Breaking News
April 25, 2019 - Vanderbilt investigators discover link between vascular biology and eye disease
April 25, 2019 - Feces transplantation is effective and provides economic benefits
April 25, 2019 - Eisenhower Health first in Southern California to offer new lung valve treatment for COPD/emphysema
April 25, 2019 - Johns Hopkins researchers uncover role of neurotransmitter in the spread of aggressive cancers
April 25, 2019 - Porvair Sciences offers highly effective P3 microplate for biological sample clean-up
April 25, 2019 - Air pollution increases risk for respiratory hospitalization among childhood cancer survivors
April 25, 2019 - We are sitting more! How bad is that?
April 25, 2019 - ADHD Screening: MedlinePlus Lab Test Information
April 25, 2019 - Cellular alterations increase vulnerability of obese and diabetic individuals to infection
April 25, 2019 - Association Insurance Pushes On Despite Court Ruling
April 25, 2019 - Traditional and e-cigarette users may be more receptive to smoking cessation interventions
April 25, 2019 - Delving into tumor’s cellular lineage may offer clues for customized therapies
April 25, 2019 - Two studies uncover brain mechanisms underlying decision making process
April 25, 2019 - Cardiometabolic Risk Better ID’d in Children Reclassified to Higher BP
April 25, 2019 - How the obesity epidemic is taking a toll on our bones and joints
April 25, 2019 - E-cigarettes contaminated with dangerous microbial toxins
April 25, 2019 - Researchers document specific characteristics of storefront tobacco advertisements
April 25, 2019 - Oncotype DX-guided treatment could reduce cost for breast cancer care, study suggests
April 25, 2019 - New review highlights how lifestyle affects our genes
April 25, 2019 - Study provides evidence that blood tests can detect Alzheimer’s risk
April 25, 2019 - Computer program mimics natural speech using brain signals from epilepsy patients
April 25, 2019 - Physicians turning to antibiotic alternatives for long-term acne treatment
April 25, 2019 - Preschool Is Prime Time to Teach Healthy Lifestyle Habits
April 25, 2019 - Study finds insidious and persistent discrimination among physician mothers
April 25, 2019 - Newly identified skin-gut communication helps illuminate link between food allergy and eczema
April 25, 2019 - Thiazide use linked with reduced risk of low energy fractures in people with Alzheimer’s
April 25, 2019 - Some women are biologically more resilient than others to PTSD
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Researchers use brain scans to provide better understanding of unconscious bias
April 24, 2019 - Blocking BRAF ubiquitination may be an effective treatment approach in melanoma
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
Case Western Reserve professor wins $2 million grant to study colorectal cancer

Case Western Reserve professor wins $2 million grant to study colorectal cancer

image_pdfDownload PDFimage_print

Lan Zhou, MD, PhD, associate professor of pathology at Case Western Reserve University School of Medicine, has received a five-year, $2 million grant from the National Cancer Institute of the National Institutes of Health to study human colorectal cancer. Her work focuses on the effect of the imbalance of the gut microbiome, the immune response, and genetics in the development of adenocarcinoma (cancer that forms in the lining of the glands) through the serrated pathway.

The “serrated pathway” is a molecular pathway postulated for a subset of colorectal cancers that develop from certain serrated adenomas/polyps–growths that have a saw-tooth appearance when viewed under the microscope. It is distinct from the conventional adenoma-carcinoma (cancer) pathway, which involves “flat” growths. As many as 15 percent of all colorectal cancers start from serrated adenoma polyps with dysplasia (cells that look distinctively abnormal under the microscope). Serrated lesions are also found in patients with irritable bowel disease and colitis, often contributing to colon cancer development in that population. Serrated cancer lesions are not well described, do not respond well to chemotherapy compared to other tumors, and are associated with worse prognoses.

“Colon cancer can start from different adenomas and have different mechanisms, which is why it is imperative to recognize these variations and apply specific preventive treatment,” said Zhou, who is also a Case Comprehensive Cancer Center member.

Under the grant, Zhou and her collaborating team will use a combination of approaches in mouse models and human tissue to study the carcinogenic transformation of colon epithelium (tissue that lines bodily organs) characterized by the loss of HES1, an important signaling molecule that regulates cell homeostasis and the differentiation of stem cells into specialized cells. This process, known as Notch signaling, is crucial for maintaining the balance between cell proliferation, differentiation, and normal cell death.

Zhou’s findings from mouse models strongly support an inflammation- and dysplasia-suppressive function of epithelial Notch/HES1 signaling. But malfunctions may lead to the development and/or progression of colorectal cancer. The investigators aim to determine how this transformation occurs and how it is enhanced by pro-inflammatory activity in the body. Inflammation is a known risk factor for developing many diseases, including colorectal cancer.

The approaches they will draw on include the use of organoid culture (3D mouse cell aggregates that function like organs); network bioinformatics analysis; assessment of microorganisms such as bacteria by deep gene-sequencing (sequencing a genomic area up to thousands of times to profile the microbial community).

Zhou previously reported that expression of HES1 is lost in 92 percent of serrated pre-cancer lesions (as well as being a prominent feature of irritable bowel disease-associated serrated lesions), whereas its expression in normal colon tissue and in benign polyps remains intact. “Our hypothesis is that HES1-loss disrupts epithelial homeostasis and causes increased inflammation that promotes transformation of serrated adenocarcinoma,” said Zhou. The research team will aim to describe how this process operates both singularly and in interaction with interleukin-1 beta, a protein that initiates and propagates inflammation. Blocking it may prevent or suppress tumor development and progression.

“At the end of this study, we will gain a deeper and broader understanding of the mechanism by which epithelial HES1-loss disrupts epithelial homeostasis and orchestrates a pro-inflammatory and pro-carcinogenic microenvironment,” said Zhou. “We hope our findings will result in more effective and targeted preventive treatments for a subset of colorectal cancer.”

Among cancers affecting both men and women, colorectal cancer is the second leading cause of cancer-related deaths in the United States. It is the third most common cancer in both men and women. Worldwide rates for colorectal cancer are similar. Surgery, combined with chemotherapy, is the conventional treatment, although resistance to chemotherapy is common in advanced cases.

“The high death rate of advanced colorectal cancer is attributable to limited treatment options,” added Zhou. “In the search for better therapeutic options, malfunctioning Notch/HES1 signaling has emerged as a potential target and a potential source of hope for a subgroup of patients with this terrible disease.”

Source:

http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1454&news_category=8

Tagged with:

About author

Related Articles