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Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer

2026-12-01T00:00:00Z

Title: Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer Authors: Chen, Zhe; Qiang, Min; Dong, Junxue; Gong, Kejian; Zhang, Xinjun; Huo, Peng; Zhu, Jingjun; Shao, Yifeng; Ma, Jianzun; Zhang, Bowei; Liu, Wei; Tang, Mingbo Abstract: IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple mechanisms. First, reduction of drug deposition due to altered uptake or enhanced efflux decreases intracellular cisplatin levels. Second, dysregulation of apoptotic pathways, including overexpression of anti-apoptotic proteins such as Bcl-2, allows tumor cells to evade chemotherapy-induced cell death. Third, enhanced DNA damage repair restores cisplatin-induced lesions, limiting cytotoxicity. Fourth, the tumor microenvironment can induce resistance through stromal and immune interactions. Fifth, metabolic adaptations enable tumor cells to survive under chemotherapeutic stress. Sixth, SCLC subtype transitions alter cellular phenotype and chemosensitivity. Seventh, epigenetic changes drive transcriptional programs that confer resistance.Targeted therapies, such as multidrug resistance (MDR) inhibitors and Bcl-2 family inhibitors, can restore tumor sensitivity but are limited by toxicity and tumor-specific efficacy. Immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, shows potential, although effectiveness is constrained by the immunosuppressive tumor microenvironment and rapid progression. Targeted therapies, such as PARP inhibitors, demonstrate variable efficacy influenced by genetic heterogeneity, biomarker expression, and microenvironmental factors. Novel chemotherapeutic agents offer alternative options for cisplatin-resistant patients. Preclinical and early clinical studies suggest that combining these approaches may further enhance antitumor activity, potentially improving progression-free survival and quality of life. Biomarker-guided strategies may optimize personalized therapy and patient selection.DiscussionCisplatin resistance in SCLC arises through multiple mechanisms. First, reduction of drug deposition due to altered uptake or enhanced efflux decreases intracellular cisplatin levels. Second, dysregulation of apoptotic pathways, including overexpression of anti-apoptotic proteins such as Bcl-2, allows tumor cells to evade chemotherapy-induced cell death. Third, enhanced DNA damage repair restores cisplatin-induced lesions, limiting cytotoxicity. Fourth, the tumor microenvironment can induce resistance through stromal and immune interactions. Fifth, metabolic adaptations enable tumor cells to survive under chemotherapeutic stress. Sixth, SCLC subtype transitions alter cellular phenotype and chemosensitivity. Seventh, epigenetic changes drive transcriptional programs that confer resistance.Targeted therapies, such as multidrug resistance (MDR) inhibitors and Bcl-2 family inhibitors, can restore tumor sensitivity but are limited by toxicity and tumor-specific efficacy. Immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, shows potential, although effectiveness is constrained by the immunosuppressive tumor microenvironment and rapid progression. Targeted therapies, such as PARP inhibitors, demonstrate variable efficacy influenced by genetic heterogeneity, biomarker expression, and microenvironmental factors. Novel chemotherapeutic agents offer alternative options for cisplatin-resistant patients. Preclinical and early clinical studies suggest that combining these approaches may further enhance antitumor activity, potentially improving progression-free survival and quality of life. Biomarker-guided strategies may optimize personalized therapy and patient selection.ConclusionCisplatin resistance in SCLC is a complex, multifactorial process involving cellular, molecular, and microenvironmental mechanisms. Integrating mechanistic insights with emerging therapies, including immunotherapy, targeted therapy, and novel chemotherapeutics, offers a promising path to overcome resistance, guiding future research and the development of more effective, personalized treatment strategies for patients with cisplatin-resistant SCLC.

A large puncture closer of aortic wall by multi-memory actions with thrombo-hemodynamic control

2026-05-01T00:00:00Z

Title: A large puncture closer of aortic wall by multi-memory actions with thrombo-hemodynamic control Authors: Cho, Sungwoo; Ha, Hyun-Su; Lee, Sangmin; Kim, Hyunjae; Lee, Seok Joon; Kim, Jueun; Lee, Yerin; Lee, Kang Suk; Joo, Hyun-Chel; Sung, Hak-Joon; 하현수; 이예린 Abstract: The vascular wall regulates the pattern and pressure of blood flow. In cardiovascular interventions, catheters are deployed by puncturing the vessel wall, without exception. Despite continuous progress, the outcomes remain highly operator-dependent, and large punctures with high-pressure bleeding continue to pose clinical challenges. As a translatable solution, this study introduces a shape memory vascular wall plug (VWP) that automates both the Body and Wing functions within a single component, supported by a Ring assembly to maximize pressure resistance. The VWP is deployed into a 6-mm puncture in a porcine thoracic aorta under peak blood pressure, and shape recovery is triggered by a 45 degrees C saline flush to enable automated activation. Upon recovery, Body expansion combined with Ring compression tightly seals the puncture tract. The curved Wing induces hemostatic sealing and then flattens to maintain healthy blood flow and physiologic pressures. The VWP achieves suturinglevel performance in aortic puncture closure, demonstrating effective hemostasis, patency, and endothelialization. The flow-blockage ratio required to balance hemostasis with hemodynamics is computationally modeled and validated using whole-blood microfluidics. Pressure resistance is maximized by tuning Ring strain through polymer blending, indicating multi-level strategies in polymer, device design, and memory function to advance the vascular closure technology.

Effect of Donor Lung Resection Technique on Bronchopleural Fistula in Transplantation: Pulmonary Tailoring Versus Hilar Dissection

2026-04-01T00:00:00Z

Title: Effect of Donor Lung Resection Technique on Bronchopleural Fistula in Transplantation: Pulmonary Tailoring Versus Hilar Dissection Authors: Yang, Young Ho; Lee, Ruari Krueger; Jun, Zhu Jing; Dung, Nguyen Minh; Hong, Tae Hee; Kim, Ha Eun; Park, Byung Jo; Lee, Chang Young; Kim, Dae Joon; Lee, Jin Gu Abstract: Purpose: Donor shortages in many countries necessitate the use of marginal donor lungs despite challenges such as size mismatch, and donor lung pathologies requiring resection, such as consolidation or anatomical abnormalities. One way to address these challenges is through major pulmonary resection of the donor lung, which can be in the form of hilar dissection (HD), an anatomical resection, or pulmonary tailoring (PT), a non-anatomical resection. No studies have compared these two techniques; hence, we aimed to compare their intraoperative and postoperative outcomes. Materials and Methods: We retrospectively analyzed 40 lung transplant recipients who underwent major pulmonary resection of donor lungs between January 2014 and May 2023. The patients were divided into HD (n=18) and PT (n=22) groups, and their intraoperative and postoperative outcomes were compared. Results: Postoperative bronchopleural fistula (BPF) occurred in 22.2% of patients in the HD group but was absent in the PT group (p=0.033). There were no significant differences between the two groups in terms of total operative time, ischemic time for each lung, occurrence of primary graft dysfunction, bronchial anastomotic dehiscence, bronchial stenosis, or pneumothorax. The survival curves were also similar between the two groups. Conclusion: The PT technique significantly reduced the risk of BPF compared with the HD technique, suggesting its potential as a safer technique for managing oversized donor lungs and addressing other pathologies requiring resection.

Hydrodynamic Characteristics of Bovine Pericardial and Porcine Valves Using a Mock Circulatory System Mimicking the Aortic and Pulmonary Positions

2026-04-01T00:00:00Z

Title: Hydrodynamic Characteristics of Bovine Pericardial and Porcine Valves Using a Mock Circulatory System Mimicking the Aortic and Pulmonary Positions Authors: Shin, Yu Rim; Lee, Seung-Hyun; Shim, Jae-Kwang; Kim, Yongwoo; Lee, Sak Abstract: Purpose: Aortic prostheses are used in pulmonary positions due to structural similarities between the pulmonary and aortic valves. However, there are no available studies that have comprehensively evaluated the mechanism of bioprosthetic aortic valves under pulmonary conditions. Materials and Methods: Using a mock circulatory system, we evaluated the hydrodynamic characteristics of bovine pericardial and porcine valves. Geometric orifice area, regurgitant and leakage volume, regurgitant fraction, peak pressure gradient, and forward flow volume were evaluated in different pulmonary pressure conditions (from 15/5 mm Hg to 75/35 mm Hg) and normal aortic pressure (110/80 mm Hg). Results: Bovine pericardial valves were associated with larger opening area (0.93 +/- 0.01 vs.1.70 +/- 0.01 for 23-mm valve; 0.99 +/- 0.01 vs.1.75 +/- 0.01 for 25-mm valve; 1.58 +/- 0.01 vs. 2.25 +/- 0.02 for 27-mm valve; all p<0.01) and forward flow volume (42.27 +/- 0.05 vs. 64.79 +/- 0.14 for 23-mm valve; 46.41 +/- 0.06 vs. 64.28 +/- 0.18 for 25-mm valve; 72.64 +/- 0.17 vs.73.25 +/- 0.07 for 27-mm valve; all p<0.01). Porcine valves were associated with incomplete opening, smaller opening area, and lower regurgitant fraction. Bovine pericardial valves demonstrated lower peak pressure gradients (15.75 +/- 0.14 vs. 12.57 +/- 0.47 for 23-mm valve; 14.85 +/- 0.05 vs. 12.87 +/- 0.28 for 25-mm valve; 15.72 +/- 0.32 vs. 7.91 +/- 0.03 for 27-mm valve). Conclusion: Bovine pericardial and porcine bioprosthetic valves has different hydrodynamic characteristics under various pulmonary pressure conditions.