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点击上方蓝字 关注我们 编者按：激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）乳腺癌是乳腺癌中最常见的亚型之一，约占总体乳腺癌的70%。这类患者晚期一线治疗通常依赖于内分泌治疗联合CDK4/6抑制剂，尽管这一方案显著延长了患者的无进展生存期（PFS），但大部分患者最终会出现耐药，导致疾病进展。因此，寻找新的有效治疗策略，以延长患者的生存期并提高生活质量，成为医学界亟待解决的问题。近年来，随着分子生物学研究的深入，PAM（PI3K/AKT/mTOR）信号通路在乳腺癌发生发展中的重要性逐渐凸显，为HR+/HER2-晚期乳腺癌的治疗提供了新的靶点。肿瘤瞭望特邀重庆医科大学附属第一医院甘露教授从HR+/HER2-晚期乳腺癌的治疗现状与挑战、PAM通路的重要性、后CDK4/6抑制剂时代患者治疗新选择等方面，深入探讨HR+/HER2-晚期乳腺癌患者的未来之路。 一、HR+/HER2-晚期乳腺癌的治疗现状与挑战 乳腺癌是全球女性最常见的恶性肿瘤，2020年中国乳腺癌新发病例41.6万例，死亡病例约11.7万例。在每年新发乳腺癌患者中，约3%～10%的患者在确诊时即有远处转移。早期患者中约有30%可发展为晚期乳腺癌，晚期乳腺癌患者5年生存率仅为20%，中位总生存时间为2～3年[1]。HR+/HER2-乳腺癌约占总体乳腺癌的70%，内分泌治疗是其重要治疗选择[2]。PALOMA、MONARCH、MONALIEESA、DAWAN等一系列研究显示[3-7]，CDK4/6抑制剂（哌柏西利、阿贝西利、瑞波西利和达尔西利）联合内分泌治疗，能显著提高乳腺癌患者的治疗敏感性，延长患者的生存时间。目前CDK4/6抑制剂联合内分泌治疗已成为HR+/HER2-晚期乳腺癌（不合并内脏危象）患者的一线治疗优选方案。 CDK4/6抑制剂联合芳香化酶抑制剂（aromatase inhibitor, AI）的临床研究结果显示（MONALEESA-2研究、PALOMA-2研究、MONARCH-3研究和DAWNA-2），一线使用 CDK4/6抑制剂联合AI后无进展生存期（PFS）约为2年左右（各研究结果存在差异），与AI单药相比，CDK4/6抑制剂联合AI方案均显著降低疾病进展风险近50%[2]。但CDK4/6抑制剂失败后的治疗选择是临床治疗难题，国内外指南无标准治疗方案推荐，且既往多项研究显示，与PAM通路正常的乳腺癌患者相比，存在通路基因改变者肿瘤进展风险更高，DFS及OS更差。 二、PAM通路的重要性 磷脂酰肌醇3-激酶（phosphoinositide 3-kinase，PI3K）/蛋白激酶B（protein kinase，AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号转导通路（简称PAM通路）的过度活化广泛存在于各类癌种，包括乳腺癌、肺癌、头颈部肿瘤、子宫内膜癌、前列腺癌、结直肠癌等，调节肿瘤细胞存活、增殖、分化、凋亡等多种过程，从而对肿瘤的发生、发展起到关键性作用[8-9]。PAM信号通路过度激活是内分泌治疗、化疗、靶向治疗耐药的重要机制之一，不仅使乳腺癌细胞适应雌激素剥夺，通过多药耐药相关蛋白和抗凋亡作用促进化疗耐药，还通过激活PAM信号通路相关蛋白参与CDK4/6抑制剂和抗HER2治疗耐药的发生[10]。 尽管HR+/HER2-乳腺癌细胞对CDK4/6抑制剂耐药的机制多种多样，但PAM信号通路表达上调是常见的，在HR+乳腺癌中，约30%～40%的患者存在PAM信号通路被激活的现象[11]，因此，PAM信号通路可能成为逆转耐药性的重要靶点[12]。一项针对中国乳腺癌患者的研究显示，PAM通路突变率高达62.6%，高于欧美人群，其中PIK3CA突变率为45%，这些突变的数量和位置对患者的预后有显著影响[13]。 三、CDK4/6抑制剂后的新选择 在CDK4/6抑制剂联合内分泌治疗成为HR+/HER2-晚期乳腺癌一线治疗优选方案后，对于治疗进展后出现耐药的患者，医学界一直在探索新的治疗方案。目前，化疗仍是治疗选择之一，但仅能带来中位4～5个月的PFS[14-15]，且接受化疗的患者会出现众多不良反应，严重影响患者生活质量。针对CDK4/6抑制剂跨线治疗的探索由来已久，但目前仅有有限数据支持CDK4/6抑制剂跨线治疗，且只有postMONARCH这一项III期研究显示了PFS获益（6.0个月 vs 5.3个月）[16]。 PAM通路抑制剂的出现，为CDK4/6抑制剂耐药后的患者提供了新的治疗选择。PI3K位于PAM信号通路上游，在该通路中扮演着重要角色[17]。PIK3CA突变可以异常激活PI3K通路，促进肿瘤的增殖、转移和侵袭，因此，PI3K通路为治疗靶点成为了PIK3CA突变乳腺癌患者的重要治疗手段，这为PIK3CA突变型HR+/HER2-晚期乳腺癌患者带来新的治疗希望。多项研究显示了PI3K抑制剂可为PIK3CA突变人群带来更长的PFS获益，2024版NCCN指南推荐对于PIK3CA突变的HR+/HER2-绝经后乳腺癌患者，二线治疗首选PI3K抑制剂联合内分泌治疗（Ⅰ级推荐）。 AKT位于PAM通路的核心位置，其异常激活在乳腺癌的发生与发展中起着重要作用。AKT信号通路的激活可以通过多种机制实现，包括PIK3CA的激活突变、PTEN的失活突变以及上游信号通路的异常激活等。AKT一旦被激活，可磷酸化细胞核和细胞质中的许多靶点并激活多个具有调控细胞增殖功能的下游底物，从而促进肿瘤细胞生长、增殖和血管生成。此外，AKT通过抑制促凋亡基因Bcl-2家族成员BAD和BAX、负向调节FOXO等叉头转录因子等机制促进肿瘤细胞存活并抑制其凋亡[11]。AKT抑制剂相关研究正在大量开展中。 mTOR是PAM信号通路的关键下游效应分子，通过其两个不同的复合体mTORC1和mTORC2，调控多种细胞内过程。mTOR信号通路的异常激活在约30%的癌症中被发现,对肿瘤的发生、发展和转移起着重要的促进作用。mTOR过度激活会增加促癌蛋白的翻译，直接影响细胞生长、迁移和血管新生等过程。mTOR通过影响细胞周期、生长、存活和代谢等多个方面来促进肿瘤进展，在乳腺癌中，mTOR通路的异常在约70%的病例中被发现[18]。我国一项多中心回顾性研究数据显示，在CDK4/6抑制剂哌柏西利治疗进展后的HR/HER2-晚期乳腺癌患者中，应用内分泌治疗联合mTOR抑制剂依维莫司的患者中位PFS获益达5.1个月[19]。 四、未来展望 随着分子生物学研究的不断深入和精准医疗理念的逐渐普及，针对PAM通路的精准治疗为HR+/HER2-晚期乳腺癌患者带来了新的希望。通过检测PAM通路的突变状态，并结合患者的临床特征，临床医生可以为患者制定更加个体化的治疗方案。这不仅有助于延长患者的生存期，还能提高患者的生活质量。同时，NCCN、CSCO等国内外权威指南也将PI3K抑制剂、AKT抑制剂和mTOR抑制剂依维莫司纳入到了HR+/HER2-晚期乳腺癌患者的治疗药物推荐之中，但基于药物可及性及或内获批相关原因，目前在CSCO指南中对HR+晚期乳腺癌TAM治疗失败、非甾体类AI治疗失败及甾体类AI治疗失败的患者均II级推荐依维莫司联合内分泌治疗，而对于CDK4/6抑制剂治疗失败的患者，目前暂无I级推荐，在III级推荐中提及AKT抑制剂+内分泌治疗。 △2024版CSCO BC指南HR+晚期乳腺癌的解救内分泌治疗相关推荐* *指南内容涉及AZ未获批产品/适应症，阿斯利康不推荐任何未获批药品/适应症的使用。 未来，随着更多针对PAM信号通路抑制剂的研发和临床应用，HR+/HER2-晚期乳腺癌的治疗将更加精准和有效。同时，也期待更多的基础研究能够揭示PAM通路在乳腺癌发生与发展中的具体机制，为新药的研发提供理论依据，为HR+/HER2-晚期乳腺癌患者带来更多新的治疗希望。 甘露 教授 重庆医科大学附属第一医院 中国抗癌协会乳腺癌专业委员会常委 中国抗癌协会肿瘤临床研究管理学专委会常委 中国抗癌协会肿瘤科普防治专业委员会委员 中国抗癌协会肿瘤临床化疗专业委员会委员 重庆市抗癌协会肿瘤心理学专业委员会副主任委员 重庆市医学会乳腺病分会常委 重庆市肿瘤医疗质量控制中心乳腺癌诊疗专家组成员 审批编号CN-145761 过期日期 2025-10-18 *本材料由阿斯利康提供，仅供医疗卫生专业人士参考 参考文献 上下滑动查看更多内容 [1]、国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会乳腺癌专业委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. 中国晚期乳腺癌规范诊疗指南(2022版)[J]. 中华肿瘤杂志, 2022, 44(12):1262-1287.DOI: 10.3760/cma.j.cn112152-20221007-00680. [2]、国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. CDK4/6抑制剂治疗激素受体阳性人表皮生长因子受体2阴性乳腺癌临床应用专家共识(2023版)[J]. 中华肿瘤杂志, 2023, 45(12):1003-1017.lDOI: 10.3760/cma.j.cn112152-20230428-00188. [3]、Cristofanilli, Massimo et al. “Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.” The Lancet. Oncology vol. 17,4 (2016): 425-439. doi:10.1016/S1470-2045(15)00613-0 [4]、Goetz, Matthew P et al. “MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 35,32 (2017): 3638-3646. doi:10.1200/JCO.2017.75.6155 [5]、Slamon, Dennis J et al. “Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 36,24 (2018): 2465-2472. doi:10.1200/JCO.2018.78.9909 [6]、Tripathy, Debu et al. “Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.” The Lancet. Oncology vol. 19,7 (2018): 904-915. doi:10.1016/S1470-2045(18)30292-4 [7]、Xu B, Zhang Q, Zhang P, et al. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021;27(11):1904-1909. doi:10.1038/s41591-021-01562-9 [8]、Dey, Nandini et al. “PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials.” Pharmacology & therapeutics vol. 175 (2017): 91-106. doi:10.1016/j.pharmthera.2017.02.037 [9]、Castaneda, Carlos A et al. “The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer.” Cancer metastasis reviews vol. 29,4 (2010): 751-9. doi:10.1007/s10555-010-9261-0 [10]、中国抗癌协会肿瘤药物临床研究专业委员会, 国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会肿瘤病理专业委员会, 等. PI3K/AKT/mTOR信号通路抑制剂治疗乳腺癌临床应用专家共识[J]. 中华肿瘤杂志, 2022, 44(7):673-692.DOI: 10.3760/cma.j.cn112152-20220412-00251. [11]、姚荟斌 ，赵伟鹏，史业辉. CDK4/6抑制剂治疗晚期乳腺癌的研究进展. [J].《天津医科大学学报》2021，27（5）：549 [12]、O'Brien, Neil A et al. “Targeting activated PI3K/mTOR signaling overcomes acquired resistance to CDK4/6-based therapies in preclinical models of hormone receptor-positive breast cancer.” Breast cancer research : BCR vol. 22,1 89. 14 Aug. 2020, doi:10.1186/s13058-020-01320-8 [13]、Xiao, Weikai et al. “Mutational Landscape of PI3K-AKT-mTOR Pathway in Breast Cancer: Implications for Targeted Therapeutics.” Journal of Cancer vol. 12,14 4408-4417. 27 May. 2021, doi:10.7150/jca.52993 [14]、Kaufman, Peter A et al. “Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 33,6 (2015): 594-601. doi:10.1200/JCO.2013.52.4892 [15]、Li, Yi et al. “A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2- metastatic breast cancer.” Therapeutic advances in medical oncology vol. 13 17588359211022890. 11 Jun. 2021, doi:10.1177/17588359211022890 [16]、Kevin Kalinsky, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial. 2024 ASCO abstract LBA1001. [17]、Vanhaesebroeck, Bart et al. “PI3K signalling: the path to discovery and understanding.” Nature reviews. Molecular cell biology vol. 13,3 195-203. 23 Feb. 2012, doi:10.1038/nrm3290 [18]、Marafie, Sulaiman K et al. “mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.” International journal of molecular sciences vol. 25,11 6141. 2 Jun. 2024, doi:10.3390/ijms25116141 [19]、Mo H, et al. Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors. Clin Breast Cancer. 2022 Feb;22(2):143-148. （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Celebrating its golden anniversary, Nikon Small World honors a stunning photo of brain tumor cell structures, advancing our understanding of neurodegenerative diseases. MELVILLE, N.Y., Oct. 17, 2024 /PRNewswire/ -- Nikon Instruments Inc. today announced the winners of the 50th annual Nikon Small World Photomicrography Competition, celebrating five decades of excellence in microscopy and digital imaging. This year's first place prize was awarded to Dr. Bruno Cisterna, with assistance from Dr. Eric Vitriol of Augusta University, for his groundbreaking image of differentiated mouse brain tumor cells, highlighting the actin cytoskeleton, microtubules, and nuclei. This image reveals how disruptions in the cell's cytoskeleton – the structural framework and "highways" known as microtubules – can lead to diseases like Alzheimer's and ALS. Continue Reading Differentiated mouse brain tumor cells (actin, microtubules, and nuclei) Dr. Cisterna's research revealed that profilin 1 (PFN1), a protein crucial for building the cell's structure, plays a key role in maintaining the microtubule highways essential for cellular transport. When PFN1 or related processes are disrupted, these highways can malfunction, leading to cellular damage similar to what is observed in neurodegenerative diseases. "One of the main problems with neurodegenerative diseases is that we don't fully understand what causes them," said Dr. Cisterna. "To develop effective treatments, we need to figure out the basics first. Our research is crucial for uncovering this knowledge and ultimately finding a cure. Differentiated cells could be used to study how mutations or toxic proteins that cause Alzheimer's or ALS alter neuronal morphology, as well as to screen potential drugs or gene therapies aimed at protecting neurons or restoring their function." His patience and determination were crucial in capturing his image. "I spent about three months perfecting the staining process to ensure clear visibility of the cells. After allowing five days for the cells to differentiate, I had to find the right field of view where the differentiated and non-differentiated cells interacted. This took about three hours of precise observation under the microscope to capture the right moment, involving many attempts and countless hours of work to get it just right." The hard work behind this discovery underscores its significance, bringing researchers closer to answers that could potentially transform millions of lives. "After three years of research, we finally published our findings four months ago in the Journal of Cell Biology, and there's still more work to be done," said Dr. Cisterna. "I'm deeply passionate about scientific imaging; I've been following the Nikon Small World contest for about 15 years. It's an incredible contest that highlights the beauty of photomicrography but also inspires continued exploration and innovation in the field." Eric Flem, Senior Manager, CRM and Communications at Nikon Instruments, shares a similar perspective on the competition. "At 50 years, Nikon Small World is more than just an imaging competition – it's become a gallery that pays tribute to the extraordinary individuals who make it possible. They are the driving force behind this event, masterfully blending science and art to reveal the wonders of the microscopic world and what we can learn from it to the public." He went on to add, "Sometimes, we overlook the tiny details of the world around us. Nikon Small World serves as a reminder to pause, appreciate the power and beauty of the little things, and to cultivate a deeper curiosity to explore and question." Second place was awarded to Dr. Marcel Clemens for his image of an electrical arc between a pin and a wire, produced by applying a potential difference of 10,000 volts. Third place was awarded to Chris Romaine for his image of a cannabis plant leaf. The bulbous structures are trichomes, or hair-like plant appendages, and the bubbles inside are cannabinoid vesicles, fluid-filled, blister-like structures. In total, Nikon Small World recognized 87 photos out of thousands of entries from scientists and artists across the globe. The 2024 judging panel included: Adrian Coakley, Director of Photography at National Geographic Books Michelle S. Itano, Ph.D., Assistant Professor of Cell Biology and Physiology and Director of the Neuroscience Microscopy Core at the University of North Carolina at Chapel Hill Emily Petersen, Photography Managing Editor at Science Magazine Clare Waterman, Ph.D., Cell Biologist and Member of the National Academy of Sciences Jennifer C. Waters, Ph.D., Director of the Core for Imaging Technology & Education at Harvard Medical School Samantha Yammine, Ph.D., Neuroscientist and Science Communicator For additional information, please visit , or follow the conversation on Facebook, Twitter @NikonSmallWorld and Instagram @NikonInstruments. NIKON SMALL WORLD WINNERS 1st Place Dr. Bruno Cisterna & Dr. Eric Vitriol Medical College of Georgia at Augusta University Department of Neuroscience & Regenerative Medicine Augusta, Georgia, USA Differentiated mouse brain tumor cells (actin, microtubules, and nuclei) Super-Resolution 100X (Objective Lens Magnification) 2nd Place Dr. Marcel Clemens Verona, Veneto, Italy Electrical arc between a pin and a wire Image stacking for the pin and wire combined with long exposure for the electrical arcs 10X (Objective Lens Magnification) 3rd Place Chris Romaine Kandid Kush Port Townsend, Washington, USA Leaf of a cannabis plant. The bulbous glands are trichomes. The bubbles inside are cannabinoid vesicles. Image Stacking 20X (Objective Lens Magnification) 4th Place Dr. Amy Engevik Medical University of South Carolina Department of Regenerative Medicine & Cell Biology Charleston, South Carolina, USA Section of a small intestine of a mouse Fluorescence 10X (Objective Lens Magnification) 5th Place Thomas Barlow & Connor Gibbons Columbia University Department of Neurobiology and Behavior New York, New York, USA Cluster of octopus (Octopus hummelincki) eggs Darkfield, Stereomicroscopy, Focus Stacking 3X (Objective Lens Magnification) 6th Place Henri Koskinen Helsinki University Helsinki, Uudenmaan lääni, Finland Slime mold (Cribraria cancellata) Image Stacking, Polarized Light, Reflected Light 10X (Objective Lens Magnification) 7th Place Gerhard Vlcek Maria Enzersdorf, Austria Cross section of European beach grass (Ammophila arenaria) leaf Brightfield, Image Stacking 10X (Objective Lens Magnification) 8th Place Stephanie Huang Victoria University of Wellington School of Biological Sciences; School of Psychology Wellington, New Zealand A neuron densely covered in dendritic spines from the striatum of an adult rat brain Confocal, Deconvolution, Image Stacking 60X (Objective Lens Magnification) 9th Place John-Oliver Dum Medienbunker Produktion Bendorf, Rheinland Pfalz, Germany Pollen in a garden spider (Araneus) web Image Stacking 20X (Objective Lens Magnification) 10th Place Jan Martinek Charles University Department of Experimental Plant Biology Prague, Czech Republic Spores of black truffle (Tuber melanosporum) Confocal 63X (Objective Lens Magnification) 11th Place Dr. Ferenc Halmos Bánd, Veszprém, Hungary Slime mold on a rotten twig with water droplets Image Stacking 0.7X - 4.5X (Objective Lens Magnification) 12th Place Daniel Knop Oberzent-Airlenbach, Hessen, Germany Wing scales of a butterfly (Papilio ulysses) on a medical syringe needle Image Stacking 20X (Objective Lens Magnification) 13th Place Paweł Błachowicz Bedlno, Świętokrzyskie, Poland Eyes of green crab spider (Diaea dorsata) Image Stacking, Reflected Light 20X (Objective Lens Magnification) 14th Place Marek Miś Marek Miś Photography Suwalki, Podlaskie, Poland Recrystallized mixture of hydroquinone and myoinositol Polarized Light 10X (Objective Lens Magnification) 15th Place Sébastien Malo Saint Lys, Haute-Garonne, France Isolated scales on Madagascan sunset moth wing (Chrysiridia ripheus) Darkfield, Image Stacking, Reflected Light 40X (Objective Lens Magnification) 16th Place Marek Miś Marek Miś Photography Suwalki, Podlaskie, Poland Two water fleas (Daphnia sp.) with embryos (left) and eggs (right) Darkfield, Polarized Light 10X (Objective Lens Magnification) 17th Place Dr. Frantisek Bednar Svosov, Zilinsky, Slovak Republic Stonewort algae (Chara virgata) reproductive organs - oogonia (female organs) and antheridia (male organs) Darkfield 4X (Objective Lens Magnification) 18th Place Alison Pollack San Anselmo, California, USA An insect egg parasitized by a wasp Image Stacking, Reflected Light 10X (Objective Lens Magnification) 19th Place Alison Pollack San Anselmo, California, USA Seed of a Silene plant Image Stacking, Reflected Light 10X (Objective Lens Magnification) 20th Place Dr. Bruno Cisterna & Dr. Eric Vitriol Medical College of Georgia at Augusta University Department of Neuroscience & Regenerative Medicine Augusta, Georgia, USA Early stage of mouse neuroblastoma cell differentiation (actin, microtubules, and mitochondria) Super-Resolution 100X (Objective Lens Magnification) HM Christopher Algar Hounslow, Middlesex, United Kingdom Brine shrimp Darkfield, Image Stacking, Polarized Light 4X (Objective Lens Magnification) HM Dr. Kseniia Bondarenko University of Edinburgh Institute for Immunology and Infection Research Edinburgh, MidLothian, United Kingdom Acute-stage parasites of Toxoplasma gondii in a human skin cell Expansion Microscopy, Confocal, Deconvolution 100X (Objective Lens Magnification) HM Dr. Anja de Lange University of Cape Town Neuroscience Institute & Department of Human Biology Cape Town, Western Cape, South Africa Astrocytes surrounding a blood vessel in a thin slice of human brain Confocal 40X (Objective Lens Magnification) HM Dr. Amy Engevik Medical University of South Carolina Department of Regenerative Medicine & Cell Biology Charleston, South Carolina, USA Intestinal villi Fluorescence 20X (Objective Lens Magnification) HM Daniel Evrard Aywaille, Liege, Belgium Vinyl player needle on scratched vinyl disk Image Stacking, Polarized Light 20X (Objective Lens Magnification) HM Randy Fullbright Fullbright Studio Vernal, Utah, USA Agatized dinosaur bone Image Stacking 10X (Objective Lens Magnification) HM Dr. David Maitland St. Andrews, Fife, United Kingdom Transverse section of rachis (stem) of bracken fern (Pteridium aquilinum) Differential Interference Contrast (DIC) 5X (Objective Lens Magnification) HM Angus Rae Australian National University Centre for Advanced Microscopy MacGregor, Australian Capital Territory, Australia Autofluorescence in the face of a little two-spotted ladybird (Diomus notescens) Fluorescence lifetime imaging microscopy (FLIM) 20X (Objective Lens Magnification) HM Dr. Igor Robert Siwanowicz Howard Hughes Medical Institute (HHMI), Janelia Research Campus Ashburn, Virginia, USA Antenna of a mole crab Confocal 10X (Objective Lens Magnification) HM Jochen Stern Mannheim, Baden-Wuerttemberg, Germany Golden bug eggs on a sage leaf Image Stacking 20X (Objective Lens Magnification) HM Dr. Bruce Douglas Taubert Glendale, Arizona, USA Ocelli between the compound eyes of a yellow jacket Reflected Light 10X (Objective Lens Magnification) HM Kevin Terretaz CRBM-CNRS Montpellier, Hérault, France Mosquito cells in culture with fluorescent markers for DNA and microtubules Confocal 63X (Objective Lens Magnification) IoD Dr. Sherif Abdallah Ahmed Tanta University, Faculty of Science Department of Zoology Tanta, Egypt, Arab Republic Anterior section of palm weevil Image Stacking 4X (Objective Lens Magnification) IoD Anne Patricia Algar Hounslow, Middlesex, United Kingdom Mosquito larva Darkfield, Image Stacking, Polarized Light 4X (Objective Lens Magnification) IoD Dr. Florian Alonso University of Bordeaux BioTis-INSERM U1026 Pessac, Gironde, France Mouse aortic endothelium stained for beta-catenin (green), laminin (purple), smooth muscle actin (red), and Hoechst (cyan) Confocal 63X (Objective Lens Magnification) IoD Didier Barbet Club Français de Microscopie Bailly, France Fracture surface of mica (mineral) Differential Interference Contrast (DIC) 10X (Objective Lens Magnification) IoD Timothy Boomer WildMacro.com Vacaville, California, USA Slime mold (Prototrichia metallica) Image Stacking 10X (Objective Lens Magnification) IoD Zhang Chao National Astronomical Observatories, Chinese Academy of Sciences Beijing, China Beach sand Reflected Light 10X (Objective Lens Magnification) IoD Joshua Coogler Dallas, North Carolina, USA Moss sporophyte with spores (green) Image Stacking 10X (Objective Lens Magnification) IoD Nikky Corthout & Miranda Dyson VIB (Flanders Institute of Biotechnology) Center for Brain and Disease Research Leuven, Vlaams-Brabant, Belgium Fruit fly (Drosophila) brain vasculature Confocal, Fluorescence, Image Stacking, Super-Resolution 25X (Objective Lens Magnification) IoD Nadia Efimova Amicus Therapeutics Philadelphia, Pennsylvania, USA Dandelion pappus Confocal, Fluorescence 20X (Objective Lens Magnification) IoD Dr. Laurent Formery & Dr. Nathaniel Clarke Stanford University Department of Molecular and Cell Biology Pacific Grove, California, USA Nervous system of a young sea star Confocal, Fluorescence 10X (Objective Lens Magnification) IoD Karl Gaff Dublin, Ireland Larva of a midge fly (Chironomidae) Darkfield, Image Stacking, Polarized Light 20X (Objective Lens Magnification) IoD Dr. Nick Gatford University of Oxford Nuffield Department of Clinical Neurosciences (NDCN) Oxford, Oxfordshire, United Kingdom A network of dopaminergic neurons generated from human stem cells Super-Resolution 63X (Objective Lens Magnification) IoD Dr. Saikat Ghosh National Institutes of Health NICHD Bethesda, Maryland, USA Human neurons Confocal 40X (Objective Lens Magnification) IoD Gerd A. Günther Düsseldorf, Germany Cross section of a beach grass (Ammophila arenaria) leaf Fluorescence 20X (Objective Lens Magnification) IoD Anna-Mari Elisabeth Haapanen-Saaristo University of Turku Turku Bioscience Centre / Cell Imaging & Cytometry Core and Zebrafish Core RAISIO, Varsinais-Suomi, Finland Nutrient storage cells in a tardigrade Confocal 25X (Objective Lens Magnification) IoD Dr. Martin Hein Lions Eye Institute Physiology and Pharmacology laboratory Nedlands, Western Australia, Australia Abnormal blood vessel formation in a human retina with severe diabetic retinopathy Confocal 20X (Objective Lens Magnification) IoD Wen Jie Ji Yin Works The Bureau of Microworld Exploration Beijing, China Integrated circuit chip Reflected Light 10X (Objective Lens Magnification) IoD Ted Kinsman Rochester Institute of Technology Photosciences Department Rochester, New York, USA A common house cat claw Polarized Light 10X (Objective Lens Magnification) IoD Daniel Knop Oberzent-Airlenbach, Hessen, Germany Opening of a hibiscus flower (Hibiscus moscheutos) exposing the pollen in four stages, each ten minutes apart Image Stacking 20X (Objective Lens Magnification) IoD Daniel Knop Oberzent-Airlenbach, Hessen, Germany Dorsal part of cuckoo wasp (Hedychrum gerstaeckeri) abdomen Image Stacking 20X (Objective Lens Magnification) IoD Dr. Håkan Kvarnström Bromma, Sweden Peacock plume feather Epi-Illumination, Image Stacking 4X (Objective Lens Magnification) IoD Dr. Ewa Langner Washington University in St Louis Department of Medicine - Renal Division, Mahjoub Lab St Louis, Missouri, USA Mouse embryonic kidney showing interstitial fibroblasts (yellow), tubular epithelium (cyan), and nuclei (magenta) Confocal, Fluorescence, Image Stacking 40X (Objective Lens Magnification) IoD Dr. Amir Maqbool Lovely Professional University Department of Zoology Srinagar, Jammu and Kashmir, India Small fly killed by "zombie fly" fungus (Entomophthora muscae) Image Stacking 2X (Objective Lens Magnification) IoD Dr. Robert Markus University of Nottingham School of Life Sciences, Super Resolution Microscopy Nottingham, Nottinghamshire, United Kingdom Dandelion (Traxacum officinale) cross section showing curved stigma with pollen Confocal 10X (Objective Lens Magnification) IoD Dr. Robert Markus, Dr. Zeeshan Mohammad, Dr. Sarah Pashley & Dr. Rita Tewari University of Nottingham School of Life Sciences, Super Resolution Microscopy Nottingham, Nottinghamshire, United Kingdom Malaria parasites and mouse blood cells - tubulin (green), all proteins (purple), DNA (red) Confocal 63X (Objective Lens Magnification) IoD Jan Martinek Charles University Department of Experimental Plant Biology Prague, Czech Republic Spores of a black Bagnoli truffle (Tuber mesentericum) Confocal 63X (Objective Lens Magnification) IoD Dr. Guillermo Moya Johns Hopkins University Department of Biology Baltimore, Maryland, USA Neuronal axons connecting to the muscles of the iris and the cornea Confocal, Fluorescence 10X (Objective Lens Magnification) IoD Jacek Myslowski Wloclawek, Kujawko-Pomorskie, Poland Water mite (Arrenurus) Fluorescence, Image Stacking 6.3X (Objective Lens Magnification) IoD Aryah Nagarajan Falmouth University Institute of Photography Penryn, Cornwall, United Kingdom Spores releasing from the sori of a Polypody fern (Polypodium vulgare) Reflected Light, Transmitted Light, Focus Stacking 10X (Objective Lens Magnification) IoD Thomas Neumann Tübingen, Baden-Württemberg, Germany Ink dot on Japanese washi paper Brightfield, Image Stacking 20X (Objective Lens Magnification) IoD Satu Paavonsalo & Dr. Sinem Karaman University of Helsinki Individualized Drug Therapy Research Program, Faculty of Medicine, Helsinki, Finland Helsinki, Finland Blood vessels (color gradient) and endothelial cell nuclei (white) in the intestinal villi of a mouse Confocal 10X (Objective Lens Magnification) IoD Uwe Lange Hannover, Niedersachsen, Germany Pollen on the compound eyes of a fly Image Stacking 60X (Objective Lens Magnification) IoD Dr. Marko Pende MDI Biological Laboratory Murawala Lab Bar Harbor, Maine, USA Ladybug (Coccinellidae) on a clover (Trifolium repens) Confocal, Fluorescence, Image Stacking 4X (Objective Lens Magnification) IoD Dr. Felice Placenti FP Nature and Landscape Photography Siracusa, Sicilia, Italy Potato tuber sprout Image Stacking, Reflected Light 1X (Objective Lens Magnification) IoD Alison Pollack San Anselmo, California, USA Slime mold (Lamproderma arcyrioides) Image Stacking, Reflected Light 10X (Objective Lens Magnification) IoD Dr. Gonzalo Quiroga Artigas CRBM-CNRS Montpellier, Herault, France Tardigrade (Hypsibius exemplaris) Confocal 40X (Objective Lens Magnification) IoD Chris Romaine Kandid Kush Port Townsend, Washington, USA Bract (part of the plants reproductive structures) of a cannabis plant. The bulbous glands are trichomes. Image Stacking 20X (Objective Lens Magnification) IoD Dr. Adolfo Ruiz De Segovia PARTICULAR Madrid, Spain Plant root Fiber Optic 2X (Objective Lens Magnification) IoD Yurim Seo, Dr. Mark Looney & Dr. Simon Cleary University of California, San Francisco Pulmonary, Critical Care, Allergy and Sleep Medicine San Francisco, California, USA Lymphatic vasculature (cyan) and vessels (red) of a mouse lung Confocal 4X (Objective Lens Magnification) IoD Dr. Leo Serra University of Cambridge Sainsbury Laboratory Cambridge, Cambridgeshire, United Kingdom Leaves arising from thale cress (Arabidopsis thaliana) meristem Confocal 20X (Objective Lens Magnification) IoD Dr. Igor Robert Siwanowicz Howard Hughes Medical Institute (HHMI), Janelia Research Campus Ashburn, Virginia, USA Aster anther cross section with pollen grains (green) Confocal 40X (Objective Lens Magnification) IoD Dr. Igor Robert Siwanowicz Howard Hughes Medical Institute (HHMI), Janelia Research Campus Ashburn, Virginia, USA Floret of a common chicory with pollen grains (spiky balls) Confocal 40x (Objective Lens Magnification) IoD Luna Šošo Zdravković, Michael Surala & Christian Madry Charité Universitätsmedizin Berlin Institute of Neurophysiology Berlin, Germany Pyramidal neuron in mouse hippocampus Confocal, Fluorescence, Image Stacking 30X (Objective Lens Magnification) IoD Dr. Bruce Douglas Taubert Glendale, Arizona, USA Mid-tibial tuft on a male orchid bee, used to attract mates Reflected Light 10X (Objective Lens Magnification) IoD Maxime Teixeira Laval University Department of Molecular Medicine Québec, Canada Cultured monkey kidney cells labeled for tubulin (blue) and actin (orange) showing pathological accumulation of alpha-syn aggregates (red) Confocal, Deconvolution, Image Stacking, Super-Resolution 100X (Objective Lens Magnification) IoD Dr. Theo Theune Oost-Souburg, Zeeland, Netherlands Abdominal skin of a tick that engorged with blood Image Stacking 50X (Objective Lens Magnification) IoD Dr. Grigorii Timin & Dr. Michel Milinkovitch University of Geneva Department of Genetics and Evolution Geneva, Switzerland Skin scales of a snake embryo stained with Fast Green dye Confocal 63X (Objective Lens Magnification) IoD Steven A. Valley Oregon Department of Agriculture (ODA) Entomology Lab Albany, Oregon, USA Immature male damselfly (Calopteryx aequabilis) Image Stacking, Reflected Light 5X (Objective Lens Magnification) IoD Dr. Bruno Vellutini Max Planck Institute of Molecular Cell Biology and Genetics Dresden, Saxony, Germany Gene expression patterns in a drain fly embryo (Clogmia albipunctata) with an open eggshell Confocal 20X (Objective Lens Magnification) IoD Susannah Waxman & Dr. Ian Sigal University of Pittsburgh Department of Ophthalmology Pittsburgh, Pennsylvania, USA Optic nerve head collagen of a pig Image Stacking, Multiphoton 25X (Objective Lens Magnification) IoD Shao Yang Beijing Miteyide Culture Co., Ltd. Beijing, China Fiber of nylon stockings Polarized Light 5X (Objective Lens Magnification) IoD Chew Yen Fook Woodend, Waimakiriri, New Zealand Graffiti from Berlin Wall stone section Image Stacking, Top Illumination 10X (Objective Lens Magnification) IoD Chew Yen Fook Woodend, Waimakiriri, New Zealand Water mite (Hydrachna sp.) Darkfield, Image Stacking, Polarized Light 20X (Objective Lens Magnification) IoD Elkhan Yusifov & Dr. Martina Schaettin University of Zurich Department of Molecular Life Sciences Zurich, Switzerland Developing nervous system in the eye of a 7-day-old chick embryo Stereomicroscopy 10X (Objective Lens Magnification) IoD Ou Zhilei Guangdong Radio and Television Guangzhou, Guagndong, China Stamens of flowers (Anemone cathayensis Kitag. ex Ziman & Kadota) Image Stacking 10X (Objective Lens Magnification) About Nikon Small World Photomicrography Competition The Nikon Small World Competition is open to anyone with an interest in photography or video. Participants may upload digital images and videos directly at . For additional information, contact Nikon Small World, Nikon Instruments Inc., 1300 Walt Whitman Road, Melville, NY 11747, USA, or phone (631) 547-8569. Entry forms for Nikon's 2025 Small World and Small World in Motion Competitions are available at . About Nikon Instruments Inc. Nikon Instruments Inc. is the US microscopy arm of Nikon Healthcare, a world leader in the development and manufacturing of optical, digital imaging technology and software for biomedical applications. For more information, please visit or contact us at 1-800-52-NIKON. SOURCE Nikon Instruments Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED