Expression of GRP78 and its copartners in HEK293 and pancreatic cancer cell lines (BxPC-3/PANC-1) exposed to MRI and CT contrast agents.

Endoplasmic reticulum (ER) stress-associated chaperones trigger a defense mechanism called as unfolded protein response (UPR) which can manage apoptosis and be determinative in cell fate. Both anticancer drug effects and potential toxicity effects of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were aimed to be evaluated. For this purpose, we investigated expression profiles of endoplasmic reticulum stress-associated chaperone molecules in human pancreatic tumor lines BxPC-3 and PANC-1 and control human embryonic kidney cells 293 (HEK293) induced with a variety of gadolinium and iohexol contrast agents. Protein expression levels of ER stress-associated chaperones (master regulator: GRP78/Bip and its copartners: Calnexin, Ero1, PDI, CHOP, IRE1α and PERK) were evaluated with Western blotting. Expression levels at mRNA level were also assessed for GRP78/Bip and CHOP with real-time PCR. Induction of cells was carried out with four different Gd-based contrast agents (GBCAs): (Dotarem, Optimark, Primovist and Gadovist) and two different iohexol agents (Omnipol, Omnipaque). CT contrast agents tested in the study did not result in significant ER stress in HEK293 cells. However, they do not seem to have theranostic potential in pancreas cancer through ER pathway. The potential efficiency of macrocyclic MRI contrast agents to provoke apoptosis via ER stress-associated chaperones in BxPC-3 cells lends credibility for their future theranostic use in pancreas cancer as long as undesired toxicity effects were carefully considered. ER stress markers and/or contrast agents seem to have promising potential to be translated into the clinical practice to manage pancreas cancer progression.

Elevated expression levels of COX-2, IL-8 and VEGF in colon adenocarcinoma.

There is growing evidence of a connection between inflammation and tumor development and NF-κB is an important transcription factor in the inflammation pathway. Genetic approaches have proven the role of NF-κB responsive genes in tumorigenesis. The NF-κB responsive genes products such as IL-8, VEGF and COX-2 are the key components of angiogenesis. MMP-2 and MMP-9 are playing important roles in the disruption of the extracellular matrix that may contribute to the metastasis of tumor cells. This study aimed to investigate gene expression levels of COX-2, IL-8, VEGF, MMP-2 and MMP-9 in colon tumors. A total of 34 fresh colon carcinoma specimens and paired normal adjacent tissues (NAT) were collected during the surgery and RNA isolations were carried out from specimens. Synthesis of cDNA was carried out from these RNAs with oligo dT18 primers. The transcribed cDNA was used for PCR amplification reactions for the investigated genes with ß-actin being the internal reference via the semi-quantitative RT-PCR method. A statistically significant difference was observed for COX-2, IL-8 and VEGF which were all upregulated in colon tumors compared with adjacent normal tissues (p<0.05). However, MMP-2 and MMP-9 expression levels did not change between tumor and normal tissues (p>0.05). Upregulated expression levels of COX-2, IL-8 and VEGF might occur in the early stages of tumorigenesis and detection of these mRNA levels may be beneficial for early diagnosis and management of colon tumors.

Short-Course Radiotherapy Followed by Consolidation Chemotherapy Is Safe and Effective in Locally Advanced Rectal Cancer: Comparative Short-term Results of Multicenter Propensity Score Case-Matched Study.

BACKGROUND: Consolidation chemotherapy strategies have demonstrated improved pathological complete response and tumor downstaging rates for patients diagnosed with rectal cancer. OBJECTIVE: This study aimed to compare perioperative outcomes and pathological complete response rates among different neoadjuvant treatment strategies in patients undergoing total mesorectal excision for locally advanced rectal cancer. DESIGN: Propensity score case-matched study. SETTING: High-volume tertiary care centers. PATIENTS: Consecutive patients undergoing curative total mesorectal excision between January 2014 and June 2021 were queried. INTERVENTIONS: Patients were divided into 3 groups: long-course chemoradiation therapy with (N = 128) or without (N = 164) consolidation chemotherapy or short-course radiotherapy (N = 53) followed by consolidation chemotherapy. MAIN OUTCOME MEASURES: Demographics, preoperative tumor characteristics, histopathologic outcomes, and postoperative complication rates were reviewed and compared. Propensity score match analysis was conducted. RESULTS: A total of 345 patients (mean age: 58 ± 12 years; female: 36%) met the study inclusion criteria. Time interval from neoadjuvant treatment until surgery was longer for patients receiving consolidation chemotherapy ( p < 0.001). Pathological complete response rates were comparable among patients receiving long-course chemoradiation therapy (20.3%) and short-course radiotherapy with consolidation chemotherapy (20.8%) compared to long-course chemoradiation therapy alone (14.6%) ( p = 0.36). After the propensity score case-matched analysis, 48 patients in the long-course chemoradiation therapy with consolidation chemotherapy group were matched to 48 patients in the short-course radiotherapy with consolidation chemotherapy group. Groups were comparable with respect to age, sex, clinical stage, tumor location, type of surgical approach, and technique. Pathological complete response rate was comparable between the groups (20.8% and 18.8%, p = 0.99). LIMITATIONS: Study was limited by its retrospective nature. CONCLUSIONS: Among recent neoadjuvant treatment modalities, pathological complete response rates, and short-term clinical outcomes were comparable. Short-course radiotherapy with consolidation chemotherapy is safe and effective as long-course chemoradiation therapy as in a short-term period. See Video Abstract at http://links.lww.com/DCR/C174 . LA RADIOTERAPIA DE CORTA DURACIN SEGUIDA DE QUIMIOTERAPIA DE CONSOLIDACIN ES SEGURA Y EFICAZ EN EL CNCER DE RECTO LOCALMENTE AVANZADO RESULTADOS COMPARATIVOS A CORTO PLAZO DEL ESTUDIO MULTICNTRICO DE CASOS EMPAREJADOS POR PUNTAJE DE PROPENSION: ANTECEDENTES: Las estrategias de quimioterapia de consolidación han demostrado una mejor respuesta patológica completa y tasas de reducción del estadio del tumor para pacientes diagnosticados con cáncer de recto.OBJETIVO: Comparar los resultados perioperatorios y las tasas de respuesta patológica completa entre diferentes estrategias de tratamiento neoadyuvante en pacientes sometidos a escisión mesorrectal total por cáncer de recto localmente avanzado.DISEÑO: Estudio de casos emparejados por puntaje de propensión.ENTORNO CLINICO: Centros de atención terciaria de alto volumen.PACIENTES: Pacientes consecutivos sometidos a escisión mesorrectal total curativa por cáncer de recto localmente avanzado entre enero de 2014 y junio de 2021.INTERVENCIONES: Los pacientes se dividieron en tres grupos según la modalidad de tratamiento neoadyuvante: quimiorradioterapia de ciclo largo con (N = 128) o sin (N = 164) quimioterapia de consolidación o radioterapia de ciclo corto (N = 53) seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO: El punto final primario fue la respuesta patológica completa. Se revisaron y compararon los datos demográficos, las características preoperatorias del tumor, los resultados histopatológicos y las tasas de complicaciones posoperatorias entre los grupos de estudio. Se realizó un análisis de casos emparejados por puntaje de propensión.RESULTADOS: Un total de 345 pacientes (edad media de 58 ± 12 años y mujeres: 36%) cumplieron los criterios de inclusión del estudio. El intervalo de tiempo desde el tratamiento neoadyuvante hasta la cirugía fue mayor para los pacientes que recibieron quimioterapia de consolidación ( p < 0,001). Las tasas de respuesta patológica completa fueron comparables entre los pacientes que recibieron quimiorradioterapia de larga duración con quimioterapia de consolidación (20,3 %) y radioterapia de corta duración con quimioterapia de consolidación (20,8%) en comparación con la quimiorradiación de larga duración sola (14,6%) ( p = 0,36). Después del análisis de casos emparejados por puntaje de propensión, 48 pacientes en el grupo de quimiorradioterapia de ciclo largo con quimioterapia de consolidación se emparejaron con 48 pacientes en el grupo de radioterapia de ciclo corto con quimioterapia de consolidación. Los grupos fueron comparables con respecto a la edad, sexo, estadio clínico, ubicación del tumor, tipo de abordaje quirúrgico y la técnica. La tasa de respuesta patológica completa fue comparable entre los grupos (20,8% y 18,8%, p = 0,99). La morbilidad postoperatoria a los 30 días y las tasas de fuga anastomótica fueron similares.LIMITACIONES: El estudio estuvo limitado por su naturaleza retrospectiva.CONCLUSIONES: Entre las modalidades de tratamiento neoadyuvante recientes, las tasas de respuesta patológica completa y los resultados clínicos a corto plazo fueron comparables. La radioterapia de corta duración con quimioterapia de consolidación es segura y eficaz como terapia de quimiorradioterapia de larga duración en un período corto. Consulte Video Resumen en http://links.lww.com/DCR/C174 . (Traducción-Dr. Fidel Ruiz Healy ).

Gene expression of ING4 gene in pancreatic cancers and splice forms of ING4 gene.

Pancreatic cancer is characterized by rapid metastasis and resistant to medical treatments. As the other cancers, mutations of tumor suppressor genes that involved in suppression of cell growth are observed in pancreatic cancers. ING4 protein is one of the proteins involved in the regulation of p53 tumor suppressor gene functions. ING4 involved in suppression of cell proliferation, chromosome rearrangement, cell migration, and angiogenesis. In this study, gene expressions and splicing variants of ING4 gene were investigated. Fresh tumor and normal specimens of the same pancreatic cancer patients were used. Gene expression study carried out by calculating the brightness of the bands on agarose gel and splicing variants were detected by direct sequencing.  According to the results, three splice forms of ING4 and a decrease in gene expression of ING4 were determined. Splicing type of ING4 affects the translocation of ING4 proteins into the nucleus. To determine the gene expression of each splicing variant, will further clarify the role of ING4 in pancreatic cancers.

Vitamin D can be used as a supplement against cancer stem cells.

Cancer is standing like a bottomless pit or a black hole in front of mankind. Scientists are trying all possible ways to find a solution against to cancer. As known, cancer is a phenomenon fed from internal dynamics. One of internal dynamic is cancer stem cells that are involved in the formation and development of cancer. Because of these dynamics, scientists began to search solution inside of the body. Another internal dynamic is vitamin D and it is not only important in calcium homeostasis but also it is important for cell proliferation, differentiation, and apoptosis. In this study, we investigated the effect of vitamin D on cancer stem cells that sorted from MCF-7 cell line and on HEK293 cell line as control. Our results showed that calcitriol treatment reduced the number of CSC (Cancer Stem Cell) in the MCF-7 cell while increased in HEK293 cell population. Gene expression analyses showed that effect of calcitriol on apoptosis plays an important role in this reduction. Deficiency or unavailability of vitamin D may take a role in the pathogenesis of breast cancer.

Effects of melatonin on apoptosis and cell differentiation in MCF-7 derived cancer stem cells.

Melatonin is a hormone of the pineal gland that has a wide range of biological effects such as antioxidant, anti-inflammatory, and anti-tumor activity. Previous studies have shown that melatonin also affects survival, proliferation, and apoptosis of the cells. In this study, we investigated the effect of melatonin on apoptosis, self-renewal, and differentiation. For this purpose, MCF-7 and HEK293 cells were subjected to melatonin treatment. Expression of genes related to apoptosis (Bax and Bcl2) and self-renewal and differentiation (Oct4, Sox2, and Nanog) analyzed after the sorting of cancer stem cells from MCF-7 cells. Results showed that the effect of melatonin is dependent on the melatonin concentration and treatment periods. Melatonin treatment decreased the cell proliferation rate of MCF-7 in contrast to HEK293. Also, this treatment increased apoptosis in MCF-7 cells and decreased in HEK293 cells. Gene expression of Nanog was decreased and Sox2 was increased in both cell groups after the melatonin treatment. Expression of Oct4 was decreased in MCF-7 cells and increased in HEK293 cells. We determined that melatonin decreases apoptosis and differentiation of stem cells in normal HEK293 stem cells, but increases apoptosis and differentiation in the MCF-7 cancer stem cells.

TLR4 Asp299Gly and Thr399Ile and TLR2 intron 2 microsatellite gene polymorphism in patients with acute biliary pancreatitis: Does it cause the disease?

OBJECTIVES: There has been coverage of Toll-like receptor 4 and Toll-like receptor 2 gene polymorphisms in inflammatory episodes in a number of studies. In view of the inflammatory nature of acute pancreatitis, we aimed to determine the predictive value of mutations in Asp299Gly and Thr399Ile of the Toll-like receptor 4 gene, and the intron 2 microsatellite polymorphism of the Toll-like receptor 2 gene on the occurrence of acute biliary pancreatitis. MATERIAL AND METHODS: The study included 86 patients for the Toll-like receptor 4 Thr399Ile polymorphism, 100 patients for the Toll-like receptor 4 Asp299Gly polymorphism with acute biliary pancreatitis, and 101 healthy volunteers. At the same time, 93 patients and 92 healthy volunteers were included in the study to research the Toll-like receptor 2 intron 2 microsatellite polymorphism. Genotypes were determined using the restriction fragment length polymorphism analysis of PCR products and by an allele-specific PCR. RESULTS: The Toll-like receptor 4 Thr399Ile homozygotes mutant variants (p=0.005) and Toll-like receptor 2 MM genotype (p<0.001) were detected with a significantly higher frequency in patients with acute biliary pancreatitis than in the healthy blood donors. CONCLUSION: The Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms and the Toll-like receptor 2 intron 2 microsatellite polymorphism are statistically associated with ABP.

Studying the C1772T polymorphism of Hif-1α and TGF-ß3 IVS5+104 A/G polymorphism in children with congenital non-syndromic neural tube defects and their mothers.

Prevalence of neural tube defect (NTD) has reduced after folic acid intake. However; which mechanisms are effective in NTD are not known exactly. In this study; due to the possible effects on hypoxic pathway and embryonic development, particularly on extracellular matrix components, Hif-1α Pro582Ser and TGF-ß3 IVS5+104 A/G SfaN1 polymorphisms were studied by PCR-RFLP method both on children with NTDs and mothers. Statistical differences were seen for Hif-1α and TGF-ß3 IVS5+104 A/G SfaN1 polymorphisms in children with NTDs but no difference was seen in mothers. Both genes are effective on many pathways and our results suggest that regulation of extracellular matrix components of children during fetal life is important in neural tube defects formation. The results of this study show that Hif-1α Pro582Ser and TGF-ß3 IVS5+104 A/G SfaN1 polymorphisms may play a role in NTDs.

Fentanyl Inhibits Tumorigenesis from Human Breast Stem Cells by Inducing Apoptosis

Fentanyl is an opioid analgesic that it is widely used in cancer patients. Since there have been reports of effects of analgesic medications on the recurrence and development of resistance to treatment, influences of of fentanyl on MCF-7 and HEK293 cells were evaluated. Cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Gene expression analysis was performed by quantitative real-time PCR assay for the Oct4, Sox2 and Nanog genes as stem cell markers and Bax, Bcl2, and p53 genes as apoptosis markers. MTT assay results showed that fentanyl significantly inhibited the growth of MCF-7 cells in a dose-and time-dependent manner while significantly increasing apoptosis. In contrast, decrease was noted in HEK-293 cells. In MCF-7 derived cancer stem cells, fentanyl treatment decreased the expression of Bax, Bcl2, Oct4, Sox2, Nanog genes when compared to untreated cells. In HEK-293 stem cells, decrease was noted for Sox2, Nanog and Bax, but increase for Oct4. Our study supports an antitumor role of fentanyl by inducing apoptosis and reducing numbers of cancer stem cells in the MCF-7 human breast adenocarcinoma line.

IL-8 gene polymorphism in acute biliary and non biliary pancreatitis: probable cause of high level parameters?

BACKGROUNDS/AIMS: Inflammatory mediators of the innate immune response play fundamental roles in the pathogenesis of acute pancreatitis. The correlation between interleukin-8 (IL-8) gene polymorphism with types of acute pancreatitis and severity of pancreatitis, was evaluated in this study. METHODS: According to the diagnostic criteria, 176 patients with acute pancreatitis were grouped into biliary (n=83) and nonbiliary pancreatitis (n=93). Healthy blood donors (n=100) served as controls. Serum alanine transaminase, aspartate transaminase, total and direct bilirubin, amylase, lypase, white blood cell count and c-reactive protein levels were evaluated to correlate with IL-8 rs4073 (-251T/A) polymorphism, which was analyzed using a real-time polymerase chain reaction method with melting point analysis. RESULTS: The IL-8 AA genotype was detected with a significantly higher frequency among the patients with acute biliary pancreatitis having higher alanine transaminase levels than the median range. Homozygote alleles were significantly higher among patients with acute biliary pancreatitis having amylase levels higher than the median range. CONCLUSIONS: Determination of the frequency of IL-8 polymorphism in acute pancreatitis is informative and provides further evidence concerning the role of IL-8 in laboratory tests.

Testis-Sparing Surgery in Small Testicular Masses Not Suspected to Be Malignant.

UNLABELLED: Fifteen patients with small testicular masses not suspected to be malignant were included in the study, and permanent and frozen section analyses were evaluated. As a result frozen analysis, preoperative externalization of the suspected malignancy with a physical examination, ultrasonographic evaluation, and serum tumor marker analysis were concluded as key points for accurate decision making between TSS and radical orchiectomy. BACKGROUND: We aimed to determine the safety, efficacy, and the concordance of permanent and frozen section analysis (FSA) of testis-sparing surgery (TSS) in patients who had small testicular masses that were not suspected to be malignant. PATIENTS AND METHODS: Fifteen patients who underwent TSS were included in the study. TSS was performed for the patients who had testicular lesions <25 mm and testicular lesion volume <30% of the whole testis. All patients had normal serum tumor marker levels and ultrasonographic evaluation did not indicate malignancy. Surgery was performed via an inguinal approach with temporary cord occlusion and FSA of the lesions. Benign findings allowed for TSS, and cancer prompted total orchiectomy. RESULTS: The mean patient age was 25.33 (range, 20-36) years. The predominant complaint was swelling (9 patients). The mean lesion diameter was 16 mm (range, 5-26 mm). Fourteen of all cases (93%) had benign pathology and underwent TSS. Only 1 patient, whose FSA revealed malignant formation, underwent radical orchiectomy. Final pathology of this patient was seminoma. Complete histopathologic concordance was observed between the results of frozen and permanent sections. TSS was performed with no intra- or postoperative complications. After a mean follow-up of 23 months (range, 6-44 months) all patients, except 3 who were lost to follow-up, were free of disease. CONCLUSION: The main key points for accurate decision-making between TSS and radical orchiectomy are intraoperative FSA and preoperative externalization of possible suspected malignancy with physical examination, ultrasonographic evaluation, and serum tumor marker analysis.

A prospective controlled study to determine the duration of antibiotherapy in the patients with elevated serum PSA levels.

BACKGROUND: The aim of this study was to determine the duration that antibiotherapy should have in order to make total prostate-specific antigen (tPSA) levels decrease to normal ranges in patients without prostatitis symptoms but with total PSA levels around 4.01-9.9 ng/dL. METHODS: A total of 129 male patients were enrolled and divided into either study group (N.=102) or control group (N.=27). The study group received a 21-day treatment with ofloxacin 400 mg/day, while the control group did not receive any treatment. tPSA and free PSA levels were measured on the 7th, 14th and 21st day, and at the 3rd, 6th, and 12th month of the study. tPSA levels and the number of patients whose tPSA levels decreased ≤4.0 ng/dL levels was recorded and analyzed for statistical significance. RESULTS: At 7, 14, and 21 days mean tPSA values were all lower than baseline values and the differences were statistically significant (P<0.05). Of 102 patients 31, 38 and 36 patients had decreased tPSA levels at 7, 14, and 21 days, respectively. But when we compared 7th day mean tPSA levels with days 14 and 21, we found no statistical differences (P>0.05). Sixty-six patients had persistently high tPSA levels and 64 of them underwent prostate biopsy. Prostate cancer was detected in 8 of them (12.5%). CONCLUSIONS: A seven-day course of antibiotherapy is enough to normalize PSA levels in gray-zone patients. If recurrence of PSA increase is seen during follow-up, antibiotherapy can be useful again in those patients who previously benefited from it, while it will prove unnecessary in those who did not have their tPSA level normalized by it.

Does hypericin boost the efficacy of high-power laser? A preliminary experimental study on rats / A hipericina aumenta a eficácia do laser de alta potência? Um estudo preliminar e experimental em ratos

CONTEXT AND OBJECTIVE: Lasers are widely used in treating symptomatic benign prostatic hyperplasia. In current practice, potassium titanyl phosphate (KTP) lasers are the most common type of laser systems used. The aim here was to evaluate the rapid effect of high-power laser systems after application of hypericin. DESIGN AND SETTING: Experimental animal study conducted in the Department of Urology, Gülhane Military Medical Academy, Ankara, Turkey, in 2012. METHODS: Sixteen rats were randomized into four groups: 120 W KTP laser + hypericin; 120 W KTP laser alone; 80 W KTP laser + hypericin; and 80 W KTP laser alone. Hypericin was given intraperitoneally two hours prior to laser applications. The laser incisions were made through the quadriceps muscle of the rats. The depth and the width of the laser incisions were evaluated histologically and recorded. RESULTS: To standardize the effects of the laser, we used the ratio of depth to width. These new values showed us the depth of the laser application per unit width. The new values acquired were evaluated statistically. Mean depth/width values were 231.6, 173.6, 214.1 and 178.9 in groups 1, 2, 3 and 4, respectively. The most notable result was that higher degrees of tissue penetration were achieved in the groups with hypericin (P < 0.05). CONCLUSIONS: The encouraging results from our preliminary study demonstrated that hypericin may improve the effects of KTP laser applications. .

CONTEXTO E OBJETIVO: Lasers são amplamente utilizados no tratamento de hiperplasia benigna de próstata sintomática. Na prática atual, lasers de fosfato de titanilo de potássio (KTP) são os tipos mais comuns usados dos sistemas. O objetivo foi avaliar o efeito rápido do sistema laser de alta potência após a aplicação de hipericina. TIPO DE ESTUDO E LOCAL: Estudo experimental animal, realizado no Departamento de Urologia, Academia de Medicina Militar de Gülhane, Ancara, Turquia, em 2012. MÉTODOS: 16 ratos foram divididos aleatoriamente em 4 grupos: 120W KTP laser + hipericina; 120W KTP laser somente; 80W KTP laser + hipericina; 80W KTP laser somente. Hipericina foi dada intraperitonealmente duas horas antes da aplicação do laser. As incisões a laser foram feitas através do músculo quadríceps dos ratos. A profundidade e a largura das incisões a laser foram avaliadas histologicamente e registradas. RESULTADOS: Para padronizar o efeito do laser foi utilizada a razão entre profundidade e largura. Estes novos valores nos mostraram a profundidade da aplicação do laser de largura por unidade. Os novos valores adquiridos foram avaliados estatisticamente. Os valores da média de profundidade/largura foram 231,6, 173,6, 214,1 e 178,9 nos grupos 1, 2, 3 e 4, respectivamente. O resultado mais notável foi atingir altos graus de penetração tecidual nos grupos com hipericina (P < 0,05). CONCLUSÕES: Os resultados promissores do nosso estudo preliminar mostraram que hipericina pode melhorar os efeitos das aplicações do laser KTP. .

Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive production of free oxygen radicals. Free Oxygen radicals cause cellular injury by inducing nicks in DNA. The enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) involved in the process of repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. Thus, we designed a study to evaluate the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, against extracorporeal shock wave induced renal injury. METHODS: Twenty-four Sprague-Dawley rats were divided into three groups: control, ESW, ESW + 3-AB groups. All groups except control group were subjected to ESW procedure. ESW + 3-AB group received 20 mg/kg/day 3-aminobenzamide intraperitoneally at 2 h before ESW and continued once a day for consecutive 3 days. The surviving animals were sacrificed at the 4th day and their kidneys were harvested for biochemical and histopathologic analysis. Blood samples from animals were also obtained. RESULTS: Serum ALT and AST levels, serum neopterin and tissue oxidative stress parameters were increased in the ESW group and almost came to control values in the treatment group (p < 0.05, ESW vs. ESW + 3-AB). Histopathological injury score were significantly lower in treatment group than the ESW group (p < 0.05, ESW vs. ESW + 3-AB). CONCLUSION: Our data showed that PARP inhibition protected renal tissue against ESW induced renal injury. These findings suggest that it would be possible to improve the outcome of ESW induced renal injury by using PARP inhibitors as a preventive therapy.

Fibrous pseudotumors of the testis: The balance between sparing the testis and preoperative diagnostic difficulty.

OBJECTIVE: To determine a paradigm that will be helpful for urologists to manage fibrous pseudotumors, which are a very rare condition of the testis. MATERIAL AND METHODS: We retrospectively evaluated the patients with fibrous pseudotumors in our uropathological database from 1995 to 2013. Patients who had tumor markers and ultrosonography (USG) screening before surgery and a final pathology report of a fibrous pseudotumor were included in the study. RESULTS: In total, 838 patients with a testis mass were evaluated. Only 6 of these patients met the inclusion criteria. The mean age was 34 years (min: 20, max: 72). Serum tumor markers were in the normal range for all patients. The scrotal tumors were not clearly related to the testis parenchyma, and the radiologists could not definitively determine the nature of the masses (benign or malignant). A concomitant hydrocele was detected in 2 patients. After inguinal exploration, radical orchiectomy was performed in one patient with an ipsilateral atrophic testis, and biopsies were taken from the lesions for frozen section analysis in the other 5 patients. Pathologists reported benign tumors for all of these patients based on the frozen sections, and testicular sparing surgery was then performed in these 5 patients. CONCLUSION: If scrotal tumors are detected by ultrasonography in patients with normal tumor markers, and the tumor cannot be clear distinguished from the testis, these patients might have a fibrous pseudotumor, and organ-sparing surgery can be performed on these patients.

Inflammatory Markers: C-Reactive Protein, Erythrocyte Sedimentation Rate, and Leukocyte Count in Vitamin D Deficient Patients with and without Chronic Kidney Disease.

Although some studies revealed a positive relationship between vitamin D3 deficiency and inflammatory markers, there have been also many studies that failed to find this relationship. The aim of this large scaled study is to determine the association between the level of plasma 25 hydroxy vitamin D3 [25-(OH) D3] and inflammatory markers in the general population without chronic kidney disease (CKD) and in patients with CKD. Participants with simultaneously measured inflammatory markers and 25-(OH) D3 levels were retrospectively analyzed (n = 1897). The incidence of all-cause inflammation infection, hospitalization, chronic renal failure, and vitamin B12 deficiency was evaluated. The medians of serum creatinine levels in subjects without renal failure were lower in 25-(OH) D3 deficient group. Patients with CKD were more likely to have vitamin D3 deficiency compared with normal GFR. 25-(OH) D3 levels were associated with a greater incidence of all-cause hospitalization, hypoalbuminemia, and vitamin B12 deficiency. However, there was no relationship between inflammatory markers and vitamin D3 levels. In 25-(OH) D3 deficient patients, inflammatory markers can be related to other inflammatory and infectious status such as malnutrition and cachexia. We believed that there must be a relationship between vitamin deficiency and inflammatory markers due to other causes than low 25-(OH) D3 status.

Bilateral renal metastasis of an inguinal malignant solitary fibrous tumor, 9 years after primary surgical treatment.

OBJECTIVE: To report the first case of a bilateral renal solitary fibrous tumor (SFT) as a metastasis of an inguinal malignant SFT. CLINICAL PRESENTATION AND INTERVENTION: A 60-year-old male patient with a history of a right inguinal 7 × 8 cm soft tissue mass excision 9 years ago was referred to our clinic with abdominal pain. Both physical examination and chest X-ray were normal. Computed tomography revealed bilateral renal tumor. He was successfully treated with left partial and right radical nephrectomy. Histopathological examination showed a metastasis of the previous inguinal SFT. CONCLUSION: This case showed that although malignant SFT is extremely rare in the urogenital tract, this tumor should be included in the differential diagnosis when identified in the kidneys.

Intralymphatic delivery of platinum-based chemotherapeutics is possible: an experimental study.

PURPOSE: Systemic chemotherapy regimens with cisplatinum have been associated with several toxicities. Thus, a loco-regional therapy approach may greatly reduce the toxicity. For this purpose, we designed this experimental study to investigate whether local chemotherapeutic injection is superior to systemic cisplatinum injection for retroperitoneal lymph nodes. METHODS: A total of 48 male Wistar rats were included to the study. Rats were divided into six groups. In the first three groups, systemic applications of cisplatinum, carboplatinum and oxaliplatin were performed, respectively. In the last three, local administration of cisplatinum, carboplatinum and oxaliplatin was performed, respectively. One hour after the chemotherapeutic agent applications, retroperitoneal lymph nodes were dissected and platinum concentrations were analyzed. RESULTS: When compared with systemic route, achieving higher platinum concentrations in the local chemotherapeutic application groups was the most spectacular result of the study. Serum platinum concentrations were also lower in the local application groups than systemic ones. When we compared local and systemic applications between three chemotherapeutic agents, the most significant concentration difference was seen in carboplatinum group. CONCLUSION: The results of this study demonstrate that intralymphatic delivery of cisplatinum, carboplatinum and oxaliplatin leads to higher drug concentrations in the retroperitoneal lymph nodes when compared with intravenous administration.

Testosterone relaxes human internal spermatic vein through potassium channel opening action.

OBJECTIVES: To investigate the relation of testosterone-induced relaxation with smooth muscle K+ channels in human internal spermatic veins. Testosterone induces relaxation in human isolated internal spermatic veins, and this effect decreases in high-grade varicocele (recently reported). METHODS: The responses of isolated internal spermatic veins from patients with varicocele were recorded isometrically using a force displacement transducer. After contracting the venous rings with 45 mM KCl, relaxation with testosterone (0.1-300 µM) was recorded in the absence or presence of large conductance calcium-activated K+ channel and the voltage-sensitive K+ channel inhibitor tetraethylammonium, adenosine triphosphate-sensitive K+ channel inhibitor glibenclamide, voltage-dependent inward rectifier K+ channel inhibitor barium chloride, and voltage-sensitive K+ channel inhibitor 4-aminopyridine. RESULTS: Testosterone induced relaxation in human isolated internal spermatic veins in the absence of inhibitors (maximal effect 52.88±6.72, n=24). Although tetraethylammonium, barium chloride, and 4-aminopyridine did not alter the testosterone-induced relaxant responses, GLI inhibited these responses. CONCLUSIONS: These results have demonstrated that testosterone induces relaxation in human isolated internal spermatic veins of patients with varicocele by way of adenosine triphosphate-sensitive K+ channels.

Different clinical presentations of pelvic ectopic kidneys: report of two cases and review of the literature.

Pelvic kidney is the most common type of renal ectopia. These abnormally positioned kidneys are often clinically asymptomatic. However, they are prone to urinary infection, stone formation and trauma. Admitted patients often complain of lower abdominal pain and urinary infection. Pelvic kidneys may also lead to misdiagnosis when it is associated with hydronephrosis or large cystic structures. Thus, it is rather difficult to pinpoint the origin of the problem. We reported here different clinical presentations of our two patients with pelvic kidneys.