Tag: kidney cancer

Categories : Cancer Metabolic DisordersTags :

Do Lifetime Body Weight Patterns Affect the Risk of Kidney Cancer?

On By ModernMedia

Study links higher body mass index at various ages across adulthood with greater risks of developing different types of kidney cancer.

Photo by I Yunmai on Unsplash

Excess weight in mid-life is a known risk factor for kidney cancer, but new research indicates that weight patterns throughout life may also affect an individual’s likelihood of developing this malignancy. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

To assess weight patterns and their associations with kidney cancer and its different subtypes, investigators analysed data from 204 364 individuals from the NIH-AARP Diet and Health Study, including body mass index (BMI) data when participants entered the study (an average age of 61.6 years), and prior BMI recordings at 18, 35, and 50 years of age. The team noted that there were 1,425 cases of kidney cancer, or renal cell carcinoma (RCC), among the study’s participants, with 583 having aggressive RCC and 339 having fatal RCC. The researchers also recorded the different subtypes of RCC, including clear cell RCC (541 patients), papillary RCC (146 patients), and chromophobe RCC (64 patients).

Higher BMI at any of the ages assessed was linked with higher risks of overall RCC and all subtypes (except chromophobe RCC), with a 10-40% higher risk for each 5-unit increase in BMI. Similar increased risks were linked to weight gain during adulthood that resulted in overweight or obesity, compared with maintaining normal BMI.

Also, long-term excess weight was associated with higher risks of overall RCC, aggressive RCC, fatal RCC, and clear cell RCC, but not papillary RCC and chromophobe RCC. Weight loss in which BMI was reduced by at least 10%, particularly later in life, was associated with a lower risk of RCC. Specifically, weight loss from age 18–35 years and after age 50 years was associated with 21% and 28% reductions in RCC incidence, respectively.

“These findings emphasise that maintaining a healthy weight across one’s lifetime is important for reducing RCC risk. More importantly, weight loss, even later in life, may offer protective benefits,” said lead author Zhengyi Deng, PhD, of Stanford University School of Medicine. “We should support initiatives that promote healthy weight maintenance and weight loss strategies. Some of these include lifestyle interventions, weight-loss programs, and emerging medical treatments for obesity; however, individuals should consult with their healthcare providers prior to initiation of any plan.” 

Source: Wiley

Categories : CancerTags :

Topping up Mitochondrial Content to Fight Kidney Cancer

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Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Researchers at Karolinska Institutet in Sweden have linked resistance to treatment for VHL syndrome-induced kidney cancer to low mitochondrial content in the cell. When the researchers increased the mitochondrial content with an inhibitor, the cancer cells responded to the treatment. Their findings, which are published in Nature Metabolism, may lead to more targeted cancer drugs.

Mitochondria are the most oxygen-demanding component of the cell, but it was not known how mitochondria adapt in a low-oxygen environment and how they are linked to cancer therapy resistance.

“We’ve shown for the first time how the formation of new mitochondria is regulated in cells that lack oxygen and how this process is altered in cancer cells with VHL mutations,” explained Associate Professor Susanne Schlisio, group leader at the Karolinska Institutet.

A gene called von Hippel-Lindau (VHL) prevents healthy cells from turning cancerous. The 2019 Nobel Prize in Physiology or Medicine was awarded to the discovery that VHL was part of the cell’s oxygen detection system. Normally, VHL breaks down another protein called HIF – but when VHL is mutated, HIF accumulates and causes a disease called VHL syndrome in which the cells react as if they were lacking oxygen. This syndrome greatly increases the risk of tumours, both benign and malignant. VHL syndrome-induced kidney cancer has a poor prognosis, with a five-year survival rate of just 12%.

Researchers analysed the protein content of cancer cells from patients with different variants of VHL syndrome, to see how they differed from another group of individuals with a special VHL mutation called Chuvash, a mutation involved in hypoxia-sensing disorders without any tumour development. Those with the Chuvash VHL-mutation had normal mitochondria in their cells, while those with VHL syndrome mutation had few.

To increase the amount of mitochondrial content in VHL related kidney cancer cells, the researchers treated these tumours with an inhibitor of a mitochondrial protease called “LONP1.” This resulted in the cells becoming susceptible to the cancer drug sorafenib, which they had previously resisted. In mouse studies, this combination treatment led to reduced tumour growth.

The study’s first author Shuijie Li, postdoctoral researcher in the Schlisio’s group, suggested that the findings could be applied to more than just VHF syndromic kidney cancers.

“We hope that this new knowledge will pave the way for more specific LONP1 protease inhibitors to treat VHL-related clear cell kidney cancer,” Dr Li said. “Our finding can be linked to all VHL syndromic cancers, such as the neuroendocrine tumours pheochromocytoma and paraganglioma, and not just kidney cancer.”

Source: Karolinska Institutet

Categories : CancerTags :

New Insights into How Kidney Cancer Cells Respond to Treatment

On By ModernMedia
Photo by National Cancer Institute on Unsplash

Researchers from the University of Michigan Rogel Cancer Center have uncovered clues as to why kidney cancers respond so differently to treatment, opening up new tailored treatment options.

Not all kidney cancers behave the same, and some have wildly differing responses to immunotherapy or other treatments – resulting in wildly different outcomes for patients.

By sequencing the RNA of individual cells within multiple benign and cancerous kidney tumors, the researchers have identified the cells from which different subtypes of kidney cancer originate, the pathways involved and how the tumor microenvironment impacts cancer development and response to treatment.

The findings, published in PNAS, could help researchers better understand renal cell carcinoma development and guide oncologists in optimising therapies for each patient.

“Single cell RNA sequencing was key to allowing us to monitor gene expression patterns in each individual cell, revealing the mechanisms at play within the tumour microenvironment that can predict overall survival,” says study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology and SP Hicks Professor of Pathology at Michigan Medicine.

Researchers produced gene expression atlases for normal kidney and renal cell carcinoma samples. They predicted the putative cell of origin for more than 10 subtypes of renal cell cancer. Their analysis also uncovered pathways and interactions within the tumour microenvironment that predicted if the tumour would respond to immunotherapy. These findings could help develop biomarkers to guide kidney cancer treatment.

“By understanding the cell type where a cancer originates, it may allow us to target more precise treatments for that cancer type as well as better understand response to therapy,” Dr Chinnaiyan said.

Source: University of Michigan

Journal information: “Single-cell analyses of renal cell cancers reveal insights into tumor microenvironment, cell of origin, and therapy response,” PNAS. DOI: 10.1073/pnas.2103240118