Contrary to what most people think - especially women - breast cancer is not unique in its category and has different types of disease that deserve special attention and reacts according to the body of its host.
When breast cancer begins to develop in the human body, it generally causes breast cells (known as breast cells), causing them to multiply uncontrollably and disorderly, which ends up changing the shape and size of the breast accordingly.
Like most acts of this type of cancer in the breast duct, his best-known version goes by the name of Ductal Carcinoma, may be in situ - when only limited to the first cells of this duct - or known as the attacker, when there is limited more cells and only begins to reach the tissues around it.
A second type of breast cancer goes by the name of Lobular Carcinoma, precisely because of its characteristic of having its beginnings originated in the lobes of the breast, although this type is not as common to be found. Despite this infrequently diagnosed in general has the characteristic of achieving both breasts.
There are many other types of breast cancer found that although less frequently, have the same performance with treatment developed by the medical and equally respected by most patients. With the union of these two forces, without prejudice, breast cancer is being tackled very efficiently.
Thursday, February 9, 2012
Pictures Of Breast Cancer
Many patients when they have breast cancer diagnosed readily seek all kinds of information about the disease, how to fight it and how to overcome all obstacles. Through the exchange of statements and photos of the treatment, these patients take courage to face the challenge.
A simple web search can display many photos of surgery and treatment of breast cancer, showing step by step without the need to indicate what the person owns the body on display. Through these photos, the patient can see how the surgery is performed, as your body may change later, exactly how and where will the cuts and everything that can be avoided to allow the body remains in its original form the best possible way.
Many magazines and disease prevention centers have been dedicated enough to display pictures of breast cancer in an attempt to educate the entire population - especially women who are most affected by the disease. These pictures are shown how to perform the test from the tap itself to the pictures of how the disease develops in the body and how the body can stay if no treatment is not performed.
To view some shocking photos of breast cancer has helped many women become aware of the need to care for themselves and start preventing disease, improving their quality of individual life, which has considerably reduced the rate of disease in many regions of the country .
A simple web search can display many photos of surgery and treatment of breast cancer, showing step by step without the need to indicate what the person owns the body on display. Through these photos, the patient can see how the surgery is performed, as your body may change later, exactly how and where will the cuts and everything that can be avoided to allow the body remains in its original form the best possible way.
Many magazines and disease prevention centers have been dedicated enough to display pictures of breast cancer in an attempt to educate the entire population - especially women who are most affected by the disease. These pictures are shown how to perform the test from the tap itself to the pictures of how the disease develops in the body and how the body can stay if no treatment is not performed.
To view some shocking photos of breast cancer has helped many women become aware of the need to care for themselves and start preventing disease, improving their quality of individual life, which has considerably reduced the rate of disease in many regions of the country .
Human Breast Cancer
Although breast cancer currently reaches one in every twenty women in Brazil, it is not an exclusively female disease, although admittedly most of the audience is really hit women. Despite the low rate, the disease also manifests itself in men.
When comparing the rate of men and women affected by breast cancer, the first are at an advantage, occurring in every man in comparison with each one hundred women. Despite the low frequency - and therefore the low level of interest from the scientific community to study and explore this kind of manifestation in nature - it is increasingly easy to find the testimony of a man who has been affected by this disease. His low voice in the market should be purely for the great prejudice of the community with the disease.
Breast cancer will generally reach the man with older age, as the case may happen. In general a range greater than sixty years, the man knows the realization of self-examination by touch, which makes tumor control while still being benign, since most patients will only seek help - when they seek - when the tumor is already in advanced development and the only possible solutions are surgery and radiotherapy.
Once they overcome the prejudice against himself, man must still face the prejudice from friends and society. If we all could be conscious, perhaps many men could look better and prevent the development of breast cancer themselves.
When comparing the rate of men and women affected by breast cancer, the first are at an advantage, occurring in every man in comparison with each one hundred women. Despite the low frequency - and therefore the low level of interest from the scientific community to study and explore this kind of manifestation in nature - it is increasingly easy to find the testimony of a man who has been affected by this disease. His low voice in the market should be purely for the great prejudice of the community with the disease.
Breast cancer will generally reach the man with older age, as the case may happen. In general a range greater than sixty years, the man knows the realization of self-examination by touch, which makes tumor control while still being benign, since most patients will only seek help - when they seek - when the tumor is already in advanced development and the only possible solutions are surgery and radiotherapy.
Once they overcome the prejudice against himself, man must still face the prejudice from friends and society. If we all could be conscious, perhaps many men could look better and prevent the development of breast cancer themselves.
Wednesday, February 8, 2012
Carcinoma Mama
Cancer is a group of more than 100 diseases that allow some cells to multiply wildly, invading tissues and organs. This growth may lead to tumors, which are often known as malignant, the times in which the cells multiplied no longer correspond exactly to the original. Then they are known as malignant.
Benign tumors undergo a training process very similar, indeed almost the same. The cells begin to multiply wildly, with no natural explanation, but in this case, when analyzed, they have very few changes compared to its original and not life-threatening for the person.
Treatment of these diseases remains a challenge to modern medicine, as a result of treatment is very different from one organism to another, from one person to another. Factors that may lead to the development of a tumor may be external and internal. As we mention outside smoking and sun exposure can cause lung cancer and skin, respectively, to internal factors, quoted principalmenteo genetic code, since people with a history of cancer in the family may have a greater chance of risk of contracting the disease .
A very common and well researched in recent years is breast cancer, which has increased in women. Breast carcinoma, as it is called a malignant tumor, attacks mostly women, who should get tested regularly touch after 40 years to check for breast lumps. Whilst not offering great danger to life, the risk cases are on average 52 per 100 thousand women.
Benign tumors undergo a training process very similar, indeed almost the same. The cells begin to multiply wildly, with no natural explanation, but in this case, when analyzed, they have very few changes compared to its original and not life-threatening for the person.
Treatment of these diseases remains a challenge to modern medicine, as a result of treatment is very different from one organism to another, from one person to another. Factors that may lead to the development of a tumor may be external and internal. As we mention outside smoking and sun exposure can cause lung cancer and skin, respectively, to internal factors, quoted principalmenteo genetic code, since people with a history of cancer in the family may have a greater chance of risk of contracting the disease .
A very common and well researched in recent years is breast cancer, which has increased in women. Breast carcinoma, as it is called a malignant tumor, attacks mostly women, who should get tested regularly touch after 40 years to check for breast lumps. Whilst not offering great danger to life, the risk cases are on average 52 per 100 thousand women.
Diagnosis Of Breast Cancer
Breast cancer is the most common type of cancer among women, and is most often a benign tumor. Nevertheless, it is very important to follow all the family history of cases and, when perceived nodules, monitor and evaluate the growth removed promptly.
These diseases occur when cells begin to multiply wildly and can reach other cells and tissues around them. As they enter the bloodstream, they can also infect other organs and tissues, thanks to the characteristics of metastasis, of malignant cases themselves. Moreover, in benign cases, the tumors did not usually grow too much and does not spread to other tissues or organs.
The easiest way for women to identify this type of disease is still performing a mammogram, which is a kind of x-ray of the breasts, and can verify the presence of nodules that can not yet be felt by breast self-exams and palpable touch . Performing tests such as mammography, the diagnosis of breast cancer is immediate, and if so, can be treated and eliminated with a much better chance of success.
It is important to remember that self-physical examination, palpate the breasts, does not replace the examination with the doctor, who can assess and recognize disorders and injuries millimeter, which can be treated quickly, without the patient suffers, for example, with removal of a breast, which is psychologically devastating for women. The self-examination, while recognizing the tumor physically, may delay the treatment of smaller tumors, which are still perceptible to the touch. Thus, it is always advisable to consult a doctor periodically over the 40 years of age.
These diseases occur when cells begin to multiply wildly and can reach other cells and tissues around them. As they enter the bloodstream, they can also infect other organs and tissues, thanks to the characteristics of metastasis, of malignant cases themselves. Moreover, in benign cases, the tumors did not usually grow too much and does not spread to other tissues or organs.
The easiest way for women to identify this type of disease is still performing a mammogram, which is a kind of x-ray of the breasts, and can verify the presence of nodules that can not yet be felt by breast self-exams and palpable touch . Performing tests such as mammography, the diagnosis of breast cancer is immediate, and if so, can be treated and eliminated with a much better chance of success.
It is important to remember that self-physical examination, palpate the breasts, does not replace the examination with the doctor, who can assess and recognize disorders and injuries millimeter, which can be treated quickly, without the patient suffers, for example, with removal of a breast, which is psychologically devastating for women. The self-examination, while recognizing the tumor physically, may delay the treatment of smaller tumors, which are still perceptible to the touch. Thus, it is always advisable to consult a doctor periodically over the 40 years of age.
Signs Of Breast Cancer
Breast cancer is cancer that affects the breast tissue. Once this tissue is so common in women as in men, both sexes are prone to develop this type of cancer. Although, in males, the incidence is less than 1% of diagnoses. Moreover, in women, is the second leading cause of fatal diseases classified as carcinogenic.
The epithelial tumors (carcinomas) may be of lobular or ductal (most common) and rarely sarcomas (connective tissue originated).
Breast cancer does not cause physical pain (probably in the later stages of the disease), so the importance of doing breast self-examination for early identification. Through self-examination can detect signs of illness such as a change in the shape of the breast, hardening of the breast, appearance of lumps in the breast or under the arm (and in 90% of cases are benign. Already malignant, usually are solitary, in a single breast), retraction of the breast skin or nipple, significant bloating, breast pain, redness and continuous secretion by a duct (spontaneous and bloody).
People with family cases, both the cancer and the other, should have careful attention to prevent the onset of the disease or prevent its expansion. For those cases with no family, but they are in the age of greatest number of cases (between 40 and 60 years), self-examination is essential. Overweight women with more reproductive phase, with high levels of estrogen receptor positive are more likely to develop the disorder.
The epithelial tumors (carcinomas) may be of lobular or ductal (most common) and rarely sarcomas (connective tissue originated).
Breast cancer does not cause physical pain (probably in the later stages of the disease), so the importance of doing breast self-examination for early identification. Through self-examination can detect signs of illness such as a change in the shape of the breast, hardening of the breast, appearance of lumps in the breast or under the arm (and in 90% of cases are benign. Already malignant, usually are solitary, in a single breast), retraction of the breast skin or nipple, significant bloating, breast pain, redness and continuous secretion by a duct (spontaneous and bloody).
People with family cases, both the cancer and the other, should have careful attention to prevent the onset of the disease or prevent its expansion. For those cases with no family, but they are in the age of greatest number of cases (between 40 and 60 years), self-examination is essential. Overweight women with more reproductive phase, with high levels of estrogen receptor positive are more likely to develop the disorder.
Tuesday, February 7, 2012
Image Of Breast Cancer
Many people ask us to provide some pictures and photos of breast cancer . So we have prepared this post where we will occasionally post pictures new , so come back ofter to see whether we add more. Here below you can see a tumor in one breast that is evolved over time untreated ...
Breast Cancer Cure
Nowadays, the cure rate of breast cancer is high, with a survival rate of 97% in five years, when diagnosed in the early stages. Soon the early diagnosis is very important. Breast cancer treatment is individual, i.e. varies depending on the time of development of the disease in the body. However, there are common procedures adopted, such as hormone therapy, radiotherapy, chemotherapy and/or surgery, in isolation or in combination.Hormone therapy is useful for tumors with estrogen and progesterone receptor positive, since in this type of case, the tumors feed on the hormones to grow with this through hormone treatment, there are blocking this growth.
Radiotherapy can be made before and/or after the affected sinus removal surgery (mastectomy). Before, aiming to decrease the size of the tumor in order to facilitate the withdrawal and then seeking to kill possible leftover tumor cells near the tumor removed.
Chemotherapy, which is stronger, can be given orally or intravenously, seeking to kill cells that are spread throughout the body. The combination of certain drugs is more effective than when individual. Noting that in all of these procedures to side effects such as swelling, malaise, etc.Some factors that should be considered by the oncologist for treatment of the patient are: analyze the stage and grade of the tumor, the presence of hormone receptors in tumor, patient profile (such as age, overall health, the family disease history, if you're already in menopause or not). The achievement of common within mastectomy is affected for most cases in addition to the adjacent procedures already mentioned.
Breast cancer Estadimento
>Breast cancer is the second leading cause of death of women due to cancer. Occurs when the breast cells divide and reproduce very quickly and chaotic. The causes of breast cancer may be associated with the interaction of genetic factors with lifestyles, environment and reproductive habits. There are certain risk factors that increase the possibility of a woman having a breast cancer, such as heredity.
When it is done an exam in which breast cancer is detected, this survey also highlights the extent or stage of cancer, i.e. it is possible to know the size of the cancer, and whether it has spread from its original location. Done the diagnosis, doctors will decide what treatment is best suited.
Generally speaking, there are four stages of evolution of breast cancer from stage 1, in which the tumor is still small and localized, even at stage 4, in which the tumor has already spread to other parts of the body. When the tumor spreads to distant parts of the body, it is said that this is a secondary or metastatic cancer.
Based on the classification of malignant tumours, TMN (Tumor-node-Metastasis). This classification was proposed by the International Union against cancer, according to the characteristics of the primary tumor, lymph nodes, lymphatic drainage chains of the body in which the tumor is located and the presence or absence of distant metastases.
Monday, February 6, 2012
Race of Breast Cancer
Breast cancer is the second leading cause of death of women due to cancer. It occurs when breast cells reproduce and divide very quickly and disorderly. The causes of breast cancer may be associated with interaction of genetic factors to lifestyle, environment and reproductive habits. There are certain risk factors that increase the chances that a woman will have a breast cancer, such as inheritance.
When is an exam that is detected breast cancer, this test also shows the extent or stage of cancer, ie, it is possible to know the size of the cancer and whether it has spread from its original location. After the diagnosis, doctors may decide the most appropriate treatment.
In general, there are four stages of development of breast cancer, from the first stage, in which the tumor is still small and localized to the stage 4, in which the tumor has spread to other parts of the body. When the tumor had spread to distant body sites, it is said that it is a secondary or metastatic cancer.
The estadimento breast cancer is based on the classification of malignant tumors, TMN (Tumor-Node-Metastasis). This classification was proposed by the International Union Against Cancer, according to the characteristics of the primary tumor, lymph node chains lymphatic drainage of the body in which the tumor is located and the presence or absence of distant metastases.
When is an exam that is detected breast cancer, this test also shows the extent or stage of cancer, ie, it is possible to know the size of the cancer and whether it has spread from its original location. After the diagnosis, doctors may decide the most appropriate treatment.
In general, there are four stages of development of breast cancer, from the first stage, in which the tumor is still small and localized to the stage 4, in which the tumor has spread to other parts of the body. When the tumor had spread to distant body sites, it is said that it is a secondary or metastatic cancer.
The estadimento breast cancer is based on the classification of malignant tumors, TMN (Tumor-Node-Metastasis). This classification was proposed by the International Union Against Cancer, according to the characteristics of the primary tumor, lymph node chains lymphatic drainage of the body in which the tumor is located and the presence or absence of distant metastases.
Wednesday, February 1, 2012
Further Investigation Needed To Understand Link Between Parabens And Breast Cancer
New research into the potential link between parabens and breast cancer has found traces of the chemicals in breast tissue samples from all of the women in the study. Parabens are commonly used as preservatives in cosmetics, food products and pharmaceuticals. As the research shows that parabens are measurable in the tissue of women who do not use underarm cosmetics the parabens must enter the breast from other sources.
Breast tissue samples were taken from 40 women, with the results showing that all of the women had at least one paraben in their tissue. The research, published in the Journal of Applied Toxicology, was a collaborative study led by Dr Philippa Darbre, University of Reading and Mr Lester Barr, University Hospital of South Manchester.
The research team studied tissue samples from 40 women undergoing mastectomies between 2005 and 2008 for first primary breast cancer in England. In total, 160 samples were collected, four from each woman, covering serial locations from the axilla (nearest the armpit) to the sternum (breast bone). 99% of the tissue samples contained at least one paraben and 60% of the samples had five.
A number of studies since 1998 have raised concerns about the potential role of parabens in breast cancer as these chemicals possess oestrogenic properties and oestrogen is known to play a central role in the development, growth and progression of breast cancer. In particular, a link was proposed between the disproportionate incidence of breast cancer in the upper outer quadrant of the breast and oestrogenic chemicals in that region, maybe from local application of underarm cosmetic products.
"Our study appears to confirm the view that there is no simple cause and effect relationship between parabens in underarm products and breast cancer" said Mr Lester Barr, consultant surgeon at the University Hospital of South Manchester and Chairman of the Genesis Breast Cancer Prevention Appeal, which part sponsored the study.
"The intriguing discovery that parabens are present even in women who have never used underarm products raises the question: where have these chemicals come from?"
Key findings of the study included: One or more paraben esters were detected in 158 of the 160 samples studied (99%) and 96 of the samples (60%) contained all five of the most common paraben esters. The overall median value for total parabens in the breast tissue was 85.5 ng/g - one billionth of a gram of parabens per gram of breast tissue - ranging from 0 ng/g to 5134.5 ng/g. This level was four times higher than the 20.6 ng/g recorded by a smaller study in 2004. Overall median values for the individual parabens were highest for npropylparaben (16.8 ng/g) and methylparaben (16.6 ng/g), with lower levels for nbutylparaben (5.8 ng/g), ethylparaben (3.4 ng/g) and isobutylparaben (2.1 ng/g). There was a disproportionate incidence of breast cancer in the upper outer quadrant nearest the armpit and significantly higher levels of n-propylparaben were detected in the axilla region, closest to the armpit, than in the mid or medial regions. The other four parabens were equally distributed across all parts of the breast."The fact that parabens were detected in the majority of the breast tissue samples cannot be taken to imply that they actually caused breast cancer in the 40 women studied," said Dr Philippa Darbre, Reader in Oncology at the University of Reading, who also led the 2004 study. "However, the fact that parabens were present in so many of the breast tissue samples does justify further investigation."
Discovery Of Novel Therapeutic Target To Slow Breast Cancer Cell Motility
Interferon-stimulated gene 15 (ISG15), a ubiquitin like protein, is highly elevated in a variety of cancers including breast cancer. How the elevated ISG15 pathway contributes to tumorigenic phenotypes remains unclear and is the subject of a study published in the January 2012 issue of Experimental Biology and Medicine. Dr. Shyamal Desai and her co-investigators from the Louisiana State University School of Medicine in New Orleans, the University of Pennsylvania School of Medicine in Philadelphia, and the Robert Wood Johnson School of Medicine in New Jersey report that gene knock-down studies demonstrate that elevated ISG15 pathway results in disruption of the cytoskeletal architecture of breast cancer cells. ISG15 also inhibits degradation of cellular proteins involved in cell motility, invasion, and metastasis, promoting breast cancer cell migration.
Dr. Desai said "Using ISG15 and UbcH8 gene knocked-down approach, our recent published and unpublished results explicitly demonstrated that the ISG15 pathway inhibits the ubiquitin-mediated proteasome-dependent protein degradation in breast cancer cells. We were the first to recognize this antagonizing effect of ISG15 in cancer cells"; however, others are increasingly coming to the same conclusion in their observations that ISG15 conjugation stabilizes cellular proteins.
Dr. Arthur Haas said "Given the crucial role of the ubiquitin/26S proteasome pathway in normal cell homeostasis, one expects that ISG15-induced downregulation of the ubiquitin pathway must contribute to breast tumor cell viability. Concurrently, in this manuscript we demonstrate that ISG15 promotes breast cancer cell migration by inhibiting ubiquitin-mediated degradation of cellular proteins associated with cell motility, invasion and metastasis".
The authors report that the elevated ISG15 pathway results in disruption of the cytoskeletal architecture effecting actin polymerization and formation of focal adhesions in breast cancer cells. Targeted knockdown of both ISG15 and UbcH8 resulted in reconstitution of the cytoskeletal architecture. Dr. Desai said "Disruption of cellular architecture is a hallmark of cancer. The ISG15 pathway is also elevated in a variety of tumors. Our results therefore reveal that the ISG15 pathway which is aberrantly elevated in tumors could disrupt cell architecture and contribute to breast cancer cell motility". "Because the cellular architecture is conserved and the ISG15 pathway is constitutively activated in tumor cells of different lineages, our observations in breast cancer must hold true for many other tumors".
If ISG15 confers motility to tumor cells in vivo, as suggested in this manuscript, then Dr. Desai concludes that "strategies to decrease ISGylation could provide a therapeutic advantage for patients diagnosed with metastatic tumors overexpressing the ISG15 pathway".
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said that "these intriguing studies by Desai and colleagues suggests that modulation of the ISG15 pathway may provide future therapeutic targets for breast cancer and other metastatic tumors".
New, Noninvasive Way To Identify Lymph Node Metastasis
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Using two cell surface markers found to be highly expressed in breast cancer lymph node metastases, researchers at Moffitt Cancer Center, working with colleagues at other institutions, have developed targeted, fluorescent molecular imaging probes that can non-invasively detect breast cancer lymph node metastases. The new procedure could spare breast cancer patients invasive and unreliable sentinel lymph node (SLN) biopsies and surgery-associated negative side effects.
Their study was published in a recent issue of Clinical Cancer Research (18:1), a publication of the American Association for Cancer Research.
"The majority of breast cancer patients, up to 74 percent, who undergo SLN biopsy are found to be negative for axillary nodal, or ALN, metastases," said corresponding author David L. Morse, Ph.D., an associate member at Moffitt whose research areas include experimental therapeutics and diagnostic imaging. "Determining the presence or absence of ALN metastasis is critical to breast cancer staging and prognosis. Because of the unreliability of the SLN biopsy and its potential for adverse effects, a noninvasive, more accurate method to assess lymph node involvement is needed."
The authors note that the postoperative complications to the SLN biopsy can include lymphedema, seroma formation, sensory nerve injury and limitations in patient range of motion. In addition, biopsies fail to identify disease in axillary lymph nodes in five to 10 percent of patients.
In developing targeted molecular probes to identify breast cancer in axillary lymph nodes, the research team from Moffitt, the University of Arizona and University of Florida used two surface cell markers - CAIX and CAXII. CAIX is a cell surface marker known to be "highly and broadly expressed in breast cancer lymph node metastases" and absent in normal tissues.
CAIX and CAXII are both integral plasma membrane proteins with large extracellular components that are accessible for binding of targeted imaging probes, explained Morse. In addition, several studies have shown that CAIX expression is associated with negative prognosis and resistance to chemo and radiation therapy for breast cancer. CAXII is a protein expressed in over 75 percent of axillary lymph node metastases.
The researchers subsequently developed their targeting agents by using monoclonal antibodies specific for binding CAIX and CAXII, both of which are known to promote tumor growth.
According to the researchers, a number of noninvasive optical imaging procedures for SLN evaluation have been investigated, but the approaches have lacked the ability to target tumor metastasis biomarkers.
"These methods provide only anatomic maps and do not detect tumor cells present in lymph nodes," explained Morse. "Using mouse models of breast cancer metastasis and a novel, monoclonal anti-body-based molecular imaging agents, we developed a targeted, noninvasive method to detect ALN metastasis using fluorescence imaging."
In addition to the imaging study with mice, the researchers also reported that the combination of CAIX and CAXII covered 100 percent of patient-donated samples used in their tissue microarray (TMA) study.
"The imaging probes detected tumor cells in ALNs with high sensitivity," explained Morse. "Either CAIX or CAXII were expressed in 100 percent of the breast cancer lymph node metasatsis samples we surveyed in this study. These imaging probes have potential for providing a noninvasive way to stage breast cancer in the clinic without unneeded and costly surgery."
Using two cell surface markers found to be highly expressed in breast cancer lymph node metastases, researchers at Moffitt Cancer Center, working with colleagues at other institutions, have developed targeted, fluorescent molecular imaging probes that can non-invasively detect breast cancer lymph node metastases. The new procedure could spare breast cancer patients invasive and unreliable sentinel lymph node (SLN) biopsies and surgery-associated negative side effects.
Their study was published in a recent issue of Clinical Cancer Research (18:1), a publication of the American Association for Cancer Research.
"The majority of breast cancer patients, up to 74 percent, who undergo SLN biopsy are found to be negative for axillary nodal, or ALN, metastases," said corresponding author David L. Morse, Ph.D., an associate member at Moffitt whose research areas include experimental therapeutics and diagnostic imaging. "Determining the presence or absence of ALN metastasis is critical to breast cancer staging and prognosis. Because of the unreliability of the SLN biopsy and its potential for adverse effects, a noninvasive, more accurate method to assess lymph node involvement is needed."
The authors note that the postoperative complications to the SLN biopsy can include lymphedema, seroma formation, sensory nerve injury and limitations in patient range of motion. In addition, biopsies fail to identify disease in axillary lymph nodes in five to 10 percent of patients.
In developing targeted molecular probes to identify breast cancer in axillary lymph nodes, the research team from Moffitt, the University of Arizona and University of Florida used two surface cell markers - CAIX and CAXII. CAIX is a cell surface marker known to be "highly and broadly expressed in breast cancer lymph node metastases" and absent in normal tissues.
CAIX and CAXII are both integral plasma membrane proteins with large extracellular components that are accessible for binding of targeted imaging probes, explained Morse. In addition, several studies have shown that CAIX expression is associated with negative prognosis and resistance to chemo and radiation therapy for breast cancer. CAXII is a protein expressed in over 75 percent of axillary lymph node metastases.
The researchers subsequently developed their targeting agents by using monoclonal antibodies specific for binding CAIX and CAXII, both of which are known to promote tumor growth.
According to the researchers, a number of noninvasive optical imaging procedures for SLN evaluation have been investigated, but the approaches have lacked the ability to target tumor metastasis biomarkers.
"These methods provide only anatomic maps and do not detect tumor cells present in lymph nodes," explained Morse. "Using mouse models of breast cancer metastasis and a novel, monoclonal anti-body-based molecular imaging agents, we developed a targeted, noninvasive method to detect ALN metastasis using fluorescence imaging."
In addition to the imaging study with mice, the researchers also reported that the combination of CAIX and CAXII covered 100 percent of patient-donated samples used in their tissue microarray (TMA) study.
"The imaging probes detected tumor cells in ALNs with high sensitivity," explained Morse. "Either CAIX or CAXII were expressed in 100 percent of the breast cancer lymph node metasatsis samples we surveyed in this study. These imaging probes have potential for providing a noninvasive way to stage breast cancer in the clinic without unneeded and costly surgery."
Possible Receptor For Key Breast Cancer Regulator Identified By Researchers
A key protein potentially involved in regulating breast cancer progression has been identified by researchers at Clarkson University in Potsdam, N.Y. Led by professor Costel Darie, the team worked to identify the binding partner of Tumor Differentiating Factor (TDF), a pituitary hormone that had previously been shown to reduce cancer progression in breast cancer cells.
Earlier studies had shown that breast cancer cells treated with TDF lost their cancerous characteristics and began acting like normal mammary cells, suggesting that TDF had tumor-suppressing capabilities. However, how TDF acted remained unclear, leading Darie's group to initiate a search for a cellular receptor in cancer cells that might bind TDF and transmit its anti-tumorigenic cues.
Darie's group found that a receptor, labeled TDF-R, was found exclusively in breast, but not other cancer, cells, suggesting a level of specificity that agrees with previous reports of the efficacy of TDF. This result, which is being reported in a forthcoming issue of the Journal of Biological Chemistry, has substantial potential implications for developing new therapies for treating breast cancers known to be unresponsive to standard steroid hormone-based therapies, such as tamoxifen treatment.
Looking toward the next step, Darie asserted that "finding the receptor for the TDF hormone will allow us to rationally design drugs that will have a potent ability to stop cancer progression." He continued, "We will also be able to use TDF as a biomarker for breast cancer onset, thereby improving diagnoses."
Though cancer incidence and mortality rates have declined over the past 30 years, breast cancer remains a major killer: In 2007, breast cancer accounted for about 40,000 deaths in the U.S., while another 200,000 women were diagnosed, according to the Center for Disease Control.
Researchers Identify Changes In Tumor Cells That Lead To Metastasis
Researchers at the Centro de Gen0mica e Investigaci0n Oncologica (GENYO) - of which the University of Granada, Pfizer and the Andalusian Regional Government are members - have identified the genetic and phenotypic changes that cause tumor progression and metastasis. The process of metastasis - which is the main cause of cancer death - is caused by tumor cells invading distant organs with no direct anatomical relationship with the organ originally affected. For this to happen, it is necessary that these cells - which researchers call "circulating tumor cells" (CTCs) - , travel to these organs through blood.
The researchers detected CTCs undergoing cell division in a breast cancer patient on systemic treatment. Thus, CTCs have been demonstrated both to be able to adapt to hostile microenvironments as blood, and to resist treatment and divide and proliferate in other organs and tissues, causing metastasis. So far, this behavior had not been observed in this type of microenvironments.
The results of this study were described in the article "Biodynamics of Circulating Tumor Cell, Tumor Microenvironment and Metastasis", published in the journals Cancer Biology & Therapy, Clinical Translational Oncoly and Annals of Oncology. The researchers found that breast cancer patients with circulating tumor cells (CTCs) at baseline tend to develop metastasis and have shorter disease-free survival after treatment. Thus, detecting CTCs during and after treatment allows physicians to identify which patients are responding favorably to chemotherapy. Consequently, patients with CTCs while receiving chemotherapy have shorter disease-free survival and lower overall survival rates. This is due to the fact that these cells are resistant to conventional treatments performed according to the genetic characteristics of the tumor. Therefore, CTCs can survive chemotherapy and produce metastasis to other organs.
More Efficient Individualized Treatments
University of Granada professor José Antonio Lorente -GENYO manager director and coordinator of the research group- affirms that the study of Circulating Tumor Cells (CTCs) is crucial "not only because they may be responsible for the development of metastasis, but also because they have genetic characteristics different to those found in the primary tumor and in metastatic cells. Such characteristics make these very aggressive cells resistant to the immunologic system and to the therapeutic agents generally used in cancer patients". Most of these treatments are targeted against proliferating tumor cells. Conversely, CTCs are found in a "dormant" phase, i.e. in a "non-proliferation" phase.
As these cells may indicate negative response to treatment, if they were isolated and genetically characterized, patients could be classified according to their chances of relapse, which would allow individualized follow-up.
A Protein May Trigger Spread Of Breast Cancer
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Cancers rarely are deadly unless they evolve the ability to grow beyond the tissues in which they first arise. Normally, cells - even early-stage tumor cells - are tethered to scaffolding that helps to restrain any destructive tendencies. But scientists from the University of Helsinki, Finland, and from UCSF have identified a cleaver-wielding protein that frees some tumor cells, allowing them to further misbehave.
The protein, they discovered, often blankets the surface of breast tumor cells and can help untether the cells from the matrix of their native tissue. Once released, they may continue to expand their numbers into other tissues where their normal counterparts do not tread.
The protein, called hepsin, is a protease, a class of enzymes that cleaves, or cuts, other proteins. Proteases have been targeted successfully by drugs, and hepsin presents a new possible drug target, the researchers said.
"If we could delay or prevent a tumor from switching from one that grows in place to one that invades, then that would be a major milestone in cancer treatment," said study co-author Zena Werb, PhD, a professor of anatomy at UCSF. Werb has for decades studied the ways in which the behavior of tumor cells is influenced by their surroundings, with a focus on breast tumors.
Working with mouse models of breast development and breast cancer in Werb's UCSF laboratory during a visiting professorship, University of Helsinki scientist Juha Klefström, PhD - along with Johanna Partanen, a University of Helsinki graduate student - designed and led experiments that resulted in the discovery of the hepsin protein's role.
Their findings are published in the January 16, 2012 edition of the Proceedings of the American Academy of Sciences (PNAS).
The scientists studied mammary glands in mice and tissue fragments - called organoids - isolated from these glands.
They found that inactivation of a tumor suppressor gene known as liver kinase B1 (Lkb1) caused abnormal development of parts of the mammary gland, including milk-secreting structures. Specifically, they determined that a tightly knit matrix of protein fibers called the basement membrane - which normally surrounds the milk-secreting structures - was damaged and degraded.
These events may be triggered in many tumors, the team said, as they found that Lkb1 was abnormally missing in 1 out of every 4 human breast cancer samples they looked at.
Most solid tumors arise from "epithelial" cells, which line the surfaces and cavities of organs. The basement membrane, in turn, lines epithelial cell layers in tissues.
In their mouse studies, the researchers quickly settled on hepsin as a suspect in the destruction of the basement membrane that in turn allows tumor cells to become unbound. In the absence of Lkb1, the protein-cleaving enzyme was abnormally spread over the cell surface. They found that deactivating hepsin allowed the basement membrane to recover.
Graduate student Partanen sought to recapitulate the development of cancer by re-engineering the mice, knocking Lkb1 out of normal mammary epithelial cells. Again, hepsin spread abnormally and basement membrane proteins were sliced and diced. After a year, though, she found that the mice had not grown mammary tumors.
"I was disappointed with the results," she said. "However, then I realized that although broken basement membrane may give cells more freedom to proliferate, the cells may just lay there, resting, and not start to over-proliferate unless they are pushed into cycles of cell division."
Partanen then re-engineered the mice so that they also abnormally activated a gene called Myc, which, is known to help initiate tumors in many tissues, including breast epithelium. She soon saw the mice begin to form tumors.
"We found in our study that genetic removal of hepsin from the mammary gland organoids prevents formation of cancerous tissue," Klefström said. "This finding excites us, as it leads us to think that inhibition of hepsin by drug-like molecules could restrain cancer progression.
"However, we do not know yet if we can cure already-formed tumors by blocking hepsin activity. We need to first improve our experimental systems to properly address this question."
According to Web, "We have observed that loss of Lkb1, combined with activation of a weak inducer of breast cancer - an oncogene such as Myc - can produce aggressive cancers.
"In humans, breast cancers that have diminished amounts of Lkb1 show strong hepsin expression. Since hepsin sits on the cell membrane, it should be accessible to drugs. We believe that hepsin forms a novel target for treatment of a subset of breast cancer patients."
Cancers rarely are deadly unless they evolve the ability to grow beyond the tissues in which they first arise. Normally, cells - even early-stage tumor cells - are tethered to scaffolding that helps to restrain any destructive tendencies. But scientists from the University of Helsinki, Finland, and from UCSF have identified a cleaver-wielding protein that frees some tumor cells, allowing them to further misbehave.
The protein, they discovered, often blankets the surface of breast tumor cells and can help untether the cells from the matrix of their native tissue. Once released, they may continue to expand their numbers into other tissues where their normal counterparts do not tread.
The protein, called hepsin, is a protease, a class of enzymes that cleaves, or cuts, other proteins. Proteases have been targeted successfully by drugs, and hepsin presents a new possible drug target, the researchers said.
"If we could delay or prevent a tumor from switching from one that grows in place to one that invades, then that would be a major milestone in cancer treatment," said study co-author Zena Werb, PhD, a professor of anatomy at UCSF. Werb has for decades studied the ways in which the behavior of tumor cells is influenced by their surroundings, with a focus on breast tumors.
Working with mouse models of breast development and breast cancer in Werb's UCSF laboratory during a visiting professorship, University of Helsinki scientist Juha Klefström, PhD - along with Johanna Partanen, a University of Helsinki graduate student - designed and led experiments that resulted in the discovery of the hepsin protein's role.
Their findings are published in the January 16, 2012 edition of the Proceedings of the American Academy of Sciences (PNAS).
The scientists studied mammary glands in mice and tissue fragments - called organoids - isolated from these glands.
They found that inactivation of a tumor suppressor gene known as liver kinase B1 (Lkb1) caused abnormal development of parts of the mammary gland, including milk-secreting structures. Specifically, they determined that a tightly knit matrix of protein fibers called the basement membrane - which normally surrounds the milk-secreting structures - was damaged and degraded.
These events may be triggered in many tumors, the team said, as they found that Lkb1 was abnormally missing in 1 out of every 4 human breast cancer samples they looked at.
Most solid tumors arise from "epithelial" cells, which line the surfaces and cavities of organs. The basement membrane, in turn, lines epithelial cell layers in tissues.
In their mouse studies, the researchers quickly settled on hepsin as a suspect in the destruction of the basement membrane that in turn allows tumor cells to become unbound. In the absence of Lkb1, the protein-cleaving enzyme was abnormally spread over the cell surface. They found that deactivating hepsin allowed the basement membrane to recover.
Graduate student Partanen sought to recapitulate the development of cancer by re-engineering the mice, knocking Lkb1 out of normal mammary epithelial cells. Again, hepsin spread abnormally and basement membrane proteins were sliced and diced. After a year, though, she found that the mice had not grown mammary tumors.
"I was disappointed with the results," she said. "However, then I realized that although broken basement membrane may give cells more freedom to proliferate, the cells may just lay there, resting, and not start to over-proliferate unless they are pushed into cycles of cell division."
Partanen then re-engineered the mice so that they also abnormally activated a gene called Myc, which, is known to help initiate tumors in many tissues, including breast epithelium. She soon saw the mice begin to form tumors.
"We found in our study that genetic removal of hepsin from the mammary gland organoids prevents formation of cancerous tissue," Klefström said. "This finding excites us, as it leads us to think that inhibition of hepsin by drug-like molecules could restrain cancer progression.
"However, we do not know yet if we can cure already-formed tumors by blocking hepsin activity. We need to first improve our experimental systems to properly address this question."
According to Web, "We have observed that loss of Lkb1, combined with activation of a weak inducer of breast cancer - an oncogene such as Myc - can produce aggressive cancers.
"In humans, breast cancers that have diminished amounts of Lkb1 show strong hepsin expression. Since hepsin sits on the cell membrane, it should be accessible to drugs. We believe that hepsin forms a novel target for treatment of a subset of breast cancer patients."
In Breast Cancer, The Quality Of Life For Younger Patients More Adversely Affected Than For Older Women
Quality of life in younger patients treated for breast cancer is seriously compromised and these women suffer from severe psychological distress, infertility, premature menopause, a decrease in physical activity and weight gain, according to a study by researchers at UCLA's Jonsson Comprehensive Cancer Center.
The study, published in the peer-reviewed Journal of the National Cancer Institute, found that the mental issues faced by younger breast cancer survivors were more serious than the physical impacts compared to a general age-matched population of women who didn't have cancer and those more than 50 years old who did.
The study points to the need for oncologists to let these younger patients know from the beginning of their therapy what may happen to them after it's finished, said study lead author Dr. Patricia Ganz, director of cancer prevention and control research at UCLA's Jonsson Comprehensive Cancer Center.
"We know that educating and providing younger breast cancer patients with information about what they might experience once their treatment ends is very helpful," said Ganz, who has been conducting research on quality of life after cancer treatment for 25 years. "If they know what to expect, their anxiety level will be greatly reduced. Up to now, oncologists have not done a good job of preparing these women for what will come."
Reducing anxiety is crucial, Ganz said, as pre-clinical studies have shown that stress can promote cancer growth and spread in animal models. A study by Jonsson Cancer Center researchers published in 2010 in Cancer Research showed that chronic stress acted as a sort of fertilizer that fed breast cancer progression, significantly accelerating the spread of disease.
The need to prepare younger breast cancer survivors for any adverse effects they may experience and seek ways to address those problems is vital as more and more younger women are surviving their cancer diagnosis due to improvements in early detection and treatment, Ganz said.
"A cancer diagnosis can challenge younger women with issues that don't impact older patients," she said. "A younger breast cancer patient may have young children and may be worried about living to raise them to adulthood. A younger breast cancer patient may not have had children yet and may be faced with infertility following her treatment or may return to the dating scene following treatment. We need to find ways to reduce the stress and anxiety that dealing with these issues may create."
Ganz recently received a grant from the Centers for Disease Control and Prevention that will fund a leading-edge program that seeks to enhance outcomes for young breast cancer survivors in the Los Angeles region. The program is being done in collaboration with the Jonsson Cancer Center, the UCLA-LIVESTRONG Survivorship Center of Excellence and the Simms/Mann - UCLA Center for Integrative Oncology.
The three-year, $700,00 grant will focus on making life after breast cancer better for women aged 21 to 45 in Los Angeles County by funding a program designed to meet their unique needs, Ganz said. UCLA is one of seven organizations nationwide to receive funding for this focus on young breast cancer survivors. The resources and strategies developed in this diverse and populous region will serve as a model for other organizations across the country.
Services will be offered to these women through the UCLA Health System and with collaborators at Torrance Memorial Medical Center and the South Bay Cancer Survivorship Consortium, as well as the Olive View-UCLA Medical Center, a public hospital in northern Los Angeles County which treats mostly minority women who are underinsured or who have no insurance.
"These three health systems provide breast cancer services for a substantial number of ethnically diverse, newly-diagnosed women with breast cancer under 45 years old. They see about 225 new cases annually," Ganz said Ganz. "We estimate that there are hundreds of young breast cancer survivors who are being followed in these institutions, who will directly benefit from the programs that we will develop."
Ganz anticipates such services might include a regional resource with information and assistance in obtaining fertility preservation services, a website that hosts specialized information about community and hospital resources for younger women with breast cancer, as well as specialized programs to meet the unique psychosocial needs and concerns of this population.
Ganz also has received a grant from the Susan G. Komen foundation that is testing the practice of mindful awareness, a form of meditation, as a way to combat stress and anxiety in younger breast cancer patients.
For the Journal of the National Cancer Institute study, Ganz and her team did a review of studies that focused on overall quality of life, psychosocial effects, menopause and fertility-related concerns and behavioral outcomes related to weight gain and physical activity. The 28 studies reviewed were published between January 1990 and July 2010.
Ganz said that weighing therapies with the thought of quality of life after treatment in mind may help reduce some of the issues these younger women face.
"By tailoring adjuvant therapy regimens and giving cytotoxic therapy only to those who may benefit, we can mitigate some of these side effects, but the long life expectancy for these young women also provides a window of opportunity for cancer prevention and health promotion activities," the study states.
The Genome And The Timing Of Menopause
5 (1 votes)
An international team of researchers has discovered 13 new regions of the genome associated with the timing of menopause. These genes shed light on the biological pathways involved in reproductive lifespan and will provide insights into conditions connected to menopause, such as breast cancer and heart disease.
Menopause is a major hormonal change that affects most women when they are in their early 50s. The timing of menopause can have a huge impact on fertility, as well as influencing the risk of a range of common diseases such as breast cancer. It has been known for some time that genetic factors influenced the onset of menopause, however until recently very few genes had been identified.
In the new study, published in the journal Nature Genetics, Dr Anna Murray, University of Exeter, Peninsula College of Medicine and Dentistry (PCMD) Dr John Perry, PCMD and WTCHG, University of Oxford, and dozens of international collaborators, examined the genomes of over 50,000 women. They identified 13 novel gene regions associated with menopause onset, and confirmed four previously identified. Most of the 17 regions include genes related to DNA damage/repair or the immune system, whilst others are linked to hormonal regulation.
Dr Perry said: "The new findings highlight biological pathways not previously associated with reproductive lifespan, and may provide insights into the other conditions connected with menopause age, such as cardiovascular disease and breast cancer."
The association with breast cancer is related to the length of time a woman menstruates in total and is thought to be related to oestrogen exposure over a lifetime - in fact earlier menopause is protective for breast cancer. Cardiovascular risk is increased in post-menopausal women compared to pre-menopausal and reduced oestrogen is thought to be a key component of this increased risk. Genetic studies will be beneficial in working out exactly what the relationships are between these conditions.
Dr. Murray added: "Menopause is a process most women go through, yet we know very little about what governs the timing of this key event in a woman's life. By finding out which genes control the timing of menopause we hope to be able understand why this happens very early to some women, reducing their chances of having children naturally."
The authors said they expected further research will identify additional genes, and also assess the impact of these genetic regions on related reproductive disorders. The research team are currently investigating women who had very early menopause, before 45 years, to determine whether the new menopause genes play a role in this clinically important condition which affects over five per cent of women.
Besides Dr Murray and Dr Perry, senior authors on the study include Professor Kathryn Lunetta and Dr Joanne Murabito at the Boston University schools of Public Health and Medicine, and Jenny A. Visser, a scientist at Erasmus Medical Center in Rotterdam (Netherlands).
An international team of researchers has discovered 13 new regions of the genome associated with the timing of menopause. These genes shed light on the biological pathways involved in reproductive lifespan and will provide insights into conditions connected to menopause, such as breast cancer and heart disease.
Menopause is a major hormonal change that affects most women when they are in their early 50s. The timing of menopause can have a huge impact on fertility, as well as influencing the risk of a range of common diseases such as breast cancer. It has been known for some time that genetic factors influenced the onset of menopause, however until recently very few genes had been identified.
In the new study, published in the journal Nature Genetics, Dr Anna Murray, University of Exeter, Peninsula College of Medicine and Dentistry (PCMD) Dr John Perry, PCMD and WTCHG, University of Oxford, and dozens of international collaborators, examined the genomes of over 50,000 women. They identified 13 novel gene regions associated with menopause onset, and confirmed four previously identified. Most of the 17 regions include genes related to DNA damage/repair or the immune system, whilst others are linked to hormonal regulation.
Dr Perry said: "The new findings highlight biological pathways not previously associated with reproductive lifespan, and may provide insights into the other conditions connected with menopause age, such as cardiovascular disease and breast cancer."
The association with breast cancer is related to the length of time a woman menstruates in total and is thought to be related to oestrogen exposure over a lifetime - in fact earlier menopause is protective for breast cancer. Cardiovascular risk is increased in post-menopausal women compared to pre-menopausal and reduced oestrogen is thought to be a key component of this increased risk. Genetic studies will be beneficial in working out exactly what the relationships are between these conditions.
Dr. Murray added: "Menopause is a process most women go through, yet we know very little about what governs the timing of this key event in a woman's life. By finding out which genes control the timing of menopause we hope to be able understand why this happens very early to some women, reducing their chances of having children naturally."
The authors said they expected further research will identify additional genes, and also assess the impact of these genetic regions on related reproductive disorders. The research team are currently investigating women who had very early menopause, before 45 years, to determine whether the new menopause genes play a role in this clinically important condition which affects over five per cent of women.
Besides Dr Murray and Dr Perry, senior authors on the study include Professor Kathryn Lunetta and Dr Joanne Murabito at the Boston University schools of Public Health and Medicine, and Jenny A. Visser, a scientist at Erasmus Medical Center in Rotterdam (Netherlands).
Breast Cancers And Leukemias Slowed By A Single Therapy
Targeting a single protein can help fight both breast cancers and leukemias, according to two reports published online in the Journal of Experimental Medicine.
The single protein is HSP90, which acts as a chaperone to protect other proteins in the cell.
A team led by Ute Moll at the University of Göttingen in Germany found that blocking HSP90 activity rendered normally protected proteins vulnerable to attack and destruction. One of these proteins - called migration inhibitory factor - drives the growth of breast tumors. HSP90 inhibitors slowed the growth of MIF-expressing breast tumors in mice but had little effect on tumors lacking MIF.
HSP90 inhibitors also look promising for certain forms of leukemia, according to a study by David Weinstock and coworkers at the Dana-Farber Cancer Institute. They showed that HSP90 inhibitors slowed the growth of leukemias driven by hyperactive versions of the enzyme JAK2, many of which become resistant to JAK2-blocking drugs. The HSP90 inhibitors delayed the growth of resistant leukemia cells in mice.
Together these studies suggest that HSP90 may represent a therapeutic target in many cancers.
Musculoskeletal Side Effects From Breast Cancer Treatment Are Not Long Term
4 (1 votes)
Around 75% of the 48,000 women annually diagnosed with breast cancer in the UK suffer from an estrogen receptor positive tumor, which implies the involvement of the hormone estrogen in cancer growth. Tamoxifen and exemestane are both hormone treatments, and whilst tamoxifen blocks the tumor's ability to use estrogen, aromatase inhibitors, such as exemestane reduce the body's production of estrogen.
Findings in The Lancet Oncology now reveal that a drug therapy that reduces the risk of women dying from breast cancer exposes these women to a higher risk of developing carpal tunnel syndrome, however, this can be managed and does not persist once treatment has finished.
Women with early stage estrogen receptor-positive (ER
Around 75% of the 48,000 women annually diagnosed with breast cancer in the UK suffer from an estrogen receptor positive tumor, which implies the involvement of the hormone estrogen in cancer growth. Tamoxifen and exemestane are both hormone treatments, and whilst tamoxifen blocks the tumor's ability to use estrogen, aromatase inhibitors, such as exemestane reduce the body's production of estrogen.
Findings in The Lancet Oncology now reveal that a drug therapy that reduces the risk of women dying from breast cancer exposes these women to a higher risk of developing carpal tunnel syndrome, however, this can be managed and does not persist once treatment has finished.
Women with early stage estrogen receptor-positive (ER
Discovery Of Rotational Motion Of Cells That Plays A Critical Role In Their Normal Development Has Major Implications For Breast Cancer Research
5 (1 votes)
In a study that holds major implications for breast cancer research as well as basic cell biology, scientists with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have discovered a rotational motion that plays a critical role in the ability of breast cells to form the spherical structures in the mammary gland known as acini. This rotation, which the researchers call "CAMo," for coherent angular motion, is necessary for the cells to form spheres. Without CAMo, the cells do not form spheres, which can lead to random motion, loss of structure and malignancy.
"What is most exciting to me about this stunning discovery is that it may finally give us a handle by which to discover the physical laws of cellular motion as they apply to biology," says Mina Bissell, a leading authority on breast cancer and Distinguished Scientist with Berkeley Lab's Life Sciences Division.
Bissell is a corresponding author of a paper describing this work in the Proceedings of the National Academy of Sciences (PNAS), along with Kandice Tanner, a post-doctoral physicist in Bissell's research group. The PNAS paper is titled "Coherent angular motion in the establishment of multicellular architecture of glandular tissues." Other authors were Hidetoshi Mori, Rana Mroue and Alexandre Bruni-Cardoso, also members of Bissell's research group.
Healthy human epithelial cells in breast and other glandular tissue form either sphere-shaped acini or tube-shaped ducts. The cell and tissue polarity (function-enabling spatial orientations of cellular and tissue structures) that comes with the formation of acini is essential for the health and well-being of the breast. Loss of this polarity as a result of cells not forming spheres is one of the earliest signs of malignancy. However, despite all that is known about cell morphogenesis, the fundamental question as to how epithelial cells are able to assemble into spheres that are similar in size and shape to organs in vivo has until now been a mystery.
"We've discovered a novel type of cell motility where single cells undergo multiple rotations and cohesively maintain that rotational motion as they divide and assemble into acini," says Tanner. "We've also demonstrated that this CAMo is a critical function for the establishment of spherical architecture and not simply a consequence of multicellular aggregates. If CAMo is disrupted, the final geometry is not a sphere."
Working with both immortalized and primary human epithelial cells, cultured in a unique 3D gel that serves as a surrogate for the basement membrane (an assay developed by Bissell and colleagues two decades ago), and using 4D live-imaging (3D plus time) confocal microscopy, Tanner, Bissell and their colleagues found that CAMo arises from a centripetal force generated by the flexing of crescent-shaped muscle-like molecules called actomyosin in the cell's cytoskeleton. This centripetal force sets the cell to rotating about an axis. The rotation is slow, barely once an hour, it may run clockwise or counterclockwise, and its axis might shift, but this rotational motion is cohesive. It continues as the cell divides and the subsequent progeny form into acini, bestowing on cells and acini the polarity and the cavity needed for proper form and function.
"Without CAMo, the cells lose their way and do not form structures that allow mammary cells to make and secrete milk," says Tanner. "In order to form a polarized sphere, the cells have to be properly oriented so that certain components are up and certain components are down. The CAMo rotation provides the cells with this orientation."
Bissell is renowned for her pioneering work that elucidated the critical role in breast cancer development played by the extracellular matrix (ECM), a network of fibrous and globular proteins in the microenvironment that surrounds a breast cell. Her experiments have shown that when the nucleus of a breast cell fails to receive the proper biochemical cues and signals from the ECM and other components of the microenvironment, cells and tissue lose structure, which opens the door to malignancy. The discovery of CAMo now provides an important missing mechanism that facilitates the reception and response of a breast cell to the cues and signals from the ECM.
"In addition to wanting to know how a single cell and its progeny assemble into polar tissue, we also wanted to know whether cellular dynamics are corrupted by malignant transformation," Bissell says. "In this study, we found that malignant cells do not display CAMo but instead become randomly motile and do not form spheres."
In recent research, Bissell and her group demonstrated that through manipulation of the ECM, malignant cells cultured in an ECM enriched with laminin - a protein that they had shown induces cell quiescence - can undergo a reversion in which their normal phenotype is restored despite their malignant genome. In this new study, Tanner, Bissell and their colleagues found that when malignant cells cultured in the 3D ECM surrogate gel underwent phenotypic reversion in response to signaling inhibitors, CAMo was restored. When CAMo was restored, the reverted cancer cells formed polarized spheres.
"These results complement our early hypothesis that signaling and support by the ECM when cells are in proper context informs both form and function in cells," Bissell says. "The results also suggest that in response to microenvironmental cues from the ECM, cells execute a program of cytoskeletal movements that dictate different kinds of motilities. We hypothesize that these motilities direct the formation of a given type of tissue and preclude other multicellular geometries. We believe this is a crucial evolutionary phenomena for multicellular organisms."
In this new study, Tanner and Bissell and their colleagues were surprised to observe a significant delay between the second and third round of breast cell divisions in the 3D ECM surrogate gel. This mitotic delay is similar to the mitotic delay that's been observed during human blastocyst formation and is critical for normal embryogenesis. Tanner says the delay is probably necessary for the progeny to acquire sufficient adhesion so that the CAMo can be maintained for the adhere cells. This finding may provide a possible explanation for how the mammary gland reorganizes after each pregnancy and involution.
"Once the cells are sufficiently adhered to one another, they can continue CAMo as a cohesive unit," Tanner says. "We postulate that this cohesive CAMo motility is the mechanism by which the original structure of the breast tissue is restored following lactation and breast feeding."
The next step for the research team will be to study the effects of CAMo from the perspective of the ECM.
"We would like to look at the interaction of the ECM with a single cell as it undergoes CAMo and show the in vivo relevance," Tanner says.
In a study that holds major implications for breast cancer research as well as basic cell biology, scientists with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have discovered a rotational motion that plays a critical role in the ability of breast cells to form the spherical structures in the mammary gland known as acini. This rotation, which the researchers call "CAMo," for coherent angular motion, is necessary for the cells to form spheres. Without CAMo, the cells do not form spheres, which can lead to random motion, loss of structure and malignancy.
"What is most exciting to me about this stunning discovery is that it may finally give us a handle by which to discover the physical laws of cellular motion as they apply to biology," says Mina Bissell, a leading authority on breast cancer and Distinguished Scientist with Berkeley Lab's Life Sciences Division.
Bissell is a corresponding author of a paper describing this work in the Proceedings of the National Academy of Sciences (PNAS), along with Kandice Tanner, a post-doctoral physicist in Bissell's research group. The PNAS paper is titled "Coherent angular motion in the establishment of multicellular architecture of glandular tissues." Other authors were Hidetoshi Mori, Rana Mroue and Alexandre Bruni-Cardoso, also members of Bissell's research group.
Healthy human epithelial cells in breast and other glandular tissue form either sphere-shaped acini or tube-shaped ducts. The cell and tissue polarity (function-enabling spatial orientations of cellular and tissue structures) that comes with the formation of acini is essential for the health and well-being of the breast. Loss of this polarity as a result of cells not forming spheres is one of the earliest signs of malignancy. However, despite all that is known about cell morphogenesis, the fundamental question as to how epithelial cells are able to assemble into spheres that are similar in size and shape to organs in vivo has until now been a mystery.
"We've discovered a novel type of cell motility where single cells undergo multiple rotations and cohesively maintain that rotational motion as they divide and assemble into acini," says Tanner. "We've also demonstrated that this CAMo is a critical function for the establishment of spherical architecture and not simply a consequence of multicellular aggregates. If CAMo is disrupted, the final geometry is not a sphere."
Working with both immortalized and primary human epithelial cells, cultured in a unique 3D gel that serves as a surrogate for the basement membrane (an assay developed by Bissell and colleagues two decades ago), and using 4D live-imaging (3D plus time) confocal microscopy, Tanner, Bissell and their colleagues found that CAMo arises from a centripetal force generated by the flexing of crescent-shaped muscle-like molecules called actomyosin in the cell's cytoskeleton. This centripetal force sets the cell to rotating about an axis. The rotation is slow, barely once an hour, it may run clockwise or counterclockwise, and its axis might shift, but this rotational motion is cohesive. It continues as the cell divides and the subsequent progeny form into acini, bestowing on cells and acini the polarity and the cavity needed for proper form and function.
"Without CAMo, the cells lose their way and do not form structures that allow mammary cells to make and secrete milk," says Tanner. "In order to form a polarized sphere, the cells have to be properly oriented so that certain components are up and certain components are down. The CAMo rotation provides the cells with this orientation."
Bissell is renowned for her pioneering work that elucidated the critical role in breast cancer development played by the extracellular matrix (ECM), a network of fibrous and globular proteins in the microenvironment that surrounds a breast cell. Her experiments have shown that when the nucleus of a breast cell fails to receive the proper biochemical cues and signals from the ECM and other components of the microenvironment, cells and tissue lose structure, which opens the door to malignancy. The discovery of CAMo now provides an important missing mechanism that facilitates the reception and response of a breast cell to the cues and signals from the ECM.
"In addition to wanting to know how a single cell and its progeny assemble into polar tissue, we also wanted to know whether cellular dynamics are corrupted by malignant transformation," Bissell says. "In this study, we found that malignant cells do not display CAMo but instead become randomly motile and do not form spheres."
In recent research, Bissell and her group demonstrated that through manipulation of the ECM, malignant cells cultured in an ECM enriched with laminin - a protein that they had shown induces cell quiescence - can undergo a reversion in which their normal phenotype is restored despite their malignant genome. In this new study, Tanner, Bissell and their colleagues found that when malignant cells cultured in the 3D ECM surrogate gel underwent phenotypic reversion in response to signaling inhibitors, CAMo was restored. When CAMo was restored, the reverted cancer cells formed polarized spheres.
"These results complement our early hypothesis that signaling and support by the ECM when cells are in proper context informs both form and function in cells," Bissell says. "The results also suggest that in response to microenvironmental cues from the ECM, cells execute a program of cytoskeletal movements that dictate different kinds of motilities. We hypothesize that these motilities direct the formation of a given type of tissue and preclude other multicellular geometries. We believe this is a crucial evolutionary phenomena for multicellular organisms."
In this new study, Tanner and Bissell and their colleagues were surprised to observe a significant delay between the second and third round of breast cell divisions in the 3D ECM surrogate gel. This mitotic delay is similar to the mitotic delay that's been observed during human blastocyst formation and is critical for normal embryogenesis. Tanner says the delay is probably necessary for the progeny to acquire sufficient adhesion so that the CAMo can be maintained for the adhere cells. This finding may provide a possible explanation for how the mammary gland reorganizes after each pregnancy and involution.
"Once the cells are sufficiently adhered to one another, they can continue CAMo as a cohesive unit," Tanner says. "We postulate that this cohesive CAMo motility is the mechanism by which the original structure of the breast tissue is restored following lactation and breast feeding."
The next step for the research team will be to study the effects of CAMo from the perspective of the ECM.
"We would like to look at the interaction of the ECM with a single cell as it undergoes CAMo and show the in vivo relevance," Tanner says.
Breast Cancer Surgery Often Repeated To Take Out More Tissue
22.9% of breast cancer patients who undergo partial mastectomies need further operations to remove more tissue, researchers reported in JAMA (Journal of the American Medical Association). The authors, from Michigan State University, added that rates of reexcision vary considerably between surgeons and clinics/hospitals; this variation does not appear to be caused by patients' clinical characteristics.
"Excision" means the surgical removal of something, which in this text means a tumor. "Reexcision" means additional surgery in the same area.
Current health care reforms that are taking place in the USA call for more doctor and hospital transparency and accountability of patient outcomes.
The authors wrote:
"Breast-conserving therapy, or partial mastectomy, is one of the most commonly performed cancer operations in the United States. Currently, there are no readily identifiable quality measures that allow for meaningful comparisons of breast cancer surgical outcomes among treating surgeons and hospitals."
A surgeon's aim when performing a mastectomy is to achieve adequate surgical margins - there should be a rim of normal tissue around the excised tumor so that there is no cancerous tissue left behind. Additionally, the cosmetic appearance of the breast should be maintained as much as possible.
If clear margins are not achieved after the initial surgery, further surgical intervention will be required. Additional operations cause significant physical, emotional, mental and economic stress for patients, and also delay vital supplemental therapies.
The authors wrote:
"Thus, the effect of reexcision on altering a patient's initial treatment of choice is significant."
Laurence E. McCahill, M.D., and team set out to measure what the reexcision rates are across surgeons and hospitals in the USA that treat patients with comparable clinical conditions. They specifically looked at female patients with invasive breast cancer who underwent partial mastectomy across 4 institutions and 3 large health plans. They gathered data from various sources, including electronic medical records, outpatient records, and pathology archives.
Out of 2,206 women in their study, 2,220 had been recently diagnosed with invasive breast cancer and had breast-conserving surgery performed on them. Their average age was 62 years. 92.8% of them were non-Hispanic white.
Below are some highlighted findings from this study:22.9% (509) had additional surgery on the affected breast89.2% of those who had additional surgery underwent a single reexcision9.4% (48) of the additional surgery patients underwent 2 reexcisions1.4% (7) underwent 3 reexcisions8.5% (190) of them had a total mastectomyThe researchers wrote:
"Reexcision rates for margin status following initial surgery were 85.9 percent for initial positive margins
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