To mark World Cancer Day on 4th February 2019, ZEISS wants to spread the word (e.g. by showcasing advances in cancer research and treatment) and raise awareness about the disease. Every single one of us can help prevent cancer and reduce the impact of the disease on patients and those around them.
Fluorescence image of cultured HeLa cells. Cellular components marked with fluorescent proteins. Imaged with Apotome.2.
HeLa is an immortal cell line most commonly used in scientific research, e.g. to better understand general processes in cancer development.
… the number of new cancer cases worldwide in 2018 is estimated at 18 million?1
… between 30 and 50% of cancer cases could actually be prevented by steering clear of the risk factors?2
… Cancer Research UK has announced that, by 2034, it aims to ensure that 3 out of 4 patients beat cancer?3
People use the word “cancer” to refer to a whole range of diseases. Cancer actually manifests when irreparable mutations occur in sections of our genetic material. This results in uncontrollable cell growth that can wreak havoc on the body. In 2018, the number of new cancer cases worldwide was estimated at around 18 million1 – and that number is rising. This is due in part to demographic change, but also to a lack of exercise, which is linked to obesity. However, advances in research have enabled enhanced early detection and diagnosis, as well as brand-new treatment methods – and this has certainly benefited patients.
For some time past innovations and advances in the development of medicines and diagnostic methods have resulted in improvements with regard to early cancer detection and therapy. Furthermore, the efficacy and tolerability of these cancer treatments have been enhanced – here’s an overview.
In the 17th century, Wilhelm Fabry (von Hilden) (1560–1634), a major German surgeon of his time and the founder of scientific surgery , begins extracting enlarged lymph nodes during breast surgeries, while Johann Scultetus (1595–1645) focuses on radical mastectomies.
Groundbreaking cancer research using microscopes: Sir Paul M. Nurse, Leland H. Hartwell and Timothy Hunt are awarded the Nobel Prize for Physiology or Medicine. Their fundamental discoveries on controlling the cell cycle make a big impact on all aspects of cell growth. Defects in cell cycle control can result in the chromosome changes that are observed in cancer cells. In the long term, this can open up whole new possibilities in cancer treatment.
In 2018, doctors James Allison and Tasuku Honjo receive the Nobel Prize for Medicine for developing immune-based cancer therapies – a milestone in the fight against cancer. They discover that the immune system is capable of attacking cancer cells – provided that the immune cells release their own brakes.
While conducting experiments in 1895, physicist Wilhelm Röntgen discovers the rays that now bear his name (Röntgen is the German word for X-rays). Doctors begin X-raying their patients to detect bone fractures and lung shadows – and notice the effects that rays have on rapidly growing cancer tissue. Just one year later, the first patient is X-rayed – a breast cancer sufferer in the USA. This marks the start of radiooncology.
The approval of the first antibody to treat follicular lymphomas marks a new chapter in the fight against lymph node cancer. Alongside radiation therapy and chemotherapy, antibody therapy has been a standard treatment ever since – for lymphomas as well as for breast and colon cancer.
In cancer research, scientists often use microscopes to understand how healthy cells are different to cancer cells. Live cell imaging helps to monitor the dynamic processes in the cell cycle and is often used in cell or animal models. Autofluorescence or fluorescent labels help to distinguish tumor cells and tissue from healthy cells. Such basic research is the very foundation for the development of novel diagnosis, treatment, and cures.
The most groundbreaking research using microscopes in this area has even been awarded a Nobel Prize. Sir Paul M. Nurse, Leland H. Hartwell and Timothy Hunt were awarded the Nobel Prize for Physiology or Medicine in 2001. Their fundamental discoveries regarding the control of the cell cycle have a great impact on all aspects of cell growth. Defects in cell cycle control may lead to the type of chromosome alterations seen in cancer cells. In the long term, this can open new possibilities for cancer treatment. Harald zur Hausen received the Nobel Prize for Physiology or Medicine in 2008. He revealed that a virus infection can cause cervical cancer – contrary to prevailing doctrines. His discovery was a starting point to successful construction of biosynthetic preventive vaccines against this carcinoma.
ZEISS Medical Technology helps doctors to identify and treat cancer - in a large number of different areas.
Early signs of an eye disease, e.g. ocular tumors, are often subtle and frequently occur in the outermost periphery of the retina. Ultra-widefield imaging provides doctors with better visibility of the entire fundus and hence enables early detection of ocular tumors. If a tumor, in the brain for example, has to be surgically removed, precise magnification through a surgical microscope is extremely important. The fluorescence technology often integrated into the surgical microscope additionally assits doctors in differentiating between diseased and healthy tissue. Intraoperative radiotherapy can then be used during the surgical removal of the tumor. Unlike external radiotherapy, this involves the tumor bed being irradiated immediately after the surgery. The surrounding healthy tissue is protected and, with breast cancer for example, follow-up radiotherapy can be reduced and in some cases even eliminated completely.
ZEISS is working on solutions for the future: a digital biopsy tool visualizes microstructures of the tissue in real time, enabling doctors to examine tissue samples immediately without needing to remove tissue.
Heather Knies has experienced two dangerous brain tumors and is now the mother of a little daughter. Her story shows the excellent work performed by brain surgeons and how medical technology can help to achieve optimal treatment outcomes.
This image is from Wills Eye Hospital, Ocular Oncology Service: It is a color image of the retina captured with Ultrawidefield Fundus Imaging and it shows a melanoma in the right eye. Orange pigment overlying the tumor indicates malignancy.
With ultra-widefield fundus Imaging, a doctor can take a snapshot of a patient’s retina to examine, identify and document changes that may be signs of eye diseases. Unlike traditional fundus cameras, the CLARUS ultra-widefield fundus imaging system provides doctors the ability to see the retina in ultra-widefield high definition color, providing a larger and more comprehensive image.
Slight discoloration or changes in the retina may be early signs of eye disease such as diabetic retinopathy, AMD or ocular cancer.
Joe W. Gray and his team at the Oregon Health & Science University in Portland, USA use integrated omic and imaging technologies to elucidate mechanisms by which advanced breast, prostate and pancreatic cancers escape therapeutic control. Their goal is to use this information to develop therapeutic strategies to counter emerging resistance mechanisms. Analysis using multicolor immunofluorescence is a key tool in these studies and imaging is performed using the ZEISS Axio Scan.Z1 slide scanner.
Sir Paul M. Nurse, Leland H. Hartwell and Timothy Hunt were awarded the Nobel Prize for Physiology or Medicine in 2001. Their fundamental discoveries regarding the control of the cell cycle have a great impact on all aspects of cell growth. Defects in cell cycle control may lead to the type of chromosome alterations seen in cancer cells. In the long term, this can open new possibilities for cancer treatment. Harald zur Hausen received the Nobel Prize for Physiology or Medicine in 2008. He revealed that viruses can cause cancer – contrary to prevailing doctrines. His discovery was a starting point to successful construction of biosynthetic preventive vaccines against this carcinoma.
Less than two percent of cancer cases in humans are brain tumors. A rare, but greatly feared disease, diagnosis often means the patient only has a few years or even months to live. The tumor constantly increases the pressure within the brain until it becomes life-threatening.
Treatment possibilities are still limited, but surgery can improve and prolong the patient's quality of life.
Neurosurgeons are often facing the challenge to remove a maximum amount of diseased tissue and without harming healthy ones. Fluorescence technology can help neurosurgeons walk this fine line during surgery on a brain tumor.
Prof. h.c. Walter Stummer, M.D., Ph.D. (image on the left side), today works at the University Hospital of Münster, Germany. He was one of the driving forces when fluorescence technology was invented for tumor resection.
Associate Prof. Jun Zhan, of Prof. Hongquan Zhang’s team at Peking University Health Science Center, studies the molecular mechanisms of cancer metastasis. She uses ZEISS laser scanning microscopes to observe cancer cells in animal models and patient samples to understand the influence of interacting proteins at cellular level on cancer progression. The research group is part of a nationwide project aiming to find new drugs to stop cancer metastasis, and has published dozens of leading papers using this system.
The research center for telomeres at Children’s Medical Research Institute (CMRI) in Sydney, Australia focuses on the study of telomeres – the structures at chromosome ends, and their roles in cell proliferation, cancer and aging with the aim of supporting medical and biological research projects. One big challenge is to find ways to slow or stop cancer growth by disabling mechanisms that cancer cells use to escape the normal limits on proliferation.
Several widefield and confocal state-of-the-art microscope systems from ZEISS allow researchers at the core facility to analyze the length of telomeres, to automate scans for metaphase cells and telomeres, and to perform high-resolution fluorescence microscopy and live cell imaging.
At the CCRI in Vienna more than 100 scientists conduct basic, translational and clinical research and provide state-of-the-art diagnostics to advance diagnosis, prognosis and treatment strategies for children and adolescents with cancer.
A number of ZEISS fluorescence microscopes are in use for e.g. multi-color FISH analyses to identify prognostic and pathognomonic genomic aberrations of leukemia and solid tumor patients used for therapy stratification. Moreover, automatic fluorescence microscopes enable an ultra-sensitive minimal residual disease (MRD) diagnosis in pediatric tumor patients. Moreover, researchers at CCRI are e.g. studying the pathogenesis of pediatric cancers and new treatment targets in vitro and in zebrafish models supported by bright field and fluorescence microscopes. Currently, deep learning algorithms are implemented to automatically quantify biomarkers at the single cellular and sub-cellular level, aiming to establish objective microscopical evaluation procedures for diagnostics and research.
The Ingham Institute for Applied Medical Research at Liverpool Hospital in Sydney, Australia conducts world-class medical research. The Institute’s research team is dedicated to finding better ways to improve health and to exploring new medical approaches across various research streams including cancer.
The ZEISS GeminiSEM 300 field emission scanning electron microscope (FE-SEM) at Ingham Institute is specifically configured and optimized for examination of cancer tissue and new nanotechnology-based probes. It is used to characterize tumor cells and assist with patient prognostic assessment. It does this by allowing examination of the same structure within a single section of a tissue specimen by multiple methods of microscopy and microanalysis.
At the German Research Center (DKFZ) in Heidelberg scientists conduct research in over 70 departments, research groups and clinical cooperative units. Scientists focusing their research on cell and tumor biology examine, for example, what signal pathways within the cell and between cells are responsible for the proliferation and survival of cancer cells. Researchers concentrating on functional and structural genome research investigate the genetic basis of cancer. To achieve this goal, they compare the genetic makeup of cancer cells to that of healthy cells.
A large number of traditional widefield and confocal laser scanning microscopes and imaging systems for slide-scanning and high-throughput live cell microscopy from ZEISS support the scientists in addressing these and other scientific issues.
The Icahn School of Medicine at Mount Sinai is an international leader in medical and scientific training, biomedical research, and patient care. The Aaronson laboratory is involved in cancer gene discovery and function with the goal of identifying novel targets for therapy. The lab’s research has contributed to various novel cancer drugs.
Dr Stuart Aaronson is the recipient of numerous awards including the Distinguished Service Medal from the U.S. Public Health Service, the AACR Outstanding Achievement in Cancer Research Award, and the Paul Ehrlich Prize from Germany.
The Ishikawa laboratory has been proposing new therapeutic strategies to improve outcomes in leukemia patients. One of the obstacles for successful treatment of leukemia is its genetic heterogeneity and complexity, with different patients harboring different genetic abnormalities.
To create effective treatments, the Ishikawa Laboratory at RIKEN created “humanized mice” in collaboration with Dr. Shultz at The Jackson Laboratory. In these mice, leukemia reflecting patient-to-patient heterogeneity is recapitulated in vivo. Through microscopic examination, the researchers identified the location of chemotherapy-resistant human leukemic cells in the bone marrow and clarified a mechanism underlying treatment resistance.
The mission of Johns Hopkins Medicine is to improve the health of the community and the world by medical education, research and clinical care.
Dr Saraswati Sukumar and her team focus on molecular alterations in breast cancer. The lab has performed a genome wide searches for genes with genetic and epigenetic changes involved in breast cancer. They have analyzed potential oncogenes and tumor suppressor genes identified by this analysis – and continue to exploit these for early detection and therapy.
Katharina Gaus is a Scientia Professor and Head of EMBL Australia Node in Single Molecule Science at UNSW Medicine. She studies the body’s T-cells – the “front-line soldiers” of the immune system that switch on to fight disease. Her research focuses on understanding the decision-making processes of these cells. Gaus uses superresolution ﬂuorescence microscopes from ZEISS to examine why the immune system activates to fight disease or remains dormant and fails to protect the body against infection. These microscopes allow Gaus’ team to identify the individual parts within functioning T-cells.
Patricia Howland was diagnosed with breast cancer. After receiving the news she reached out to Lakeland Health Center as they offered intraoperative radiotherapy treatment with the ZEISS INTRABEAM®.
For detailed information about her experience, visit lakelandhealth.org
Copyright: Lakeland Health.
The low availability and poor access to external beam radiotherapy (EBRT) in developing countries makes it hard for women with breast cancer to receive breast conserving therapy. A team of clinicians led by Juan Enrique Bargallo-Rocha et al1 studied the effect of providing intraoperative radiotherapy (IORT) on the travel time, distance, and costs of in the Mexico City Metropolitan Area (MCMA). Sixty-nine patients treated between January 2013 and September 2014 were analyzed.
IORT led to a 12% reduction in costs per patient. By reducing costs and time needed for patients to receive radiotherapy,
IORT could potentially enhance access to breast conservation in resource-limited developing countries – concluded the team of clinicians.
1 Juan Enrique Bargallo-Rocha, Departamento de Investigación y de Tumores Mamarios del Instituto Nacional de Cancerología. Avenida
San Fernando 22, Sección XVI, Tlalpan, Mexico City, Mexico. Email: ebar gallo @yahoo .com
Treating brain tumors is a complex business. Prof. Dr. med. Frederik Wenz, Director of the Department of Radiotherapy and Radiooncology, and Medical Director of the University Medical Center Mannheim, spoke to us about treatment strategies and success stories in radiotherapy
Dr Tony Cesare is the Head of the Genome Integrity Unit at CMRI. His research explores how molecular changes at the chromosome ends, or “telomeres”, during cellular ageing functions to prevent cancer and how these processes are affected during carcinogenesis. He discovered that during the ageing process molecular changes at telomeres result in a unique DNA damage response that causes protective growth arrest. This research also elucidated why pre-cancerous and cancerous cells are able to bypass this protective growth arrest, which can often result in genome instability and oncogenic transformation. ZEISS LSM 880 with Airyscan allows him and his team to image telomere structures.
A team of Sydney scientists have made a groundbreaking discovery in telomere biology. Telomeres are DNA segments at the ends of every human chromosome. The team found that telomere structure is an important marker of disease risk for conditions such as cancer.
Focusing on breast cancer, Dr Saraswati Sukumar’s research aims to save patients the difficulties related to treatment and improve the ability to assess therapies. Furthering early detection will pave the way to advancing and applying the right treatment.
Treating brain tumors is a complex business. Prof. Dr. med. Frederik Wenz, Director of the Department of Radiotherapy and Radiooncology, and Medical Director of the University Medical Center Mannheim, spoke to us about treatment strategies and success stories in radiotherapy.
TARGIT-A is currently the largest multicenter randomized clinical trial in the field of Accelerated Partial Breast Irradiation (APBI). In 33 centers from 11 countries the Targeted Intraoperative Radiotherapy (TARGIT) has been performed on 3451 patients with mainly good prognosis.
1 World Health Organization: http://www.who.int/mediacentre/factsheets/fs297/en/
2 Wolrd Health Organization: http://www.who.int/mediacentre/factsheets/fs297/en/