UTSW Research: Improved bladder cancer detection, tracking gamma waves, and more

Blue light improves bladder cancer detection across races

White light cystoscopy (WLC) – a procedure in which doctors illuminate a patient’s bladder with a white light and peer into it with a tiny camera – has long been a gold standard for diagnosing bladder cancer, the sixth most common cancer diagnosis in the U.S. Blue light cystoscopy (BLC), a related procedure that uses a blue light to activate a drug that makes bladder tumors fluoresce, has improved bladder cancer diagnosis in several clinical trials. However, because most patients in these trials were Caucasian, it has been unclear whether this diagnostic improvement applied to all races. Using data from nearly 1,300 Caucasian, African American, Asian, and Hispanic patients with suspected bladder cancer from multiple medical institutions, a team that included UT Southwestern reported in Cancers that combining WLC with BLC improved diagnosis by an average of 10% across all races compared with WLC alone. Asian patients benefited the most from the combined technique’s ability to spot potential tumors, and Hispanic patients benefited the most from its ability to rule tumors out. These findings suggest that supplementing WLC with BLC helps improve bladder cancer diagnoses across races.

UTSW researcher Yair Lotan, M.D., Professor of Urology, Chief of Urologic Oncology, and a member of the Harold C. Simmons Comprehensive Cancer Center, contributed to the study. Dr. Lotan is a paid consultant for Photocure, the company that developed the fluorescent drug used with BLC.

Gamma waves distinguish goal-oriented movements

Movements guided by vision (such as touching an elevator button) and those guided by sensing the body’s position in space (such as reaching to scratch one’s face) are driven by different brain activity. Characterizing this activity has been a challenge. Researchers from UT Southwestern and other institutions report in the Journal of Neural Engineering that these movement types spark irregularities in brain waves called gamma oscillations in different parts of the brain. They monitored brain activity in patients who received an implant for deep brain stimulation as they repeatedly touched a clinician’s finger (visually guided) and their own chins (proprioception). In these tests, researchers found more gamma wave irregularities in the motor cortex during the visually guided movements and more irregularities in the posterior parietal cortex during proprioception movements. Monitoring gamma waves also helped them identify connections among brain regions involved in these movements.

UTSW researchers Nader Pouratian, M.D., Ph.D., Chair and Professor of Neurological Surgery and Investigator in the Peter O’Donnell Jr. Brain Institute, and Jeong Woo Choi, Ph.D., Senior Research Scientist, contributed to the study.

Giving abnormal bone formation a closer look

The inappropriate formation of bone within muscle, tendon, and other soft tissues, called heterotopic ossification (HO), is a common consequence of joint replacements and traumatic injuries. Although researchers have traced the origin of HO to aberrant transformation of stem cells known as mesenchymal progenitor cells (MPCs) led by a protein called HIF-1a, the molecular mechanism behind this phenomenon has been unclear. A team of scientists led by UTSW researchers shows in Bone Research that this transformation is caused by changes in the role MPCs play in organizing the extracellular matrix, a mixture of proteins and carbohydrates that surrounds cells and provides structural and biochemical support. By selectively deleting the gene for HIF-1a in MPCs, researchers determined that this protein appears to cause MPCs to consume more blood sugar. This increases the production of enzymes called PLOD2 and LOX involved in making collagen, the predominant component of the extracellular matrix. In addition to HIF-1a, PLOD2 and LOX could eventually serve as targets for drugs to prevent or treat HO.

UTSW researchers contributing to this study include Benjamin Levi, M.D., Associate Professor of Surgery and Division Chief of Burn, Trauma, Acute and Critical Care Surgery; Lin Xu, Ph.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health; Robert Tower, Ph.D., Assistant Professor of Surgery; Lei Guo, Ph.D., Computational Biologist; Senior Research Scientists Heeseog Kang, Ph.D., and Yuxiao Sun, Ph.D.; medical student Conan Juan; Research Assistants Ji Hae Choi and Michael Woodard; and Chase A. Pagani, graduate student researcher.

Dissecting the HIV-1 transcriptional circuitry

Developing a cure for HIV-1, the primary virus that causes AIDS, has been difficult due to the virus’s ability to lie dormant in T cells and its potential to reactivate. As reported in Viruses, researchers from UT Southwestern investigated transcription, a process necessary for HIV-1 to produce RNAs and proteins needed for viral reactivation and spread in cells. During reactivation, HIV-1 becomes transcribed, which has two layers of control. First, human proteins activate the virus (called the “host phase”), which leads to expression of the Tat protein, turning on the “viral phase” where Tat drives the high levels of transcription required to replicate and perpetuate infection. Because this process happens in a sequential feedback loop, it has been difficult to understand the contributions of either phase to HIV-1 reactivation, limiting therapeutic approaches. Researchers used CRISPR gene editing to create HIV-1 integrated T cell clones with mutations in the tat gene. By comparing them to paired control T cell clones, researchers teased apart molecular contributions from the host and viral phases of HIV-1 transcription. This study provides a novel tool that could lead to new drugs for treating HIV-1 more effectively.  

UTSW researchers contributing to the study include Usman Hyder, Ph.D., first author and a former graduate student; Ivan D’Orso, Ph.D., Professor of Microbiology; Ashutosh Shukla, Ph.D., Instructor of Internal Medicine; and Ashwini Challa, M.S., Research Associate.

About UT Southwestern Medical Center  

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.