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The tumor immune microenvironment plays a key role in the regulation of cancer progression. Recent studies have suggested a relation between diverse tumor genotypes and tumor immune microenvironment phenotypes for cholangiocarcinoma (CCA). However, the contribution of tumor‐infiltrating immune cells to CCA progression has remained unclear, underscoring the need for genetically defined CCA models in immunocompetent mice. We here aimed to generate genetically engineered and transplantable CCA organoids from C57BL/6 mice and to investigate the role of tumor‐infiltrating immune cells in CCA progression with this model. CCA organoids were generated ex vivo with the use of the CRISPR/Cas9 system. Orthotopic transplantation of CCA organoids harboring mutations in Smad4, Trp53, and Kras into wild‐type C57BL/6 mice resulted in tumor formation accompanied by distant metastasis. Selective depletion of immune cell types in the tumor‐bearing mice revealed an antitumor action of tumor‐infiltrating neutrophils (TINs) that was mediated by direct killing of cancer cells through the production of reactive oxygen species. Furthermore, administration of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) increased the number and cytotoxicity of TINs, suppressed tumor growth, and prolonged the survival of tumor‐bearing mice. Finally, combination treatment with rhG‐CSF and standard chemotherapy resulted in a synergistic attenuation of tumor growth. Our study therefore provides a syngeneic and genetically defined mouse model of CCA and highlights the therapeutic potential of targeting TINs with rhG‐CSF. This study developed a genetically engineered and transplantable cholangiocarcinoma (CCA) organoid model in immunocompetent mice to investigate the role of tumor‐infiltrating immune cells in CCA progression. The findings revealed that tumor‐infiltrating neutrophils (TINs) exhibit antitumor activity by directly killing cancer cells through reactive oxygen species, and their effects were enhanced by recombinant human granulocyte colony‐stimulating factor (rhG‐CSF), which suppressed tumor growth and improved survival. Additionally, combining rhG‐CSF with standard chemotherapy showed synergistic tumor suppression, highlighting the therapeutic potential of targeting TINs in CCA.

A 36‐year‐old man with severe acute kidney injury (AKI) was admitted to Shonan Kamakura General Hospital in Japan. He was diagnosed with refractory hypertension based on a severely elevated blood pressure of 224/116 mmHg and retinal, cardiac, and brain damage revealed by electrocardiogram, fundoscopy, and magnetic resonance imaging, respectively. Although hemodialysis was withdrawn following strict blood pressure control by an angiotensin receptor blocker, severe kidney insufficiency persisted. Therefore, we performed an autologous granulocyte colony‐stimulating factor‐mobilized peripheral blood CD34‐positive cell transplantation. Collected CD34‐positive cells were directly infused to both renal arteries. The patient's general condition was unremarkable after intervention, and the serum creatinine level gradually improved to 2.96 mg/dL 23 weeks after cell therapy. Although transient fever and thrombocytosis were observed after intervention, no major adverse events were observed. This patient is the first case in a phase I/II clinical trial of autologous granulocyte colony‐stimulating factor‐mobilized peripheral blood CD34‐positive cell transplantation for severe AKI with a CD34‐positive cell dose‐escalating protocol (trial number jRCTb030190231).

Background Experiments have previously demonstrated the therapeutic potential of mobilized dental pulp stem cells (MDPSCs) for complete pulp regeneration. The aim of the present pilot clinical study is to assess the safety, potential efficacy, and feasibility of autologous transplantation of MDPSCs in pulpectomized teeth. Methods Five patients with irreversible pulpitis were enrolled and monitored for up to 24 weeks following MDPSC transplantation. The MDPSCs were isolated from discarded teeth and expanded based on good manufacturing practice (GMP). The quality of the MDPSCs at passages 9 or 10 was ascertained by karyotype analyses. The MDPSCs were transplanted with granulocyte colony-stimulating factor (G-CSF) in atelocollagen into pulpectomized teeth. Results The clinical and laboratory evaluations demonstrated no adverse events or toxicity. The electric pulp test (EPT) of the pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging (MRI) of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental pulp in the untreated control. Finally, cone beam computed tomography demonstrated functional dentin formation in three of the five patients. Conclusions Human MDPSCs are safe and efficacious for complete pulp regeneration in humans in this pilot clinical study.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that is primarily secreted by monocytes or macrophages and has traditionally been recognized for its role in stimulating the proliferation and differentiation of neutrophils. Recent research has revealed the presence of G-CSF in non-hematopoietic cells such as vascular endothelial cells, placental cells, and trophoblast cells. This discovery has led to the belief that G-CSF plays a significant role in ensuring the success of pregnancy. In this review, we investigate and summarize the mechanisms of G-CSF in the reproductive system, specifically addressing its roles in endometrial repair at the maternal-fetal interface, trophoblast development, suppression of autoimmunity, ovulation, and its therapeutic effects in reproductive-related diseases. As an important cytokine in normal pregnancy, our study demonstrate that G-CSF could improve endometrial receptivity through multiple mechanisms: not only by inhibiting apoptosis, regulating cytokine expression, and mobilizing cells, but also by increasing the number of endometrial pinopodes and attenuating degeneration, as supported by recent studies. Our aim is to provide a comprehensive reference for future scientific research and clinical treatment endeavors.

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Introduction Trifluridine-tipiracil (FTD/TPI) is approved as monotherapy and in combination with bevacizumab for the treatment of metastatic colorectal cancer (mCRC). This UK real-world retrospective analysis aimed to evaluate the use of granulocyte colony stimulating factor (G-CSF) to prevent FTD/TPI induced neutropenia in patients with mCRC. Methods Retrospective data were collected across five UK Healthcare sites. Consecutive patients with mCRC having received at least 2 cycles of FTD/TPI in addition to G-CSF administered as primary or secondary prophylaxis were included. The study assessed the timing and duration of G-CSF treatment, incidence of neutropenia, and subsequent dose delays/reductions. Time on FTD/TPI treatment, Progression free Survival (PFS), and Overall Survival (OS) were also calculated for this patient cohort. Results The data set included 55 mCRC patients in total; 25 receiving primary prophylaxis, and 30 receiving secondary prophylaxis. 68% of G-CSF prophylaxis commenced on day 15, with 99% initiated between days 14 and 22. Following G-CSF use, 25% of patients experienced a dose delay and 18% a dose reduction due to neutropenia. 14.5% of patients reported grade ≥3 neutropenia. In patients receiving primary prophylaxis a mean of 18.4 weeks of FTD/TPI were completed, whereas in those receiving secondary prophylaxis the mean was 28.8 weeks. Primary prophylaxis patients exhibited a median PFS of 3 months, and a median OS of 9.7 months. In secondary prophylaxis patients the median PFS was 7.2 months and the median OS 17.5 months. Conclusion G-CSF prophylaxis reduced the incidence of neutropenia, improved dose intensity, and extended PFS and OS in this real-world study of mCRC patients on FTD/TPI. G-CSF prophylaxis was commonly administered as a 5-day course of filgrastim starting on day 15.

Chemotherapy-induced neutropenia (CIN) is a potentially fatal and common complication in myelosuppressive chemotherapy. The timing and grade of CIN may play prognostic and predictive roles in cancer therapy. CIN is associated with older age, poor functional and nutritional status, the presence of significant comorbidities, the type of cancer, previous chemotherapy cycles, the stage of the disease, specific chemotherapy regimens, and combined therapies. There are many key points and new challenges in the management of CIN in adults including: (1) Genetic risk factors to evaluate the patient’s risk for CIN remain unclear. However, these risk factors urgently need to be identified. (2) Febrile neutropenia (FN) remains one of the most common reasons for oncological emergency. No consensus nomogram for FN risk assessment has been established. (3) Different assessment tools [e.g., Multinational Association for Supportive Care in Cancer (MASCC), the Clinical Index of Stable Febrile Neutropenia (CISNE) score model, and other tools] have been suggested to help stratify the risk of complications in patients with FN. However, current tools have limitations. The CISNE score model is useful to support decision-making, especially for patients with stable FN. (4) There are still some challenges, including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN. In view of the current reports, our group discusses the key points, new challenges, and management of CIN.

Background Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile patients with recurrent implantation failure (RIF). Nevertheless, their efficiencies were controversial and there lack of consensus on which intrauterine treatment is the most effective. Methods All prospective trials (in Chinese or English) were searched in Databases PubMed, Cochrane, Web of Science, and CNKI from July 2013 to July 2023. We included studies that investigated various uterine infusions, including chorionic gonadotropin, granulocyte colony-stimulating factor, monocytes, platelet-rich plasma, etc. during IVF treatment and reported subsequent pregnancy outcomes. Results We finally included 56 researches, including 40 randomized controlled trials, 14 non-randomized controlled trials, and 3 prospective cohort studies. This study included a total of 11 uterine perfusion methods: Placebo, Human Chorionic Gonadotropin (HCG), Granulocyte Colony-Stimulating Factor (G-CSF), platelet-rich plasma (PRP), Peripheral Blood Mononuclear Cell (PBMC), Growth hormone (GH), dexamethasone (DEX), Embryo culture supernatant (ESC), PRP combined with G-CSF (PRP + G-CSF), RPR combined with subcutaneous injection of G-CSF (RPR + G-CSFsc), G-CSF combined with subcutaneous injection of AXaIU (G-CSF + AXaIUsc). Intrauterine infusion of HCG, PBMC, G-CSF, and PRP significantly improves pregnancy outcomes in patients with repeated implantation failure compared with blank controls or placebo, and PRP improved the clinical pregnancy and live birth most. GH and ESC infusion might improve the pregnancy outcomes, but uterine infusion of DEX was shown with high miscarriage. The combination therapy did not show a significant advantage over the mono-therapy. Conclusions Intrauterine infusion of HCG, PBMC, G-CSF, and PRP are promising strategies for improving pregnancy outcomes for infertile patients with recurrent implantation failure. Among these treatments, PRP may be the best. More researches are required to explore the effect of drug combinations and less commonly used drugs as well. Trial registration Our study was registered in PROSPERO and the ID was CRD42023467188.

Purpose Pegfilgrastim is a pegylated form of filgrastim, a recombinant protein of granulocyte colony-stimulating factor, that is used to reduce the risk of febrile neutropenia (FN). Here, we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide (TC) chemotherapy. Methods We conducted a double-blind, placebo-controlled, randomized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients. A total of 351 women (177 in the pegfilgrastim group and 174 in the placebo group) between 20 and 69 years of age with stage I–III invasive breast carcinoma who were to receive TC chemotherapy (docetaxel 75 mg/m 2 and cyclophosphamide 600 mg/m 2 every 3 weeks) as either neoadjuvant or adjuvant therapy were enrolled; 346 of these patients were treated with either pegfilgrastim ( n  = 173) or placebo ( n  = 173). Results The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group (1.2 vs. 68.8 %, respectively; P  < 0.001). In addition, patients in the pegfilgrastim group required less hospitalization and antibiotics for FN. Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy. Conclusions Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients.

This report presents a case of malignant pleural mesothelioma (MPM) producing granulocyte colony‐stimulating factor (G‐CSF) that was treated by tumor resection. A 76‐year‐old male presented with a huge right‐side chest wall tumor, along with a slight fever and chest wall pain. Laboratory findings showed an increased white blood cell count (64600 cells/μL) and C‐reactive protein level (20.57 mg/dL). The patient underwent surgical removal of the tumor along with tissue from the chest wall and histopathological analysis led to a diagnosis of sarcomatous type of MPM. Immunohistochemical findings for both anti‐human G‐CSF and interleukin‐6 monoclonal antibodies were positive. Although the general condition of the patient quickly improved after surgery, local recurrence occurred two months later and he died of respiratory failure seven months after the operation, though surgery provided symptom relief. G‐CSF‐producing MPMs usually show a poor prognosis, though less‐invasive surgery may be considered for relief of symptoms.