Intra-articular tumors in the ankle are a rare presentation for metastatic disease. Metastatic breast disease presenting distal to the knee or within any joint is especially rare. We present a case of a painful intra-articular breast metastasis in a 56-year-old female with known breast carcinoma. The patient presented with anterior ankle pain and was found to have an intra-articular ankle tumor that was eroding into the anteromedial talus. The distinct soft tissue tumor was excised from the ankle and the talar lesion curetted and treated with adjuvant chemical ablation. The void in the talus was filled with cement. Despite the patient's poor prognosis, she did not have ankle pain at 6 months postoperatively and was able to ambulate without assistive devices. When treating unknown tumors in the ankle, the treating surgeon must be prepared with different operative plans that will depend on the preliminary pathology report to best treat their patients safely.

Exophytic oral verrucous hyperplasia (OVH) is a new entity described by an expert working group from South Asia. First reported in Taiwan, there are no reports so far from an Indian population. The aim was to use the microscopic features described by the expert group to differentiate OVH from other oral verruco-papillary lesions in an Indian archive.

The use of galectin-3 ThyroTest in the preoperative evaluation of cytologically indeterminate (Thy-3) thyroid nodules has been largely validated by retrospective and prospective multicentre studies. Here we report the results of galectin-3 ThyroTest routinely applied in the management of Thy-3 nodules in combination with clinical and ultrasonography (US) examination, in which galectin-3 positive nodules were directly referred to surgery whereas galectin-3 negative lesions were considered for clinical and US long-term follow-up. A cohort of 331 patients, bearing 340 thyroid Thy-3 nodules, was enrolled and subjected to galectin-3 expression analysis. A total of 256 galectin-3 negative nodules were directed to periodical clinical and US examination, while 84 galectin-3 positive cases were referred to surgery. Excluding 63 dropout patients plus 15 patients that were operated because of clinical reasons the remaining 176 galectin-3 negative nodules were followed with clinical and US examination for an average period of 31 months. During the follow-up, the volume of galectin-3 negative nodules was unchanged in 85 cases (48 %), reduced in 47 (27 %), and increased in 44 (25 %). Based on combined clinical features and US follow-up results, a total of 36 out of 191 galectin-3 negative nodules (19 %) were referred to surgery, with a final histological finding of 28 benign lesions, three follicular tumor of uncertain malignant potential (FT-UMP), and five malignant lesions, corresponding to a 7 % false negative rate. In the group of 84 galectin-3 positive nodules, we detected 65 thyroid cancers with a prevalence of 77 %, 12 FT-UMPs, and 7 false positive lesions, corresponding to a 4 % false positive rate. A total of 150 patients were not operated and are still under clinical and US monitoring while surgery was performed in 118 patients with a final 70 thyroid cancers diagnosed, corresponding to a 59 % prevalence of malignancy detected at surgery and to a 26 % prevalence of malignancy among the entire Thy-3 nodule population. Galectin-3 ThyroTest is an easy and cheap diagnostic procedure that integrates conventional fine-needle-aspiration cytology, reduces the number of unnecessary thyroidectomies and increases the rate of malignancy at surgery. Clinical and US follow-up of galectin-3 negative lesions allows to further reduce false negative cases.

CXCL8 is secreted by both normal human thyrocytes (NHT) and thyroid cancer cell lines. CXCL8 displays several tumor-promoting effects and recent evidences indicate that its concentrations within the tumor microenvironment can impact the clinical course of the malignancy. Aim of this study was to compare the basal secretion of CXCL8 among NHT and thyroid cancer cell lines (TPC-1 and BCPAP), and to assess the specific cell response to TNF-α in terms of CXCL8 secretion. NHT primary cultures, TPC-1 and BCPAP cell lines were cultured with or without TNF-α (0, 0.1, 1, 10, and 100 ng/ml). CXCL8 levels were measured in the cell supernatants after 24 h. In basal condition, significant differences in the mean levels of CXCL8 were observed among the three cell types: NHT (110.5 ± 56.2 pg/ml), TPC1 (467.4 ± 43.2 pg/ml), and BCPAP (1731.8 ± 493.3 pg/ml), (F = 35.06; p < 0.0001). TNF-α significantly and in a dose-response manner induced CXCL8 secretion in NHT (F = 25.53; p < 0.00001), TPC-1 (F = 13.38; p < 0.0001), and BCPAP (F = 9.88; p < 0.001) cells. The magnitude of the TNF-α effect (fold-increase vs. basal level of CXCL8) differed significantly among the three cell types (F = 10.47; p < 0.0001). BCPAP were identified as the cells showing the highest basal secretion of CXCL8 and the less responsive to TNF-α. NHT, TPC-1, and BCPAP display significant differences in the secretion of both basal and TNF-α-induced CXCL8 secretion. These results indicate that the mechanisms regulating the secretion of CXCL8 differ in tumor cells harboring different genetic alterations suggesting that specific strategies aimed at inhibiting CXCL8 secretion will be required.

Uncontrolled cell proliferation is a common feature of human cancer. Some of herbal extract or plant-derived medicine had been shown as an important source of effective anticancer agents. We previously reported that an n-BuOH-soluble fraction of Kalanchoe tubiflora has antiproliferative activity by inducing mitotic catastrophe. In this study, we showed that the H2 O-soluble fraction of Kalanchoe tubiflora (KT-W) caused cell cycle arrest, and senescence-inducing activities in A549 cells. We used 2 dimensional PAGE to analyze the protein expression levels after KT-W treatment, and identified that the energy metabolism-related proteins and senescence-related proteins were disturbed. In vivo experiments showed that the tumor growths in A549-xenografted nude mice were effectively inhibited by KT-W. Our findings implied that KT-W is a putative antitumor agent by inducing cell cycle arrest and senescence. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1663-1673, 2016.

Although reports have shown that α-phellandrene (α-PA) is one of the monoterpenes and is often used in the food and perfume industry, our previous studies have indicated that α-PA promoted immune responses in normal mice in vivo. However, there is no available information to show that α-PA induced cell apoptosis in cancer cells, thus, we investigated the effects of α-PA on the cell morphology, viability, cell cycle distribution, and apoptosis in mice leukemia WEHI-3 cells in vitro. Results indicated that α-PA induced cell morphological changes and decreased viability, induced G0/G1 arrest and sub-G1 phase (apoptosis) in WEHI-3 cells. α-PA increased the productions of reactive oxygen species (ROS) and Ca2+ and decreased the levels of mitochondrial membrane potential (ΔΨm ) in dose- and time-dependent manners in WEHI-3 cells that were analyzed by flow cytometer. Results from confocal laser microscopic system examinations show that α-PA promoted the release of cytochrome c, AIF, and Endo G from mitochondria in WEHI-3 cells. These results are the first findings to provide new information for understanding the mechanisms by which α-PA induces cell cycle arrest and apoptosis in WEHI-3 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1640-1651, 2016.

Prostate cancer is the most frequently diagnosed malignancy in men and the second highest contributor of male cancer mortality. The crude extract of Euphorbia formosana (CEEF) has been used for treatment of different diseases but the cytotoxic effects of CEEF on human cancer cells have not been reported. The purpose of the present experiments was to determine effects of CEEF on cell cycle distribution and induction of apoptosis in DU145 human prostate cancer cells in vitro. Contrast-phase microscope was used for examining cell morphological changes. Flow cytometric assays were used for cell viability, cell cycle, apoptosis, reactive oxygen species, and Ca2+ production and mitochondria membrane potential (ΔΨm ). Western blotting was used for examining protein expression of cell cycle and apoptosis associated proteins. Real-time PCR was used for examining mRNA levels of caspase-3, -8, and -9, AIF, and Endo G. Confocal laser microscope was used to examine the translocation of AIF, Endo G, and cytochrome in DU145 cells after CEEF exposure. CEEF-induced cell morphological changes, decreased the percentage of viable cells, and induced S phase arrest and apoptosis in DU145 cells. Furthermore, CEEF promoted RAS and Ca2+ production and reduced ΔΨm levels. Real-time QPCR confirmed that CEEF promoted the mRNA expression of caspase-3 and -9, AIF and Endo G and we found that AIF and Endo G and cytochrome c were released from mitochondria. Taken together, CEEF-induced cytotoxic effects via ROS production, induced S phase arrest and induction of apoptosis through caspase-dependent and independent and mitochondria-dependent pathways in DU245 cancer cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1600-1611, 2016.