Prevalence and genomic characteristics of becAB-carrying Clostridium perfringens strains.

Clostridium perfringens, as a foodborne pathogen, can cause various intestinal diseases in both humans and animals according to its repertoire of toxins. In recent years, a multitude of studies have highlighted its threat to infants and young children. C. perfringens carries numerous toxins, with the newly identified BEC toxin confirmed as the second toxin to cause diarrheal illness, after CPE. However, the global dissemination of C. perfringens strains carrying becAB genes, which encode BEC toxins, has not been extensively studied. Following epidemiological surveillance of the prevalence of C. perfringens from different sources in various provinces of China, we identified two becAB-carrying strains and one strain carrying a sequence similar to becAB from distinct provinces and sources. When combined with genomic analysis of other becAB-carrying C. perfringens strains from public databases, we found that becAB was present in strains from different lineages. Our analysis of the plasmid and genetic environment corroborates previous findings on becAB-carrying strains, confirming that it currently achieves horizontal transmission through one type of evolutionarily conserved Pcp plasmid. This study provides a comprehensive analysis of the prevalence and transmission patterns of the newly emerged toxin gene locus, becAB, in C. perfringens. Despite the relatively low identification rate of becAB-carrying strains, their potential impact requires ongoing surveillance and investigation of their features, particularly their antimicrobial resistance.

All-trans retinoic acid-mediated ADAR1 degradation synergizes with PD-1 blockade to suppress pancreatic cancer.

As a double-stranded RNA-editing enzyme and an interferon-stimulated gene, double-stranded RNA-specific adenosine deaminase (ADAR1) suppresses interferon signaling and contributes to immunotherapy resistance. Suppression of ADAR1 overcomes immunotherapy resistance in preclinical models, but has not yet been translated to clinical settings. By conducting a screening of a subset of the FDA-approved drugs, we found that all-trans retinoic acid (ATRA, also known as tretinoin) caused ADAR1 protein degradation through ubiquitin-proteasome pathways and concomitantly increased PD-L1 expression in pancreatic and breast cancers. In addition, the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment and unleashed antitumor immunity and thereby impeded tumor growth in pancreatic cancer mouse models. In a pilot clinical trial, a higher dose of ATRA plus the anti-PD-1 antibody nivolumab prolonged median overall survival in patients with chemotherapy-resistant pancreatic cancer compared to a lower dose of the same regimen. In this study, ATRA was the first drug to be found to cause ADAR1 degradation. We propose translation of a promising 2-pronged antitumor strategy using ATRA and nivolumab to convert immunologically "cold" into "hot" tumors susceptible to immune checkpoint blockade.

Two new abietane diterpenoids from Caryopteris trichosphaera.

Two new abietane diterpenoids, cartrisine A (1) and cartrisine B (2) were isolated from Caryopteris trichosphaera. Their structures were elucidated based on HR-ESI-MS and NMR spectral data. Compound 2 exhibited moderate antibacterial bioactivity against MRSA and VRE, and showed a strong synergistic effect with market antibiotics against MRSA and VRE.

INTEGRATE IIa Phase III Study: Regorafenib for Refractory Advanced Gastric Cancer.

PURPOSE: Treatment options for refractory advanced gastric and esophagogastric junction cancer (AGOC) are limited. Regorafenib, an oral multikinase inhibitor, prolonged progression-free survival (PFS) versus placebo in the INTEGRATE I phase II trial. INTEGRATE IIa was designed to examine whether regorafenib improved overall survival (OS). METHODS: A double-blind placebo-controlled phase III trial compared regorafenib and best supportive care (BSC) versus placebo and BSC for participants with confirmed evaluable metastatic/advanced AGOC who failed ≥two prior therapies on a 2:1 random assignment, stratified by tumor location, geographic region (Asia v rest of world), and prior vascular endothelial growth factor inhibitors. The primary end point was OS. Treatment efficacy on OS was first tested in the pooled INTEGRATE I + INTEGRATE IIa cohort and, if significant, then in the INTEGRATE IIa cohort. Secondary end points were PFS, objective response rate, safety, and quality of life (QoL). RESULTS: INTEGRATE IIa enrolled 251 participants: 157 from Asia and 94 from rest of world and 169 received regorafenib and 82 received placebo. No significant heterogeneity was observed between INTEGRATE I and INTEGRATE IIa studies on OS. Pooled OS analysis hazard ratio (HR) was 0.70 (95% CI, 0.56 to 0.87; P = .001; 361 events). INTEGRATE IIa alone OS HR was 0.68 (95% CI, 0.52 to 0.90; P = .006; 238 events), the median OS was 4.5 months versus 4.0 months, and 12-month survival rates were 19% and 6%, for regorafenib versus placebo, respectively. After a preplanned adjustment for multiplicity, there were no statistically significant differences across regions or other prespecified subgroups. Regorafenib improved PFS (HR, 0.53 [95% CI, 0.40 to 0.70]; P < .0001) and delayed deterioration in global QoL (HR, 0.68 [95% CI, 0.52 to 0.89]; P = .0043). The toxicity profile was consistent with that of previous reports. CONCLUSION: Regorafenib improves survival compared with placebo in refractory AGOC.

Effect of Xuefu zhuyu oral liquid on tension-type headache: A randomized clinical trial.

BACKGROUND: Tension-type headache (TTH) is the most common neurological disorder worldwide, incurring immense social and economic costs and affecting quality of life. However, due to adverse reactions and inadequate effectiveness, there is still an unmet need for treatment. Xuefu zhuyu oral liquid (XZOL) is a Chinese patent medicine widely used for TTH in China, but evidence of its efficacy remains scant. PURPOSE: The aim of this study was to assess the efficacy and safety of XZOL for TTH patients. METHODS: This multicenter, double-blind, randomized placebo-controlled trial enrolled 174 patients with TTH in six centers in China from March 2020 to October 2021. Patients were randomly assigned to receive XZOL or a matched placebo for 4weeks. The primary outcome was the change in the mean headache intensity as measured by a visual analogue scale (VAS) from baseline to the end of treatment (Week 4). Secondary outcomes were the change in VAS from baseline to Week 12, the area-under-the-headache curve (AUC), response rate, number of headache days, average headache duration, rescue medication use proportion, etc. RESULTS: Of the 174 patients who were randomized, 160 completed the study. There was no significant difference in the mean change in VAS from baseline to the end of treatment between the XZOL group and the placebo group (-0.29; (95 % CI:0.81 to 0.23; p = 0.279) in the full analysis set (FAS), while there were statistically significant results (-0.9; 95 % CI:1.47 to -0.33; p = 0.002) in the per-protocol set (PPS). There were no significant differences in any of the secondary outcomes. The incidence of adverse events was similar in the two groups. CONCLUSION: XZOL may be an alternative option to relieve pain for TTH patients with high compliance in clinical practice. However, XZOL did not improve headache measurements in the FAS population.

Characteristics of walk-in clinic physicians and patients in Ontario: Cross-sectional study.

OBJECTIVE: To describe family physicians who primarily practise in a walk-in clinic setting and compare them with family physicians who provide longitudinal care. DESIGN: A cross-sectional study that linked results from a 2019 physician survey to provincial administrative health care data in Ontario. The characteristics, practice patterns, and patients of physicians primarily working in a walk-in clinic setting were compared with those of family physicians providing longitudinal care. SETTING: Ontario. PARTICIPANTS: Physicians who primarily worked in a walk-in clinic setting in 2019, as indicated by an annual physician survey. MAIN OUTCOME MEASURES: Physician demographic and practice characteristics, as well as their patients' demographic and health care utilization characteristics, were reported according to whether the physician was a walk-in clinic physician or a family physician who provided longitudinal care. RESULTS: Compared with the 9137 family physicians providing longitudinal care, the 597 physicians who self-identified as practising primarily in walk-in clinics were more frequently male (67% vs 49%) and more likely to speak a language other than English or French (43% vs 32%). Walk-in clinic physicians tended to have more encounters with patients who were younger (mean 37 vs 47 years), who had lower levels of prior health care utilization (15% vs 19% in highest band), who resided in large urban areas (87% vs 77%), and who lived in highly ethnically diverse neighbourhoods (45% vs 35%). Walk-in clinic physicians tended to have more encounters with unattached patients (33% vs 17%) and with patients attached to another physician outside their group (54% vs 18%). CONCLUSION: Physicians who primarily work in walk-in clinics saw many patients from historically underserved groups and many patients who were attached to another family physician.

A bispecific antibody targeting the Ig domains of Siglec-E displays enhanced antitumor effects.

Siglec-9 is a promising immune checkpoint molecule, and therapeutics targeting Siglec-9 have the potential to augment anti-tumor immunity. Here, we generated a bispecific antibody, named as aSE4-1-Fc, by fusing two distinct alpaca derived nanobodies, which can simultaneously target the extracellular Ig variable (V)-set domain and C2-set domains of murine Siglec-9 (also known as Siglec-E) with high affinity. In vivo studies showed that aSE4-1-Fc was better than its component antibodies in inhibiting tumor growth/metastasis, and Siglec-E blockade using aSE4-1-Fc generated protective anti-tumor T cell memory. Furthermore, the combination of aSE4-1-Fc with anti-PD-L1 therapy greatly improved the antitumor effects by augmenting both T and NK cells. Taken together, this study emphasizes the importance of Siglec-9 as a potential cancer therapeutic target, demonstrates the synergistic effect of co-inhibition of Siglec-9 and PD-L1, and may have implications for developing engineered antibodies targeting Siglec-9 with enhanced therapeutic efficacy.

FK4H4-: Planar Tetracoordinate Fluorine Stabilized by Multicenter Ionic Bonding.

Planar tetracoordinate fluorine (ptF) species are very exotic and scarce due to high electronegativity of fluorine. Herein we report the ternary square ptF cluster, D4h FK4H4-, which is composed of a F center, a square K4 ring, and four outer H bridges. It is a true global minimum (GM) structure and possesses good dynamic stability. Bonding analyses indicate that there are four lone pairs for the central F atom, along with four K-H-K three-center two-electron (3c-2e) σ bonds for the peripheral K4H4 ligand ring. The stability of ptF is dominated by multicenter ionic bonds rather than the supposed σ aromaticity of the system. Excitingly, it is a pseudohalogen anion with the VDE 3.57 eV at the CCSD(T) level. The merge of ptF with pseudohalogen anion character makes the FK4H4- cluster an exotic species, which will motivate theoretical and experimental studies on novel ptF species as well as superhalogens.

Contamination of Hepatitis E Virus in Pig Livers of Different Market Types Collected from Seven Provinces of China.

Foodborne transmission of the Hepatitis E virus (HEV) is becoming an important public health problem in China, but the food associated with the HEV transmission route remains unclear. Pig liver is among the suspected food products involved in HEV transmission. Our research aimed to survey the contamination rate and genotype identification of HEV in pig livers from different types of markets in selected provinces of China. reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to screen for HEV in pig livers, nest RT-PCR was used for partial amplification of opren reading frame (ORF) 2, followed by sequencing, and phylogenetic analysis to determine the genotype of positive samples. A total of 787 pig liver samples from 7 provinces were collected. The average positive rate of HEV was 8.13% (64/787), Inner Mongolia (14.29%, 1/7) and Hebei province (14.29%, 23/161) showed the highest positive rate. There was a significant difference among the provinces (p < 0.01). Three major market types (wholesale market, supermarket, and butcher's shop) were included in this study, and the positive rates were 5.28% (21/398), 15.86% (23/145), and 8.20% (20/244), respectively. There was no significant difference among the three market types. Eleven of the positive samples were partially sequenced and identified genotypes 4a, 4d, and 3a.

A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria.

Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo.

CD206 accelerates hepatocellular carcinoma progression by regulating the tumour immune microenvironment and increasing M2-type polarisation of tumour-associated macrophages and inflammation factor expression.

OBJECTIVE: This study aims to investigate the effect of CD206 on the progression of hepatocellular carcinoma (HCC) and the regulation of the tumour immune microenvironment. METHODS: A subcutaneous mouse model of HCC was established and treated with CD206-overexpressing adenovirus by tail vein injection or CD206 antibody C068C2 by intratumoral injection. The hepatocarcinoma-bearing mice were divided into four groups (IgG+ tail vein adenovirus group, IgG group, C068C2+ tail vein adenovirus group and C068C2 group) to observe the changes in tumour weight and volume with different expression levels of CD206. The proportion of M2-type tumour-associated macrophages (TAMs) was detected by flow cytometry and immunofluorescence. The apoptosis of tumour cells was detected using terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining, and inflammatory factors in serum and tissues were detected using the ENZYME-LINKED IMMUNOSORBENT ASSAY. RESULTS: Compared with the mice with low CD206 expression, the hepatocarcinoma-bearing mice with high CD206 expression in HCC exhibited faster tumour growth and more aggressive progression. Flow cytometry and immunofluorescence staining revealed that the expression level of CD206-positive M2-type TAMs was highest in the IgG + adenovirus group and lowest in the C068C2 group (p < 0.001). Compared with the IgG + adenovirus group, the proportion of TUNEL-positive cells in tumour cells was significantly reduced in the C068C2 group. The IgG + adenovirus group had the highest concentrations of transforming growth factor-ß (TGF-ß) and interleukin 6 (IL-6) in both serum and tumour tissues. CONCLUSION: The overexpression of CD206 accelerates the progression of HCC and changes the tumour immune microenvironment. The high expression of CD206 in HCC increases the M2-type polarisation of TAMs and induces the expression of both TGF-ß and IL-6 in tumour tissues and serum, thereby promoting HCC progression.

Analysis of ZNF208 Polymorphisms on the Clinicopathologic Characteristics of Asian Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a major form of liver cancer, is characterized by high lethality and a multifactorial etiology that includes hepatitis virus infections, lifestyle factors, and genetic predispositions. This study aimed to explore the impact of ZNF208 gene polymorphisms on the clinicopathological features of Taiwanese HCC patients, focusing on three specific single nucleotide polymorphisms (SNPs): rs2188971, rs2188972, and rs8105767. Our cohort consisted of 438 HCC patients and 1193 control individuals. Clinical staging was determined using the tumor/node/metastasis (TNM) system, and various clinical indicators were collected. Our analysis revealed a statistically significant increase in ZNF208 expression in HCC patients compared to controls, indicating a potential role in HCC progression. Although no substantial association was observed between ZNF208 SNPs and increased HCC risk, specific clinical features such as distant metastasis and vascular invasion showed significant associations with these SNPs, suggesting their influence on disease aggressiveness. Demographic analyses highlighted the importance of factors like alcohol consumption and viral hepatitis markers in HCC. Our study underscores the complexity of genetic influences on HCC, with ZNF208 polymorphisms potentially affecting tumor progression and patient outcomes.

The prevalence of neuropsychiatric symptoms and correlation with MRI findings in CADASIL patients.

OBJECTIVE: To assess the prevalence, timing, and functional impact of neuropsychiatric symptoms in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to assess whether these neuropsychiatric symptoms are associated with magnetic resonance imaging (MRI) features of the patients. METHODS: Our study included a total of 78 patients with CADASIL. To assess neuropsychiatric symptoms, we evaluated the caregivers using the Neuropsychiatric Inventory (NPI). Patients were considered to have an irritability, depression, apathy, aggression, or anxiety disorder if they scored ≥1 in the NPI. Subsequently, we conducted a more detailed assessment of irritability, depression, apathy, aggression, and anxiety. Multivariate logistic regression was employed to analyze the relationships between neuropsychiatric symptoms and clinical/MRI features in the patients. RESULTS: Overall, 57.69% of patients with CADASIL experienced neuropsychiatric symptoms. Among these symptoms, irritability was the most prevalent (52.56%), followed by depression (19.23%), apathy (17.95%), aggression (7.69%), and anxiety (6.41%). The mean age of onset for irritability was the youngest, followed by anxiety, apathy, aggression, and depression. Among patients with both stroke/TIA and neuropsychiatric symptoms, 31.03% reported experiencing neuropsychiatric symptoms prior to stroke/TIA. Furthermore, both irritability and apathy had a negative impact on the patients' daily functioning. Additionally, there was a correlation between the presence of neuropsychiatric symptoms and the patients' MRI lesion burden. INTERPRETATION: Our study has discovered that neuropsychiatric symptoms are highly prevalent in patients with CADASIL and may occur before cerebrovascular events, suggesting that neuropsychiatric symptoms of CADASIL deserve more attention and earlier exploration.

CB11S3+: A Triangular Boron-Based Cluster with One Planar Tetracoordinate Carbon at Its Edge.

Boron-based clusters containing planar tetracoordinate carbon (ptC) are unique and scarce. Isoelectronic-replacing after proper vulcanization is an effective strategy to obtain the ptC based on the B12 cluster. Herein we report computational evidence for a ternary CB11S3+ (C2v, 1A1) cluster, which possesses a concentric double-triangle structure containing one ptC atom at the peripheral edge. The unbiased structural explorations of potential energy surfaces and high-level CCSD(T) calculations indicate that the ptC CB11S3+ cluster is a true global minimum. Born-Oppenheimer molecular dynamics (BOMD) simulations reveal that it is dynamically stable against isomerization and decomposition. Chemical bonding analysis reveals that three delocalized π bonds endow the π aromaticity to the CB11 unit of CB11S3+. In addition, the strong S → B π back-bonding is also conducive to the stability of CB11S3+. The current findings offer opportunities for further boron-based ptC clusters.

Unveiling the formation and influence mechanisms of PCDD/F memory effect in wet scrubbers: Fundamental research and field verification.

The "memory effect" of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/Fs) in wet scrubber (WS) has become a frequent negative phenomenon in waste incineration field. This work focuses on studying the major influence factors and pathways of memory effect of PCDD/Fs in WS from the aspects of PCDD/F carriers and operating conditions. The PCDD/F contents of fillings used for over three years is 0.098 ng I-TEQ/g, which performs as a stable source of PCDD/Fs for thousands of hours with PCDD/F desorption rates ranged in 0.023-0.116 pg I-TEQ/g·h at 65 °C-93 °C. On the one hand, the filling layer has been the biggest PCDD/F storage part in WS (6845.1 µg). On the other hand, the generated yellow wrapping layer in long-term operation can limit the desorption of inner PCDD/Fs. The solubility of PCDD/Fs in scrubbing water (SW) performs a positive correlation with the content of suspended substances, and the increased temperature and pH value of SW both lead to a higher toxic concentration of PCDD/Fs dissolved from the fly ash to solutions. In addition, the built mass balance of PCDD/Fs around WS suggests the incomplete SW refreshing and sludge cleaning also contribute to the memory effect of PCDD/Fs through enhancing the liquid-phase PCDD/Fs in flue gas from SW. Based on this study, three suggestions are propounded on the operation of WS. The results of this study will provide essential evidence and guidelines for optimizing operation and inhibiting the PCDD/F memory effect in WS.

Polycyclic aromatic hydrocarbons emissions from biomass-fueled boilers in China.

Biomass serves as a sustainable energy source; however, the environmental risks associated with polycyclic aromatic hydrocarbons (PAHs) emitted from industrial biomass-fueled boilers are not well understood. This study analyzed 16 priority PAHs in both particulate and gaseous phases from 13 representative real-world industrial biomass-fueled boilers. Flue gas samples were collected from the stacks and analyzed using advanced techniques. Total PAHs concentrations ranged from 1.36 to 8870 µg m-3 (9 % O2 v/v), with benzo[a]pyrene emissions from certain boilers exceeding the allowable emissions standards for the coking chemical and petroleum refining industries in China. PAHs were predominantly found in the gaseous phase, with both gas and particle phases exhibiting similar toxicity. The average emission factor (EFmass) was 9.23 mg kg-1, while the toxicity-equivalent emission factors (EFCEQ, EFMEQ, and EFTEQ) were 1.96 × 10-2, 1.39 × 10-2 and 7.61 × 10-4 mg kg-1, respectively. It is estimated that annual PAH emissions from 2020 to 2050 will significantly decrease if biomass is used as industrial fuel in boilers (0.61 to 1.32 Gg y-1) instead of being openly burned in the field (3.39 to 7.21 Gg y-1). Overall, this study provides a comprehensive evaluation of PAH emissions from industrial biomass combustion, offering valuable data for future research and policy-making.

Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. AIM OF THE STUDY: To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. MATERIALS AND METHODS: Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. RESULTS: Six antibacterial diterpenoids against MRSA and VRE with MIC values 4-32 µg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. CONCLUSIONS: The results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.

Phase I-II study of OBI-888, a humanized monoclonal IgG1 antibody against the tumor-associated carbohydrate antigen Globo H, in patients with advanced solid tumors.

PURPOSE: OBI-888 is a humanized, monoclonal IgG1 antibody specific to the tumor-associated carbohydrate antigen Globo H. We conducted a phase I-II study of OBI-888 in patients with advanced cancer. METHODS: Patients were treated with OBI-888 5, 10, or 20 mg/kg IV weekly in Part A ("3 + 3" design) and 20 mg/kg IV weekly in Part B (Simon's 2-stage design) (1 cycle = 28 days). RESULTS: Overall, 54 patients were treated (Part A, n = 14; Part B, n = 40). OBI-888 was safe and well tolerated across the doses studied, with a low incidence of OBI-888-related treatment emergent adverse events. The maximum tolerated dose of OBI-888 was not reached. No dose-limiting toxicities were noted up to the 20 mg/kg dose level (recommended phase 2 dose). Stable disease (SD) was noted in 28.6% and 20% of Parts A and B, respectively, including three patients with SD for 6+, 7+, and 9 months. Antibody-dependent cellular cytotoxicity (ADCC) was induced after each OBI-888 treatment (average increase, 3.8-fold and 4.7-fold in Parts A and B, respectively), suggesting that ADCC induction is a potential mechanism of action of OBI-888. CONCLUSIONS: OBI-888 was well tolerated. Prolonged SD was noted in three patients. ADCC was induced after each OBI-888 treatment.