Simple test could hold key to early diagnosis of cancers

ScienceDaily (June 10, 2011) — Cancers of the gut, stomach and pancreas could be detected much sooner with a simple urine test, research suggests. Researchers at the University of Edinburgh have identified key proteins in the urine of patients with advanced cancers.

See Also:Health & MedicineBreast CancerColon CancerCancerPancreatic CancerLymphomaToday's HealthcareReferenceMetastasisOvarian cancerBreast cancerStomach cancer

The findings could help the detection of these cancers in people who have not yet started to show symptoms of the disease.

This would enable patients to be diagnosed much earlier, leading to improved survival rates.

Only around 10 per cent of patients with these cancers -- known as cancers of the upper gastrointestinal tract -- are still alive five years after diagnosis.

This is because such cancers, which tend to be aggressive, are often diagnosed at an advanced stage.

Dr Holger Husi, of the University of Edinburgh's Tissue Injury and Repair Group, said: "The aim of this work is to enable these cancers to be diagnosed much earlier. This would help us to treat the cancer before it has a chance to spread. The majority of these cancers are currently diagnosed late where no surgery is possible due to its advanced stage. Earlier diagnosis would mean that curative surgery or chemotherapy would be possible for more patients."

The research, published in the journal Proteomics-Clinical Applications, compared urine samples from patients with upper gastrointestinal cancers with urine samples from people who were cancer-free.

Scientists analysed the samples to identify thousands of proteins. They then identified six particular proteins, which were present in 98 per cent of the cancer cases but absent in almost 90 per cent of samples from patients without cancer.

The researchers then narrowed molecules down to the two proteins -- S100A6 and S1009 -- most likely to appear in samples from patients with cancer but be absent from the other samples.

The scientists now intend to see whether people with early stage cancers, which have not yet been diagnosed, have the same levels of proteins present.

This would involve analysing samples from at least 1,000 volunteers and tracking the participants over a number of years to identify those who are then later diagnosed with upper gastrointestinal cancers.

Email or share this story:

Novel pathway regulating angiogenesis: May fight retinal disease, cancers

ScienceDaily (May 31, 2011) — Scientists have identified in the journal Nature a new molecular pathway used to suppress blood vessel branching in the developing retina -- a finding with potential therapeutic value for fighting diseases of the retina and a variety of cancers.

See Also:Health & MedicineLymphomaBrain TumorHeart DiseaseImmune SystemLung CancerLeukemiaReferencePeripheral visionVitreous humourHeat shock proteinEmbryonic stem cell

Researchers report that myeloid cells, blood cells involved in the immune system, use this molecular pathway to guide blood vessel patterning in the retina. Furthermore, in the same study researchers were able to reverse this pathway to accelerate the growth of branching vessels, which could be important to developing new methods for repairing damaged tissues.

"We show in the setting of retina that myeloid cells use this pathway to direct vascular traffic," explained Richard Lang Ph.D., senior investigator on the study and director of the Visual Systems Group in the Division of Ophthalmology at Cincinnati Children's Hospital Medical Center. "We think modulation of this pathway might become a promising therapeutic option.''

The study, to be published online May 29, demonstrates how retinal myeloid cells regulate blood vessel branching in the still-developing retinas of postnatal mice by using the Wnt protein signaling network. The Wnt pathway is known for its role in embryonic and early development as well as in cancer. Although myeloid cells play an important part in the immune system, these cells are also found in many different tumor types and promote tumor progression.

Through a series of experiments in cell cultures and mouse models, researchers determined the new pathway works by myeloid cells utilizing the Wnt pathway to regulate expression of a gene known as Flt1. Flt1 encodes a protein called vascular endothelial growth factor receptor-1 (VEGFR1), which suppresses vascular growth by binding vascular endothelial growth factor (VEGF). The expression of Flt1 can be adjusted so that when ramped up it inhibits VEGF and vascular branching, or when turned down it allows VEGF to increase branching.

Dr. Lang said the Wnt-Flt1 response is a new pathway for regulating VEGF-stimulated angiogenesis (blood vessel formation). This presents a number of new research opportunities to test its influence on retinal diseases that are often associated with abnormal blood vessel development and in tumor formation, he added.

The current study's first author, James (Tony) Stefater, a member of Dr. Lang's laboratory, is an M.D.-Ph.D. graduate student at the University of Cincinnati College of Medicine. Lang, Stefater and their colleagues are already conducting new experiments to see how the pathway influences molecular reactions in retinal disease and in cancer. The cancer studies are being done in collaboration with Jeff Pollard, Ph.D., a cancer cell biologist at the Albert Einstein College of Medicine and co-author on the current study.

The study was supported by funding from the National Eye Institute of the National Institutes of Health, the Howard Hughes Medicine Institute, and included collaborators from those institutions as well as the London Research Institute (Vascular Biology Laboratory) in the United Kingdom and the Center for Skeletal Disease Research, Grand Rapids, Mich.

Email or share this story:

New therapy for blood cancers using drug combo

ScienceDaily (June 3, 2011) — Reported in the journal Clinical Cancer Research, the study determined the maximum tolerated dose with acceptable side effects for this novel drug combination. The trial represented the first time a proteasome inhibitor such as Bortezomib was combined with a cell cycle inhibitor such as Alvocidib to treat patients with cancer. Proteasome inhibitors work by blocking the action of proteasomes, which are large protein complexes that help destroy proteins that are no longer needed by the cell. Cell cycle inhibitors disrupt the sequence of events that allow cells to undergo cell division and duplication. They also have the ability to block gene transcription.

See Also:Health & MedicineLymphomaPersonalized MedicineLung CancerBreast CancerDiseases and ConditionsCancerReferenceClinical trialCOX-2 inhibitorChemotherapyTransplant rejection

The trial included 16 patients who had either indolent (non-aggressive) non-Hodgkin's lymphoma, mantle cell lymphoma or multiple myeloma. After they received the treatments over a 21-day cycle, there were two complete responses, meaning that all detectable traces of the cancer were gone, and five partial responses.

"Therapeutic responses tend to be rare in Phase I trials, but 44 percent of our patient sample responded to the therapy. Interestingly, some patients who previously had no response to Bortezomib, or progressed after Bortezomib therapy, responded to the combination," says Beata Holkova, M.D., a hematologist-oncologist at VCU Massey and co-investigator on this clinical trial. "Because of the small patient sample size, we can't draw definitive conclusions about the effectiveness of the therapy, but we were quite encouraged by the results."

The patients received Bortezomib intravenously on days 1, 4, 8 and 11 and Alvocidib on days 1 and 8. Bortezomib's therapeutic dose alone was not tested because it has already been established and approved to treat certain blood cancers. However, for Alvocidib, the researchers escalated the dose until the maximum tolerated dose was identified. The same researchers are also currently completing a second Phase I clinical trial testing a different delivery schedule of Alvocidib. Although not yet completed, the initial results of this trial appear comparable to the present study.

"This is one of the first trials of its type in which two targeted agents which interfere with two very different biological processes are being combined to treat patients with blood cancers," says co-investigator Steven Grant, M.D., associate director for translational research, co-program leader of Developmental Therapeutics and professor of internal medicine at VCU Massey.

The rationale for this study was developed in Grant's laboratory when synergistic interactions between proteasome and cell cycle inhibitors in malignant blood cancer cells were discovered by Yun Dai, M.D., Ph.D., associate professor of internal medicine at VCU Massey. This laboratory research established the basis for a V Foundation Translational Research Award, which with additional funding from the National Institutes of Health provided the resources necessary to translate the laboratory findings into clinical trials.

Moving forward, the researchers are working with the NCI to develop a Phase II clinical trial to test the effectiveness of this drug therapy. The trial will be conducted in collaboration with multiple institutions to compare the effectiveness of fixed doses of the drug combination in a larger patient population.

Grant and Holkova collaborated with John Roberts, M.D., E. Brent Perkins, M.D., Viswanathan Ramakrishnan, Ph.D., Mary Beth Tombes, R.N., M.N., Ellen Shrader, R.N., Martha Wellons, R.N., Kevin Hogan, Ph.D., Sarah Kolla, M.D., and Talreja, Neha, all from VCU Massey Cancer Center and the VCU School of Medicine; G. David Roodman, M.D., Ph.D., from the University of Pittsburgh Department of Medicine; Domenico Coppola, M.D., Loveleen Kang, Jana Dawson and Daniel Sullivan, M.D., from H. Lee Moffitt Cancer Center and Research Institute; Robert K. Stuart, M.D., from the University of South Carolina Department of Medicine; and William D. Figg, Sr., Pharm.D., Austin Doyle, M.D., and John Wright, M.D., Ph.D., from the National Cancer Institute.

Email or share this story:

Patients referred to dermatologists skin lesions evaluations also found to have other skin cancers

ScienceDaily (May 17, 2011) — Among patients referred by non-dermatologists to dermatologists for evaluation of skin lesions suspected of being malignant, only apparently one-fifth were found to be cancerous, although dermatologists identified and biopsied other incidental lesions, approximately half of which were malignant, according to a report in the May issue of Archives of Dermatology, one of the JAMA/Archives journals.

See Also:Health & MedicineSkin CarePsoriasisSkin CancerWounds and HealingDiseases and ConditionsCosmetic SurgeryReferenceMole (skin marking)BlackheadUterine fibroidsCellulite

"More than one million skin cancers are diagnosed annually in the United States , with one in five Americans developing skin cancer during their lifetime," the authors write as background information in the article. "Non-dermatologists, particularly primary care physicians, play an important role in skin lesion assessment and initiation of referrals to the dermatologist."

Kate V. Viola, M.D., of the Robert Wood Johnson Clinical Scholars Program and Yale University School of Medicine, New Haven , Conn. , and colleagues sought to evaluate the proportion of suspicious lesions identified by non-dermatologists that are found to be malignant compared to the number of secondary skin lesions identified at the time of dermatology referral.

The authors evaluated medical records of 400 patients who were referred by a non-dermatologist to the dermatology service at the Veterans Affairs (VA) Connecticut Health System for evaluation of suspicious skin lesions between January 1, 2006 and December 31, 2009.

Of the 400 patients included in the study, the average age was 77.7 years, 98 percent were white men and 74 (18.5 percent) had a history of skin cancer. Most lesions (224 of 400 or 56 percent) were considered to be non-malignant by the consulting dermatologist, requiring no biopsy. Of the 176 lesions that needed biopsies, 88 were malignant according to the dermatopathology report, meaning 88 of 400 patients (22 percent) had an index lesion (lesions that prompted the referral) that was positive for cancer.

Dermatologists biopsied an additional 111 incidental lesions (secondary lesions identified, not the reason for referral), of which 61 (55 percent) were malignant. Twelve of 61 patients (19.7 percent) with a malignant incidental lesion had an index lesion that was not biopsied. Nearly half of all skin cancers identified were not the referral lesion, and 9.8 percent of the incidental lesions discovered by the dermatologist were melanomas.

In the present study, "a substantial proportion of malignant lesions was incidentally identified by the consulting dermatologist in addition to the primary lesion of concern," the authors write. The authors also suggest that "non-dermatologists may benefit from focused educational initiatives on skin cancer detection, particularly the significance of the total body skin examination and the expectations for and limitations of teledermatology."

Email or share this story:

Half of prostate cancers could potentially benefit from new type of cancer drugs

ScienceDaily (May 19, 2011) — About half of prostate cancers have a genetic anomaly that appears to make tumor cells responsive to a new class of cancer-fighting drugs, a new study from the University of Michigan Comprehensive Cancer Center finds.

See Also:Health & MedicineProstate CancerBreast CancerMen's HealthUrologyCancerDiseases and ConditionsReferenceBRCA1BRCA2Tumor suppressor geneMetastasis

The drugs, called PARP inhibitors, are currently being tested in breast cancer patients with mutations in the BRCA1 and BRCA2 genes, which are found in up to 10 percent of all breast cancers.

Half of prostate cancers have a genomic rearrangement that causes the fusion of two genes called TMPRSS2 and ERG. This gene fusion, believed to be the triggering event of prostate cancer, was initially discovered in 2005 by U-M researchers led by Arul Chinnaiyan, M.D., Ph.D.

"This type of gene fusion occurs in about 50 percent of prostate cancers, but the genes involved have been notoriously difficult to target therapeutically. We found that instead of targeting the gene fusion product directly, we could block the function of critical interacting partners, such as PARP1," says Chinnaiyan, a Howard Hughes Medical Institute researcher, director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the U-M Medical School.

Chinnaiyan is the senior author of the current study, which appears in the May 17 issue of Cancer Cell.

"Our studies suggest that the total population of patients who could benefit from PARP inhibition could be significantly expanded," says Chad Brenner, Ph.D. candidate at U-M, who is the first author on the study.

Working with prostate cancer models in cell lines and mice, researchers found that therapies using the PARP inhibitor Olaparib helped shrink tumors expressing the TMPRSS2:ERG gene fusion and blocked the ability of tumors to spread. Olaparib had no effect on tumors that did not have the gene fusion.

PARP inhibitors are not currently approved by the U.S. Food and Drug Administration, but initial trials in breast cancer patients indicate they can be administered safely and are well-tolerated.

Study authors Maha Hussain, M.D., and Felix Y. Feng, M.D., are currently working on two clinical trials based on these study findings to test if the TMPRSS2:ERG gene fusion could be used as to predict response to treatments, including a PARP inhibitor. These studies are not yet recruiting participants.

Prostate cancer statistics: 217,730 Americans will be diagnosed with prostate cancer this year and 32,050 will die from the disease, according to the American Cancer Society

Additional authors: Bushra Ateeq, Yong Li, Anastasia K. Yocum, Qi Cao, Irfan A. Asangani, Sonam Patel, Xiaoju Wang, Hallie Liang, Jindan Yu, Nallasivam Palanisamy, Javed Siddiqui, Wei Yan, Xuhong Cao, Rohit Mehra, Aaron Sabolch, Venkatesha Basrur, Robert J. Lonigro, Scott A. Tomlins, Christopher A. Maher, Kojo S.J. Elenitoba-Johnson, Kenneth J. Pienta, Sooryanarayana Varambally, all from U-M; Jun Yang, Nora M. Navone, from M.D. Anderson Cancer Center

Funding: National Institutes of Health, U-M Prostate Specialized Program in Research Excellence grant, Early Detection Research Network, U.S. Department of Defense, Prostate Cancer Foundation

The University of Michigan has received a patent on the detection of gene fusions in prostate cancer (US 7,718,369), on which Tomlins and Chinnaiyan are co-inventors. The diagnostic field of use has been licensed to Gen-Probe Inc. Chinnaiyan also has a sponsored research agreement with Gen-Probe.

Email or share this story:

Recurring cancers in women with a history of breast cancer differ from the original tumors

ScienceDaily (May 18, 2011) — When women with a history of breast cancer learn they have breast cancer again, one of the first questions they and their doctors ask is: Has my cancer come back, or is this a new case? Now, new data from Fox Chase Cancer Center suggest that both new and recurring cancers will differ significantly from the original tumors, regardless of how many months or years women spent cancer-free, and doctors should tailor treatment to the specific qualities of the second tumor, regardless of whether it's old or new.

See Also:Health & MedicineBrain TumorCancerBreast CancerOvarian CancerLung CancerWomen's HealthReferenceMetastasisTumor suppressor geneTumorMammography

Anita Patt, MD, surgical oncology fellow at Fox Chase and lead author on the study, will be presenting the findings at the 2011 Annual Meeting of the American Society of Clinical Oncology on Monday, June 6.

"There tends to be a stigma and a lot of anxiety about the word 'recurrence,'" says Richard J. Bleicher, MD, FACS, attending surgeon at Fox Chase and senior author on the study. "Sometimes women will worry more if they believe their original cancer is back, meaning they didn't 'beat it' the first time around. These findings suggest they should not get hung up on that idea, because any subsequent diagnosis -- whether it's a recurrence or a new tumor -- will look significantly different from their first cancer."

In women with a history of breast cancer, doctors often approach new tumors differently depending on whether they believe it's a recurrence of the first tumor, or a totally new one, Bleicher explains. But there are no official ways to distinguish between the two types, so doctors typically rely on a few criteria, then form their own opinion based on an "overall gestalt," he says.

One of the criteria doctors have used to distinguish between new and recurring cancers is the amount of time women spent cancer-free, reasoning that the longer the time between the two tumors, the more likely the second one is to be an entirely new case.

To investigate if this and other criteria indeed distinguish new and recurring tumors, Bleicher, Patt, and their colleagues looked at data collected from 4,420 women with a history of breast cancer. Two-hundred and thirty five women were eventually diagnosed with another tumor in the same breast, suggesting it could be a recurrence.

However, when the researchers compared the first and second tumors, they saw that 89% differed in at least one key characteristic that could potentially affect treatment or prognosis, regardless of whether the second tumors were new cases or a recurrence of the original cancer. Sixty percent of the second tumors differed from the first by at least 2 or more criteria, including whether or not it would respond to hormones, how it was diagnosed, and whether at least 25 percent of the tumor was confined to the ducts, and therefore less able to spread throughout the body.

Half of the women experienced a second tumor within 60.5 months of their first. And, importantly, the amount of time they spent cancer-free appeared to have no bearing on whether the two tumors differed in any key characteristics.

The findings suggest that patients and doctors shouldn't spend much time determining if the second tumor is a recurrence of the first, or a totally new entity, says Bleicher, and should instead tailor treatment to the specific qualities of the second tumor, regardless of whether it's old or new.

"When a patient comes back with a relapse, whether it's a new tumor or a recurrence, it really doesn't make a difference," he says. "We treat them both as potentially curable."

Co-authors on the study include Tianyu Li, Massimo Cristofanilli, and Elin Sigurdson, from Fox Chase and Gary Freedman from the Hospital of the University of Pennsylvania.

Email or share this story: