The role of miRNAs targeting K-ras and APC genes in colorectal cancer.

OBJECTIVES: The occurrence of abnormal expression patterns in different types of cancer suggests that micro RNAs (miRNAs) may play an important role in tumorigenesis. The aim of this study was to examine the expression levels of miRNAs known to be associated with the regulation of the expression levels of the APC and K-ras, which are important in the development of colorectal cancer (CRC). METHODS: The expression levels of miR-27, miR-663, miR-217, miR-181d, APC and K-ras in the serum, tumor and adjacent tumor-free (healthy) tissues of the patients and serum of the healthy controls were investigated with qRT-PCR. RESULTS: Expression levels of miR-217, mR-181d, miR-663, miR-27 and K-ras were found to be higher in CRC tissues than in adjacent tumor-free tissues of the patients. In patient serum samples, miR-663 levels were statistically more elevated than in controls. In patient tumor tissues, miR-217, miR-181d and miR-27 expressions were found to be higher. CONCLUSIONS: Increased miR-181d and miR-217 expression levels are associated with increased K-ras expression in the tumor tissues, and the expression of K-ras, which takes part as an oncogene in the CRC development, might be regulated by these miRNAs (Tab. 4, Ref. 33).

Are there possible associations between MnSOD and GPx1 gene variants for laryngeal cancer risk or disease progression?

Laryngeal squamous cell carcinoma (LSCC) is a multifaceted and genomically complex disease and cellular and preclinical studies have demystified wide ranging molecular mechanisms which underpin its development and progression and resistance against wide ranging molecular therapeutics. Oxidative stress is a widely studied molecular mechanism and reportedly involved in carcinogenesis. Increasingly it is being realized that accumulation of Reactive Oxygen Species (ROS) activates defensive mechanism to counteract oxidative stress induced damage. Manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) are important members of defensive machinery. We investigated whether the polymorphisms of MnSOD (Ala-9Val, rs4880) and GPx1 (Pro198Leu, rs1050450) are associated with LSCC and also evaluated possible interactions between these polymorphisms and various lifestyle factors or pathological features of patients. For this purpose, 67 LSCC patients and 73 healty controls were enrolled. Molecular assessment of MnSOD and GPx1 variants were determined with polymerase chain reaction-restriction fragment length polymorphism techniques. We found that the frequency of both heterozygous PL genotype and P allele was considerably higher in patients with advanced tumor stage (T3/T4) than in those with early tumor stage (T1/T2) (OR= 5.106; 95% CI=1.372-19.004; p<0.001, OR=5.787; 95% CI =1.564-21.414; p<0.001 respectively). Although the frequency of ValVal/LL combine genotype was significantly decreased (OR=0.204, 95% CI=0.055-0.760; p=0.021), the frequency of ValAla/PL combine genotypes was higher in patients with stage T3/T4 than in those patients with stage T1/T2 (p=0.027). Consequently, we have concluded that variants of GPx1 and MnSOD should not be considered as a risk factor of LSCC, only may be accepted as a prognostic markers. Use of new technologies such as metabolomics and deep DNA sequencing will prove to be helpful in developing a deeper knowledge related to how cancer cell metabolism adapts and provides a buffer against increased oxidative stress.

An association between MPO -463 G/A polymorphism and type 2 diabetes.

Myeloperoxidase (MPO) is an enzyme which is a member of the haem-peroxidase superfamily and plays a role in production of reactive oxygen species. The most common polymorphism in the promoter region of MPO gene is -463 G/A. It was shown that carrying the GG genotype means increased activity of the gene approximately 2-3-fold compared to GA and AA genotypes. It was found that hyperglycaemia, modified oxidized proteins and increased advanced glycosylated end products (AGE) are related to oxidative stress in diabetes. Under the hyperglycaemic conditions, production of reactive oxygen radical is elevated in smooth muscle endothelial cells, mesengial and tubular endothelial cells. Especially, elevated lipid oxidation plays an important role in pathogenesis of diabetic complications such as cardiovascular complications. We examined the MPO -463 G/A polymorphism by using the PCR-RFLP method in 145 type 2 diabetic patients and 151 healthy controls. We observed that the AA genotype and A allele were protective variants against type 2 diabetes and the GG genotype was a risk factor for diabetes. While we studied the relationship between genotypes and biochemical parameters, we found that patients with the A allele had decreased serum cholesterol, triglyceride, VLDL levels and body mass index. We suggest that the MPO gene has an important role in pathogenesis of type 2 diabetes because of the increased frequency of GG genotype, which is related to increased activity and oxidant capacity of MPO in the patients.

Expression levels of elastin and related genes in human varicose veins.

Among the suspected reasons for varicose vein formation are changes in the quantity and content of the elastin protein; however, comprehensive investigations about elastin assembly in varicose vein formation are yet lacking. In this study, we aimed to determine the changes in mRNA levels of elastin and some of its functionally related proteins, fibulin 5, LOXL-1, MMP-2 and MMP-9 in varicose vein formation. We analysed the mRNA levels of elastin, fibulin-5, LOXL1, MMP2 and MMP9 in samples of 35 healthy and 35 varicose great saphenous vein tissues. mRNA levels of these genes were determined by using real-time PCR and normalized with HPRT1. When we compared the patient and control groups, elastin mRNA levels were significantly higher in the patient group than in the control group (P = 0.047), although there were no significant differences in fibulin 5, LOXL1, MMP2 and MMP9 mRNA levels between the patient and control groups. We showed that up-regulation of MMP2 mRNA expression was significantly correlated with hyperlipidaemia (P = 0.029). The up-regulation of elastin expression may play an important role in the pathogenesis of primary varicose veins. Additionally, the up-regulation of MMP2 expression was strongly correlated with hyperlipidaemia in varicose veins.

Endoscopically operated 15 ventral skull-base dermoid and epidermoid cysts: Outcomes of a case series and technical note.

BACKGROUND: Epidermoid and dermoid tumors in the sellar region are rare. These cystic lesions are a surgical challenge, as the thin capsule adheres firmly to nearby structures. A case series of 15 patients is presented. METHODS: The patients were operated on in our clinic between April 2009 and November 2021. The endoscopic transnasal approach (ETA) was used. Lesions were located in the ventral skull base. In addition, the literature was reviewed to compare clinical features and outcomes of ventral skull-base epidermoid/dermoid tumors operated on via ETA. RESULTS: In our series, removal of cystic contents and tumor capsule (gross total resection: GTR) was achieved in 3 patients (20%). GTR was not possible for the others, because of adhesions to vital structures. Near total resection (NTR) was achieved in 11 patients (73.4%), and subtotal resection (STR) in 1 (6.6%). At a mean follow-up of 55±26.27 months, there were no cases of recurrence requiring surgery. CONCLUSION: Our series demonstrates that ETA is suitable for resection of epidermoid and dermoid cysts in the ventral skull base. GTR cannot always be the absolute clinical aim, because of inherent risks. In patients with expected long-term survival, the aggressiveness of surgery should be weighed on an individual risk/benefit basis.

Coronary artery calcifications in hemodialysis patients and their correlation with the prevalence of erectile dysfunction.

INTRODUCTION: Our aim in this study was to investigate the prevalence and correlation with coronary artery calcium scores (CACS) and erectile dysfunction (ED) among hemodialysis patients. PATIENTS AND METHODS: Thirty-five male patients with chronic renal failure were selected to participate in this study. All patients underwent examinations for CACS using 16-channel multidetector computed tomography. The presence and severity of ED were determined by calculating the erectile function domain of the self-administered International Index of Erectile Function (IIEF). RESULTS: The patients' ages ranged from 22 to 78 with a mean of 51.6 years. The mean duration of hemodialysis was 75.7 months (range = 12 to 232). Twenty-six patients had a history of one or more systemic diseases. The prevalence of any level of ED was 82.9% for all hemodialysis patients, and severe ED, 40%. The CACS was significantly higher among patients with severe ED (P = .032). The IIEF-5 score was also shown to have a moderate negative correlation with the CACS (r = -.420, P = .012). Age, duration of hemodialysis, body mass index, diabetes mellitus, hypertension, coronary heart diseases, hyperlipidemia, thyroid disease, depression, tobacco consumption, and medication were not associated with the presence of ED (P > .05). CONCLUSION: ED is prevalent in hemodialysis patients. Although many possible factors contribute to ED, the severity of ED increases with greater CACS.

Clinical significance of serum ferritin in patients with renal cell carcinoma.

OBJECTIVES: We examined the serum ferritin levels in 158 patients with renal cell carcinoma and 101 healthy control subjects between 1987 and 1994 to investigate the value of this intracellular protein as a tumor marker. METHODS: Preoperative and postoperative serum ferritin values were analyzed and the patients were stratified to three groups accordingly: group 1, patients with normal values (N-N); group 2, those with preoperative high and postoperative normal (H-N); and group 3, those with preoperative normal or high with postoperative high ferritin levels (H-H). RESULTS: The mean serum ferritin level in 101 healthy control subjects was 85.7 +/- 63.6 ng/mL (range, 3.7 to 265.2). The upper limit of normal, which was calculated by adding 2 standard deviations to the mean was 219.9 ng/mL. Mean serum ferritin in patients with renal cell carcinoma was 274.2 +/- 276.3 ng/mL, which was significantly higher than that of control values (P < 0.01). The sensitivity, specificity, and overall accuracy rate for ferritin increase was 94%, 50%, and 61%, respectively. Multivariate analysis showed that the aforementioned grouping and stage of the disease were the two independent prognostic parameters. Preoperative ferritin levels lost its significance on multivariate analysis. CONCLUSIONS: Our study shows that although serum ferritin was a useful tool in diagnosing and staging patients, it was not ideal in early stages. However serum ferritin seems to be more valuable for follow-up; postoperative values, indeed, predict the prognosis.

Postchemotherapeutic surgery for metastatic testicular germ cell tumors: results of extended primary chemotherapy and limited surgery.

OBJECTIVE: Postchemotherapy surgery has become an increasingly important treatment for residual masses in germ cell tumors of the testis. However, it is still a challenge to find the optimal combination of chemotherapy and surgery for better survival and cure rates with lowest morbidity. This study evaluated the effectiveness of extended chemotherapy followed by surgery resecting only the residual masses. METHODS: After an extended course (one or two additional courses after there is no decrease in tumor size and/or after the normalization of tumor markers) of combination chemotherapies with cisplatin-based regimens, 32 patients underwent surgery for metastatic germ cell tumors of the testis. Complete excision of radiologically determined residual masses and macroscopically suspicious neighboring nodes was performed rather than a conventional retroperitoneal lymph node dissection. RESULTS: Histopathologic examination of the resected specimens revealed teratoma in 17 (55%), fibrosis and/or necrosis in 9 (26.5%), and active residual tumor in 8 (23.5%) of the patients. The patients with residual tumor have been treated with additional chemotherapy. In the follow-up (mean, 28.5 months) 4 patients have relapsed, and 1 died. None of the patients with residual teratomas have shown relapse. Only 1 of the 32 patients has had retrograde ejaculation. CONCLUSIONS: A more conservative approach, such as excision of the residual masses after an extended course of chemotherapy, has given excellent results both in the outcome of the patients in the follow-up and in the rate of retrograde ejaculation. We therefore suggest that this approach would be a good alternative to nerve-sparing surgery following chemotherapy.

Combined use of prostate-specific antigen derivatives decreases the number of unnecessary biopsies to detect prostate cancer.

The authors evaluated the prostate cancer detection rate in Turkish patients with prostate-specific antigen (PSA) levels of 4 ng/ml to 10 ng/ml and who had normal digital rectal examination (DRE) findings. They also aimed to evaluate the value of PSA density and percent free PSA in minimizing unnecessary prostate biopsies for these PSA ranges. This prospective study included 134 consecutive men referred for early prostate cancer detection or lower urinary tract symptoms. All men underwent transrectal ultrasound with systematic sextant needle biopsies. The ability of PSA density and percent free PSA to improve the power of PSA in the detection of prostate cancer was evaluated with statistical analyses as well as receiver operating characteristics curves. Among the 134 men, 124 (92.5%) had a benign histology and 10 (7.5%) had cancer diagnosed on the initial biopsies. Despite the disappointing results in regard to the sensitivity and specificity of PSA derivatives alone, the combination of PSA density and percent free PSA significantly increased the area under the curve compared with the use of each test alone. To increase the specificity of PSA in this patient population, the authors recommend combining two PSA derivatives in deciding whether to perform a biopsy. In a PSA range of 4 ng/ml to 10 ng/ml and with normal DRE, a percent free PSA < 21% and a PSA density > 0.18 yields highest specificity with 90% sensitivity.

Short-term chlorambucil for refractory uveitis in Behcet's disease.

AIM: To evaluate the effects of short-term chlorambucil therapy in the management of uveitis due to Behcet's disease. METHODS: Forty-four patients with refractory uveitis associated with Behcet's disease who had had short-term chlorambucil therapy for about 23 weeks were included in the study. The frequency of attacks (number of attacks per year) and the longest period between the attacks were analyzed to evaluate the efficiency of the therapy. The therapy was judged to be effective if the patient had < or =1 attack a year and/or > or =1 year between the attacks. RESULTS: The mean follow-up time was 51.4 +/- 32.5 months (range: 13-122 months). Following the therapy, the mean frequency of attacks had decreased from 4.9 +/- 2.3 to 0.9 +/- 1.4 (p < 0.0001) and the mean longest period between the attacks was prolonged from 4.4 +/- 2.3 months to 25.7 +/- 23.1 months (p < 0.0001). The ratio of severe attacks had decreased from 74.1 +/- 34% to 51.3 +/- 36.6% (p = 0.0218). The best-corrected visual acuity was increased in 32.9%, decreased in 34.2%, and the same in 32.9% of the eyes. Phytsis bulbi developed in three (3.8%) eyes. New attacks were seen in 56.8% of patients and another immunosuppressive agent(s) was given to 40.9% of the patients 1-8 months after treatment. No serious side effects were observed during the chlorambucil therapy. CONCLUSION: Short-term chlorambucil therapy for refractory uveitis in Behcet's disease is effective in controlling the disease in two-thirds of patients.

Surveillance-only policy in clinical stage-I non-seminomatous germ-cell tumors of the testis.

With the advanced imaging techniques, the sensitive assays for tumor markers and the curability of small-volume metastatic disease with cis-platinum-based chemotherapy, surveillance has gained popularity in clinical stage-I non-seminomatous germ-cell tumors. This study reports our experience on 58 patients who have been included in a surveillance protocol. Patients with normal tumor-marker levels following surgery, no evidence of metastases on the CT scans of the abdomen and the chest and no residual tumor at the surgical margin were followed. Relapsing patients were treated with cis-platinum-based combination chemotherapy. Of the 58 patients, 17 relapsed (29.3%) in a period of 2-18 months (median 5 months). None of the relapsing patients later presented with evidence of disease in the follow-up period 14-79 months (median 39 months) after chemotherapy. Prognostic factors were evaluated by univariate analysis and the data for risk factors, such as the presence of embryonal carcinoma, absence of yolk-sac elements and scrotal violation, were evaluated by multivariate analysis. Statistical analysis showed that none of the risk factors were significantly different in predicting the relapse. Of the 6 relapsing patients with preorchiectomy elevated tumor-marker levels, 4 had shown a slower decline in tumor-marker levels than expected and they all relapsed with elevated levels of the same tumor markers. A surveillance-only policy actually seems to be a safe and logical approach if the patients are properly selected and cooperate fully.

Long-term treatment of nocturnal enuresis with desmopressin intranasal spray.

The purpose of this study was to determine the efficacy and safety of long-term treatment of nocturnal enuresis with desmopressin intranasal spray. Sixty-five children with primary nocturnal enuresis with a mean age of 11.3 years (range 7-17) underwent a 2-week observation period followed by dose titration period of 1 week. Those children completely dry with desmopressin entered a randomized, placebo-controlled, double-blind phase lasting 2 weeks, followed by a 6-month open treatment. The enuretic status of the children was documented for 2 weeks after the treatment was stopped. Eleven children had no change from baseline wetting with desmopressin. Thirty-two children receiving 20 mg and 9 children with 40 mg desmopressin were completely dry. Thirteen children were wet 1-2 nights per week, which was better than in the pretreatment period. During the 6-month open-treatment period, the effect of desmopressin was found to be stable. No side effects or adverse reactions were encountered. Two weeks after the treatment was stopped, 25 children were still completely dry (38% of the initial study population, 50% of the responders). The cure rate appeared to continue beyond 18 months after discontinuation of the treatment.

Stone fragility in shock wave lithotripsy can be predicted in vitro.

OBJECTIVE: To investigate the effect of stone size, chemical structure, radiologic appearance, stone weight and stone mineral density on in vitro stone fragility. METHODS: A total of 216 stones obtained by open surgery were stratified according to their size, chemical structure (X-ray crystallography), radiologic appearance, mineral content and density (dual photon absorptiometry) and weight. Stone fragility was measured by the number of shock waves needed to completely fragment the stones in a phantom model by Dornier. RESULTS: Stone weight increased according to stone size and mineral density varied in relation to chemical composition. The radiologic appearance was not predictive of the chemical content. The most significant variable to predict the number of shock waves needed for full fragmentation was the stone weight. The stone weight could be formulated as a function of mineral content and the equation had statistical significance (p = 0.000). The necessary number of shock waves for complete disintegration also could be estimated by using stone weight, stone size and mineral density. This equation was also statistically significant (p = 0.000). CONCLUSIONS: Stone weight which is a function of stone mineral content seems to be the single most important parameter to predict stone fragility in vitro. Stone weight can be estimated by using the stone mineral content. Prediction of the necessary number of shock waves for full fragmentation seems possible and is formulated into an equation that proved to be statistically significant in vitro. In vivo application of this estimation awaits further research.

Zinc plasma levels in prostatic carcinoma and BPH.

Zinc in serum from patients with prostatic carcinoma and BPH before and after treatment was analyzed by atomic absorption spectrometry. There were significant differences between prostatic cancer and BPH. We also found distinct differences in the plasma content of zinc in patients with prostatic carcinoma before and after therapy. We conclude that the zinc concentration in serum may be a valuable index for the differential diagnosis and therapy of prostatic carcinoma.

Enuresis nocturna: new concepts in pathophysiology.

Although nocturnal enuresis was first described centuries ago, there is still a lot unknown about its pathophysiology. The functional bladder capacities, diurnal vasopressin levels, urine osmolalities and urine output of enuretic and normal children were compared. We have concluded that enuretics have normal bladder capacities insufficient for increased nocturnal urine volumes because of loss of diurnal variation in serum vasopressin levels and related decrease in urinary osmolalities.

Dynamic cavernosography in the evaluation of impotence.

Dynamic cavernosography before and after papaverine injection into the corpus cavernosum of 6 sexually normal volunteers and 44 impotent patients was performed with digital subtracting angiography technique. The average infusion rates in 26 patients with venous leakage were 325.5 ml/min for induction of erection and 161 ml/min for maintenance. The results for the remaining 18 impotent patients without venous leakage were 128.8 ml/min for induction and 56.9 ml/min for induction and 58.3 ml/min for maintenance. After papaverine injection the average infusion rates decreased to 131 ml/min (induction) and 59 ml/min (maintenance) in patients with venous leakage, 38.4 ml/min and 14.6 ml/min in the impotent patients without venous leakage and 35 ml/min and 14.1 ml/min in the control group, respectively. It was also noticed that in the control group filling of the superficial and deep veins may occur during the flaccid phase which disappeared with induced erection. Therefore we suggest intracavernous papaverine injection with dynamic cavernosography. The digital subtracting technique eliminates unnecessary images, providing a more accurate diagnosis of venous incompetence.

Immunohistochemical detection of beta-human chorionic gonadotropin in urothelial carcinoma.

Histologic sections from the specimens of 60 patients with urothelial carcinoma were stained immunohistochemically to search for beta-human chorionic gonadotropin (B-HCG) production. There were 6 doubtful, 5 weak and 1 strong positive B-HCG stainings among 65 sections from 60 patients. De novo acquisition of B-HCG production capability of tumour cells seemed to be predictive for early haematogenous dissemination of the disease, but the data obtained in this particular study were insufficient to suggest B-HCG as a routine prognostic marker.

Acute experimental unilateral orchitis in the rabbit and its effect on fertility.

We examined the nature of contralateral damage following unilateral orchitis to see if an immunologically mediated mechanism was present. Experimentally induced orchitis in 18 white New Zealand rabbits were examined and compared to 20 in the control groups. Serum antisperm antibody presence and bilateral testicular biopsies (Johansen biopsy score, mean seminiferous tubule diameter) were examined and pregnancy rates were noted. Acute orchitis seemed to be a causative factor in production of antisperm antibody and the presence of antisperm antibody caused histologic changes in contralateral testicles and therefore impaired fertility.

Genital infections in men associated with Chlamydia trachomatis.

The advent of new diagnostic procedures has made it possible for urologists to detect chlamydial presence in genital infections. Many studies have shown chlamydial association with urethritis. However, its presence in prostatitis and epididymitis has not been clearly defined yet. In this study we investigated the presence of Chlamydia trachomatis using enzyme linked immuno assay (ELISA) antigen and antibody detection method in sexually active men with different genital infections. We have found that in 32.1% of patients with non-gonococcal urethritis chlamydial antigen is detectable. We also have been able to detect chlamydial antigen in two patients with chronic non-bacterial prostatitis, but in no patients with epididymitis. We conclude that besides its presence in urethritis, there is an association between chlamydia and chronic prostatitis. Yet, further studies are needed to delineate this association more clearly.

Collision metastasis of bladder and prostate carcinoma to a single pelvic lymph node.

Genitourinary organs are at greater risk for multiple primary malignant neoplasms because of the high incidence of these tumours as primaries among all other organs. We present a case of prostate and bladder carcinoma metastasized to a single pelvic lymph node, called a "collision" metastasis, in a patient with four primary tumours.