Characterising the adipose-inflammatory microenvironment in male breast cancer
We examined the microenvironment of archival and contemporary cohorts of MBC, diagnosed 1940–1970 and 1998–2006, respectively, with two cohorts of, archival and contemporary gynaecomastia, diagnosed 1940–1979 and 1996–2011, respectively, serving as controls. We quantified adipocytes, crown-like structures (CLS) and the presence of CD8, α smooth muscle actin (αSMA) and CD68+ macrophages in both cohorts, and determined how these affected survival, in the contemporary MBC cohort. In both MBC cohorts, mean adipocyte diameter was larger in the distant stroma compared with stroma close to the ...
Source: Endocrine-Related Cancer - May 31, 2018 Category: Endocrinology Authors: Lees, T., Cullinane, A., Condon, A., Shabaan, A. M., Humphries, M. P., Speirs, V. Tags: Research Source Type: research

The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells
In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - May 31, 2018 Category: Endocrinology Authors: Verdelli, C., Forno, I., Morotti, A., Creo, P., Guarnieri, V., Scillitani, A., Cetani, F., Vicentini, L., Balza, G., Beretta, E., Ferrero, S., Vaira, V., Corbetta, S. Tags: Research Source Type: research

The role of IL-1B in breast cancer bone metastasis
Approximately 75% of patients with late-stage breast cancer will develop bone metastasis. This condition is currently considered incurable and patients’ life expectancy is limited to 2–3 years following diagnosis of bone involvement. Interleukin (IL)-1B is a pro-inflammatory cytokine whose expression in primary tumours has been identified as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In this review, we discuss how IL-1B from both the tumour cells and the tumour microenvironment influence growth of primary breast tumours, dissemination into the b...
Source: Endocrine-Related Cancer - May 31, 2018 Category: Endocrinology Authors: Tulotta, C., Ottewell, P. Tags: Review Source Type: research

Advances in adrenal tumors 2018
We present the academic output measured by active clinical trials and peer-reviewed published manuscripts. The most important and contributory manuscripts were summarized for each diagnostic entity, with a particular focus on manuscripts that describe translational research that have the potential to improve clinical care. Finally, we highlight the importance of collaborations in adrenal tumor research, which allowed for these recent advances and provide structures for future success in this scientific field. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - May 24, 2018 Category: Endocrinology Authors: Crona, J., Beuschlein, F., Pacak, K., Skogseid, B. Tags: Review Source Type: research

Chromatin reprogramming in breast cancer
Reprogramming of the chromatin landscape is a critical component to the transcriptional response in breast cancer. Effects of sex hormones such as estrogens and progesterone have been well described to have a critical impact on breast cancer proliferation. However, the complex network of the chromatin landscape, enhancer regions and mode of function of steroid receptors (SRs) and other transcription factors (TFs), is an intricate web of signaling and functional processes that is still largely misunderstood at the mechanistic level. In this review, we describe what is currently known about the dynamic interplay between TFs ...
Source: Endocrine-Related Cancer - May 24, 2018 Category: Endocrinology Authors: Swinstead, E. E., Paakinaho, V., Hager, G. L. Tags: Review Source Type: research

GREB1 isoforms regulate proliferation independent of ER{alpha} co-regulator activities in breast cancer
Activation of the transcription factor estrogen receptor α (ERα) and the subsequent regulation of estrogen-responsive genes play a crucial role in the development and progression of the majority of breast cancers. One gene target of ERα, growth regulation by estrogen in breast cancer 1 (GREB1), is associated with proliferation and regulation of ERα activity in estrogen-responsive breast cancer cells. The GREB1 gene encodes three distinct isoforms: GREB1a, GREB1b and GREB1c, whose molecular functions are largely unknown. Here, we investigate the role of these isoforms in regulation of ERα activ...
Source: Endocrine-Related Cancer - May 22, 2018 Category: Endocrinology Authors: Haines, C. N., Braunreiter, K. M., Mo, X. M., Burd, C. J. Tags: Research Source Type: research

Optimising endocrine therapy in postmenopausal women with advanced breast cancer
Hormone receptor-positive breast cancer is commonly treated with endocrine therapy (ET); however, over time, cancer cells can develop endocrine resistance. This review aims to document combination therapy and sequential therapy in the use of endocrine agents and targeted agents, by conducting two systematic searches using four databases: Cochrane Library, MEDLINE, EMBASE and Web of Science. A total of 26 studies that covered combination therapy were obtained and included for the review. Fourteen were phase III documenting combinations of mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), vascular end...
Source: Endocrine-Related Cancer - May 22, 2018 Category: Endocrinology Authors: Yau, T. H. L., Cheung, K.-L. Tags: Research Source Type: research

Cellular kinetics of MED12-mutant uterine leiomyoma growth and regression in vivo
Cellular mechanisms of uterine leiomyoma (LM) formation have been studied primarily utilizing in vitro models. However, recent studies established that the cells growing in the primary cultures of MED12-mutant LM (MED12-LM) do not carry causal mutations. To improve the accuracy of LM research, we addressed the cellular mechanisms of LM growth and regression utilizing a patient-derived xenograft (PDX) model, which faithfully replicates the patient tumors in situ. The growth and maintenance of MED12-LMs depend on 17β-estradiol (E2) and progesterone (P4). We determined E2 and P4-activated MAPK and PI3K pathways in PDXs w...
Source: Endocrine-Related Cancer - May 21, 2018 Category: Endocrinology Authors: Serna, V. A., Wu, X., Qiang, W., Thomas, J., Blumenfeld, M. L., Kurita, T. Tags: Research Source Type: research

TERT aberrancies: a screening tool for malignancy in follicular thyroid tumours
Telomerase reverse transcriptase (TERT) promoter mutations have been linked to adverse clinical parameters in thyroid cancer, but TERT-expressing tumours are not always mutated. Little is known regarding other TERT-related genetic aberrations. To delineate the role of TERT gene aberrancies in follicular thyroid tumours, 95 follicular carcinomas (FTCs), 43 follicular adenomas (FTAs) and 33 follicular tumours of uncertain malignant potential (FT-UMPs) were collected. The tumours were assayed for TERT expression, TERT promoter mutations, TERT promoter hypermethylation and TERT gene copy number (CN) alterations and the results...
Source: Endocrine-Related Cancer - May 21, 2018 Category: Endocrinology Authors: Paulsson, J. O., Mu, N., Shabo, I., Wang, N., Zedenius, J., Larsson, C., Juhlin, C. C. Tags: Research Source Type: research

Prolonged duration of response in lenvatinib responders with thyroid cancer
We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib respond...
Source: Endocrine-Related Cancer - May 11, 2018 Category: Endocrinology Authors: Gianoukakis, A. G., Dutcus, C. E., Batty, N., Guo, M., Baig, M. Tags: Research Source Type: research

Open issues on G3 neuroendocrine neoplasms: back to the future
The recent recognition that grade 3 (G3) neuroendocrine neoplasms (NENs) can be divided into two different categories according to the histopathological differentiation, that is G3 neuroendocrine tumors (NETs) and G3 neuroendocrine carcinomas (NECs) has generated a lot of interest concerning not only the diagnosis, but also the differential management of such new group of NENs. However, several issues need to be fully clarified in order to put G3 NETs and G3 NECs in the right place. The aim of this review is to focus on those issues that are still undetermined starting from the current knowledge, evaluating the available e...
Source: Endocrine-Related Cancer - May 11, 2018 Category: Endocrinology Authors: Zatelli, M. C., Guadagno, E., Messina, E., Lo Calzo, F., Faggiano, A., Colao, A., NIKE Group Tags: Review Source Type: research

The endocrinology of male breast cancer
Male breast cancer (MBC) is a rare disease but, as a result of epidemiological collaborations, there is now greater clarity concerning endocrine risk factors. The significant rise in global age-standardised mean BMI in men is likely to lead to increases in incidence of maturity-onset diabetes and MBC. The metabolic changes accompanying obesity decrease androgens and sex hormone-binding globulin (SHBG), thereby increasing available oestrogens. The higher rates of MBC in North and Equatorial Africa are largely due to liver damage from endemic bilharziasis and hepatitis B causing elevated oestradiol (E2) levels from hepatic c...
Source: Endocrine-Related Cancer - May 11, 2018 Category: Endocrinology Authors: Fentiman, I. S. Tags: Review Source Type: research

Impact of hormone receptor status on the efficacy of HER2-targeted treatment
The introduction of human epidermal growth factor receptor 2 (HER2)–targeted drugs into routine clinical practice has a dramatic effect on the outlook for patients with HER2-positive breast cancer (BC). However, the association between efficacy of HER2-targeted therapy and hormone receptor (HR) status is still unclear. Here we conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue in both neoadjuvant and adjuvant settings. PubMed and EMBASE were searched from inception to October 2017 for studies involving trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine and neratinib. Efficac...
Source: Endocrine-Related Cancer - May 8, 2018 Category: Endocrinology Authors: Zhao, B., Zhao, H., Zhao, J. Tags: Research Source Type: research

Pasireotide in the treatment of neuroendocrine tumors: a review of the literature
Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical rel...
Source: Endocrine-Related Cancer - May 8, 2018 Category: Endocrinology Authors: Vitale, G., Dicitore, A., Sciammarella, C., Di Molfetta, S., Rubino, M., Faggiano, A., Colao, A. Tags: Review Source Type: research

Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model
In conclusion, CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on neoplasm progression in patients with NENs, mainly in those treated with mTORi, are warranted. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - May 3, 2018 Category: Endocrinology Authors: Avniel-Polak, S., Leibowitz, G., Doviner, V., Gross, D. J., Grozinsky-Glasberg, S. Tags: Research Source Type: research

Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity
We describe that high PTTG protein levels are induced by the RWD-containing sumoylation enhancer (RWDD3 or RSUME), a protein originally identified in the same pituitary tumor cell line in which PTTG was also cloned. We demonstrate that PTTG and RSUME have a positive expression correlation in human pituitary adenomas. RSUME increases PTTG protein in pituitary tumor cell lines, prolongs the half-life of PTTG protein and regulates the PTTG induction by estradiol. As a consequence, RSUME enhances PTTG transcription factor and securin activities. PTTG hyperactivity on the cell cycle resulted in recurrent and unequal divisions w...
Source: Endocrine-Related Cancer - May 2, 2018 Category: Endocrinology Authors: Fuertes, M., Sapochnik, M., Tedesco, L., Senin, S., Attorresi, A., Ajler, P., Carrizo, G., Cervio, A., Sevlever, G., Bonfiglio, J. J., Stalla, G. K., Arzt, E. Tags: Research Source Type: research

PET response assessment in apatinib-treated radioactive iodine-refractory thyroid cancer
This work evaluated the use of the positron emission tomography (PET)/computed tomography (CT) technique to assess the early therapeutic response and predict the prognosis of patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) who underwent apatinib therapy. Standardised uptake value (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), derived from 18F-FDG PET/CT and SUV from 68Ga-NOTA-PRGD2 PET/CT were evaluated. Tumour response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Sixteen of 20 patients achieved partial response (PR) and fou...
Source: Endocrine-Related Cancer - April 27, 2018 Category: Endocrinology Authors: Wang, C., Zhang, X., Yang, X., Li, H., Cui, R., Guan, W., Li, X., Zhu, Z., Lin, Y. Tags: Research Source Type: research

Androgen receptor moonlighting in the prostate cancer microenvironment
Androgen receptor (AR) signaling is vital for the normal development of the prostate and is critically involved in prostate cancer (PCa). AR is not only found in epithelial prostate cells but is also expressed in various cells in the PCa-associated stroma, which constitute the tumor microenvironment (TME). In the TME, AR is expressed in fibroblasts, macrophages, lymphocytes and neutrophils. AR expression in the TME was shown to be decreased in higher-grade and metastatic PCa, suggesting that stromal AR plays a protective role against PCa progression. With that, the functionality of AR in stromal cells appears to deviate fr...
Source: Endocrine-Related Cancer - April 27, 2018 Category: Endocrinology Authors: Cioni, B., Zwart, W., Bergman, A. M. Tags: Review Source Type: research

Diagnostic performance of PET in thyroid cancer with elevated anti-Tg Ab
We aimed to explore the role of the diagnostic accuracy of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for the detection of recurrent and/or metastatic diseases in differentiated thyroid cancer (DTC) patients with progressively and/or persistently elevated TgAb levels and negative radioactive iodine whole-body scan (RI-WBS) through a systematic review and meta-analysis. The MEDLINE, EMBASE and Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for the detection...
Source: Endocrine-Related Cancer - April 26, 2018 Category: Endocrinology Authors: Kim, S.-J., Lee, S.-W., Pak, K., Shim, S.-R. Tags: Research Source Type: research

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors
This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (trai...
Source: Endocrine-Related Cancer - April 25, 2018 Category: Endocrinology Authors: Pusceddu, S., Barretta, F., Trama, A., Botta, L., Milione, M., Buzzoni, R., De Braud, F., Mazzaferro, V., Pastorino, U., Seregni, E., Mariani, L., Gatta, G., Di Bartolomeo, M., Femia, D., Prinzi, N., Coppa, J., Panzuto, F., Antonuzzo, L., Bajetta, E., Bri Tags: Research Source Type: research

Clinical significance of RET and RAS mutations in sporadic medullary thyroid carcinoma: a meta-analysis
In this study, we aimed at investigating the prognostic value of RET and RAS mutations – the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Relevant data were extracted and pooled into odds ratios (OR), mean differences (MD) and corresponding 95% confidence intervals (CI) using the random-effect model. We used Egger’s regression test and visual of funnel plots to assess the publication bias. From 2581 studies, we included 23 studies with 964 MTCs for meta-analysis. Overall, the presence of RET mutation was associated with an elevated risk for lymph node metastas...
Source: Endocrine-Related Cancer - April 24, 2018 Category: Endocrinology Authors: Vuong, H. G., Odate, T., Ngo, H. T. T., Pham, T. Q., Tran, T. T. K., Mochizuki, K., Nakazawa, T., Katoh, R., Kondo, T. Tags: Research Source Type: research

Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs
Pancreatic neuroendocrine tumors (PanNETs) have considerable malignant potential. Frequent somatic mutations and loss of DAXX protein expression have been found in PanNETs. DAXX is known as a transcriptional repressor; however, molecular functions underlying DAXX loss remain unclear in PanNETs. We evaluated DAXX expression by immunohistochemistry in 44 PanNETs. DAXX-knockdown (KD) and -knockout (KO) PanNET cells were analyzed for in vitro and vivo. The target genes were screened by microarray and chromatin immunoprecipitation (ChIP) assays for DAXX, histone H3.3 and H3K9me3 complex. In clinicopathological features, low DAX...
Source: Endocrine-Related Cancer - April 24, 2018 Category: Endocrinology Authors: Ueda, H., Akiyama, Y., Shimada, S., Mogushi, K., Serizawa, M., Matsumura, S., Mitsunori, Y., Aihara, A., Ban, D., Ochiai, T., Kudo, A., Tanabe, M., Tanaka, S. Tags: Research Source Type: research

Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy
In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER– breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER– breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy resp...
Source: Endocrine-Related Cancer - April 24, 2018 Category: Endocrinology Authors: Chen, Y.-Z., Kim, Y., Soliman, H. H., Ying, G., Lee, J. K. Tags: Research Source Type: research

Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis
Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC) neoplastic epithelial component, each representing at least 30% of the tumor. At present, prognostic factors for MANECs remain largely unexplored. We investigated the clinical-pathologic features of a large multicenter series of digestive system MANECs. Surgical specimens of 200 MANEC candidates were centrally reviewed; diagnosis was confirmed in 160 cases. While morphology, proliferation (mitotic count (MC), Ki67 index) and immunophenotype (p53, SSTR2a, beta-Catenin, Bcl-2...
Source: Endocrine-Related Cancer - April 19, 2018 Category: Endocrinology Authors: Milione, M., Maisonneuve, P., Pellegrinelli, A., Grillo, F., Albarello, L., Spaggiari, P., Vanoli, A., Tagliabue, G., Pisa, E., Messerini, L., Centonze, G., Inzani, F., Scarpa, A., Papotti, M., Volante, M., Sessa, F., Fazio, N., Pruneri, G., Rindi, G., So Tags: Research Source Type: research

Periprostatic fat tissue transcriptome reveals a signature diagnostic for high-risk prostate cancer
In this study, we investigated the adipose transcriptional profiles of low- and high-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue from patients categorised as having prostate cancer with either a low or high risk of progression based on tumour characteristics at prostatectomy and profiled by RNA sequencing. The expression of selected genes was then quantified by qRT-PCR in a cross-validation cohort. In the first phase, a total of 677 differentially transcribed genes were identified, from which a subset of 14 ge...
Source: Endocrine-Related Cancer - April 19, 2018 Category: Endocrinology Authors: Mangiola, S., Stuchbery, R., Macintyre, G., Clarkson, M. J., Peters, J. S., Costello, A. J., Hovens, C. M., Corcoran, N. M. Tags: Research Source Type: research

Obesity suppresses tumor attributable PSA, affecting risk categorization
In conclusion, being very obese suppresses tumor-associated PSA resulting in a diagnostic bias that is responsible for errors in risk classification, and potentially contributes to a delay in initial presentation. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - April 16, 2018 Category: Endocrinology Authors: Chow, K., Mangiola, S., Vazirani, J., Peters, J. S., Costello, A. J., Hovens, C. M., Corcoran, N. M. Tags: Research Source Type: research

Tropomyosin receptor kinase: a novel target in screened neuroendocrine tumors
Tropomyosin receptor kinase (Trk) inhibitors are investigated as a novel targeted therapy in various cancers. We investigated the in vitro effects of the pan-Trk inhibitor GNF-5837 in human neuroendocrine tumor (NET) cells. The human neuroendocrine pancreatic BON1, bronchopulmonary NCI-H727 and ileal GOT1 cell lines were treated with GNF-5837 alone and in combination with everolimus. Cell viability decreased in a time- and dose-dependent manner in GOT1 cells in response to GNF-5837 treatment, while treatment in BON1 and NCI-H727 cells showed no effect on cellular viability. Trk receptor expression determined GNF-5837 sensi...
Source: Endocrine-Related Cancer - April 16, 2018 Category: Endocrinology Authors: Aristizabal Prada, E. T., Heinzle, V., Knosel, T., Nolting, S., Spottl, G., Maurer, J., Spitzweg, C., Angele, M., Schmidt, N., Beuschlein, F., Stalla, G. K., Blaser, R., Kuhn, K. A., Auernhammer, C. J. Tags: Research Source Type: research

The challenges of modeling hormone receptor-positive breast cancer in mice
Estrogen receptor-positive (ER+) tumors account for 70–80% of all breast cancer (BC) cases and are characterized by estrogen dependency for their growth. Endocrine therapies using estrogen receptor antagonists or aromatase inhibitors represent a key component of the standard of care for these tumors. The occurrence of de novo or acquired resistance to estrogen withdrawal represents an important clinical problem, impacting on patient survival. In addition, despite an initially favorable outcome, a part of ER+ BC patients present with disease recurrence locally or at distant sites years or even decades after apparent r...
Source: Endocrine-Related Cancer - April 9, 2018 Category: Endocrinology Authors: Ozdemir, B. C., Sflomos, G., Brisken, C. Tags: Review Source Type: research

Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells
In this study, we examined the mechanism by which T4 impairs resveratrol-induced antiproliferation in human ovarian cancer cells and found that T4 inhibited resveratrol-induced nuclear accumulation of COX-2. Furthermore, T4 increased expression and cytoplasmic accumulation of PD-L1, which in turn acted to retain inducible COX-2 in the cytoplasm. Knockdown of PD-L1 by small hairpin RNA (shRNA) relieved the inhibitory effect of T4 on resveratrol-induced nuclear accumulation of COX-2- and COX-2/p53-dependent gene expression. Thus, T4 inhibits COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with ...
Source: Endocrine-Related Cancer - April 5, 2018 Category: Endocrinology Authors: Chin, Y.-T., Wei, P.-L., Ho, Y., Nana, A. W., Changou, C. A., Chen, Y.-R., Yang, Y.-C. S., Hsieh, M.-T., Hercbergs, A., Davis, P. J., Shih, Y.-J., Lin, H.-Y. Tags: Research Source Type: research

Biomarkers of platinum resistance in ovarian cancer: what can we use to improve treatment
Ovarian cancer has poor survival rates due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High-grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60–80%, but eventually the majority of patients become platinum-resistant with subsequent relapses. Extensive research on individual biomarkers of platinum resistance has revealed many potential targets for the development new treatments. While this i...
Source: Endocrine-Related Cancer - March 29, 2018 Category: Endocrinology Authors: van Zyl, B., Tang, D., Bowden, N. A. Tags: Review Source Type: research

Pheochromocytomas and pituitary adenomas in three patients with MAX exon deletions
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - March 29, 2018 Category: Endocrinology Authors: Daly, A. F., Castermans, E., Oudijk, L., Guitelman, M. A., Beckers, P., Potorac, I., Neggers, S. J. C. M. M., Sacre, N., van der Lely, A.-J., Bours, V., de Herder, W. W., Beckers, A. Tags: Research Letter Source Type: research

Acquired resistance to aromatase inhibitors: where we stand!
Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen receptor-positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired resistance may develop, leading to tumour relapse. This resistance is thought to be the result of a change in the behaviour of ER in these breast cancer cells, presumably by PI3K/AKT pathway enhancement along with alterations in other signalling pathways. Nevertheless, biological mechanisms, such as apoptosis...
Source: Endocrine-Related Cancer - March 28, 2018 Category: Endocrinology Authors: Augusto, T. V., Correia-da-Silva, G., Rodrigues, C. M. P., Teixeira, N., Amaral, C. Tags: Review Source Type: research

Immune landscape of papillary thyroid cancer and immunotherapeutic implications
Although papillary thyroid cancer (PTC) is curable with excellent survival rate, patients with dedifferentiated PTC suffer the recurrence or death. As cancer immune escape plays a critical role in cancer progression, we aimed to investigate the relationship between differentiation and immune landscape of PTC and its implications for immunotherapy. Using The Cancer Genome Atlas data, we estimated the immune cell enrichment scores and overall immune infiltration, ImmuneScore, to characterize the immune landscape of PTC. Thyroid differentiation score (TDS) was calculated from 16 thyroid function genes. We demonstrated that Im...
Source: Endocrine-Related Cancer - March 20, 2018 Category: Endocrinology Authors: Na, K. J., Choi, H. Tags: Research Source Type: research

Time-varying effects of prognostic factors associated with long-term survival in breast cancer
The impact of some prognostic factors on breast cancer survival has been shown to vary with time since diagnosis. However, this phenomenon has not been evaluated in Asians. In the present study, 4886 patients were recruited from the Shanghai Breast Cancer Survival Study, a longitudinal study of patients diagnosed during 2002–2006, with a median follow-up time of 11.2 years. Cox model incorporating time-by-covariate interactions was used to describe the time-varying effects of prognostic factors related to overall survival and disease-free survival. Age ≥65 years showed a progressively negative effect on breast can...
Source: Endocrine-Related Cancer - March 20, 2018 Category: Endocrinology Authors: Zhang, M., Peng, P., Gu, K., Cai, H., Qin, G., Shu, X. O., Bao, P. Tags: Research Source Type: research

Frequency and consequence of the recurrent YY1 p.T372R mutation in sporadic insulinomas
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - March 20, 2018 Category: Endocrinology Authors: Parekh, V. I., Modali, S. D., Welch, J., Simonds, W. F., Weinstein, L. S., Kebebew, E., Agarwal, S. K. Tags: Research Letter Source Type: research

Attenuation of NK cells facilitates mammary tumor growth in streptozotocin-induced diabetes in mice
Diabetic patients have higher incidence and mortality of cancer. Recent study revealed that hyperglycemia-induced oxidative stress is involved in the acceleration of tumor metastasis. We used model of high-dose streptozotocin-induced diabetes to investigate its effect on tumor growth and modulation of antitumor immune response of 4T1 murine breast cancer in BALB/c mice. Diabetes accelerated tumor appearance, growth and weight, which was associated with decreased NK cells cytotoxicity against 4T1 tumor cells in vitro. Diabetes reduced frequencies of systemic NKG2D+, perforin+, granzyme+, IFN-+ and IL-17+ NK cells, while inc...
Source: Endocrine-Related Cancer - March 14, 2018 Category: Endocrinology Authors: Gajovic, N., Jurisevic, M., Pantic, J., Radosavljevic, G., Arsenijevic, N., Lukic, M. L., Jovanovic, I. Tags: Research Source Type: research

Role of biomarkers in predicting the occurrence of thyroid neoplasms in radiation-exposed children
With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation-exposed children. 764 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At baseline, 216 subj...
Source: Endocrine-Related Cancer - March 14, 2018 Category: Endocrinology Authors: Shulan, J. M., Vydro, L., Schneider, A. B., Mihailescu, D. V. Tags: Research Source Type: research

The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - March 14, 2018 Category: Endocrinology Authors: Hofving, T., Arvidsson, Y., Almobarak, B., Inge, L., Pfragner, R., Persson, M., Stenman, G., Kristiansson, E., Johanson, V., Nilsson, O. Tags: Erratum Source Type: research

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers
The human genome is ‘pervasively transcribed’ leading to a complex array of non-coding RNAs (ncRNAs) that far outnumber coding mRNAs. ncRNAs have regulatory roles in transcription and post-transcriptional processes as well numerous cellular functions that remain to be fully described. Best characterized of the ‘expanding universe’ of ncRNAs are the ~22 nucleotide microRNAs (miRNAs) that base-pair to target mRNA’s 3' untranslated region within the RNA-induced silencing complex (RISC) and block translation and may stimulate mRNA transcript degradation. Long non-coding RNAs (lncRNAs) are classifi...
Source: Endocrine-Related Cancer - March 8, 2018 Category: Endocrinology Authors: Klinge, C. M. Tags: Review Source Type: research

Ex vivo activity of cytotoxic drugs and targeted agents in small intestinal neuroendocrine tumors
Small intestinal neuroendocrine tumors (SI-NETs) are generally considered resistant to systemic treatment. To date, predictive markers for drug activity are lacking. Tumor samples from 27 patients with SI-NETs were analyzed ex vivo for sensitivity to a panel of cytotoxic drugs and targeted agents using a short-term total cell kill assay. Samples of renal cancer, colorectal cancer (CRC), ovarian cancer and chronic lymphocytic leukemia (CLL) were included for comparison. For the SI-NET subset, drug sensitivity was analyzed in relation to clinicopathological variables and pre-treatment biomarkers. For cytotoxic drugs, SI-NETs...
Source: Endocrine-Related Cancer - March 2, 2018 Category: Endocrinology Authors: Daskalakis, K., Norlen, O., Karakatsanis, A., Hellman, P., Larsson, R., Nygren, P., Stalberg, P. Tags: Research Source Type: research

GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling
Despite altered metabolism being an accepted hallmark of cancer, it is still not completely understood which signaling pathways regulate these processes. Given the central role of androgen receptor (AR) signaling in prostate cancer, we hypothesized that AR could promote prostate cancer cell growth in part through increasing glucose uptake via the expression of distinct glucose transporters. Here, we determined that AR directly increased the expression of SLC2A12, the gene that encodes the glucose transporter GLUT12. In support of these findings, gene signatures of AR activity correlated with SLC2A12 expression in multiple ...
Source: Endocrine-Related Cancer - February 27, 2018 Category: Endocrinology Authors: White, M. A., Tsouko, E., Lin, C., Rajapakshe, K., Spencer, J. M., Wilkenfeld, S. R., Vakili, S. S., Pulliam, T. L., Awad, D., Nikolos, F., Katreddy, R. R., Kaipparettu, B. A., Sreekumar, A., Zhang, X., Cheung, E., Coarfa, C., Frigo, D. E. Tags: Research Source Type: research

Development of new preclinical models to advance adrenocortical carcinoma research
Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly cancer with 35% survival at five years. Our understanding of the underlying pathobiology and our ability to test novel therapeutic targets has been limited due to the lack of preclinical models. Here, we report the establishment of two new ACC cell lines and corresponding patient-derived xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric metastasis in a patient whose primary tumor secreted aldosterone. CU-ACC2 cell line...
Source: Endocrine-Related Cancer - February 27, 2018 Category: Endocrinology Authors: Kiseljak-Vassiliades, K., Zhang, Y., Bagby, S. M., Kar, A., Pozdeyev, N., Xu, M., Gowan, K., Sharma, V., Raeburn, C. D., Albuja-Cruz, M., Jones, K. L., Fishbein, L., Schweppe, R. E., Somerset, H., Pitts, T. M., Leong, S., Wierman, M. E. Tags: Research Source Type: research

Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course
The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which suggests the involvement of additional modulators of the disease. However, genetic factors responsible for this heterogeneity of the MTC clinical course still remain unknown. The aim of this study was to determine if polymorphic variants or specific haplotypes of the RET gene may modify the MTC clinical course....
Source: Endocrine-Related Cancer - February 27, 2018 Category: Endocrinology Authors: Kaczmarek-Ryś, M., Ziemnicka, K., Pławski, A., Budny, B., Michalak, M., Hryhorowicz, S., Hoppe-Gołębiewska, J., Boruł, P., Gołąb, M., Czetwertyłska, M., Sromek, M., Szalata, M., Ruchała, M., S Tags: Research Source Type: research

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): impact on the reclassification of thyroid nodules
The 2017 edition of the WHO book on Classification of Tumours of Endocrine Organs includes a new section entitled ‘Other encapsulated follicular-patterned thyroid tumours’, in which the newly created NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features) is identified and described in detail. Despite deleting the word ‘carcinoma’ from its name, NIFTP is not a benign tumor either and is best regarded as a neoplasm with ‘very low malignant potential’. The main goal of the introduction of NIFTP category is to prevent overdiagnosis and overtreatment. Sampling c...
Source: Endocrine-Related Cancer - February 27, 2018 Category: Endocrinology Authors: Amendoeira, I., Maia, T., Sobrinho-Simoes, M. Tags: Review Source Type: research

Transcriptional profiling reveals distinct classes of parathyroid tumors in PHPT
The clinical presentation of primary hyperparathyroidism (PHPT) varies widely, although the underlying mechanistic reasons for this disparity remain unknown. We recently reported that parathyroid tumors can be functionally segregated into two distinct groups on the basis of their relative responsiveness to ambient calcium, and that patients in these groups differ significantly in their likelihood of manifesting bone disability. To examine the molecular basis for this phenotypic variation in PHPT, we compared the global gene expression profiles of calcium-sensitive and calcium-resistant parathyroid tumors. RNAseq and proteo...
Source: Endocrine-Related Cancer - February 23, 2018 Category: Endocrinology Authors: Koh, J., Hogue, J. A., Roman, S. A., Scheri, R. P., Fradin, H., Corcoran, D. L., Sosa, J. A. Tags: Research Source Type: research

Geographic epidemiology of medullary thyroid cancer families: unearthing European ancestral heritage
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 23, 2018 Category: Endocrinology Authors: Machens, A., Lorenz, K., Weber, F., Dralle, H. Tags: Research Letter Source Type: research

HSD17B1 expression induces inflammation-aided rupture of mammary gland myoepithelium
Hydroxysteroid (17-beta) dehydrogenase type 1 (HSD17B1) converts low-active estrogen estrone to highly active estradiol. Estradiol is necessary for normal postpubertal mammary gland development; however, elevated estradiol levels increase mammary tumorigenesis. To investigate the significance of the human HSD17B1 enzyme in the mammary gland, transgenic mice universally overexpressing human HSD17B1 were used (HSD17B1TG mice). Mammary glands obtained from HSD17B1TG females at different ages were investigated for morphology and histology, and HSD17B1 activity and estrogen receptor activation in mammary gland tissue were asses...
Source: Endocrine-Related Cancer - February 21, 2018 Category: Endocrinology Authors: Jarvensivu, P., Heinosalo, T., Hakkarainen, J., Kronqvist, P., Saarinen, N., Poutanen, M. Tags: Research Source Type: research

The impact of 27-hydroxycholesterol on endometrial cancer proliferation
Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC (n = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs (NR1H3, LXRα; NR1H2, LXRβ) and enzymes required for the synth...
Source: Endocrine-Related Cancer - February 21, 2018 Category: Endocrinology Authors: Gibson, D. A., Collins, F., Cousins, F. L., Esnal Zufiaurre, A., Saunders, P. T. K. Tags: Research Source Type: research

Role of iodide metabolism in physiology and cancer
Iodide (I–) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I– is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I– recycling. New research supports the exci...
Source: Endocrine-Related Cancer - February 21, 2018 Category: Endocrinology Authors: De la Vieja, A., Santisteban, P. Tags: Review Source Type: research

Treatment of refractory thyroid cancer
Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - February 21, 2018 Category: Endocrinology Authors: Berdelou, A., Lamartina, L., Klain, M., Leboulleux, S., Schlumberger, M., on behalf of the TUTHTYREF Network Tags: Review Source Type: research