- Last Updated on Monday, 17 April 2017 08:08
Peer reviewed articles and book chapters
- tracking of Giant HeLa cells, which may be undergoing neosis, a process of tumor stem cell generation;
- tracking the effects of cell cycle related toxic agents on cell lines;
- using MicroRNAs to reverse the polarization state in macrophages to induce tumor cell killing
- development of liposomal nanoformulations to overcome multi-drug resistance in ovarian cancer cells and
- development of dual sensitive micelles to specifically target matrix metalloproteinase 2.
The article is discussed in CEO commentary “Fighting cancer with nanoparticles”, read it here.
The article is discussed in CEO commentary “No Blood, No Tumor”, read it here.
“Oestrogen receptor alpha (ERα) is a well-known target of endocrine therapy for ERα-positive breast cancer. ERα-negative cells, which are enriched during endocrine therapy, are associated with metastatic relapse. Here we determine that loss of ERα in the invasive front and in lymph node metastasis in human breast cancer is significantly correlated with lymphatic metastasis. Using in vivo and in vitro experiments, we demonstrate that ERα inhibits breast cancer metastasis. Furthermore, we find that ERα is a novel regulator of vinculin expression in breast cancer. Notably, ERα suppresses the amoeboid-like movement of breast cancer cells by upregulating vinculin in 3D matrix, which in turn promotes cell–cell and cell–matrix adhesion and inhibits the formation of amoeboid-like protrusions. A positive association between ERα and vinculin expression is found in human breast cancer tissues. The results show that ERα inhibits breast cancer metastasis and suggest that ERα suppresses cell amoeboid-like movement by upregulating vinculin.”
The authors tracked and analyzed the migration of different MCF-7 cell populations in a 3D matrix. In addition to measuring the cell migration speed with HoloMonitor, the following five phenotypes were observed: ‘stable adhesion’, ‘unstable lamellipodia’, ‘bleb’, ‘stable bleb’ and ‘unstable pseudopod’.
Tamoxifen is routinely used to prevent the most common type of breast cancer by blocking the effects of estrogen. Using HoloMonitor scientists have gained valuable insight into why Tamoxifen increases the risk of other types of breast cancer. Read more about hormone treatment of breast cancer here.
Phaleria macrocarpa is a well-known medicinal plant and have been extensively used as traditional medicine for ages in treatment of various diseases.
The purpose of the study was to determine the cytotoxic effect of P. macrocarpa fruit ethyl acetate fraction (PMEAF) by using various conventional and modern microscopy techniques. The results indicate that PMEAF is a potential anticancer agent and a candidate for developing more potent anticancer drugs.
Many anti-cancer drugs that are in use today originate from traditional medicinal plants.
It has previously been shown that the hepatitis B virus gene HBx induces liver cancer in mice. The results expand these findings by providing evidence of how the HBx gene induces liver cancer.
To study the effect of HBx gene the movement of human liver cells (Huh-7) was assessed using the HoloMonitor M4 time-lapse imaging cytometer, 36 h after introducing the HBx gene. Images were captured once every 5 min during 24 h. The mean migration distance per cell was obtained using the HoloMonitor M4 cell tracking software.
Liver cancer is the fifth most common cancer worldwide, and the fourth most common cause of cancer-related death. The main cause of liver cancer is a chronic hepatitis B or C virus infection.
Investor noteStem cells are cells which develop into specific cell types. Scientists hope to be able to treat a range of currently incurable diseases by transplanting cells which has been created from stem cells in a cell laboratory.
Skin photoaging due to UV irradiation is a degenerative process that appears more and more as a growing concern. Lipids, including oxysterols, are involved in degenerative processes; as skin cells contain various lipids, the aim of our study was to evaluate first, changes in keratinocyte lipid levels induced by UV exposure and second, cellular effects of oxysterols in cell morphology and several hallmarks of keratinocyte differentiation.
Using HoloMonitor and confocal microscopy analysis, the authors highlighted cell thickening and cytoskeletal damage after incubation of keratinocytes with 25-hydroxycholesterol.
By combining HoloMonitor and fluorescence microscopy the authors investigated how UV-light and oxidized cholesterol (oxysterols) affect the aging of skin cells (keratinocytes). Skin aging is a growing concern. One in eight people in the world are today 60 years old or older.Keratinocytes are the most common cells in the outermost layer of the skin.
Lipids are a group of naturally occurring molecules that include fats, waxes and sterols.
Differentiation is the process by which a less specialized cell becomes a more specialized cell type.
It is commonly accepted that cells swell during necroptosis. However, proper cell volume measurements are still missing. Using HoloMonitor M4 the authors non-invasively measured the cell volume changes associated with necroptosis. The results were confirmed by flow cytometry measurements.
Necroptosis is a controlled form of cell death. Before necroptosis was discovered around 2000, it was believed that cells die by either being killed (necrosis) or by committing suicide (apoptosis). The discovery of necroptosis indicates that cell death is far more complicated than initially believed.
The understanding of cell death is important as it may lead to cancer treatments that precisely kill the cancer cells while sparing the normal cells, resulting in treatments with fewer side effects.
Using time courses the authors have studied hypotonic cell swelling and re-shrinking. Cell height measured by HoloMonitor M4 in HEK293 cells indicates cell swelling within seconds and completed regulatory volume decrease (RVD) within less than 2 min. The authors analyzed hypo-induced changes in cell height rather than cell volume, as an increase in cell height is not compromised by basal adhesions or cell/cell contacts.
Hypotonic is when there is a lower concentration outside a cell than inside. As water rushes into the cell to compensate for the concentration difference the cell swells. The authors have used HoloMonitor’s unique ability to continuously measure cell height and volume to study how cells respond to various concentration differences. In the above image it can be seen that cell height rapidly increase when cells are exposed to a concentration difference and thereafter slow decrease in height to abruptly drop back to normal when the concentration difference is removed. It can also be seen that the swelling response is greater at higher concentration differences.
Ovarian cancer causes more deaths than any other cancer of the female reproductive system. The disease recurs in 80% of cases because the tumor cells develop drug resistance.
The label-free quantitative technique facilitated by HoloMonitor allowed scientists from University of Chicago and Northeastern University in Boston to follow the development of mitotic arrest in real time.
It permitted the scientists to conclude that tariquidar treatment of resistant cancer cells re-sensitized the cells to paclitaxel, allowing the drug to again stop the cancer cells from multiplying by inducing almost complete mitotic arrest.
“For the analysis in a 2D migratory model, cells were imaged with a HoloMonitor M4 system. The automated stage allowed multiple collection of fields of view over time. Images were segmented and a list of features, including cell volume, thickness, and area were obtained, along with cell positional information. Values for the migration and motility of the cells were calculated and presented as cell tracks with the HoloMonitor software.
Methods for producing 4D plot were developed. Images from the time course were exported to ImageJ and treated as an image stack, creating a volume rendering of the cellular motion over time of analysis. The brightness threshold was adjusted to view all cells within the imaging area or only the thicker cells, a feature that allows identification of mitosis, apoptosis, and transition between mesenchymal and amoeboid cellular morphologies.”
Pseudomonas aeruginosa is one of the antibiotic resistant bacteria types that cause hospital-acquired infections. In combination with other imaging techniques, the authors used HoloMonitor M4 to study how these bacteria interact with the immune system.
Pseudomonas aeruginosa infection is a serious problem in patients hospitalized with cancer, cystic fibrosis and burns. The case fatality rate in these patients is exceedingly high. Research for the discovery of new antibiotics and drugs against P. aeruginosa is therefore very much needed.
C-150 – a Mannich-type curcumin derivative – exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma.
Glioblastoma is the most common and most aggressive cancer originating within the brain.
During recent years, vertical nanowire arrays have received increasing attention for their possible use in life sciences, as electrodes, biosensors, as well as for axonal guidance, cell injections and anti-bacterial properties. The rapidly expanding number of nanowire applications calls for a better understanding of the interactions between cells and nanowires.
Using HoloMonitor the researchers investigated the effects of nanowire density on cell movement, division and morphology. The results provide guidelines to minimize cellular stress on nanowire arrays. Additionally, the findings show that cell behavior can be controlled by adjusting nanowire density, which may have applications in drug development.
Current research in cancer therapy is shifting towards the use of combinational drug-treatment regimens. However, the efficient delivery of drug combinations is governed by a number of complex factors in the clinical setting.
The development of a novel folic acid-targeted liposomal formulation, simultaneously co-loaded with C6 ceramide and doxorubicin is reported. FA-(C6+Dox)-LP were able to significantly enhance the induction of apoptotic events in HeLa cell monolayers as compared to the other treatment groups.
Using HoloMonitor M4, it was found that FA-(C6+Dox)-LP treated HeLa cells underwent rapid progression to apoptosis (cell suicide) after 21 hours, as evidenced by a drastic drop in cell area after loss of cell membrane integrity.
The effects of alizarin, purpurin and an aqueous extract from transformed hairy root culture of Rubia tinctorum L. were examined on (1) cell proliferation, (2) apoptosis, (3) cell adhesion/morphology and (4) migration (chemotaxis, chemokinesis) of human melanoma cell lines (A2058, HT168-M1) and human fibroblast cells (MRC-5), as well as (5) the aqueous extract was analytically characterized.
All tested substances elicited chemorepellent effect in melanoma cells (malignant skin cancer cells), while in MRC-5 fibroblasts, only the alizarin exhibited such a repellent character. Indices of chemokinesis measured by HoloMonitor M4 (migration, migration directness, motility and motility speed) were significantly enhanced by alizarin and purpurin as well, while morphometric changes were weak in the two melanoma cell lines.
2012 and earlier
More about David Gisselsson Nord
- David Gisselsson Nord Research Group
- New method for identifying most aggressive childhood cancers
- New method improves detection of malignant child cancer, interview in Swedish press
- Scientists at Lund University question leading theory of how cancer arise, interview in Swedish radio
- Child cancer research awarded by the Fernström foundation (in Swedish)
- David Gisselsson and cancer research at Lund University receive 64 million kronor donation (in Swedish)
Conference papers & posters
Macrophages are an important part of the immune system. They are activated by molecules produced by infecting bacteria. Activation induces macrophages to elevate their membrane content through water specific gates. These aquaporins allow water to enter the cells and make them swell.
This poster by researchers at Linköping University in Sweden shows this increase of aquaporins after activation by bacterial molecules. Using HoloMonitor M4, morphology analysis of activated macrophages visualizes and quantifies the increase of cell volume, following the increased number of aquaporins in the cell membrane.