Clinical Factors That Affect Fiducial Tracking in Robotic SABR for Lung Tumors.

Purpose: SABR is a treatment option for patients with lung tumors that employs fiducials to track tumors during the breathing cycle. Currently, there is a paucity of data on how relative fiducial location and patient clinical characteristics affect fiducial tracking and clinical outcomes. This study aimed to identify factors that reduce the number of fiducials tracked with respiratory motion management during SABR. Methods and Materials: An institutional review board-approved retrospective review was performed of patients receiving robotic SABR for lung tumors at our institution from 2016 to 2019. Clinical data including demographics, medical history, treatment data, and follow-up were collected. Fiducial geometries were obtained with Velocity contouring software and MATLAB. Mann-Whitney U, χ2, and t tests were completed using MedCalc. Results: A total of 73 patients with 77 treatments were identified. The χ2 analysis revealed that chronic obstructive pulmonary disease was associated with having 3 or more fiducials tracked (P = .034). Tumors in lower lobes were associated with higher rates of uncertainty errors (P = .015). The number of fiducials tracked had no effect on local tumor control or overall survival, with a median of 36 months of follow-up. A total of 28 treatments had fiducial centroid data available for geometric analysis. The most common tracking errors were rigid body error (RBE; 57%) and spacing errors (36.4%). Spacing errors had a shorter average minimum interfiducial distance than nonspacing errors (1.0 cm vs 1.7 cm, respectively; P = .017). RBE treatments had a longer average maximum distance than non-RBE treatments (4.0 cm vs 3.0 cm; P = .022). Conclusions: Greater motion in lower lobes can contribute to certain tracking errors that prevent more fiducials from being tracked. Maintaining interfiducial distance between experimentally determined guidelines may limit spacing errors and RBEs, the 2 most common tracking errors. An increased number of patients in a data set may result in stronger correlations between patient and tumor factors and outcomes.

Room-temperature spin injection from a ferromagnetic semiconductor.

Spin injection using ferromagnetic semiconductors at room temperature is a building block for the realization of spin-functional semiconductor devices. Nevertheless, this has been very challenging due to the lack of reliable room-temperature ferromagnetism in well-known group IV and III-V based semiconductors. Here, we demonstrate room-temperature spin injection by using spin pumping in a BiSb/(Ga,Fe)Sb heterostructure, where (Ga,Fe)Sb is a ferromagnetic semiconductor (FMS) with high Curie temperature (TC) and BiSb is a topological insulator (TI). Despite the very small magnetization of (Ga,Fe)Sb at room temperature (45 emu/cc), we detected spin injection from (Ga,Fe)Sb by utilizing the large inverse spin Hall effect (ISHE) in BiSb. Our study provides the first demonstration of spin injection at room temperature from a FMS.

Outcomes in Ballistic Injuries to the Hand: Fractures and Nerve/Tendon Damage as Predictors of Poor Outcomes.

BACKGROUND: Gunshot injuries can be devasting, regardless of their location. However, ballistic injuries involving the upper extremity have not been thoroughly investigated. The goal of this study is to evaluate the injury patterns and outcomes of patients who sustained gunshot injuries to the hand. METHODS: A retrospective chart review of patients with gunshot injuries to the upper extremity at a single, level 1 trauma center between January 2016 and December 2017 was performed. Patient demographics and mechanisms of injuries were reviewed. The injury patterns, location, tendon/nerve involvement, and bony involvement were analyzed. Surgical interventions and long-term outcomes were reviewed. Outcomes were compared using the presence of fractures and nerve/tendon injuries as independent variables. RESULTS: In all, 32 patients met our inclusion criteria. Of these, 15 patients had gunshots to the hand, 10 patients to the fingers, and 7 patients involving both the finger and hand. In patients with isolated hand injuries, 60% had fractures and 53% had nerve/tendon injuries. The presence of fractures was associated with a 7.9-fold increase in tendon and nerve injuries (P = .032). Patients who sustained tendon/nerve injuries had significantly higher rates of permanent disability (P = .01). The presence of a fracture leads to a higher likelihood of long-term complications, although not statistically significant (P = .13). CONCLUSION: Ballistic injuries to the hand are frequently associated with fractures and neurovascular and tendon injuries. The presence of fractures is associated with a higher incidence of nerve and tendon injuries. Involvement of these structures is linked to an increased risk of long-term disability.

Ultrahigh efficient spin orbit torque magnetization switching in fully sputtered topological insulator and ferromagnet multilayers.

Spin orbit torque (SOT) magnetization switching of ferromagnets with large perpendicular magnetic anisotropy has a great potential for the next generation non-volatile magnetoresistive random-access memory (MRAM). It requires a high performance pure spin current source with a large spin Hall angle and high electrical conductivity, which can be fabricated by a mass production technique. In this work, we demonstrate ultrahigh efficient and robust SOT magnetization switching in fully sputtered BiSb topological insulator and perpendicularly magnetized Co/Pt multilayers. Despite fabricated by the magnetron sputtering instead of the laboratory molecular beam epitaxy, the topological insulator layer, BiSb, shows a large spin Hall angle of θSH = 10.7 and high electrical conductivity of σ = 1.5 × 105 Ω-1 m-1. Our results demonstrate the feasibility of BiSb topological insulator for implementation of ultralow power SOT-MRAM and other SOT-based spintronic devices.

Efficient spin current source using a half-Heusler alloy topological semimetal with back end of line compatibility.

Topological materials, such as topological insulators (TIs), have great potential for ultralow power spintronic devices, thanks to their giant spin Hall effect. However, the giant spin Hall angle (θSH > 1) is limited to a few chalcogenide TIs with toxic elements and low melting points, making them challenging for device integration during the silicon Back-End-of-Line (BEOL) process. Here, we show that by using a half-Heusler alloy topological semi-metal (HHA-TSM), YPtBi, it is possible to achieve both a giant θSH up to 4.1 and a high thermal budget up to 600 °C. We demonstrate magnetization switching of a CoPt thin film using the giant spin Hall effect of YPtBi by current densities lower than those of heavy metals by one order of magnitude. Since HHA-TSM includes a group of three-element topological materials with great flexibility, our work opens the door to the third-generation spin Hall materials with both high θSH and high compatibility with the BEOL process that would be easily adopted by the industry.

Antibiotic use and prescription and its effects on Enterobacteriaceae in the gut in children with mild respiratory infections in Ho Chi Minh City, Vietnam. A prospective observational outpatient study.

BACKGROUND AND OBJECTIVES: Treatment guidelines do not recommend antibiotic use for acute respiratory infections (ARI), except for streptococcal pharyngitis/tonsillitis and pneumonia. However, antibiotics are prescribed frequently for children with ARI, often in absence of evidence for bacterial infection. The objectives of this study were 1) to assess the appropriateness of antibiotic prescriptions for mild ARI in paediatric outpatients in relation to available guidelines and detected pathogens, 2) to assess antibiotic use on presentation using questionnaires and detection in urine 3) to assess the carriage rates and proportions of resistant intestinal Enterobacteriaceae before, during and after consultation. MATERIALS AND METHODS: Patients were prospectively enrolled in Children's Hospital 1, Ho Chi Minh City, Vietnam and diagnoses, prescribed therapy and outcome were recorded on first visit and on follow-up after 7 days. Respiratory bacterial and viral pathogens were detected using molecular assays. Antibiotic use before presentation was assessed using questionnaires and urine HPLC. The impact of antibiotic usage on intestinal Enterobacteriaceae was assessed with semi-quantitative culture on agar with and without antibiotics on presentation and after 7 and 28 days. RESULTS: A total of 563 patients were enrolled between February 2009 and February 2010. Antibiotics were prescribed for all except 2 of 563 patients. The majority were 2nd and 3rd generation oral cephalosporins and amoxicillin with or without clavulanic acid. Respiratory viruses were detected in respiratory specimens of 72.5% of patients. Antibiotic use was considered inappropriate in 90.1% and 67.5%, based on guidelines and detected pathogens, respectively. On presentation parents reported antibiotic use for 22% of patients, 41% of parents did not know and 37% denied antibiotic use. Among these three groups, six commonly used antibiotics were detected with HPLC in patients' urine in 49%, 40% and 14%, respectively. Temporary selection of 3rd generation cephalosporin resistant intestinal Enterobacteriaceae during antibiotic use was observed, with co-selection of resistance to aminoglycosides and fluoroquinolones. CONCLUSIONS: We report overuse and overprescription of antibiotics for uncomplicated ARI with selection of resistant intestinal Enterobacteriaceae, posing a risk for community transmission and persistence in a setting of a highly granular healthcare system and unrestricted access to antibiotics through private pharmacies. REGISTRATION: This study was registered at the International Standard Randomised Controlled Trials Number registry under number ISRCTN32862422: http://www.isrctn.com/ISRCTN32862422.

Ultralow power spin-orbit torque magnetization switching induced by a non-epitaxial topological insulator on Si substrates.

The large spin Hall effect in topological insulators (TIs) is very attractive for ultralow-power spintronic devices. However, evaluation of the spin Hall angle and spin-orbit torque (SOT) of TIs is usually performed on high-quality single-crystalline TI thin films grown on dedicated III-V semiconductor substrates. Here, we report on room-temperature ultralow power SOT magnetization switching of a ferrimagnetic layer by non-epitaxial BiSb TI thin films deposited on Si/SiO2 substrates. We show that non-epitaxial BiSb thin films outperform heavy metals and other epitaxial TI thin films in terms of the effective spin Hall angle and switching current density by one to nearly two orders of magnitude. The critical SOT switching current density in BiSb is as low as 7 × 104 A/cm2 at room temperature. The robustness of BiSb against crystal defects demonstrate its potential applications to SOT-based spintronic devices.

A conductive topological insulator with large spin Hall effect for ultralow power spin-orbit torque switching.

Spin-orbit torque switching using the spin Hall effect in heavy metals and topological insulators has a great potential for ultralow power magnetoresistive random-access memory. To be competitive with conventional spin-transfer torque switching, a pure spin current source with a large spin Hall angle (θSH > 1) and high electrical conductivity (σ > 105 Ω-1 m-1) is required. Here we demonstrate such a pure spin current source: conductive topological insulator BiSb thin films with σ ≈ 2.5 × 105 Ω-1 m-1, θSH ≈ 52 and spin Hall conductivity σSH ≈ 1.3 × 107 [Formula: see text]Ω-1 m-1 at room temperature. We show that BiSb thin films can generate a very large spin-orbit field of 2.3 kOe MA-1 cm2 and a critical switching current density as low as 1.5 MA cm-2 in Bi0.9Sb0.1/MnGa bilayers, which underlines the potential of BiSb for industrial applications.

4ß-hydroxycholesterol correlates with dose but not steady-state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation?

AIM: 4ß-hydroxycholesterol (4ßOHC) is an endogenous CYP3A(4) biomarker, which is elevated by use of the CYP3A4 inducer carbamazepine. Our aim was to compare to what extent serum concentration of 4ßOHC correlates with dose (presystemic exposure) and steady-state concentration (systemic exposure) of carbamazepine. METHODS: The study was based on a therapeutic drug monitoring material, including information about daily doses and steady-state concentrations (Css ) of carbamazepine. 4ßOHC concentrations were determined in residual serum samples of 55 randomly selected carbamazepine-treated patients and 54 levetiracetam-treated patients (negative controls) by UPLC-APCI-MS/MS after liquid-liquid extraction. Correlation analyses between 4ßOHC concentration and daily dose and Css of carbamazepine, respectively, were performed by Spearman's tests. In addition, 4ßOHC concentrations in females vs. males were compared in induced and non-induced patients. RESULTS: Median 4ßOHC concentration was ~10-fold higher in carbamazepine- vs. levetiracetam-treated patients (650 vs. 54 nmol l(-1) , P < 0.0001). There was a significant, positive correlation between carbamazepine dose and 4ßOHC concentration (Spearman r = 0.53, 95% confidence interval [CI] 0.27, 0.72, P < 0.001). No significant correlation between carbamazepine Css and 4ßOHC concentration was found (Spearman r = 0.14; 95% CI -0.14, 0.40, P = 0.3). Enzyme-induced females had significantly higher 4ßOHC concentrations than males (P < 0.001), while no significant gender difference was found in non-induced patients (P = 0.52). CONCLUSION: Serum concentrations of 4ßOHC correlate with presystemic, but not systemic exposure of the CYP3A4 inducer carbamazepine. This suggests a stronger inductive effect of carbamazepine on presystemic than systemic CYP3A4 phenotype and might indicate a role of the intestine in 4ßOHC formation. Moreover, CYP3A4 inducibility seems to be higher in females than males.

CSF-1 receptor-dependent colon development, homeostasis and inflammatory stress response.

The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) directly regulates the development of Paneth cells (PC) and influences proliferation and cell fate in the small intestine (SI). In the present study, we have examined the role of CSF-1 and the CSF-1R in the large intestine, which lacks PC, in the steady state and in response to acute inflammation induced by dextran sulfate sodium (DSS). As previously shown in mouse, immunohistochemical (IHC) analysis of CSF-1R expression showed that the receptor is baso-laterally expressed on epithelial cells of human colonic crypts, indicating that this expression pattern is shared between species. Colons from Csf1r null and Csf1(op/op) mice were isolated and sectioned for IHC identification of enterocytes, enteroendocrine cells, goblet cells and proliferating cells. Both Csf1r(-/-) and Csf1(op/op) mice were found to have colon defects in enterocytes and enteroendocrine cell fate, with excessive goblet cell staining and reduced cell proliferation. In addition, the gene expression profiles of the cell cycle genes, cyclinD1, c-myc, c-fos, and c-myb were suppressed in Csf1r(-/-) colonic crypt, compared with those of WT mice and the expression of the stem cell marker gene Lgr5 was markedly reduced. However, analysis of the proliferative responses of immortalized mouse colon epithelial cells (lines; Immorto-5 and YAMC) indicated that CSF-1R is not a major regulator of colonocyte proliferation and that its effects on proliferation are indirect. In an examination of the acute inflammatory response, Csf1r(+/-) male mice were protected from the adverse affects of DSS-induced colitis compared with WT mice, while Csf1r(+/-) female mice were significantly less protected. These data indicate that CSF-1R signaling plays an important role in colon homeostasis and stem cell gene expression but that the receptor exacerbates the response to inflammatory challenge in male mice.

The CSF-1 receptor fashions the intestinal stem cell niche.

Gastrointestinal (GI) homeostasis requires the action of multiple pathways. There is some controversy regarding whether small intestine (SI) Paneth cells (PCs) play a central role in orchestrating crypt architecture and their relationship with Lgr5+ve stem cells. Nevertheless, we previously showed that germline CSF-1 receptor (Csf1r) knock out (KO) or Csf1 mutation is associated with an absence of mature PC, reduced crypt proliferation and lowered stem cell gene, Lgr5 expression. Here we show the additional loss of CD24, Bmi1 and Olfm4 expression in the KO crypts and a high resolution 3D localization of CSF-1R mainly to PC. The induction of GI-specific Csf1r deletion in young adult mice also led to PC loss over a period of weeks, in accord with the anticipated long life span of PC, changed distribution of proliferating cells and this was with a commensurate loss of Lgr5 and other stem cell marker gene expression. By culturing SI organoids, we further show that the Csf1r(-/-) defect in PC production is intrinsic to epithelial cells as well as definitively affecting stem cell activity. These results show that CSF-1R directly supports PC maturation and that in turn PCs fashion the intestinal stem cell niche.

Adipose tissue can be generated in vitro by using adipocytes from human fat tissue mesenchymal stem cells seeded and cultured on fibrin gel sheet.

The current study has developed an innovative procedure to generate ex novo fat tissue by culturing adipocytes from human fat tissue mesenchymal stem cells (hFTMSCs) on fibrin gel sheet towards applications in medicine and cosmetology. Fibrin gel has been obtained by combining two components fibrinogen and thrombin collected by human peripheral blood. By this procedure it was possible to generate blocks of fibrin gel containing adipocytes within the gel that show similar features and consistency to human fat tissue mass. Results were assessed by histological staining methods, fluorescent immune-histochemistry staining as well photos by scanning electron microscopy (SEM) to demonstrate the adhesion and growth of cells in the fibrin gel. This result opens a real possibility for future clinical applications in the treatment of reconstructive and regenerative medicine where the use of stem cell may eventually be a unique solution or in the field of aesthetic medicine where autograft fat stem cells may grant for a safer and better outcome with long lasting results.

The co-selection of fluoroquinolone resistance genes in the gut flora of Vietnamese children.

Antimicrobial consumption is one of the major contributing factors facilitating the development and maintenance of bacteria exhibiting antimicrobial resistance. Plasmid-mediated quinolone resistance (PMQR) genes, such as the qnr family, can be horizontally transferred and contribute to reduced susceptibility to fluoroquinolones. We performed an observational study, investigating the copy number of PMQR after antimicrobial therapy. We enrolled 300 children resident in Ho Chi Minh City receiving antimicrobial therapy for acute respiratory tract infections (ARIs). Rectal swabs were taken on enrollment and seven days subsequently, counts for Enterobacteriaceae were performed and qnrA, qnrB and qnrS were quantified by using real-time PCR on metagenomic stool DNA. On enrollment, we found no association between age, gender or location of the participants and the prevalence of qnrA, qnrB or qnrS. Yet, all three loci demonstrated a proportional increase in the number of samples testing positive between day 0 and day 7. Furthermore, qnrB demonstrated a significant increase in copy number between paired samples (p<0.001; Wilcoxon rank-sum), associated with non-fluoroquinolone combination antimicrobial therapy. To our knowledge, this is the first study describing an association between the use of non-fluoroquinolone antimicrobials and the increasing relative prevalence and quantity of qnr genes. Our work outlines a potential mechanism for the selection and maintenance of PMQR genes and predicts a strong effect of co-selection of these resistance determinants through the use of unrelated and potentially unnecessary antimicrobial regimes.

Effect of current breastfeeding on sleep patterns in infants from Asia-Pacific region.

AIM: The aim of this study was to assess the relationship between breastfeeding and sleep patterns in infants from Asia-Pacific region. METHODS: Parents of 10 321 infants (0-11 months) from Australia, China, Hong Kong, India, Indonesia, Korea, Japan, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand and Vietnam completed an expanded version of the Brief Infant Sleep Questionnaire. RESULTS: Overall, 4714 (45.72%) were currently being breastfed; 61.3% of those between 0 and 5 months and 36.6% of those between 6 and 11 months. Currently breastfed infants, when compared with not currently breastfed infants, had a significant increase in the number and duration of night-time wakings and less consolidated sleep. Interestingly, currently breastfed infants less than 6 months also showed longer duration of daytime sleep and obtained more sleep overall. Of note, of those who were currently breastfed, those infants who were nursed back to sleep during night, woke up more often at night (2.41 vs. 1.67 times) and had shorter continuous night-time sleep period (5.58 vs. 6.88 h; P < 0.001). There was no significant difference between breastfeeding and non-breastfeeding infants in the number of night wakings, when the nursing to sleep variable was controlled for in the analysis of variance. CONCLUSION: Breastfeeding is associated with reduced sleep consolidation in infants. This relationship, however, may be moderated by parenting practices of nursing to sleep and back to sleep during the night. Thus, parents of infants with night waking problems should be encouraged to limit the association between nursing and falling to sleep, to improve sleep while maintaining breastfeeding.

In vitro culture of Keratinocytes from human umbilical cord blood mesenchymal stem cells: the Saigonese culture.

There have been many attempts to acquire and culture human keratinocytes for clinical purposes including from keratotome slices in media with fetal calf serum (FCS) or pituitary extract (PE), from skin specimens in media with feeder layers, from suction blister epidermal roofs' in serum-free culture and from human umbilical cord blood (hUCB) mesenchymal stem cells (MSCs) in media with skin feeder layers. Conversely this study was designed to investigate whether keratinocytes could be obtained directly from hUCB MSCs in vitro. It is widely established that mesenchymal stem cells from human umbilical cord blood have multipotent capacity and the ability to differentiate into disparate cell lineages hUCB MSCs were directly induced to differentiate into keratinocytes by using a specific medium composed of primary culture medium (PCM) and serum free medium (SFM) in a ratio 1:9 for a period of 7 days and tested by immunostain p63 and K1-K10. Cells thus cultured were positive in both tests, confirming the possibility to directly obtain keratinocytes from MSCs hUCB in vitro.

Culture and differentiation of osteoblasts on coral scaffold from human bone marrow mesenchymal stem cells.

In this paper we describe an approach that aims to provide fundamental information towards a scientific, biomechanical basis for the use of natural coral scaffolds to initiate mesenchymal stem cells into osteogenic differentiation for transplant purposes. Biomaterial, such as corals, is an osteoconductive material that can be used to home human derived stem cells for clinical regenerative purposes. In bone transplantation, the use of biomaterials may be a solution to bypass two main critical obstacles, the shortage of donor sites for autografts and the risk of rejection with allograft procedures. Bone regeneration is often needed for multiple clinical purposes for instance, in aesthetic reconstruction and regenerative procedures. Coral graft Porites lutea has been used by our team for a decade in clinical applications on over a thousand patients with different bone pathologies including spinal stenosis and mandibular reconstruction. It is well accepted that human bone marrow (hBM) is an exceptional source of mesenchymal stem cells (MSCs), which may differentiate into different cell phenotypes such as osteoblasts, chondrocytes, adipocytes, myocytes, cardiomyocytes and neurons. Isolated MSCs from human bone marrow were induced into osteoblasts using an osteogenic medium enriched with two specific growth factors, FGF9 and vitamin D2. Part of the cultured MSCs were directly transferred and seeded onto coral scaffolds (Porites Lutea) and induced to differentiate into osteoblasts and part were cultured in flasks for osteocell culture. The data support the concept that hBM is a reliable source of MSCs which may be easily differentiated into osteoblasts and seeded into coral as an optimal device for clinical application. Within this project we have also discussed the biological nature of MSCs, their potential application for clinical transplantation and the prospect of their use in gene therapy.

In vitro culture and differentiation of osteoblasts from human umbilical cord blood.

It is well accepted that human umbilical cord blood (UCB) is a source of mesenchymal stem cells (MSCs) which are able to differentiate into different cell phenotypes such as osteoblasts, chondrocytes, adipocytes, myocytes, cardiomyocytes and neurons. The aim of this study was to isolate MSCs from human UCB to determine their osteogenic potential by using different kinds of osteogenic medium. Eventually, only those MSCs cultured in osteogenic media enriched with vitamin D(2) and FGF9, were positive for osteocalcin by RT-PCR. All these cells were positive for alizarin red, alkaline phosphatase and Von Kossa. The results obtained from RT-PCR have confirmed that osteogenesis is complete by expression of the osteocalcin marker. In conclusion, vitamin D(2), at least in vitro, may replace vitamin D(3) as an osteogenic stimulator factor for MSC differentiation.

Colony stimulating factor-1 dependence of paneth cell development in the mouse small intestine.

BACKGROUND & AIMS: Paneth cells (PCs) secrete defensins and antimicrobial enzymes that contribute to innate immunity against pathogen infections within the mucosa of the small intestine. We examined the role of colony stimulating factor-1 (CSF-1) in PC development. METHODS: CSF-1-deficient and CSF-1 receptor (CSF-1R)-deficient mice and administration of neutralizing anti-CSF-1R antibody were used to study the requirement of CSF-1 for the development of epithelial cells of the small intestine. CSF-1 transgenic reporter mice and mice that express only the membrane-spanning, cell-surface CSF-1 isoform were used to investigate regulation by systemic versus local CSF-1. RESULTS: Mice deficient in CSF-1 or CSF-1R had greatly reduced numbers of mature PCs. PCs express the CSF-1R, and administration of anti-CSF-1R antibody to neonatal mice significantly reduced the number of PCs. Analysis of transgenic CSF-1 reporter mice showed that CSF-1-expressing cells are in close proximity to PCs. CSF-1/CSF-1R-deficient mice also had reduced numbers of the proliferating epithelial cell progenitors and lamina propria macrophages. Expression of the membrane-spanning, cell-surface CSF-1 isoform in CSF-1-deficient mice completely rescued the deficiencies of PCs, proliferating progenitors, and lamina propria macrophages. CONCLUSIONS: These results indicate local regulation by CSF-1 of PC development, either directly, in a juxtacrine/paracrine manner, or indirectly, by lamina propria macrophages. Therefore, CSF-1R hyperstimulation could be involved in hyperproliferative disorders of the small intestine, such as Crohn's disease and ulcerative colitis.

Oncogenic properties of HIV-Tat in colorectal cancer cells.

With the advent of Highly-Active-Anti-Retroviral-Therapy (HAART), HIV patients can expect to live beyond 10-15 years following diagnosis. An unexpected result of increased survival is the emergence of opportunistic, oncogenic virus-associated cancers such as Burkitt's lymphoma (Epstein-Barr Virus), cervical cancer (Human Papilloma Virus) and Kaposi's sarcoma (Kaposi's sarcoma-associated herpesvirus) in this immuno-compromised population. Furthermore, there are reports of colorectal cancers (CRC) in long-term HIV-AIDS survivors. Compared to the general, non-immuno-compromised population, long-term AIDS patients have 4 and 3.3-fold increased risk of developing colorectal and anorectal cancer respectively. Unlike oncogenic virus-associated cancers, CRC is not known to have a viral etiology. Our study aimed to investigate one aspect of HIV infection and colorectal carcinogenesis. We proposed that the HIV transactivator protein Tat; a protein with known oncogenic properties that is secreted and can re-enter non-infected cells may have a role in CRC. Using two CRC cell lines, LIM1215 and LIM2537 we found that Tat inhibits epithelial cyto-differentiation, blocks apoptosis in vitro and accelerates tumour formation in vivo. In addition, Tat significantly increases in vitro migration in the absence of foetal calf serum. These properties underpin CRC, and as HIV infection is initiated in the gut lymphoid system, these data provide a basis for the increased incidence of CRC in long term AIDS patients.