Fibroblast growth factor-2, derived from cancer-associated fibroblasts, stimulates growth and progression of human breast cancer cells via FGFR1 signaling

Cancer-associated fibroblasts (CAFs) constitute a major compartment of the tumor microenvironment. In the present study, we investigated the role for CAFs in breast cancer progression and underlying molecular mechanisms. Human breast cancer MDA-MB-231 cells treated with the CAF-conditioned media manifested a more proliferative phenotype, as evidenced by enhanced messenger RNA (mRNA) expression of Cyclin D1, c-Myc, and proliferating cell nuclear antigen. Analysis of data from The Cancer Genome Atlas revealed that fibroblast growth factor-2 (FGF2) expression was well correlated with the presence of CAFs. We noticed that the mRNA level of FGF2 in CAFs was higher than that in normal fibroblasts. FGF2 exerts its biological effects through interaction with FGF receptor 1 (FGFR1). In the breast cancer tissue array, 42% estrogen receptor-negative patients coexpressed FGF2 and FGFR1, whereas only 19% estrogen receptor-positive patients exhibited coexpression. CAF-stimulated MDA-MB-231 cell migration and invasiveness were abolished when FGF2-neutralizing antibody was added to the conditioned media of CAFs. In a xenograft mouse model, coinjection of MDA-MB-231 cells with activated fibroblasts expressing FGF2 dramatically enhanced tumor growth, and this was abrogated by silencing of FGFR1 in cancer cells. In addition, treatment of MDA-MB-231 cells with FGF2 enhanced expression of Cyclin D1, a key molecule involved in cell cycle progression. FGF2-induced cell migration and upregulation of Cyclin D1 were abolished by siRNA-mediated FGFR1 silencing. Taken together, the above findings suggest that CAFs promote growth, migration and invasion of MDA-MB-231 cells via the paracrine FGF2-FGFR1 loop in the breast tumor microenvironment.

The Usefulness of Maximum Standardized Uptake Value at the Delayed Phase of Tc-99m sestamibi single-photon emission computed tomography/computed tomography for Identification of Parathyroid Adenoma and Hyperplasia

Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism. Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 +/- 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells. SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 +/- 6.68, 7.90 +/- 5.49, and 7.01 +/- 2.62 at 10min (early phase), decreasing to 7.46 +/- 5.66, 4.65 +/- 3.14, and 2.21 +/- 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P < .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of oxyphil cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant oxyphil cells (rho = 0.418,P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions. SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.Y

Height Restoration after Balloon Kyphoplasty in Rheumatoid Patients with Osteoporotic Vertebral Compression Fracture

Study DesignRetrospective study.PurposeThis study was conducted to compare vertebral body height restoration rate in rheumatoid arthritis (RA) patients who had undergone percutaneous balloon kyphoplasty (KP) with that of control group who had matched age, sex, body mass index, and bone mineral density.Overview of LiteratureThere is no report on result of KP in RA patients.MethodsPostoperative height restoration rate of RA group consisting of 15 patients (18 vertebral bodies) who had undergone KP due to osteoporotic vertebral compression fracture with a 30% or higher vertebral compression rate between May 2005 and January 2013 were compared to control group consisting of 38 patients (39 vertebral bodies) who had matched age, sex, body mass index, and bone mineral density.ResultsNo statically significant difference in age (p=0.846), sex (p=0.366), body mass index (p=0.826), bone mineral density (p=0.349), time to surgery (p=0.528), polymethylmethacrylate injection time (p=0.298), or amount (p=0.830) was found between the RA group and the control group. However, preoperative compression rate in the RA group was significantly (p=0.025) higher compared to that in the control group. In addition, postoperative height restoration rate showed significant correlation with the RA group (p=0.008). Although higher incidence of recollapse occurred in the RA group compared to that in the control group, the difference was not statistically significant (p=0.305).ConclusionsCompared to the control group, RA patients showed higher compression rate and higher vertebral restoration rate after KP, indirectly indicating weaker bone quality in patients with RA. Higher incidence of recollapse occurred in the RA group compared to that in the control group, although it was not statistically significant

Outcomes of Revision Surgery Following Instrumented Posterolateral Fusion in Degenerative Lumbar Spinal Stenosis: A Comparative Analysis between Pseudarthrosis and Adjacent Segment Disease

Study DesignRetrospective study.PurposeWe examined the clinical and radiological outcomes of patients who received revision surgery for pseudarthrosis or adjacent segment disease (ASD) following decompression and instrumented posterolateral fusion (PLF).Overview of LiteratureAt present, information regarding the outcomes of revision surgery for complications such as pseudarthrosis and ASD following instrumented PLF is limited.MethodsThis study examined 60 patients who received PLF for degenerative lumbar spinal stenosis and subsequently developed pseudarthrosis or ASD leading to revision surgery. Subjects were divided into a group of 21 patients who received revision surgery for pseudarthrosis (Group P) and a group of 39 patients who received revision surgery for ASD (Group A). Clinical outcomes were evaluated using the visual analogue scales for back pain (VAS-BP) and leg pain (VAS-LP), the Korean Oswestry disability index (K-ODI), and each patient's subjective satisfaction. Radiological outcomes were evaluated from the extent of bone union, and complications in the two groups were compared.ResultsVAS-LP at final follow-up was not statistically different between the two groups (p =0.353), although VAS-BP and K-ODI at final follow-up were significantly worse in Group P than in Group A (all p <0.05), and only 52% of the patients in Group P felt that their overall well-being had improved following revision surgery. Fusion rates after the first revision surgery were 71% (15/21) in Group P and 95% (37/39) in Group A (p =0.018). The rate of reoperation was significantly higher in Group P (29%) than in Group A (5%) (p =0.021) due to complications.ConclusionsClinical and radiological outcomes were worse in patients who had received revision surgery for pseudarthrosis than in those who had revision surgery for ASD. Elderly patients should be carefully advised of the risks and benefits before planning revision surgery for pseudarthrosis

Pituitary Carcinoma with Mandibular Metastasis: A Case Report

Pituitary carcinomas are rare primary adenohypophyseal tumors with cerebrospinal or extracranial metastasis. The present case, the first report of the disease in Korea, involved a 36-yr-old woman who presented with a 3-week history of headache. Brain magnetic resonance imaging revealed a 2.5-cm sellar and suprasellar mass showing heterogeneous enhancement with suspicious invasion of both cavernous sinuses. The patient underwent gross-total resection. The tumor cells were composed of polygonal cells singly or in variable-sized nests. The nuclei were large and round with prominent nucleoli. The cytoplasms was acidophilic and granular. Marked pleomorphism and frequent mitoses (3 per 10 HPFs) were found. By immunohistochemistry, tumor cells were strongly positive for prolactin, but negative for ACTH and GH. Additional immunostainings for cytokeratin, vimentin, and glial fibrillary acidic protein (GFAP) were negative. After the surgery, the patient received radiotherapy because of the atypical histologic features. The prolactin level fell from 123.17 ng/mL to 5.17 ng/mL after surgery. Nine months after the initial diagnosis, the patient died from mandibular metastasis associated with the pituitary carcinoma