Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

FLNB overexpression promotes tumor progression and associates with immune suppression, evasion and stemness in pancreatic cancer.

Pancreatic cancer (PC) is an immunosuppressive cancer. Immune-based therapies that enhance or recruit antitumor immune cells into the tumor microenvironment (TME) remain promising strategies for PC treatment. Consequently, a deeper understanding of the molecular mechanisms involved in PC immune suppression is critical for developing immune-based therapies to improve survival rates. In this study, weighted gene co-expression network analysis (WGCNA) was used to identify Filamin B (FLNB) correlated with the infiltration of CD8+ T cells and tumor-associated macrophages (TAMs). The clinical significance and potential biological function of FLNB were evaluated using bioinformatic analysis. The oncogenic role of FLNB in PC was determined using in vitro and in vivo studies. We further analyzed possible associations between FLNB expression and tumor immunity using CIBERSORT, single sample gene set enrichment analysis, and ESTIMATE algorithms. We found FLNB was overexpressed in PC tissues and was correlated with poorer overall survival, tumor recurrence, larger tumor size, and higher histologic grade. Moreover, FLNB overexpression was associated with the mutation status and expression of driver genes, especially for KRAS and SMAD4. Functional enrichment analysis identified the role of FLNB in the regulation of cell cycle, focal adhesion, vascular formation, and immune regulation. Knockdown of FLNB expression inhibited cancer cell proliferation and migration in-vitro and suppressed tumor growth in-vivo. Furthermore, FLNB overexpression caused high infiltration of Treg cells, Th2 cells, and TAMs, but reduced infiltration of CD8+ T cells and Th1/Th2. Collectively, our findings suggest FLNB promotes PC progression and may be a novel biomarker for PC.

Prognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy.

BACKGROUND AND AIMS: Dual programmed death 1 (PD-1) and angiogenesis blockade therapy is a frontline treatment for hepatocellular carcinoma (HCC). An accepted model for survival prediction and risk stratification in individual patients receiving this treatment is lacking. Aimed to develop a simple prognostic model specific to these patients. APPROACH AND RESULTS: Patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy were included in training cohort (n=168) and validation cohort (n=72). We investigated the prognostic value of clinical variables on overall survival using a Cox model in the training set. A prognostic score model was then developed and validated. Predictive performance and discrimination were also evaluated. Largest tumor size and Alpha-fetoprotein concentration at baseline and Neutrophil count and Spleen volume change after 6 weeks of treatment were identified as independent predictors of overall survival in multivariable analysis and used to develop LANS score. Time-dependent receiver operating characteristic analysis, calibration curves, and C-index showed LANS score had favorable performance in survival prediction. Patients were divided into three risk categories based on LANS score. Median survival for patients with low, intermediate, and high LANS scores was 31.7, 23.5, and 11.5 months, respectively (p<0.0001). The disease control rates were 96.4%, 64.3%, and 32.1%, respectively (p<0.0001). The predictive performance and risk stratification ability of the LANS score were confirmed in validation and entire cohorts. CONCLUSION: The LANS score model can provide individualized survival prediction and risk stratification in patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy.

Immune suppressive microenvironment in liver metastases contributes to organ-specific response of immunotherapy in advanced non-small cell lung cancer.

BACKGROUND: The liver is a frequent site of metastases and liver metastases (LM) correlate with diminished immunotherapy efficacy in non-small cell lung cancer (NSCLC). This study aimed to analyze whether tumor response to immunotherapy differs between pulmonary lesions (PL) and LM in NSCLC and to explore potential mechanisms through multiomics analysis. METHODS: This observational longitudinal clinical cohort study included patients with NSCLC with LM receiving immunotherapy was conducted to evaluate organ-specific tumor response of PL and LM. We collected paired PL and LM tumor samples to analyze the organ-specific difference using whole-exome sequencing, RNA sequencing, and multiplex immunohistochemistry. RESULTS: A total of 52 patients with NSCLC with LM were enrolled to evaluate the organ-specific response of immunotherapy. The objective response rate (21.1% vs 32.7%) and disease control rate of LM were lower than that of PL (67.3% vs 86.5%). One-third of patients showed mixed response, among whom 88.2% (15/17) presented with LM increasing, but PL decreasing, while the others had the opposite pattern (p=0.002). In another independent cohort, 27 pairs of matched PL and LM tumor samples from the same individuals, including six simultaneously collected pairs, were included in the translational part. Genomic landscapes profiling revealed similar somatic mutations, tumor mutational burden, and neoantigen number between PL and LM. Bulk-RNA sequencing showed immune activation-related genes including CD8A, LCK, and ICOS were downregulated in LM. The antigen processing and presentation, natural killer (NK) cell-mediated cytotoxicity and T-cell receptor signaling pathway were enriched in PL compared with LM. Multiplex immunohistochemistry detected significantly lower fractions of CD8+ cells (p=0.036) and CD56dim+ cells (p=0.016) in LM compared with PL. Single-cell RNA sequencing also characterized lower effector CD8+ T cells activation and NK cells cytotoxicity in LM. CONCLUSIONS: Compared with PL, LM presents an inferior organ-specific tumor response to immunotherapy. PL and LM showed limited heterogeneity in the genomic landscape, while the LM tumor microenvironment displayed lower levels of immune activation and infiltration than PL, which might contribute to developing precise immunotherapy strategies for patients with NSCLC with LM.

Organ-specific efficacy in advanced non-small cell lung cancer patients treated with first-line single-agent immune checkpoint inhibitors.

BACKGROUND: Response to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People's Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated. RESULTS: Forty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs . 15.5 months, P  = 0.0005) and OS (11.1 months vs . not reached, P  = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs . 15.5 months, P  = 0.0532) rather than OS ( P  = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs . 4.3 months, P  = 0.1894). More metastatic organs involved were associated with inferior PFS ( P  = 0.0052) but not OS ( P  = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[ϕ]: 0.516, P  = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4). CONCLUSIONS: Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription.

Glioblastoma multiforme (GBM) is the most common cancer in nervous system around the world. Little advancement has been achieved in promoting prognosis of GBM patients. Circular RNAs (circRNAs) are suggested as crucial effectors in modulating GBM development. Hsa_circRNA_092437 (circPOLR2A), an up-regulated circRNA in GBM cells, has not been studied yet. In this study, RT-qPCR and western blot assays were applied to detect RNA and protein levels. Cell proliferation and apoptosis were analyzed via functional assays. Subcellular fractionation assay was carried out to determine circPOLR2A distribution in cells. Bioinformatics analysis and mechanism assays were done for detecting relationships among different factors. Rescue assays were performed to confirm validity of circPOLR2A/SOX9 axis. According to experimental results, circPOLR2A was up-regulated in GBM cells and promoted GBM cell proliferation while inhibiting GBM cell apoptosis. CircPOLR2A mainly existed in cell cytoplasm and sponged miR-2113 to positively regulate POU3F2 expression. POU3F2 activated the transcription of SOX9 through interacting with SOX9 promoter (1-500). Rescue assays validated that circPOLR2A influenced GBM cell proliferation and apoptosis via SOX9. To conclude, circPOLR2A enhanced the transcription of SOX9 through miR-2113/POU3F2 axis, thus exacerbating GBM cells growth.

Feasibility and Clinical Value of CT-Guided 125I Brachytherapy for Pain Palliation in Patients With Breast Cancer and Bone Metastases After External Beam Radiotherapy Failure.

Objectives: To evaluate the feasibility and clinical value of CT-guided iodine-125 (125I) brachytherapy for pain palliation in patients with breast cancer and bone metastases after external beam radiotherapy failure. Methods: From January 2014 to July 2016, a total of 90 patients, who had received the standard therapies for bone metastases but still suffered moderate-to-severe pain, were retrospectively studied. About 42 patients were treated with both 125I brachytherapy and bisphosphonates (Group A), and 48 patients were treated with bisphosphonates alone (Group B). Results: In Group A, 45 125I brachytherapy procedures were performed in 42 patients with 69 bone metastases; the primary success rate of 125I seed implantation was 92.9%, without severe complications. Regarding pain progression of the two groups, Group A exhibited significant relief in "worst pain," "least pain," "average pain," and "present pain" 3-day after treatment and could achieve a 12-week-remission for "worst pain," "least pain," "average pain," and "present pain." The morphine-equivalent 24-h analgesic dose at 3 days, 4 weeks, 8 weeks, and 12 weeks was 91 ± 27, 53 ± 13, 31 ± 17, and 34 ± 12 mg for Group A, and 129 ± 21, 61 ± 16, 53 ± 15, and 105 ± 23 mg for Group B. Group A experienced a lower incidence of analgesic-related adverse events and better quality of life than Group B. Conclusion: The CT-guided 125I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure.

Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy for advanced biliary tract cancers with biliary obstruction: a multicentre, retrospective, controlled study.

OBJECTIVE: To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). METHODS: We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. RESULTS: Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1-9.3) than in the control group (4.3 months, 95% CI: 3.6-5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1-16.5; control: 8.5 months, 95% CI: 7.6-9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. CONCLUSIONS: Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. KEY POINTS: • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.

Steroid 5 alpha-reductase 3 (SRD5A3) promotes tumor growth and predicts poor survival of human hepatocellular carcinoma (HCC).

Steroid 5 alpha-reductase 3 (SRD5A3) is an important molecule in glycosylation metabolism and steroid hormone formation. It is differentially expressed in human fetal liver, endometrial cancer and prostate cancer; however, its prognostic value and biological function in hepatocellular carcinoma (HCC) remain unclear. Here, bioinformatics analysis was employed to explore the expression and prognostic significance of SRD5A3 in various cancers including HCC. Additionally, clinical specimens of HCC were applied to analyze the expression of SRD5A3. SRD5A3-underexpressed HCC cell lines were established to test the effect of SRD5A3 on cell proliferation in in vitro and in vivo. We found that the elevated expression of SRD5A3 was common in many cancers with poor prognosis. Moreover, public datasets and our specimens revealed that SRD5A3 was also upregulated in HCC tissues and associated with clinical stage and patient's gender. Kaplan-Meier survival analysis showed that higher SRD5A3 level predicted poor overall survival, progression-free survival, relapse-free survival and disease specific survival in HCC patients. Further experiments showed that the lack of SRD5A3 inhibited the growth of HCC. Collectively, these findings indicate that SRD5A3 functions as an oncogene and might serve as a potential biomarker for prognosis and a therapeutic target for HCC.

Feasibility and clinical value of computed tomography-guided125I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases.

AIMS: The aim was to evaluate the feasibility and clinical value of computed tomography (CT)-guided125 I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases. MATERIALS AND METHODS: A total of 23 patients with retroperitoneal lymph node metastases and those who had moderate-to-severe pain from January 2014 to December 2018 were enrolled in the study. The primary tumors included pancreatic (n = 12), gastric (n = 4), hepatocellular (n = 4), colorectal (n = 2), and esophageal carcinomas (n= 1). Patients were treated with CT-guided percutaneous125 I brachytherapy during the study. The Brief Pain Inventory-Short Form was used to record and compare pain intensity and interference by pain. Treatment-related complications were also evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Criteria. Statistical analysis was performed using SPSS software version 22.0. RESULTS: The primary success rate of125 I seed implantation was 95.7% (22 of the 23 patients). As pain evolved, the patients achieved obvious pain palliation ratings for "worst pain" and "average pain" at 72 h and 4 weeks after brachytherapy, respectively, whereas "pain right now" at 12 weeks was significantly relieved after brachytherapy. No serious complications developed during the perioperative period. CONCLUSIONS: In the treatment of intractable carcinomatous pain in patients with retroperitoneal lymph node metastases, CT-guided125 I brachytherapy is a feasible and effective modality for pain palliation.

[Advances and Challenges of Local Thermal Ablation in Non-small Cell Lung Cancer].

Non-small cell lung cancer (NSCLC) is the most common pathological type of primary lung cancer. Currently, main treatment approaches for NSCLC patients include surgical resection, radiotherapy, chemotherapy, targeted therapy and so on. In recent years, thermal ablation has received increasing attention in the treatment of various stages of NSCLC. As a safe and efficient local treatment, thermal ablation may bring potential clinical benefits to NSCLC patients. However, many issues remain unsolved and further investigation is needed in the clinical application of thermal ablation in NSCLC. In this review, we aim to summarize the applications of thermal ablation in NSCLC and further discuss the emerging controversies as well as future research directions.

Radiofrequency Ablation Following Downstaging of Hepatocellular Carcinoma by Using Transarterial Chemoembolization: Long-term Outcomes.

Background Transarterial chemoembolization (TACE) is an effective downstaging procedure for hepatocellular carcinoma (HCC). However, knowledge of the effectiveness of radiofrequency ablation (RFA) after downstaging of HCC is currently lacking. Purpose To evaluate the clinical outcomes of RFA after downstaging of HCC by using TACE. Materials and Methods This retrospective study investigated a cohort of patients who underwent RFA with curative intent after downstaging with TACE to meet Milan criteria (one lesion up to 5 cm or no more than three lesions ≤3 cm without vascular invasion or extrahepatic metastasis) from January 2012 to July 2017. A control group of patients initially meeting the Milan criteria also underwent RFA as first-line treatment in the same period. Overall survival (OS), disease-free survival (DFS), and major complication rates were compared by using the log-rank test. To reduce potential bias, a propensity score analysis was also performed. Results There were 72 patients (median age, 56.5 years; range, 30-78 years; 67 men) in the downstaging group and 357 patients meeting the Milan criteria (median age, 58.0 years; range, 25-87 years; 313 men) included in this study. After propensity score matching, the 1-, 3-, and 5-year OS rates were 99%, 80%, and 66%, respectively, for the patients in the downstaging group and 94%, 84%, and 69%, respectively, for the patients in the Milan criteria group. The 1-, 3-, and 5-year DFS rate were 73%, 34%, and 24% for the downstaging group and 74%, 43%, and 37% for the Milan criteria group. There were no differences in the OS, DFS, or major complication rates between the two groups (P = .74, P = .39, P = .73, respectively). Conclusion The long-term patient survival and major complication rates of radiofrequency ablation following transarterial chemoembolization downstaging for hepatocellular carcinoma were similar to that of patients initially meeting the Milan criteria. © RSNA, 2019 See also the editorial by vanSonnenberg and Mueller in this issue.

Efficacy and safety of sorafenib versus apatinib in the treatment of intermediate and advanced hepatocellular carcinoma: a comparative retrospective study.

OBJECTIVE: To compare the efficacy and safety profiles of sorafenib and apatinib in patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC). METHODS: This was a single-center, retrospective study where we collected the clinical data of 72 patients, diagnosed with intermediate or advanced HCC from January 2014 to December 2016. Depending on the treatment received, 38 patients were categorized into group S (sorafenib group) and 34 into group A (apatinib group). The patients in group A received the initial recommended dose of 750 mg once daily (QD), which was reduced to 250 mg QD in the case of any class 3 or 4 adverse event (AE). Sorafenib was administered orally 400 mg twice daily (BID), and dose was modified to 400 mg or 200 mg QD in the case of grade 3 or 4 AEs. The median overall survival (OS), progression-free survival (PFS), and AEs reported in the two groups were analyzed and compared. RESULTS: Among the 38 patients treated with sorafenib, one patient had complete response (CR), 5 patients had partial response (PR), and 10 patients had stable disease (SD), and among the 34 patients treated with apatinib, 6 patients had PR and 7 patients had SD with no cases of CR. PFS in group S was significantly longer compared with that in group A (7.39 vs 4.79 months, respectively, P=0.031). Similar observations were made for median OS (10.4 months in group S vs 7.18 months in group A, P=0.011). However, there was no significant difference in the objective response rates (ORRs) among the study population (15.7 vs 17.6%, P=0.829). Common AEs in group S included hand and foot syndrome (HFS) and diarrhea, whereas common AEs in group A included hypertension, proteinuria, and increased transaminase. CONCLUSION: Our study showed promising clinical outcome with apatinib, but the sorafenib group exhibited better clinical efficacy with no significant difference in safety profile.

Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells.

Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

Effects of obesity on dynamic plantar pressure distribution in Chinese prepubescent children during walking.

The purpose of this study was to examine the effects of obesity on dynamic plantar pressure distribution during walking for prepubescent children. A footscan(®) plantar pressure plate system was used to collect the gait data. Fifty obese prepubescent children and fifty non-obese prepubescent children walked across the plate at preferred speed while barefoot. SPSS11.5 was used for analysis and significance is defined as p<0.05. Obese subjects had longer midstance duration (p=0.004) and shorter propulsion duration (p=0.047) compared to non-obese subjects. The peak pressures under the metatarsal heads II-V, midfoot and heel lateral (p=0.004, p=0.03, p=0.004) were significantly higher for obese subjects. The time to peak pressures under the toes II-V, the metatarsal heads IV, V and midfoot (p=0.008, p=0.009, p=0.01, p=0.006), and pressure rate under the heel medial and lateral heel (p=0.03, p=0.009) were also significantly higher. In addition, the arch index for the left foot (p=0.01), the left and right foot axis angle (p=0.027, p=0.03) were significant larger among obese subjects. We also found that obese subjects had significantly higher relative regional impulses of contact with the plate at the midfoot of left foot (p=0.01) and the forefoot of right foot (p=0.047). There were also differences in foot balance during the midstance and propulsion phase (p=0.0004, p=0.03) and in pronation extent during midstance and propulsion phases between left and right foot in the obese group (p=0.03, p=0.01). In conclusion, the obese children have weaker walking stability with flatter foot pattern, the larger foot axis angle and dynamic plantar pressure distribution changes compared to non-obese children.

Copper as an antibacterial agent for human pathogenic multidrug resistant Burkholderia cepacia complex bacteria.

The Burkholderia cepacia complex (Bcc) consists of 17 closely related multidrug resistant bacterial species that are difficult to eradicate. Copper has recently gained attention as an antimicrobial agent because of its inhibitory effects on bacteria, yeast, and viruses. The objective of this study was to evaluate the antibacterial activity of copper surfaces and copper powder against members of the B. cepacia complex. The antibacterial activity of different copper surfaces was evaluated by incubating them with Bcc strain suspensions (5×10(7)cfu/ml). The bacterial survival counts were calculated and the data for various copper surfaces were compared to the data for stainless steel and polyvinylchloride, which were used as control surfaces. The antibacterial activity of copper powder was determined with the diffusimetrical technique and the zone of inhibition was evaluated with paper disks. A single cell gel electrophoresis assay, staining assays, and inductively coupled plasma mass spectroscopy were performed to determine the mechanism responsible for the bactericidal activity. The results showed a significant decrease in the viable bacterial count after exposure to copper surfaces. Moreover, the copper powder produced a large zone of inhibition and there was a significantly higher influx of copper ions into the bacterial cells that were exposed to copper surfaces compared to the controls. The present study demonstrates that metallic copper has an antibacterial effect against Bcc bacteria and that copper adversely affects the bacterial cellular structure, thus resulting in cell death. These findings suggest that copper could be utilized in health care facilities to reduce the bioburden of Bcc species, which may protect susceptible members of the community from bacterial infection.