| 1. |
- Iglesias-Gato, Diego, et al.
(författare)
-
SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer
- 2014
-
Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 35:1, s. 24-33
-
Tidskriftsartikel (refereegranskat)abstract
- Anabolic signals such as androgens and the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis play an essential role in the normal development of the prostate but also in its malignant transformation. In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2) as mediator of the cross talk between androgens and GH signals in the prostate and its potential role as tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels assayed by immunohistochemistry are elevated in hormone therapy-naive localized prostatic adenocarcinoma in comparison with benign tissue. In contrast, however, castration-resistant bone metastases exhibit reduced levels of SOCS2 in comparison with localized or hormone naive, untreated metastatic tumors. In PCa cells, SOCS2 expression is induced by androgens through a mechanism that requires signal transducer and activator of transcription 5 protein (STAT5) and androgen receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF-1 in the prostate in response to GH. Our results suggest that the use of GH-signaling inhibitors could be of value as a complementary treatment for castration-resistant PCa. Summary: Androgen induced SOCS2 ubiquitin ligase expression and inhibited GH signaling as well as cell proliferation and invasion in PCa, whereas reduced SOCS2 was present in castration-resistant cases. GH-signaling inhibitors might be a complementary therapeutic option for advanced PCa.
|
|
| 2. |
- Lembrechts, Jonas J., et al.
(författare)
-
SoilTemp : A global database of near-surface temperature
- 2020
-
Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629
-
Tidskriftsartikel (refereegranskat)abstract
- Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
|
|
| 3. |
- Seipel, Amanda
(författare)
-
Ductal adenocarcinoma of the prostate : a morphological, immunohistochemical and genetic study
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ductal adenocarcinoma of the prostate (DAC) is the second most common prostate cancer subtype. Patients with DAC often present at an advanced clinicopathological stage, with or without metastases. Patients have a high rate of extraprostatic extension, seminal vesicle invasion, a shortened time to biochemical recurrence as well as regional and distant metastases. The diagnosis of DAC continues to challenge pathologists half a century after its discovery. Histologically, DAC is an adenocarcinoma with papillary, cribriform, glandular or mixed architecture. The epithelium is tall, columnar, pseudostratified and the nuclei elongated with high-grade features. Our aim was to characterize the entity of DAC by morphology, immunohistochemistry and genetic analyses to provide better understanding and tools for diagnosis. The prognostic significance of histopathological features of DAC were analyzed. Classic DAC shows tall, columnar, pseudostratified epithelium, elongated nuclei and papillary, glandular and/or cribriform architecture. The tumors may lack elongated nuclei or classical architecture and still have similar prognosis, which justifies their classification as DAC. However, cases with only stratified, high grade nuclei had better prognosis and should not be considered DAC. The reproducibility of the DAC diagnosis was evaluated among international experts on prostate pathology. The most useful diagnostic feature of DAC was papillary architecture while nuclear and cellular features were less important. The most common differential diagnoses to DAC included intraductal prostate cancer, acinar adenocarcinoma and high-grade PIN. The immunohistochemical profile of DAC showed overlap with staining patterns of acinar adenocarcinomas, but differences consistent with the more aggressive phenotype of DAC were noted, such as a higher expression of Ki-67, p53 and p16. The immunohistochemical profile of DAC was also compared with that of adenocarcinomas of non-prostatic origin. To diagnose the site of origin of metastases may be challenging as DAC resembles some other adenocarcinomas morphologically. The expression of cytokeratins and intestinal markers in DAC were not specific and may lead to diagnostic errors if not combined with prostate specific markers. In men with adenocarcinoma of unknown primary, the threshold for applying prostate specific immunomarkers should be low even when the morphology suggests a non-prostatic origin. The genetic profile of DAC was analyzed by sequencing and was found to be similar to that of advanced and/or metastatic acinar adenocarcinoma of the prostate. This can explain the aggressive behavior of this prostate cancer subtype and may also offer targets for future tailored therapies.
|
|
