99mTc-methoxyisobutylisonitrile single-photon emission computed tomography/computed tomography parathyroid imaging in the diagnosis of functional parathyroid cysts: an initial experience.

Background: Functional parathyroid cysts (FPCs) are rare and difficult to diagnose with noninvasive methods. The aim of this study was to evaluate the diagnostic value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computerized tomography (SPECT/CT) parathyroid imaging in the diagnosis of FPCs and to account for its performance. Methods: The data from 10 patients with suspected parathyroid cysts (PCs) who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2012 and 2022 were retrospectively evaluated. The diagnostic value of 99mTc-MIBI SPECT/CT parathyroid imaging for FPCs was analyzed. Results: Surgical resection was performed in six cases and parathyroid puncture was performed in four cases. The sensitivity of 99mTc-MIBI SPECT/CT for FPCs was 100.0% (3/3), with a specificity of 100.0% (7/7) and an accuracy of 100.0% (10/10). The postoperative pathological findings in three cases of FPCs were parathyroid adenoma, parathyroid adenoma with hemorrhage, and parathyroid adenoma with cystic degeneration, respectively. The diagnostic accuracy of ultrasound and CT for PCs was only 22.22% (2/9) and 25.0% (1/4), respectively, and neither modality could indicate whether the cysts were functional or not. Conclusions: 99mTc-MIBI parathyroid SPECT/CT imaging has a high value in the diagnosis of FPCs in patients with suspected PCs, and an intense ring-shaped accumulation of radioactivity in the cyst wall on 99mTc-MIBI imaging suggests that the patient may have FPCs.

Analysis of false-positive and false-negative results in 99mTc-MIBI SPECT/CT parathyroid imaging.

Background: Exact preoperative localization is desirable to perform minimally invasive parathyroidectomy for hyperparathyroidism (HPT). This study aimed to evaluate the diagnostic values of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) of parathyroid glands by analyzing the relationship between lesion weight and false-negative (FN) results, as well as to explain the possible reason. Methods: The data from 314 patients with suspected HPT who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2011 and 2022 were retrospectively evaluated. The sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of parathyroid 99mTc-MIBI SPECT/CT were calculated, and the false-positive (FP) and FN findings were analyzed. Results: Accurate localization by 99mTc-MIBI SPECT/CT was significantly associated with the parathyroid hormone (PTH) level. The 99mTc-MIBI SPECT/CT for diagnosis/lesion location reached a sensitivity of 84.6%/56.8%, a PPV of 97.3%/98.4%, an NPV of only 23.7%/4.18%, and an accuracy of 83.4%/57.1%, respectively. The largest diameter, shortest diameter, and lesion volume were lower in the FN group than in the TP group. A total of 7 FP cases were found, including 2 cases of thyroid nodules, 4 cases of thyroid tissue, and 1 case of hibernoma. A total of 45 FN patients, including 321 FN lesions, were confirmed, of which parathyroid hyperplasia accounted for 97.8%. Lesion weights greater than 20 µg were able to be detected, but lightweight lesions less than 100 mg were the principal source of FN results, accounting for approximately 39.3%. With lesion weights 0-100, 101-300, 301-1,000, and >1,000 mg, the FN rate was 70.8% (126/178), 51.8% (103/199), 34.6% (81/234), and 8.33% (11/132), respectively. Conclusions: 99mTc-MIBI SPECT/CT parathyroid imaging provides good sensitivity and high specificity in HPT location. Correct localization by 99mTc-MIBI SPECT/CT correlates positively with lesion weight and PTH levels. The smaller the lesion, the higher the FN rate in 99mTc-MIBI SPECT/CT parathyroid imaging, and lesions weighing less than 100 mg are the main source of FN results in 99mTc-MIBI SPECT/CT parathyroid imaging.

Evaluation of integrin αvß3-targeted imaging for predicting disease progression in patients with high-risk differentiated thyroid cancer (using 99mTc-3PRGD2).

BACKGROUND: High-risk differentiated thyroid cancer (DTC) needs effective early prediction tools to improving clinical management and prognosis. This cohort study aimed to investigate the prognostic impact of 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) SPECT/CT in high-risk DTC patients after initial radioactive iodine (RAI) therapy. METHODS: Thirty-three patients with high-risk DTC were prospectively recruited; all patients underwent total thyroidectomy and received 99mTc-3PRGD2 SPECT/CT before RAI ablation. Follow-up was done with serological and imaging studies. The correlation between 99mTc-3PRGD2 avidity and remission rate for initial RAI therapy was evaluated using logistic regression analysis. The prognostic value of 99mTc-3PRGD2 SPECT/CT was evaluated by Kaplan-Meier curve and Cox regression analysis. RESULTS: 99mTc-3PRGD2 avidity was significantly correlated with the efficacy of initial RAI ablation and an effective predictor for non-remission in high-risk DTC (OR = 9.36; 95% CI = 1.10-79.83; P = 0.041). 99mTc-3PRGD2 avidity was associated with poor prognosis in patients with high-risk DTC and an independent prognostic factor for shorter progression-free survival (PFS) (HR = 9.47; 95% CI = 1.08-83.20; P = 0.043). Survival analysis, which was performed between DTC patients with concordant (131I positive/99mTc-3PRGD2 positive) and discordant (131I negative/99mTc-3PRGD2 positive) lesions, indicated that patients with concordant lesions had significantly better PFS than those with discordant lesions (P = 0.022). Moreover, compared with repeated RAI, additional surgery or targeted therapy with multikinase inhibitors could lead to a higher rate of remission in 99mTc-3PRGD2-positive patients with progressive disease. CONCLUSIONS: 99mTc-3PRGD2 SPECT/CT is a useful modality in predicting progression of the disease after initial RAI and guiding further treatment in high-risk DTC patients.

Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer.

Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (p < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.

Combining Phenotypes of Nucleotide Excision Repair Pathway to Predict the Risk of Head and Neck Squamous Cell Carcinomas in a Chinese Population.

Background: Nucleotide excision repair (NER) is pivotal in the development of smoking-related malignancies. Nine core genes (XPA, XPB, XPC, XPD, XPF, XPG, ERCC1, DDB1, and DDB2) are highly involved in the NER process. We combined two phenotypes of NER pathway (NER protein and NER gene mRNA expression) and evaluated their associations with the risks of the head and neck squamous cell carcinomas (HNSCCs) in a Chinese population. Methods: We conducted a case-control study of 337 HNSCC patients and 285 cancer-free controls by measuring the expression levels of nine core NER proteins and NER gene mRNA in cultured peripheral lymphocytes. Results: Compared with the controls, cases had statistically significantly lower protein expression levels of XPA (P < 0.001) and lower mRNA expression levels of XPA and XPB (P = 0.005 and 0.001, respectively). After dividing the subjects by controls' medians of expression levels, we found an association between increased risks of HNSCCs and low XPA protein level (P trend = 0.031), as well as low mRNA levels of XPA and XPB (P trend = 0.024 and 0.001, respectively). Subsequently, we correlated the two phenotypes and found associations between the NER mRNA and protein levels. Finally, the sensitivity of the expanded model with protein and mRNA expression levels, in addition to demographic variables, on HNSCCs risk was significantly improved. Conclusions: Combining two phenotypes of NER pathway may be more effective than the model only including one single phenotype for the assessment of risks of HNSCCs.

Fucosyltransferase 8 is Overexpressed and Influences Clinical Outcomes in Lung Adenocarcinoma Patients.

Background: Lung adenocarcinoma (LUAD), the most prevalent type of lung cancer, is often metastatic and has a poor prognosis. Recent studies have demonstrated an important role for fucosyltransferase 8 (FUT8) in carcinogenesis and cancer progression. Methods: A meta-analysis with 15 eligible datasets from Gene Expression Omnibus (GEO) was performed to explore the expression of FUT8 in LUAD. The results were further verified in The Cancer Genome Atlas (TCGA) database, followed by survival analysis using Kaplan-Meier plotter. We also validated the protein expression of FUT8 by immunohistochemistry (IHC). In vitro experiments were conducted to determine the biological effects of FUT8 in LUAD cells. Results: The meta-analysis showed the FUT8 expression in LUAD tissues was significantly higher than those in normal lung tissues [standard mean difference (SMD): 1.40; 95% confidence interval (CI): .95-1.85]. The results of TCGA database verified the expression of FUT8 increased in LUAD tissues versus normal tissues. IHC analyses indicated that the protein levels of FUT8 were up-regulated in LUAD, and elevated FUT8 expression was significantly correlated with poor prognosis in LUAD patients. Multivariable Cox regression analysis revealed that FUT8 expression was an independent prognostic factor. Besides, in vitro experiments showed that knockdown of FUT8 in LUAD cells markedly restrained cell proliferation, and stimulated cell apoptosis. Conclusion: This study indicates that increased FUT8 expression is correlated with shortened survival of LUAD patients and might favor the progression of the disease.

EHF enhances malignancy by modulating AKT and MAPK/ERK signaling in non­small cell lung cancer cells.

Overexpression of ETS­homologous factor (EHF) in non­small cell lung cancer (NSCLC) is associated with poor patient prognosis. To explore the mechanism of the effect of EHF in NSCLC, EHF expression was examined in NSCLC and its role in cell proliferation, invasion, cell cycle, and apoptosis of NSCLC cells was evaluated by overexpressing EHF and/or knocking down EHF expression in NSCLC cells in vitro and in cancer cell grafted mice in vivo. The results revealed that the knockdown of EHF expression in NSCLC with siRNA significantly inhibited cell proliferation and invasion, arrested the cell cycle at the G0/G1 phase, and induced apoptosis, whereas overexpression of EHF in NSCLC promoted cell proliferation, tumor growth, and cancer cell migration in vitro. The in vivo experiments demonstrated that siRNA­mediated downregulation of EHF expression in NSCLC cells significantly suppressed tumor growth in xenografted nude mice as compared to cancer progression in the mice grafted with NSCLC cells transfected with non­specific control siRNA. The biochemical analyses revealed that EHF promoted NSCLC growth by regulating the transcription of Erb­B2 receptor tyrosine kinase 2/3 (ERBB2, ERBB3) and mesenchymal­epithelial transition (MET) factor tyrosine kinase receptors and modulating the AKT and ERK signaling pathways in the NSCLC cells. The present findings indicated that EHF could be used as a prognostic marker for NSCLC, and tyrosine kinase receptors of ERBB2, ERBB3 and MET could be drug targets for NSCLC treatment.

Establishment of normal reference ranges for total and separate glomerular filtration rates in living kidney donors by Gates' method after renal depth measured using single-photon emission computed tomography/computed tomography.

BACKGROUND: The underestimation of renal depth by Tønnesen formula in Gates' method, which has been confirmed by many scholars, leads to the underestimation of both separate glomerular filtration rate (gSGFR) and total glomerular filtration rate (gTGFR). This study aimed to establish the normal reference ranges of renal depth-calibrated gTGFR and gSGFR in Chinese healthy adults, and to analyze the influencing factors. METHODS: Renal depth was measured by CT scan followed by technetium 99m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) in 329 living kidney donors. The renal depth-calibrated gTGFR and gSGFR were calculated by Gates' method with renal depth measured by CT instead of being calculated by the Tønnesen formula. A general linear model based on age, gender, body height, body weight, and BMI was used to analyze factors influencing gSGFR (L), gSGFR (R) and gTGFR. RESULTS: The average gSGFR (L), gSGFR (R), and gTGFR for patients aged 23-64 years old were 49.3±10.1, 49.9±10.4, and 99.1±18.7 mL/min/1.73 m2, respectively. The gSGFR (L), gSGFR (R) and gTGFR for patients aged 41-50 years old were 26.9-69.3, 27.7-68.8, and 57.5-135.3 mL/min/1.73 m2, respectively, and those for patients aged 51-60 years old were 31.0-61.5, 29.5-63.3, and 64.6-120.7 mL/min/1.73 m2, respectively. gSGFR (L), gSGFR (R) and gTGFR had statistical significance with body height and age (P<0.05); however, there was no significant difference with gender, body weight, and BMI (P>0.05). For each 1 year increase in age, the gSGFR (L), gSGFR (R), and gTGFR decreased by 0.17, 0.28, and 0.44 mL/min/1.73 m2, respectively, while for every 1 cm increase in body height, the gSGFR (L), gSGFR (R), and gTGFR decreased by 0.37, 0.36, and 0.74 mL/min/1.73 m2, respectively. CONCLUSIONS: Normal reference ranges for renal depth-calibrated gSGFR (L), gSGFR (R), and gTGFR were established in healthy Chinese adults aged 23-64 years, and gSGFR (L), gSGFR (R), and gTGFR decreased with age and body height.

Alterations in serum protein glycopatterns related to small cell lung cancer, adenocarcinoma and squamous carcinoma of the lung.

Background: The main reason why lung cancer has maintained a high rate of morbidity and mortality is that its early diagnosis is difficult. No current lung cancer screening is recommended by any major medical organization due to the lack of sensitive and specific screening technologies. Thus, this study aimed to systematically investigate the correlation between the alterations in serum glycosylation and three main types of lung cancers (SCLC, ADC and SqCC). Materials and methods: We investigated the protein glycopatterns in sera from 333 subjects (65 healthy volunteers, 38 benign lung disease patients, 49 small cell lung cancer patients, and 181 NSCLC patients) using a lectin microarray. A serum microarray was produced to evaluate and verify the terminal carbohydrate moieties of the glycoproteins in individual serum samples from 30 cases simultaneously. Results: There were 16 lectins (e.g., RCA120, BS-I, and UEA-I), 24 lectins (e.g., HHL, PTL-I, and MAL-II), and 18 lectins (e.g., GSL-I, LEL, and ACA) that exhibited significant differences in serum protein glycopatterns in the patients with SCLC, ADC and SqCC compared with the controls (HV and BPD). There were 6 lectins (e.g., EEL, NPA, and LEL) that exhibited significantly increased NFIs in ADC and SqCC compared with SCLC. Also, there were 5 lectins (e.g., Jacalin, BS-I, and UEA-I) that exhibited significantly decreased NFIs in ADC compared with SCLC and SqCC. Conclusions: This study can facilitate the discovery of potential biomarkers for the differential diagnosis of lung cancer based on the precise alteration in serum protein glycopatterns.

Associations between expression levels of nine core nucleotide excision repair genes in lymphocytes and risk of head and neck squamous cell carcinomas in a Chinese population.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are one of the most common cancers in the world, and nucleotide excision repair (NER) is involved in HNSCCs susceptibility. We investigated whether mRNA expression levels of nine core NER genes were associated with risk of HNSCCs in a Chinese population. METHODS: In this study of 251 HNSCC patients and 232 healthy controls, we quantified NER gene mRNA expression levels in cultured peripheral lymphocytes using a quantitative real-time PCR. RESULTS: Compared with the controls, HNSCC patients had statistically significantly lower expression levels of XPA and XPB (P = 0.029 and 0.001, respectively). After dividing the subjects by the controls' median values of expression levels, we found a dose-dependent association between an increased risk of HNSCCs and low expression levels of XPB (adjusted OR 1.56 and 95% CI 1.07-2.28; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status as well as alcohol status and mRNA expression levels of XPB (P = 0.014 and 0.042, respectively). Finally, after integrating demographic variables, we found the addition of smoking status and XPB expression levels to the model significantly improved the sensitivity of the expanded model on HNSCC risk. CONCLUSION: Reduced mRNA expression levels of XPB were associated with an increased risk of HNSCCs in a Chinese population.

Retroperitoneal Malignant Peripheral Nerve Sheath Tumor on 99mTc-DTPA Renal Scintigraphy.

Findings of Tc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.

Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in China and around the world. Early detection is key to improving the survival rate of non-small cell lung cancer (NSCLC). Alteration in glycosylation has been observed in cancers, and glycans can be a source for the development of new biomarkers for NSCLC. METHODS: In this glycan biomarker discovery study, we measured serum N- and O-glycan profiles in NSCLC patients with different stages and healthy controls by performing lectin microarray analysis. The alterations of serum glycopatterns were compared between NSCLC patients and controls, and the stage-related changes in serum glycosylation were evaluated. RESULTS: There were 18 lectins (e.g., AAL, Jacalin, GSL-I and DBA) to give significantly alterations of serum glycopatterns in lung adenocarcinoma compared with control group. Meanwhile, 16 lectins (e.g., Jacalin, HHL, and PHA-E+L) exhibited significantly alterations of serum glycopatterns in squamous cell carcinoma (SCC) compared with control group. Importantly, most of the lectins showing altered signals exhibited significantly increased or decreased NFIs in patients with early stage adenocarcinoma and SCC. CONCLUSIONS: The serum glycan profiles were significantly different between NSCLC and healthy control, and most of the glycosylation changes had occurred at early stage. Further evaluation is needed to examine the diagnostic value of the glycan markers identified in this study.

Papillary Thyroid Micro Carcinoma: The Incidence of High-Risk Features and Its Prognostic Implications.

Background: The current management of papillary thyroid micro carcinoma (PTMC) has become more conservative. However, high-risk characteristics that can only be revealed post-surgically exist. Patients and clinicians need to estimate the risks and understand the prognostic meaning of these factors. Methods: We retrospectively analyzed 246 consecutive patients with PTMC who underwent surgery at our institution between 2015 and 2017. Clinical and histopathological parameters that may indicate recurrent disease were investigated. The responses to therapy in cases with different risks of recurrence were analyzed. Results: A total of 79.26% (195/246) of patients received total thyroidectomy (TT), of whom 177 (90.77%) also received central lymph node dissection. Radioiodine ablation (RAI) was applied in 64.23% (158/246) of patients. Intermediate-high risk features were identified in 27.64% (68/246) after primary treatment. After a median follow-up of 18 months (range, 6-39 months), 121 of 158 (76.58%) patients who received TT+RAI were evaluated as an excellent response. An incomplete response (IR) was observed in 14.56% (23/158) of this group of PTMC. Multivariate analysis identified extra thyroid extension (P = 0.001) and intermediate-high risk stratification (P = 0.014) as significant and independent risk factors for an IR. Conclusions: A total of 27.64% of PTMC cases evaluated as a low risk of recurrence pre-surgery showed intermediate to high risk disease post-surgery, and this leads to a higher rate of IR.

Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.

Lung cancer is the most frequent cancer and the leading cause of cancer around the world. As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis. Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC. In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs. And we further analyzed their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns. The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs. There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues. And the abundance of the fucosylated N-glycans was increased from 40.9% (PCTs) to 48.3% (LUSC). These finding is helpful to elucidate the molecular mechanisms underlying the lung diseases and develop new treatment strategies.

Comparison between technetium-99m methoxyisobutylisonitrile scintigraphy and ultrasound in the diagnosis of parathyroid adenoma and parathyroid hyperplasia.

OBJECTIVE: The aim of this study was to evaluate the value of technetium-99m methoxyisobutylisonitrile (Tc-MIBI) imaging and ultrasound in preoperative localization of parathyroid adenoma (PA) and parathyroid hyperplasia (PH). PARTICIPANTS AND METHODS: A retrospective study of Tc-MIBI double-phase scintigraphy (DPS) was performed in 187 hyperparathyroidism cases with pathologically diagnosed PA or PH. Of these patients, 167 cases underwent ultrasound, and 146 cases underwent Tc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT). The sensitivity and diagnostic accuracy of ultrasound, Tc-MIBI DPS, and SPECT/CT were compared between PA and PH. Differences in Tc-MIBI DPS, serum parathyroid hormone (PTH), serum calcium and phosphorus, as well as the weight and longest diameter of lesion between PA and PH were also compared. RESULTS: As per patient-based analysis, the sensitivity of ultrasound, Tc-MIBI DPS, and SPECT/CT was 90.70% (39/43), 95.56% (43/45), and 100.00% (30/30), respectively, for PA, and 93.55% (116/124), 90.85% (129/142), and 93.10% (108/116), respectively, for PH. There were no significant differences in sensitivity of these three imaging methods between PA and PH. However, per lesion-based analysis, the accuracy of ultrasound, Tc-MIBI DPS, and SPECT/CT in detecting PA was 78.43% (40/51), 86.79% (46/53) and 96.88% (31/32), respectively, and the accuracy of Tc-MIBI DPS was higher than that of ultrasound (χ=6.507, P=0.011), and for PH, it was 49.69% (160/322), 40.71% (171/420), and 43.80% (152/347), respectively. The accuracy of ultrasound was higher than that of Tc-MIBI DPS (χ=5.940, P=0.015). The accuracy of a combination of all three examinations of ultrasound+Tc-MIBI DPS, ultrasound+Tc-MIBI SPECT/CT, Tc-MIBI DPS+SPECT/CT, and ultrasound+Tc-MIBI DPS+Tc-MIBI SPECT/CT was 51.51% (154/299), 53.85% (161/299), 50.17% (150/299), and 54.18% (162/299), respectively, which was higher than that of ultrasound (χ=5.273, P=0.022; χ=8.226, P=0.004; χ=3.880, P=0.049; χ=8.702, P=0.003, respectively). Serum levels of PTH and phosphorus were lower in patients with PA than in patients with PH (P<0.001), and serum calcium level, the weight, and the longest diameter of lesion and early uptake rate of Tc-MIBI DPS were higher in patients with PA than in patients with PH (P<0.01). Serum PTH level is often less than 1000 pg/ml in PA, but usually more than 1000 pg/ml in PH. CONCLUSION: Ultrasound, Tc-MIBI DPS, and SPECT/CT all have a higher value in the diagnosis of PA than PH. Tc-MIBI SPECT/CT should be optimal for detecting PA, and early SPECT/CT scan might be better than delayed scan. Compared with Tc-MIBI DPS and SPECT/CT, ultrasound has a slight advantage in localization of PH lesions. The combination of ultrasound and Tc-MIBI DPS or SPECT/CT imaging could improve the accuracy in localization of PH lesions and should be considered as the first-line method for detecting PH.

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome.

AIMS: To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. METHODS: A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvß3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. RESULTS: Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. CONCLUSIONS: The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake.

Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level.

The aim of this study was to assess the usefulness of integrin imaging with 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS) and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total thyroidectomy followed by radioactive iodine ablation and had negative radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance indicators, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated. The correlations between SPECT/CT results and clinic-pathological characteristics were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively. The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels. 99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of recurrence among DTC patients with higher Tg levels and negative WBS, and the probability of obtaining a positive SPECT/CT result was related with the level of Tg.

Expression and clinicopathological significance of S100 calcium binding protein A2 in lung cancer patients of Chinese Han ethnicity.

BACKGROUND: S100 family of calcium-binding proteins plays a significant role in the process of many kinds of tumors, including lung cancer. As an important member of this family, S100 calcium binding protein A2 (S100A2) has been confirmed to be associated with many biological processes, and has an abnormal expression in non-small cell lung cancer (NSCLC). However, the S100A2 status in lung cancer is still controversial and undefined. METHODS: We evaluated the pattern and distribution of S100A2 in 109 cases of lung cancer, including five histological types (47 adenocarcinoma, 46 squamous cell carcinoma, 7 small cell carcinoma, 3 large cell carcinoma, and 6 atypical carcinoid), and 30 cases of paired adjacent normal lung tissues by means of immunohistochemistry. RESULTS: Compared with the normal tissues (0/30), S100A2 experienced a dramatically upward trend of positive expression in lung cancer, with a positive rate of 68/109 (P<0.001). Specifically, squamous cell carcinoma, with 34/12, had the highest expression ratio, followed by large cell carcinoma (2/1), adenocarcinoma (31/16), and atypical carcinoid (1/5) respectively, while no S100A2 protein was detected in small cell carcinoma. Meanwhile, we firstly demonstrated that the high expression of S100A2 was significantly associated with the incidence of lymph node metastasis in adenocarcinoma (P=0.013). CONCLUSIONS: The association between high S100A2 expression and NSCLC at the level of tissue, and S100A2 may serve as an effective biomarker for the diagnosis and prognosis of NSCLC in future.

Blockade efficacy of MEK/ERK-dependent autophagy enhances PI3K/Akt inhibitor NVP-BKM120's therapeutic effectiveness in lung cancer cells.

NVP-BKM120 (BKM120) is a new pan-class I phosphatidylinositol-3 kinase (PI3K) inhibitor and has been tested in clinical trials as an anticancer agent. In this study, we determined whether BKM120 induces autophagy and the impact of autophagy induction on BKM120's growth-inhibitory activity. BKM120 potently induced elevation of autophagosome-bound type II LC3 (LC3-II) protein, predominantly in cell lines insensitive to BKM120, thereby inducing autophagy. The presence of lysosomal protease inhibitor chloroquine further enhanced the levels of LC3-II. BKM120 combined with chloroquine, enhanced growth-inhibitory effects including induction of apoptosis, suggesting that autophagy is a protective mechanism counteracting BKM120's growth-inhibitory activity. Interestingly, BKM120 increased p-ERK1/2 levels. When blocking the activation of this signaling with MEK inhibitors or with knockdown of ERK1/2, the ability of BKM120 to increase LC3-II was attenuated and the growth-inhibitory effects including induction of apoptosis were accordingly enhanced, suggesting that the MEK/ERK activation contributes to BKM120-induced authophagy. In mouse xenograft model, we also found that the combination of BKM120 and PD0325901 synergistically suppressed cell growth in human lung cancer cells. Thus, the current study not only reveals mechanisms accounting for BKM120-induced autophagy, but also suggests an alternative method to enhance BKM120's therapeutic efficacy against non-small cell lung cancer(NSCLC) by blocking autophagy with either a lysosomal protease inhibitor or MEK inhibitor.

miRNA-204 suppresses human non-small cell lung cancer by targeting ATF2.

MicroRNAs (miRNAs) play a critical role in cancer development and progression. Deregulated expression of miR-204 has been reported in several cancers, but the mechanism through which miR-204 modulates human non-small cell lung cancer (NSCLC) is largely unknown. In this study, we investigate the expression and functional role of miR-204 in human NSCLC tissues and cell lines. RNA isolation, qRT-PCR, MTT, colony formation assay, cell cycle assay, cell apoptosis assay, cell migration assay, and Western blot were performed. Statistical analysis was performed using SPSS 18.0 software and statistical significance was accepted at p value <0.05. miR-204 level was significantly reduced in NSCLC tissues as compared to that of non-neoplastic tissues. Transient over-expression of miR-204 by transfecting with miR-204 mimics suppressed NSCLC cell proliferation, migration, and induced apoptosis and G1 arrest, whereas inhibition of miR-204 showed the converse effects. Additionally, activating transcription factor 2 (ATF2), an important transcription factor, was demonstrated as a potential target gene of miR-204. Subsequent investigations found a negative correlation between miR-204 level and ATF2 expression in NSCLC tissue samples. Moreover, we observed that miR-204 expression inversely affected endogenous ATF2 expression at both mRNA and protein levels in vitro. Taken together, miR-204 may act as a tumor suppressor by directly targeting ATF2 in NSCLC.