Mimicking disease progression features by modulation of the tumour microenvironment in stirred-tank culture systems

Gynaecological malignancies represent a heterogeneous group of neoplasms with vastly different aetiology, risk factors, molecular drivers, and disease outcomes. From HPV-driven cervical cancer where early screening and molecular diagnostics efficiently reduced the number of advanced-stage diagnosis, prevalent and relatively well-treated endometrial cancers, to highly aggressive and mostly lethal high-grade serous ovarian cancer, malignancies of the female genital tract have unique presentations and distinct cell biology features. Recent discoveries of stem cell regulatory mechanisms, development of organoid cultures, and NGS analysis have provided valuable insights into the basic biology of these cancers that could help advance new-targeted therapeutic approaches. This review revisits new findings on stemness and differentiation, considering main challenges and open questions. We focus on the role of stem cell niche and tumour microenvironment in early and metastatic stages of the disease progression and highlight the potential of patient-derived organoid models to study key events in tumour evolution, the appearance of resistance mechanisms, and as screening tools to enable personalisation of drug treatments.

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Growth rates of Haliotis rufescens and Haliotis discus hannai in tank culture systems in southern Chile (41.5ºS)

Latin American Journal of Aquatic Research ◽

10.3856/vol41-issue5-fulltext-14 ◽

2013 ◽

Vol 41 (5) ◽

pp. 959-967 ◽

Cited By ~ 6

Author(s):

Alfonso Mardones ◽

Alberto Augsburger ◽

Rolando Vega ◽

Patricio de Los Rios Escalante

Keyword(s):

Growth Rates ◽

Haliotis Discus Hannai ◽

Southern Chile ◽

Haliotis Rufescens ◽

Tank Culture ◽

Culture Systems ◽

Haliotis Discus

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Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression

BMC Cancer ◽

10.1186/s12885-021-08529-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Stefano Mangiola ◽

Patrick McCoy ◽

Martin Modrak ◽

Fernando Souza-Fonseca-Guimaraes ◽

Daniel Blashki ◽

...

Keyword(s):

Prostate Cancer ◽

Disease Progression ◽

Cancer Progression ◽

Immune Modulation ◽

Dominant Role ◽

Transcript Abundance ◽

Tumour Microenvironment ◽

Cancer Microenvironment ◽

Transcriptional Landscape

Abstract Background Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities. Results In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. Conclusions This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.

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Role of Microenvironment in Ovarian Tumourisation

Creative Surgery and Oncology ◽

10.24060/2076-3093-2021-11-4-278-283 ◽

2021 ◽

Vol 11 (4) ◽

pp. 278-283

Author(s):

L. V. Khalikova ◽

N. N. Shevlyuk ◽

Sh. Kh. Gantsev ◽

A. A. Khalikov ◽

I. R. Khasanova

Keyword(s):

Disease Progression ◽

Primary Tumour ◽

Tumour Microenvironment ◽

Greater Omentum ◽

Malignant Neoplasms ◽

Tissue Samples ◽

Advanced Malignancy ◽

Cell Counts ◽

Multistep Process ◽

The Impact

Background. Metastasis is a formidable complication of malignant neoplasms, with therapy not always effective in advanced malignancy. Metastasis is a multistep process involving the cancer cell detachment from primary tumour, intravasation, extravasation and invasion into the target organ. Early metastasis stages are well understood, whilst the impact of tumour microenvironment on the disease progression and advancement remains a matter of debate.Aim. An immunohistochemical study of the adaptive and reactive properties of greater omentum with metastatic involvement in ovarian cancer.Materials and methods. We examined greater omentum tissue samples from 40 patients with verifi ed stage 3a and b ovarian cancers. For light microscopy, samples were fi xed in 10 % formalin, dehydrated, paraffi n-embedded and stained with Mayer’s haematoxylin and eosin. Immunohistochemical assays used monoclonal antibodies against CD7, CD4, CD8, CD 68, VEGF, D2-40 and CD44 proteins. Statistical data analysis was performed with Statistica v. 7.0 soft ware.Results and discussion. Analyses of the greater omentum tissues revealed cases of leucocyte-bank encapsulation of metastatic foci. Higher CD7+ and CD8+ cell counts were observed in encapsulation, possibly influencing the greater omentum reactive and adaptive properties. Higher CD44-expressing cell counts were also detected in greater omentum samples lacking encapsulation. Angiogenesis marker-expressing cells (e.g., VEGF and CD34) predominated in greater omentum tissues lacking leucocyte-bank encapsulation of metastatic foci.Conclusion. Events in tumour microenvironment may be indicative of a preserved or reduced organ adaptivity, the latter facilitating disease progression.

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Dissection of prostate tumour, stroma and immune transcriptional components reveals a key contribution of the microenvironment for disease progression

10.1101/2020.03.16.993162 ◽

2020 ◽

Author(s):

Stefano Mangiola ◽

Patrick McCoy ◽

Martin Modrak ◽

Fernando Souza-Fonseca-Guimaraes ◽

Daniel Blashki ◽

...

Keyword(s):

Prostate Cancer ◽

Disease Progression ◽

Cancer Progression ◽

Immune Modulation ◽

Transcript Abundance ◽

Cell Types ◽

Tumour Microenvironment ◽

Disease Recurrence ◽

Transcriptional Landscape

AbstractProstate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities. In this study, the experimental enrichment of selected cell-types and the development of a Bayesian inference model for continuous differential transcript abundance permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry. This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.

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Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression

Biomaterials ◽

10.1016/j.biomaterials.2015.11.030 ◽

2016 ◽

Vol 78 ◽

pp. 50-61 ◽

Cited By ~ 55

Author(s):

Marta F. Estrada ◽

Sofia P. Rebelo ◽

Emma J. Davies ◽

Marta T. Pinto ◽

Hugo Pereira ◽

...

Keyword(s):

Disease Progression ◽

Tumour Microenvironment ◽

Phenotypic Features

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Alterations of ultrastructure and elemental composition in cultured human epidermal keratinocytes after treatment with nitrofurazone and silver sulfadiazine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127803 ◽

1987 ◽

Vol 45 ◽

pp. 676-677

Author(s):

A. R. Crooker ◽

M. C. Myers ◽

T. L. Beard ◽

E. S. Graham

Keyword(s):

Electron Microscopy ◽

Elemental Composition ◽

Pyrolytic Carbon ◽

Human Keratinocytes ◽

Silver Sulfadiazine ◽

Epidermal Keratinocytes ◽

Human Epidermal Keratinocytes ◽

Culture Systems ◽

Cytotoxicity Endpoints

Cell culture systems have become increasingly popular as a means of screening toxic agents and studying toxic mechanisms of drugs and other chemicals at the cellular and subcellular levels. These in vitro tests can be conducted rapidly in a broad range of relevant mammalian culture systems; a variety of biological and biochemical cytotoxicity endpoints can be examined. The following study utilized human keratinocytes to evaluate the relative cytotoxicities of nitrofurazone (NF) and silver sulfadiazine (SS), the active ingredients of FURACIN(R) Topical Cream and SILVADENE(R) Cream, respectively. These compounds are anti-infectives used in the treatment of burn patients. Cell ultrastructure and elemental composition were utilized as cytotoxicity endpoints.Normal Human Epidermal Keratinocytes (HK) were prepared from the EpiPackTM culture system (Clonetics Corporation, Boulder, CO). For scanning electron microscopy (SEM) and transmission electron microscopy (TEM), cells were seeded on sterile 35 mm Falcon plastic dishes; for elemental microanalysis, cells were plated on polished pyrolytic carbon discs (E. Fullam, Latham, NY) placed in the culture dishes.

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