A City of Hope scientist and his colleagues have developed a user-friendly approach to creating “theranostics” – therapy combined with diagnostics – that target specific tumours and diseases.
Key to the process are molecules called metallocorroles, which serve as versatile platforms for the development of drugs and imaging agents. City of Hope’s John Termini, Ph.D., and his colleagues at the California Institute of Technology and the Israel Institute of Technology developed a novel method to prepare cell-penetrating nanoparticles called “metallocorrole/protein nanoparticles.” The theranostics could both survive longer in the body and better snipe disease targets.
The study details a unique way the researchers prepared the theranostics that may be generalizable to many similar molecules.
“Through collaborative brainpower, we were able to create something that has huge chemotherapeutic potential,” Termini said. “Down the road, theranostics such as this could shorten treatment duration and diminish the dreaded side effects so many cancer patients fear.”
City of Hope https://tinyurl.com/y67c26em

A new study confirms the long-suspected role of obesity as a risk factor for developing renal cell carcinoma (RCC), a type of kidney cancer, and identifies several specific obesity-related factors.
These factors include multiple measures of obesity, diastolic blood pressure and fasting insulin. In contrast, the study found little evidence for an association with RCC risk for systolic blood pressure, circulating lipids, diabetes or fasting glucose.
“This study provided robust and confirmatory evidence of the important role of obesity and diastolic blood pressure as important risk factors of RCC and novel evidence of an important role of circulating insulin in the disease’s etiology,” said Spectrum Health urologist Richard Kahnoski, MD. “But further research is needed to fully understand these important relationships.”
Renal cell carcinoma is also known as hypernephroma, renal cell cancer and renal cell adenocarcinoma. According to the National Cancer Institute, in 2018 it was estimated that there were 65,340 new cases of kidney and renal pelvis cancer in the U.S. and an estimated 14,970 people died of the disease. Kidney and renal pelvis cancer are the 8th most common cancer type in the U.S., representing 3.8% of all new cancer cases.
The development of RCC has not been fully understood by researchers. An increased risk for the disease has been observed for individuals with high body mass index (BMI), and elevated blood pressure and triglycerides.  However, traditional observational studies are subject to confounding and reverse causation errors. This study used an alternative methodology commonly referred to as mendelian randomization, which allows researchers to test for a causal effect from observational data in the presence of confounding factors.
“These obesity-related factors are inherently interrelated, and traditional observational studies have not been able to determine which individual factors directly influence RCC risk and which are merely correlated with the underlying causal factor,” said Brian Lane, MD, PhD, a board-certified urologist and Betz Family Endowed Chair for Cancer Research at Spectrum Health.
“Mendelian randomization allows us to circumvent many of the limitations of traditional observational study by use of genetic proxies of suspected risk factors.”
Lane, along with Kahnoski and colleague Sabrina Noyes, provided investigative and methodological input into the study, which evaluated genetic markers from multiple centres in a genome-wide association study of 10,784 RCC patients and 20,406 control participants. The markers included obesity measures, blood pressure, lipids, type 2 diabetes, insulin and glucose, which were initially identified as instrumental variables.
Spectrum Health https://tinyurl.com/y2ac73md

A research team, led by investigators from Georgetown University Medical Center and Fudan University in China, has devised a very promising non-invasive and individualized technique for detecting and treating bladder cancer.
The method uses a “liquid biopsy” — a urine specimen — instead of the invasive tumour sampling needed today, and a method developed and patented by Georgetown to culture cancer cells that can reveal the molecular underpinnings of each patient’s unique bladder cancer.
Their study sets forth a cost-friendly, simpler and painless technique that can determine the best treatment for each person’s bladder tumour, monitor the progress of that treatment, predict or detect cancer recurrence early, and identify new drugs that are sorely needed for this common cancer.
“This is the first study to show, using patient samples, that a ‘living liquid biopsy’ from urine can help determine treatment. This work also suggests that we might be able to grow and test cancer cells for treatment from other ‘living biomarkers’ found in blood and saliva. We are just at the beginning of this new diagnostic innovation,” says study co-senior author Xuefeng Liu, MD, professor of pathology and oncology and member of the Center for Cell Reprogramming at Georgetown University and Georgetown Lombardi Comprehensive Cancer Center.
The ability to use a patient’s urine to grow cells is a transformational innovation from Georgetown called “conditional reprogramming,” or CR. Patient-derived cells using CR can grow indefinitely without genetic manipulation, says Liu. Before this technique, which is less than a decade old, normal cells could not grow in lab culture, and cancer cells acquired numerous genetic mutations using previous culturing techniques.
“The analysis of the mutation ratio for both patient tissue and corresponding CRC confirmed that both single nucleotide variants and DNA insertions and deletions were retained during the culturing,” says Liu.
This means that a patient’s urine produced cancer cells that molecularly matched their cancer tissue sample. “We also identified some mutations not identified in the original tumour biopsies, suggesting that the urine cell cultures better reflect overall tumour diversity than a single biopsy,” he says. “The CRC technique may also expand our understanding of how low frequency mutations help lead to bladder cancer development and progression. Overall, CRC cultures may identify new actionable drug targets and help explain why this cancer is so often resistant to treatment.”
After determining that the urine colonies and tumour tissue samples had matching molecular characteristics and genetic alterations, the researchers tested urine-based CRC cancer cells with 64 clinical oncology drugs. They found that, overall, the urine-based cancer cells were resistant to more than half of the drugs. And they discovered that many of the urine cancer cells were highly sensitive to one of the drugs, bortezomib, which is currently being tested for a different genitourinary tumour, urothelial cancer.
Georgetown University Medical Center https://tinyurl.com/y46httzz

Researchers have demonstrated that an optical technique known as Raman spectroscopy can be used to differentiate between benign and cancerous thyroid cells. The new study shows Raman spectroscopy’s potential as a tool to improve the diagnosis of thyroid cancer, which is the ninth most common cancer with more than 50,000 new cases diagnosed in the United States each year.
“Our encouraging results show that Raman spectroscopy could be developed into a new optical modality that can help avoid invasive procedures used to diagnose thyroid cancer by providing biochemical information that isn’t currently accessible,” said James W. Chan from the University of California, Davis, U.S.A. “This could have a major impact in the field of pathology and could lead to new ways to diagnose other diseases.”
A lump — or nodule — in the neck is a common symptom of thyroid cancer. However, most thyroid nodules aren’t cancerous. Ultrasound-guided fine needle aspiration biopsies are typically used to check for cancer by inserting a thin needle into the nodule to obtain cells that are prepared on a microscope slide, stained and analysed by a pathologist. For about 15 to 30 percent of cases, the pathologist cannot determine whether cells acquired from the biopsy are benign or malignant. For these cases, a surgical procedure known as a thyroidectomy is required to remove tissue, which provides more information for a more accurate diagnosis. The researchers turned to Raman spectroscopy as a possible solution because it is a non-invasive technique that requires no sample preparation or staining to determine subtle differences in the molecular composition of complex samples such as cells.
“We would like to use Raman spectroscopy to improve the pathologist’s analysis of the cells obtained with fine needle aspiration to reduce the number of thyroidectomies necessary,” said Chan. “This would both minimize surgical complications and reduce healthcare costs.”
For the new study, the researchers used a line-scan Raman microscope that allowed them to rapidly acquire Raman signals from an entire cell volume. This allowed them to more accurately capture the chemical composition of entire cells compared to other approaches that acquire a Raman spectrum from only part of a cell’s volume. Multivariate statistical methods and classification methods were then used to analyse the Raman data and classify the cells in an objective, unbiased manner.
The researchers applied this Raman spectroscopy approach to individual cells isolated from 10 patient thyroid nodules diagnosed as benign or cancerous. The data analysis identified unique spectral differences that could distinguish cancerous cells from benign with 97 percent diagnostic accuracy. They also showed that other subtypes could be identified by their spectral differences.
“These preliminary results are exciting because they involve single cells from human clinical samples, but more work will need to be done to take this from a research project to final clinical use,” said Chan.
The Optical Society (OSA) https://tinyurl.com/y6hw35z8

Randox Laboratories recently announced its achievement in being awarded the Manufacturer Certification by the National Glycohemoglobin Standardization Program (NGSP) for direct HbA1c testing on three of its clinical chemistry analysers: the RX modena, RX imola and RX daytona+.

NGSP is recommended for laboratories conducting diabetes-related clinical trials and is only granted on the basis of 98% accuracy. With the global prevalence of diabetes mellitus increasing rapidly, affecting roughly 8% of the total population, the achievement of this certification emphasizes that the Randox RX series clinical chemistry analysers correlate with global standards and deliver accurate, reliable and precise results for direct HbA1c testing, helping clinicians make informed decisions for patients with diabetes.

The Randox automated immunoturbidmetric HbA1c test exhibits high accuracy and reproducibility with the added advantages of using liquid reagents with good stability, and on-board pre-treatment of samples; therefore, offering an improved method for the rapid direct measurement of HbA1c in human blood.

Randox Direct HbA1c assay features
· Sample type – suitable for use with whole blood samples
· Latex enhanced immunoassay method – the Randox assay utilizes an immunoassay method making it simple and quick to perform
· Liquid ready to use reagents – for ease of use and convenience
· Excellent stability – all reagents are stable to expiry date when stored at +2-8ºC or 28 days on board the analyser at approximately 10°C

Advantages of the RX series direct HbA1c testing
· Fully automated on-board hemolysis function for HbA1c testing
· Continuous loading and STAT sample functionality to enhance productivity in the laboratory (analyser dependent)
· Low sample volumes required
· 1200 tests per hour including ISE (RX modena)

www.randox.com