Local thermal ablative therapies for extracranial oligometastatic disease of non-small-cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Clinically, 40-50% of patients with NSCLC are found to have systemic metastasis at the initial diagnosis. Meanwhile, 30-75% of patients with lung cancer who have undergone radical surgical resection have local recurrence and distant metastases. However, not all distant metastases are multiple, and some are potentially curable. In this study, among the patients with NSCLC having distant organ metastasis, approximately 7% showed extrapulmonary solitary metastasis and remained in this relatively stable state for a long time. This form of metastasis is known as NSCLC oligometastases. This review describes the concept and classification of oligometastases, as well as the local treatment and prognosis of extracranial oligometastases.

Image-guided thermal ablation for patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer.

Nonsmall cell lung cancer (NSCLC) is treated by various therapies such as surgical intervention, radiotherapy, chemotherapy, molecular targeted therapy, and immunotherapy. Currently, molecular targeted therapy, including epidermal growth factor receptor (EGFR) inhibitors and Anaplastic Lymphoma Kinase (ALK) and Kirsten Rat Sarcoma viral Oncogene (KRAS) inhibitors, has received much attention and improved the prognosis of NSCLC. Nevertheless, the terminal point of molecular targeted drugs is resistance. Drug resistance has been classified into oligoprogression and extensive progression based on the tumor lesion progression after drug resistance. There is extensive research demonstrating that local therapy (surgical resection, radiotherapy, and thermal ablation) can prolong the survival of patients with drug resistance. This review is intended to determine the efficacy of image-guided thermal ablation in patients with NSCLC with EGFR mutation.

Microwave ablation plus camrelizumab monotherapy or combination therapy in non-small cell lung cancer.

Purpose: Immunotherapy has become widely applied in non-small cell lung cancer (NSCLC) patients. However, the relatively low response rate of immunotherapy monotherapy restricts its application. Combination therapy improves the response rate and prolongs patient survival; however, adverse events (AEs) associated with immunotherapies increase with combination therapy. Therefore, exploring combination regimens with equal efficacy and fewer AEs is urgently required. The aim of this study was to evaluate the efficacy and safety of microwave ablation (MWA) plus camrelizumab monotherapy or combination therapy in NSCLC. Materials and methods: Patients with pathologically confirmed, epidermal growth factor receptor/anaplastic lymphoma kinase-wild-type NSCLC were retrospectively enrolled in this study. Patients underwent MWA to the pulmonary lesions first, followed by camrelizumab monotherapy or combination therapy 5-7 days later. Camrelizumab was administered with the dose of 200 mg every 2 to 3 weeks. Treatment was continued until disease progression or intolerable toxicities. The technical success and technique efficacy of ablation, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), complications of ablation, and AEs were recorded. Results: From January 1, 2019 to December 31, 2021, a total of 77 patients underwent MWA and camrelizumab monotherapy or combination therapy. Technical success was achieved in all patients (100%), and the technique efficacy was 97.4%. The ORR was 29.9%. The PFS and OS were 11.8 months (95% confidence interval, 9.5-14.1) and not reached, respectively. Smoking history and response to camrelizumab were correlated with PFS, and response to camrelizumab was correlated with OS in both the univariate and multivariate analyses. No periprocedural deaths due to ablation were observed. Complications were observed in 33 patients (42.9%). Major complications included pneumothorax (18.2%), pleural effusion (11.7%), pneumonia (5.2%), bronchopleural fistula (2.6%), and hemoptysis (1.3%). Grade 3 or higher AEs of camrelizumab, including reactive capillary endothelial proliferation, fatigue, pneumonia, edema, and fever, were observed in 10.4%, 6.5%, 5.2%, 2.6%, and 2.6% of patients, respectively. Conclusion: MWA combined with camrelizumab monotherapy or combination therapy is effective and safe for the treatment of NSCLC.

Recent advances in nonsurgical treatment of pulmonary ground-glass nodules.

Since the 1990s, low-dose computed tomography technology has been used in lung cancer screening. With the increase of computed tomography screening, the detection rate of ground-glass nodules (GGN) has increased dramatically. At present, the main treatment strategy for GGN is surgical resection. However, for patients with poor cardiopulmonary functions, a history of lung resection, multiple pulmonary nodules, or the age of >75 years, surgical resection is very difficult and not medically encouraged. This article reviews the applications and outcomes evaluation of nonsurgical treatments, such as chemotherapy, radiotherapy, moleculartargeted drug therapy, immunity therapy, and image-guided thermal ablation in patients with GGN.

Microwave ablation of non-small cell lung cancer tumors changes plasma levels of cytokines IL-2 and IFN-γ.

Background: Combined therapy with immune checkpoint inhibitors (ICIs) and microwave ablation (MWA) is known to improve outcome in non-small cell lung cancer (NSCLC). However, the mechanism underlying the synergistic effect of these two treatments is unknown. Tumor immune microenvironment is known to affect the efficacy of ICI. Therefore, in the present study, we evaluated changes in the levels of peripheral cytokines at 48 h and 1-month post-ablation in patients with NSCLC. Materials and Methods: A total of 44 patients with primary NSCLC were retrospectively enrolled. All patients underwent MWA of the primary tumors. Plasma samples were collected pre- and post-ablation to examine the levels of various cytokines, including interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor (TNF)-α, and interferon-gamma (IFN-γ). Results: Although the levels of the majority of cytokines remained within normal range, levels of IL-2 and IFN-γ were significantly decreased at 48 h post-ablation and increased at 1-month post-ablation. In the subgroup analyses, changes in IL-2 and IFN-γ levels were commonly identified. Moreover, the Eastern Cooperative Oncology Group status, sex, pathology type, tumor site, and tumor size were associated with cytokines' levels pre-ablation or post-ablation. Conclusion: MWA of NSCLC tumors influenced the plasma levels of cytokines IL-2 and IFN-γ.

Immune abscopal effect of microwave ablation for lung metastases of endometrial carcinoma.

Increasing evidence support that microwave ablation (MWA) induces spontaneous abscopal regression of the tumor, also called as the abscopal effect. Although the abscopal effect after MWA is a rare event, several studies have suggested that this effect is the result of the activation of the immune system induced by the death of immunogenic tumor cells. Here, we have presented the case of a 65-year-old woman with primary endometrial cancer who developed bilateral pulmonary metastases. After local MWA of one lesion in her right lung, progressive regression of the other lesions in the right and left lungs was recorded. This case supports the hypothesis that the abscopal effect is attributable to the activation of the systemic immune response.

Protective effects and mechanisms of Terminalia catappa L. methenolic extract on hydrogen-peroxide-induced oxidative stress in human skin fibroblasts.

BACKGROUND: Oxidative stress plays a crucial role in aging-related phenomenon, including skin aging and photoaging. This study investigated the protective role and possible mechanism of Terminalia catappa L. methanolic extract (TCE) in human fibroblasts (Hs68) against hydrogen peroxide (H2O2)-induced oxidative damage. METHODS: Various in vitro antioxidant assays were performed in this study. The effect and mechanisms of TCE on oxidative stress-induced oxidative damage were studied by using western blotting. RESULTS: The IC50 of TCE was 8.2 µg/mL for 1,1-diphenyl-2-picrylhydrazyl radical scavenging, 20.7 µg/mL for superoxide anion radical scavenging, 173.0 µg/mL for H2O2 scavenging, 44.8 µg/mL for hydroxyl radical scavenging, and 427.6 µg/mL for ferrous chelation activities. Moreover, TCE inhibited the H2O2-induced mitogen-activated protein kinase signaling pathway, resulting in the inhibition of c-Jun, c-Fos, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, and cyclooxygenase-2 expression. TCE also increased hemeoxygenase-1 expression inhibited by H2O2. Finally, TCE was demonstrated reverse type I procollagen expression in fibroblasts after H2O2 treatment. CONCLUSIONS: According to our findings, TCE is a potent antioxidant and protective agent that can be used in antioxidative stress-induced skin aging.

Alleviation of Ultraviolet B-Induced Photodamage by Coffea arabica Extract in Human Skin Fibroblasts and Hairless Mouse Skin.

Coffea arabica extract (CAE) containing 48.3 ± 0.4 mg/g of chlorogenic acid and a trace amount of caffeic acid was found to alleviate photoaging activity in human skin fibroblasts. In this study, polyphenol-rich CAE was investigated for its antioxidant and antiinflammatory properties, as well as for its capability to alleviate ultraviolet B (UVB)-induced photodamage in BALB/c hairless mice. The results indicated that 500 µg/mL of CAE exhibited a reducing power of 94.7%, ferrous ion chelating activity of 46.4%, and hydroxyl radical scavenging activity of 20.3%. The CAE dose dependently reduced UVB-induced reactive oxygen species (ROS) generation in fibroblasts. Furthermore, CAE inhibited the UVB-induced expression of cyclooxygenase-2 and p-inhibitor κB, and the translocation of nuclear factor-kappa B (NF-κB) to the nucleus of fibroblasts. In addition, CAE alleviated UVB-induced photoaging and photodamage in BALB/c hairless mice by restoring the collagen content and reduced UVB-induced epidermal hyperplasia. CAE also inhibited UVB-induced NF-κB, interleukin-6, and matrix metalloproteinase-1 expression in the hairless mouse skin. The results indicated that CAE exhibits antiphotodamage activity by inhibiting UV-induced oxidative stress and inflammation. Therefore, CAE is a candidate for use in antioxidant, antiinflammatory, and antiphotodamage products.

TDAG8 involved in initiating inflammatory hyperalgesia and establishing hyperalgesic priming in mice.

Chronic pain, resulting from injury, arthritis, and cancer, is often accompanied by inflammation. High concentrations of protons found in inflamed tissues results in tissue acidosis, a major cause of pain and hyperalgesia. Acidosis signals may mediate a transition from acute to chronic hyperalgesia (hyperalgesic priming) via proton-sensing G-protein-coupled receptors (GPCRs). The expression of T-cell death-associated gene 8 (TDAG8), a proton-sensing GPCR, is increased during inflammatory hyperalgesia. Attenuating TDAG8 expression in the spinal cord inhibits bone cancer pain, but whether TDAG8 is involved in inflammatory hyperalgesia or hyperalgesic priming remains unclear. In this study, we used TDAG8-knockout or -knockdown to explore the role of TDAG8 in pain. Suppressed TDAG8 expression delayed the onset of inflammatory hyperalgesia and shortened hyperalgesic time in mice. In a dual acid-injection model (acid [pH 5.0] injected twice, 5 days apart), shRNA inhibition of TDAG8 shortened the duration of the second hyperalgesia. Similar results were found in TDAG8-deficient mice. The dual administration of TDAG8 agonist also confirmed that TDAG8 is involved in hyperalgsic priming. Accordingly, TDAG8 may mediate acidosis signals to initiate inflammatory hyperalgesia and establish hyperalgesic priming.

Heteromerization of G2A and OGR1 enhances proton sensitivity and proton-induced calcium signals.

Proton-sensing G-protein-coupled receptors (GPCRs; OGR1, GPR4, G2A, TDAG8), with full activation at pH 6.4 ∼ 6.8, are important to pH homeostasis, immune responses and acid-induced pain. Although G2A mediates the G13-Rho pathway in response to acid, whether G2A activates Gs, Gi or Gq proteins remains debated. In this study, we examined the response of this fluorescence protein-tagged OGR1 family to acid stimulation in HEK293T cells. G2A did not generate detectable intracellular calcium or cAMP signals or show apparent receptor redistribution with moderate acid (pH ≥ 6.0) stimulation but reduced cAMP accumulation under strong acid stimulation (pH ≤ 5.5). Surprisingly, coexpression of OGR1- and G2A-enhanced proton sensitivity and proton-induced calcium signals. This alteration is attributed to oligomerization of OGR1 and G2A. The oligomeric potential locates receptors at a specific site, which leads to enhanced proton-induced calcium signals through channels.

Distinct expression of Mas1-related G-protein-coupled receptor B4 in dorsal root and trigeminal ganglia--implications for altered behaviors in acid-sensing ion channel 3-deficient mice.

Mas1-related G-protein-coupled receptors (Mrgprs), comprising more than 50 distinct members, are specifically expressed in primary sensory neurons. Reflecting the diversity and specificity of stimuli they detect, Mrgprs are involved in pain, touch, and itch-related behaviors. Sensory-neuron-specific acid-sensing ion channel 3 (ASIC3) is essential for touch and inflammatory pain, but mice lacking ASIC3 have complex behavioral alterations in various modalities of pain and touch. To understand whether Mrgprs are involved in complex behavioral alterations found in ASIC3-deficient mice, we examined Mrgpr gene expression in ASIC3(-/-) mice. Only MrgprB4 expression has shown significant change. MrgprB4 expression was increased in ASIC3(-/-) dorsal root ganglia (DRG) but decreased in ASIC3(-/-) trigeminal ganglia. The distinct alterations in DRG and trigeminal ganglia imply that MrgprB4 could have multiple functions. Given that MrgprB4 is expressed in neurons that may detect gentle touch and that ASIC3(-/-) mice have altered sensitivity of mechanoreceptors for light touch, the expression change of MrgprB4 is more likely related to the altered touch behaviors of ASIC3(-/-) mice.