Breast Cancer Research Center
Breast Cancer Research Center
News Article | April 26, 2017
A mutant, see-through variety of zebrafish may be the key to understanding how to treat breast cancer in humans, new research with the fish shows. Derek Walsh, who oversees the zebrafish facility at the Boston University Medical Campus, says there are 15,000 to 20,000 fish swimming in the tanks there. Each adult fish is about an inch long, silver with black stripes, just like the kind you’d see at a pet store. Others, mutants called “Casper,” are so transparent that you can see their ovaries lumpy with eggs. One tank, labeled “Fli1:GFP,” holds fish whose blood vessels glow green under UV light. These marvelous mutants, and others, are under the charge of Hui Feng, director of the university’s Lab of Zebrafish Genetics and Cancer Therapeutics, and they may hold clues to treating breast cancer. Although it might seem odd to study breast cancer in an animal with no breasts, zebrafish do have lungs, hearts, brains, eyes, and blood vessels that respond to cancer cells much as human vasculature does. Also, since scientists have used zebrafish to model disease for decades, their genetics are well understood and easily manipulated. Finally—especially useful for studying cancer—the fish are transparent during development, and mutants like Casper are transparent as adults, so scientists can easily monitor tumor growth and metastasis. “The zebrafish can model human systems, and using them allows her to do pharmacological and genetics work quickly and relatively cheaply,” says David Farb, professor in the School of Medicine and chair of pharmacology and experimental therapeutics. Feng’s strategy is to combine observations and experiments in zebrafish with tests in human cells and analysis of human cancer genome databases. By linking all three approaches, she hopes to pinpoint new drug targets and potential therapies for breast cancer. “If we find something in the fish, we go to the human patient cancer cell and ask: is this true for human cancer or not?” says Feng, assistant professor of pharmacology and medicine. “If everything we find is true for fish, but not true in humans, nobody cares.” Feng’s research focuses on the gene MYC, often called the “cancer gene from hell,” because it is altered in nearly all human cancers. Usually, alterations push MYC into overdrive, and because it codes for a transcription factor—a protein that turns genes on or off—hyperactive MYC can lead to runaway expression of many genes, and cancer. Feng says that many different cancers, seemingly caused by many different gene mutations, all eventually lead back to MYC. And MYC is disproportionately elevated in triple-negative breast cancer, or TNBC, which lacks hormone receptors and therefore doesn’t respond to hormone therapy. While TNBC often responds well to chemotherapy, it can grow quickly, spread aggressively, and is more likely to recur than other types of breast cancer, according to the Susan G. Komen Breast Cancer Foundation. “If you had a way of killing cancer cells or blocking the spread or metastasis of these cells,” says Farb, “that could apply not just to triple-negative breast cancer, but to all cancers.” MYC’s ubiquity made the gene a particularly attractive target for Feng. The problem, though, is that MYC is also important in normal cell division and cellular metabolism, so simply shutting it off doesn’t work. “Directly targeting MYC is very challenging and toxic,” says Feng. “That’s why this problem is so hard. If it were so easy, we would have found a cure for cancer already.” Feng’s strategy is twofold. Scientists in her lab look for genes, biological pathways, and molecules that impair MYC-driven cancer cells, while leaving normal cells alone. She and her colleagues are also teasing apart the basic process of metastasis: how cancer cells enter blood vessels, travel through the body, and take hold elsewhere. The zebrafish are critical for both lines of research. Some scientists in Feng’s lab use zebrafish that have been bred to develop MYC-driven cancer, and through painstaking genetic and molecular intervention, they use the cancer-riddled fish to look for any drug, pathway, or chemical compound that may decrease tumor size and spread. If anything looks promising, they test it in human cancer cells to see if the effect translates. The work is basic science at its most basic. One early discovery involves glutamine, an amino acid involved in cell metabolism and protein synthesis. The finding, published in Leukemia: targeting glutamine metabolism by inhibiting a metabolic enzyme called DLST could represent a novel approach for treating MYC cancers. “MYC-driven cancers are addicted to glutamine, but normal cells are not,” Feng says. “So if you withdraw glutamine from normal cells, they tolerate it. But if you withdraw glutamine from a MYC cancer, they just die. They crash.” This research is still in its infancy: Feng is now working with John Porco, professor of chemistry and director of the university’s Center for Molecular Discovery, to develop a small molecule that inhibits DLST and might easily block glutamine’s access to certain cellular functions. If it works, she will test it rigorously in fish, then in human cells, then in mice. Eventually it may lead to a therapy for humans. The other major project in Feng’s laboratory is to understand the molecular pathways that regulate the very first step of metastasis, called intravasation, the entry of tumor cells into blood vessels. By untangling this process, she and her colleagues hope to find ways to block the spread of tumor cells from their primary site. One approach Feng’s students and colleagues use is to inject cancer cells into tiny, two-day-old fish embryos, using a microscope and minuscule capillary tubes. “At this stage, the zebrafish already has a tail and a head, a vascular system. It already looks like a fish,” says Fabrice Laroche, a postdoctoral fellow in Feng’s lab. “It’s already a little animal that we can use to study cancer.” Laroche and his colleagues inject the cancer cells into a fish’s yolk sac, which harbors the cancer cells much as a breast might. Then they watch the cancer cells, tagged in fluorescent red, migrate through the fish as it grows. Feng has filmed the process, and the microscopic movies of glowing red cancer cells barging into glowing green blood vessels are both chilling and enlightening. “The zebrafish has the advantage of being particularly transparent, so we can really look inside the tissues in a live animal and see how the cancer spreads,” says Laroche. “In that aspect, the zebrafish is a perfect model to study cancer.” Laroche focuses on triple-negative breast cancer, which “tends to be very aggressive,” Feng says. He is studying a gene called S1PR1, which codes for a cellular receptor with many biological functions, including cell migration. He says his preliminary results seem to indicate “that when we make the breast cancer cell make more of this gene, or overexpress this gene, then the cancer cells spread more into the fish.” “Cancer is lethal because the cells are rapidly growing and because they can spread,” says Farb. “When the cancer cells spread, the disease becomes, in many cases, an insurmountable clinical problem. If you can stop the cells from spreading once the cancer is diagnosed, and then kill the cancer cells that have already spread, we’d have a better chance of controlling or even curing the disease.” To better understand metastasis, Feng is also looking beyond biology into engineering and physics. For instance, she is collaborating with physicist Igor Sokolov, a Tufts University professor of mechanical engineering, to study the physical properties that allow cancer cells to leave their place of origin and travel throughout the body. “We think the reason these tumor cells have such a great ability to metastasize is their strength—they are much tougher,” says Feng. “So when they try to squeeze through the blood vessels, they have more force, and they can actually really squeeze through.” Support for Feng’s work comes from Boston University’s Shamim and Ashraf Dahod Breast Cancer Research Center, the National Institutes of Health, and a number of private foundations, including the Leukemia Research Foundation and the Mary Kay Foundation.
Najafi S.,Breast Cancer Research Center |
Payandeh M.,Kermanshah University of Medical Sciences |
Sadeghi M.,Kermanshah University of Medical Sciences
Iranian Journal of Cancer Prevention | Year: 2017
Background: Non-Hodgkin’s lymphoma (NHL) is the fifth most frequently diagnosed cancer whose incidence has risen by at least 100 percent over the past five decades especially in the West. Objectives: The aim of this study is to investigate Clinicopathology figures, overall survival (OS) and Progression-free survival (PFS) in patients with NHL in Iran. Methods: In a descriptive study, 143 patients referred to Clinic of Hematology in two centers between 2005 and 2014. We checked age, sex, types and subtypes of NHL; recurrence, Ki-67, organomegaly, lymphadenopathy, radiotherapy, OS and PFS in the patients. The mean follow-up was 49 months. All patients received R-CHOP regimen for 6 to 8 cycles. Results: The mean age at diagnosis for the patients was 46 years (range, 16 - 82) and 76.9% had age < 60 years and 62.2% were male. 58% patients had primary nodal NHL and out of 139 patients, 88.5% were aggressive NHL. Organomegaly and lymphadenopathy were in 12 patients (8.4%) and 80 (55.9%), respectively. Of all patients, 106 patients (74.1%) were treated with radiotherapy. 2-year OS rate was 91.5% and 5-year OS rate was 85%.2-and 5-year PFS rates were 79.6% and 63.3%, respectively. Conclusions: Percentage of NHL in males is more than females and the median age is around 45 years. Also, the prevalence of nodal is more compared with extranodal in NHL patients. © 2017, Iranian Journal of Cancer Prevention.
Najafi S.,Breast Cancer Research Center |
Mozaffari H.R.,Kermanshah University of Medical Sciences |
Sadeghi M.,Kermanshah University of Medical Sciences
Iranian Journal of Blood and Cancer | Year: 2017
Background: Triple negative breast cancer (TNBC) is reported to be associated with a high risk of recurrence, poor overall survival (OS), and disease-free survival (DFS) rates. This study evaluated the clincopathological features and survival of non-metastatic TNBC women in the capital of Iran compared with other areas of the world. Methods: In a retrospective study, 119 women with TNBC based on the criteria were analyzed in this study during 2007-2015. A number of clinicopathological variables, OS and DFS were determined in all patients. The mean follow-up was 38 months, which 6 patients lost to follow-up and 16 died of the disease and therefore were censored from the study. Results: The mean age at diagnosis was 44.9 years (range: 21-85 years). 31.9% were older than 50 years. The 2-and 5-years OS rates were 96% and 88.1%, respectively; whereas, the 2-and 5-years DFS rates were 87% and 74.1%, respectively. Right breast tumor and lymph node involvement were more common in patients younger than 50 years, but vascular invasion was more observed in patients aged ≥50 years. There was no significant difference between menopause status, age and Ki-67 index for OS or DFS. Conclusion: The prevalence of TNBC was more common in women younger than 50 years. Ki-67 index, menopausal status and age could contribute to prognosis and survival of patients. © 2017, Iranian Pediatric Hematology and Oncology Society. All rights reserved.
Darvishi B.,Baqiyatallah Medical Sciences University |
Panahi Y.,Baqiyatallah Medical Sciences University |
Ghanei M.,Baqiyatallah Medical Sciences University |
Farahmand L.,Breast Cancer Research Center
Basic and Clinical Pharmacology and Toxicology | Year: 2017
Among the most readily existing chemical warfare agents, sulphur mustard (SM), also known as mustard gas, is the most commonly used agent owing to its ease of synthesis and stockpiling. Unprotected exposure mostly results in debilitation rather than lethal injuries, leaving an exposed victim incapacitated for days to even months. Although acute toxicity of sulphur mustard has been fairly established, the long-term post-exposure effects either chronic or short-term but significant are still evolving. A total of 30,000 Iranian victims of the Iran–Iraq imposed war have now – after 30 years – formed the key population demonstrating long-term effects from sulphur mustard exposure. Recent studies have shown that the prevalence of several long-term cardiovascular disorders (CVDs) has significantly increased among SM-exposed victims including coronary artery disorders (CAD), coronary artery ectasia (CAE), congestive heart failure (CHF) and myocardium abnormalities. The more important point is the lack of a determinant biomarker for early screening, recognizing, treating, monitoring and estimating exposed victims’ response to applied therapy. Additionally, unidentified risk factors significantly decrease the chance of a successful therapy and result in undesired failure of a comprehensive therapeutic strategy. In this MiniReview, we examined the literature in detail to evaluate relevant reports considering long-term cardiovascular complications of SM, detecting possible risk factors and determining possible preventing events. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
Shahbazi S.,Tarbiat Modares University |
Alavi S.,Pasteur Institute of Iran |
Majidzadeh-A K.,Breast Cancer Research Center |
Ghaffarpour M.,Iran National Institute of Genetic Engineering and Biotechnology |
And 3 more authors.
Medical Oncology | Year: 2013
There is growing evidence of a malignancy-protective role for vitamin D in breast cancer. The effects of vitamin D are mediated via the vitamin D receptor (VDR) which is encoded by VDR gene. Several SNPs on VDR gene has attracted research interest, although the magnitude of the impact of VDR allelic variations on breast cancer has been controversial. In the present study, we focused on the distribution of VDR FokI and BsmI polymorphisms in Iranian breast cancer patients. A case-control study was conducted on 296 samples including 140 breast cancer patients and 156 age matched control women. Restriction fragment length polymorphism (RFLP) analysis was performed for BsmI and FokI genotyping. Randomly selected PCR products were subjected to sequencing to verify the RFLP results. A significantly increased risk of breast cancer was observed with BsmI bb or even Bb genotype (OR 2.39, CI 1.17-4.85 and OR 2.28, CI 1.16-4.47, respectively). Nevertheless, statistically significant association between FokI genotypes and breast cancer risk was not observed. This study lends support for an increased risk of breast cancer associated with the VDR BsmI polymorphism. © 2012 Springer Science+Business Media New York.
Chan A.,Curtin University |
Chan A.,Breast Cancer Research Center |
McGregor S.,Breast Cancer Research Center |
Liang W.,National Health Research Institute
Breast | Year: 2014
Optimal outcome for early breast cancer patients receiving adjuvant chemotherapy requires adequate dose delivery, commonly defined as >85% of planned dose of chemotherapy agents. Outside the clinical trial setting, reports from community oncology centres have demonstrated that a significant proportion of patients fail to receive this dose intensity, with neutropenia being the most commonly cited reason for sub-optimal treatment. Data collected prospectively on 1655 patient treated in a single breast cancer centre demonstrates that patients at risk of sub-optimal dose delivery can be identified by routine assessment of neutropenic events during the first cycle. The uniform administration of secondary G-CSF for all subsequent cycles enables dose delivery ≥85%, which was shown to lead to improved survival outcomes when compared with those patients who received <85%. © 2014 Elsevier Ltd.
Haghighat S.,Shahid Beheshti University of Medical Sciences |
Haghighat S.,Breast Cancer Research Center |
Akbari M.E.,Shahid Beheshti University |
Ghaffari S.,Iranian Social Security Organization |
Yavari P.,Shahid Beheshti University of Medical Sciences
Asian Pacific Journal of Cancer Prevention | Year: 2012
Introduction: Breast cancer is the most common cancer in women. Improvements of early diagnosis modalities have led to longer survival rates. This study aimed to determine the 5, 10 and 15 year mortality rates of breast cancer patients compared to the normal female population. Materials and Methods: The follow up data of a cohort of 615 breast cancer patients referred to Iranian Breast Cancer Research Center (BCRC) from 1986 to 1996 was considered as reference breast cancer dataset. The dataset was divided into 5 year age groups and the 5, 10 and 15 year probability of death for each group was estimated. The annual mortality rate of Iranian women was obtained from the Death Registry system. Standardized mortality ratios (SMRs) of breast cancer patients were calculated using the ratio of the mortality rate in breast cancer patients over the general female population. Results: The mean age of breast cancer patients at diagnosis time was 45.9 (±10.5) years ranging from 24-74. A total of 73, 32 and 2 deaths were recorded at 5, 10 and 15 years, respectively, after diagnosis. The SMRs for breast cancer patients at 5, 10 and 15 year intervals after diagnosis were 6.74 (95% CI, 5.5- 8.2), 6.55 (95%CI, 5-8.1) and 1.26 (95%CI, 0.65-2.9), respectively. Conclusion: Results showed that the observed mortality rate of breast cancer patients after 15 years from diagnosis was very similar to expected rates in general female population. This finding would be useful for clinicians and health policy makers to adopt a beneficial strategy to improve breast cancer survival. Further follow-up time with larger sample size and a pooled analysis of survival rates of different centres may shed more light on mortality patterns of breast cancer.
Mohammadpour H.,Tarbiat Modares University |
Majidzadeh-A K.,Breast Cancer Research Center |
Majidzadeh-A K.,Tehran University of Medical Sciences
Photodiagnosis and Photodynamic Therapy | Year: 2015
Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photodynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Material and methods: Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2cm to achieve a total light dose of 5 Joules (J)/cm2. Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Results: Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells ( P< 0.05). Growth of cancer cells remarkably decreased after treatment with MSCs conditioned media and PDT in time-dependent manner ( P< 0.01). Conclusion: Results revealed that MSCs conditioned media induced the apoptosis in 4T1 breast cancer cells and apoptotic effects of MSCs conditioned media were intensified following photodynamic therapy. This study showed that MSCs conditioned media combined with PDT may be useful as a novel treatment modality into the development of therapeutic strategies for treatment of breast cancer. © 2015 Elsevier B.V.
Mobarakeh Z.S.,Breast Cancer Research Center |
Mirzaei K.,Tehran University of Medical Sciences |
Hatmi N.,Tehran University of Medical Sciences |
Ebrahimi M.,Breast Cancer Research Center |
And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014
Background: The aim of this study was to investigate demographic features, dietary habits, and some possible risk factors for being susceptible to breast cancer in Iranian women. Materials and Methods: A study of dietary habits and breast cancer was conducted among 53 Iranian women with histological confirmed disease and 40 matched controls. A dietary habits questionnaire was used to evaluate the pattern of selected food intakes. The risk of cancer was analyzed after adjustment for confounding factors. Age, weight, body mass index (BMI), waist circumference, educational status, parity, lactation, marital status, menopause, history of estrogen therapy, and family history of breast disease or cancer were assessed among participants. Special attention was given to the relationship between consumption of high fat meat, milk, yogurt and cheese as well use of frying oils for frying foods, use of olive/liquid oils for cooking, removing fat from meat and poultry, removing chicken skin and not use of mayonnaise as salad dressing and the risk of breast cancer. Moreover, salad, vegetable and fruit consumption, and eating outdoors owere investigated. Results: Our results revealed significant lower education and higher BMI and waist circumference levels in patients with breast cancer. There was significantly increased breast cancer risk in overweight women in comparison with normal weight (OR=2.91, 95%CI 1.24 to 6.82). High intake of fat dairy products including milk and cheese was found to be a statistically significant factor for increasing breast cancer risk in models adjusting for age, BMI and education. Use of olive/liquid oils for cooking and avoidance of mayonnaise as salad dressing are related to lower risk of breast cancer. The frequency of vegetable and fruit consumption was significantly lower in patients with breast cancer compared to healthy women. Conclusions: Dietary habits might be risk factors for breast cancer among Iranian women. Adoption of a prudent diet could be an appropriate strategy for preventing breast cancer.
PubMed | Breast Cancer Research Center
Type: Review | Journal: Cell proliferation | Year: 2016
Despite numerous remarkable achievements in the field of anti-cancer therapy, tumour relapse and metastasis still remain major obstacles in improvement of overall cancer survival, which may be at least partially owing to epithelial-mesenchymal transition (EMT). Multiple signalling pathways have been identified in EMT; however, it appears that the role of the Hedgehog and WNT/-catenin pathways are more prominent than others. These are well-known preserved intracellular regulatory pathways of different cellular functions including proliferation, survival, adhesion and differentiation. Over the last few decades, several naturally occurring compounds have been identified to significantly obstruct several intermediates in Hedgehog and WNT/-catenin signalling, eventually resulting in suppression of signal transduction. This article highlights the current state of knowledge associated with Hedgehog and WNT/-catenin, their involvement in metastasis through EMT processes and introduction of the most potent naturally occurring agents with capability of suppressing them, eventually overcoming tumour relapse, invasion and metastasis.