Long-term survival with a combination of immunotherapy, anti-angiogenesis, and traditional radiotherapy in brain metastatic small cell lung cancer: a case report.

Purpose: Brain metastases (BMs) are common in Small Cell Lung Cancer (SCLC), but the prognosis is very poor. Currently, there is no standard of care on what constitutes optimal treatment, and there is no consensus regarding maintenance therapy in SCLC. Case description: We report the case of a 55-year-old man with advanced SCLC. After the initial diagnosis, he received routine chemotherapy and chest radiotherapy but developed brain metastases with 2 lesions seven months later. We used an effective combination therapy consisting of the antiangiogenic inhibitor, Anlotinib and whole-brain radiotherapy. We then administered anti-PD-L1 immunotherapy Atezolizumab in combination with Anlotinib as long-term maintenance therapy. Twelve months later, there was a progression in one of the brain metastases. The patient underwent further stereotactic radiotherapy (SRT) for the lesion. However, after four months of treatment with SRT, the lesion began to gradually grow in size. The patient underwent surgical resection of the lesion, which confirmed radioactive brain necrosis. After a full 3-year course of anti-PD-L1 therapy, the patient discontinued immunotherapy and was administered only Anlotinib as maintenance. At the time of writing up this report, the patient was alive and the overall survival reached 41 months after the onset of BM. Conclusion: This indicated a potential synergistic effect of combined immunotherapy and antiangiogenic targeted therapy with local radiotherapy in patients with BM-SCLC and can provide directions for future clinical decisions.

A Perspective of Epigenetic Regulation in Radiotherapy.

Radiation therapy (RT) has been employed as a tumoricidal modality for more than 100 years and on 470,000 patients each year in the United States. The ionizing radiation causes genetic changes and results in cell death. However, since the biological mechanism of radiation remains unclear, there is a pressing need to understand this mechanism to improve the killing effect on tumors and reduce the side effects on normal cells. DNA break and epigenetic remodeling can be induced by radiotherapy. Hence the modulation of histone modification enzymes may tune the radiosensitivity of cancer cells. For instance, histone deacetylase (HDAC) inhibitors sensitize irradiated cancer cells by amplifying the DNA damage signaling and inhibiting double-strand DNA break repair to influence the irradiated cells' survival. However, the combination of epigenetic drugs and radiotherapy has only been evaluated in several ongoing clinical trials for limited cancer types, partly due to a lack of knowledge on the potential mechanisms on how radiation induces epigenetic regulation and chromatin remodeling. Here, we review recent advances of radiotherapy and radiotherapy-induced epigenetic remodeling and introduce related technologies for epigenetic monitoring. Particularly, we exploit the application of fluorescence resonance energy transfer (FRET) biosensors to visualize dynamic epigenetic regulations in single living cells and tissue upon radiotherapy and drug treatment. We aim to bridge FRET biosensor, epigenetics, and radiotherapy, providing a perspective of using FRET to assess epigenetics and provide guidance for radiotherapy to improve cancer treatment. In the end, we discuss the feasibility of a combination of epigenetic drugs and radiotherapy as new approaches for cancer therapeutics.

Phase Separation and Histone Epigenetics in Genome Regulation.

Liquid-liquid phase separation is increasingly recognized as a phenomenon that affects cell behavior. For example, phase separation of transcription factors and coactivators has been shown to drive efficient transcription. For many years, phase separation of intracellular components has been observed; however, only recently have researchers been able to garner functional significance from such events. Inspired from recent literature that describes phase separation of chromatin in a histone-dependent manner, we review the role and effect of phase separation and histone epigenetics in regulating the genome and discuss how these phenomena can be leveraged to control cell behavior.

Association of Epstein-Barr virus infection with peripheral immune parameters and clinical outcome in advanced nasopharyngeal carcinoma.

The purpose of this study was to investigate the association of Epstein-Barr virus (EBV) with peripheral blood immune cell counts and clinical outcomes in advanced nasopharyngeal carcinoma (NPC) patients. In a retrospective design, 146 patients with NPC at stage IV were enrolled in this study. The association of EBV status with peripheral blood immune cell counts, distant metastases, and long-term survival in patients with advanced NPC were determined. Eighty-seven (59.6%) of all patients were positive for EBV. Compared with patients with normal NK cell count, patients with lower NK cell count showed a significantly lower EBV viral load (median: 614.0 vs. 2190.0 copies/mL, P = 0.024). EBV-positive patients showed a significantly higher incidence of liver metastasis than EBV-negative patients (32.6% vs. 23.7%, P = 0.021). Multi-variant regression analysis showed that EBV infection was independently associated with liver metastasis (OR: 2.33, P = 0.043). EBV positive patients showed a significantly worse PFS (P = 0.001) and OS (P = 0.001) than EBV negative patients. Multivariate Cox regression analysis revealed that EBV infection was independently associated with a worse PFS (HR: 1.94, P = 0.003), and OS (HR: 2.12, P = 0.014) in advanced NPC. In conclusion, EBV infection is associated with a high risk of liver metastasis and is also an independent negative predictor for PFS and OS in patients with advanced NPC. EBV infection is associated with lower CD8% and higher NK%, while lower NK cell count is associated with lower EBV viral load.

The Role of Additional Chemotherapy in Combination with Concurrent Chemoradiotherapy for Locally Advanced Inoperable Non-Small Cell Lung Cancer, a Systematic Review and Meta-Analysis of 12 Randomized Trials.

This meta-analysis aims to evaluate the effectiveness of chemotherapy before (I-CRT) or after (CRT-C) chemoradiotherapy (CRT) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC). According to the object response rate (ORR) and disease control rate (DCR), there were no differences among I-CRT, CRT, and CRT-C treatments. I-CRT did not have significant survival benefits compared with CRT alone. Similar results comparing CRT-C with CRT were observed. Furthermore, I-CRT was not associated with improved survival compared to CRT-C with respect to OS and PFS. Our meta-analysis suggests the effects of additional chemotherapy added to CRT were limited for unselected LA-NSCLC.

The PI3K/AKT axis modulates AATF activity in Wilms' tumor cells.

Previous studies have reported excessive expression of apoptosis-antagonizing transcription factor (AATF) in various tumors, where it reinforces the generation and development of cancers and is linked to the clinical outcome. Nevertheless, the expression and influence of AATF in Wilms' tumor (WT) is largely unknown. Here, we discovered that AATF expression was markedly increased in WT tissues as compared to the surrounding normal tissues. Elevated levels of AATF expression were related to tumor relapse and pulmonary metastasis, congruent with it being a predictor of clinical outcome in people suffering from WT. Proliferation, invasion, and migration of WT cells were suppressed by knockdown of AATF and promoted by AATF overexpression in vitro. Furthermore, the tumor generation capability of WT cells noticeably decreased after knockout of AATF in vivo. The phosphoinositide-3-kinase (PI3K)/AKT pathway modulated the activity of AATF in WT. The findings of our study indicate that AATF expression is increased in WT and can serve as a predictor of clinical outcome; in addition, it may enhance the development of WT via the PI3K/AKT axis and may be a promising marker for WT diagnosis and therapy.

Soy food intake and risk of gastric cancer: A dose-response meta-analysis of prospective studies.

Epidemiological studies were inconsistent on the association between soy food intake and risk of gastric cancer (GC). This study aimed to determine the role of soy food intake in the development of GC.A systematic search was conducted in PubMed and Web of Science to identify all relevant studies. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, and the dose-response relationship between soy food intake and GC risk was also assessed.Thirteen prospective studies were identified with a total of 517,106 participants and 5800 cases. Among 11 types of soy food, high intake of total soy food (the highest vs the lowest category: RR: 0.78, 95% CI: 0.62-0.98) and nonfermented soy food (RR: 0.63, 95% CI: 0.50-0.79) were inversely associated with GC risk, while high intake of miso soup was associated with the risk in male (RR: 1.17, 95% CI: 1.02-1.36). In dose-response meta-analysis, total soy food intake (0-150 g/day) showed no significant association with GC risk, while high intake of nonfermented soy food was inversely related, especially an intake of more than 100 g/day. In male, miso soup intake (1-5 cups/day) was significantly associated with GC risk.High intake of nonfermented soy food might reduce the risk of GC, while miso soup intake might increase the risk in male.