Cerebellar Degeneration as Presenting Symptom of Recurrent Endometrial Stromal Sarcoma with Sex-Cord Elements

We report a 66-year-old woman with slowly progressive ataxia due to cerebellar atrophy. Imaging studies revealed multiple lesions in both the lungs and dorsal subpleural space. A biopsy identified the lesions as metastases of a low-grade endometrial stromal sarcoma containing sex-cord elements. The histological appearance was identical to a uterine tumor the patient was treated for with hysterectomy 16 years before. The metastases were removed surgically, and after 3 months ataxia had regressed. We conclude that the presenting cerebellar degeneration in this patient resulted from the metastatic recurrence of the endometrial tumor

The role of apoptosis repressor with a CARD domain (ARC) in the therapeutic resistance of renal cell carcinoma (RCC): the crucial role of ARC in the inhibition of extrinsic and intrinsic apoptotic signalling

Background: Renal cell carcinomas (RCCs) display broad resistance against conventional radio- and chemotherapies, which is due at least in part to impairments in both extrinsic and intrinsic apoptotic pathways. One important anti-apoptotic factor that is strongly overexpressed in RCCs and known to inhibit both apoptotic pathways is ARC (apoptosis repressor with a CARD domain). Methods: Expression and subcellular distribution of ARC in RCC tissue samples and RCC cell lines were determined by immunohistochemistry and fluorescent immunohistochemistry, respectively. Extrinsic and intrinsic apoptosis signalling were induced by TRAIL (TNF-related apoptosis-inducing ligand), ABT-263 or topotecan. ARC knock-down was performed in clearCa-12 cells using lentiviral transduction of pGIPZ. shRNAmir constructs. Extrinsic respectively intrinsic apoptosis were induced by TRAIL (TNF-related apoptosis-inducing ligand), ABT263 or topotecan. Potential synergistic effects were tested by pre-treatment with topotecan and subsequent treatment with ABT263. Activation of different caspases and mitochondrial depolarisation (JC-1 staining) were analysed by flow cytometry. Protein expression of Bcl-2 family members and ARC in RCC cell lines was measured by Western blotting. Statistical analysis was performed by Student’s t-test. Results: Regarding the extrinsic pathway, ARC knockdown strongly enhanced TRAIL-induced apoptosis by increasing the activation level of caspase-8. Regarding the intrinsic pathway, ARC, which was only weakly expressed in the nuclei of RCCs in vivo, exerted its anti-apoptotic effect by impairing mitochondrial activation rather than inhibiting p53. Topotecan- and ABT-263-induced apoptosis was strongly enhanced following ARC knockdown in RCC cell lines. In addition, topotecan pre-treatment enhanced ABT-263-induced apoptosis and this effect was amplified in ARC-knockdown cells. Conclusion: Taken together, our results are the first to demonstrate the importance of ARC protein in the inhibition of both the extrinsic and intrinsic pathways of apoptosis in RCCs. In this context, ARC cooperates with anti-apoptotic Bcl-2 family members to exert its strong anti-apoptotic effects and is therefore an important factor not only in the therapeutic resistance but also in future therapy strategies (i.e., Bcl-2 inhibitors) in RCC. In sum, targeting of ARC may enhance the therapeutic response in combination therapy protocols

Разработка эффективных центраторов обсадной колонны

Основной целью работы является разработка эффективных центраторов обсадной колонны. Для выполнения поставленной цели рассмотрены основные решаемые задачи: 1 Провести обзор сортамента центраторов обсадных колонн различных производителей. 2 Провести патентный обзор центраторов обсадных колонн. 3 Провести анализ, существующих центраторов и разработать эффективный центратор обсадной колонны, лишенный недостатков, выделенных в анализе. Также выполнены разделы "Социальная ответственность" и "Производственный менеджмент, ресурсоэффективность и ресурсосбережение".The main goal of the work is to develop efficient casing centralizers. To accomplish this goal, the main tasks are addressed: 1 Review the range of casing centralizers from different manufacturers. 2 Conduct a patent review of casing centralizers. 3 Carry out an analysis of existing centralizers and develop an effective casing centering device that is free from the weaknesses highlighted in the analysis. Also the sections "Social Responsibility" and "Production Management, Resource Efficiency and Resource Saving"

Bilateral multifocal Warthin's tumors in upper neck lymph nodes. report of a case and brief review of the literature

Cystadenolymphomas (Warthin's tumors) are the second most frequent lesions of the parotid gland. Due to their benign clinical behavior, the low rates of recurrence and malignant transformation they were classified as tumor-like lesions. In addition, a polyclonal growth of the epithelial components of the tumor could be detected. Warthin's tumors occur bilateral in 7-10%, whereas a multifocal appearance is extremely rare. Even if the pathogenesis is still unclear a heterotopia of salivary tissue during embryogenesis is the most likely explanation for the origin of these tumors in the upper neck and periparotideal region. Here we present a rare case of bilateral, multifocal, extraglandular Warthin's tumors in lymph nodes of the upper neck and give a brief review of the literature. If a primary malignancy can be excluded by a careful staging procedure prior to the operation an isolated excision of the lesions of the neck is the adequate treatment

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Calcium Pyrophosphate Dihydrate Crystal Deposition Disease of the Sternoclavicular Joint

Deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the articular structures affects predominantly temporomandibular, knee, hip, spine, and wrist joints, and is a rare condition, often mimicking malignancy. Sternoclavicular joint is extremely rarely involved. We present a patient with swelling of the right upper extremity, in whom on computed tomography a mass posterior to the sternoclavicular joint causing compression of the brachiocephalic vein was detected. A modified resection arthroplasty was performed, and the histopathological findings revealed massive deposits of CPPD in the articular cartilage. To our knowledge, there is only one similar case published in the literature

PIDDosome Expression and the Role of Caspase-2 Activation for Chemotherapy-Induced Apoptosis in RCCs

Background: The importance of caspase-2 activation for mediating apoptosis in cancer is not clear and seems to differ between different tumour types. Furthermore, only few data have been obtained concerning the expression of caspase-2, which can be alternatively spliced into caspase-2L and caspase-2S, and the other PIDDosome members PIDD and RAIDD in human tumours in vivo. We, therefore, investigated their expression in renal cell carcinomas (RCCs) of the clear cell type in vivo and analysed the role of caspase-2 in chemotherapy-induced apoptosis in RCCs in vitro

Expression of the apoptosis repressor with caspase recruitment domain (ARC) in liver metastasis of colorectal cancer and its correlation with DNA mismatch repair proteins and p53

Apoptotic signaling is one of the most important processes in the measurement of chemotherapeutic effectiveness. In apoptotic machinery, various pathways and proteins are involved (i.e., mismatch repair proteins, p53). One of the regulatory proteins is ARC, which can inhibit not only the extrinsic but also the intrinsic apoptotic signaling. In this study, we investigated the expression levels of ARC in colorectal liver metastasis and compared them with the expression of mismatch repair proteins and p53. Furthermore, we investigated ARC expression level depending on sex, age, tumor grade, mucin production, tumor size and number of liver metastasis. ARC expression level in colorectal cancer liver metastasis was independent from clinical data (i.e., age, gender, tumor size, tumor number or mucin production) but strongly correlated with MSH2 and MSH6 expression, which further supported the evidence for the regulatory role of MSH2 and MSH6 in apoptosis; i.e., in case of sufficient MSH2 and MSH6 expression, significantly higher ARC level is required to suppress the apoptosis. A regulatory interaction between ARC and p53 has been described, but we found no correlation between p53 expression levels and ARC levels. Further studies are needed to define the exact role of ARC in apoptotic signaling and thus its role in chemoresistance and survival of tumor cells

HA14-1 is Able to Reconstitute the Impaired Mitochondrial Pathway of Apoptosis in Renal Cell Carcinoma Cell Lines

Renal cell carcinomas (RCCs) exhibit a marked resistance towards apoptosis. Although most apoptotic stimuli converge at the level of the mitochondria, little is known about the mitochondrial apoptosis pathway in renal cell carcinomas. The aim of the present study, therefore, was to investigate the functionality of the mitochondrial apoptosis pathway in renal cell carcinoma cell lines by exposure to TRAIL, etoposide, HA14-1 and betulinic acid activating the mitochondria by different mechanisms. Sensitivity to TRAIL-induced apoptosis correlated with cleavage of the initiator caspase-8, but the mitochondrial apoptosis pathway was not induced. Similarly, etoposide and betulinic acid could not induce mitochondrial damage. In contrast, HA14-1 was able to activate mitochondrial apoptosis, thereby demonstrating functionally inducible signalling pathways downstream of the mitochondria. The intactness of the pathways upstream of the mitochondria was shown by pretreatment of TRAIL-sensitive cell lines with HA14-1, which could reconstitute TRAIL-induced mitochondrial damage and resulted in a synergistic apoptosis induction