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Breakthrough Case Study Highlights New Biomarker for Cancer and Inflammation

A groundbreaking peer reviewed case report by Dr. Isaac Eliaz, M.D. of Amitabha Medical Clinic, demonstrates for the first time the clinical use of novel biomarker galectin-3 to assess cancer progression and inflammation. The case study titled, “The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities,” was published in the July 2013 issue of Case Reports in Oncology. This report is the first of its kind to expand the diagnostic and prognostic applications of the galectin-3 blood serum test, introducing an important clinical tool to assess risk and progression of metastatic cancer and inflammatory diseases.

In 2011, the galectin-3 blood test was approved by the U.S. Food and Drug Administration for the screening and prognosis of congestive heart failure and cardiovascular disease. Approval was granted after an extensive body of published data, including long-term population studies, demonstrated the active role of elevated galectin-3 in cardiovascular conditions, fibrosis and early mortality. However, a rapidly expanding field of published galectin-3 research also highlights the significance of this rogue molecule as a novel biomarker that is both an active culprit as well as a byproduct of numerous inflammatory and malignant cellular processes beyond cardiovascular disease.

An expert on galectin-3, Dr. Eliaz applies the data obtained in this case study to shed further light on excess galectin-3’s mechanisms of action, specifically inflammatory response to injury and cancer progression. In this report, Dr. Eliaz presents the first published case documenting the clinical use of galectin-3 to monitor cancer progression and treatment response, as well as inflammatory conditions. These findings point to an expanded clinical model using galectin-3 testing in the diagnostic and prognostic assessment of numerous chronic, inflammatory diseases.

Unlike biomarkers such as C-reactive protein (CRP), which only indicate the presence of inflammation, galactin-3 is shown to play a direct role in initiating disease progression. It is a protein normally present in the body at low concentrations, where it is involved in numerous functions including cell growth and communication. At elevated levels, however, galectin-3 fuels numerous pathologic processes including chronic inflammation and the progression of inflammation to fibrosis; cancer cell adhesion, migration, angiogenesis, and metastasis. Elevated galectin-3 also allows cancer cells to evade immune response. Research demonstrates elevated galectin-3 levels in patients with melanoma, lung, breast, prostate, colorectal, ovarian, and head and neck cancers as well as non-Hodgkin’s lymphoma and others. Galectin-3 levels are also found to be higher in patients with metastatic disease than in patients with localized tumors.

Dr. Eliaz states, “This new case report and significant clinical observation supports the need for further research on the role of galectin-3. The galectin-3 test could well become one of our most important clinical tools in assessing and monitoring a wide range of conditions beyond cardiovascular disease, including metastatic cancer and inflammatory conditions.”

Study: The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities. [Case Reports in Oncology]

Source: PR Newswire

Breakthrough Case Study Highlights New Biomarker for Cancer and Inflammation

A groundbreaking peer reviewed case report by Dr. Isaac Eliaz, M.D. of Amitabha Medical Clinic, demonstrates for the first time the clinical use of novel biomarker galectin-3 to assess cancer progression and inflammation. The case study titled, “The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities,” was published in the July 2013 issue of Case Reports in Oncology. This report is the first of its kind to expand the diagnostic and prognostic applications of the galectin-3 blood serum test, introducing an important clinical tool to assess risk and progression of metastatic cancer and inflammatory diseases.

In 2011, the galectin-3 blood test was approved by the U.S. Food and Drug Administration for the screening and prognosis of congestive heart failure and cardiovascular disease. Approval was granted after an extensive body of published data, including long-term population studies, demonstrated the active role of elevated galectin-3 in cardiovascular conditions, fibrosis and early mortality. However, a rapidly expanding field of published galectin-3 research also highlights the significance of this rogue molecule as a novel biomarker that is both an active culprit as well as a byproduct of numerous inflammatory and malignant cellular processes beyond cardiovascular disease.

An expert on galectin-3, Dr. Eliaz applies the data obtained in this case study to shed further light on excess galectin-3’s mechanisms of action, specifically inflammatory response to injury and cancer progression. In this report, Dr. Eliaz presents the first published case documenting the clinical use of galectin-3 to monitor cancer progression and treatment response, as well as inflammatory conditions. These findings point to an expanded clinical model using galectin-3 testing in the diagnostic and prognostic assessment of numerous chronic, inflammatory diseases.

Unlike biomarkers such as C-reactive protein (CRP), which only indicate the presence of inflammation, galactin-3 is shown to play a direct role in initiating disease progression. It is a protein normally present in the body at low concentrations, where it is involved in numerous functions including cell growth and communication. At elevated levels, however, galectin-3 fuels numerous pathologic processes including chronic inflammation and the progression of inflammation to fibrosis; cancer cell adhesion, migration, angiogenesis, and metastasis. Elevated galectin-3 also allows cancer cells to evade immune response. Research demonstrates elevated galectin-3 levels in patients with melanoma, lung, breast, prostate, colorectal, ovarian, and head and neck cancers as well as non-Hodgkin’s lymphoma and others. Galectin-3 levels are also found to be higher in patients with metastatic disease than in patients with localized tumors.

Dr. Eliaz states, “This new case report and significant clinical observation supports the need for further research on the role of galectin-3. The galectin-3 test could well become one of our most important clinical tools in assessing and monitoring a wide range of conditions beyond cardiovascular disease, including metastatic cancer and inflammatory conditions.”

Study: The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities [Case Reports in Oncology]

Source: PR Newswire

Unexpected Synergy Between Two Cancer-linked Proteins Offers Hope for Personalised Cancer Therapy

A team of scientists led by Associate Professor Zeng Qi from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have discovered a new biomarker which will help physicians predict how well cancer patients respond to cancer drugs. Having the means to identify patients who are most likely to benefit from currently available cancer drugs not only reduces substantially the healthcare cost for the patient, it could mean saving precious lives by getting the right drugs to the right patient at the onset of the treatment. This study published and featured on August cover of the Journal of Clinical Investigation will boost the development of personalised medicine in cancer care and therapy.

Metastasis is the rapid and uncontrollable spread of cancer cells from the primary tumour to other parts of the body. It is often the leading cause of death in cancer patients. Increasingly, there is evidence to show that in many cancers that have metastasised, a protein called PRL-3 is often found to be present at unusually high levels. Since it was first identified in 1998 by Associate Professor Zeng, several other research groups have found evidence to support the strong link between elevated levels of PRL-3 protein and the metastasis of aggressive cancers in the lung, liver, colon and breast. This cancer-promoting action of PRL-3 makes it an ideal target for cancer diagnostics and treatment.

In this study, the IMCB team discovered a curious synergy between PRL-3 and EGFR, another well-known cancer-linked protein frequently associated with breast and lung cancers in humans. They found that cancer cells with higher levels of PRL-3 not only hyperactivate EGFR, but also develop an ‘addiction’ for it to survive. Consequently, by suppressing EGFR activity with EGFR inhibitor drugs, the scientists observed that cancer cells with higher levels of PRL-3 were more rapidly destroyed. To validate these findings in humans, the team collaborated with Associate Professor Wee Joo Chng from the National University Health System to run an analysis on pre-existing clinical data of colorectal cancer patients. The results confirmed that patients who respond better to EGFR inhibitor drugs were those suffering from cancers with abnormally high levels of PRL-3.

Associate Professor Zeng said, “This unexpected synergy has revealed a vulnerable spot of aggressive cancers and brought new hope of treating PRL-3 driven cancers successfully. The addiction phenomenon we observed in cancer cells is akin to depriving alcohol from an alcoholic, thereby inducing the severe ‘withdrawal effects’. In the same way, by selecting cancer patients with elevated levels of PRL-3 and greater ‘addiction’ of EGFR for anti-EGFR treatment, we can deliver more effective and targeted cancer therapy with the existing EGFR inhibitor cancer drugs.”

Professor Sir David Lane, Chief Scientist of A*STAR said, “This is an excellent example of how years of basic research lay the foundation for advancement in translational and clinical applications. I am pleased that the team is exploring the potentials of developing this new predictive biomarker into a rapid diagnostic kit for identifying patients who will respond favourably to current anti-EGFR treatment. I believe that this study will open new avenues for personalised medicine in cancer therapy.”

Study: Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells [Journal of Clinical Investigation]

Source: Agency for Science, Technology and Research (A*STAR)

Cancer Research Implies Future for Personalized Medicine, Reduction in Animal Testing

On August 6th, JoVE, the Journal of Visualized Experiments, published two new methods for scientists to study and treat tumor growth. The methods introduce a lab-born, human tissue structure with replicated human biochemistry – offering scientists the opportunity to grow, observe, and ultimately learn how to treat biopsied human tumor cells.

The University Hospital of Würzburg scientists behind the experiment have created a new version of the testing structures known as biological vascularized scaffolds (BioVaSc). Their three-dimensional human-tissue structures are the first of their kind to be built with multiple human cell types. The structures offer two methods for study: a three-dimensional (3D) static system for short term testing that is beneficial for microscopy imaging, and a dynamic system that introduces a flow-simulation to simulate actual conditions of the human body. This is especially helpful in long term studies of metastasis, or, the spreading of cancer cells through the human vascular system.

“Our 3D tumor model is reducing or even replacing animal experiments,” said engineer Jenny Reboredo. In their article, Reboredo and her colleagues explained that this human-tissue based testing system could eliminate the potential for the misinterpretation that often accompanies animal testing. Furthermore, this method solves the shortfalls of typical in-vitro testing, which is limited by the lack of intercellular interactions.

The authors also suggest that their use of primary cells derived from tumor biopsies is a “very important step towards personalized medicine.” With the method the team has created, a lab could in the future take a biopsy of a cancer cell and do tests to find the most effective treatment before ever administering drugs to the human patient.

Further implications of Reboredo and her colleagues’ work involve the use of a BioVaSc-type method for studying non-tumorous diseases. “In the long term we want to be able to develop disease models, especially for diseases where no animal models are available,” Reboredo said.

When asked why she and her colleagues published in JoVE, Reboredo noted that their models “can be explained and visualized best in a movie [and] to publish in such a media is made possible by JoVE.”

Source: EurekAlert!

Biomarker Identification May Lead to New Noninvasive Test for Colorectal Cancer Detection

The average 5-year survival for colorectal cancer (CRC) is less than 10% if metastasis occurs, but can reach 90% if detected early. A new non-invasive test has been developed that measures methylation of the SDC2 gene in tissues and blood sera. This test detected 87% of all stages of colorectal cancer cases (sensitivity) without significant difference between early and advanced stages, while correctly identifying 95% of disease-free patients (specificity). The results are published in the July issue of The Journal of Molecular Diagnostics.

According to the US Centers for Disease Control and Prevention, CRC is the second leading cancer killer in the US affecting both men and women. In 2009, close to 137,000 people in the US were diagnosed with CRC, with close to a 40% mortality rate.

There are other screening choices for CRC, including fecal occult blood testing (FOBT), fecal immunochemical testing, and colonoscopy. Colonoscopy is the gold standard of CRC screening, but patient resistance – mostly due to the unpleasant preparation – has curbed widespread adoption. FOBT is non-invasive but has limited sensitivity, particularly for early disease. A sensitive and specific non-invasive test using blood or stool could to be a more preferable option with the potential of saving many lives.

In their search for a biomarker that could be used for the early detection of CRC, investigators from Genomictree, Inc. and Yonsei University College of Medicine in Seoul, South Korea, performed DNA microarray analysis coupled with enriched methylated DNA using tissues from primary tumors and non-tumor tissues from 12 CRC patients. After step-wise filtering, they found a set of genes that were highly methylated across all of the CRC tumors. Ultimately they identified one gene, SDC2, which encodes the membrane syndecan-2 protein, a protein that is known to participate in cell proliferation, cell migration, and is expressed in colon mesenchymal cells. The methylation level of target region of SDC2 assessed in tumor tissue was found to be significantly higher than that from paired adjacent non-tumor tissue.

The next step was to clinically validate the biomarker by analyzing SDC2 methylation levels in primary tumors and paired-adjacent non-tumor tissue samples from 133 CRC patients. Investigators found that in the transcriptional regulatory region of the SDC2 gene, tumor samples showed significantly higher levels of methylation than the control samples. SDC2 methylation positivity ranged from 92.9% to 100% when samples were stratified according to stages of cancer.

Further, investigators found that the SDC2 biomarker could be measured in serum samples from CRC patients and healthy individuals. “The SDC2 methylation test was able to detect 92% for detection of stage I cancer patients indicating that SDC2 is suitable for early detection of CRC where therapeutic interventions have the greatest likelihood of curing the patient from the disease,” says first author TaeJeong Oh, PhD.

The authors suggest that the SDC2 methylation test they describe could possibly be used as an alternative to or in conjunction with colonoscopy. It could also be used to monitor cancer progression and treatment. Dr. Sungwhan An, corresponding author and CEO of Genomictree, Inc., commented: “We are very excited with this result using a small amount of serum DNA from less than 1ml of blood. I believe a greater volume of blood will further improve the clinical performance of this test. We are currently preparing another set of clinical validation studies evaluating SDC2 methylation in serum DNA from patients with early adenoma.” In future research the authors will explore whether this biomarker is specific to CRC or universal among other cancers.

Source: Gnome-Wide Identification and Validation of a Novel Methylation Biomarker, SDC2, for Blood-Based Detection of Colorectal Cancer

Source: EurekAlert!