Tumor Cells
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2022 ◽  
Vol 52 (4) ◽  
Renato Luiz Silveira ◽  
Ana Claudia de Menezes Cruz ◽  
Phillipe Bauer de Araújo Doria ◽  
Joao Marcelo Silva Silveira ◽  
Carlos Otávio de Paula Vasconcelos ◽  

ABSTRACT: Tumors are rarely diagnosed in swine specie because of the short lifespan of production animals. Normally, these tumors do not present any clinical signs and are often detected at the time of slaughter. A 2-year-old Large White boar, used in the reproductive management of a farm and without a history of pre-existing problems, was examined for skin lesions on the scrotum. Samples were collected from skin segments containing lesions for histopathological and immunohistochemical diagnosis. Microscopically, the nodes in the scrotum pouch consisted of poorly demarcated, highly cellular, expansile, and multifocally invasive neoplasms, composed of immature endotheliocytes organized into neovascular formations. The tumor cells were pleomorphic, slightly oval to spindle-shaped, with eosinophilic cytoplasm and hyperchromatic nuclei with one to three nucleoli. All the nodules analyzed were compatible with hemangiosarcoma. After immunohistochemical evaluation, for the quantification of tissue angiogenesis the neoplastic cells immunoexpressed the CD31 monoclonal antibodies and factor VIII, through the identification of proteins expressed on the surface of endothelial cells. The Ki67 cell proliferation marker was positive in approximately 10% of the neoplastic cells, demonstrating a high degree of malignancy. Hemangiosarcoma in swine species has already been identified in several organs and tissues; however, to date, no study has demonstrated the diagnosis of this condition on the skin of the scrotum, as reported in this study. Therefore, it is expected that this report will contribute to the knowledge of the frequency of neoplasms in swine species.

2021 ◽  
Vol 130 (15) ◽  
pp. 153301
Bolun Pang ◽  
Zhijie Liu ◽  
Sitao Wang ◽  
Yuting Gao ◽  
Huaiyan Zhang ◽  

2021 ◽  
pp. 174751982110458
Jing Wang ◽  
Bin Huang ◽  
Liqiang Wang ◽  
Guijjuan Jiang ◽  
Jianxin Cheng ◽  

Two novel oxovanadium(IV) complexes ([VO(hntdtsc)(BPIP)] and [VO(hntdtsc)(MOPIP)] (hntdtsc = 2-hydroxy-1-naphthaldehydethiosemicarbazone, BPIP = 2-(4-bromophenyl)-imidazo[4,5- f]-1,10-phenanthroline, MOPIP = 2-(4-methoxyphenyl)-imidazo[4,5- f]1,10-phenanthroline), are synthesized and characterized. Subsequently, the Methyl Thiazolyl Tetrazolium (MTT) assay is used to investigate the antitumor activity of the ligand and two complexes in vitro.The results indicate that both complexes could significantly inhibit selected tumor cells (SH-SY5Y, MCF-7, and SK-N-SH). In addition, the antibacterial activity of VO(hntdtsc)(BPIP) against Staphylococcus aureus is further investigated. Interestingly, VO(hntdtsc)(BPIP) can efficiently attenuate S. aureus growth and abrogate α-hemolysin secretion and biofilm formation. The plasmid DNA cleavage activity of both complexes is also investigated. The results suggest that supercoiled plasmid DNA is efficiently cleaved after treatment with each complex, which might contribute to the biological activity of these oxovanadium(IV) complexes.

2021 ◽  
Hanbing Song ◽  
Simon Bucher ◽  
Katherine Rosenberg ◽  
Margaret Tsui ◽  
Deviana Burhan ◽  

Pediatric hepatoblastoma (HB) is the most common primary liver cancer in infants and children. Studies of HB that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, HB tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we used single- cell genomic techniques to analyze resected human pediatric HB specimens. This study establishes that tumor heterogeneity can be defined by the relative proportions of five distinct subtypes of tumor cells. Notably, patient-derived HB spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. Collectively, these results define HB tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

2021 ◽  
Vol 12 (1) ◽  
Franziska Olm ◽  
Lena Panse ◽  
Josefina H. Dykes ◽  
Daniel Bexell ◽  
Thomas Laurell ◽  

Abstract Background Graft-contaminating tumor cells correlate with inferior outcome in high-risk neuroblastoma patients undergoing hematopoietic stem cell transplantation and can contribute to relapse. Motivated by the potential therapeutic benefit of tumor cell removal as well as the high prognostic and diagnostic value of isolated circulating tumor cells from stem cell grafts, we established a label-free acoustophoresis-based microfluidic technology for neuroblastoma enrichment and removal from peripheral blood progenitor cell (PBPC) products. Methods Neuroblastoma patient-derived xenograft (PDX) cells were spiked into PBPC apheresis samples as a clinically relevant model system. Cells were separated by ultrasound in an acoustophoresis microchip and analyzed for recovery, purity and function using flow cytometry, quantitative real-time PCR and cell culture. Results PDX cells and PBPCs showed distinct size distributions, which is an important parameter for efficient acoustic separation. Acoustic cell separation did not affect neuroblastoma cell growth. Acoustophoresis allowed to effectively separate PDX cells from spiked PBPC products. When PBPCs were spiked with 10% neuroblastoma cells, recoveries of up to 98% were achieved for PDX cells while more than 90% of CD34+ stem and progenitor cells were retained in the graft. At clinically relevant tumor cell contamination rates (0.1 and 0.01% PDX cells in PBPCs), neuroblastoma cells were depleted by more than 2-log as indicated by RT-PCR analysis of PHOX2B, TH and DDC genes, while > 85% of CD34+ cells could be retained in the graft. Conclusion These results demonstrate the potential use of label-free acoustophoresis for PBPC processing and its potential to develop label-free, non-contact tumor cell enrichment and purging procedures for future clinical use.

2021 ◽  
Alia Hadefi ◽  
Morgane Leprovots ◽  
Max Thulliez ◽  
Orianne Bastin ◽  
Anne Lefort ◽  

Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with global response to oxidative stress, fetal-like regeneration reprogramming and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258599
Elnaz Abbasifarid ◽  
Azam Bolhassani ◽  
Shiva Irani ◽  
Fattah Sotoodehnejadnematalahi

Cervical cancer is the most common malignant tumor in females worldwide. Human papillomavirus (HPV) infection is associated with the occurrence of cervical cancer. Thus, developing an effective and low-cost vaccine against HPV infection, especially in developing countries is an important issue. In this study, a novel HPV L1-E7 fusion multiepitope construct designed by immunoinformatics tools was expressed in bacterial system. HEK-293T cells-derived exosomes were generated and characterized to use as a carrier for crocin and curcumin compounds. The exosomes loaded with crocin and curcumin compounds as a chemotherapeutic agent (ExoCrocin and ExoCurcumin) were used along with the L1-E7 polypeptide for evaluation of immunological and anti-tumor effects in C57BL/6 mouse model. In vitro studies showed that ExoCrocin and ExoCurcumin were not cytotoxic at a certain dose, and they could enter tumor cells. In vivo studies indicated that combination of the L1-E7 polypeptide with ExoCrocin or ExoCurcumin could produce a significant level of immunity directed toward Th1 response and CTL activity. These regimens showed the protective and therapeutic effects against tumor cells (the percentage of tumor-free mice: ~100%). In addition, both ExoCrocin and ExoCurcumin represented similar immunological and anti-tumor effects. Generally, the use of exosomal crocin or curcumin forms along with the L1-E7 polypeptide could significantly induce T-cell immune responses and eradicate tumor cells.

2021 ◽  
Jia-Hao Jiang ◽  
Chang-Yue Chen ◽  
Jian Gao ◽  
Jing Li ◽  
Yuan Lu ◽  

Abstract Backgrounds: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) holds great promise for improving pathological diagnosis and selecting treatment in non-small cell lung cancer (NSCLC). In addition, previous studies have shown that DNA methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: we first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus and further identified the results by performing whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: the bioinformatic analysis revealed that an NSCLC-specific DNA methylation marker panel which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between CTCs and their primary tumors and found very high similarities between CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. CTCs also showed some characteristics that were different from those of the primary tumor tissues, suggesting that CTCs evolve some unique characteristics after migrating from the primary tumor; these characteristics may be one of the reasons for the ability of tumor cells to evade immune surveillance.Conclusion: thus, our study provides insight into the potential use of CTCs in pathological classification of NSCLC patients as well as CTC primary tumor inheritance and CTC evolution influence metastasis and immune escape.

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5144
Annalena Wieland ◽  
Pamela L. Strissel ◽  
Hannah Schorle ◽  
Ezgi Bakirci ◽  
Dieter Janzen ◽  

Background: Glioblastoma multiforme (GBM) and metastatic triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with poor patient outcome, thus new therapeutic targets are needed. To understand signaling, controlling the dynamics and mechanics of brain tumor cell migration, we implemented GBM and TNBC cell lines and designed 3D aligned microfibers and scaffolds mimicking brain structures. Methods: 3D microfibers and scaffolds were printed using melt electrowriting. GBM and TNBC cell lines with opposing PTEN genotypes were analyzed with RHO-ROCK-PTEN inhibitors and PTEN rescue using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while scanning electron microscopy and confocal microscopy addressed cell morphology. Results: In contrast to the PTEN wildtype, GBM and TNBC cells with PTEN loss of function yielded enhanced durotaxis, topotaxis, adhesion, amoeboid migration on 3D microfibers and significant high RHOB expression. Functional studies concerning RHOB-ROCK-PTEN signaling confirmed the essential role for the above cellular processes. Conclusions: This study demonstrates a significant role of the PTEN genotype and RHOB expression for durotaxis, adhesion and migration dependent on 3D. GBM and TNBC cells with PTEN loss of function have an affinity for stiff brain structures promoting metastasis. 3D microfibers represent an important tool to model brain metastasizing tumor cells, where RHO-inhibitors could play an essential role for improved therapy.

2021 ◽  
Vol 102 (5) ◽  
pp. 757-764
D E Tsyplakov

Aim. Morphological study of the microvasculature of regional lymph nodes in relation to the cancer of the lymph nodes as possible additional or alternative metastasis pathways. Methods. The lymph nodes of 150 cancer patients (1263 nodes in total), regional to cancer of various localization, were studied. Histological sections staining with hematoxylin and eosin by Van-Giesons method, pyronine by Brachets method, toluidine blue and picro-Mallory were prepared. An immunohistochemical study was performed using monoclonal antibodies to pan-cytokeratins, CD31, type IV collagen, CD3, CD20, and CD68. The area of metastases to the lymph nodes was determined by using a morphometric grid and used to identify the four study groups. In addition, the immunomorphological reactions of the lymph nodes were taken into account in each group. Results. It was identified that the microvasculature of the lymph nodes can be involved in the metastatic process along with the lymphatic pathways. At the same time, there is a decrease in vascular wall function and violation of the rheological properties of blood, accompanied by the deposition of intra- and extravascular fibrin. Hematogenous metastasis is largely influenced by the state of lymph node sinuses, in which blood is found, and in some observations by the expression of CD31 (a marker of blood endothelium). Hematogenous dissemination of cancer often begins after the appearance of lymph node metastases. The greater the anatomical extent of lymph node metastases, the more often tumor cells are present in the blood vessels. In addition, an isolated lesion of the microvasculature with the presence of tumor cells in the extranodal vessels without metastases in the lymph node itself was revealed. It was observed that the invasion of tumor cells into the microvasculature depended on the immunomorphological reactions of the lymph nodes. Conclusion. The microvasculature of regional lymph nodes can be both an additional and an alternative lymphogenous metastasis pathway of cancer; at the same time, vascular invasion is accompanied by microcirculation disorders and depends on the volume of metastases and the immunomorphological reactions of the lymph nodes.

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