How Breast Cancer Spreads

In a breakthrough study appearing in advance online publication of Nature Methods, researchers at Albert Einstein College of Medicine of Yeshiva University describe for the first time a method of viewing individual breast cancer cells for several days at a time. The study, by scientists in Einstein's Gruss Lipper Biophotonics Center, provides detail on how cancer cells invade surrounding tissue and reach blood vessels. These movements are the first steps of the potentially deadly stage of cancer known as metastasis.
The new method of viewing cancer cells over several days in their natural environment is considered significant because prior methods of study only allowed cells to be viewed clearly for several hours at one time. Having a longer and clearer window into how cancer cells move during the early stages of metastasis may help scientists develop more effective cancer therapies. For 2007, the American Cancer Society reported that a woman with metastatic breast cancer had an average survival rate of two years.
Using intravital imaging, the researchers developed a "photoswitch" to mark cancer cells of their choosing within a tumor and observe how these tumor cells in mice move in their surrounding tissue. The technique allowed researchers to see individually labeled tumor cells move in real time and in living mice.
"One focus of our laboratories has been developing methods to see what cancer cells are doing when followed over time in the most realistic setting," explained Jeffrey Segall, Ph.D., professor of anatomy and structural biology. "Mapping the fate of tumor cells in different regions of a tumor was not possible before the development of the photoswitching technology," explained John Condeelis, Ph.D., co-chair and professor of anatomy and structural biology and co-director of the Gruss Lipper Biophotonics Center.
The new method involves the placement of a frame containing a small glass window onto the breast tumor of a mouse formed from cancerous cells that have a specific tag. Through the glass, individual breast tumor cells are targeted with a laser that 'marks' the cancer cells red. By viewing the cells through the window using a microscope, researchers can follow the cells as they spread. The mouse can move around and live normally with the glass plate and then be anesthetized briefly for observance under the microscope. The marked cancer cells are followed over a period of days until they lose their brightness.
Using this technique, investigators found that breast cancer cells closer to blood vessels were more aggressive and directed in their invasiveness than cancer cells farther from blood vessels. The cancer cells near blood vessels also appeared in the lung indicating that they are disseminated throughout the body.
As co-lead author, Bojana Gligorijevic Ph.D., explained, "Our work showed how important the microenvironment of a tumor is to the behavior of a cancer cell and the metastatic outcome of the tumor itself. We can now look at the early steps of metastasis in high resolution and specific regions of the tumor."
This finding marks the first time a direct link was shown between the presence of blood vessels and the invasive ability of a cancer cell, which strengthens the growing theory that blood supply is crucial to effective metastasis. It also suggests that many cancer therapies currently in development, which are directed at cutting off blood supply to tumors, may be on the right track.
The research was conducted by Dmitriy Kedrin, Bojana Gligorijevic, Ph.D. and team leader Jacco van Rheenen, Ph.D. under the direction of Drs. Segall and Condeelis. Vladislav Verkhusha, Ph.D., associate professor of anatomy and structural biology, and Jeffrey Wyckoff, M.F.A., B.S., senior associate of anatomy and structural biology, both members of the Biophotonics Center, contributed novel photo-switching protein, and expertise in intravital imaging, respectively. This study required this broad multidisciplinary team and the resources of the Center to make the technical leap needed to achieve this new result. The Center has been supported by the generous contributions of Evelyn Lipper.
Each year, cancer kills 553,000 people in the U.S. Most cancer deaths are caused by complications from metastasis, the spread of cancer cells to distant tissues and organs through the blood, rather than from the primary tumor itself. This research provides a powerful tool for studying cancer metastasis and is part of a growing body of Einstein cancer research that sheds light on how cancer spreads.
The study has been chosen for highlight at the 48th Annual Meeting of The American Society of Cell Biology in San Francisco on December 15, 2008 to be presented by Dr. Gligorijevic.
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Today, Einstein receives more than $150 million annually in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island " which includes Montefiore Medical Center, Einstein's officially designated University Hospital " the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.aecom.yu.edu. (source :newswise.com)

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​ How Breast Cancer Spreads In a breakthrough study appearing in advance online publication of Nature Methods, researchers at Albert Einstein College of Medicine of Yeshiva University describe for the first time a method of viewing individual breast cancer cells for several days at a time.

Milk production hormone can help prevent aggressive breast cancer

Washington, Feb 4 (ANI): A mechanism by which a hormone responsible for milk production blocks an oncogene that makes breast cancer more aggressive has been discovered by researchers from the Kimmel Cancer Center at Jefferson.

The researchers found that prolactin, a pituitary hormone that normally stimulates breast development and milk production, in fact reduces levels of an oncogene called BCL6.

The BCL6 protein has previously been shown to play a role in poorly differentiated breast cancer, which carries a poorer prognosis.

According to Hallgeir Rui, a professor of Cancer Biology and Medical Oncology at Jefferson Medical College of Thomas Jefferson University, prolactin's role in breast cancer is, to a large extent, carried out by a protein pathway called Stat5.

In breast cancer, the inactivation of Stat5 is related to poorly differentiated breast cancer, and thus poorer prognosis.

"We found that prolactin will block expression of the BCL6 protein, and showed that Stat5a, but not the very similar Stat5b variant, is involved in this process as a mediator of prolactin," said Dr. Rui.

"We think that prolactin plays an important role in preventing aggressive breast cancers, and that there is a connection between the loss of Stat5 and the increase of BCL6 in making breast cancer more aggressive," Dr. Rui added.

Dr Rui and his laboratory investigated the phenomenon in several different breast cancer cell lines grown in the laboratory, and also in mice and in human breast cancer samples. The relationship held up across all three.

Receptors for prolactin are present on a majority of breast cancers. Prolactin levels in blood are relatively unaffected by menopause, and breast cancer patients across all age groups are exposed to the hormone.

The new findings, published in the journal Cancer Research, could lead to better diagnostic tests for breast cancer, and also the development of new treatments, according to the researchers. (source:oneindia)

New Hope for Cancer Patients

Addressing the Press at the International Modern Hospital, Dubai alongside the official contract signing ceremony offering his services to the hospital, Prof. Dr. Karl Reinhard Aigner said – “The treatment called Regional Chemotherapy (RCT) is tolerated well by 95% of all patients; they suffer neither nausea nor hair loss. For me, my highest goal has always been to relieve pain.” Survival rates and prognoses for recovery lie significantly above those of the results for conventional chemotherapy especially in Breast and Pancreatic cancer. Good chances for treatment success exist for most cancers of other body organs, such as lung cancer, carcinomas of the stomach, liver, bladder, prostate, ovaries, anus as well as head and neck tumors.

Prof. Dr. Karl Reinhard Aigner and his highly specialized team of physicians will now be available for consultation and to administer Regional Chemotherapy at the International Modern Hospital in Dubai. Dr. Dia Hassan CEO International Modern Hospital said: “ I am extremely happy to be a witness to this historic moment. It is indeed our privilege to have the world-renowned oncologist Prof. Aigner, one of the pioneers in Regional Chemotherapy as a member of our team. This is sure to bring a big relief and hope to a lot of cancer patients from the region.”

Specialization in the treatment of critical diseases has shown globally to produce significantly improved outcomes. Importantly however the decision made here highlights how the Middle East and especially Dubai is now welcoming experts from across the globe to offer patients an increased choice in the options available.

Mortality figures for the region prove that cancer is one of the major causes of death in the region. The availability of Dr Aigner in the region can only help in the action that is required to reduce the figures. Cancer is considered to be an insidious, difficult to treat disease with many bad side effects on the bodies and the spirits of its victims. New hope is offered to cancer patients with a very effective therapy used on the tumor or the tumor area, what is called regional chemotherapy (RCT). Prof. Dr. Karl Reinhard Aigner, the pioneer of regional chemotherapy, will from now on be practicing the method he helped develop for the treatment of solid tumors at the International Modern Hospital in the United Arab Emirates.

Prof. Dr. Karl Reinhard Aigner, head of oncologic surgery at the Medias Klinikum GmbH & Co KG in Burghausen, Germany, has been successfully using regional chemotherapy for years. The basic concept is to treat organs and body parts affected by cancer very aggressively in one region only while filtering the chemotherapeutic agents out of the rest of the body. In doing so, the tumor shrinks and later can be removed without problems, or it may even completely disappear as a result of the therapy.

Regional Chemotherapy – different from other chemotherapies

Chemotherapy has been and continues to be one of the most common treatment methods for tumors. Poisonous chemical agents (cytotoxins) attack and destroy the tumor. For patients with carcinomas that have already metastasized, the use of poisonous chemical agents in the total body blood circulatory system is often the last chance to combat the illness. Despite newer developments, the poisonous agents damage not only the tumor cells but also healthy cells in areas like the hair follicles, bone marrow, and the mucous membrane of the digestive tract; they reduce the number of white corpuscles. As a result the patients lose their hair and complain about intense nausea and physical exhaustion. Moreover, conventional chemotherapy does not have great success in many patients since the concentration of poisonous agents that are administered is distributed over the entire body, leaving only a proportionally small number of cytotoxins to have an effect on the tumor cells.

Prof. Dr. Karl Reinhard Aigner uses a special form of chemotherapy that he himself developed, one that attacks the tumor in a sustained fashion because of its highly concentrated action. Working with his highly specialized team, he injects cytotoxins directly into the blood vessels that supply the tumor or the region of the body affected by the tumor – hence the name of the procedure: regional chemotherapy. “It’s like the fire department,” explains Prof. Aigner. “We aim our hoses at the actual source of the fire and not at the intact surroundings.”

The advantages of this treatment are obvious. By injecting the cancer medication into the artery serving the tumor or tumor region, the poisonous chemicals can be administered with a very high concentration into the affected region. This leads in turn to a higher transfer of these poisonous chemicals into the tumor cells and results in a superior and more rapid effect at that spot. In contrast to conventional chemotherapy and depending on the type, size and state of metastasis of a tumor, a three to ten-fold higher concentration of cytotoxins can be injected, and in especially difficult cases up to 70 times as much. Nonetheless, there are hardly any side effects on the total body, since with the process of chemo filtration, “depoisoning," in connection with every intervention the blood is cleaned. The quality of life of patients is generally significantly improved. All of the techniques developed by Prof. Aigner and his team for regional chemotherapeutic treatment is designed to minimize as far as possible actual operations. Between treatments, the patients can lead a normal life, and usually hold down a normal job.

Prof Aigner continues: “Most of the patients who come to us are those who have not responded well to chemotherapy or those who have had a relapse. Various medical studies have published results pointing to convincing data in terms of tumour response, quality of life and survival of those treated with RCT. For instance, it has been well established that pancreatic cancer, a killer cancer, responds well to RCT when other chemotherapies have failed. Breast cancer too has been treated with almost no side effects and without amputation. The response rate of breast cancer has been 80 to 95 per cent with RCT.

“Additionally, even advanced cancers of the bladder and the prostate are treated by means of the isolated pelvic perfusion technique with chemofiltration, avoiding mutilating surgery, impotence and incontinence,” he says.

Regional Chemotherapy - for whom?

Regional chemotherapy is suitable for all patients with solid tumors. To be sure, not every type of tumor is suitable for highly concentrated chemotherapy. Professor Aigner adds: “Our method either works right away or not at all.” In essence, just as in conventional cancer treatment, the greater the proportion of the body affected by the tumor, the smaller are the chances for success. Even in regional chemotherapy the dose of poisonous chemical agents cannot be increased without limit. Tumors in their early stages are especially good to treat with regional chemotherapy. Still, Prof. Aigner and his team have achieved very good results even in late stages and in supposedly hopeless cases.

Good chances for treatment success exist for most cancers of body organs, such as breast and lung cancer, carcinomas of the stomach, liver, pancreas, bladder, prostate, ovaries, and anus, and head and neck tumors. (source:eyeofdubai)