| 1. |
- Andreasen, S., et al.
(författare)
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Genomic profiling of a combined large cell neuroendocrine carcinoma of the submandibular gland
- 2016
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 35:4, s. 2177-2182
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Tidskriftsartikel (refereegranskat)abstract
- A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small-cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection and selective neck dissection was performed and histopathologic examination revealed a combined large-cell neuroendocrine carcinoma (LCNEC) with a squamous component and without lymph node metastases. Resection of the lung tumor revealed a papillary adenocarcinoma that was morphologically distinctly different from the LCNEC. The patient died of her lung cancer after 19 months without evidence of recurrence of the LCNEC. Genomic profiling of the salivary gland LCNEC revealed a hypodiploid genome predominated by losses of whole chromosomes or chromosome arms involving chromosomes 3p, 4, 7q, 10, 11, 13, 16q and gains of 3q and 16p. In addition, there was a segmental gain of 9p23-p22.3 including the NFIB oncogene. Continued studies of salivary gland LCNEC may provide new knowledge concerning potential diagnostic biomarkers and may ultimately also lead to the identification of new treatment targets for patients with these aggressive carcinomas.
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| 2. |
- Burgos, Jonathan R, et al.
(författare)
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MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.
- 2016
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Ingår i: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 35:4, s. 2425-2430
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.
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| 3. |
- Dalmo, Johanna, et al.
(författare)
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Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2.
- 2012
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Ingår i: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 27:1, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177Lu-octreotate and 111In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177Lu-octreotate or 111In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111In-MG0. Animals were sacrificed 1-7 days after injection in the 177Lu-octreotate study and 1 h after injection of 111In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177Lu were calculated. There was a specific tumor uptake of either 177Lu-octreotate or 111In-MG0. 177Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.
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| 4. |
- Göstring, L., et al.
(författare)
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17AAG-induced internalisation of HER2-specific Affibody molecules
- 2016
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082 .- 1021-335X .- 1791-2431. ; 12:4, s. 2574-2580
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Tidskriftsartikel (refereegranskat)abstract
- The geldanamycin derivative 17-allylamino- 17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled211At-ABY-025 and radiometal-labelled111In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of 111In-ABY-025 from the cell surface to intracellular compartments in the two cell lines. ABY-025 labelled with the high-linear energy transfer α emitter211At was also internalised to a higher degree; however, due to its physiological properties, this nuclide was excreted faster. The results indicate that 17-AAG may be used to facilitate cell-specific intracellular localisation of a suitable cytotoxic or radioactive agent coupled to ABY-025 in HER2-overexpressing cells. © 2016, Spandidos Publications. All rights reserved.
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| 5. |
- Khan, Maria, et al.
(författare)
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Reduced tumor growth in EP2 knockout mice is related to signaling pathways favoring an increase local anti-tumor immunity in the tumor stroma
- 2022
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 47:6
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well‑established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor‑stroma, at conditions of reduced disease progression due to decreased host inflammation. In the present study, wild‑type tumor cells, producing high levels of prostaglandin E2 (MCG 101 cells, EP2+/+), were inoculated into EP2 knockout (EP2‑/‑) and EP2 wild‑type (EP2+/+) mice. Solid tumors were dissected into tumor‑ and tumor‑stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. Immunohistochemistry was used to confirm adequate dissections of tissue compartments, and to assess cell proliferation (Ki‑67), prostaglandin enzymes (cyclooxygenase 2) and immunity biomarkers (CD4 and CD8) at the protein level. Microarray analyses revealed statistically significant alterations in gene expression in the tumor‑stroma compartment, while significantly less pathway alterations occurred in the tumor tissue compartment. The host knockout of EP2 receptors led to a significant downregulation of cell cycle regulatory factors in the tumor‑stroma compartment, while interferon γ‑related pathways, chemokine signaling pathways and anti‑tumor chemokines [chemokine (C‑X‑C motif) ligand 9 and 10] were upregulated in the tumor compartment. Thus, such gene alterations were likely related to reduced tumor growth in EP2‑deficient hosts. On the whole, pathway analyses of both tumor‑ and tumor‑stroma compartments suggested that absence of host EP2 receptor signaling reduces ‘remodeling’ of tumor microenvironments and increase local immunity, probably by decreased productions of stimulating growth factors, perhaps similar to well‑recognized physiological observations in wound healing.
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| 6. |
- Krona, Annika, 1973, et al.
(författare)
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Oncostatin M signaling in human glioma cell lines.
- 2005
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Ingår i: Oncology reports. - 1021-335X .- 1791-2431. ; 13:5, s. 807-11
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Tidskriftsartikel (refereegranskat)abstract
- We have recently found that oncostatin M (OSM) is overexpressed in most human brain tumors. The effects of OSM are unclear with conflicting reports of growth stimulatory or inhibitory effects in various cell types. The aim of this study was to investigate the effects of OSM in 5 glioma cell lines and 7 short-term cultures of human gliomas and in normal cultured human astrocytes. None of the cell lines and short-term cultured tumor cells expressed OSM in vitro. OSM signals through a gp130 containing receptor complex over the JAK/STAT pathway. Immunofluorescence and RT-PCR analysis showed that the tumor cells express gp130 and the other receptor components, LIFRbeta and OSMRbeta. OSM treatment induced phosphorylation of STAT3 and STAT1 indicating presence of a functional JAK/STAT pathway. No OSM effect on proliferation was observed. OSM gave no protective effects against tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced cytotoxicity.
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| 7. |
- Lagerstedt-Robinson, K., et al.
(författare)
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Mismatch repair gene mutation spectrum in the Swedish Lynch syndrome population
- 2016
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 36:5, s. 2823-2835
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Tidskriftsartikel (refereegranskat)abstract
- Lynch syndrome caused by constitutional mismatch-repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2. After 20 years of genetic counseling and genetic testing for Lynch syndrome, we have compiled the mutation spectrum in Sweden with the aim to provide a population-based perspective on the contribution from the different MMR genes, the various types of mutations and the influence from founder mutations. Mutation data were collected on a national basis from all laboratories involved in genetic testing. Mutation analyses were performed using mainly Sanger sequencing and multiplex ligation-dependent probe amplification. A total of 201 unique disease-predisposing MMR gene mutations were identified in 369 Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder mutation that accounted for 15% of the families with mutations in MLH1. In conclusion, the Swedish Lynch syndrome mutation spectrum is diverse with private MMR gene mutations in two-thirds of the families, has a significant contribution from internationally recognized mutations and a limited effect from founder mutations.
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| 8. |
- Lennernäs, Bo, 1963, et al.
(författare)
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Silicon diodes as detectors for backscatter radiation in photon fields.
- 2001
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Ingår i: Oncology reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 8:1, s. 181-3
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the use of unencapsulated silicon semiconductor detectors for backscatter radiation detection. The results were compared with Monte Carlo (MC) calculations modelling the experimental set-up. A special diode was manufactured, which was designed so that it allowed the positioning of different materials in close contact with the detector surface. Polymethylmethacrylate (PMMA), Pb, Ti and Fe (stainless steel) were used as backscatter materials. The diode signal was measured by integrating the current when irradiating the diode with an equal photon fluence obtained from a medical Co-60 source. When compared to the signal with PMMA as backscatter material the increase in signal was 21%, 27% and 73% for Ti, Fe and Pb, respectively. This is in reasonable agreement with the MC calculations, when taking the effective measurement depth in the Si diode detector into account.
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| 9. |
- Rasmussen, J. O., et al.
(författare)
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Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma
- 2014
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 32:4, s. 1447-1450
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Tidskriftsartikel (refereegranskat)abstract
- A 71-year-old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.
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| 10. |
- Silén, A, et al.
(författare)
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Evaluation of the UBC test in the urine of healthy individuals, patients with benign disorders and urinary bladder cancer.
- 2000
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Ingår i: Oncology reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 7:6, s. 1269-74
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Tidskriftsartikel (refereegranskat)abstract
- Using the UBC test, the specificity, sensitivity and prognostic information were evaluated in patients with recently diagnosed transitional cell carcinoma (TCC) and in a control group consisting of apparently healthy individuals and individuals with benign disorders. Frozen urine samples from the 485 individuals in the control group and 100 newly diagnosed TCC patients were analyzed with the UBC test, specific for epitopes on cytokeratin fragments released from the urothelial cells. All the samples were analyzed and corrected for creatinine. No significant concentration difference was found between males and females (p=0.65) and there was no age dependent relation. The median concentration for the entire control group was estimated at 3.7 microg/g and the 95th percentile was calculated at 53.0 microg/g. The apparently healthy individuals in the control group had a median value of 3.4 microg/g with a 95th percentile of 24.3 microg/g. An increased frequency of elevated UBC concentrations was found in some benign disorders e.g., anemia, thyroid disorders, diabetes mellitus, hyperlipemia, urosepsis and cystitis. Patients with superficial tumors exhibited a 66% sensitivity (at 95% specificity), and the UBC concentrations did not differ statistically (p=0.16) from those patients with muscle invasive lesions with a 52% sensitivity. When the UBC concentrations were related to histopathological grade, a significant concentration difference (p<0.004) was found between low grade tumors (sensitivity 41%) and high grade tumors (sensitivity 72%). Survival analysis showed that patient with muscle invasive tumors, high-grade tumors and high UBC concentrations have a significantly reduced survival (five-year survival was estimated to 30%, 35% and 30% respectively) compared to patients with superficial tumors, low-grade tumors or low UBC concentrations (five-year survival, 60%, 85% and 75% respectively). The UBC test showed good accuracy and repeatability. Clinically the test could assist in tumor grading and the detection of recurrent disease, which in turn could assist in treatment selection for the individual patient and possibly improve prognosis.
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