Fine needle aspiration biopsy does not permit to distinguish between benign and malignant follicular thyroid lesions (category IV in the Bethesda Cytopathology System). Some reports have suggested an association between increased serum TSH levels and thyroid cancer, so the aim of this study was to investigate the association between TSH levels and malignancy in patients with follicular thyroid nodules. Therefore, we conducted a retrospective study of all subjects who underwent surgical treatment for Bethesda IV thyroid nodules in a single center (years 2012-2017). A total of 127 patients were analyzed, and malignancy was present in 38.6% of the patients. Using ROC analysis, the best TSH cut-off point to differentiate benign from malignant disease was 2.1mU/l and the age cut-off with better sensitivity and specificity was 47years. The proportion of subjects with TSH ≥ 2.1mU/l was greater among subjects with cancer than in those with benign diseases (65.3 vs 44.9%, P = 0.029). The concurrence of both cut-off points (TSH ≥ 2.1mU/l and age ≥ 47years) showed a higher diagnostic accuracy than either of the two variables separately. Therefore, the present study supports an association between serum concentrations of TSH and risk of malignancy among subjects with Bethesda IV thyroid nodules. TSH levels could modify the diagnostic and therapeutic approach of patients with Bethesda IV nodules.

Glioblastomas (GBM) are the most frequent and aggressive primary tumor of the central nervous system. In recent years, it has been proposed that sex hormones such as progesterone play an essential role in GBM biology. Membrane progesterone receptors (mPRs) are a group of G protein-coupled receptors with a wide distribution and multiple functions in the organism. There are five mPRs subtypes described in humans: mPRα, mPRβ, mPRγ, mPRδ, and mPRε. It has been reported that human-derived GBM cells express the mPRα, mPRβ, and mPRγ subtypes, and that progesterone promotes GBM progression in part by mPRα specific activation; however, it is still unknown if mPRδ and mPRε are also expressed in this type of tumor cells. In this study, we characterized the expression and hormonal regulation of mPRδ and mPRε in human GBM cells. We also analyzed a set of biopsies from TCGA. We found that the expression of these receptors is dependent on the tumor's grade and that mPRδ expression is directly correlated to patients' survival while the opposite is observed for mPRε. By RT-qPCR, Western blot, and immunofluorescence, the expression of mPRδ and mPRε was detected for the first time in human GBM cells. An in silico analysis showed possible progesterone response elements in the promoter regions of mPRδ and mPRε, and progesterone treatments downregulated the expression of these receptors. Our results suggest that mPRδ and mPRε are expressed in human GBM cells and that they are relevant to GBM biology.

In hepatocellular carcinoma (HCC), the hypoxic tumor microenvironment can drive enhance tumor malignancy and recurrence. The microRNA (miRNA) miR-196-5p has been shown to modulate the progression of several cancer types, but its roles in HCC remain uncertain. In the present report we observed significant miR-196-5p downregulation in HCC tissues and cells, and we found that the expression of this miRNA significantly impaired the proliferation and metastatic potential of HCC in vitro and in vivo. We identified high-mobility group AT-hook 2 (HMGA2) as a miR-196-5p target gene that was associated with the ability of miR-196-5p to modulate the progression of HCC. Expression of miR-196-5p and HMGA2 were correlated with the clinical characteristics and poor outcomes in patients with HCC. Finally, we found that hypoxic conditions were linked with reduced miR-196-5p expression in the context of HCC. Together these results highlight the role for miR-196-5p as an inhibitor of the proliferation and metastasis of HCC via the targeting of HMGA2, with this novel hypoxia/miR-196-5p/HMGA2 pathway serving as a potential target for future therapeutic intervention.

Pregnancy has a dual effect on the risk of breast cancer. On one hand, pregnancy at a young age is known to be protective. However, pregnancy is also associated with a transient increased risk of breast cancer. For women that have children after the age of 30, the risk remains higher than women who never had children for decades. Involution of the breast has been identified as a window of mammary development associated with the adverse effect of pregnancy. In this review, we summarize the current understanding of the role of involution and describe the role of collagen in this setting. We also discuss the role of a collagen-dependent protease, pappalysin-1, in postpartum breast cancer and its role in activating both insulin-like growth factor signaling and discoidin domain collagen receptor 2, DDR2. Together, these novel advances in our understanding of postpartum breast cancer open the way to targeted therapies against this aggressive breast cancer sub-type.

The study aimed to determine whether 25-OH vitamin D3 deficiency is present in patients with diagnosed BCC, and the effect of vitamin D replacement on the rates of BCC recurrence in patients with 25-OH vitamin D3 deficiency. In this prospective study, between 2012 and 2017, in the first stage, 25-OH vitamin D3 levels of all patients diagnosed with BCC between 2012 and 2013 were evaluated. In the second stage between 2014 and 2015, we evaluated the 25-OH vitamin D3 level of patients who had 25-OH vitamin D3 level < 25 ng/mL. All the patients included in the second stage had BCC recurrence. In the third stage, the patients who were diagnosed 25-OH vitamin D3 deficiency with BCC, between 2015 and 2017, were studied. The mean 25-OH vitamin D3 level of the patients in the second stage was 10.12 ng/mL. Recurrence was observed in 9.64% of the patients in the second stage. The mean level of serum 25-OH vitamin D3 in the third stage was 40.1 ng/mL, and 3.49% of these patients presented with recurrence. In all the patients as the initial diagnosis and following the 25-OH vitamin D3 level in all the patients with BCC recurrence, maintaining 25-OH vitamin D3 levels above 25 ng/mL can significantly reduce the recurrence rate.

The purpose of the current study was to investigate the diagnostic performance of F-18 Fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for localization of hyperfunctioning parathyroid gland in patients with hyperparathyroidism (HPT) through a systematic review and meta-analysis. The MEDLINE/PubMed and EMBASE database, from the earliest available date of indexing through April 30, 2018, were searched for studies evaluating the diagnostic performance of F-18 FCH PET/CT for localization of hyperfunctioning parathyroid gland in patients with HPT. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. Across eight studies (272 patients), the pooled sensitivity for F-18 FCH PET/CT was 0.90 (95% CI, 0.86-0.94) without heterogeneity (I2= 7.1) and a pooled specificity of 0.94 (95% CI, 0.90-0.96) with heterogeneity (I2= 79.8). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.3 (95% CI, 1.2-24.3) and negative likelihood ratio (LR-) of 0.15 (95% CI, 0.08-0.29). The pooled diagnostic odds ratio (DOR) was 38 (95% CI, 8-174). Hierarchical summary receiver operating characteristic (ROC) curve indicates that the areas under the curve were 0.9492 (SE, 0.0215). In meta-regression analysis, no definite variable was the source of the study heterogeneity. The current meta-analysis showed the high sensitivity and specificity of F-18 FCH PET/CT for localization of hyperfunctioning parathyroid gland. At present, the literature regarding the use of F-18 FCH PET/CT for localization of hyperfunctioning parathyroid gland remains still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of F-18 FCH PET/for localization of hyperfunctioning parathyroid gland in patients with HPT.

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000IU vitamin D3 supplements (n=29) or placebo (n=29) every 2weeks for 6months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P=0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3±11.4 vs. -0.1±3.7ng/mL, P<0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3±7.3 vs. +2.4±5.9 μIU/mL, P<0.001), homeostasis model of assessment-insulin resistance (-1.2±1.6 vs. +0.5±1.2, P<0.001), homeostatic model assessment-Beta cell function (P=0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03±0.04 vs. -0.007±0.02, P<0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5±10.3 vs. +4.0±13.4μmol/L, P=0.001), total antioxidant capacity (TAC) (P=0.04), total glutathione (GSH) (+11.8±153.5 vs. -294.2±595.1μmol/L, P=0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8±1.0 vs. -0.03±1.4μmol/L, P=0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels. Clinical trial registration number www.irct.ir : IRCT201412065623N30.

Systems that model cancer form the backbone of research discovery, and their accuracy and validity are a key determinant to ensure successful translation. In many tumour types, patient-derived specimens are an important model of choice for pre-clinical drug development. In this review, we consider why this has been such a challenge for prostate cancer, resulting in relatively few patient-derived xenografts (PDXs) of prostatic tumours compared to breast cancers, for example. Nevertheless, with only a few patient specimens and PDXs, we exemplify in three vignettes how important new clinical insights were obtained resulting in benefit for future men with prostate cancer.

Significant progress has been made in the understanding of how surgical technique impacts outcome in patients with adrenal cancer. Current and future areas of investigation center on expanding the role of surgery in patients with locally recurrent or metastatic disease, use of neoadjuvant therapy as a bridge to surgery, the impact of formal lymphadenectomy on survival, and improved diagnosis, prognosis, and selection of patients for surgery and other treatments using morphomic analysis.