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
In conclusion, in radiation-exposed children, higher thyroglobulin levels indicated an increased risk of developing thyroid nodules but did not differentiate between benign and malignant neoplasms. There was no association between the baseline TSH level and the risk of developing thyroid nodules or cancer. (Source: Endocrine-Related Cancer)
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
