Brain Regeneration in Humans: Can We Manipulate This Process?

Brain Regeneration in Humans: Can We Manipulate This Process?

Multiple evidence collected over the past 30 years supports the notion of brain neurogenesis in animals. Until recently, however, regeneration of neurons in humans seemed impossible. Proof that humans are not unique came from the laboratory of Fred Gage of the Salk Institute for Biological Studies in California in November 1998.

The brains of five cancer patients, who were injected with bromodeoxyuridine (BrdU) to tract their tumor cells, were analyzed post mortem. BrdU is a non-specific marker of DNA replication and, thus, tracts any dividing cell. The researchers found ample evidence of cell division in neurons of the dentate gyrus of hippocampus, a region involved in learning and memory.

Dentate gyrus is the first relay station for sensory information entering the hippocampus. It gets hit with a lot of glutamate, an excitatory neurotransmitter that damages brain cells. Thus, neurogenesis in dentate gyrus may be part of brain repair. The new neurons are short-lived (only a few weeks) and could play a role in new memory formation. These memories may then be stored elsewhere for the long term.

If brain neurons can regenerate, what are the factors potentiating or retarding this process? Studies of mice that suffered a stroke showed that exercise speeds up the recovery. Interestingly, exercising had to be absolutely voluntary or else it did not induce neuronal proliferation. Also, living in spacious well-equipped cages resulted in the doubling of the number of new brain cells. Surprisingly, learning did not induce neuronal formation in mice, unlike in rats.

Neurogenesis can be chemically manipulated. For example, increasing serotonin raises the number of neurons in rodents. Importantly, this happens even if serotonin is increased by an anti-depressant such as Prozac. Estrogen also increases neurogenesis. This is expected since for a long time it has been theorized that hormone replacement therapy protects older women against mental decline. In contrast, corticosteroids (stress hormones) stunt neuronal regeneration and survival. Stress is well known to impair memory. Also, the levels of corticosteroids are three times higher in the elderly than in young people. Interestingly, when corticosteroid levels are lowered in older rats, cell division of neurons is increased.

Thus, neuronal regeneration appears to be a reality. On going studies are looking into various ways of manipulating and controlling this process. Hopefully, this will enable us to induce neuronal recovery in cases where brain damage has occured.

Suggested Reading

1. Motluk A. Grow your own. New Scientist, 12 February 2000, p. 24.
2. Zigova T, Sanberg PR. Neural stem cells for brain repair. Science & Medicine, Sep/Oct 1999, p.18.

Antitelomere Agents A Promising Cancer Therapy

Antitelomere Agents A promising Cancer Therapy

A group of scientists have identified a family of compounds that inhibit telomerase, leading to death of cancer-like cells in vitro. Dr. B.S. Hurbet and colleagues report that peptide nucleic acid and 2'-0-MeRNA oligomers inhibit telomerase, leading to telomere shortening, and causing immortal cells to undergo apoptosis with increasing frequency. These cells were able to regain their original telomere length after the therapy was stopped which suggests that the side effects of antitelomerase agents might be minimal. However, this also implies that continuous administration of the drug will be necessary to prevent telomere re-growth in cancerous cells.

These agents could potentially be used to treat cancer in combination with other chemotherapy agents. The combination therapy is necessary because it takes a substantial period of time before antitelomere agents start to have effect on cancerous cells. Similar compounds are already being tested for conditions other than cancer. The researchers report that it should be possible to test these agents in both animals and humans in the near future.

Source: Proceedings of the National Academy of Science 1999;96:14276-14281.

North America’s First Approved Digital Mammography Suite Opens at Princess Margaret Hospital in Toronto

Olya Lechky

Two Toronto hospitals--The Princess Margaret and Mount Sinai--have the distinction of being on the cutting edge in the early detection of breast cancer.

These two pre-eminent institutions in the study, diagnosis and treatment of breast cancer are the first centres in North America to have installed full field digital mammography systems. At a recent press conference, experts hailed General Electric's Senographe 2000D as the single biggest breakthrough in mammography during the past 30 years. This claim is based on over 8,000 clinical studies performed on five prototype machines during the past decade. "Digital mammography represents a milestone in the diagnosis of breast disease and it will soon replace conventional mammography all over the world," said Dr. Patrice Brett, professor of radiology at the University of Toronto.

While conventional film mammography has been of great benefit in the screening and diagnosis of breast disease, the technique has always had inherent limitations, said Dr. Karina Bukhanov, head of the division of breast imaging, joint department of breast imaging, University Health Network and Mount Sinai Hospital. "Digital mammography will bring breast cancer diagnosis into the digital age, enabling all the benefits of modern computer technology and software to be applied to the fight against cancer," she said.

In digital mammography an electronic detector replaces the traditional film screen.

New non-invasive screening test for bladder cancer could be automated

Screening for cancers of internal organs is notoriously difficult, and by the time the disease has progressed to symptoms in the patient that indicate cancer, the outlook is often poor. In the October 30th issue of The Lancet, Kai Stoeber and colleagues from Cambridge, UK, with the Cancer Research Campaign, describe the result of a new screening test for cancer of the urinary tract that does not involve invasive procedures. The test detects the minichromosome maintenance (Mcm5) protein involved in the replication of DNA that occurs when cells divide. The protein is expressed at a high concentration in many cancers, probably because the cancer cells divide rapidly. The investigators used an immunofluorometric assay to show that the protein was detected in cells shed in the urine of all eight patients with a cancer of the urinary tract, and in only one of 28 control individuals. This particular test could be automated, and because the Mcm5 protein is over-expressed in other cancers, the same test could potentially be used to screen for these.

Dr. Carol Sawka: A Leader in Women’s Health Care and Cancer Research

Jocalyn P. Clark, BSc, MSc

It is an exciting time to be involved in cancer research in Canada and Dr. Carol Sawka is helping lead the way. Over the last fifteen years Dr. Sawka has established an impressive clinical and research career in women's health, focusing on optimizing breast cancer care. Dr. Sawka's leadership roles bridge clinical, research, and policy-making activities, linking scientific research evidence to the development of clinical practice guidelines, and setting the stage for promising new treatments and outcomes for cancer patients.

Like many high profile academic physicians, Dr. Sawka wears several hats. Her eleven year involvement with the Toronto-Sunnybrook Regional Cancer Centre culminated recently in her appointment as Chief Executive Officer. Her career began at the cancer centre in 1988 as a staff oncologist, followed by her appointment in April 1998 as a Division Head. Currently she is also the CEO of the Central East Regional Cancer Centre and a Vice-President of Cancer Care Ontario. In addition, Dr. Sawka is Head of the cancer program at Sunnybrook and Women's College Health Science Centre, as well as an Associate Professor in the Departments of Public Health Sciences and Medicine at the University of Toronto and an Adjunct Senior Scientist at the Institute for Clinical Evaluative Sciences (ICES).

Dr.

Gynaecologic Cancers Remain Leading Cause of Cancer-related Deaths in Women

Nariman Malik, BSc

Gynaecologic cancers remain a leading cause of cancer-related deaths in Canadian women. The three malignancies focussed on in this article, endometrial cancer, ovarian cancer and cervical cancer, have good prognoses if they are detected in their early stages. As such, it is of utmost importance that primary health care physicians be aware of Canadian guidelines for detecting these conditions and their limitations.

Endometrial Cancer

When diagnosed early, endometrial cancer is highly treatable and has a high survival rate. Stage I, grade I endometrial cancer has a five-year survival rate of 98%. This type of cancer most often presents as post-menopausal vaginal bleeding early in the course of the disease. Any woman who presents with unexplained post-menopausal bleeding should undergo endometrial assessment which can lead to early detection and improve the chances for a cure.

Detection

To identify women at risk of developing endometrial cancer, the progesterone challenge test can be used. In the United States, it had been recommended that all post-menopausal women should undergo this test at each annual examination. There are currently no Canadian recommendations regarding this test.

Some Cancer Vaccines Successful in Early Clinical Trials

Ruwaida Dhala, BSc, MSc

Vaccination has one of the greatest impacts on disease prevention. Most vaccines generate protective immune responses against a pathogen, preventing disease initiation. Often the immunity generated by vaccines to specific pathogens is lifelong. Preventative vaccines are not effective in cancer prevention, however, mostly because cancer antigens elicit poor immune responses. For this reason many cancers evade the immune system. Cancer vaccine strategy focuses on eliciting anti-tumour responses in patients that are already afflicted with cancer. These vaccines will presumably prevent cancer progression and reoccurrence rather than prevent cancer initiation.

In order for the body to mount an immune response, the invading pathogen, or components of it, must be exposed to the immune system. There are two major components of the immune system, humoral and cellular. Humoral immunity is involved in the generation of antibody responses. These antibodies are usually directed against extracellular pathogens such as bacteria. Most preventative vaccines rely on this arm of the immune system.

Cancer and Nutrition: Be Cautious When Making Dietary Recommendations

Cancer and Nutrition: Be Cautious When Making Dietary Recommendations

Eleanor Brownridge,
Registered Dietitian

While a number of major dietary components--including fat, total energy, salt, red meat and alcohol--have been implicated as contributing to specific cancers, current case-control and cohort studies do not support some of the predominant hypotheses that are influencing Canadian eating habits. A major reason for the current level of certainty is the challenges inherent in nutrition epidemiology.

Diets are extremely complex. Nutrients are found in a multitude of foods, and their absorption and activity is influenced by other dietary components eaten at the same time. People change their eating habits over time and we have no idea as to the relevant latency period for various diet-related effects.

"The only clear recommendation we can make at this time is to eat more fresh fruits and vegetables. Related Terms: Cancer, Preventive Health, cancer, nutrition Sign in Buy Article Subscribe Incidence of Skin Cancer Reaching Epidemic Proportions Michelle Durkin, BSc The most common form of cancer today is skin cancer. Approximately half of all new cancers diagnosed are one of three defined types: basal cell carcinoma (BCC) , squamous cell carcinoma (SCC), or malignant melanoma (MM). Although the age of diagnosis is decreasing, most skin cancers do not appear until after the age of fifty, making this disease a serious threat to the elderly population. Fortunately it is also a disease which is successfully treated if detected early. Epidemiology The incidence of nonmelanoma (BCC and SCC) and MM skin cancers has increased so significantly over the past few decades it may have reached epidemic proportions, particularly in the United States and Canada. It has been projected by the National Cancer Institute along with the Center for Disease Control that in 1999 alone, skin cancer (all types combined) will claim the lives of nearly 9,200 people in the United States. Besides increasing annual incidence, more women are getting skin cancer and people are getting skin cancer at younger ages. Individual types of skin cancer follow different morbidity and mortality distributions. About 80% of skin cancers are BCC, 16% SCC, and 4% MM. The mortality rate for nonmelanoma skin cancer is decreasing and that of melanoma is increasing. Related Terms: Cancer, cancer, skin, skin cancer Sign in Buy Article Subscribe Over Half of Breast Cancer Patients are Over 65 at Diagnosis Lilia Malkin, BSc Breast cancer has the dubious distinction of being the most frequently diagnosed neoplasm and the second leading cause of cancer deaths in Canadian women today. Since the incidence of breast cancer increases with age, its appropriate diagnosis, management, and prevention are highly important in the geriatric population. Epidemiology A widely quoted statistic is that one in nine Canadian women will develop breast cancer in her lifetime, while one in twenty-five will die from it. The National Cancer Institute of Canada (NCIC) estimates that 18,700 Canadian women will be diagnosed with breast cancer and that 5,400 will succumb to it in 1999. In Ontario alone, more than 7,000 new cases are reported and approximately 2,000 women die each year. Although breast cancer affects men as well as women, male patients make up less than one percent of all cases. In 1994, when nearly 16,000 Canadians were diagnosed with breast cancer, only 97 of them were male. Breast cancer remains a significant contributor to morbidity and mortality in the female geriatric population. More than 50% of breast cancer patients are older than 65 at diagnosis. According to NCIC's 1999 estimates, 6,000 of the new breast cancer cases will occur in Canadian women aged 70 and over. Related Terms: Cancer, breast cancer, diagnosis Sign in Buy Article Subscribe Subscribe to Cancer