Understanding of complex diseases likely to improve following the unexpected discovery of the ways Cells Move

Main category: Cancer / Oncology
Also included in: respiratory / asthma;??Biology / biochemistry
Article Date: June 25, 2013 - 1:00 PDT current ratings for:
Understanding of complex diseases likely to improve following the unexpected discovery of the ways Cells Move

A new discovery about how cells move within the organization can provide scientists with crucial information about the mechanisms of diseases such as the spreading of the cancer or constriction of the Airways caused by asthma. Led by researchers from the Harvard School of Public Health (HSPH) and the Institute for bioengineering of Catalonia (IBEC), investigators found that the epithelial cells - the type that form a barrier between the inside and the outside of the body, such as skin cells - move group, powered by forces both of in and from neighbouring cells - to fill the empty spaces that they encounter.

The study appears in Nature Materials advanced online edition.

"We have tried to understand the fundamental relationship between cellular movements collective and collective forces of cell phones, which may occur during the invasion of the cancer cells, for example. But, in so doing, we are fallen on a phenomenon that was totally unexpected, "said lead author Jeffrey Fredberg, Professor of Bioengineering and physiology to the investigator HSPH Department of Environmental Health and co-Minister of HSPH molecular laboratory and integrative cellular dynamics.

Biologists, engineers and physicists at HSPH and IBEC worked together to shed light on the collective cell movement because it plays a key role in functions such as the healing of wounds, organ development and tumor growth. Using a technique called stress monolayer microscopy--which they invented themselves - they have measured the forces affecting a single layer of epithelial cells in motion. They examined cells speed and direction as traction - how certain cells either pull or push themselves and thus force the collective movement.

As they expected, the researchers found that when an obstacle was placed in the path of a layer of advanced cell - in this case, a gel that provided no traction - cells settled around him, closely hugging the sides of the gel as they passed. However, the researchers also found something amazing - cells, in addition to moving forward, continued to collectively back to frost, as if the desire to fill the space empty. Researchers have dubbed this movement "kenotaxis", Greek words "keno" (empty) and "taxi" (arrangement), because it seemed that cells are trying to fill a void.

This new discovery could help researchers to better understand the behaviour of the cell - and evaluate the potential influence that behavior - in a variety of complex diseases, such as cancer, asthma, cardiovascular diseases, developmental anomalies and glaucoma. The findings could also help with regenerative medicine and tissue engineering, which rely on cell migration.

In carcinomas, for example - who represent 90% of all cancers and involve epithelial cells - new information on cell movement could improve understanding of how cancer cells migrate through the body. Research on asthma could also get a boost, because scientists believe the migration of epithelial cells damaged in the lungs are involved in narrowing of the Airways caused by the disease.

"Kenotaxis is a property of the cell collective, not the individual cell," said Jae Hun Kim, first author of the study. "It was amazing to us that the collective cell can organize itself draw systematically in one direction while moving consistently in a quite different direction. ''

Article adapted by Medical News Today press release original. Click on "references" tab above for the source.
Visit our cancer / Oncology section for the latest news on this subject. Other authors HSPH included James Butler, senior lecturer on physiology in the Department of health environmental and investigator co-Minister of the laboratory; and researchers Dhananjay Tambe, Enhua Zhou Chan Young Park, Monirosadat Sadati, Park Jin-Ah, Bomi Gweon and Emil Millet.

Support for the study came from the Spanish Ministry of Science and Innovation (BFU2012-38146 FPU fellowship XS) and the Swiss National Science Foundation (PBEZP2-140047), the National Research Foundation of Korea (2012R1A6A3A03040450), the European Research Council (Grant Agreement 242993) Parker B. Francis (RK Fellowship), American Heart Association (13SDG14320004) and the National Institutes of Health (R01HL102373, R01HL107561).

"Propulsion and navigation within the advanced single layer sheet," Jae Hun Kim, Xavier Serra-Picamal, Dhananjay T. Tambe, Enhua H. Zhou, Chan Young Park, Monirosadat Sadati, Park Jin-Ah, Krishnan Ramaswamy, Bomi Gweon, Emil Millet, James P. Butler, Xavier Trepat, Jeffrey J. Fredberg, Nature of materials, online, June 23, 2013

Harvard School of Public Health

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Study Finds Bladder Cancer Recurrence And Mortality Could Improve With Better Treatment Compliance

Main Category: Cancer / Oncology
Also Included In: Urology / Nephrology;??Compliance
Article Date: 05 Jun 2013 - 0:00 PDT Current ratings for:
Study Finds Bladder Cancer Recurrence And Mortality Could Improve With Better Treatment Compliance

Researchers at UCLA's Jonsson Comprehensive Cancer Center led by Dr. Karim Chamie, assistant professor-in-residence in the department of urology, have found that the burden of bladder cancer on the population is very high, and that more intense surveillance and treatment in the first two years after diagnosis could reduce the number of patients whose cancer returns after treatment and lower the death rate from this disease. The study was published online ahead of press today in the journal Cancer.

Based on their previous research showing underutilization of care for patients with bladder cancer, this is the first study to examine the natural history of the disease from a population standpoint. To date no one has examined the morbidity of recurrence of disease in the US. Chamie and colleagues found that nearly three quarters of patients with high-grade, non-muscle-invasive bladder cancer will suffer return of the disease (recurrence) within 10 years. Thirty-three percent of patients will have their cancers progress to a more advanced form requiring removal of their bladder, radiation therapy, or systemic chemotherapy. An additional 41% will recur without further spread of the disease (progression).

"Even though 80% of bladder cancer patients don't die of their disease within 5 years, most patients will either die of other causes or bladder cancer, require aggressive treatment (removal of the bladder, radiation, and/or chemotherapy), or have recurrence of their disease. What this study hopes to do is highlight the need to comply with treatment guidelines--prevent recurrences by instilling anticancer agents inside the bladder (intravesical) and follow patients more closely within the first two years of diagnosis," said Chamie.

The study was based on a nationwide sample of Medicare Beneficiaries who had high-grade, non-muscle-invasive bladder cancer. "We have level-one evidence that demonstrates that a single instillation of chemotherapy into the bladder can minimize recurrences, and that six instillations can minimize recurrence and progression," Chamie stated further, "Efforts should be increased to offer patients intravesical therapy with the goal of minimizing the burden of this disease."

The researchers also found that the elderly, women, and African-American patients had higher likelihood of dying of bladder cancer than younger patients, men, and whites, respectively.

This study was supported by the American Cancer Society, Ruth L. Kirschstein National Research Service Award Extramural, Jonsson Comprehensive Cancer Center, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases.

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'Study Finds Bladder Cancer Recurrence And Mortality Could Improve With Better Treatment Compliance'

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Additional Lymph Node Removal May Not Improve Survival in Breast Cancer Patients with Small Amounts of Cancer in Sentinel Node

Among women with early-stage breast cancer and small amounts of cancer (micrometastases) in the sentinel lymph node, removal of additional lymph nodes (completion axillary lymph node dissection) does not appear to improve overall survival. The results of this study were presented at the 2010 annual meeting of the American Society of Clinical Oncology.

For women with early breast cancer, determining whether the cancer has spread to the axillary (under the arm) lymph nodes is an important part of cancer staging. Evaluation of the axillary nodes may involve either an axillary lymph node dissection (ALND), in which many lymph nodes are surgically removed and evaluated or a less extensive procedure known as a sentinel lymph node biopsy.

The sentinel nodes are the first lymph nodes to which cancer is likely to spread. If the sentinel nodes are free of cancer, no further lymph node evaluation is performed. If the sentinel nodes contain cancer, however, most women then undergo ALND to remove additional nodes. This additional lymph node surgery has been shown to help control cancer locally, but the effect on survival has been controversial. Establishing the benefits of completion ALND is important because it can cause significant side effects such as pain, discomfort, and swelling (lymphedema).

To evaluate the effects of ALND in breast cancer patients with micrometastases in the sentinel node, researchers conducted a Phase III study among 991 women. Half the women underwent completion ALND, and half did not.

Five-year overall survival was 91.9% among women who underwent ALND and 92.5% among women who did not undergo ALND.Disease-free survival was 82.2% among women who underwent ALND and 83.8% among women who did not undergo ALND.The rate of local/regional recurrence (recurrence in or near the breast) was 4.3% among women who underwent ALND and 3.4% among women who did not undergo ALND.

In a prepared statement, the lead author of the study explained, “Our findings suggest that there may not be a benefit to removing more lymph nodes than the sentinel node only, and that women can avoid the risk of additional side effects that come with more extensive lymph node removal. Axillary lymph node dissection will still be needed in some cases, but these findings show it may be necessary for far fewer women.”

Reference: Giuliano AE, McCall LM, Beitsch PD et al. ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract CRA 506.

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Avastin May Improve Breast Cancer Response Rates

Among women with HER2-negative breast cancer that has not spread to distant sites in the body, the addition of Avastin to neoadjuvant (before-surgery) chemotherapy may increase the likelihood of a complete response to treatment (a disappearance of detectable cancer). These results were published in the New England Journal of Medicine.

Avastin is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin is used in the treatment of several types of cancer, but its approval for breast cancer was revoked by the US Food and Drug Administration (FDA) in November, 2011.??

Avastin was originally for breast cancer in 2008 under the FDA’s accelerated approval program. The accelerated approval program provides earlier access to promising drugs for life-threatening health conditions while confirmatory studies are conducted. The approval was for use of Avastin in combination with chemotherapy for women with metastatic, HER2-negative breast cancer. The approval was based on the finding that Avastin delayed the progression (worsening) of metastatic breast cancer. There was no evidence that Avastin improved overall survival.??

After 2008, additional studies were reported to the FDA. These studies found that Avastin had only a small effect on rate of cancer progression and no effect on overall survival. The FDA concluded that the potential benefits of Avastin for breast cancer did not outweigh the risks, and revoked Avastin’s approval for breast cancer. Risks of Avastin include severe high blood pressure; bleeding problems; the development of perforations (holes) in the nose, stomach, and intestines; and heart attack or heart failure. It remains possible that Avastin will be found to benefit specific subgroups of breast cancer patients, and the FDA noted that it is open to considering data from additional studies that address this question.???

Results from Avastin clinical trials continue to be reported. Two of these were published in the New England Journal of Medicine and address the use of Avastin in women with earlier-stage (nonmetastatic), HER2-negative breast cancer.?

The first study—the Phase III GeparQuinto trial—enrolled 1,948 women with nonmetastatic, HER2-negative breast cancer.[1] Study participants received neoadjuvant treatment with chemotherapy alone or in combination with Avastin. The primary outcome of interest was a complete response, which was defined in this study as no detectable cancer in the breast or axillary (under-the-arm) lymph nodes.????

A complete response to treatment occurred in 14.9 percent of women treated with chemotherapy alone and 18.4 percent of women treated with chemotherapy plus Avastin.?The greatest benefit of Avastin was observed among women with triple-negative breast cancer (breast cancer that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative). Among these women, the complete response rates were 27.9 percent with chemotherapy alone and 39.3 percent with chemotherapy plus Avastin.?Serious side effects that were more common in the Avastin group included febrile neutropenia (low white-blood cell counts accompanied by fever), mouth sores, hand-foot syndrome, infection, and high blood pressure.?

The second study—the Phase III NSABP B-40 trial—involved 1,206 women with nonmetastatic, HER2-negative breast cancer.[2] Once again, study participants received neoadjuvant treatment with chemotherapy alone or in combination with Avastin. In this study, a complete response was defined as no detectable cancer in the breast; this is a less stringent definition than was used by the GeparQuinto study, which required no detectable cancer in the breast or axillary lymph nodes.????

A complete response to treatment occurred in 28.2 percent of women treated with chemotherapy alone and 34.5 percent of women treated with chemotherapy plus Avastin.?When a more stringent definition of complete response was used (similar to what was used in the GeparQuinto study), the difference between study groups was not statistically significant, suggesting that it could have occurred by chance alone.?The greatest benefit of Avastin was observed among women with estrogen receptor-positive cancer. This differs from what was found in the GeparQuinto study.?Side effects that were more common in the Avastin group included high blood pressure, heart problems, hand-foot syndrome, and mouth sores.?

These results suggest that the addition of Avastin to neoadjuvant chemotherapy may increase the likelihood of a complete response among women with nonmetastatic, HER2-negative breast cancer. Whether this will ultimately translate into improved survival, however, remains uncertain. Overall survival results are not yet available from these studies. The question of whether certain subgroups of patients are more likely to benefit from Avastin than others also remains unanswered, but research is ongoing. Outside of a clinical trial, Avastin should not be used in the preoperative setting; neither of these studies is practice-changing at this time.?

Posted January 30, 2012?

References:?
?[1] von Minckwitz G, Eidtmann H, Rezai M et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. New England Journal of Medicine. 2012;366:299-309.?

?[2] Bear HD, Tang G, Rastogi P et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. New England Journal of Medicine. 2012;366:310-20.?

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Social Support May Improve Breast Cancer Outcomes

Social well-being during the first year after a breast cancer diagnosis may have a beneficial effect on cancer outcomes. These results were published in the Journal of Clinical Oncology.

A diagnosis of breast cancer often affects a woman’s quality of life, but it’s been less clear whether quality of life affects breast cancer outcomes. Quality of life has physical, psychological, social, and material aspects, and any one these (or a combination) may affect health.?

To explore the relationship between post-diagnosis quality of life and breast cancer outcomes, researchers evaluated information from the Shanghai Breast Cancer Study. The study enrolled more than 2,000 women. Information about quality of life was collected six and 36 months after diagnosis.

Women were followed for close to five years after their initial quality-of-life assessment.???

Social well-being at six months after diagnosis was linked with both survival and risk of recurrence. Women with the highest level of social well-being had a 38% reduction in risk of death and a 48% reduction in risk of recurrence. The aspects of social well-being that appeared to provide the most benefit were marriage and family, social support, and interpersonal relationships.The other measures of quality of life (physical, psychological, and material) at six months after diagnosis did not significantly cancer outcomes, although there was a suggestion that psychological well-being may be important.By 36 months after diagnosis, none of the quality of life measures were strongly linked with cancer outcomes.

The researchers conclude “Social well-being in the first year after cancer diagnosis is a significant prognostic factor for breast cancer recurrence or mortality, suggesting a possible avenue of intervention by maintaining or enhancing social support for women soon after their breast cancer diagnosis to improve disease outcomes.”

Reference: Epplein M, Zheng Y, Zheng W et al. Quality of life after breast cancer diagnosis and survival. Journal of Clinical Oncology. Early online publication December 20, 2010.

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Ovarian Suppression During Chemotherapy Fails to Improve Post-Treatment Menstrual Function

Among young women undergoing chemotherapy for breast cancer, use of the drug triptorelin to suppress ovarian function during treatment does not appear to improve post-treatment menstrual function. These results were published in the Journal of Clinical Oncology.???

Fertility preservation is increasingly being recognized as an important issue for young people with cancer. In premenopausal women, many chemotherapy drugs are toxic to the egg cells (oocytes) in the ovaries. If the number of remaining oocytes in the ovaries reaches a critically low point during treatment, women experience “acute ovarian failure.” This means that the ovaries stop functioning during or shortly after cancer treatment. If oocytes are lost during treatment but do not reach this critically low point, women are at risk for early menopause but may still be able to get pregnant for some time after treatment.????

Freezing embryos prior to cancer treatment is one of the most well established approaches to fertility preservation in young women, but is not always an option. One of the alternative approaches being evaluated involves the use of drugs known as gonadotropin-releasing hormone (GnRH) agonists to suppress ovarian function during chemotherapy. The hope is that this will protect the ovaries and improve post-treatment ovarian function.????

To explore the effects of the GnRH agonist triptorelin during chemotherapy for breast cancer, researchers conducted a study among premenopausal women age 44 or younger. Study participants were assigned to receive either triptorelin or a placebo. The study was originally designed to enroll 124 women, but it was stopped after only 49 women were enrolled because preliminary results indicated no benefit from triptorelin.????

Menstruation resumed in 88 percent of women in the triptorelin group and 90 percent of women in the placebo group.?Menstrual cycles resumed after a median of 5.8 months in the triptorelin group and 5.0 months in the placebo group.?

These results suggest that triptorelin does not improve post-treatment menstrual function in young breast cancer patients. Other, ongoing studies will provide more information on this topic.? ?

Premenopausal women who are interested in preserving their fertility during cancer treatment are advised to discuss their options with their physician before treatment begins.?????

Reference: Munster PN, Moore AP, Ismail-Khan R et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. Early online publication January 9, 2012.?

Posted January 13, 2012?

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