Development of a drug resistance model for hepatoblastoma

Multidrug resistance (MDR) is a major reason for poor treatment results in hepatoblastoma (HB). The objective of this study was to establish a drug resistance model for HB to analyse alternative treatment options in vitro. Both HB cell lines HUH6 and HepT1 were xenotransplanted in NMRI mice (nu/nu) and 2 cycles of cisplatin (CDDP) treatment were administered. Thereafter, xenotransplants were excised and viable tumour cells were re-cultured. 3D cultures of HUH6 and HepT1 cells were generated on a low binding culture surface. Cell viability in response to CDDP/DOXO (doxorubicin) and apoptosis was assessed by MTT-assay and caspase 3 activity, respectively. Efflux of doxorubicin was measured by flow cytometry. Cellular levels of ABC-transporters (MDR1, MRP1, cMOAT and BRCP) were determined by real time rt-PCR. Only HepT1 cells isolated from HB xenografts showed resistance to CDDP, but did not survive repeated passages. Culturing HUH6 and HepT1 cells as spheroids was successful and 3D cultures showed an IC50-drift to higher drug concentrations for CDDP and DOXO compared to 2D cultures. Treatment with CDDP and DOXO led to homogeneous apoptosis in spheroids. Increased doxorubicin efflux in HUH6 spheroids was not influenced by the P-glycoprotein inhibitor tariquidar. Expression levels of MDR1, MRP1, cMOAT and BRCP in 3D cultures were similar to those in 2D cultures and were higher in HepT1 than in HUH6 cells. In conclusion, a 3D cell culture model for multidrug resistance was established for hepatoblastoma. The underlying mechanism involves altered accessibility of the cells for drugs rather than up-regulation of ABC-transporters.     

Malignant primary pulmonary tumor with hemangiopericytoma-like features: conventional hemangiopericytoma versus solitary fibrous tumor

Although extremely rare, the primitive lung hemangiopericytoma in adults is similar to hemangiopericytomas with other soft tissue localizations. Although generally benign and curable after radical surgery, it might also have a malignant clinical course with dissemination in both lungs, infiltration of vital organs (heart, pulmonary artery), extension to the adjacent tissues, and even pulmonary metastases. The treatment of choice is the complete tumor resection with negative surgical margins after excision. Certain histologic features might indicate a malignant potential. The clinical outcome of patients is variable: some are cured after radical surgery and others might present relapse and recurrences that necessitate a second intervention, radiation therapy, and/or chemotherapy. Over the years, the conventionally-defined hemangiopericytoma concept has evolved because of the nonspecific histologic growth pattern (characteristic monotonous appearance, moderate or high cellularity, and a well-developed branching vascular pattern) shared by numerous, unrelated benign or malignant lesions. Hemangiopericytoma is no longer considered a specific entity but rather as a characteristic growth pattern; in the heterogeneous group of hemangiopericytoma-like neoplasms, many lesion categories have been individualized and defined. We report an uncommon case of primitive lung tumor exhibiting hemangiopericytoma-like features, with an aggressive, fatal clinical course. Because of the major histologic overlap between solitary fibrous tumor and hemangiopericytoma and lack of clear classification criteria, we encountered difficulty in including this case in a known clinical entity; primitive solitary fibrous tumor of the lung, which mimics lung hemangiopericytoma, seemed to be the most plausible diagnosis. We discuss the case particularities and the radiologic and pathologic correlations.     

Ten-year multicentric retrospective analysis regarding postoperative complications and impact of comorbidities in hemorrhoidal surgery with literature review

BACKGROUNDHemorrhoidal disease (HD) is considered a low-severity pathology by both general population and physicians, but the lengthy conservative therapy and postoperative complications suggest otherwise.AIMTo assess the effectiveness of different treatment options, both conservative and surgical, in contrast with some preexisting comorbidities.METHODSWe conducted a retrospective, 10-yearlong study between January 2011 and December 2021 in two surgical centers, a private and a state-owned hospital. We compared the efficacy and safety of several treatment options, such as open hemorrhoidectomy, stapled hemorrhoidopexy, rubber band ligation and infrared coagulation in terms of complication rates and types and their correlation with different preexisting comorbidities such as inflammatory bowel disease (IBD), use of anticoagulant medication (AM) and liver cirrhosis. We also conducted a 20-years long PubMed research (1.263 articles) for relevant comparisons.RESULTSOur study recorded 10940 patients with HD, 10241 with conservative and 699 with surgical treatment. Out of these, the male-to-female ratio of 1.3, and a peak in age distribution between 59 and 68 years old (32% of patients). For the entire study, we recorded a 90% incidence of immediate pain, immediate bleeding in 1.5% (11 cases), delayed bleeding in 1.0% (7 cases), and 0.6% surgical site infections. Urinary retention was also present, with 0.2% of patients, anal stricture in 1% and fecal incontinence for 0.5% of patients (4 cases). We recorded no severe complications such as Fournier`s gangrene or rectovaginal perforations. IBD accounted for 6% of the patients, with ulcerative colitis in 12% and Chron`s disease in 10.5%. 6.6% of the patients had AM, determining 4% immediate and 2% delayed bleeding, in surgically treated patients.CONCLUSIONOur study determined that most common complications (pain, urinary retention, bleeding, and stricture) are correlated with each surgical technique and pre-existing comorbidities.     

Network of telocytes in the temporomandibular joint disc of rats

The phenotypes of the temporomandibular joint (TMJ) disc cells range from fibroblasts to chondrocytes. There are relatively few reported studies using transmission electron microscopy (TEM) to determine the ultrastructural features of these cells. It was hypothesized that at least a subpopulation of TMJ stromal cells could be represented by the telocytes, cells with telopodes. In this regard a TEM study was performed on rat TMJ samples. Collagen-embedded networks were found built-up by cells with telopodes with subplasmalemmal caveolae, moderate content in matrix secretory organelles and well-represented intermediate filaments. Appositions of cell bodies were found. Prolongations of such cells were closely related to nerves and microvessels. Our study indicates that the TMJ disc attachment seems equipped with telocytes capable of stromal signaling. However, further studies are needed to assess whether the telocytes belong to a renewed cell population derived from circulating precursors.     

Reduction of Cracks in Marble Appeared at Hydro-Abrasive Jet Cutting Using Taguchi Method

The appearance of cracks in brittle materials in general and in marble, in particular, is a problem in the hydro-abrasive jet cutting process. In this paper is presented a method to reduce the appearance of cracks when cutting with a hydro-abrasive jet of marble by using statistical analysis. The Taguchi method was used, establishing the main parameters that influence the process. Research design was based on performing experiments by modifying the parameters that influence the process. In this way, it has been shown that the stochastic effects resulting from the marble structure can be reduced. A careful study was made of the behavior of marble under the action of the hydro-abrasive jet, and of the behavior of the whole process in the processing of brittle materials. Results of experiments confirmed the hypothesis that statistical analysis is a procedure that can lead to a decrease in the number of cracks in processing. The measurement was performed with precise instruments and analyzed with recognized software and according to the results obtained, the reduction of the number of cracks is achieved through use of low pressure, a minimum stand-off distance and a small tube diameter. In this way, the paper presents a new and effective tool for optimizing the cutting with a hydro-abrasive jet of marble.