Cultivated sunflower (Helianthus annuus L.) has lower tolerance of moderate drought stress than its con-specific wild relative, but the underlying traits remain elusive.

Cultivated crops are generally expected to have less abiotic stress tolerance than their wild relatives. However, this assumption is not well supported by empirical literature and may depend on the type of stress and how it is imposed, as well as the measure of tolerance being used. Here, we investigated whether wild and cultivated accessions of Helianthus annuus differed in stress tolerance assessed as proportional decline in biomass due to drought and whether wild and cultivated accessions differed in trait responses to drought and trait associations with tolerance. In a greenhouse study, H. annuus accessions in the two domestication classes (eight cultivated and eight wild accessions) received two treatments: a well-watered control and a moderate drought implemented as a dry down followed by maintenance at a predetermined soil moisture level with automated irrigation. Treatments were imposed at the seedling stage, and plants were harvested after 2 weeks of treatment. The proportional biomass decline in response to drought was 24% for cultivated H. annuus accessions but was not significant for the wild accessions. Thus, using the metric of proportional biomass decline, the cultivated accessions had less drought tolerance. Among accessions, there was no tradeoff between drought tolerance and vigor assessed as biomass in the control treatment. In a multivariate analysis, wild and cultivated accessions did not differ from each other or in response to drought for a subset of morphological, physiological, and allocational traits. Analyzed individually, traits varied in response to drought in wild and/or cultivated accessions, including declines in specific leaf area, leaf theoretical maximum stomatal conductance (gsmax), and stomatal pore length, but there was no treatment response for stomatal density, succulence, or the ability to osmotically adjust. Focusing on traits associations with tolerance, plasticity in gsmax was the most interesting because its association with tolerance differed by domestication class (although the effects were relatively weak) and thus might contribute to lower tolerance of cultivated sunflower. Our H. annuus results support the expectation that stress tolerance is lower in crops than wild relatives under some conditions. However, determining the key traits that underpin differences in moderate drought tolerance between wild and cultivated H. annuus remains elusive.

The #SeePainMoreClearly Phase II Pain in Dementia Social Media Campaign: Implementation and Evaluation Study.

BACKGROUND: Social media platforms have been effective in raising awareness of the underassessment and undertreatment of pain in dementia. OBJECTIVE: After a successful pilot campaign, we aimed to scale our pain-in-dementia knowledge mobilization pilot initiative (ie, #SeePainMoreClearly) to several social media platforms with the aid of a digital media partner. The goal of the initiative was to increase awareness of the challenges in the assessment and management of pain among people with dementia. A variety of metrics were implemented to evaluate the effort. Through this work, we endeavored to highlight key differences between our pilot initiative (which was a grassroots initiative), focusing largely on Twitter and YouTube, and the current science-media partnership. We also aimed to generate recommendations suitable for other social media campaigns related to health or aging. METHODS: Evidence-based information about pain in dementia was summarized into engaging content (eg, videos) tailored to the needs of various knowledge users (eg, health professionals, families, and policy makers). We disseminated information using Facebook (Meta Platforms), Twitter (X Corp), YouTube (Alphabet Inc), Instagram (Meta Platforms), and LinkedIn (LinkedIn Corp) and measured the success of the initiative over a 12-month period (2020 to 2021). The evaluation methods focused on web analytics and questionnaires related to social media content. Knowledge users' web responses about the initiative and semistructured interviews were analyzed using thematic analysis. RESULTS: During the course of the campaign, >700 posts were shared across all platforms. Web analytics showed that we drew >60,000 users from 82 countries to our resource website. Of the social media platforms used, Facebook was the most effective in reaching knowledge users (ie, over 1,300,000 users). Questionnaire responses from users were favorable; interview responses indicated that the information shared throughout the initiative increased awareness of the problem of pain in dementia and influenced respondent behavior. CONCLUSIONS: In this investigation, we demonstrated success in directing knowledge users to a resource website with practical information that health professionals could use in patient care along with pain assessment and management information for caregivers and people living with dementia. The evaluation metrics suggested no considerable differences between our pilot campaign and broader initiative when accounting for the length of time of each initiative. The limitations of large-scale health campaigns were noted, and recommendations were outlined for other researchers aiming to leverage social media as a knowledge mobilization tool.

Human amnion epithelial cell therapy reduces hypertension-induced vascular stiffening and cognitive impairment.

Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8-12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9-11, P < 0.05). Administration of amnion epithelial cells attenuated these effects of angiotensin II (P < 0.05). Angiotensin II-induced cognitive impairment was prevented by amnion epithelial cell therapy (n = 7-9, P < 0.05). In the brain, amnion epithelial cells modulated some of the inflammatory genes that angiotensin II promoted differential expression of (n = 6, p-adjusted < 0.05). These findings suggest that amnion epithelial cells could be explored as a potential therapy to inhibit vascular pathology and cognitive impairment during hypertension.

Are mobile apps meeting the needs of caregivers of people living with dementia? An evaluation of existing apps for caregivers.

OBJECTIVES: Informal caregivers of people living with dementia (ICPDs) experience stressors that can lead to adverse outcomes. Although apps for ICPDs are available, evidence to support their effectiveness is limited. This investigation was aimed at providing an evaluation of available apps for ICPDs. METHODS: We conducted two studies: 1) search and evaluation of available apps; and 2) controlled trial of two apps identified in the Study 1 (NCT05217004). For Study 2, participants were randomly assigned to one of the two app-using groups or a control group. Outcome measures were administered before, post-intervention, and at a follow-up. Interviews with caregivers were conducted to examine their needs regarding the development of future apps. RESULTS: Sixteen apps were examined in Study 1. Results suggest that the number and type of features present in each app may not be sufficient to address the multifaceted needs of ICPDs. In Study 2, contrary to expectation, we did not identify differences between the app-using and control conditions on our outcome measures. Participants noted several content and user-experience needs to consider in developing new apps. CONCLUSION: Findings from the investigation can inform future developments of apps to address the needs of ICPDs.

Sex-specific effects of a high fat diet on aortic inflammation and dysfunction.

Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. A high fat diet (HFD) is often used to model obesity in mice, but the sex-specific effects of this diet on aortic inflammation and function are unclear. Therefore, we characterized the aortic immune cell profile and function in 6-week-old male and female C57BL/6 mice fed a normal chow diet (NCD) or HFD for 10 weeks. Metabolic parameters were measured weekly and fortnightly. At end point, aortic immune cell populations and endothelial function were characterized using flow cytometry and wire myography. HFD-male mice had higher bodyweight, blood cholesterol, fasting blood glucose and plasma insulin levels than NCD mice (P < 0.05). HFD did not alter systolic blood pressure (SBP), glycated hemoglobin or blood triglycerides in either sex. HFD-females had delayed increases in bodyweight with a transient increase in fasting blood glucose at week 8 (P < 0.05). Flow cytometry revealed fewer proinflammatory aortic monocytes in females fed a HFD compared to NCD. HFD did not affect aortic leukocyte populations in males. Conversely, HFD impaired endothelium-dependent vasorelaxation, but only in males. Overall, this highlights biological sex as a key factor determining vascular disease severity in HFD-fed mice.

Pathophysiological Links Between Obesity and Dementia.

Obesity is a major global health concern, with prevalence rates rapidly rising due to increased availability of highly processed foods rich in fats and/or sugars and technological advances promoting more sedentary behaviour. There is increasing evidence to suggest that obesity predisposes individuals to developing cognitive impairment and dementia. However, the relationship between the brain and the peripheral metabolic state is complex, and many of the underlying mechanisms of cognitive impairment in obesity are yet to be fully elucidated. To better understand the links between obesity and dementia, further work is required to determine pathological changes occurring in the brain during obesity. In this mini-review, we discuss the role of two pathological features of obesity (the gut-brain axis and systemic inflammation) and their potential contribution to dementia.

Implementation and evaluation of a pain assessment app and novel community platform for long-term care health professionals.

OBJECTIVE: A tablet app, based on the Pain Assessment Checklist for Seniors with Limited Ability to Communicate-II (PACSLAC-II), has been shown to have clinical utility and unique advantages. We aimed to replicate and extend the previous validation of the app through the implementation and evaluation of a new community platform involving a quality indicator (QI) monitoring feature and a resource community portal (CP) that work in conjunction with an updated version of the app. METHODS: We employed a mixed-methods multiple-baseline design across 11 long-term care (LTC) units. Units were randomly assigned to conditions which varied in number of app features available. Data included unit-level QIs as well as questionnaires and semi-structured interviews with health professionals. RESULTS: Following use of the app, we found improvements in unit-level QIs regardless of availability of the QI/CP features. During interviews, participants expressed a preference for the app over a paper version of the PACSLAC-II due to reasons such as the app's ability to summarize information. Utilization of the community portal websites was unrelated to staff questionnaire-assessed stress/burnout. CONCLUSIONS: Despite the positive effects on the care of residents, the COVID-19 pandemic presented challenges and interfered with the long-term maintenance of the QI results.

Clinicopathological and Epidemiological Findings in Pet Cats Naturally Infected with Feline Immunodeficiency Virus (FIV) in Australia.

Feline immunodeficiency virus (FIV) infection in experimentally infected domestic cats produces characteristic clinical manifestations including hematological changes, neurological disease, neoplasia (most notably lymphoma) and lymphopenia-mediated immunodeficiency predisposing cats to a range of secondary infections. Conflicting reports exist, however, with regard to disease associations and survival time in naturally FIV-infected cats. The purpose of this retrospective case−control study was to investigate the effect of natural FIV infection on hematological, blood biochemical and urinalysis parameters and survival time in three cohorts of pet cats in Australia. Cohorts 1 and 2 were recruited from a large veterinary hospital in Melbourne, Victoria (n = 525 and 282), while a third cohort consisted of cats recruited from around Australia as part of a FIV field vaccine efficacy trial (n = 425). FIV-infected cats in cohorts 1, 2 and 3 were found to have 15/37 (41%), 13/39 (33%) and 2/13 (15%) clinicopathological parameters significantly different to FIV-uninfected cats, respectively. Two changes in FIV-infected cats in cohort 1, hypochromia (low hemoglobin) and hyperglobulinemia, were outside the supplied reference intervals and should serve as diagnostic triggers for FIV testing. Kaplan−Meier survival analysis of cats in cohorts 1 and 2 combined did not find any difference between FIV-infected and FIV-uninfected cats, however a confounding factor was a large euthanasia rate within the first 12 months in both groups. Three significant (p < 0.05) spatial clusters of FIV infection were identified in Melbourne. A possible relationship between FIV infection status and socioeconomic disadvantage was discovered, based on three government indices of socioeconomic status (p < 0.001). Until longitudinal field studies are performed in Australia to further investigate the long-term effects of natural FIV infection, Australian veterinarians should consider FIV to be an important infection of pet cats, and recommend measures to prevent FIV infection.

Sex hormones, intestinal inflammation, and the gut microbiome: Major influencers of the sexual dimorphisms in obesity.

Obesity is defined as the excessive accumulation of body fat and is associated with an increased risk of developing major health problems such as cardiovascular disease, diabetes and stroke. There are clear sexual dimorphisms in the epidemiology, pathophysiology and sequelae of obesity and its accompanying metabolic disorders, with females often better protected compared to males. This protection has predominantly been attributed to the female sex hormone estrogen and differences in fat distribution. More recently, the sexual dimorphisms of obesity have also been attributed to the differences in the composition and function of the gut microbiota, and the intestinal immune system. This review will comprehensively summarize the pre-clinical and clinical evidence for these sexual dimorphisms and discuss the interplay between sex hormones, intestinal inflammation and the gut microbiome in obesity. Major gaps and limitations of this rapidly growing area of research will also be highlighted in this review.

Predictors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following High-Risk Exposure.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are recommended for COVID-19 prevention. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified. METHODS: We conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-12 November, 2021. We used conditional logistic regression to estimate adjusted odds ratios (aORs) of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 ("high-risk exposure") ≤14 days before testing. RESULTS: 751 of 1448 cases (52%) and 255 of 1443 controls (18%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 3.02-fold (95% confidence interval: 1.75-5.22) higher when high-risk exposures occurred with household members (vs. other contacts), 2.10-fold (1.05-4.21) higher when exposures occurred indoors (vs. outdoors only), and 2.15-fold (1.27-3.67) higher when exposures lasted ≥3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Cases were less likely than controls to report mask usage during high-risk exposures (aOR = 0.50 [0.29-0.85]). The adjusted odds of case status was lower for fully-vaccinated (aOR = 0.25 [0.15-0.43]) participants compared to unvaccinated participants. Benefits of mask usage were greatest among unvaccinated and partially-vaccinated participants, and in interactions involving non-household contacts or interactions occurring without physical contact. CONCLUSIONS: NPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.

Renal morphology and glomerular capillarisation in young adult sheep born moderately preterm.

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman's spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman's space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.

Unhealthy weight control behaviors among a sample of U.S. journalists.

OBJECTIVE: Research on body image and weight control behaviors among journalists is limited. To fill this knowledge gap, we conducted a cross-sectional study to assess the experiences of unhealthy weight control behaviors (UWCBs), binge eating, and appearance-related pressures among a sample of journalists in the United States (U.S.). METHOD: We administered an online survey to journalists assessing their roles in the news industry, engagement in UWCBs (e.g., vomiting, laxative use, dieting, fasting) and binge eating. Odds ratios of the outcomes were estimated using a series of multivariate logistic regression models. RESULTS: Over 68%, 19%, and 30% of participants reported they went on a diet, fasted for weight control, and binge ate, respectively. Our results suggest on-air journalists demonstrated higher odds of dieting compared to their counterparts who do not work in front of the camera. Furthermore, some journalists reported being subjected to appearance-related pressures in the industry. DISCUSSION: Our results provide a glimpse of weight control behaviors, binge eating, and appearance-related pressures among workers in the U.S. journalism industry. Given the concerning prevalence of purging and binge eating in our sample, future studies should assess whether journalists represent an occupation group that is at high risk of developing eating disorders.

The Vascular Consequences of Metabolic Syndrome: Rodent Models, Endothelial Dysfunction, and Current Therapies.

Metabolic syndrome is characterized by visceral obesity, dyslipidemia, hyperglycemia and hypertension, and affects over one billion people. Independently, the components of metabolic syndrome each have the potential to affect the endothelium to cause vascular dysfunction and disrupt vascular homeostasis. Rodent models of metabolic syndrome have significantly advanced our understanding of this multifactorial condition. In this mini-review we compare the currently available rodent models of metabolic syndrome and consider their limitations. We also discuss the numerous mechanisms by which metabolic abnormalities cause endothelial dysfunction and highlight some common pathophysiologies including reduced nitric oxide production, increased reactive oxygen species and increased production of vasoconstrictors. Additionally, we explore some of the current therapeutics for the comorbidities of metabolic syndrome and consider how these benefit the vasculature.

MRI does not predict pathologic complete response after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: This study assessed whether magnetic resonance imaging (MRI) could accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for patients receiving standardized treatment, pre- and post-NAC MRI on the same instrumentation using a consistent imaging protocol, interpreted by a single breast fellowship-trained radiologist. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all patients with breast cancer treated with NAC from 2015 to 2018. Radiographic complete response (rCR) was defined as absence of suspicious MRI findings in the ipsilateral breast or lymph nodes. pCR was defined as the absence of invasive cancer or ductal carcinoma in-situ in breast or lymph nodes after operation (ypT0N0M0). RESULTS: Data for 102 consecutive patients demonstrated that 44 (43.1%) had rCR and 41 (40.1%) had pCR. pCR occurred in 12 (25.0%) of 48 estrogen receptor positive (ER+) patients, 29 (53.7%) of 54 ER- patients, and 25 (52.1%) of 48 human epidermal growth factor receptor 2 positive patients. The positive predictive value for MRI after NAC was 84.5% and the negative predictive value was 72.7%. The accuracy rate for MRI was 78.6%. Of the 44 patients with rCR, 12 (27.3%) had residual cancer on the pathologic specimen after surgical excision. CONCLUSION: rCR is not accurate enough to serve as a surrogate marker for pCR on MRI after NAC.

Risk of Feline Immunodeficiency Virus (FIV) Infection in Pet Cats in Australia is Higher in Areas of Lower Socioeconomic Status.

Feline immunodeficiency virus (FIV), feline calicivirus (FCV), and feline herpesvirus (FHV-1) are common viral infections of domestic cats in Australia. A study was performed to investigate the possible effect of area-based socioeconomic factors on the occurrence of FIV, FCV, and FHV-1 infection in Australian client-owned cats. A total of 1044 cases, reported to a voluntary Australian online disease surveillance system between January 2010 and July 2017, were analysed with respect to their postcode-related socioeconomic factors using the Socio-Economic Indexes For Areas (SEIFA). SEIFA consists of four different indexes which describe different aspects of socioeconomic advantage and disadvantage. Signalment details including age, sex, neuter status, and breed were also considered. A significant correlation was observed between areas of lower socioeconomic status and a higher number of reported cases of FIV infection for all four SEIFA indexes (p ≤ 0.0002). Postcodes with SEIFA indexes below the Australian median ("disadvantaged" areas) were 1.6-2.3 times more likely to have reported cases of FIV infection than postcodes with SEIFA indexes above the median ("advantaged" areas). In contrast, no correlation was observed between the number of reported cases of FCV or FHV-1 infection and any of the four SEIFA indexes (p > 0.05). When signalment data were analysed for the three infections, FIV-infected cats were more likely to be older (p < 0.00001), male (p < 0.0001), neutered (p = 0.03), and non-pedigree (p < 0.0001) compared to FCV and FHV-1 infected cats. Results from this study suggest that area-based disease control strategies, particularly in areas of social disadvantage, might be effective in reducing the prevalence of FIV infection in pet cats in Australia.

Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System.

OBJECTIVE: In 2013, the American College of Rheumatology (ACR) participated in the Choosing Wisely campaign and devised a recommendation to avoid testing antinuclear antibody (ANA) subserologies without a positive ANA and clinical suspicion of disease. The goals of our study were to describe ANA and subserology ordering practices and predictors of ordering concurrent ANA and subserologies in a safety-net hospital. METHODS: We identified ANA and subserologies (dsDNA, Sm, RNP, SSA, SSB, Scl-70 and centromere) completed at Denver Health between 1/1/2005 and 12/31/2011. Variables included demographics, primary insurance, service, and setting from which the test was ordered. We performed multivariable logistic regression to determine predictors of concurrent ordering of ANA and subserologies. RESULTS: During seven years, 3221 ANA were performed in 2771 individuals and 211 (6.6%) were performed concurrently with at least one subserology. The most common concurrent subserologies were dsDNA (21.8%), SSA (20.8%), and SSB (19.7%). In the multivariable logistic analysis, significant predictors of concurrent ANA and subserologies were the labs being ordered from subspecialty care (OR 8.12, 95% CI 5.27-12.50, p-value <0.0001) or from urgent/inpatient care (OR 3.86, 95% CI 1.78-8.38, p-value 0.001). A significant predictor of decreased odds was male gender (OR 0.32, 95% CI 0.21-0.49, p-value <0.0001). Five individuals (2.2% of the negative ANA with subserologies ordered) had a negative ANA but positive subserologies. CONCLUSION: Of 3221 ANA, 6.6% were performed concurrently with subserologies, and subspecialists were more likely to order concurrent tests. A negative ANA predicted negative subserologies with rare exceptions, which validates the ACR's recommendations.

The effects of H-bonding and sterics on the photoreactivity of a trimethyl butyrophenone derivative.

The irradiation of ester 1 in methanol and chloroform does not yield any photoproducts, whereas the photolysis of 1 in dry argon-saturated benzene produces cyclobutanol 4, which is converted to lactone 5 by the addition of HCl. Laser-flash photolysis of ester 1 demonstrates that 1 undergoes intramolecular H-atom abstraction to form the biradical 2 (λ(max)∼ 310 nm, τ = 200 ns, benzene), which intersystem crosses to photoenols, Z-3 (λ(max)∼ 380 nm, τ = 30-60 µs, benzene) and E-3 (λ(max)∼ 380 nm, τ = 11 ms, benzene). Density functional theory calculations were performed to support the proposed mechanism for forming cyclobutanol 4 and to explain how steric demand facilitates photoenol E-3 to form cyclobutanol 4 rather than lactone 5.

Comparison of techniques used to support the nasal tip and their long-term effects on tip position.

OBJECTIVES: To examine the indications for the use of septal extension grafts, columellar struts, and tongue-and-groove techniques to provide support and set the tip position during rhinoplasty, and to compare the strength of their support and analyze their long-term effects on tip position. METHODS: The medical records and photographs of patients who underwent external septorhinoplasty during a 2-year period were analyzed. Forty patients had photographs from short-term follow-up (<12 weeks) and were included in the study. The short-term and long-term (>52 weeks) tip positions were compared to determine the maintenance of tip position with each technique. Each stabilization technique was performed on 5 fresh cadavers, and the resistance to displacement of the tip was measured and compared. RESULTS: Objective measurements in the cadaver analysis show increased resistance to tip displacement with the use of caudal septal extension grafts and tongue-and-groove techniques. There was no difference in the maintenance of tip position between the techniques in analysis of the patients who have undergone rhinoplasty. CONCLUSIONS: Many factors influence the maintenance of tip position in patients who have undergone rhinoplasty. One should consider using a stabilization technique to help resist displacement of the nasal tip. Clinical and operative findings, as well as secondary effects, are used to help determine which technique should be used.

Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.

PURPOSE: The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model. MATERIALS AND METHODS: A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) viral particles per injection) and docetaxel (1 mg/kg per injection). Tumor size, weight, toxicity, and overall and disease-free survival rates were determined. RESULTS: Intratumoral treatments with either docetaxel alone or Ad-p53 alone resulted in statistically significant antitumor activity and improved survival compared with control group. Furthermore, combined delivery of Ad-p53 and docetaxel resulted in a statistically significant reduction in tumor weight when compared to treatment with either Ad-p53 or docetaxel alone. CONCLUSION: Intratumoral delivery of docetaxel enhanced the antitumor effect of Ad-p53 in murine head and neck cancer xenograft model. The result of this preclinical in vivo study is promising and supports further clinical testing to evaluate efficacy of combined intratumoral docetaxel and Ad-p53 in treatment of head and neck cancer.