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International Journal of Molecular... May 2024(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects...
(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects of radiotherapy. We compared the effects of the PARP inhibitors talazoparib and niraparib and that of the DNA-PKcs inhibitor AZD7648, combined with ionizing radiation. (2) Seven HNSCC cell lines, including Cal33, CLS-354, Detroit 562, HSC4, RPMI2650 (HPV-negative), UD-SCC-2 and UM-SCC-47 (HPV-positive), and two healthy fibroblast cell lines, SBLF8 and SBLF9, were studied. Flow cytometry was used to analyze apoptosis and necrosis induction (AnnexinV/7AAD) and cell cycle distribution (Hoechst). Cell inactivation was studied by the colony-forming assay. (3) AZD7648 had the strongest effects, radiosensitizing all HNSCC cell lines, almost always in a supra-additive manner. Talazoparib and niraparib were effective in both HPV-positive cell lines but only consistently in one and two HPV-negative cell lines, respectively. Healthy fibroblasts were not affected by any combined treatment in apoptosis and necrosis induction or G2/M-phase arrest. AZD7648 alone was not toxic to healthy fibroblasts, while the combination with ionizing radiation reduced clonogenicity. (4) In conclusion, talazoparib, niraparib and, most potently, AZD7648 could improve radiation therapy in HNSCC. Healthy fibroblasts tolerated AZD7648 alone extremely well, but irradiation-induced effects might occur. Our results justify in vivo studies.
Topics: Humans; Phthalazines; Indazoles; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Cell Line, Tumor; Radiation-Sensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Apoptosis; Head and Neck Neoplasms; DNA-Activated Protein Kinase
PubMed: 38891817
DOI: 10.3390/ijms25115629 -
BMC Musculoskeletal Disorders Jun 2024At present, the core decompression (CD) has become the main surgical procedure for the treatment of osteonecrosis of the femoral head (ONFH); however, the CD surgery... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparison of clinical efficacy of robot-assisted and freehand core decompression in the treatment of osteonecrosis of the femoral head: a systematic review and meta-analysis.
OBJECTIVE
At present, the core decompression (CD) has become the main surgical procedure for the treatment of osteonecrosis of the femoral head (ONFH); however, the CD surgery requires high operator experience and repeated fluoroscopy increases the radiation damage to patients, and medical staff. This article compares the clinical efficacy of robot-assisted and freehand CD for ONFH by meta-analysis.
METHODS
Computer searches of PubMed, Web of Science, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, and Chinese BioMedical Literature Database were conducted from the time of database inception to November 15, 2023. The literature on the clinical efficacy of robot-assisted and freehand CD in the treatment of ONFH was collected. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and strictly evaluated the quality of the included literature. Outcome measures encompassed operative duration, intraoperative blood loss volume, frequency of intraoperative fluoroscopies, visual analog scale (VAS) score, Harris hip score (HHS), complications, and radiographic progression. Data synthesis was carried out using Review Manager 5.4.1 software. The quality of evidence was evaluated according to Grades of Recommendation Assessment Development and Evaluation (GRADE) standards.
RESULTS
Seven retrospective cohort studies involving 355 patients were included in the study. The results of meta-analysis showed that in the robot-assisted group, the operative duration (MD = -17.60, 95% CI: -23.41 to -11.78, P < 0.001), intraoperative blood loss volume (MD = -19.98, 95% CI: -28.84 to -11.11, P < 0.001), frequency of intraoperative fluoroscopies (MD = -6.60, 95% CI: -9.01 to -4.20, P < 0.001), and ΔVAS score (MD = -0.45, 95% CI: -0.67 to -0.22, P < 0.001) were significantly better than those in the freehand group. The GRADE evidence evaluation showed ΔVAS score as low quality and other indicators as very low quality. There was no significant difference in the terms of ΔHHS (MD = 0.51, 95% CI: -1.34 to 2.35, P = 0.59), complications (RR = 0.30, 95% CI: 0.03 to 2.74, P = 0.29), and radiographic progression (RR = 0.50, 95% CI: 0.25 to 1.02, P = 0.06) between the two groups.
CONCLUSION
There is limited evidence showing the benefit of robot-assisted therapy for treatment of ONFH patients, and much of it is of low quality. Therefore, caution should be exercised in interpreting these results. It is recommended that more high-quality studies be conducted to validate these findings in future studies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/ #recordDetails, CRD42023420593.
Topics: Humans; Femur Head Necrosis; Decompression, Surgical; Treatment Outcome; Robotic Surgical Procedures; Operative Time
PubMed: 38890631
DOI: 10.1186/s12891-024-07592-x -
Cancer Radiotherapie : Journal de La... Jun 2024Stereotactic body radiotherapy is a highly effective form of radiation therapy for palliation of bone metastases, but it can also lead to rare but severe side effects,... (Review)
Review
Stereotactic body radiotherapy is a highly effective form of radiation therapy for palliation of bone metastases, but it can also lead to rare but severe side effects, such as myonecrosis. According to the literature, the incidence of myonecrosis after stereotactic body radiotherapy is low and mostly dose dependent. It is crucial to consider the potential impact of immunotherapy and other systemic therapies in the assessment. The course of radiation myonecrosis can vary, and corticosteroids or vascular endothelial growth factor inhibitors may potentially play a role in its treatment. Herein, we report two patients presenting with myonecrosis after stereotactic body radiotherapy for bone metastasis.
Topics: Humans; Radiosurgery; Necrosis; Bone Neoplasms; Male; Aged; Middle Aged; Female; Muscular Diseases; Radiation Injuries; Muscle, Skeletal
PubMed: 38890033
DOI: 10.1016/j.canrad.2023.10.001 -
Translational Cancer Research May 2024Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had...
Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur. We then used immune deconvolution of RNA sequencing datasets to evaluate immunologic cell subset enrichment. This identified M2 macrophage signaling associated with type I IFN pathway expression in RT-recurrent disease. To further dissect mechanism, we then evaluated differential gene expression between pre-treatment and RT-resistant HNCs from sampled from the same patients at the same anatomical location in the oral cavity. Here, recurrent samples exhibited upregulation of type I IFN-stimulated genes (ISGs) including members of the IFN-induced protein with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane (IFITM) gene families. While several ISGs were upregulated in each recurrent cancer, IFIT2 was significantly upregulated in all recurrent tumors when compared with the matched pre-RT specimens. Based on these observations, we hypothesized sustained type I IFN signaling through ISGs, such as IFIT2, may suppress the intra-tumoral immune response thereby promoting radiation resistance.
PubMed: 38881922
DOI: 10.21037/tcr-23-2104 -
Radiotherapy and Oncology : Journal of... Jun 2024Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates...
BACKGROUND AND PURPOSE
Preclinical research demonstrated that the exposure of microbubbles (intravascular gas microspheres) to focussed ultrasound within the targeted tumour upregulates pro-apoptotic pathways and enhances radiation-induced tumour cell death. This study aimed to assess the safety and efficacy of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubbles (MRgFUS-MB) for head and neck cancers (HN).
MATERIALS AND METHODS
This prospective phase 1 clinical trial included patients with newly diagnosed or recurrent HN cancer (except nasopharynx malignancies) for whom locoregional radiotherapy with radical- or palliative-intent as deemed appropriate. Patients with contraindications for microbubble administration or contrast-enhanced MR were excluded. MR-coupled focussed ultrasound sonicated intravenously administered microbubbles within the MR-guided target volume. Patients receiving 5-10 and 33-35 radiation fractions were planned for 2 and 3 MRgFUS-MB treatments, respectively. Primary endpoint was toxicity per CTCAEv5.0. Secondary endpoint was tumour response at 3 months per RECIST 1.1 criteria.
RESULTS
Twelve patients were enrolled between Jun/2020 and Nov/2023, but 1 withdrew consent. Eleven patients were included in safety analysis. Median follow-up was 7 months (range, 0.3-38). Most patients had oropharyngeal cancer (55 %) and received 20-30 Gy/5-10 fractions (63 %). No systemic toxicity or MRgFUS-MB-related adverse events occurred. The most severe acute adverse events were radiation-related grade 3 toxicities in 6 patients (55 %; dermatitis in 3, mucositis in 1, dysphagia in 6). No radiation necrosis or grade 4/5 toxicities were reported. 8 patients were included in the 3-month tumour response assessment: 4 had partial response (50 %), 3 had complete response (37.5 %), and 1 had progressive disease (12.5 %).
CONCLUSIONS
MRgFUS-MB treatment was safe and associated with high rates of tumour response at 3 months.
PubMed: 38879128
DOI: 10.1016/j.radonc.2024.110380 -
IEEE Journal of Biomedical and Health... Jun 2024GB (Glioblastoma WHO Grade 4) is the most aggressive type of brain tumor in adults that has a short survival rate even after aggressive treatment with surgery and...
GB (Glioblastoma WHO Grade 4) is the most aggressive type of brain tumor in adults that has a short survival rate even after aggressive treatment with surgery and radiation therapy. The changes in magnetic resonance imaging (MRI) for patients with GB after radiotherapy are indicative of either radiation-induced necrosis (RN) or recurrent brain tumor (rBT). Screening for rBT and RN at an early stage is crucial for facilitating faster treatment and better outcomes for the patients. Differentiating rBT from RN is challenging as both may present with similar radiological and clinical characteristics on MRI. Moreover, learning-based rBT versus RN classification using MRI may suffer from class imbalance due to a lack of patient data. While synthetic data generation using generative models has shown promise to address class imbalances, the underlying data representation may be different in synthetic or augmented data. This study proposes computational modeling with statistically rigorous repeated random sub-sampling to balance the subset sample size for rBT and RN classification. The proposed pipeline includes multiresolution radiomic feature (MRF) extraction followed by feature selection with statistical significance testing (p<0.05). The five-fold cross validation results show the proposed model with MRF features classifies rBT from RN with an area under the curve (AUC) of 0.892±0.055. Moreover, considering the dependence between survival time and censoring time (where patients are not followed up until death), the feasibility of using MRF radiomic features as a non-invasive biomarker to identify patients who are at higher risk of recurrence or radiation necrosis is demonstrated. The cross-validated results show that the MRF model provides the best overall survival prediction with an AUC of 0.77±0.032. Comparison with state-of-the-art methods suggest the proposed method is effective in RN versus rBT classification and patient survivability prediction.
PubMed: 38875078
DOI: 10.1109/JBHI.2024.3406256 -
Journal of Applied Clinical Medical... Jun 2024The study aimed to investigate the optimal isodose line (IDL) in linear accelerator-based stereotactic radiotherapy for single brain metastasis, using HyperArc. We...
PURPOSE
The study aimed to investigate the optimal isodose line (IDL) in linear accelerator-based stereotactic radiotherapy for single brain metastasis, using HyperArc. We compared the dosimetric parameters for target and normal brain tissue among six plans with different IDLs.
METHODS
This study included 30 patients with single brain metastasis. We retrospectively generated six plans for each tumor with different IDLs (80%, 70%, 60%, 50%, 40%, and 33%) using HyperArc. All treatment plans were normalized to the prescription dose of 35 Gy in five fractions which was covered by 95% of the planning target volume (PTV), defined by adding a 1.0 mm margin to the gross tumor volume (GTV). The dosimetric parameters were compared among the six plans.
RESULTS
For GTV > 0.1 cm, the ratio of brain-GTV volumes receiving 25 Gy to PTV (V/PTV) was significantly lower at IDL 40%-70% than at IDL 80% and 33% (p < 0.01, retrospectively). For GTV < 0.1 cm, V/PTV decreased continuously as IDL decreased. The values of D and D for GTV increased with decreasing IDL. An IDL of 50% or less was required to achieve D of greater than 43 Gy and D of greater than 50 Gy. The mean values of D and D for IDL 50% were 44.3 and 51.9 Gy.
CONCLUSION
The optimal IDL is 40%-50% for GTV > 0.1 cm. These lower IDLs could increase D and D of GTV while lowering V of normal brain tissue, which may help reduce the risk of radiation necrosis and improve local control.
PubMed: 38863310
DOI: 10.1002/acm2.14408 -
Breast Cancer (Tokyo, Japan) Jun 2024The safety and outcome of breast reconstruction after radiotherapy are controversial, and the aesthetic aspects have not been studied extensively. We compared the...
BACKGROUND
The safety and outcome of breast reconstruction after radiotherapy are controversial, and the aesthetic aspects have not been studied extensively. We compared the results of vascular anastomosis, the incidence of postoperative complications, and aesthetic appearance between patients who had and had not received radiotherapy who then had undergone delayed breast reconstruction with autologous free flaps from the abdomen, thighs, and buttocks.
METHODS
In total, 257 flaps in 241 patients were investigated; 194 and 63 flaps implanted in patients who did not receive radiotherapy and who received radiotherapy before breast reconstruction, respectively. Of the 257 flaps, 221, 20, 14, and 2 came from the abdomen, thighs, buttocks, and other anatomic locations, respectively. We evaluated aesthetic outcomes in 105 patients who had not received radiotherapy and 35 who had.
RESULTS
We found no significant differences between the two groups in the incidence of vascular reanastomosis, the time required for anastomosis, or the incidence of unplanned reoperation. Complications such as flap necrosis were rare in both groups. Aesthetic outcomes were significantly better in the patients who had not received radiotherapy.
CONCLUSIONS
Breast reconstruction with autologous free flaps can be performed safely in patients who have received radiotherapy, but the aesthetic result is slightly inferior to that in patients who had not received radiotherapy.
PubMed: 38862869
DOI: 10.1007/s12282-024-01593-3 -
Medical Oncology (Northwood, London,... Jun 2024Resistance to caspase-dependent apoptosis is often responsible for treatments failure in cancer. Necroptosis is a type of programmed necrosis that occurs under...
Resistance to caspase-dependent apoptosis is often responsible for treatments failure in cancer. Necroptosis is a type of programmed necrosis that occurs under caspase-deficient conditions that could overcome apoptosis resistance. Our purpose was to investigate the interrelationship between apoptotic and necroptotic death pathways and their influence on the response of breast cancer cells to radiotherapy in vitro. Human BC cell lines MCF-7 and MDA-MB-231 were treated with ionizing radiation, and then several markers of apoptosis, necroptosis, and survival were assessed in the presence and absence of necroptosis inhibition. MLKL knockdown was achieved by siRNA transfection. Our main findings emphasize the role of necroptosis in cellular response to radiation represented in the dose- and time-dependent elevated expression of necroptotic markers RIPK1, RIPK3, and MLKL. Knockdown of necroptotic marker MLKL by siRNA led to a significant elevation in MDA-MB-231 and MCF-7 survival with a dose modifying factor (DMF) of 1.23 and 1.61, respectively. Apoptotic markers Caspase 8 and TRADD showed transitory or delayed upregulation, indicating that apoptosis was not the main mechanism by which cells respond to radiation exposure. Apoptotic markers also showed a significant elevation following MLKL knockdown, suggesting its role either as a secondary or death alternative pathway. The result of our study emphasizes the critical role of the necroptotic pathway in regulating breast cancer cells responses to radiotherapy and suggests a promising utilization of its key modulator, MLKL, as a treatment strategy to improve the response to radiotherapy.
Topics: Humans; Apoptosis; Breast Neoplasms; Female; Necroptosis; Protein Kinases; Cell Line, Tumor; RNA, Small Interfering; Signal Transduction; MCF-7 Cells
PubMed: 38862702
DOI: 10.1007/s12032-024-02415-4 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2024To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.
OBJECTIVE
To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism.
METHODS
Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100 μL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections. On the 15th day after irradiation, histopathological changes of the lungs of the mice were examined using HE staining, the levels of TNF-α, TGF-β, IL-1α and IL-6 in the lung tissue and serum were detected using ELISA, and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry. High-throughput sequencing of exosome miRNA was carried out to explore the changes in the signaling pathways. The mRNA expression levels of the immune-related genes were detected by qRT-PCR, and the protein expressions of talin-1, tensin2, FAK, vinculin, α-actinin and paxillin in the focal adhesion signaling pathway were detected with Western blotting.
RESULTS
In the mouse models of radiation pneumonitis, injections of normal mouse serum significantly decreased the lung organ coefficient, lowered the levels of TNF-α, TGF-β, IL-1α and IL-6 in the serum and lung tissues, and ameliorated infiltration of CD45, CD4 and T lymphocytes in the lung tissue (all <0.05). The expression levels of and genes at both the mRNA and protein levels and the protein expressions of talin-1, tensin2, FAK, vinculin, α‑actinin and paxillin were all significantly down-regulated in the mouse models after normal mouse serum treatment.
CONCLUSION
Normal mouse serum ameliorates radiation pneumonitis in mice by inhibiting the expressions of key proteins in the Focal adhesion signaling pathway.
Topics: Animals; Mice; Signal Transduction; Radiation Pneumonitis; Focal Adhesions; Lung; Interleukin-6; Disease Models, Animal; Tumor Necrosis Factor-alpha; Transforming Growth Factor beta; MicroRNAs; Interleukin-1alpha
PubMed: 38862437
DOI: 10.12122/j.issn.1673-4254.2024.05.01