Hypofractionated Radiation Therapy Suppresses Radioresistance in U87 Human Glioma Cells by Inhibiting Yap1 and Hsp90 Proteins.

BACKGROUND: Radiotherapy plays a vital role in the management of high-grade gliomas. However, the radio resistance of glioma cells limits the effect of radiation and drives recurrence inside the irradiated tumor volume leading to poor outcomes for patients. METHODS: High-grade glioma cell radioresistance significantly contributes to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. An increasing body of evidence complies with the Yes Associated Protein 1 (Yap-1) and heat shock protein 90 (Hsp90) as biomarkers for radioresistance in glioma cells. A number of studies suggest the potential of radioresistance-associated factors as biomarkers and/ or novel therapeutic targets in glioma cells. Thus, it is essential for glioblastoma patients to identify robust druggable targets involved in radioresistance, optimizing irradiation protocol, and understanding their underlying molecular mechanisms. RESULTS: Therefore, in the present study, we hypothesized that hypofractionated Gamma Knife radiation therapy (HF-GKRT) could target Yap-1 and Hsp90 and downregulate the mechanism of radioresistance in high-grade glioma cells. CONCLUSION: For this purpose, expression levels of radioresistance markers Yap-1 and Hsp90 were evaluated after treatment with HF-GKRT, and this was compared with single fraction Gamma Knife radiation therapy (SF-GKRT) in U87MG primary human glioblastoma cell line model. This would help design a novel radiation therapy regimen for glioblastoma patients by reducing the risk of radioresistance.

An Investigation into the Relationship of SUR-1TRPM4 Receptor with Peritumoral Edema in High-Grade Glial Tumors.

AIM: To investigate the presence of Sur1-Trpm4 receptors in high-grade glial tumors, and their relationship with edema volumes in preoperative magnetic resonance imaging (MRI) sequences. MATERIAL AND METHODS: MRI sections were extracted from T1-weighted (T1W) and T2-weighted (T2W) sequences and fluidattenuated inversion recovery (FLAIR) images. After that, T1W 3D magnetization-prepared rapid gradient echo (MP-RAGE) sequences were taken with and without contrast medium. Tumor and peritumoral edema volumes were calculated in cubic centimeters. Sur1- Trpm4 receptors were studied by immunohistochemical examination of tissue samples. Relationships between data were analyzed using Spearman's correlation coefficient. RESULTS: In the immunohistochemical examinations, 58% of the samples from patients with high-grade glial tumors were positive for Sur1 and 74% were positive for Trpm4. The volume of tumors was correlated with the volume of peritumoral edema. CONCLUSION: The presence of the Sur1-Trpm4 receptor complex in high-grade glial tumors was confirmed. Further preclinical or clinical studies are required to identify and validate the role of Sur1-Trpm4 in glial tumor subgroups.

CD47 expression in urothelial carcinoma and its correlation with histopathological findings.

BACKGROUND: The incidence of bladder cancers (BCs) is increasing day by day in both males and females with increased smoking. New treatment protocols are required due to the long follow-up times and high recurrence rates. CD47 (integrin-associated protein) is a membrane receptor that is effective in normal and pathophysiological events such as apoptosis, proliferation, adhesion, and immunity. Phagocytosis of both normal and tumor cells is prevented, by binding to the ligand signal regulatory protein-1 (SIRP-1)α on macrophages. Anti-CD47 antibodies can eliminate the binding and may be effective in treatment. METHODS: The study included 194 cases with urothelial carcinoma (UC) who underwent transurethral resection (TUR) of the bladder and had been followed up for one year. Cytoplasmic and membranous staining was preferred for CD47-positive staining. Staining results were compared with tumor grades, pathologic tumor stage, recurrence, and metastasis grade. RESULTS: The prevalence and intensity of CD47 staining in BCs were evaluated in this study. High-grade tumors were stained more pronouncedly compared with low-grade tumors and normal epithelium. The prevalence of CD47 staining was significant in pT2 (Pathological tumor stage 2, invades of muscularis propria) tumors, and its correlation with pTa (Pathological tumor stage a, noninvasive papillary carcinoma) tumors was significant ( P < 0.001). In the intensity evaluation, there was a significant difference between pTa and pT2 and between pT1 (Pathological tumor stage 1, invades lamina propria) and pT2 ( P = 0.003). CONCLUSION: CD47 is expressed strongly in high-grade tumors. The prevalence and intensity of CD47 staining are high in pathologic tumor stage, recurrence, and distant metastases and are considered poor prognostic markers. We believe that anti-CD47 antibodies can be used as an alternative to the current treatment or in combination with other medications, and the systemic side effects that may occur with intravesical treatment can be prevented.

Characteristics of the Patients Aged Less than 40 Years Operated for a Renal Mass.

The incidence of renal cell cancer (RCC) is low in individuals aged less than 40 years; however several studies have shown this increasing trend over the years. Hereditary syndromes are associated with RCC and are more frequently observed in early-onset cases. In this study, we investigated the characteristics of the patients, aged less than 40 years, who were operated for a renal mass with the suspicion of RCC. We analyzed patients aged <40 years who underwent partial or radical nephrectomy between January 2012 and December 2022. A total of 618 patients underwent partial or radical nephrectomy and 60 (9.7%) patients were aged <40 years. A total of 62 renal masses were resected. The median age of the patients was 34 (31.75-38) years. RCC was detected in 50 (80.6%) lesions, while 12 (19.4%) lesions were benign. The most commonly observed benign tumors were oncocytoma and multicystic nephroma. Low-stage RCC (stage 1) was detected in 78% of patients. Recurrence was observed in two patients and both had von Hippel-Landau gene mutation. During follow-up, two patients were found to have lung metastasis, while another patient had bone metastasis. Three patients died during the follow-up period. Disease free survival rate was 89.58% and cancer specific survival rate was 93.88%. The incidences of kidney cancer in young adults are increasing; therefore, early discovery and the diagnosis are important. Further research is required to gain a better understanding.

Histopathological View of Benign Essential Blepharospasm: Orbicularis Oculi Hormone Receptor Levels.

Objectives: Benign essential blepharospasm (BEB) is a focal dystonia characterized by involuntary contractions of the orbicularis oculi and periocular muscles. We aimed to investigate the effects of muscle receptor levels on the etiopathogenesis of blepharospasm by evaluating the orbicularis oculi estrogen receptor (ER) and androgen receptor (AR) levels. Methods: Four blepharospasm patients (2 females and 2 males) who underwent upper lid blepharoplasty and/or orbicularis myomectomy and 4 healthy cases (2 females, 2 males) that had upper lid blepharoplasty were included. The pretarsal, preseptal, and orbital parts of the orbicularis muscles of the patients who underwent orbicularis myomectomy and the waste muscle tissue materials taken from the preseptal orbicularis muscles of the patients who had only upper blepharoplasty were analyzed. Immunohistochemical staining was performed with estrogen alpha and androgen. Results: In healthy men, the orbicularis oculi muscle was stained with ER at a moderate intensity and with AR at a high intensity. In men with blepharospasm, the orbicularis oculi were not stained with ER at all, but at a high intensity with AR. In healthy women, the orbicularis oculi were stained with ER and AR at a high intensity (>50%). In women with blepharospasm, the staining intensities of both receptors were moderate. Conclusion: We determined a decrease in ER and AR in females and almost the absence of ER in males with BEB. This decrease in ER may be associated with a functional abnormality in mitochondria and the decrease in hormonal receptors may be associated with sarcopenia in orbicularis oculi muscle fibers.

Can CXCL13 be a prognostic marker in clear cell renal cell carcinoma?

Background: CXCL13, B-lymphocyte chemoattractant, has been associated with many diseases and cancers. One of the malignancies that CXCL13 has been investigated is clear cell renal cell carcinomas which are the most common subtype of renal cancers. Aims and Objectives: The aim of this study is to evaluate the immunohistochemical staining patterns of CXCL13 in clear cell renal cell carcinomas and to determine its relationship with pathological tumor stage, risk factors, and prognostic parameters. Materials and Methods: In this study, 99 patients who underwent partial/radical nephrectomy diagnosed with clear cell renal cell carcinoma were included. Four micron sections were taken from paraffin embedded blocks containing sufficient tumor and kidney tissue. Samples were immunohistochemically stained with CXCL13 antibody. During microscopic examination, CXCL13 positive stained cells in ten high magnification fields were counted and evaluated using a semiquantitative H score: 3 × strongly stained + 2 × moderately stained + 1 × weakly stained. The cut-off value was set as 40 for values between 0 and 300. The low and high stained groups were compared with prognostic parameters and risk factors. Statistics: The difference of continuous variables between the two groups was examined with the t test and the distribution of categorical variables with the Chi-square test. A value of P < 0.05 was considered to be statistically significant. Results: The number of lymphocytes stained with CXCL13 in the tumor was higher than in the normal kidney parenchyma (p = 0.07). Intratumoral lymphocytes were highly stained with CXCL13 in 57.5% of pT3 cases and 31.7% of pT1 cases. The amount of intratumoral lymphocytes stained with CXCL13 increased in advanced pathological stages (p = 0.05). Nonsmoking cases were mostly in the low staining group (p = 0.06). Conclusion: The relationship we found between advanced pathological stage and intratumoral CXCL13 staining in our study suggests that CXCL13 has a prognostic value in this cancer.

An incidental diagnosis of an unusually located echinococcus alveolaris.

ABSTRACT: Hydatid cyst disease is a zoonotic infection caused by the genus Echinococcus. Hydatid cysts are usually located in the liver or lungs whereas the brain is an unusual location. A 45-year-old male patient was diagnosed with an intracranial mass suggesting a metastasis in the frontal region shown in the cranial computed tomography (CT) scan following a cranial trauma. The histological evaluation revealed an acellular laminated lesion surrounded with reactive changes, compatible with a cuticle. These findings were evaluated in favour of a hydatid cyst caused by Echinococcus multilocularis. Alveolar echinococcosis is a zoonotic disease caused by the genus Echinococcus multilocularis. Hydatid cyst is a common public health issue in the countries where livestock farming is common. Primary or metastatic tumours and abscesses should be considered in the differential diagnosis of hydatid cysts regardless of their location.

Significance of CD47 expression in endometrial carcinoma.

Objectives: CD47 is a membrane protein that belongs to the immunoglobulin superfamily and regulates macrophage phagocytosis negatively. As CD47 expression at the cancer cell membrane would inhibit the phagocytic activity of immune cells, it is connected to an unfavorable prognosis in leukemia and malignancies of various solid organs. Materials and. Methods: In this study, retrospectively evaluated 72 patients who had been diagnosed with endometrial carcinoma at Pathology Department and had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO) and/or lymphadenectomy. CD47 expression was evaluated in tumorous and nontumor areas in all patients considering cytoplasmic and membranous brown staining in cells. The proportion of expression was evaluated as well as the intensity and an "h score" was obtained. This score was compared with known prognostic parameters. Results: CD47 expressions showed a statistically significant correlation with tumor grade (P < 0.05); however, no significant relationship was observed with myometrial invasion depth and lymph vascular invasion status (P = 0.923 and P = 0.754, respectively). Conclusions: As with other tumors, anti-CD47 antibody may be an alternative treatment option in patients with high-grade endometrial carcinoma.

Multiple recurrences of unknown primary tumor in a meningioma: A case report.

Metastasis of a systemic tumor into a primary brain tumor has been rarely reported in the literature. These metastases could be seen mostly in meningiomas and in less frequently in the other intracranial tumors. Carcinoma of an unknown primary site (CUP) metastasizing into an intracranial meningioma is not a common occasion. According to the best of our knowledge, in this report, we present the first case with multiple recurrent CUP, which metastasized to intracranial meningioma, reported in the literature. The whole body was investigated with FDG PET/CT and biomarkers of the most common carcinomas for primary cancer. However, these tests showed no primary affected region. Despite all adjuvant therapies, the tumor had multiple recurrences. Such cases are still a challenge to offer optimal management.

Metastatic Breast Carcinoma Mimicking Urothelial Carcinoma.

Besides being the most frequently diagnosed cancer in women, breast cancer is the main cause of cancer-related deaths in this group of patients. Breast cancer frequently metastasizes to bone, lung, brain, and liver. Renal metastasis from the breast is extremely rare. Here we aimed to report a case of breast cancer with metastasis to bone and left renal pelvis. A 58-year old woman with a mass lesion in the left renal pelvis that mimicked urothelial carcinoma was referred to our clinic. The left nephroureterectomy procedure was performed, and the pathology revealed that a renal pelvis metastasis secondary to breast cancer.

Expression of transient receptor potential melastatin 4 in differential diagnosis of eosinophilic renal tumors.

Immunohistochemical and molecular studies to differentiate eosinophilic kidney tumors are gradually increasing. The present study investigated the role of transient receptor potential cation channel subfamily M member 4 (TRPM4), a non-selective cation channel associated with migration, proliferation and invasion in cancer cells, in this differentiation. The aim was to investigate the effectiveness of TRPM4 in differentiation of eosinophilic kidney tumors. The study included a total of 112 patients, including 97 eosinophilic kidney tumors with the diagnoses of 33 eosinophilic clear cell renal cell carcinoma (CCRCC), 35 eosinophilic chromophobe renal cell carcinoma (ChRCC), 8 papillary renal cell carcinoma type 2 (P2RCC), 21 renal oncocytoma (RO), as well as 15 papillary renal cell carcinoma type 1 to differentiate from P2RCC. For TRPM4, diffuse staining (>10%) was observed in 2 CCRCC, 15 ChRCC, 20 RO and 4 P2RCC cases. There was a significant difference between eosinophilic CCRCC and other eosinophilic tumors (P<0.05). While basolateral staining was observed in papillary tumors, membrane staining was observed in other stained cases. It was hypothesized that the use of TRPM4 along with morphological findings, cytokeratin 7 and other markers may be useful for the differentiation of eosinophilic kidney tumors.

Primitive Neuroectodermal Tumor of the Testis.

A 21-year male presenting with left testicular mass and retroperitoneal lymphadenopathy underwent radical orchiectomy; and his pathological examination showed a mixed germ cell tumor composed of primitive neuroectodermal tumor mixed with mature teratoma. Six cycles of IE (ifosfamide, etoposide) and VAC (vincristine, doxorubicin, cyclophosphamide) chemotherapy were given after sperm preservation. He then underwent retroperitoneal lymph node dissection (RPLND). No tumor was detected in the removed lymph nodes, and all lymph nodes were reported as showing reactive changes. Key Words: Chemotherapy, Primitive neuroectodermal tumor, Surgery, Teratom, Testis.

An investigation of the effects of amniotic fluid on experimental ischemia/reperfusion damage in rat testes.

INTRODUCTION: Various agents have been tested as preventive treatments for ischemia/reperfusion (IR) damage. In this study, we have investigated for the first time in the literature the efficacy of injection of amniomax (AMX) into testicular parenchyma, which is a commercial medium of rat amniotic fluid, in preventing testicular IR damage related to testicular torsion. OBJECTIVE: This study aims to evaluate whether or not amniomax has an effect on experimental IR damage in rat testes using biochemical and histopathological methods based on data in the literature. Even if testicular torsion is repaired surgically in early term injury because of de IR damage still occurs. Is it possible to reduce the ischemia reperfusion injury with amniotic fluid and increase the success of treatment? STUDY DESIGN: 40 male Wistar albino rats were included. Four groups were formed with 10 rats in each group: Sham, Ischemia/Reperfusion (IR), injection 1 min before detorsion (AMX-BD), injection 1 min after detorsion (AMX-AD). Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) were computed for oxidative stress, and Total Antioxidant Status (TAS) levels were computed for the antioxidant system, for both serum and tissue. Necrosis and microcalcification levels were assessed in the evaluation of testicular histology. P < 0.05 was considered statistically significant. RESULTS: AMX-AD group has low necrosis degree than IR, Mean serum and tissue levels of TAS, TOS, and OSI parameters were respectively determined as; for TAS: 0.64 ± 0.11 and 0.96 ± 0.25 mmol Trolox Equivalent/L; for TOS: 6.71 ± 0.87 and 9.40 ± 1.03 µmol H2O2 equivalent/L; for OSI: 11.94 ± 3.74 and 10.70 ± 4.23 arbitrary unit. DISCUSSION: Our study has investigated for the first time in the literature the efficacy of amniotic fluid in preventing testicular IR damage, and used amniomax (AMX) for this purpose. The limitation of our study may be the small number of rat in the groups. CONCLUSION: We think an injection after detorsion is more favorable considering that the AMX-AD group demonstrated significantly lower levels of TOS in serum and tissue and OSI in serum, and significantly higher serum levels of TAS compared to the AMX-BD group, as well as the fact that the morphological protection effect was only observed for injections performed immediately after detorsion.

Is lymph node dissection necessary for staging while undergoing nephrectomy in patients with renal cell carcinoma?

OBJECTIVE: The essential treatment for patients with renal cell carcinoma is nephrectomy. As no lymph node dissection (LND) could be performed in the majority of these patients, healthy staging could not be carried out. In this study, we investigated the impact of LND during nephrectomy on patient survival. METHODS: A total of 181 patients-58 (32%) were female and 123 (68%) were male-were included in the study. Median follow-up period was 48 months. The patients were separated into 4 groups according to their stage during diagnosis; group 1 (T1-3N0M0), group 2 (T1-3NXM0), group 3 (T1-3N1M0), and group 4 (T1-4N0/XM1). The disease-free survival of nonmetastatic patients and the overall survival of all groups were calculated. RESULTS: Mean age was 58.4 ± 12.0 years. Median survival for Group 1 could not be reached. Median survival was 89 months in Group 2, 50 months in Group 3, and 39 months in Group 4 (P <0.001). There was no statistically significant difference between the N1 and M1 groups (P = 0.297). For the NX patient group without LND, median survival was 89 months, which is worse than the N0 group and better than the N1 group (P = 0.002). CONCLUSIONS: Our study presumes that the patients without LND are not staged sufficiently, NX patients have worse survival rates when compared with N0 patients, node-positive patients have poor survival rates as do the metastatic patients, and it should be defined as TNM stage4.

The role of diffusion-weighted MRI and contrast-enhanced MRI for differentiation between solid renal masses and renal cell carcinoma subtypes.

PURPOSE: To assess the value of diffusion-weighted magnetic resonance imaging (DW-MRI) and contrast-enhanced MRI (CE-MRI) for differentiation between benign and malignant solid renal masses, renal cell carcinoma (RCC) subtypes, oncocytomas, and lipid-poor angiomyolipomas (LP-AML). METHODS: Minimum or lowest 'apparent diffusion coefficient' (ADC1) and representative ADC values (ADC2) of 112 renal masses (n: 46 benign renal mass, n: 66 malignant renal mass) were measured on DW-MRI images (b 50, 400, 800 s/mm2). Signal intensity (SI) measurements were performed in normal renal parenchyma and most avid enhanced area of the renal masses at precontrast, corticomedullary, and nephrographic phases on CE-MRI. Contrast enhancement rate (CER) and contrast enhancement index (CEI) values of renal masses were compared between benign-malignant renal masses and RCC subtypes, oncocytomas, and LP-AMLs. RESULTS: There was no significant difference between ADC1, ADC2 values, and SI of benign and malignant renal masses (p = 0.721, p = 0.255, p = 0.872). Mean ADC1 and ADC2 values of clear cell RCCs were significantly higher than nonclear cell RCCs (p = 0.005 p = 0.002). Mean CER value of clear cell RCCs was significantly higher than nonclear cell RCCs in nephrographic phase (p = 0.003). Mean CEI values of clear cell RCCs were significantly higher than nonclear cell RCCs in the corticomedullary and nephrographic phase (p = 0.027 vs. 0.008). LP-AMLs were differentiated from other renal masses with wash-out phenomenon. CONCLUSION: Combined usage of ADC, SI, CER, and CEI values may be useful for discrimination between RCC subtypes, oncocytomas, and lipid-poor AMLs.

An Extraordinary Complication in a Child With Combined Familial Mediterranean Fever and Inflammatory Bowel Disease: Multiple Ileal Perforations.

Familial Mediterranean fever (FMF) is a recurrent disease with autosomal recessive trait and fever that is generally self-limiting. Clinical manifestations are pain in the abdomen, chest, and joints as a result of inflammation in the serous surfaces. No case of multiple intestinal perforations has been reported in children with FMF, whereas cases with a single intestinal perforation have been encountered, although very rarely. In addition, co-occurrence of FMF and inflammatory bowel disease is a situation that is very rarely reported in the literature. Here, we report a case of a 5-year-old girl who was being followed up with the diagnosis of FMF and who also had inflammatory bowel disease, which was complicated with multiple ileal perforations. Our aim is to point out a rarely encountered co-occurrence and also the importance of evaluation of additional diseases with FMF that are unresponsive to treatment so as to prevent complications.

Does ozone administration have a protective or therapeutic effect against radiotherapy-induced testicular injury?

OBJECTIVE: We investigate the protective and therapeutic effects of ozone therapy (OT) in radiotherapy (RT)-induced testicular damage. METHODS: Thirty healthy adult male Wistar rats divided into five groups consisting of six animals each as follows: (1) Control (C), (2) RT, (3) OT, (4) OT + RT, and (5) RT + OT group. Histopathological findings, Johnsen scores, thiobarbituric acid-reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) levels were evaluated. RESULTS: RT caused a significant decrease in testicular weight and Johnsen score compared to the control group. In addition, TBARS level was significantly higher, whereas GSH, SOD, catalase, and GPx levels were significantly lower in the RT group when compared to the control group. Pre and postRT OT significantly increased GSH, SOD, catalase, and GPx levels and decreased TBARS level. Furthermore, testicular weight and Johnsen score were increased with OT. CONCLUSIONS: The present study showed that OT is protective and therapeutic in radiation-induced testicular damage. OT may be beneficial to the patients who underwent RT.

Unusual Histopathological Findings in Appendectomy Specimens: A Retrospective Analysis of 2047 Cases.

BACKGROUND: In this study, we retrospectively evaluated cases of patients who had undergone appendectomy in our hospital and aimed to present the efficiency of diagnostic tests and demographic data of cases. Pathological reports were analyzed for the following parameters: age, gender, and pathological diagnosis. In addition, the demographic and clinicopathologic characteristics of patients with unusual histopathologic findings were evaluated in detail, and reanalysis of archived resected appendix specimens was carried out. METHODS: Files of 2047 patients (1329 males, 718 females, sex ratio: 1.85, age range: 1-87 years, mean age: 26, 50 years), who had been operated with a diagnosis of acute appendicitis in the emergency department of Bezmialem Vakif University Medical Faculty from November 2011 to June 2014, were retrospectively evaluated. RESULTS: Cases were separated into 2 groups. Cases with histopathologic examination reported as acute appendicitis constituted group 1 (n = 2013, 98.34%), and cases with pathologic findings other than acute appendicitis constituted group 2 (n = 34, 1.66%). The second group consisted of 8 low-grade mucinous neoplasms, 7 mucoceles, 6 carcinoid, 5 granulomatous inflammation, 4 intraluminal Enterobius vermicularis, 1 endometriosis externa, 1 adenocarcinoma infiltrated to serosa, 1 mesenteric cyst, and 1 low-grade adenocarcinoma formed in mucinous cystic neoplasm background. CONCLUSION: Acute appendicitis is the most common emergency surgical condition. Although most of the resected appendectomy specimens showed typical histopathologic findings, some (1.66%) showed unusual histopathologic findings. Even if the macroscopic appearance of the specimen is normal or acute appendicitis, we suggest routine histopathological examination.