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关键词： methylseleninic acid   cytotoxicity   cancer   selenoproteins  

摘要： Studies of recent decades have repeatedly demonstrated the cytotoxic effect of selenium-containing compounds on cancer cells of various origins. Particular attention in these studies is paid to methylseleninic acid, a widespread selenium-containing compound of organic nature, for several reasons: it has a selective cytotoxic effect on cancer cells, it is cytotoxic in small doses, it is able to generate methylselenol, excluding the action of the enzyme beta-lyase. All these qualities make methylseleninic acid an attractive substrate for the production of anticancer drugs on its basis with a well-pronounced selective effect. However, the studies available to date indicate that there is no strictly specific molecular mechanism of its cytotoxic effect in relation to different cancer cell lines and cancer models. This review contains generalized information on the dose- and time-dependent regulation of the toxic effect of methylseleninic acid on the proliferative properties of a number of cancer cell lines. In addition, special attention in this review is paid to the influence of this selenium-containing compound on the regulation of endoplasmic reticulum stress and on the expression of seven selenoproteins, which are localized in the endoplasmic reticulum.

关键词： radiation therapy   electrochemotherapy   bleomycin   uveal melanoma   3D tumor spheroids   cytotoxic effects   long-time survival  

摘要： Simple Summary Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Treatment options for UM include radiotherapy, thermotherapy and tumor resection. Electrochemotherapy (ECT) is a new therapeutic modality for local tumor control in various cancer entities. The current study assesses the radiosensitizing effect of concomitant ECT with bleomycin and irradiation on 3D tumor spheroids with primary and radioresistant uveal melanoma cell lines. The evaluation of the radiosensitizing effect of ECT as a drug delivery system was based on the changes in the spheroid growth, the cell viability as well as the cytotoxic long-term effect of the combined treatment. The primary cell lines showed a higher radiosensitivity and required lower irradiation and bleomycin doses in comparison to cell lines originating from previously irratiated tumors. ECT should be further assessed for its applicability in clinical settings as a therapeutic radiosensitizing option for radioresistant tumors. Electrochemotherapy (ECT) is emerging as a complementary treatment modality for local tumor control in various cancer entities. Irradiation is an established therapeutic option for oncologic patients, which is commonly combined with chemotherapy due to its insufficient targeting ability. The efficiency of radiotherapy for tumors can be enhanced with different radiosensitizers. ECT can potentiate the radiosensitizing effect of chemotherapeutic agents such as bleomycin. The present study aims to evaluate the radiosensitizing effect of concomitant ECT with bleomycin on 3D tumor spheroids with primary and radioresistant uveal melanoma cell lines (UPMD2, UPMM3, UM92.1, Mel270) and irradiation. The changes in the spheroid growth and the cell viability as well the cytotoxic long-term effect of the combination treatment were evaluated with various combinations of electroporation settings and bleomycin concentrations as well as radiotherapy doses. A broad range of radiosensitivity was do

关键词： Ricci semi-symmetric   A-isotropic   A-principal   Kahler structure   Complex conjugation   Complex quadric  

摘要： First we introduce the notion of Ricci semi-symmetric real hypersurfaces in the complex quadric Q(m) = SOm+2/SOmSO2 and show that the unit normal vector field N is singular. Next we give a new classification of real hypersurfaces in the complex quadric Q(m) = SOm+2/SOmSO2 with semi-symmetric Ricci tensor. (C) 2021 Elsevier B.V. All rights reserved.

关键词： hyperglycemia   glucose   TNF alpha   colon   large intestine   intestinal epithelium   primary tissue  

摘要： Hyperglycemia is thought to increase production of inflammatory cytokines and permeability of the large intestine. Resulting intestinal inflammation is then often characterized by excess secretion of tumor necrosis factor alpha (TNF alpha). Thus, hyperglycemia in hospitalized patients suffering from severe trauma or disease is frequently accompanied by TNF alpha secretion, and the combined impact of these insults on the intestinal epithelium is poorly understood. This study utilized a simple yet elegant model of the intestinal epithelium, comprised of primary human intestinal stem cells and their differentiated progeny, to investigate the impact of hyperglycemia and inflammatory factors on the colonic epithelium. When compared to epithelium cultured under conditions of physiologic glucose, cells under hyperglycemic conditions displayed decreased mucin-2 (MUC2), as well as diminished alkaline phosphatase (ALP) activity. Conditions of 60 mM glucose potentiated secretion of the cytokine IL-8 suggesting that cytokine secretion during hyperglycemia may be a source of tissue inflammation. TNF alpha measurably increased secretion of IL-8 and IL-1 beta, which was enhanced at 60 mM glucose. Surprisingly, intestinal permeability and paracellular transport were not altered by even extreme levels of hyperglycemia. The presence of TNF alpha increased MUC2 presence, decreased ALP activity, and negatively impacted monolayer barrier function. When TNF alpha hyperglycemia and <= 30 mM glucose and were combined, MUC2 and ALP activity remained similar to that of TNF alpha alone, although synergistic effects were seen at 60 mM glucose. An automated image analysis pipeline was developed to assay changes in properties of the zonula occludens-1 (ZO-1)-demarcated cell boundaries. While hyperglycemia alone had little impact on cell shape and size, cell morphologic properties were extraordinarily sensitive to soluble TNF alpha. These results suggest that TNF alpha acted as the dominant modul

关键词： CD30-positive T cell lymphoproliferative disorder   Extranodal NK/T-cell lymphoma   Gamma-delta T-cell lymphoid proliferations of the skin   Hydroa vacciniforme-like lymphoproliferative disorder   Lymphomatoid papulosis type D   Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma   Primary cutaneous γδ T-cell lymphoma   Subcutaneous panniculitis-like T-cell lymphoma  

摘要： Primary cutaneous T-cell lymphomas pose a diagnostic challenge for dermatopathologists, hematopathologists, and general surgical pathologists. Recognition of gamma/delta phenotype in cutaneous T proliferations has been enhanced by the availability of antibodies against TCRgamma and delta for immunohistochemistry. Thus, reporting gamma/delta phenotype in a cutaneous T-cell lymphoid proliferation may indicate a significant change in therapy and a challenge for dermatologists and oncologists who treat these patients. Herein, we discuss primary cutaneous gamma/delta T-cell lymphoma, its differential diagnosis, and other skin lymphoid proliferations that may show gamma/delta phenotype. Awareness of the occurrence of gamma/delta phenotype in both T-cell lymphomas and benign lymphoid proliferations involving skin is crucial for a better interpretation of histopathologic findings. Integration of clinical presentation, morphology, immunoprofile, and molecular findings is key for a correct diagnosis and appropriate therapy of lesions displaying gamma/delta T-cell phenotype.

关键词： Diffuse large B-cell lymphoma   Epigenetics   EZH2-target genes   Exosome  

摘要： Aims Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma. This study was designed to compare epigenetic alterations observed in Enhancer of Zeste Homolog 2 (EZH2)-target genes between plasma-derived exosomes and primary tumors in DLBCL patients. Main methods Exosomes were isolated from plasma of 21 DLBCL patients and 21 controls. We analyzed the methylation status of the target genes using methylation-specific PCR. We also examined whether the exosomes and the tumor samples contained transcripts of the target genes. Key findings We found that CDKN2A and CDKN2B were methylated in both plasma exosomes and primary tumor tissue samples. None of the transcripts were found in the exosomes except CDKN1B which was expressed in 8 (38%) of the exosome samples. Significance This study showed that plasma exosomes might preferably package certain target molecules from primary tumors and the exosomes containing dual methylated DNAs of CDKN2A and CDKN2B, or CDKN1B transcript may contribute to DLBCL pathogenesis.

摘要： Background For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three-dimensional histology (3D-histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections. Objectives To investigate the rate of local recurrence (LR) as well as the number of required re-excisions for basal cell carcinomas with serial section histology vs. 3D-histology. Methods We compared serial sections histology with 3D-histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections. Results Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re-excisions were required in 21%;24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D-histology group, re-excisions were required in 39%;10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow-up was 4.5 years. Conclusions 3D-histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re-excisions. 3D-histology was associated with a significantly lower LR rate than serial section histology.

关键词： Oral squamous cell carcinoma   Preemptive postsurgical therapy   Cetuximab   Postsurgical treatment   Major risk  

摘要： A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients treated at the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine. OSCC patients with major risk (n = 88) in the follow-up period were divided into groups with no postsurgical treatment (NP group), with standard postsurgical treatment (SP group), and with postsurgical treatment including cetuximab (CP group), and prognosis were compared among those groups. The 5-year overall survival rate was significantly higher in patients who received postsurgical treatment with cetuximab (CP) compared to that in the other two groups ((CP vs. NP, p = 0.028;CP vs. SP, p = 0.042). Furthermore, we performed multivariate analysis to evaluate the effects of the main components of the treatment. Among CDDP, radiotherapy, and cetuximab, only cetuximab significantly contributed to improved survival by univariate analysis (crude HR:0.228, 95%CI:0.05-0.968, p = 0.045). cetuximab also showed the same tendency in multivariate analysis, although p value did not reach significant level (Adjusted HR: 0.233, 95%CI: 0.053-1.028, p = 0.054). The results suggest that the postsurgical treatment with cetuximab as a preemptive postsurgical therapy after complete surgical resection of a visible tumor is considerably effective for OSCC patients with major risk, in other words, invisible dormant metastasis.

关键词： Signal stability   Aerosol LIBS   Energy normalization   Analysis chamber  

摘要： Signal stability is a fundamental requirement for an analytical spectroscopic technique. An auxiliary-flow based chamber is presented for emission signal stability in aerosol laser-induced breakdown spectroscopy (LIBS). The performance of the designed chamber was evaluated with the traditional aerosol LIBS scheme. Factors influencing optical emission including laser energy and particle size were carefully considered. Both intra-experiment and inter-experiment results exhibited excellent short-term and long-term stability of emission signals with the novel sampling scheme while traditional cross-chamber suffered 15% and 40% intensity decrease, respectively. The systematic air analysis before and after aerosol experiment determined that major cause of signal decrease in the cross-chamber was degraded optical transmission due to aerosol contamination on optical path which was eliminated in the auxiliary flow-based chamber. The proposed scheme can be used for the analysis of diverse aerosols types in various optical emission based analytical techniques.

摘要： 2127