Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and ...distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinoma and 67% (10/15) of intraductal cribriform proliferations compared with 13% (5/39) of PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.
Hypoxia Inducible Factor-1 alpha and Hypoxia Inducible Factor-2 alpha (HIF-1α and HIF-2α) are crucial in Renal Cell Carcinoma (RCC) formation. Hypoxia Associated Factor (HAF) prompts HIF-1α ...degradation regardless of oxygen levels, but no such link exists for HIF-2α. This study encompassed 239 cases, where tissue microarray (TMA) sections were exposed to HIF-1α, HIF-2α, and HAF antibodies. Staining intensity and tumor cell percentage determined scores for HIF-1α, HIF-2α, and HAF, with median histoscore establishing "high" or "low" cutoffs. Among the cases, 64.9% (155 cases) were negative for HIF-1α, 17.6% (42 cases) displayed low, and another 17.6% (42 cases) showed strong HIF-1α expression. HIF-1α expression correlated significantly with histological type and World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade. Regarding HIF-2α, 15.5% (37 cases) were negative, 23.4% (56 cases) exhibited low, and 61.1% (146 cases) displayed high expression, with larger tumor size in the high HIF-2α group. Among 239 cases, 41.4% (99 cases) were negative for HAF, 36.8% (88 cases) showed low, and 21.8% (52 cases) displayed high HAF scores. HAF expression correlated with WHO/ISUP nuclear grade and metastasis presence. Notably, HIF-2α staining intensity directly correlated with increased HAF intensity (rho=0.146; p=0.024), while HIF-1α intensity decrease corresponded with heightened HAF intensity, showing a statistically significant negative correlation (rho=-0.180; p=0.005). In this rare examination of tumor tissue, a reverse connection between HIF-1α and HAF expression was uncovered, while a linear link emerged between HIF-2α and HAF expression. Overall, this study established that HIF-1α, HIF-2α, and HAF expression are associated with an unfavorable prognosis.
A 72-year-old male patient presented to the hospital with right flank pain, fever and haematuria. Computed tomography revealed a horseshoe kidney, grade 2 hydronephrosis and a focal hyperdense ...lesion, of which differential diagnosis between mass and abscess could not be made, in the right kidney. Magnetic resonance imaging was performed subsequently and revealed a mass. Right radical nephroureterectomy was then performed. Pathological examination described a fragile, necrotic lesion, which was a sign of chronic pyelonephritis that dilated the pelvicalyceal system. It was also associated with the mucosa and formed cystic structures with a size of 5×4 cm in the cortex. Chronic pyelonephritis cases with acute episodes should be considered in the differential diagnosis of renal tumours.
Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC. Targeting immune checkpoints with ...the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment.
Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1α, and HIF-2α in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment.
PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2α expression. Low or high expression of HIF-1α was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3-4 tumors was significantly higher in PD-L1-positive cases than in negative ones.
PD-L1 tumor cell expression is strongly associated with increased HIF-2α expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment.
Abstract
Background
Chondral injury is a common problem around the world. Currently, there are several treatment strategies for these types of injuries. The possible complications and problems ...associated with conventional techniques lead us to investigate a minimally invasive and biotechnological alternative treatment. Combining tissue-engineering and microencapsulation technologies provide new direction for the development of biotechnological solutions. The aim of this study is to develop a minimal invasive tissue-engineering approach, using bio-targeted microspheres including autologous cells, for the treatment of the cartilage lesions.
Method
In this study, a total of 28 sheeps of Akkaraman breed were randomly assigned to one of the following groups: control (group 1), microfracture (group 2), scaffold (group 3), and microsphere (group 4). Microspheres and scaffold group animals underwent adipose tissue collection prior to the treatment surgery. Mesenchymal cells collected from adipose tissue were differentiated into chondrocytes and encapsulated with scaffolds and microspheres. Osteochondral damage was conducted in the right knee joint of the sheep to create an animal model and all animals treated according to study groups.
Results
Both macroscopic and radiologic examination showed that groups 3 and 4 have resulted better compared to the control and microfracture groups. Moreover, histologic assessments indicate hyaline-like cartilage formations in groups 3 and 4.
Conclusion
In conclusion, we believe that the bio-targeted microspheres can be a more effective, easier, and safer approach for cartilage tissue engineering compared to previous alternatives.
We aimed to investigate antioxidant and neuroprotective properties of chlorogenic acid in spinal cord injury (SCI).
Twenty-one rats were divided into three groups. Laminectomy was performed in group ...L (n=7), spinal cord trauma was induced in group T (n=7), and spinal cord trauma was induced and chlorogenic acid treatment was started in group C (n=7). Blood samples were collected to analyze baseline values and the 12th h, 1st day, 3rd day, and 5th day catalase, native thiol (NT), total thiol (TT), disulfide (SS), SS/TT, SS/NT, and NT/TT levels. Functional analysis with Basso-Beattie and Bresnahan scores was performed at the same time points. Total antioxidant status (TAS), total oxidative stress, oxidative stress index, and cyclooxygenase-2 (Cox-2) were examined in the spinal cord of rats euthanized on day 7; results were statistically analyzed.
On day 7, catalase levels in Group C were significantly higher than baseline levels, whereas those in Group T were significantly lower than baseline levels; Group L showed no significant difference (p=0.008). SS values on day 7 were lower in Group T than in Groups C and L. Group C showed the lowest decrease in NT/TT level after trauma. On day 7, SS/TT level was high in Group T but stable in Groups C and L (p=0.04). Histopathological examination revealed significantly lower Cox-2 and TAS levels in Group C than in Group T (p=0.003, p=0.017, respectively).
In this study, SCI was primarily examined through thiol-SS balance, and it was demonstrated by experimental models that chlorogenic acid has antioxidant and neuroprotective effects in SCI.
To compare the patients who underwent robot assisted radical cystectomy (RARC) and extended pelvic lymph node dissection (EPLND) and whose pathology result was reported as micropapillary variant ...(MV), plasmacytoid variant (PV) and pure urothelial carcinoma (PUC).
The data of 133 patients who underwent RARC and EPLND with the postoperative pathology results reported as MV, PV and PUC were analyzed. According to the postoperative pathology results, patients were divided into two groups in initial analyses as variant pathologies group (n=14) and PUC group (n=119). In secondary analyses, patients were divided into three groups as MV group (n=7), PV group (n=7) and PUC group (n=119). The operative data, oncologic outcomes and complications were compared between the groups.
Median operation time and estimated blood loss were significantly increased in variant pathologies group (P <0.001 and P = .001, respectively). The postoperative pathological T stage, positive surgical margin rate and lymph node involvement were also significantly increased in variant pathologies (P = .001, P = 0.004, P <0.001, respectively). Kaplan-Meier analysis revealed significant decrease in OS and CSS times in PV group compared to PUC group (P = .048 and P = .016, respectively).
MV and PV are rarely seen variant pathologies with higher pathological T stages. RARC is a minimally invasive surgical technique that can be performed successfully by an experienced surgical team with low morbidity rates and similar oncological results, even in challenging cases.
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