Drug for pulmonary hypertension may become an option against cancer - EurekAlert
Drug for pulmonary hypertension may become an option against cancer - EurekAlert |
| Drug for pulmonary hypertension may become an option against cancer - EurekAlert Posted: 15 Dec 2020 08:16 AM PST  By André Julião | Agência FAPESP - A drug used to treat pulmonary hypertension significantly reduced the capacity of tumor cells to migrate and invade other tissues in trials involving pancreatic, ovarian, breast cancer, and leukemia cell lines. Furthermore, in mice with an aggressive form of breast cancer, the drug reduced the incidence of metastasis in the liver and lungs by 47% and lengthened survival compared with untreated animals. The study is published in Scientific Reports. "The drug ambrisentan is an inhibitor of the endothelin type A receptor, which is known to play a role in vasoconstriction, so the drug is used to treat pulmonary hypertension [typically caused by autoimmune diseases such as lupus and systemic sclerosis]. In the laboratory, we found that the drug prevented migration of tumor cells to other tissues and had other effects we're still investigating," said Otávio Cabral Marques, a researcher at the University of São Paulo's Biomedical Sciences Institute (ICB-USP) in Brazil and principal investigator for the study, which was funded by FAPESP. Marques conducted the study while he was a postdoctoral fellow at the University of Freiburg in Germany, collaborating with researchers there and in the United Arab Emirates. He is currently principal investigator for a project supported by FAPESP via a Young Investigator Grant. Endothelin type A receptor is expressed in endothelium, the layer of cells that line the inner surface of blood vessels, and in the cells of the immune system. Other research has also shown its involvement in tumor growth and metastasis. "The effects of the drug appear not to be confined to preventing tumor cell migration, but also to include inhibition of neoangiogenesis, the formation of new blood vessels required to sustain tumor growth," Marques said. "We're currently doing experiments to confirm this. If so, the drug must have a systemic effect, preventing tumor migration to other tissues and inhibiting tumor growth by blocking the generation of new vessels." The drug's benefits in cancer treatment have yet to be proven. Its use without a physician's guidance can be harmful to health, especially in pregnancy. Experiments Using special techniques to measure cell migration, the researchers found that the drug significantly reduced both migration of tumor cells that received a stimulus and spontaneous migration. They tested ovarian, pancreatic, breast and leukemia cancer cell lines. Next, 4T1 cells derived from the mammary gland tissue of a mouse strain were injected into mice to mimic the initial stage of an aggressive form of breast cancer in humans. The mice were treated with the drug for two weeks before the injection and another two weeks afterward. In this experiment, the drug reduced metastasis by about 43% and enhanced median survival by about 30%. "Metastasis of 4T1 cells is very fast in mice, so we began treatment earlier in order to approximate what happens in humans," Marques explained. Marques is now preparing to perform clinical trials with other researchers at ICB-USP. The drug will be tested on a group of cancer patients undergoing chemotherapy to see if they recover better than the control group that will not be given the drug. Although the drug can be administered by mouth, which is an advantage, Marques wants to test applying it directly to the tumor in order to enhance its effect. The type of cancer on which it will be tested has not yet been decided. ### About São Paulo Research Foundation (FAPESP) The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www. Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.  |
| Posted: 14 Dec 2020 12:00 AM PST  Transthoracic echocardiography (TTE) may overestimate pulmonary artery pressure (PAP) compared with right heart catheterization, particularly in women with hypertension and arrhythmia, as well as in patients receiving diuretic treatment. This is according to a study published in Heart, Lung and Circulation. This retrospective, observational study included 141 consecutive patients with suspected or confirmed pulmonary hypertension from a single center. The mean age of the population was 63.6±11.5 years, and the majority were women (n=84). All patients included in the study underwent TTE and subsequent right heart catheterization within 3 hours. The investigators assessed the correlation between TTE and right heart catheterization in their ability to estimate systolic PAP (SPAP) and mean PAP (MPAP). Out of the 124 patients who were eligible for the study, 106 patients had pulmonary hypertension diagnosed at right heart catheterization. Investigators found a moderate correlation between both SPAP (r=0.65) and MPAP (r=0.60) estimated by TTE in those assessed by right heart catheterization. In the Bland-Altman analysis, there was a bias of -11.9 mmHg (95% limits of agreement, -45.4 to 121.5 mmHg) for SPAP estimation vs -4.6 mmHg (95% limits of agreement, -27.9 to 118.8 mmHg) for MPAP estimation. According to the researchers, this finding suggests a general overestimation of PAP using TTE. Continue Reading The researchers also noted that the primary factors that contributed to the discrepancies between right heart catheterization and TTE were female gender, arrhythmic cardiac electrical activity, systemic arterial hypertension, and diuretic treatment with furosemide. Limitations of the study included its retrospective nature, monocentric design, as well as the small number of patients in the final sample. While the investigators concluded that the echocardiographic method is a valid screening tool for classifying PAP, "the echocardiographic measurements cannot replace [right heart catheterization], and should always be verified through the invasive approach, especially when important clinical decisions are required for prognostic purposes." Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors' disclosures. Reference Sonaglioni A, Cassandro R, Luisi F, et al. Correlation between doppler echocardiography and right heart catheterisation-derived systolic and mean pulmonary artery pressures: Determinants of discrepancies between the two methods. Published online November 19, 2020. Heart Lung Circ. doi: 10.1016/j.hlc.2020.10.009  |
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