ABSTRACT
Prostate cancer is the fifth leading cause of cancer-related mortality in men, primarily because of treatment resistance, recurrence, and metastasis. In the present study, we investigated the role of paracrine interleukin-8 (IL-8) in the antagonistic expression of IL-8 and androgen receptor (AR), and the contribution of IL-8 to prostate cancer aggressiveness. In hormone-responsive LNCaP cells that do not express IL-8, recombinant IL-8 treatment significantly increased expressions of IL-8, CXC chemokine receptor 2 (CXCR2), matrix metalloproteinase (MMP)-2/9, Snail, and vimentin. IL-8 treatment significantly decreased AR and E-cadherin expression. IL-8-induced gene expression changes were suppressed by navarixin, a CXCR1/2 inhibitor, and gallein, a Gβγ inhibitor. In PC-3 androgen-refractory prostate cancer cells, IL-8 knockdown reduced expressions of CXCR2, MMP-2/9, Snail, and vimentin, and increased AR and E-cadherin expressions at the mRNA and protein levels. Co-culture with MEG-01 human megakaryocytic cells secreting high levels of IL-8 induced gene expression changes in both LNCaP and PC-3 cells, similar to those induced by IL-8 treatment. The altered gene expressions were accompanied by significant activation of transcription factor Snail in LNCaP and PC-3 cells. Treatment with the CXCR blocker navarixin inhibited the invasion of PC-3 cells but not LNCaP cells. However, invasion induced by MEG-01 was inhibited by navarixin in both LNCaP and PC-3 cells. The collective findings demonstrate that IL-8 enhances CXCR2 expression, which antagonistically regulates AR expression. More importantly, through changes in IL-8/CXCR2-regulated gene expression, IL-8 induces antiandrogen therapy resistance and epithelial-mesenchymal transition in prostate cancer.
ABSTRACT
<b>Background</b>: The intestinalcoccidian protozoa <i>Cyclospora cayetanensis </i>has emerged as an important cause of parasitic diarrhea among the childrenliving in developing countries. This study aimed to determine the prevalence of <i>Cyclospora</i> among the school childrenof Kathmandu with relation to various associated risk factors. <b>Methodology</b>: A total of fivehundred and seven stool samples from students between the age group 3-14 years,studying in 13 different schools of Kathmandu were collected during the studyperiod (May- November, 2014) and processed in Public Health ResearchLaboratory, Institute of Medicine, Kathmandu, Nepal. A modified Acid Faststaining technique (Kinyoun’s method) was used to detect oocyst of <i>Cyclospora</i> from the formal-etherconcentrated stool samples. <b>Results</b>: <i>Cyclospora</i> was detected in 3.94% (20/507) of the stool samplesexamined. The prevalence was found to be highest among the students between theage group 3-5 years i.e. 10.15% (13/128), peaking during the rainy season(June-August). The detection rate of the parasite was found to be significantlyhigher (p<0.05) among the children presenting with diarrheal symptom,household keeping livestock(s) and consumers of raw vegetables/fruits withprevalence10.57 % (11/104), 10.11% (9/89) and 7.25% (14/193) respectively. <b>Conclusion: </b>Consumptionof untreated drinking water, fresh produce (raw fruits/vegetables) withoutproper washing and livestock presence at home were found to be some of thepredisposing factors for higher susceptibility of infection due to <i>Cyclospora</i>. This finding confirms apublic-health issue with potentially serious consequences whereby, children canbe infected through the exposure to oocyst contaminated food, water and getill.
ABSTRACT
Background: The intestinal coccidian protozoa <i>Cyclospora cayetanensis</i> has emerged as an important cause of parasitic diarrhea among children living in developing countries. This study aimed to determine the prevalence of <i>Cyclospora</i> among the school children of Kathmandu with reference to various associated risk factors.Methodology: A total of five hundred and seven stool samples from students between the age of 3–14 years, studying in 13 different schools in Kathmandu were collected during the study period (May–November, 2014) and processed at the Public Health Research Laboratory, Institute of Medicine, Kathmandu, Nepal. A modified acid fast staining technique (Kinyoun’s method) was used to detect oocyst of <i>Cyclospora</i> from the formal-ether concentrated stool samples.Results: <i>Cyclospora</i> was detected in 3.94% (20/507) of the stool samples examined. The prevalence was found to be highest among the students in the 3–5 year age group i.e. 10.15% (13/128), peaking during the rainy season (June–August). The detection rate was found to be significantly higher (p < 0.05) among children presenting with diarrheal symptoms, household keeping livestock and consumers of raw vegetables/fruits, showing a prevalence of 10.57% (11/104), 10.11% (9/89) and 7.25% (14/193) respectively.Conclusion: Consumption of untreated drinking water, fresh produce (raw fruits/vegetables) without proper washing and the presence of livestock at home were found to be predisposing factors for higher susceptibility of infection due to <i>Cyclospora</i>. This finding confirms the existence of a public-health issue with potentially serious consequences whereby children can be infected through exposure to oocysts in contaminated food and water and get ill as a result.
ABSTRACT
Objective To compare and evaluate the efficacy of diagnosis and excision for appropriately selected breast multi-focal lesions and solitary lesion by ultrasound-guided vacuum-assisted biopsy (UGVAB). Methods Among 392 appropriately selected patients, 187 patients with multi-focal lesions and 205 patients with solitary lesion were treated by the 8-gauge UGVAB from May 2007 to June 2009. All lesions were removed as completely as possible. The patients with benign pathology underwent physical and ultrasound examinations at one week and 6 months after procedure. Results During the procedure, only three patients had vasovagal syncope and twenty others complained of other intraoperative discomfort. An accurate pathological diagnosis was obtained in all lesions. There was no apparent false-negative result among the 696 lesions with benign pathology at a follow-up of 6 months after procedure. The rates of malignant or premalignant pathology, postoperative complications and residual lesions in patients with multi-focal lesions were higher than those in patients with solitary lesion. If each lesion was considered as a subject of study, there was no significant difference between the two groups. Conclusion UGVAB is an effective method for diagnosis and excision of appropriately selected breast multi-focal lesions and can be used routinely.