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Background Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. Methods In a 2 × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. Findings 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66–1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75–1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. Interpretation We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration.

Perturbations in the gut microbiome have been associated with colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite its significance in the promotion of CRC, genomic studies of Fusobacterium is limited. We enrolled 43 Vietnamese CRC patients and 25 participants with non-cancerous colorectal polyps to study the colonic microbiomes and genomic diversity of Fusobacterium in this population, using a combination of 16S rRNA gene profiling, anaerobic microbiology, and whole genome analysis. Oral bacteria, including F. nucleatum and Leptotrichia, were significantly more abundant in the tumour microbiomes. We obtained 53 Fusobacterium genomes, representing 26 strains, from the saliva, tumour and non-tumour tissues of six CRC patients. Isolates from the gut belonged to diverse F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and a potential new subspecies of Fusobacterium periodonticum. The Fusobacterium population within each individual was distinct and in some cases diverse, with minimal intra-clonal variation. Phylogenetic analyses showed that within four individuals, tumour-associated Fusobacterium were clonal to those isolated from non-tumour tissues. Genes encoding major virulence factors (Fap2 and RadD) showed evidence of horizontal gene transfer. Our work provides a framework to understand the genomic diversity of Fusobacterium within the CRC patients, which can be exploited for the development of CRC diagnostic and therapeutic options targeting this oncobacterium.

Background: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. As tetanus toxin acts within the central nervous system, where there is limited penetration of peripherally-administered antitoxin, intrathecal antitoxin administration may improve clinical outcomes compared to intramuscular injection. Methods: In a 2x2 factorial trial, adults with tetanus in a single-centre in Vietnam were randomized first to 3,000 IU human or 21,000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff blind to treatment allocations. The primary outcome was requirement for mechanical ventilation. Secondary outcomes included in-hospital mortality, death and disability at 240-days, duration of intensive care unit (ICU) stay, and adverse events. The study was registered at ClinicalTrials.gov, NCT 02999815 (status: recruitment completed). Findings: 272 adults were randomized. Mechanical ventilation was given to 56/130 (43%) of patients allocated to intrathecal antitoxin and 65/131 (50%) allocated to sham procedure (RR 0.87; 95% CI 0.66 to 1.13; p=0.29). For the intramuscular allocation 48/107 (45%), patients allocated to human antitoxin received mechanical ventilation compared to 48/108 (44%) patients allocated to equine antitoxin (relative risk (RR) 1.01, 95% confidence interval (CI) 0.75, 1.36, p=0.95). No clinically-relevant differences in secondary outcomes or adverse events were seen except for shorter length of ICU stay in those treated with intrathecal antitoxin compared to sham. Interpretation: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe but did not provide overall benefit in addition to intramuscular antitoxin administration. Funding: The Wellcome Trust, grant number 107367/Z/15/Z.

In this paper, an economic model is proposed to jointly optimize profits for participants in a heterogeneous IoT wireless-powered backscatter communication network. In the network under considerations, a power beacon and IoT devices (with various communication types and energy constraints) are assumed to belong to different service providers, i.e., energy service provider (ESP) and IoT service provider (ISP), respectively. To jointly maximize the utility for both service providers in terms of energy efficiency and network throughput, a Stackelberg game model is proposed to study the strategic interaction between the ISP and ESP. In particular, the ISP first evaluates its benefits from providing IoT services to its customers and then sends its requested price together with the service time to the ESP. Based on the request from the ISP, the ESP offers an optimized transmission power that maximizes its utility while meeting energy demands of the ISP. To study the Stackelberg equilibrium, we first obtain a closed-form solution for the ESP and propose a low-complexity iterative method based on block coordinate descent (BCD) to address the non-convex optimization problem for the ISP. Through simulation results, we show that our approach can significantly improve the profits for both providers compared with those of conventional transmission methods, e.g., bistatic backscatter and harvest-then-transmit communication methods.

Background: Several meta-analyses have tried to defi ne the role of minimally invasive approaches. However, further evidence to get a wider spread of these methods is necessary. Current studies describe minimally invasive surgery as a possible alternative to open surgery but deserving further clarifi cation. However, despite the increasing interest, the difficulty of planning prospective studies of adequate size accounts for the low level of evidence, which is mostly based on retrospective experiences. A multi-institutional prospective study allows the collection of an impressive amount of data to investigate various aspects of minimally invasive procedures with the opportunity of developing several subgroup analyses. A prospective data collection with high methodological quality on minimally invasive and open gastrectomies can clarify the role of diff erent procedures with the aim to develop specifi c guidelines. Methods and analysis: a multi-institutional prospective database will be established including information on surgical, clinical and oncological features of patients treated for gastric cancer with robotic, laparoscopic or open approaches and subsequent follow-up. The study has been shared by the members of the International study group on Minimally Invasive surgery for GASTRIc Cancer (IMIGASTRIC) The database is designed to be an international electronic submission system and a HIPPA protected real time data repository from high volume gastric cancer centers.

© 2013 IEEE. Social distancing plays a pivotal role in preventing the spread of viral diseases illnesses such as COVID-19. By minimizing the close physical contact among people, we can reduce the chances of catching the virus and spreading it across the community. This two-part paper aims to provide a comprehensive survey on how emerging technologies, e.g., wireless and networking, artificial intelligence (AI) can enable, encourage, and even enforce social distancing practice. In this Part I, we provide a comprehensive background of social distancing including basic concepts, measurements, models, and propose various practical social distancing scenarios. We then discuss enabling wireless technologies which are especially effect- in social distancing, e.g., symptom prediction, detection and monitoring quarantined people, and contact tracing. The companion paper Part II surveys other emerging and related technologies, such as machine learning, computer vision, thermal, ultrasound, etc., and discusses open issues and challenges (e.g., privacy-preserving, scheduling, and incentive mechanisms) in implementing social distancing in practice.

Algorithmic trading (AT) strategies aim at executing large orders discretely, in order to minimize the order’s impact, whilst also hiding the traders’ intentions. The contribution of this paper is twofold. First we presented a method for identifying the most suitable market simulation type, based on the specific market model to be investigated. Then we proposed an extended model of the Bayesian execution strategy. We implemented and assessed this model using our tool AlTraSimBa (ALgorithmic TRAding SIMulation BAcktesting) against the standard Bayesian execution strategy and naive execution strategies, for momentum, random and noise markets, as well as against historical data. Our results suggest that: (i) momentum market is the most suitable model for testing AT strategies, since it quickly fills the Limit Order book and produces results comparable to those of a liquid stock; (ii) the priors estimation method proposed in this paper \(-\) within the Bayesian adaptive agent model \(-\) can be advantageous in relatively stable markets, when trading patterns in consecutive days are strongly correlated, and (iii) there exists a trade-off between the frequency of decision making and more complex decision criteria, on one side, and the negative outcome of lost trading on the agents’ side due to them not participating actively in the market for some of the execution steps.

© 2019 IEEE. In this paper, we propose a novel approach to jointly address energy management and network throughput maximization problems for heterogeneous IoT low-power wireless communication networks. In particular, we consider a low-power communication network in which the IoT devices can harvest energy from a dedicated RF energy source to support their transmissions or backscatter the signals of the RF energy source to transmit information to the gateway. Different IoT devices may have dissimilar hardware configurations, and thus they may have various communications types and energy requirements. In addition, the RF energy source may have a limited energy supply source which needs to be minimized. Thus, to maximize the network throughput, we need to jointly optimize energy usage and operation time for the IoT devices under different energy demands and communication constraints. However, this optimization problem is non-convex due to the strong relation between energy supplied by the RF energy source and the IoT communication time, and thus obtaining the optimal solution is intractable. To address this problem, we study the relation between energy supply and communication time, and then transform the non-convex optimization problem to an equivalent convex-optimization problem which can achieve the optimal solution. Through simulation results, we show that our solution can achieve greater network throughputs (up to five times) than those of other conventional methods, e.g., TDMA. In addition, the simulation results also reveal some important information in controlling energy supply and managing low-power IoT devices in heterogeneous wireless communication networks.

BACKGROUND:Abnormally high estimated glomerular filtration rates (eGFRs) are associated with endothelial dysfunction and frailty. Previous studies have shown that low eGFR is associated with increased morbidity, but few reports address high eGFR. The purpose of this study is to evaluate the association of high eGFR with surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. METHODS:We identified patients who underwent elective surgery for gastrointestinal malignancies from 2005 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program database. We evaluated associations of eGFR with surgical outcomes by Cox or logistic models with restricted cubic spline functions, adjusting for case mix variables (i.e. age, gender, race and diabetes). RESULTS:The median eGFR is 83 (interquartile range 67-96) mL/min/1.73 m2. Thirty-day mortality was 1.9% (2555/136 896). There is a U-shaped relationship between eGFR and 30-day mortality. The adjusted hazard ratios (95% confidence intervals) for eGFRs of 30, 60, 105 and 120 mL/min/1.73 m2 (versus 90 mL/min/1.73 m2) are 1.73 (1.52-1.97), 1.00 (0.89-1.11), 1.42 (1.31-1.55) and 2.20 (1.79-2.70), respectively. Similar associations are shown for other surgical outcomes, including return to the operating room and postoperative pneumonia. Subgroup analyses show that eGFRs both higher and lower than the respective medians are consistently associated with a higher risk of adverse outcomes across age, gender and race. CONCLUSIONS:High and low eGFRs are associated with more adverse surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. The eGFR associated with the lowest postoperative risk is approximately at the median eGFR of a given population.

© Controlled Release Society 2017. Micro and nanotechnology can potentially revolutionize drug delivery systems. Novel microfluidic systems have been employed for the cell culture applications and drug delivery by micro and nanocarriers. Cells in the microchannels are under static and dynamic flow perfusion of culture media that provides nutrition and removes waste from the cells. This exerts hydrostatic and hydrodynamic forces on the cells. These forces can considerably affect the functions of the living cells. In this paper, we simulated the flow of air, culture medium, and the particle transport and deposition in the microchannels under different angles of connection inlet. It was found that the shear stress induced by the medium culture flow is not so high to damage the cells and that it is roughly uniform in the cell culture section (CCS). However, the local shear stresses in the other parts of the microchip differ by changing the angles of the connection inlet. The results showed that the particle deposition was a function of the particle size, the properties of the fluid, and the flow rate. At a lower air flow rate, both small and large particles deposited in the entrance region and none of them reached the CCS. Once the airflow rate increased, the drag of the flow could overcome the diffusion of the small particles and deliver them to the CCS so that more than 88% of the 100 nm and 98% of the 200 nm particles deposited in the CCS. However, larger particles with average diameters in micrometers could not reach the CCS by the airflow even at high flow rate. In contrast, our findings indicated that both small and large particles could be delivered to the CCS by liquid flow. Our experimental data confirm that microparticles (with diameters of 5 and 20 μm) suspended in a liquid can reach the CCS at a well-adjusted flow rate. Consequently, a liquid carrier is suggested to transport large particles through microchannels. As a powerful tool, these numerical simulations provide a nearly complete understanding of the flow field and particle patterns in microchips which can significantly lower the trial and error in the experiment tests and accordingly save researchers considerable cost and time for drug delivery to the cell in the microchip by micro/nanocarriers.

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim There has been increasing interest in electronic systems with integrated microfluidic active cooling modules. However, the failure of 3C-SiC/Si interface with increasing temperature has prevented the development of 3C-SiC power electronic devices. Here, all integrated transparent heating, sensing, and cooling systems are developed on a single silicon carbide (SiC) chip for efficient thermal management. SiC nanofilms are grown on a silicon wafer, are transferred to a glass substrate, and then a micro electromechanical system process is employed to fabricate a SiC-on-glass system with integrated heaters and temperature sensors. A cooling system is fabricated with microchannel using 3D printing, molding, and plasma assisted bonding. The thermal management of the SiC-based system shows an excellent capability of heating and detecting temperature as well as effective cooling with an efficiency of from 0.24 to 0.28 and a maximum cooling rate of 0.1 K(µL min−1)−1. The fabrication strategy can be utilized for large production of SiC power nanoelectronics with high efficiency of integrated thermal management systems.

© 2017, Springer Science+Business Media, LLC. This paper reports the fabrication of electrospun polydimethylsiloxane (PDMS) membranes/scaffolds that are suitable for three-dimensional (3D) cell culture. Through modification the ratio between PDMS and polymethylmethacrylate (PMMA) as carrier polymer, we report the possibility of increasing PDMS weight ratio of up to 6 for electrospinning. Increasing the PDMS content increases the fiber diameter, the pore size, and the hydrophobicity. To our best knowledge, this is the first report describing beads-free, durable and portable electrospun membrane with maximum content of PDMS suitable for cell culture applications. To show the proof-of-concept, we successfully cultured epithelial lung cancer cells on these membranes in a static well plate without surface modification. Surprisingly, due to three-dimensional (3D) and hydrophobic nature of the electrospun fibers, cells aggregated into 3D multicellular spheroids. These easily detachable and cost-effective scaffolds with controllable thicknesses and high tensile strength are good candidates for cell-stretching devices, organ-on-a-chip devices, tissue engineering and studies of non-adherent mammalian cancer stem cells.

Phuc Van Pham, Nhung Thi Nguyen, Hoang Minh Nguyen, Lam Tan Khuat, Phong Minh Le, Viet Quoc Pham, Sinh Truong Nguyen, Ngoc Kim Phan Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam Background: Dendritic cell (DC) therapy is a promising therapy for cancer-targeting treatments. Recently, DCs have been used for treatment of some cancers. We aimed to develop an in vitro assay to evaluate DC therapy in cancer treatment using a breast cancer model. Methods: DCs were induced from murine bone marrow mononuclear cells in Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with GM-CSF (20 ng/mL) and IL-4 (20 ng/mL). Immature DCs were primed with breast cancer stem cell (BCSC)-derived antigens. BCSCs were sorted from 4T1 cell lines based on aldehyde dehydrogenase expression. A mixture of DCs and cytotoxic T lymphocytes (CTLs) were used to evaluate the inhibitory effect of antigen-primed DCs on BCSCs. BCSC proliferation and doubling time were recorded based on impedance-based cell analysis using the xCELLigence system. The specification of inhibitory effects of DCs and CTLs was also evaluated using the same system. Results: The results showed that impedance-based analysis of BCSCs reflected cytotoxicity and inhibitory effects of DCs and CTLs at 72 hours. Differences in ratios of DC:CTL changed the cytotoxicity of DCs and CTLs. Conclusion: This study successfully used impedance-based cell analysis as a new in vitro assay to evaluate DC efficacy in cancer immunotherapy. We hope this technique will contribute to the development and improvement of immunotherapies in the near future. Keywords: CTLs, cytotoxicity assay, dendritic cells, immunotherapy, targeting therapy

Antimicrobial resistance (AMR) is a global health problem; emerging semi-intensive farming systems in Southeast Asia are major contributors to the AMR burden. We accessed 12 pig and chicken farms at key stages of production in the Tien Giang province (Vietnam) to measure antimicrobial usage and to investigate the prevalence of AMR against five critical antimicrobials (β-lactams, 3(th)cephalosporins, quinolones, aminoglycosides and polymyxins) and their corresponding molecular mechanisms among 180Escherichia coliisolates. Overall, 94.7mg (interquartile range (IQR) 65.3-151.1) and 563.6mg (IQR 398.9-943.6) of antimicrobials were used to produce 1kg of live weight of chicken and pig, respectively. A median of 3 (out of 8) critical antimicrobials was used on pig farms.E. coliisolates exhibited a high prevalence of resistance against ampicillin (97.8% and 94.4% for chickens and pigs, respectively), ciprofloxacin (73.3% and 21.1%), gentamicin (42.2% and 35.6%) and colistin (22.2% and 24.4%). The prevalence of recently discovered colistin resistance gene,mcr-1,was 19-22% and had strong agreement with phenotypic colistin resistance. We conducted plasmid conjugation experiments with 37mcr-1gene positiveE. coliisolates and successfully observed transfer of this gene in 54.0% isolates through a plasmid of approximately 63Kb, consistent with that identified earlier in China. We found no significant correlation between total usage of antimicrobials at farm level and AMR. These data provide additional insight into the role ofmcr-1in colistin resistance on farms in Asia and begin to outline the dynamics of phenotypic and genotypic AMR in semi-intensive farming systems in Vietnam.Our study provides accurate baseline information on levels of antimicrobial use, as well as on the dynamics of phenotypic and genotypic resistance for antimicrobials of critical importance amongE. coliover the different stages of production in emerging pig and poultry production systems in Vietnam.E. coliisolates showed a high prevalence of resistance (>20%) against critically important antimicrobials such as colistin, ciprofloxacin and gentamicin. The underlying genetic mechanisms identified for of colistin (mcr-1gene) and quinolone (gyrAgene mutations), are likely to play a major role in AMR to those compounds. Conjugation experiments led to the identification of a 63 Kb plasmid, similar to that recently identified in China, as the potential carrier of themcr-1gene. These results should encourage greater restrictions of such antimicrobials in southeast Asian farming systems.

This paper presents a first step of our research on designing an effective and efficient GP-based method for symbolic regression. First, we propose three extensions of the standard Single Node GP, namely (1) a selection strategy for choosing nodes to be mutated based on depth and performance of the nodes, (2) operators for placing a compact version of the best-performing graph to the beginning and to the end of the population, respectively, and (3) a local search strategy with multiple mutations applied in each iteration. All the proposed modifications have been experimentally evaluated on five symbolic regression benchmarks and compared with standard GP and SNGP. The achieved results are promising showing the potential of the proposed modifications to improve the performance of the SNGP algorithm. We then propose two variants of hybrid SNGP utilizing a linear regression technique, LASSO, to improve its performance. The proposed algorithms have been compared to the state-of-the-art symbolic regression methods that also make use of the linear regression techniques on four real-world benchmarks. The results show the hybrid SNGP algorithms are at least competitive with or better than the compared methods.

Phuc Van Pham1, Ngoc Bich Vu1, Thuy Thanh Duong1, Tam Thanh Nguyen1, Nhung Hai Truong1, Nhan Lu Chinh Phan1, Tue Gia Vuong1, Viet Quoc Pham1, Hoang Minh Nguyen1, Kha The Nguyen1, Nhung Thi Nguyen1, Khue Gia Nguyen1, Lam Tan Khat1, Dong Van Le2, Kiet Dinh Truong1, Ngoc Kim Phan11Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, HCM City, 2Military Medical University, Ha Noi, VietnamBackground: Breast cancer stem cells with a CD44+CD24- phenotype are the origin of breast tumors. Strong CD44 expression in this population indicates its important role in maintaining the stem cell phenotype. Previous studies show that CD44 down-regulation causes CD44+CD24- breast cancer stem cells to differentiate into non-stem cells that are sensitive to antitumor drugs and lose many characteristics of the original cells. In this study, we determined tumor suppression in non-obese severe combined immunodeficiency mice using CD44 shRNA therapy combined with doxorubicin treatment.Methods: Tumor-bearing non-obese severe combined immunodeficiency mice were established by injection of CD44+CD24- cells. To track CD44+CD24- cells, green fluorescence protein was stably transduced using a lentiviral vector prior to injection into mice. The amount of CD44 shRNA lentiviral vector used for transduction was based on CD44 down-regulation by in vitro CD44 shRNA transduction. Mice were treated with direct injection of CD44 shRNA lentiviral vector into tumors followed by doxorubicin administration after 48 hours. The effect was evaluated by changes in the size and weight of tumors compared with that of the control.Results: The combination of CD44 down-regulation and doxorubicin strongly suppressed tumor growth with significant differences in tumor sizes and weights compared with that of CD44 down-regulation or doxorubicin treatment alone. In the combination of CD44 down-regulation and doxorubicin group, the tumor weight was significantly decreased by 4.38-fold compared with that of the control group.Conclusion: These results support a new strategy for breast cancer treatment by combining gene therapy with chemotherapy.Keywords: breast cancer, breast cancer stem cells, CD44, doxorubicin, gene therapy

This paper proposed a nonlinear model predictive control (MPC) method for the control of gantry crane. One of the main motivations to apply MPC to control gantry crane is based on its ability to handle control constraints for multivariable systems. A pre-compensator is constructed to compensate the input nonlinearity (nonsymmetric dead zone with saturation) by using its inverse function. By well tuning the weighting function matrices, the control system can properly compromise the control between crane position and swing angle. The proposed control algorithm was implemented for the control of gantry crane system in System Control Lab of University of Technology, Sydney (UTS), and achieved desired experimental results. © 2009 WASET.ORG.

Laminin-332 is critical for squamous cell carcinoma (SCC) tumorigenesis, but targeting it for cancer therapy has been unachievable due to key role of laminin-332 in promoting tissue integrity. Here, we show that a portion of laminin-332, termed G45, which is proteolytically removed and absent in normal tissues, is prominently expressed in most human SCC tumors and plays an important role in human SCC tumorigenesis. Primary human keratinocytes lacking G45 (DeltaG45) showed alterations of basal receptor organization, impaired matrix deposition, and increased migration. After SCC transformation, the absence of G45 domain in DeltaG45 cells was associated with deficient extracellular signal-regulated kinase and phosphotidylinositol 3-kinase (PI3K) pathway activation, impaired invasion, deficient metalloproteinase activity, and absent tumorgenicity in vivo. Expression of G45 or activated PI3K subunit in DeltaG45 cells reversed these abnormalities. G45 antibody treatment induced SCC tumor apoptosis, decreased SCC tumor proliferation, and markedly impaired human SCC tumorigenesis in vivo without affecting normal tissue adhesion. These results show a remarkable selectivity of expression and function for laminin-332 G45 in human SCC tumorigenesis and implicate it as a specific target for anticancer therapy.Laminin-332 is critical for squamous cell carcinoma (SCC) tumorigenesis, but targeting it for cancer therapy has been unachievable due to key role of laminin-332 in promoting tissue integrity. Here, we show that a portion of laminin-332, termed G45, which is proteolytically removed and absent in normal tissues, is prominently expressed in most human SCC tumors and plays an important role in human SCC tumorigenesis. Primary human keratinocytes lacking G45 (DeltaG45) showed alterations of basal receptor organization, impaired matrix deposition, and increased migration. After SCC transformation, the absence of G45 domain in DeltaG45 cells was associated with deficient extracellular signal-regulated kinase and phosphotidylinositol 3-kinase (PI3K) pathway activation, impaired invasion, deficient metalloproteinase activity, and absent tumorgenicity in vivo. Expression of G45 or activated PI3K subunit in DeltaG45 cells reversed these abnormalities. G45 antibody treatment induced SCC tumor apoptosis, decreased SCC tumor proliferation, and markedly impaired human SCC tumorigenesis in vivo without affecting normal tissue adhesion. These results show a remarkable selectivity of expression and function for laminin-332 G45 in human SCC tumorigenesis and implicate it as a specific target for anticancer therapy.