Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors.

BACKGROUND: TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach. METHODS: Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts. RESULTS: Several pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors. CONCLUSIONS: TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.

Nanopore sequencing improves construction of customized CRISPR-based gene activation libraries.

Clustered regularly interspaced short palindromic repeats (CRISPR)-based screening has emerged as a powerful tool for identifying new gene targets for desired cellular phenotypes. The construction of guide RNA (gRNA) pools largely determines library quality and is usually performed using Golden Gate assembly or Gibson assembly. To date, library construction methods have not been systematically compared, and the quality check of each batch has been slow. In this study, an in-house nanopore sequencing workflow was established for assessing the current methods of gRNA pool construction. The bias of pool construction was reduced by employing the polymerase-mediated non-amplifying method. Then, a small gRNA pool was utilized to characterize stronger activation domains, specifically MED2 (a subunit of mediator complex) and HAP4 (a heme activator protein), as well as to identify better gRNA choices for dCas12a-based gene activation in Saccharomyces cerevisiae. Furthermore, based on the better CRISPRa tool identified in this study, a custom gRNA pool, which consisted of 99 gRNAs targeting central metabolic pathways, was designed and employed to screen for gene targets that could improve ethanol utilization in S. cerevisiae. The nanopore sequencing-based workflow demonstrated here should provide a cost-effective approach for assessing the quality of customized gRNA library, leading to faster and more efficient genetic and metabolic engineering in S. cerevisiae.

A novel approach to clinical thinking training for medical students: the combined World Café discussion and case-based learning experience introduction.

It is essential for modern medical students to continuously enhance their clinical thinking abilities. This study aims to evaluate the efficacy of the combined World Café discussion and case-based learning (CBL) approach within the clinical thinking training course. The clinical thinking training course incorporated the combined World Café discussion and CBL approach. The assessment of the accuracy and rationality of clinical symptoms, medical examination, pathological processes, diagnostic results, diagnostic basis, and drug use was conducted through case-related queries. Feedback from students and instructors regarding the teaching content, teaching process, and teaching effect was gathered through questionnaires. The findings indicate that the students achieved high marks in all assessed areas, including clinical symptoms, medical examination, pathological processes, diagnostic results, diagnostic basis, and drug use. The feedback from students and instructors on the teaching content, teaching process, and teaching effect was positive. Medical educators can use our findings to implement the combined World Café discussion and CBL mode to enhance student engagement.NEW & NOTEWORTHY The combined World Café discussion and case-based learning approach was implemented in the clinical thinking training course. Students' scores for clinical symptoms, medical examination, pathological process, diagnostic results, diagnostic basis, and drug use were all excellent. Feedback from both students and teachers on the teaching content, teaching process, and teaching effect was positive.

Discriminating TB lung nodules from early lung cancers using deep learning.

BACKGROUND: In developing countries where both high rates of smoking and endemic tuberculosis (TB) are often present, identification of early lung cancer can be significantly confounded by the presence of nodules such as those due to latent TB (LTB). It is very challenging to distinguish lung cancer and LTB without invasive procedures, which have their own risks of morbidity and even mortality. METHODS: Our method uses a customized VGG16-based 15-layer 2-dimensional deep convolutional neural network (DNN) architecture with transfer learning. The DNN was trained and tested on sets of CT images set extracted from the National Lung Screening Trial and the National Institute of Allergy and Infectious Disease TB Portals. Performance of the DNN was evaluated under locked and step-wise unlocked pretrained weight conditions. RESULTS: The DNN with unlocked pretrained weights achieved an accuracy of 90.4% with an F score of 90.1%. CONCLUSIONS: Our findings support the potential for a DNN to serve as a noninvasive screening tool capable of reliably detecting and distinguishing between lung cancer and LTB.

Rebooting the Electronic Health Record.

Justifications for the widespread adoption and integration of an electronic health record (EHR) have long leaned on the purported benefits of the technology. However, the performance of the EHR has been underwhelming relative to the promises of immediate access to relevant patient information, clinical decision supports, computerized ordering, and transferable patient data. In this narrative review, we provide an overview of the historical problems and limitations of the EHR, detail the core principles that define agile processes that may overcome the barriers faced by the current EHR, and re-imagine what an integrated, seamless EHR that serves its users and patients might look like. Moving forward, the EHR should be redesigned using a middle-out framework and empowering dual-type champions to maintain the sustainable diffusion of future innovations.

Epigenetic regulation of angiogenesis in lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, in which angiogenesis is highly required for lung cancer cell growth and metastasis. Genetic regulation of this multistep process is being studied extensively, however, relatively less is known about the epigenetic regulation of angiogenesis in lung cancer. Several epigenetic alterations contribute to regulating angiogenesis, such as epimodifications of DNA, posttranslational modification of histones, and expression of noncoding RNAs. Here, we review the current knowledge of the epigenetic regulation of angiogenesis and discuss the potential clinical applications of epigenetic-based anticancer therapy in lung cancer. Overall, epigenetic-based therapy will likely emerge as a prominent approach to treat lung cancer in the future.

Human bronchial-pulmonary proteomics in coronavirus disease 2019 (COVID-19) pandemic: applications and implications.

INTRODUCTION: The outbreak of the newly discovered human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has disrupted the normal life of almost every civilization worldwide. Studies have shown that the coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 can affect multiple human organs and physiological systems, but the respiratory system remains the primary location for viral infection. AREAS COVERED: We summarize how omics technologies are used in SARS-CoV-2 research and specifically review the current knowledge of COVID-19 from the aspect of human bronchial-pulmonary proteomics. Also, knowledge gaps in COVID-19 that can be fulfilled by proteomics are discussed. EXPERT OPINION: Overall, human bronchial-pulmonary proteomics plays an important role in revealing the dynamics, functions, tropism, and pathogenicity of SARS-CoV-2, which is crucial for COVID-19 biomarker and therapeutic target discoveries. To more fully understand the impact of COVID-19, research from various angles using multi-omics approaches should also be conducted on the lungs as well as other organs.

Angiotensin-converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection.

Coronavirus (CoV) disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome CoV 2 (SARS-CoV-2). The highly contagious SARS-CoV-2 belongs to the genus Betacoronavirus, and it is phylogenetically closely related to SARS-CoV, a human CoV that caused an outbreak back in 2002 to 2003. Both SARS-CoV-2 and SARS-CoV enter human cells via the interactions between viral crown-like spike protein and human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we aim to review the involvement of ACE2 in human CoV infections by discussing the roles of ACE2 in CoV evolution, cross-species transmissibility, and COVID-19 susceptibility. We also provide our perspectives on COVID-19 treatment and prevention.

Cohort profile: Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO).

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

The First Report on Incidence of Nasopharyngeal Carcinoma in Sabah, Borneo.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the fourth common cancer in Malaysia. A few studies have looked into the incidence of NPC in Malaysia in general, but there has been no published data on its incidence in Sabah specifically, where NPC is very common among the population. The aim of this study is to present the first report on the incidence of NPC in the state of Sabah, Borneo. METHODS: Data of all patients diagnosed with NPC over a 5-year period from January 2015 to December 2019 inclusive were collected from the NPC registry of 3 main hospitals in Sabah. Age-standardized rates (ASRs) for different genders, ethnicities, and districts of origin were calculated. RESULTS: 215 NPC patients were identified with a mean age at diagnosis of 49 (range 9-82). The ASR of NPC was 7.9/100,000 where the average age-adjusted male-to-female ratio was 2.4. The highest ASR was found in Dusun ethnicity in both male (3.19/100,000) and female (1.69/100,000) individuals, followed by Chinese (both genders), and Kadazan (for male individuals) and Bajau (for female individuals). The highest ASR was found in patients originating from Sandakan, Kota Kinabalu, Keningau, and Tawau. CONCLUSION: This is the first report on the incidence of NPC in Sabah, Borneo. The data suggest high ASRs among the population, especially in male Dusun and Chinese ethnic groups. Further research looking into NPC in this state, especially on risk factors and ways to improve diagnosis and prevention among the population, is recommended.

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

Preclinical Activity of Embryonic Annexin A2-Specific Chimeric Antigen Receptor T Cells Against Ovarian Cancer.

Chimeric antigen receptors (CARs) have found clinical success in B cell malignancies, but a dearth of potential targets limits their wider clinical application, especially in solid tumours. Here, we describe the development of an anti-annexin A2 CAR, CAR(2448), derived from an antibody found to have activity against epithelial ovarian cancer cell lines. The spacer length of CAR(2448) was optimised based on in vitro cytotoxic activity against ovarian cancer (OC) cell lines via a real-time cytotoxicity assay. The longer spacer CAR(2448)L T cells exhibit significant effector activity, inducing inflammatory cytokine release and cytotoxicity against OC cell lines. Furthermore, CAR(2448)L-BBz T cells induced enhanced survival in an in vivo OC xenograft model and reduced tumour volume by 76.6%. Our preclinical studies of CAR(2448) suggest its potential for the unmet need of novel strategies for the treatment of ovarian cancer.

Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes.

Endometriosis is a common inflammatory gynecological disorder which causes pelvic scarring, pain, and infertility, characterized by the implantation of endometrial-like lesions outside the uterus. The peritoneum, ovaries, and deep soft tissues are the commonly involved sites, and endometriotic lesions can be classified into three subphenotypes: superficial peritoneal endometriosis (PE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DIE). In 132 women diagnosed laparoscopically with and without endometriosis (n = 73, 59 respectively), and stratified into PE, OE, and DIE, peritoneal fluids (PF) were characterized for 48 cytokines by using multiplex immunoassays. Partial-least-squares-regression analysis revealed distinct subphenotype cytokine signatures-a six-cytokine signature distinguishing PE from OE, a seven-cytokine signature distinguishing OE from DIE, and a six-cytokine-signature distinguishing PE from DIE-each associated with different patterns of biological processes, signaling events, and immunology. These signatures describe endometriosis better than disease stages (p < 0.0001). Pathway analysis revealed the association of ERK1 and 2, AKT, MAPK, and STAT4 linked to angiogenesis, cell proliferation, migration, and inflammation in the subphenotypes. These data shed new insights on the pathophysiology of endometriosis subphenotypes, with the potential to exploit the cytokine signatures to stratify endometriosis patients for targeted therapies and biomarker discovery.

Prefrontal Dynamics Associated with Efficient Detours and Shortcuts: A Combined Functional Magnetic Resonance Imaging and Magnetoencenphalography Study.

Central to the concept of the "cognitive map" is that it confers behavioral flexibility, allowing animals to take efficient detours, exploit shortcuts, and avoid alluring, but unhelpful, paths. The neural underpinnings of such naturalistic and flexible behavior remain unclear. In two neuroimaging experiments, we tested human participants on their ability to navigate to a set of goal locations in a virtual desert island riven by lava, which occasionally spread to block selected paths (necessitating detours) or receded to open new paths (affording real shortcuts or false shortcuts to be avoided). Detours activated a network of frontal regions compared with shortcuts. Activity in the right dorsolateral PFC specifically increased when participants encountered tempting false shortcuts that led along suboptimal paths that needed to be differentiated from real shortcuts. We also report modulation in event-related fields and theta power in these situations, providing insight to the temporal evolution of response to encountering detours and shortcuts. These results help inform current models as to how the brain supports navigation and planning in dynamic environments.

Backtracking during navigation is correlated with enhanced anterior cingulate activity and suppression of alpha oscillations and the 'default-mode' network.

Successful navigation can require realizing the current path choice was a mistake and the best strategy is to retreat along the recent path: 'back-track'. Despite the wealth of studies on the neural correlates of navigation little is known about backtracking. To explore the neural underpinnings of backtracking we tested humans during functional magnetic resonance imaging on their ability to navigate to a set of goal locations in a virtual desert island riven by lava which constrained the paths that could be taken. We found that on a subset of trials, participants spontaneously chose to backtrack and that the majority of these choices were optimal. During backtracking, activity increased in frontal regions and the dorsal anterior cingulate cortex, while activity was suppressed in regions associated with the core default-mode network. Using the same task, magnetoencephalography and a separate group of participants, we found that power in the alpha band was significantly decreased immediately prior to such backtracking events. These results highlight the importance for navigation of brain networks previously identified in processing internally-generated errors and that such error-detection responses may involve shifting the brain from default-mode states to aid successful spatial orientation.

In vivo surveillance and elimination of teratoma-forming human embryonic stem cells with monoclonal antibody 2448 targeting annexin A2.

This study describes the use of a previously reported chimerised monoclonal antibody (mAb), ch2448, to kill human embryonic stem cells (hESCs) in vivo and prevent or delay the formation of teratomas. ch2448 was raised against hESCs and was previously shown to effectively kill ovarian and breast cancer cells in vitro and in vivo. The antigen target was subsequently found to be Annexin A2, an oncofetal antigen expressed on both embryonic cells and cancer cells. Against cancer cells, ch2448 binds and kills via antibody-dependent cell-mediated cytotoxicity (ADCC) and/or antibody-drug conjugate (ADC) routes. Here, we investigate if the use of ch2448 can be extended to hESC. ch2448 was found to bind specifically to undifferentiated hESC but not differentiated progenitors. Similar to previous study using cancer cells, ch2448 kills hESC in vivo either indirectly by eliciting ADCC or directly as an ADC. The treatment with ch2448 post-transplantation eliminated the in vivo circulating undifferentiated cells and prevented or delayed the formation of teratomas. This surveillance role of ch2448 adds an additional layer of safeguard to enhance the safety and efficacious use of pluripotent stem cell-derived products in regenerative medicine. Thereby, translating the use of ch2448 in the treatment of cancers to a proof of concept study in hESC (or pluripotent stem cell [PSC]), we show that mAbs can also be used to eliminate teratoma forming cells in vivo during PSC-derived cell therapies. We propose to use this strategy to complement existing methods to eliminate teratoma-forming cells in vitro. Residual undifferentiated cells may escape in vitro removal methods and be introduced into patients together with the differentiated cells.

Do men with normal testosterone-oestradiol ratios benefit from letrozole for the treatment of male infertility?

RESEARCH QUESTION: Previous studies of aromatase inhibitors on male infertility have focused on men with low testosterone-oestradiol ratio of less than 10. Can aromatase inhibitors improve spermatogenesis in men with idiopathic male infertility with normal testosterone-oestradiol ratio? DESIGN: Prospective study of men with idiopathic severe oligozoospermia (sperm concentration <5 million/ml) carried out between February 2015 and March 2017. The objective was to assess if semen-analysis parameters improved after treatment with letrozole. Secondary objectives were to monitor the safety of letrozole in men, and to measure the alterations in serum FSH, LH, oestradiol and testosterone levels. RESULTS: Fifteen men with normal testosterone-oestradiol ratio (>10) were treated with letrozole 2.5 mg daily for 4 months. This produced a 5.5-fold increase in sperm concentration (P = 0.0068). All men had increased total serum testosterone and suppressed oestradiol levels after treatment, thus raising the overall testosterone-oestradiol ratio (P < 0.0001). Adverse effects from letrozole were relatively minor and included loss of libido (54%), headaches (25%), fatigue (21%), weakness (13%), loss of hair (8%) and dry mouth (8%). CONCLUSIONS: Letrozole improves sperm concentration and increases testosterone-oestradiol ratio for men with oligozoospermia who have normal testosterone-oestradiol ratio; its role in the treatment of male infertility may be extended to this group of patients. In addition, it is a relatively well-tolerated drug with no serious adverse effects.

Opportunities for Antibody Discovery Using Human Pluripotent Stem Cells: Conservation of Oncofetal Targets.

Pluripotent stem cells (PSCs) comprise both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The application of pluripotent stem cells is divided into four main areas, namely: (i) regenerative therapy, (ii) the study and understanding of developmental biology, (iii) drug screening and toxicology and (iv) disease modeling. In this review, we describe a new opportunity for PSCs, the discovery of new biomarkers and generating antibodies against these biomarkers. PSCs are good sources of immunogen for raising monoclonal antibodies (mAbs) because of the conservation of oncofetal antigens between PSCs and cancer cells. Hence mAbs generated using PSCs can potentially be applied in two different fields. First, these mAbs can be used in regenerative cell therapy to characterize the PSCs. In addition, the mAbs can be used to separate or eliminate contaminating or residual undifferentiated PSCs from the differentiated cell product. This step is critical as undifferentiated PSCs can form teratomas in vivo. The mAbs generated against PSCs can also be used in the field of oncology. Here, novel targets can be identified and the mAbs developed as targeted therapy to kill the cancer cells. Conversely, as new and novel oncofetal biomarkers are discovered on PSCs, cancer mAbs that are already approved by the FDA can be repurposed for regenerative medicine, thus expediting the route to the clinics.

Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.

Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb). Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development. Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested. Normal cell lines and tissue were unstained by mAb-A4. To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The mAb-A4 epitopes were found to be Fucα1-2Galß1-3GlcNAcß (H type 1) and Galß1-3GlcNAcß (type 1 LacNAc). These structures were found to be present on multiple proteins from hESC and OC. Importantly, endo-ß-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433. Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures. The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes. We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization.

Acute and chronic cadmium telluride quantum dots-exposed human bronchial epithelial cells: The effects of particle sizes on their cytotoxicity and carcinogenicity.

Quantum dots (QDs) are semiconducting nanocrystals with unique optical properties. When coated with shell/capping, QDs are not deleterious to cells and organisms. However, when QDs are retained in the cellular environment for a certain period of time, their coatings may be degraded, yielding "naked" QDs. Although some studies have documented the acute effects of cadmium telluride (CdTe) QDs in various cell lines, however, to our knowledge, there are no published studies on the chronic effects of CdTe QDs in normal lung cells. In this study, we therefore sought to study the effects of CdTe QDs of various particle sizes on their cytotoxicity and carcinogenicity in normal human bronchial epithelial cells (BEAS-2B). A total of three particle sizes of CdTe QD with emission maximum at 520, 580, and 730 nm were employed (abbreviated as 520Q, 580Q, and 730Q, respectively). Our results indicated that acute exposure to 520Q (∼2.04 nm in diameter) and 580Q (∼3.24 nm in diameter) elicited dose-dependent cytotoxicity; while acute exposure to 730Q (∼5.40 nm in diameter) elicited negligible cytotoxicity in BEAS-2B cells. Notably, chronic exposure to CdTe QD of all three tested particle sizes induced BEAS-2B cell transformation as evidenced by enhanced cell migration and anchorage-independent growth on soft agar. Taken together, our findings suggest that CdTe QDs are potent human lung carcinogens.