Elderly may be more likely to die if they have subclinical hyperthyroidism

ScienceDaily (June 5, 2011) — A common hormone abnormality in older adults -- a mild form of overactive thyroid called subclinical hyperthyroidism -- is linked to a much higher risk of dying, a new study finds.

See Also:Health & MedicineThyroid DiseaseHormone DisordersElder CareHealthy AgingDiseases and ConditionsCancerReferenceHyperthyroidismHypothyroidismThyroid hormonePituitary gland

The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

Because this condition sometimes does not even cause symptoms, elderly people may be unaware they have altered thyroid function until serious complications occur, said the study's main author, Graziano Ceresini, MD, PhD, a clinical researcher at the University of Parma in Italy.

"Subclinical hyperthyroidism can be responsible for important medical problems, such as cardiac arrhythmias -- irregular heartbeat -- as well as altered bone structure and cognitive abnormalities, especially in elderly individuals," Ceresini said. "Now we know that it also may be accompanied by increased mortality in people ages 65 and older."

In the new study, the investigators used data from the Italian Aging in the Chianti Area study to evaluate the relationship between thyroid function and death from all causes in older people. Thyroid function test results were available for 950 subjects age 65 or older. At enrollment in the study, 819 subjects (86 percent) had normal thyroid function and 83 (nearly 9 percent) had subclinical hyperthyroidism.

Technically, subclinical hyperthyroidism is a below-normal or undetectable blood concentration of thyroid-stimulating hormone (TSH) with normal levels of the thyroid hormones called free T3 and T4.

In evaluating the death statistics, the researchers adjusted for age, sex and other factors that could bias the results, such as congestive heart failure, body mass index, cancer and stroke. They found that subjects who had subclinical hyperthyroidism at the beginning of the study had a 65 percent higher risk of dying during the six-year follow-up than did subjects with normal thyroid function.

"Although our results would suggest the need for thyroid function testing in elderly people, confirmation of our data by further studies is needed before a screening recommendation can be made. There are no current recommendations to test all elderly individuals for subclinical hyperthyroidism," Ceresini said.

He suggested, however, that elderly persons with signs of subclinical hyperthyroidism, especially arrhythmias or thyroid disease, should ask their doctor about getting a thyroid function test. Other symptoms may include weight loss, feeling too hot and nervousness.

Subclinical hypothyroidism, or a mildly underactive thyroid, also is common in elderly people but in this study was not linked to decreased survival. There were not enough subjects with overt underactive or overactive thyroid to analyze their death risk, the authors reported.

The National Institute on Aging participated in and helped fund this study. Both the Italian Ministry of Health and the Italian Ministry of University and Research also provided funding.

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Hormone test predicts ovarian function after chemotherapy for breast cancer

ScienceDaily (June 5, 2011) — A test that shows how many eggs a woman has in her ovaries may help young women with breast cancer know what their reproductive function will be after chemotherapy, a new study finds.

See Also:Health & MedicineWomen's HealthBreast CancerLung CancerMenopauseOvarian CancerColon CancerReferenceMenopauseHysterectomyOvarian cancerInfertility

The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

Called the anti-Mullerian hormone (AMH) test, this blood test measures levels of an ovarian hormone that reflects the size of the ovarian reserve, or remaining egg supply. Currently, doctors use it to quantify a woman's ovarian reserve before in vitro fertilization treatments. Now researchers from Scotland have found that measurement of AMH indicates how likely it will be for a woman to still have eggs in her ovaries after chemotherapy, which can often damage a woman's eggs and cause infertility.

"Future reproductive function is a concern for many young women with cancer," said lead investigator Richard Anderson, MD, PhD, professor of clinical reproductive science at the University of Edinburgh. "This test will be of benefit to women with newly diagnosed cancer to help decide whether they need to take steps to preserve their fertility."

In the U.S. alone, breast cancer is diagnosed in more than 25,000 women younger than 45 each year, according to the American Cancer Society.

For this study, Anderson and his colleagues recruited 50 premenopausal women, ages 29 to 51, who had just received a diagnosis of early breast cancer. All women had normal menstrual cycles and were asked to keep a daily record of their menstrual cycle, as an index of ovarian activity, during the two years of the study. Before the women started chemotherapy, they gave blood samples for AMH testing. They again had AMH tests one and two years after starting treatment.

Before chemotherapy the median AMH level was 0.4 nanograms per milliliter (ng/mL). After cancer treatment the AMH level fell rapidly, becoming undetectable (below 0.16 ng/mL) in 68 percent of the women after one cycle of chemotherapy, the authors reported. By one-year follow-up, 11 women withdrew from the study, mostly because of cancer recurrence, Anderson said. Menstrual records were available for 39 women at one year and for 29 women at two years.

A low AMH measurement before treatment correlated well with amenorrhea, or absence of menstruation, after treatment. Women whose AMH before treatment was low (below 0.4 ng/mL) were 16 times likelier to have stopped menstruating after chemotherapy than women with a high pretreatment AMH value, Anderson said. The odds of losing ovarian function remained higher even after statistical analysis controlled for increasing age, which tends to lower AMH levels. Women whose AMH before chemotherapy exceeded 0.92 ng/mL were reportedly almost five times more likely to continue menstruating after treatment.

"Our data suggest that the AMH test, taken before cancer treatment, can help individualize a woman's infertility risk after chemotherapy for breast cancer," Anderson said.

He added that results of this study, which was funded by the U.K. Medical Research Council, are likely to apply to other types of cancer as well.

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Targeted cancer therapy kills prostate tumor cells, study finds

ScienceDaily (June 6, 2011) — A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds.

See Also:Health & MedicineProstate CancerMen's HealthProstate HealthUrologyCancerBreast CancerReferenceMetastasisEmbryonic stem cellUrologyTumor suppressor gene

The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

"This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer," said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones. This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

"These patients are left with very few treatment options and usually succumb quickly to the disease," she said.

Ho's team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer. They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1. They also gave G-1 to noncastrated, or "intact," male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

"Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration," Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitized prostate tumors to the cell growth-inhibiting effects of G-1.

"These results mean G-1 won't work without androgen deprivation therapy," she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy. She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer. "The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any side effects of estrogen," she said.

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Anticancer effect of mushrooms demonstrated

ScienceDaily (June 4, 2011) — City of Hope researchers have investigated compounds in natural foods for their potential anticancer benefits, with a focus on food items that are easily found in grocery stores to ensure greater access and availability. Shiuan Chen, Ph.D., associate chair and professor of City of Hope's Department of Cancer Biology, identified phytochemicals in mushrooms that block the ezyme aromatase from producing estrogen. Controlling aromatase activity can help decrease estrogen levels, which controls and kills hormone-dependent breast cancers. In addition, mushrooms also demonstrate the ability to inhibit cancer call activity and slow tumor growth.

See Also:Health & MedicineBreast CancerCancerLung CancerPlants & AnimalsMiceVeterinary MedicineFungusReferenceHormone replacement therapyMenopauseBreast cancerMetastasis

Promising data from two early stage studies using mushrooms in preventing breast cancer recurrence and treatment of lung cancer are being presented at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, running from June 3 through 7.

Research highlights include:

"A dose-finding clinical trial of mushroom powder in postmenopausal breast cancer survivors for secondary breast cancer prevention."

An estimated one in five breast cancer survivors will experience a recurrence of his or her cancer within 10 years of treatment of the initial cancer diagnosis. With more than 80 percent of cancers diagnosed in women after menopause being hormone-dependent, there is a need for preventive treatments to lower that risk. The natural aromatase-inhibiting qualities of mushrooms noted in preclinical studies has the potential to offer a dietary intervention that may help prevent recurrence of hormone-dependent breast cancers.

Postmenopausal breast cancer survivors who were cancer free after completion of cancer therapy were enrolled in the trial. Groups received a 12-week course of white button mushroom extract at 5, 8, 10 or 13 gram doses. Because aromatase inhibition leads to a decrease in estrogen levels, a specific estrogen called estradiol was monitored and response was defined as a greater than 50 percent decrease in free estradiol levels in the blood circulation. Mushroom extract was well tolerated at all doses. However, no dose could be identified that met response criteria. In spite of this, a measurement of aromatase activity developed by Dr. Chen suggested some modest transient aromatase inhibition that lasted longest at the highest dose level (6 hours), suggesting that weak aromatase inhibition by mushrooms is achievable in patients, but that likely much higher amounts would be needed to achieve a clinically significant result.

"City of Hope developed a test sensitive enough to track aromatase activity that is sensitive to short-term changes, and we were able to successfully utilize that in the trial," said Melanie Palomares, M.D., M.S., assistant professor of the High Risk Breast Program at City of Hope, and lead author of the study. "Over the course of 12 weeks, we were able to observe phytochemical activity, but not at high enough concentrations to significantly reduce estrogen levels in our patients. Future studies should focus on more highly concentrated preparations of mushroom extract. Tissue levels of estrogens may also be a better measure than circulating estrogens."

"A phase I study of MM-10-001 in advanced nonsmall cell lung cancer."

Marianna Koczywas, M.D., assistant professor in City of Hope's Department of Medical Oncology & Therapeutics Research, is the principal investigator of a lung cancer study on a novel therapy, MM-10-011, derived from Shiitake Mycelium in mushrooms. The trial is in progress and Koczywas is presenting preliminary data from an interim analysis. MM-10-001 has demonstrated the ability to provoke and immune response specific to tumor cells in laboratory tests. The phase I clinical trial is intended to determine the toxicity of treatment and the highest dose patients can tolerate. This is a first step in three phases of clinical trials in humans to establish the safety, dosing and efficacy of new therapies. To date, 20 patients with advanced nonsmall cell lung cancer have received treatment with escalating doses of MM-10-001, from 5 to 10 to 20 mg, over 28 days.

No severe adverse events were reported. Two patients reported grade 2 fatigue, and one patient each reported loss of appetite, high protein levels in the blood and joint pain. The maximum tolerated dose of MM-10-001 had not been reached at the time of interim analysis.

"The clinical trial is ongoing, but the interim data are promising, with indications that MM-10-001 may be stimulating an immune response against the tumor," said Koczywas. "In a majority of the patients, we observed a possible decrease in interleukin-12 levels corresponding to treatment cycles, suggesting that lower interleukin levels are associated with improved survival."

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Early transplants are no better than chemotherapy followed by transplant for non-Hodgkin lymphoma patients, study finds

ScienceDaily (June 3, 2011) — Patients with a very aggressive form of non-Hodgkin lymphoma who receive a stem cell transplant after standard chemotherapy during their first remission have comparable survival rates to those who receive the same standard therapy alone and, if needed, a transplant when they relapse.

See Also:Health & MedicineLymphomaWounds and HealingToday's HealthcareMultiple Sclerosis ResearchDiseases and ConditionsCancerReferenceBone marrow transplantTransplant rejectionLiver transplantationClinical trial

These findings from a U.S. and Canadian clinical trial of 370 patients conducted at 40 clinical institutions were presented by Patrick Stiff, MD, lead investigator and director, Loyola Cardinal Bernardin Cancer Center, at the annual meeting for the American Society of Clinical Oncology (ASCO).

"The trial was based on several preliminary studies that indicated a survival benefit to early stem cell transplants," Dr. Stiff said. "These findings may save some patients from undergoing a stem cell transplant unnecessarily."

However, a subset with all of the possible poor risk factors with this form of non-Hodgkin lymphoma did seem to have a higher chance of survival in a sub- analysis.

"Additional research is necessary to determine the best plan of care for the highest-risk patients," Dr. Stiff said. "In the meantime, these patients will have to consult with their physician to carefully determine their treatment plan."

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Novel experimental agent is highly active in CLL patients, interim study shows

ScienceDaily (June 3, 2011) — An interim analysis of a phase II clinical trial indicates that a novel experimental agent for chronic lymphocytic leukemia (CLL) is highly active and well tolerated both in patients who are undergoing treatment for the first time and those who have relapsed and are resistant to other therapy.

See Also:Health & MedicineToday's HealthcareLeukemiaDiseases and ConditionsWounds and HealingPersonalized MedicineMultiple Sclerosis ResearchReferenceClinical trialLeukemiaDouble blindPulmonary embolism

The agent, called PCI-32765, is the first drug designed to target Bruton's tyrosine kinase, whose function is essential for CLL-cell survival and proliferation.

Study leader Dr. John C. Byrd, director of the division of hematology at Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) presented the findings June 5 at the 2011 American Society of Clinical Oncology annual meeting in Chicago.

The analysis involved the first 21 cases in the untreated-patient group and the first 27 individuals in the relapsed/refractory-patient group. One patient in each group had a complete remission, and 13 patients (62 percent) in the previously untreated group and 12 patients (44 percent) in the relapsed group had partial remissions.

"We are excited about these early findings because they suggest that PCI-32765 is a highly active oral therapeutic that produces a high rate of durable remissions -- the remissions last months on end -- with acceptable toxicity in relapsed and refractory CLL," Byrd says.

Complete remission means there is no detectable CLL in anywhere in the body; partial remission means that the individual's disease volume has decreased 50 percent or more in a sustained manner.

"It is exciting to see a drug that was shown to be active in the laboratory translate to clinical benefit for CLL patients," says researcher Dr. Amy Johnson, assistant professor of medicine at the OSUCCC -- James. Johnson co-led the pre-clinical CLL work at Ohio State with Byrd and now coordinates several correlative studies for this clinical trial.

Byrd stresses that the patients show several benefits of the treatment, such as higher platelet counts and hemoglobin levels, and that many report that they feel dramatically better overall with less fatigue, factors that are difficult to measure and report as a number.

"These responses last for many months in part because patients are willing to remain on the drug since the side effects are very tolerable," he notes.

The ongoing phase II clinical trial involves 78 patients with previously untreated or relapsed and refractory CLL or small lymphocytic leukemia. The previously untreated patients were all age 65 or older; individuals in the relapsed group all had two or more earlier treatments followed by recurrent disease.

"These are early findings, so patients with partial remissions could improve to complete remissions with further observation," Byrd says. "Usually patients with highly resistant and refractory CLL would have progressed and possibly died by this time, but 85 percent remain on PCI-32765 and continue to improve."

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Many of those living with HIV face a new life-threatening challenge: Cancer

ScienceDaily (June 6, 2011) — As the world marks the 30-year anniversary of the first reporting of HIV/AIDS, now comes the realization of a new challenge for people with the incurable disease. For reasons not yet clear, people with HIV face a higher rate of cancers not usually associated with HIV. This increasing rate of "non-AIDS defining cancers" includes lung, head and neck, liver, kidney, and anal cancers, among others. The alarming uptick in cancer rates highlights the critical need to understand how to treat tumors in people taking highly active anti-retroviral therapy (HAART) for HIV. Given what is known about HAART drug interactions, can newer targeted cancer therapies be given safely to patients with HIV?

See Also:Health & MedicineHIV and AIDSInfectious DiseasesCancerDiseases and ConditionsColon CancerBreast CancerReferenceClinical trialAntiretroviral drugMetastasisList of medical topics

To explore potential interactions between HAART and the newer cancer drugs, the AIDS Malignancy Consortium (AMC), a National Cancer Institute (NCI)-supported clinical trials group founded in 1995 to support innovative trials for AIDS-related cancers, has conducted the first of a planned series of studies. John Deeken, M.D., a research physician at Georgetown Lombardi Comprehensive Cancer Center and national chairman of the study, presented the findings during a poster session at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

He says these early results already have the potential to change the way that cancer is treated in HIV patients.

"Up to this point, oncologists have not had much information about treating cancer in people taking HAART," says Deeken. "We're basically at square one because people with HIV usually are not included in cancer clinical trials. They're excluded because physicians are worried about causing further immune suppression in HIV patients, and because HAART drugs are notorious for causing drug-drug interactions and serious side effects."

The first drug being studied is sunitinib. Sunitinib (Sutent®) may stop the growth of cancer cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. However, agents in the HAART cocktail are thought to affect the same enzymes involved in sunitinib metabolism.

The AMC chose to study sunitinib because this oral medication was approved by the Food and Drug Administration to treat kidney cancer, which is occurring at an increasing rate among HIV patients, and the drug is being studied in other cancer types that also affect HIV patients, such as lung and liver cancers.

Safety was examined separately for two groups within the phase I study. Group one included those whose HAART combination did not include ritonavir, while patients in group two were taking a ritonavir-based protease inhibitor HAART cocktail.

Between August 2009 and April 2011, a total of 19 patients were enrolled, treated, and completed at least one cycle of therapy. Sunitinib (50mg/day) was well tolerated in patients in group one -- those taking non-ritonavir based HAART regimens. Patients treated with sunitinib who were in group two, those taking the ritonavir-based therapy, experienced more side effects including higher rates of neutropenia (compared to those reported on phase III studies of sunitinib).

"Already, we have important information that can impact treatment," says Deeken. "When the trial is complete, we may have data to recommend that patients take different dosages of sunitinib based on what HAART cocktail they are taking. We also found that patients could keep taking their HIV medications safely, and that sunitinib did not affect the HIV disease status of patients in either group."

"Our HIV disease is now frequently being well controlled with HAART medications, but we are still having multiple medical problems including getting cancer earlier and more frequently," says James Weihe, a community representative for the AIDS Malignancy Consortium. "I am 60 years old and have been diagnosed with 3 minor cancers and 2 major cancers within the last 2 years. Frequently we are rejected from clinical trials just because we are HIV positive. Dr. Deeken and the work his colleagues are doing give us new hope. Their research shows that we can be included in cancer research trials if the dosages of the medications are adjusted to avoid drug-drug interactions and other side effects."

"The NCI has called for clinical trials criteria to include people with HIV though the adoption of these criteria has been slow," says Deeken. "Here we are, years after many new and effective anti-cancer treatments have been identified and we know so little about using these drugs in people who are also on therapy for their HIV. While the need for caution is understandable, it may be scientifically unjustified as well as fundamentally unfair to exclude patients with HIV from clinical trials."

The AMC study is sponsored by the National Cancer Institute under a Clinical Trials Agreement with Pfizer, Inc who provided the sunitinib.

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