DTC than in patients without such metastases. This indicates that Tg level may be used as an early marker of either residual or metastatic DTC (even if thyroid remnants are present).     

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer

INTRODUCTION: Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. MATERIAL AND METHODS: The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. RESULTS: Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. CONCLUSIONS: 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.     

Biochemical characterization of serum thyroglobulin from patients with bone metastases from follicular carcinoma of the thyroid.

The biochemical properties of serum thyroglobulin obtained from six patients with follicular carcinoma of the thyroid and distant metastases to bone(s) have been studied. Since it is difficult to isolate sufficient thyroglobulin from serum samples, in vivo radioiodinated serum thyroglobulin obtained after radioiodine administration was used. In contrast to a sharp salting-out pattern observed with native thyroglobulin isolated from normal thyroid tissue, a broad salting-out curve was seen with metastatic serum thyroglobulin. The metastatic serum thyroglobulin eluted with low ionic strength from ion-exchange column. More than 95% of metastatic serum thyroglobulin could be bound to concanavalin-A sepharose and be eluted with 0.5 M alpha-methyl mannoside. The reactivity of metastatic serum thyroglobulin and native thyroglobulin towards concanavalin-A was comparable. Both types of thyroglobulins showed identical mobilities on sucrose linear density gradient centrifugation. The metastatic serum thyroglobulin from follicular carcinoma of the thyroid thus appears to be 19 S thyroglobulin with near normal concanavalin-A binding sugars but altered surface charges.     

Clinical course and treatment of patients with differentiated thyroid carcinoma diagnosed during the year 1995

The aim of the study was to analyze the clinical course and therapy in patients with differentiated thyroid carcinoma (DTC) diagnosed in Poland within the year 1995. The group of 478 patients with thyroid cancer (57.7% of all thyroid cancer cases diagnosed this year in Poland) was analyzed. Patients were diagnosed or treated in Maria Sk?odowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch. Detailed analysis was performed in 352 patients with DTC who were treated by surgery. 292 patients (60%) received adjuvant radioiodine therapy. Hormonal (L-thyroxine) treatment was administered to all patients. In 37 patients (8.6%) local recurrence was observed. 10-year overall survival was 96.4% and disease-free survival was respectively 68%. The comparison of Polish data to analysis in German population published by Holtzer et al. (Cancer, 2000) was also performed in this study. We conclude that DTC therapy, currently recommended in our country, gives satisfactory results and that clinical outcome and therapeutic methods are similar both in Poland and Germany.     

Assessment of genetic mutations in the XRCC2 coding region by high resolution melting curve analysis and the risk of differentiated thyroid carcinoma in Iran

Homologous recombination (HR) is the major pathway for repairing double strand breaks (DSBs) in eukaryotes and XRCC2 is an essential component of the HR repair machinery. To evaluate the potential role of mutations in gene repair by HR in individuals susceptible to differentiated thyroid carcinoma (DTC) we used high resolution melting (HRM) analysis, a recently introduced method for detecting mutations, to examine the entire XRCC2 coding region in an Iranian population. HRM analysis was used to screen for mutations in three XRCC2 coding regions in 50 patients and 50 controls. There was no variation in the HRM curves obtained from the analysis of exons 1 and 2 in the case and control groups. In exon 3, an Arg(188)His polymorphism (rs3218536) was detected as a new melting curve group (OR: 1.46; 95%CI: 0.432-4.969; p = 0.38) compared with the normal melting curve. We also found a new Ser(150)Arg polymorphism in exon 3 of the control group. These findings suggest that genetic variations in the XRCC2 coding region have no potential effects on susceptibility to DTC. However, further studies with larger populations are required to confirm this conclusion.     

BTA-TRAK combined with urinary cytology is a reliable urinary indicator of recurrent transitional cell carcinoma (TCC) of the bladder

This study evaluated the diagnostic accuracy of BTA-TRAK in combination with urinary cytology (UC) in the follow-up of patients with a history of transitional cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2% (48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and for invasive recurrences (100% (15/15)); when the two tests were used in combination, the sensitivity for superficial lesions increased to 88% (37/42). BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7% (11/16)), and when the two tests were combined the sensitivity increased to 87.5% (14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The differences in urinary BTA-TRAK levels between patients with recurrences and those without evidence of disease were statistically significant (Wilcoxon's test, p<0.05); among patients with recurrences BTA levels were significantly higher in the invasive and poorly differentiated subtypes. In the series of patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive, accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK combined with urinary cytology seems to provide additional information for the monitoring of patients treated for TCC; however, due to the presence of false positive and false negative results, this test cannot replace cystoscopy. In a selected group of patients it could, if combined with cytology and ultrasonography and if correctly used and interpreted, orient the timing and indication for cystoscopy.     

Mean growth rate when rare is not a reliable metric for persistence of species

The coexistence of many species within ecological communities poses a long‐standing theoretical puzzle. Modern coexistence theory (MCT) and related techniques explore this phenomenon by examining the chance of a species population growing from rarity in the presence of all other species. The mean growth rate when rare, , is used in MCT as a metric that measures persistence properties (like invasibility or time to extinction) of a population. Here we critique this reliance on and show that it fails to capture the effect of temporal random abundance variations on persistence properties. The problem becomes particularly severe when an increase in the amplitude of stochastic temporal environmental variations leads to an increase in , since at the same time it enhances random abundance fluctuations and the two effects are inherently intertwined. In this case, the chance of invasion and the mean extinction time of a population may even go down as increases.     

Fluorescent tag is not a reliable marker for small RNA transfection in the presence of serum

Chemically synthetic siRNA and miRNA have become powerful tools to study gene function in the past decade. Fluorescent dyes covalently attached to the 5′ or 3′ ends of synthetic small RNAs are widely used for fluorescently imaging and detection of these RNAs. However, the reliability of fluorescent tags as small RNA markers in different conditions has not attracted enough attention. We used Cy3-labelled small RNAs to explore the reliability of fluorescent tags as small RNA markers in cell cultures involving serum. A strong Cy3-fluorescence signal was observed in the cytoplasm of the cells transfected with Cy3-miR24 in the culture medium containing fetal bovine serum (FBS), but qRT-PCR results showed that little miR24 were detected in these cells. Further study demonstrated that small RNAs were degraded in the presence of FBS, suggesting that it was Cy3-RNA fragments, rather than the original Cy3-miR24, diffused into cells. These phenomena disappeared when FBS was replaced by boiled-FBS, further supporting that the Cy3-fluorescence we observed in cells in the presence of FBS could not represent the presence of intact small RNAs. These findings addressed that fluorescent tags are not reliable for small RNA transfection in the presence of serum in culture.     

Hexamethylenebisacetamide modulation of thyroglobulin and protein levels in thyroid cells is not mediated by phosphatidylinositol-3-kinase: a study with wortmannin

Hexamethylenebisacetamide (HMBA) induces in murine erythroleukemia cells (MELC) the commitment to terminal differentiation leading to globin gene expression. In the thyroid, HMBA acts as a growth factor and also as a differentiating agent. In the present paper, we studied the effect of HMBA on the very specific thyroid marker thyroglobulin (Tg) in two different thyroid cell systems, i.e., porcine cells in primary culture and ovine cells in long term culture. Using wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, we investigated whether this enzyme is involved in HMBA mode of action. We found that HMBA is a positive modulator of Tg production in porcine cells, but a negative effector in the OVNIS cell line. As all HMBA effects studied in the present paper, i.e., Tg production and total protein levels, are not inhibited by wortmannin, we suggest the non-involvement of phosphatidylinositol-3-kinase in HMBA mode of action.     

Desheathing the nodose ganglion is not a reliable method of de-efferentation in the ferret

The present study reports the results of physiological and anatomical experiments in which the purpose was to determine whether desheathing the nodose ganglion is a reliable method of vagal de-efferentation in the ferret. In physiological studies, the effects of electrically stimulating the treated and untreated vagal nerves on cardiovascular and intestinal responses were examined and compared with previously obtained data after left supranodose vagotomy. The anatomical studies illustrated the effects of desheathing the left nodose ganglion on the transport of horseradish peroxidase (HRP) within a thoracic vagal communicating branch. These data were compared to data from control animals and animals that had undergone left supranodose vagotomy. The results demonstrated that severing the fascicles overlying the left nodose ganglion and allowing the nerve fibers to degenerate, caused no reduction in labeled efferent cell bodies in the left dorsal motor nucleus of the vagus as compared to controls. However, after left supranodose vagotomy there were no efferent cell bodies labeled in the left dorsal motor nucleus of the vagus. Following degeneration of the fascicles, electrical stimulation of the peripheral cut end of this nerve did not abolish the efferent responses in 7 out of 9 animals studied, whereas supranodose vagotomy abolished the responses in all animals. These findings demonstrate that desheathing the nodose ganglion and thereby removing the nerve bundles overlying the nodose ganglion is not a guaranteed method of destroying the efferent fibers in the vagus nerve of the ferret. Supranodose vagotomy, therefore, is a more reliable method of de-efferentation in this species.     

Offspring gender ratio and the rate of recurrent spontaneous miscarriages in jewish women at high risk for breast/ovarian cancer

BRCA1/BRCA2 germline mutations are associated with an increased breast/ovarian cancer risk. Offspring gender ratios may be skewed against male births in BRCA1 mutation carriers. In addition, the lack of viable homozygous BRCA1/BRCA2-mutation carriers implies that recurrent miscarriages may be associated with homozygous fetuses. Jewish Israeli high-risk women who were tested for being carriers of the predominant BRCA1/BRCA2 mutations in Jewish high-risk families were analyzed for the sex of offspring and the rate of spontaneous miscarriages. Overall, 817 women participated: 393 BRCA1/BRCA2-mutation carriers (229 with breast/ovarian cancer) and 424 high-risk noncarriers (208 with breast/ovarian cancer). No differences between the male-to-female offspring ratios of all study groups were noted. Among mutation carriers, the offspring male-to-female ratio was 0.97 (444 : 460), and among mutation carriers with cancer it was 0.92 (262 : 284). Similarly, no offspring gender skewing was noted among high-risk noncarriers, regardless of health status. The rates of three or more spontaneous miscarriages among participants with at least one live birth were 4.37% (15/343) among mutation carriers and 3% (12/401) among high-risk women (P = not significant). In conclusion, the offspring gender ratio is similar in high-risk Jewish families and in the general population. The issue of the rate of recurrent miscarriages in high-risk Jewish women is unresolved.     

Evaluation of the therapeutic benefits in relation to the extent of surgery in patients with differentiated thyroid carcinoma

INTRODUCTION: Evaluation of the therapeutic benefits in relation to the stage of thyroid cancer and to the extent of surgery and the risk of postoperative complications. MATERIAL AND METHODS: Retrospective analysis of differentiated thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of them were treated or diagnosed in Institute of Oncology in Gliwice between 1986-1998. Previously they were operated in various surgical centers all-over Poland. The risk of death, local relapse and postoperative complications were analyzed using the decisiontree model to evaluate the therapeutic benefits. RESULTS: The recurrent laryngeal nerve injury (transient or permanent) was observed in retrospective analysis in 21% of patients, while postoperative hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in patients treated by less than total thyroidectomy). The advantage of radical surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in patients treated by total thyroidectomy and 0.69 in those who received less extensive operation. CONCLUSIONS: The analysis of therapeutic benefits confirmed the limit of 1 cm tumor diameter between less extensive surgery and total thyroidectomy. It showed that total thyroidectomy brings a significant therapeutic benefits in patients in > T1M0 stage. The improvement of overall survival and decrease of local relapse far outweigh the disadvantages related to postoperative complications.     

Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis

Objective: To determine whether or not significant differences in the risk of malignancy exist between subgroups of atypical follicular cells in The Bethesda System for Reporting Thyroid Cytology (TBSRTC) in patients who underwent surgical resection. Study Design: Between 2004 and 2009, consecutive thyroid fine-needle aspirates at our institutions with a cytologic diagnosis of 'atypical follicular cells' were retrieved and subclassified using the diagnosis and diagnostic comment as: (1) atypical follicular cells with equivocal features of papillary carcinoma [cannot exclude papillary thyroid carcinoma (PTC)] and (2) atypical follicular cells, other patterns. The risks of malignancy for excised nodules were calculated and comparisons were made between these subgroups. Categorical analysis was performed using a 2-tailed Fisher's exact test, and p < 0.05 was considered statistically significant. Results: A total of 7,072 thyroid fine-needle aspiration cases were retrieved, with 1,542 (21.8%) having a histologic follow-up. There were 222 (3.1%) cases of 'atypical follicular cells', with 127 (57.2%) having a histologic correlation and 33 having confirmed malignancies. Atypical follicular cells, cannot exclude PTC, have a significantly higher risk of malignancy than atypical follicular cells, other patterns (45.8 vs. 13.9%, p < 0.01). Conclusions: Atypical follicular cells with equivocal features of papillary carcinoma is not a low-risk cytologic diagnosis.     

The amoeba-to-flagellate transformation test is not reliable for the diagnosis of the genus Naegleria. Description of three new Naegleria spp.

Trophozoites of several isolates from one location in Australia have failed consistently to transform into flagellates, although they display all other characteristics of the genus Naegleria. When changing the standard transformation test, flagellates were produced. In phylogenetic trees derived from partial small subunit ribosomal DNA (SSUrDNA) sequences, one of these strains branches close to a cluster comprising N. clarki, N. australiensis, N. italica and N. jadini. It is proposed that these Australian isolates represent a new species, named N. fultoni (strain NG885). Failing to form flagellates since their isolation, even when different transformation procedures are used, are two Naegleria strains from Chile and Indonesia. In SSUrDNA-based phylogenetic trees the Chilean strain clusters with N. pussardi and the Indonesian strain clusters with N. galeacystis, but the degree of sequence difference from these described species (3.5% and 2.2%, respectively) is sufficient to propose that both of the strains represent new species, named N. chilensis (strain NG946) and N. indonesiensis (strain NG945), respectively. The close relationships between each of the new species and the Naegleria species with which they cluster in SSUrDNA-based trees were confirmed by ribosomal internal transcribed spacer region (ITS) sequence comparisons. In France, several non-flagellating N. fowleri strains were isolated from one location. ITS rDNA sequence comparisons indicated that they correspond to a 'type' of N. fowleri found in both Europe and the USA. A redefinition of the genus Naegleria is proposed as a consequence of these and previous findings.     

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3–4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p = 0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3–4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.Key words: anti-cetuximab antibodies, ELISA, hypersensitivity, therapeutic monoclonal antibody, ROC     

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3-4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p=0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3-4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.     

Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid

Thyroid-specific enhancer-binding protein (T/ebp)/Nkx2.1-null mouse thyroids degenerate by embryonic day (E) 12-13 through apoptosis whereas T/ebp/Nkx2.1-heterogyzgous mice exhibit hypothyroidism with elevated TSH levels. To understand the role of T/ebp/Nkx2.1 in the adult thyroid, a thyroid follicular cell-specific conditional knockout (KO) mouse line, T/ebp(fl/fl);TPO-Cre, was established that expresses Cre recombinase under the human thyroid peroxidase (TPO) gene promoter. These mice appeared to be healthy and exhibited loss of T/ebp/Nkx2.1 expression in many, but not all, thyroid follicular cells as determined by immunohistochemistry and real-time PCR, thus presenting a T/ebp-thyroid-conditional hypomorphic mice. Detailed analysis of the thyroids from T/ebp(fl/fl), T/ebp(fl/fl);TPO-Cre, and T/ebp(fl/ko) mice, where the latter mouse line is derived from crosses with the original T/ebp/Nkx2.1-heterozygous mice, revealed that T/ebp(fl/fl);TPO-Cre mice can be classified into two groups with different phenotypes: one having atrophic/degenerative thyroid follicles with frequent presence of adenomas and extremely high serum TSH levels, and the other having an altered thyroid structure with reduced numbers of extraordinary dilated follicles consisting of excessive numbers of follicular cells as compared with those usually found in the normal thyroid. The latter phenotype was also observed in aged T/ebp(fl/ko) mouse thyroids. In vitro three-dimensional thyroid primary cultures using thyroids from T/ebp(fl/fl);TPO-Cre, T/ebp(fl/ko), and T/ebp(fl/fl) mice, and the latter treated with recombinant adenovirus with and without Cre expression, demonstrated that only cells from T/ebp(fl/fl) mice without adeno-Cre treatment formed follicular structures. Taken together, these results suggest that T/ebp/Nkx2.1 is required for maintenance of the normal architecture and function of differentiated thyroids.     

The fluorescence intensities ratio is not a reliable parameter for evaluation of protein unfolding transitions

Monitoring the fluorescence of proteins, particularly the fluorescence of intrinsic tryptophan residues, is a popular method often used in the analysis of unfolding transitions (induced by temperature, chemical denaturant, and pH) in proteins. The tryptophan fluorescence provides several suitable parameters, such as steady‐state fluorescence intensity, apparent quantum yield, mean fluorescence lifetime, position of emission maximum that are often utilized for the observation of the conformational/unfolding transitions of proteins. In addition, the fluorescence intensities ratio at different wavelengths (usually at 330 nm and 350 nm) is becoming an increasingly popular parameter for the evaluation of thermal transitions. We show that, under certain conditions, the use of this parameter for the analysis of unfolding transitions leads to the incorrect determination of thermodynamic parameters characterizing unfolding transitions in proteins (e.g., melting temperature) and, hence, can compromise the hit identification during high‐throughput drug screening campaigns.