Future treatment strategies of aggressive pituitary tumors

While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR5) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing’s disease, and the SSTR5 analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR5 and SSTR2 may help reduce adenoma recurrence in the future

Thresholds: observations on motion capture.

This paper theoretically situates research that explores motion capture data visualization using customized software tools such as MxCap.01. The value of software like MxCap.01 lies in its visualization capabilities including the ability to scale the re-presentation of the force, direction and intensity of movement but also do so within a temporal and emotive structuring

Role of tumor-derived fibroblasts in the growth of primary cultures of human breast-cancer cells: Effects of epidermal growth factor and the somatostatin analogue octreotide

In the present study we have investigated the role of human breast-cancer-derived fibroblasts in the proliferation of primary cultures of epithelial cells derived from the same tumor. For this purpose, a co-culture system, using Transwell tissue-culture inserts with microporous membranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients. The co-culture system was first established using MCF-7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17β-estradiol, EGF and HF cells all significantly stimulated the growth of MCF-7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above-mentioned growth-promoting compounds, are responsible for the growth-promoting effects of fibroblasts. In half of the human breast cancers investigated, tumor-derived fibroblasts stimulated tumor-derived epithelial cell proliferation. EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were additive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblasts, in one culture the fibroblasts significantly inhibited epithelial tumor-cell proliferation. Conversely, the epithelial cells significantly stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial cell proliferation by 46% in one tumor-cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide significantly inhibited the proliferation of fibroblasts co-cultured with epithelial cells

Use of thymidine analogues to indicate vascular perfusion in tumours

Temporary reduction in blood-flow within tumour blood vessels can reduce oxygen supply leading to transient perfusion-limited hypoxia. Consequent selection of cells with mutations and reduced radiosensitivity can lead to disease progression and treatment-resistance. In the present study, we investigated whether heterogeneity of labelling after thymidine analogue administration is related to perfusion variations, and if so, could it be quantified and used as a perfusion indicator. Perfusion in murine RIF1 tumours was reduced by hydralazine or increased by nicotinamide and the mice subsequently injected with IdUrd. Tumours were halved for analysis by both flow cytometry and immunohistochemistry. Tumour sections were stained for vasculature and IdUrd. Each blood vessel was scored for the density of IdUrd-labelled cells surrounding it, using a semi-quantitative scoring system. Flow cytometry showed that the IdUrd labelling index and intensity decreased by approximately 50% after hydralazine. In tumour sections of control animals, 2.9% of vessels showed no IdUrd label. In contrast, after hydralazine almost 50% of vessels had no surrounding IdUrd labelling, whereas after nicotinamide there were fewer vessels with low labelling and a higher median score. In conclusion, changes of tumour perfusion by pharmacological agents is reflected in changes in tumour-cell labelling by the thymidine analogue IdUrd, suggesting that IdUrd labelling could be used to indicate perfusion in individual vessels in human tumours. © 2000 Cancer Research Campaig

Animation in relational information visualization

In order to be able to navigate in the world without memorizing each detail, the human brain builds a mental map of its environment. The mental map is a distorted and abstracted representation of the real environment. Unimportant areas tend to be collapsed to a single entity while important landmarks are overemphasized. When working with visualizations of data we build a mental map of the data which is closely linked to the particular visualization. If the visualization changes significantly due to changes in the data or the way it is presented we loose the mental map and have to rebuild it from scratch. The purpose of the research underlying this thesis was to investigate and devise methods to create smooth transformations between visualizations of relational data which help users in maintaining or quickly updating their mental map

Comparison of [18F]DOPA and [68Ga]DOTA-TOC as a PET imaging tracer before peptide receptor radionuclide therapy

BACKGROUND: In treatment of neuroendocrine neoplasms (NENs), confirmation of somatostatin receptor expression with 68Ga-DOTA somatostatin analogues is mandatory to determine eligibility for peptide receptor radionuclide therapy (PRRT). [18F]DOPA can detect additional lesions compared to [68Ga]DOTA-TOC. The aim of this study was to explore differences in tumour detection of both tracers and their relevance for selecting patients for PRRT. We retrospectively studied eight patients with NENs who underwent both [68Ga]DOTA-TOC and carbidopa-enhanced [18F]DOPA PET/CT, before first-time PRRT with [177Lu]DOTA-TATE. Tracer order was influenced due to stock availability or to detect suspected metastases with a second tracer. On CT, disease control was defined as a lesion showing complete response, partial response, or stable disease, according to RECIST 1.1. CRITERIA: RESULTS: Seven patients with in total 89 lesions completed four infusions of 7.4 GBq [177Lu]DOTA-TATE, one patient received only two cycles. Before treatment, [18F]DOPA PET/CT detected significantly more lesions than [68Ga]DOTA-TOC PET/CT (79 vs. 62, p < .001). After treatment, no difference in number of lesions with disease control was found for [18F]DOPA-only (5/27) and [68Ga]DOTA-TOC-only lesions (4/10, p = .25). [18F]DOPA detected more liver metastases (24/27) compared to [68Ga]DOTA-TOC (7/10, p = .006). Six patients showed inpatient heterogeneity in treatment response between [18F]DOPA-only and [68Ga]DOTA-TOC-only lesions. CONCLUSIONS: Response to PRRT with [177Lu]DOTA-TATE was comparable for both [68Ga]DOTA-TOC- and [18F]DOPA-only NEN lesions. [18F]DOPA may be capable of predicting response to PRRT while finding more lesions compared to [68Ga]DOTA-TOC, although these additional lesions are often small of size and undetected by diagnostic CT

Adolescent weak decoders writing in a shallow orthography: process and product

It has been hypothesised that students with dyslexia struggle with writing because of a word level focus that reduces attention to higher level textual features (structure, theme development). This may result from difficulties with spelling and/or from difficulties with reading. 26 Norwegian upper secondary students (M = 16.9 years) with weak decoding skills and 26 age-matched controls composed expository texts by keyboard under two conditions: normally and with letters masked to prevent them reading what they were writing. Weak decoders made more spelling errors and produced poorer quality text. Their inter key-press latencies were substantially longer pre-word, at word-end, and within-word. These findings provide some support for the word-level focus hypothesis, although we found that weak decoders were slightly less likely to engage in word-level editing. Masking did not affect differences between weak decoders and controls indicating that reduced fluency was associated with production rather than monitoring what they had produced

Radioiodinated somatostatin analogue RC-160: preparation, biological activity, in vivo application in rats and comparison with [123I-Tyr3]octreotide

We have evaluated the potential usefulness of the radioiodinated octapeptide RC-160, a somatostatin analogue, which might serve as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose, iodine-123 and iodine-125 labelled RC-160 was tested for biological activity and applied in vivo in rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. Our group has recently described the in vivo visualization of such tumours in rats and in humans with the radioiodinated somatostatin analogue [Tyr3]octreotide. Like [123I-Tyr3]octreotide, 123I-RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours. However, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. We therefore conclude that in this animal model 123I-RC-160 has no advantage over [123I-Tyr3]octreotide as a radiopharmaceutical for the in vivo use as a somatostatin receptor imager, although, like [123I-Tyr3]octreotide, 123I-RC-160 shows specific binding to different somatostatin receptor-positive organs. Recently differences were reported in affinity between somatostatin and its analogues for somatostatin receptors expressed in different human cancers, like those of the breast, ovary, exocrine pancreas, prostate and colon. Therefore 123I-RC-160 might be of interest for future use in humans as a radiopharmaceutical for imaging octreotide receptor-negative tumours

A new radiolabelled somatostatin analogue [111In-DTPA-D-Phe1]RC-160: preparation, biological activity, receptor scintigraphy in rats and comparison with [111In-DTPA-D-Phe1]octreotide

We have evaluated the potential usefulness of indium-111 labelled [DTPA-D-Phe1]RC-160, derived from the octapeptide somatostatin analogue RC-160, as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose 111In-and 111In-labelled [DTPA-D-Phe1]RC-160 was tested for its biological activity, and applied for somatostatin receptor scintigraphy in vivo to rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. We previously described the development of the 111In-labelled somatostatin analogue [DTPA-D-Phe1]octreotide and its use in the in vivo visualization of somatostatin receptor-positive tumours in rats and in humans. Like [111In-DTPA-D-Phe1]octreotide, [111In-DTPA-D-Phe1]RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours, and the tumours were clearly visualized by gamma camera scintigraphy. However, as compared to [111In-DTPA-D-Phe1]octreotide, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. Using this animal model we therefore conclude that [111In-DTPA-DPhe1]RC-160 has no advantage over [111In-DTPA-DPhe1]octreotide as a radiopharmaceutical in the visualization of somatostatin receptors which bind both analogues. However, recent reports suggest the existence of different somatostatin receptor subtypes on some human cancers, which differentially bind RC-160 and not octreotide. These tumours include cancers of the breast, ovary, exocrine pancreas, prostate and colon. [111In-DTPA-D-Phe1]RC-160 might be of interest for future use in such cancer patients as a radiopharmaceutical for imaging somatostatin receptor-positive tumours, which do not bind octreotide