WNK1

Research on breast, colorectal, head and neck, and testicular cancersNovel downregulation of WNK1 and Wnt signaling KNOXVILLE, TN, April 18, 2024 (GLOBE NEWSWIRE) -- Provectus Biopharmaceuticals, Inc. (“Provectus” or the “Company”) (OTCQB: PVCT) today announced that data from preclinical research by the University of Calgary on oral administration of Provectus’s pharmaceutical-grade rose bengal for the treatments of solid tumor cancers were published in the open access journal of oncology Cancers. Titled Identification and In Vivo Validation of Unique Anti-Oncogenic Mechanisms Involving Protein Kinase Signaling and Autophagy Mediated by the Investigational Agent PV-10, a copy of the University of Calgary’s journal article is available here: https://www.mdpi.com/2072-6694/16/8/1520. This work has been part of research conducted by Aru Narendran, M.D., Ph.D., professor in the departments of Pediatrics, Oncology, and Biochemistry & Molecular Biology, and members of the Narendran Lab at the University of Calgary’s Cumming School of Medicine in Calgary, Alberta, Canada. The Narendran Lab provided preclinical proof-of-concept data supporting the efficacy of Provectus’s rose bengal in a panel of adult solid tumors. The Lab identified that the Company’s rose bengal downregulated WNK1 and Wnt signaling. In mice, the Narendran Lab also confirmed the clinical utility of Provectus’s rose bengal by intratumoral (aka intralesional) administration and demonstrated potential utility by oral administration. Dominic Rodrigues, the Company’s President and Vice Chairman of its Board of Directors stated, “Provectus is focused on initiating an FDA-cleared, lead clinical development program for intratumoral cancer immunotherapy PV-10 to treat hepatic metastatic pancreatic cancer, and pursuing a path to an initial drug approval for PV-10. The Company previously demonstrated its systemic response and systemic immune signaling and activation in clinical settings for metastatic liver cancers.” Mr. Rodrigues added, “Building on PV-10’s clinical safety, efficacy, and immunotherapeutic profile, the Narendran Lab’s preclinical data suggest that Provectus’s pharmaceutical-grade rose bengal delivered by oral administration may have the potential to treat a larger pool of solid tumor cancers.” About Provectus Provectus Biopharmaceuticals, Inc. is a clinical-stage biotechnology company developing immunotherapy medicines for different diseases that are based on a class of synthetic small molecule immuno-catalysts called halogenated xanthenes. Provectus’s lead HX molecule is named rose bengal sodium. Provectus’s medical science platform includes clinical development programs in oncology, dermatology, and ophthalmology; proof-of-concept in vivo development programs in oncology, hematology, full-thickness cutaneous wound healing, and canine cancers; and in vitro discovery programs in infectious diseases, tissue regeneration and repair, and proprietary targets. Information about the Company’s clinical trials can be found at the National Institutes of Health (NIH) registry, ClinicalTrials.gov. For additional information about Provectus, please visit the Company’s website at www.provectusbio.com. FORWARD-LOOKING STATEMENTS: The information provided in this press release may include forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, relating to the business of Provectus and its affiliates, which are based on currently available information and current assumptions, expectations, and projections about future events and are subject to a variety of risks and uncertainties and other factors that could cause actual events or results to differ materially from those projected in the forward-looking statements. Such statements are made in reliance on the safe harbor provisions of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are often, but not always, identified by the use of words such as “aim,” “likely,” “outlook,” “seek,” “anticipate,” “budget,” “plan,” “continue,” “estimate,” “expect,” “forecast,” “may,” “will,” “would,” “project,” “projection,” “predict,” “potential,” “targeting,” “intend,” “can,” “could,” “might,” “should,” “believe,” and similar words suggesting future outcomes or statements regarding an outlook. The safety and efficacy of Provectus’s drug agents and/or their uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated or that such agents as products will achieve any revenue levels. Due to the risks, uncertainties, and assumptions inherent in forward-looking statements, readers should not place undue reliance on these forward-looking statements. The forward-looking statements contained in this press release are made as of the date hereof or as of the date specifically specified herein, and the Company undertakes no obligation to update or revise any forward-looking statements, whether because of new information, future events, or otherwise, except in accordance with applicable securities laws. The forward-looking statements are expressly qualified by this cautionary statement. Risks, uncertainties, and assumptions include those discussed in the Company’s filings with the Securities and Exchange Commission, including those described in Item 1A of: The Company’s Annual Report on Form 10-K for the period ended December 31, 2023. ##### Contact: Provectus Biopharmaceuticals, Inc.Heather Raines, CPAChief Financial OfficerPhone: (866) 594-5999

Researchers have shown that an influx of water and ions into immune cells allows them to migrate to where they're needed in the body.   Researchers at the Francis Crick Institute, working with Imperial College London, King's College London and University of Cambridge, have shown that an influx of water and ions into immune cells allows them to migrate to where they're needed in the body. Our bodies respond to illness by sending out chemical signals called chemokines, which tell immune cells called T cells where to go to fight the infection. This process had already been associated with a protein called WNK1, which activates channels on the cell surface, allowing ions (salts like sodium or potassium) to move into cells. Until now, it was not clear why ion influx was needed for T cells to move. Through a study published today in Nature Communications, the researchers imaged mouse T cells and observed that, following a chemokine signal, WNK1 is activated at the front of the cells, called the 'leading edge'. The team showed that the activation of WNK1 opens channels on the leading edge, resulting in an influx of water and ions. They propose that this flow of water causes the cells to swell on the front side, creating space for the 'actin cytoskeleton' -- the scaffolding inside the cell which holds its structure -- to grow into. This propels the whole cell forwards and the process repeats again. The researchers used gene editing to stop mice producing WNK1, or an inhibitor to prevent WNK1's activity, observing that the T cells in these mice slowed down or stopped moving completely. Importantly, they found that they could make up for the loss of WNK1 and make the cells speed up by dropping them into a watery solution, which causes the cells to take up water and swell. This shows that the uptake of water, controlled by the WNK1 protein is key for the cells to migrate. The researchers believe that the mechanism they've discovered could be involved in lots of different cell types beyond immune cells. Victor Tybulewicz, Group Leader of the Immune Cell Biology Laboratory & Down Syndrome Laboratory at the Crick, said: "Through this research, we've unravelled one of the mysteries of T cell movement, showing that WKN1 causes water and ions to flow into T cells, giving them the space to grow their scaffolding and move forward. Although we looked at T cells, it's likely that this process is happening in many of our cells and even in diseases like cancer, which is important as when cancer cells spread, it is harder to treat." Leon de Boer, former postdoctoral researcher at the Crick and now at the Karolinska Institute in Sweden, said: "This process has been speculated about for decades, but advances in technology have finally allowed us to show how WNK1 helps T cells migrate around the body -- water comes in almost like a jet engine moving the cell forward. I am excited that researchers are starting to investigate WNK1 inhibitors to treat diseases like cancer. In my new project, I'm looking at how properties of membranes help cancer cells to move around the body."