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04 December 2024 | Story André Damons | Photo André Damons
Breast Cancer Research 2024
The research team consist of Dr Beynon Abrahams (left), Viwe Fokazi, MMed.Sci student, and PhD student Songezo Vazi.

In an effort to better understand chemotherapeutic treatment response in triple negative breast cancer (TNBC) – known as an aggressive cancer with high recurrence and high mortality rate in breast cancer patients – researchers from the University of the Free State (UFS) developed a drug-resistant TNBC spheroid model that is physiologically more accurate in displaying the complexities involved in drug-resistance development.

Dr Beynon Abrahams, Lecturer in the Department of Basic Medical Sciences within the UFS Faculty of Health Sciences, says breast cancer remains the most frequently diagnosed cancer in women. It is also the most debilitating type of cancer responsible for the highest cancer mortality rates in women. Though various subtypes of breast cancer exist, TNBC is one that is of particular interest to his research team.

“TNBC is one of the most difficult cancer types to treat, due to lack of treatment targets. This often leads to treatment failure in TNBC patients, with drug resistance being a common occurrence, contributing to high death rates. TNBC is classified based on its lack of expression of common receptors such as the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, which are commonly expressed in other cancer subtypes.

“Characteristically, TNBC is known as an aggressive cancer with high metastatic potential (spreading of cancer), resulting in a poor prognosis for these patients. The current prescribed therapies for TNBC, entails multidrug combination systemic therapy including chemotherapeutic agents such as doxorubicin and cisplatin as adjuvant therapy. However, despite these therapeutic interventions, drug resistance is a common occurrence,” says Dr Abrahams.

The best available preclinical cell-based models should be used

For effective drug treatments to be developed for TNBC therapeutics, he continues, the best available disease models should be used to not only improve our understanding of the disease physiology and its numerous mechanisms involved in chemotherapeutic resistance development but also to provide accurate results when determining how safe and effective newly developed drugs are, before they may be considered for further development and testing on humans.

According to him, in preclinical cancer research the conventional methods employed to study disease mechanisms, drug action and drug resistance is ineffective. Firstly, the traditionally used preclinical 2-dimensional (2-D) cell culture models do not accurately recapitulate the architectural biology observed in vivo, second, the drug responses assessed in these models may provide inaccurate results and limit its translational potential, explains Dr Abrahams. Thus, more advanced cell-based models such as 3-dimensional (3-D) spheroids and organoids to name a few, should be considered as alternatives.

The UFS research team, in collaboration with the Centre of Excellence for Pharmaceutical Sciences (Pharmacen™) at the North-West University (NWU), recently took the undertaking to establish two triple negative breast cancer 3-D spheroid models, using the clinostat rotating bioreactor ClinoStar™ system, designed by CelVivo in Denmark. The project is funded by the National Research Foundation.

The ClinoStar™ system promotes the self-aggregation of single cells, and natural formation of 3-D spheroids, through slow rotation within a cell growth chamber known as an incubator. There are various techniques and methods available to develop spheroids and organoids, however the ClinoStar™ systems allow for the development of metabolically stable spheroids, over a longer period of time, as opposed to other methods. It also eliminates the sheer-stress conditions that are normally encountered when using 2-D cell culture models.

“We successfully established one chemotherapeutic-sensitive triple negative breast cancer spheroid model and one novel cisplatin-resistant triple negative breast cancer spheroid model. The chemo-sensitive TNBC spheroid model was evaluated for responsiveness against two clinically used chemotherapeutic agents, doxorubicin and cisplatin. We suggest that this model may be useful to screen novel compounds including traditionally used phytomedicinal material for anticancer activity.

“In our second model, the cisplatin-resistant TNBC spheroid model was also exposed to cisplatin and doxorubicin and demonstrated a resistant response in terms of growth and viability. We believe that this model may be useful to further explore drug resistance mechanisms and may also be used as a tool to assess the drug reversal potential of novel compounds. The value and impact of these models lies in that they may offer predictive drug responses that are closer to that observed in in vivo (animals), as opposed to 2-D cell cultures. This however needs to be assessed. We are currently in the process to fully characterise these spheroids models.”

Aim of the research

Dr Abrahams explains their research aims to merge the gap between conventionally used 2-D cell models and in vivo models, by providing a model that is physiologically more accurate in mimicking the in vivo conditions and complex pathways associated with drug resistance, which is otherwise not observed or accurately expressed in 2D models. “Although our research is preclinical and considered fundamental basic research, the translational potential of our spheroid models may provide options for exploring and testing alternative drugs that may be considered for translational research,” Dr Abrahams says.

Characterising other advanced cell-based cancer models

The team is currently in the process of further characterising the TNBC spheroid model based on protein and genetic expression profiles to elucidate potential therapeutic biomarkers for drug treatment as well as screening various phytomedicinal plants, to assess their antiproliferative and drug-resistance reversal potential. In addition, the researchers recently commenced a new research project that aims to develop a drug-resistant prostate cancer spheroid model using the Clinostar™ system with their collaborators at the NWU.

Advanced cell-based model research is still relatively ‘new’ in South Africa and Africa, compared to the global North. As a result, says Dr Abrahams, their NWU collaborators together with other stakeholders, initiated the establishment of the Society for Advanced Cell Culture Modelling for Africa (SACCMA) in 2021, which aims to develop the fields of advanced cell modelling, three-dimensional (3D) cell cultures, 3D bioprinting and stem cell research, in Africa. Our current inter-departmental  collaboration include researchers from the Pharmacology department, but we hope to build and expand our collaboration network in the near future.

News Archive

Academic and security arrangements on the Bloemfontein and South Campuses for the coming week
2016-02-28

All academic and administrative services on the Bloemfontein and South Campuses of the University of the Free State (UFS) will resume on Monday 29 February 2016.

The following academic and security arrangements have been put in place:

1.    Academic arrangements:
It is important to remember that losing an academic week has major implications for all students, particularly for first-year students, and for purposes of academic planning. The university will therefore resume its normal work on Monday 29 February 2016. Losing any additional time will severely disadvantage students, especially those who desperately need the time to catch up with lectures ahead of the coming tests and examinations. Many more students will struggle to complete the academic year if any further time is lost.

In order to ensure that the academic work of the university is not undermined, the UFS will extend this academic term by one week. This will allow the completion of the work scheduled for last week. Given the impact that disruptions had on the emotions and concentration of many of our students, academics are requested to manage the setting and re-setting of all tests and assignments scheduled for last week with sensitivity, and to be supportive of students as they re-start their academic work.  No student should be disadvantaged in terms of tests or assignments as a result of last week’s closure. We know you would do this anyway, but this is a reminder to all staff of what we expect to be a common approach and understanding on the part of lecturers.

We rely on the leadership of the deans in the seven faculties to support staff and students in dealing with the lost time in the most appropriate manner and in supporting all efforts to refocus energies on the academic project.

As the senior leadership and management of the university, we will continue to do everything in our power to make sure that the academic programme continues uninterrupted.

2.    Security arrangements:
The Bloemfontein Campus is secure and we have more than doubled the security arrangements, with the interdict firmly in place.

The university management condemns in the strongest possible terms the violence that took place at Xerox Shimla Park on the night of Monday 22 February 2016. It also condemns the disruptions of the university that followed Monday’s event, which resulted in the suspension of academic and administrative activities on the Bloemfontein Campus. In line with the terms of the interdict - and now that we are at full capacity to secure this very large and spread-out campus - the university will act swiftly and firmly if any protests or disruption recur.

The following security arrangements are in place:
2.1  Staff and students must have their staff and student cards with them when entering the campus. Passengers in motor vehicles will have to present their cards to security personnel before access could be granted. Security personnel will check this physically by verifying that each person has a valid staff or student card.

2.2  Buses will not be allowed to enter the campus and passengers will have to be dropped off outside the gates - passengers will enter through the turnstiles with their valid access cards. Anyone without a valid access card will have to go to the Visitors Centre and present positive proof of ID (SA ID, passport or driver’s licence).

2.3  Pedestrians will have to swipe their cards at the turnstiles at the gates. Those without cards will have to enter through the Visitors Centre by presenting positive proof of ID (SA ID, passport or driver’s licence).

2.4  Visitors must report to the Visitors Centre (at Gate 5 in DF Malherbe Drive) and present positive proof of ID (SA ID, passport or driver’s licence).

2.5  Due to anticipated delays, it is advised that people allow some additional time when planning their routes to campus and to also make use of the less busy gates, such as Gate 4 (Furstenburg Road) and Gate 2 (Roosmaryn Residence).

2.6  It is advised that walkways be used, especially at night, and that pedestrians should keep to areas that are well lit.

Security helpline: +27(0)51 401 2911 | +27(0)51 401 2634.
 

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