Hyaluronic acid

只要 “冻结” 大脑中一种叫透明质酸（HA） 的分子，让它失去灵活性，就能让胶质母细胞瘤细胞从 “侵袭状态” 切换到 “休眠状态”，甚至破解术后复发的难题。 胶质母细胞瘤（GBM）是成人最凶险的恶性脑肿瘤，美国癌症协会数据显示其五年生存率仅 15%，而更残酷的是，患者中位生存期不足 15 个月——肿瘤像 “藤蔓” 一样通过脑血管和神经间隙扩散，即使手术切除主病灶，残留的癌细胞仍会在数月内复发，放疗和化疗也难以穿透大脑的保护屏障。 近日，剑桥大学团队在《Royal Society Open Science》发表突破性研究，终于找到阻止其扩散的关键：只要 “冻结” 大脑中一种叫透明质酸（HA） 的分子，让它失去灵活性，就能让胶质母细胞瘤细胞从 “侵袭状态” 切换到 “休眠状态”，甚至破解术后复发的难题。 透明质酸是大脑细胞外基质的 “主力成分”，在胶质母细胞瘤患者的肿瘤微环境中，其浓度比正常脑组织还高，且常伴随降解（透明质酸酶 HYAL2 过表达，与患者生存期负相关）。过去学界认为，低分子量透明质酸（LMW-HA，10-250 kDa）促进癌症进展，高分子量透明质酸（HMW-HA，>500 kDa）维持组织稳定，但总有例外——剑桥团队发现，真正决定癌细胞行为的不是 HA 的分子量，而是它的分子灵活性：就像钥匙需要能弯折才能插入锁孔，HA 只有具备足够灵活性，才能与癌细胞表面的CD44 受体结合，触发扩散信号。 不同高分子量透明质酸浓度下的癌球体的行为 为验证这一猜想，研究团队用三种细胞构建 3D 球状体模型（U251、U87 胶质母细胞瘤细胞，以及患者手术切除的 SP20 肿瘤起始细胞），分别放入不同浓度的 HMW-HA 凝胶中。 结果令人意外：2wt% 的 HMW-HA 凝胶中，所有细胞球在 4 天内就大量扩散，细胞长出细长的 “侵袭伪足”；而 5wt% 的 HMW-HA 凝胶中，仅少数细胞分散，且 6 周内毫无变化——癌细胞既不生长也不死亡，进入了休眠状态。更关键的是，在 viscosity（黏度）更低的普通培养基中，U87 细胞几乎不扩散，说明不是 “物理阻碍” 而是 HA 的特性决定扩散，推翻了 “低黏度利于迁移” 的猜想。 为弄清 HA 灵活性的作用，团队用核磁共振（NMR）光谱学追踪 HA 的分子运动：HMW-HA 要与 CD44 强结合，需要在数十纳秒内扭曲出特定构象（ backbone 波动幅度超 30°，才能契合 CD44 的结合域）。2wt% 的 HMW-HA 中，分子 entanglement（缠绕）少，能自由调整构象，NMR 显示其甲基和糖环的 ¹H 自旋 - 晶格弛豫时间（T₁）差异显著，证明有纳秒级灵活性；而 5wt% 的 HMW-HA 分子缠绕紧密，无法完成构象变化，T₁值一致，意味着无法与 CD44 有效结合。当用抗体阻断 CD44 后，2wt% 凝胶中的 U87 细胞迁移面积显著缩小，92 小时后差异达统计学意义，直接证实 CD44 是 HA 介导扩散的 “关键受体”。 进一步的蛋白质组分析揭开了背后的信号通路：2wt% HMW-HA 中，癌细胞的 “侵袭装备” 全面激活 ——fascin-1（稳定 actin 束）、filamin A/C（交联 actin）等侵袭伪足相关蛋白上调 2-200 倍，MMP2 和 MMP14（降解基质的蛋白酶）也显著增加，细胞形成 “集体迁移的细胞片”；而 5wt% HMW-HA 中，Notch-2 通路被激活，dynamin-2（内吞关键蛋白）、nicastrin（γ- 分泌酶组件）等蛋白表达升高，就像给癌细胞按下 “休眠键”，这与成年大脑中 Notch-2 维持神经干细胞静息的机制如出一辙。 为验证 “灵活性而非浓度” 是关键，团队合成了交联透明质酸（oxHA） ——给 HMW-HA 加上醛基，让它与细胞外基质蛋白交联，失去灵活性。即使是 2wt% 的 oxHA 与 HMW-HA 混合凝胶，U87 细胞也完全不扩散，且蛋白质表达与 5wt% HMW-HA 一致，均激活 Notch-2 通路。这说明只要 HA 失去灵活性，无论浓度高低，都能让癌细胞休眠。 这项研究还解答了临床一大困惑：为何胶质母细胞瘤常在术后复发？团队推测，手术引发的脑水肿会稀释脑组织中的 HA，原本紧密缠绕的 HMW-HA 变得松散、灵活，反而激活残留癌细胞的扩散信号。而新的治疗思路恰恰相反——不直接攻击癌细胞，而是 “改造其生存环境”：通过药物让 HA 交联、失去灵活性，或抑制 HA 的分子运动，就能让癌细胞休眠，避免扩散和复发。 目前，团队已在细胞模型中验证了这一策略的有效性，下一步计划在动物模型中测试，并探索可用于临床的 “HA 稳定剂”。正如研究负责人 Melinda Duer 教授所说：“我们不需要杀死癌细胞，只需改变它们周围的 HA 状态——当 HA 无法灵活结合 CD44，癌细胞就会放弃侵袭，乖乖进入休眠。” 这一发现不仅为胶质母细胞瘤带来新希望，还可能适用于乳腺癌、结直肠癌等依赖 HA 扩散的实体瘤，为 “靶向肿瘤微环境” 的治疗开辟了新方向。（生物谷Bioon.com） 参考文献： Uliana Bashtanova，Agne Kuraite，Rakesh Rajan, et al. Molecular flexibility of hyaluronic acid has a profound effect on invasion of cancer cells, Royal Society Open Science (2025). DOI:10.1098/rsos.251036

Innovative hyaluronic acid technology delivers enhanced control and precision, significantly lowering the risk of rectal toxicity during prostate radiation treatment.1-4Initial cases have now been performed in Japan. WAYNE, Pa., Aug. 19, 2025 (GLOBE NEWSWIRE) -- Teleflex Incorporated (NYSE: TFX), a leading global provider of medical technologies, today announced Barrigel™ rectal spacer is now available for purchase in Japan, effective immediately following regulatory approval, insurance coverage acceptance and appropriate use criteria issuance by Japanese academic societies. First cases commenced earlier this month following the approval from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for Barrigel™ rectal spacer, the first and only sculptable non-animal stabilized hyaluronic acid (NASHA) rectal spacer proven to significantly reduce radiation that reaches the rectum during prostate radiation therapy.1,5,6,7“Japan commercialization represents a key milestone in our global expansion strategy for the Barrigel™ rectal spacer,” said Liam Kelly, Chairman, President and CEO of Teleflex. “This launch supports our mission to offer the next-generation, NASHA rectal spacer that enables precise, symmetrical placement1,2,7—providing physicians with effective and proven control over the shape and placement of the implant.8 We remain committed to making Barrigel™ rectal spacer the standard of care for men undergoing prostate cancer radiation therapy.” In 2022, prostate cancer was the most common cancer among men in Japan, with 104,318 new cases—accounting for 18 percent of all cancer diagnoses nationwide.9 Barrigel™ rectal spacer is indicated for prostate cancer patients with T1-T3b disease.5 A U.S. clinical study found that 98 percent of men who were treated with Barrigel™ rectal spacer met the primary endpoint of achieving at least a 25 percent reduction in radiation to the rectum.1 Patients who met the primary endpoint averaged an 85 percent reduction in rectal V54 Gy radiation to the rectum, and Barrigel™ rectal spacer is proven superior in the reduction of acute and long-term Grade 1+ GI toxicity at 3 and 6 months compared to control.1,6Yoshiko Inoue, Teleflex Managing Director, Japan, said with the launch of Barrigel™ rectal spacer in Japan, more men will have access to a solution that helps minimize the rectal side effects of prostate cancer radiation therapy.1 “We’re proud to support this important advancement and remain committed to educating healthcare professionals on the value of rectal spacing and its adoption throughout Japan,” she said. Beginning in late May, training took place in Chiba, Japan under the direction of Dr. Jun Itami, who is among the top radiation oncologists in the country. “Barrigel™ rectal spacer is unique in that it does not impose time constraints during injection and offers excellent visibility under ultrasound1-4. This allows physicians to monitor the injection in real time and place the required amount precisely1,7 where needed for each individual patient,” said Dr. Itami. “As a result, a reliable distance between the prostate and rectum can be maintained, enabling safer and more robust radiation therapy planning, representing a new standard in rectal protection during radiation therapy1.” About Barrigel™ Rectal SpacerBarrigel™ rectal spacer is the first and only hyaluronic acid rectal spacer that separates the prostate from the rectum to protect the rectum during radiation therapy treatment for prostate cancer.1 Barrigel™ rectal spacer is made from Non-Animal Stabilized Hyaluronic Acid (NASHA).5 Hyaluronic acid is a substance naturally present in the human body and is highly biocompatible and fully absorbable. NASHA has a proven history of safety and efficacy in a wide variety of medical applications in men, women and children worldwide.2,10 Barrigel™ rectal spacer has been proven to significantly reduce unwanted side effects from prostate cancer radiation therapy1 and is cleared for rectal spacing in the United States, Australia, Europe and Japan.11 Barrigel™ rectal spacer is indicated for prostate cancer patients with T1-T3b disease.5 For more information about Barrigel™ rectal spacer, please visit https://barrigel.com/hcp/barrigel-control-matters. Barrigel™ Rectal Spacer Important Safety InformationBarrigel™ rectal spacer is intended to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer and, in creating this space, it is the intent of Barrigel™ rectal spacer to reduce the radiation dose delivered to the anterior rectum. Barrigel™ rectal spacer is composed of biodegradable material and maintains space for the entire course of prostate radiotherapy treatment and is intended to be absorbed by the patient’s body over time.Barrigel™ rectal spacer should only be administered by qualified and properly trained physicians with experience in ultrasound guidance and injection techniques in the urogenital/pelvic area.As with any medical treatment, there are some risks involved with the use of Barrigel™ rectal spacer. Potential complications associated with the use of Barrigel™ rectal spacer include, but are not limited to: pain associated with Barrigel™ rectal spacer injection; needle penetration of the bladder, prostate, rectal wall, rectum, or urethra; injection of Barrigel™ rectal spacer into the bladder, prostate, rectal wall, rectum, urethra, or intravascularly; local inflammatory reactions; infection; urinary retention; rectal mucosal damage, ulcers, necrosis; bleeding; constipation; and rectal urgency. More information on indications, contraindications, warnings and instructions for use can be found in the Instructions For Use at www.barrigel.com. Caution: Federal (USA) law restricts this device to sale by or on the order of a physician. About Teleflex Incorporated As a global provider of medical technologies, Teleflex is driven by our purpose to improve the health and quality of people’s lives. Through our vision to become the most trusted partner in healthcare, we offer a diverse portfolio with solutions in the therapy areas of anesthesia, emergency medicine, interventional cardiology and radiology, surgical, vascular access, and urology. We believe that the potential of great people, purpose driven innovation, and world-class products can shape the future direction of healthcare. Teleflex is the home of Arrow™, Barrigel™, Deknatel™, LMA™, Pilling™, QuikClot™, Rüsch™, UroLift™ and Weck™ – trusted brands united by a common sense of purpose. At Teleflex, we are empowering the future of healthcare. For more information, please visit teleflex.com. Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements. Any forward-looking statements contained herein are based on our management’s current beliefs and expectations, but are subject to a number of risks, uncertainties and changes in circumstances, which may cause actual results or company actions to differ materially from what is expressed or implied by these statements. These risks and uncertainties are identified and described in more detail in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K. Teleflex, the Teleflex logo, Arrow, Barrigel, Deknatel, LMA, Pilling, QuikClot, Rüsch, UroLift, and Weck are trademarks or registered trademarks of Teleflex Incorporated or its affiliates, in the U.S. and/or other countries. All other trademarks are the property of their respective owners. © 2025 Teleflex Incorporated. All rights reserved. *Study sponsored by Palette Life Sciences, now part of Teleflex** Data from the Barrigel Pivotal Study analyzed using the same methodology as the Fischer-Valuck study***Drs Gejerman, Chao, Lederer, and Orio are paid consultants of Palette Life Sciences, now part of Teleflex. References Mariados NF, Orio PF III, King MT et al. JAMA Oncol (2023).*Svatos M, Chell E, King MT et al. Med Phys (2024).*Gejerman G, Goldstein MM, Chao M et al. Pract Radiat Oncol (2023).***Williams J, Mc Millan K, Chao M et al. J Med Imag Radiat Sci (2022).Japan Injectable Gel Instructions for Use (2025)Data on file. As of 4/01/2025.King MT, Svatos M, Orio PF III et al. Pract Radiat Oncol (2023).*Fischer-Valuck BW, Chundury A, Gay H, Bosch W, Michalski J. Hydrogel spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: Impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall. Pract Radiat Oncol. 2017;7(3):195-202.**Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer.Restylane® celebrates 25 years of natural-looking results with its signature line of hyaluronic acid fillers. 2021.Data on file Teleflex. 2025 Contacts:TeleflexLawrence KeuschVice President, Investor Relations and Strategy Developmentinvestor.relations@teleflex.com610-948-2836 Media ContactGlenn SilverFINN Partners National Media Relations Specialistglenn.silver@finnpartners.com646-871-8485 APM1275