Background: Two major ways of macrophage (MΦ) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MΦ activation, which play important roles in the pathogenesis of RPI. MΦ can produce chemokine MΦ inflammatory protein-1α (MIP-1α), while MIP-1α can recruit MΦ. The difference in the chemotactic ability of MIP-1α toward distinct activated MΦ is unclear. We speculated that there has been important interaction of MIP-1α with different activated MΦ, which might contribute to the pathogenesis of RPI.Methods: Classically and alternatively activated MΦ were produced by stimulating murine MΦ cell line RAW 264.7 cells with three different stimuli (LPS, IL-4 and IL-13); Then we used recombinant MIP-1α to attract two types of activated MΦ. In addition, we measured the ability of two types of activated MΦ to produce MIP-1α at the protein or mRNA level.Results: Chemotactic ability of recombinant MIP-1α toward IL-13-treated MΦ was the strongest, was moderate for IL-4-treated MΦ, and was weakest for LPS-stimulated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to secrete MIP-1α was significantly stronger than that of IL-4-treated or IL-13-treated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to express MIP-1α mRNA also was stronger than that of IL-4- or IL-13-stimulated MΦ (p < 0.01).Conclusions: The chemotactic ability of MIP-1α toward alternatively activated MΦ (M2) was significantly greater than that for classically activated MΦ (M1). Meanwhile, both at the mRNA and protein level, the capacity of M1 to produce MIP-1α is better than that of M2. Thus, chemokine MIP-1α may play an important role in modulating the transition from radiation pneumonitis to pulmonary fibrosisin vivo, through the different chemotactic affinity for M1 and M2.

To quantify the dosimetric parameters of different bone marrow sparing strategies and to determine the optimal strategy for cervical cancer patients undergoing postoperative intensity-modulated radiotherapy (IMRT). Fifteen patients with cervical cancer were selected for analysis. The planning target volume (PTV) and the organs at risks (OAR) including small bowel, bladder, rectum, femoral heads, os coxae (OC), lumbosacral spine (LS) and bone marrow (BM) were contoured. For each patient, four IMRT plans with different strategies were generated, including one plan without BM as the dose-volume constraint, namely IMRT (N) plan, and three bone marrow sparing (BMS-IMRT) plans. The three BMS-IMRT plans used the BM, OC, OC and LS respectively, as the BM OAR, namely as IMRT (BM), IMRT (OC) and IMRT (OC + LS) plans. Dose volumes for the target and the OARs were compared using analysis of variance (ANOVA). Compared with IMRT (N) plans, the dose to the small bowel, bladder, rectum and femoral heads showed no increase in the three BMS-IMRT plans. However, the irradiated dose to BM, OC and LS significantly decreased. In particular, the mean dose of BM, OC and LS decreased by about 5Gy (p < 0.05) in IMRT (BM) plans while the average volume receiving ≥20, ≥30, ≥40Gy decreased by 7.1–24.2%. The LS volume receiving 40Gy showed the highest decrease (about 31.2%, p < 0.05) in IMRT (OC + LS) plans. On the other hand, in comparison with IMRT (BM), IMRT (OC) reduced the dose volume of to the OC, but increased the dose to LS while IMRT (OC + LS) plans reduced both the OC and the LS volume at all dose levels. Specifically, the V20 of OC and LS in the IMRT (OC + LS) plan decreased by 11.5 and 11.2%, respectively. By introducing the os coxae and lumbosacral spine as the dose–volume constraints, the IMRT plans exhibited the best sparing of the bone marrow without compromising the dose to surrounding normal structures. Therefore, we recommend adding the os coxae and lumbosacral spine as the BM OAR in such plans.

Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application.

Purpose: Radiotherapy (RT) is recommended as an extensive therapeutic regimen for cancer patients; however, cancer radio-resistance results from reduced oxygen levels (hypoxia) in the tumor microenvironment. Herein, we report a therapeutic strategy that greatly enhances the treatment effects of RT. Methods: Specifically, papaverine (ppv), an FDA-approved smooth muscle relaxant, was applied in the strategy. Ppv improved blood flow via vasodilation to deliver sufficient oxygen to the hypoxic solid tumor and further resulted in increased tumor penetration of the radiosensitizer, significantly enhancing the radiosensitization compared with no ppv treatment. Additionally, tantalum oxide nanospheres were cloaked in red blood cell membranes ([email protected]) to achieve greater biocompatibility, non-immunogenicity, and a longer circulation time. Results: As a high-Z element, tantalum provides localized dose enhancement and thereby boosts the efficacy of RT. Vasodilation, the oxygenation of cancer cells, and the improved accumulation and retention of [email protected] in the tumor region were verified in vivo. Furthermore, compared with RT alone, the combined vasodilation and nanosphere camouflaging strategy more efficiently suppressed the growth of K7M2 tumors in mice. Conclusion: The results of this study suggest that the integration of [email protected] and ppv has excellent potential for improving RT efficacy.