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1.
Can J Diabetes ; 47(7): 579-586.e6, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37187438

ABSTRACT

OBJECTIVES: There was rapid uptake of pediatric diabetes telehealth at the onset of the COVID-19 pandemic and initial studies demonstrated good usability and satisfaction. As exposure to telehealth continued to increase during the pandemic, we aimed to determine changes in telehealth usability and changes in future preferences for telehealth care. METHODS: A telehealth questionnaire was administered early in the pandemic and again more than 1 year later. Survey data were linked with a clinical data registry. A multivariable proportional odds logistic mixed-effects model was used to assess the association between exposure to telehealth and outcome of future preference for telehealth. Multivariable linear mixed-effects models were used to examine associations between exposure to early and later pandemic periods and the outcome of usability scores. RESULTS: Survey response rate was 40%, with 87 early and 168 later period participants. Virtual visits increased from 46% to 92% of all telehealth visits. Virtual visits improved in "ease of use" (p=0.0013) and "satisfaction" (p=0.045); there were no improvements in telephone visits. The odds of indicating higher preference for more future telehealth visits was 5.1-fold higher in the later pandemic group (p=0.0298). Eighty percent of participants would like their future care to include telehealth visits. CONCLUSIONS: At our tertiary diabetes centre, families' desire for future telehealth care has increased during this 1-year period of additional telehealth exposure, and virtual care has now become the preferred option. This study provides important family perspectives that can help guide development of future diabetes clinical care.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 1 , Telemedicine , Humans , Child , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/therapy , Follow-Up Studies , Pandemics , COVID-19/epidemiology
2.
J Appl Phycol ; 34(5): 2551-2563, 2022.
Article in English | MEDLINE | ID: mdl-36033835

ABSTRACT

Saccharina latissima (sugar kelp) is one of the most widely cultivated brown marine macroalgae species in the North Atlantic and the eastern North Pacific Oceans. To meet the expanding demands of the sugar kelp mariculture industry, selecting and breeding sugar kelp that is best suited to offshore farm environments is becoming necessary. To that end, a multi-year, multi-institutional breeding program was established by the U.S. Department of Energy's (DOE) Advanced Research Projects Agency-Energy (ARPA-E) Macroalgae Research Inspiring Novel Energy Resources (MARINER) program. Hybrid sporophytes were generated using 203 unique gametophyte cultures derived from wild-collected Saccharina spp. for two seasons of farm trials (2019-2020 and 2020-2021). The wild sporophytes were collected from 10 different locations within the Gulf of Maine (USA) region, including both sugar kelp (Saccharina latissima) and the skinny kelp species (Saccharina angustissima). We harvested 232 common farm plots during these two seasons with available data. We found that farmed kelp plots with skinny kelp as parents had an average increased yield over the mean (wet weight 2.48 ± 0.90 kg m-1 and dry weight 0.32 ± 0.10 kg m-1) in both growing seasons. We also found that blade length positively correlated with biomass in skinny kelp x sugar kelp crosses or pure sugar kelp crosses. The skinny x sugar progenies had significantly longer and narrower blades than the pure sugar kelp progenies in both seasons. Overall, these findings suggest that sugar x skinny kelp crosses provide improved yield compared to pure sugar kelp crosses. Supplementary Information: The online version contains supplementary material available at 10.1007/s10811-022-02811-1.

3.
Can J Diabetes ; 46(4): 346-352.e1, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35527205

ABSTRACT

OBJECTIVES: Pediatric diabetes health-care providers and decision-makers in British Columbia (BC) have prioritized the creation of a provincial pediatric diabetes clinical registry to improve care quality. Our objective is to build the first BC Pediatrics Diabetes Registry (BC-PDR) for quality improvement and coordination of pediatric diabetes care across the province. METHODS: Patients <19 years of age and diagnosed with diabetes were invited to participate in our study. Recruitment began in 2017 at the BC Children's Hospital (BCCH) and expanded to 6 community-based pediatric diabetes clinics in the Interior Health Authority (HA) in 2019. In response to COVID-19, recruitment shifted from in-person to virtual using an electronic consent system. Patient-level (e.g. age at diabetes onset, ethnicity) and visit-level (e.g. glycated hemoglobin [A1C], blood pressure, diabetes regimen, technology use, medications) data were collected in addition to screening for and presence of diabetes complications. RESULTS: As of January 2021, 635 patients from the BCCH and Interior HA were included in the BC-PDR. From the BCCH, 94% of 590 patients were diagnosed with type 1 diabetes and the median A1C was 7.8% and increased with age. Just under half of the BCCH patients were using insulin pump technology and/or a continuous glucose monitoring system. CONCLUSIONS: Over the last 3 years, we have worked to adapt and operationalize the BC-PDR. The next steps for the BC-PDR include engaging diabetes stakeholders in the development of an electronic benchmarking dashboard along with linkage of the data to patient-reported outcome and experience measures and provincial administrative databases.


Subject(s)
Diabetes Mellitus, Type 1 , Registries , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , British Columbia/epidemiology , COVID-19 , Child , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/epidemiology , Glycated Hemoglobin/analysis , Humans
4.
Inquiry ; 59: 469580221082787, 2022.
Article in English | MEDLINE | ID: mdl-35352982

ABSTRACT

INTRODUCTION: Vaccination is vital for controlling the COVID-19 pandemic. Individuals' vaccination intention is a good predictor of vaccine uptake and is influenced by individuals' health belief toward vaccination. Regions with different levels of pandemic severity may present varying effects. This study aimed to determine the influence of health belief on COVID-19 vaccination intention in a region with a low level of COVID-19 infection. METHODS: This cross-sectional telephone survey was conducted on a quota sample of 800 adults in Hong Kong before the commencement of the local COVID-19 vaccination program. The Health Belief Model Scale-COVID-19 was developed to assess health belief toward COVID-19 vaccination. The contribution of health belief on explaining intention to receive the COVID-19 vaccine was assessed using logistic regression. RESULTS: The subjects demonstrated moderate levels in all aspects of health belief. Only 28.9% of the subjects indicated an intention to receive a COVID-19 vaccine. After controlling for age, educational level, marital status, and high risk status, the logistic regression analysis indicated that perceived benefits of vaccination (OR = 1.615; CI 95%: 1.443-1.807; P < .001), perceived susceptibility to COVID-19 (OR = 1.130; CI 95%: 1.032-1.237; P = .008), cues to action toward vaccination (OR = 1.212; CI 95%: 1.108-1.326; P < .001), and perceived barriers to vaccination (OR = .696; CI 95%: .641-.756; P < .001) were associated with intention to receive a COVID-19 vaccine. CONCLUSION: Vaccination campaigns in regions with good control of the pandemic should promote the benefits of vaccination, emphasizing how it can help individuals regain a sense of normalcy in their daily lives and stop the spread of COVID-19. Although the COVID-19 pandemic affects countries worldwide, this study highlights the importance of adopting specific vaccination promotion strategies for regions with different levels of pandemic severity.


Subject(s)
COVID-19 , Influenza, Human , Adult , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Hong Kong/epidemiology , Humans , Influenza, Human/epidemiology , Intention , Pandemics , Vaccination
5.
BMC Public Health ; 21(1): 1267, 2021 06 29.
Article in English | MEDLINE | ID: mdl-34187439

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, over 99% of adults in Hong Kong use face masks in public. With the limited supply of face masks in the market and the uncertainty about the future development of COVID-19, reusing face masks is a legitimate way to reduce usage. Although this practice is not recommended, reusing face masks is common in Hong Kong. This study aimed to examine the practice of reusing face masks among adults in Hong Kong during the COVID-19 pandemic and its association with their health beliefs toward this health crisis. METHODS: A cross-sectional descriptive study was conducted. A quota sample of 1000 adults was recruited in Hong Kong in April 2020. Guided by the Health Belief Model, the subjects were invited to answer questions on their practice of reusing face masks and health beliefs toward COVID-19 through telephone interview. Their practice on reuse, storage, and decontamination of used face masks were summarized by descriptive statistics. The difference in health beliefs between the subjects who reused and did not reuse face masks was examined by conducting an independent t test. The association between health beliefs and reuse of face masks was determined by conducting a logistic regression analysis. RESULTS: One-third (n = 345, 35.4%) of the subjects reused face masks in an average of 2.5 days. Among them, 207 subjects stored and 115 subjects decontaminated their used face masks by using various methods. The subjects who reused face masks significantly perceived having inadequate face masks (t = 3.905; p <  0.001). Having a higher level of perception of having inadequate face masks increased the likelihood of reusing face masks (OR = 0.784; CI 95%: 0.659-0.934; p = 0.006). CONCLUSION: Despite having 90 face masks in stock, the adults who reused face masks significantly perceived that they had inadequate face masks. Concerted effort of health care professionals, community organizations, and the government will improve individuals' practice in use of face masks and alleviate their actual and perceived feeling of having inadequate face masks, which lead them to reuse.


Subject(s)
COVID-19 , Pandemics , Adult , Cross-Sectional Studies , Hong Kong/epidemiology , Humans , Masks , Pandemics/prevention & control , SARS-CoV-2
6.
J Clin Pharm Ther ; 45(6): 1295-1300, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32697008

ABSTRACT

WHAT IS KNOWN: Opioids are often used to treat chronic non-cancer pain (CNCP) in patients on haemodialysis. Altered pharmacokinetics in this population increases risk for opioid-related adverse events. Although useful in pain management, there is a lack of opioid prescribing guidance for end-stage kidney disease. OBJECTIVE: To characterize opioid usage for CNCP in an outpatient haemodialysis unit. METHODS: Cross-sectional, single-centre, retrospective cohort study of 272 patients receiving outpatient haemodialysis between 01 June and 31 December 2017. Prevalence of prescription or non-prescription opioids, formulation, indication, dosing, prescriber type and therapeutic effectiveness were evaluated. RESULTS: A total of 27 (10%, aged 58 + 12.1 years, 59% women) patients received opioids for CNCP during the study period. Pain aetiology was diverse; 14 (52%) patients experienced multiple concurrent chronic pain conditions. Hydromorphone (55%) and oxycodone (37%) were the most common prescriptions. A majority (85%) of patients used non-opioid analgesics as adjunct therapy, while half (48%) used benzodiazepines or zopiclone concurrently. Patients who completed a pain scale (n = 10) reported a median pain intensity of 6.8/10 ([IQR], 4.5-7.3). DISCUSSION: Opioid usage was lower than expected despite a higher prevalence of concurrent chronic pain conditions. Though this was within opioid usage guidelines, pain may not be sufficiently controlled. High concomitant use of benzodiazepines and Z-drugs introduces the potential for additive adverse effects. Judicious opioid usage can be facilitated with stewardship to effectively treat pain while avoiding associated harms and manage potential drug-drug interactions with common concomitant medications. WHAT IS NEW AND CONCLUSION: The prevalence of chronic opioid use for non-cancer pain in haemodialysis patients was lower than expected at our centre. Despite following the recommended guidelines, pain management was relatively ineffective, and concomitant use of non-opioid analgesics was widespread. Opioid stewardship is recommended to optimize pain treatment and mitigate drug interaction risks.


Subject(s)
Analgesics, Opioid/administration & dosage , Analgesics/administration & dosage , Chronic Pain/drug therapy , Renal Dialysis , Aged , Ambulatory Care , Analgesics, Opioid/adverse effects , Cohort Studies , Cross-Sectional Studies , Drug Interactions , Female , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Practice Guidelines as Topic , Practice Patterns, Physicians'/statistics & numerical data , Retrospective Studies
7.
Oecologia ; 193(1): 199-209, 2020 May.
Article in English | MEDLINE | ID: mdl-32306116

ABSTRACT

Ecologists have long wondered how plants and algae persist under constant herbivory, and studies have shown that factors like chemical defense and morphology can protect these species from consumption. However, grazers are also highly diverse and exert varying top-down control over primary producers depending on traits such as body size. Moreover, susceptibility of plants and algae to herbivory may vary across life stages and size classes, with juveniles potentially the most vulnerable. Here, we focus on diverse grazing communities within giant kelp forests and compared consumption on two size classes of juvenile giant kelp (Macrocystis pyrifera) across four herbivore species ranging in size. We also integrated field and literature densities to estimate impacts on populations of juvenile kelp. We found that purple sea urchins, a species known for exerting strong control over adult M. pyrifera, had weak per capita impact on microscopic kelp, on par with a much smaller crustacean species. While urchin consumption increased with macroscopic juvenile kelp, it never surpassed the smaller brown turban snail, suggesting that feeding morphology, in addition to herbivore body size, is a predictor of consumption at these small size classes. The smaller herbivores also occurred in high densities in the field, increasing their predicted population-level impacts on juvenile kelp compared to urchins and perhaps other larger, but less abundant, herbivores. This study highlights the variation in species' roles within an herbivore guild and the importance of age-related changes in grazing vulnerability to better understand herbivore control on plant and algae population dynamics.


Subject(s)
Kelp , Macrocystis , Ecosystem , Forests , Herbivory
8.
Sci Rep ; 10(1): 5403, 2020 03 25.
Article in English | MEDLINE | ID: mdl-32214142

ABSTRACT

Species interactions are crucial for the persistence of ecosystems. Within vegetated habitats, early life stages of plants and algae must survive factors such as grazing to recover from disturbances. However, grazing impacts on early stages, especially under the context of a rapidly changing climate, are largely unknown. Here we examine interaction strengths between juvenile giant kelp (Macrocystis pyrifera) and four common grazers under hypoxia and ocean acidification using short-term laboratory experiments and field data of grazer abundances to estimate population-level grazing impacts. We found that grazing is a significant source of mortality for juvenile kelp and, using field abundances, estimate grazers can remove on average 15.4% and a maximum of 73.9% of juveniles per m2 per day. Short-term exposure to low oxygen, not acidification, weakened interaction strengths across the four species and decreased estimated population-level impacts of grazing threefold, from 15.4% to 4.0% of juvenile kelp removed, on average, per m2 per day. This study highlights potentially high juvenile kelp mortality from grazing. We also show that the effects of hypoxia are stronger than the effects of acidification in weakening these grazing interactions over short timescales, with possible future consequences for the persistence of giant kelp and energy flow through these highly productive food webs.


Subject(s)
Hypoxia/physiopathology , Kelp/physiology , Macrocystis/physiology , Biomass , Ecosystem , Food Chain , Hydrogen-Ion Concentration , Seawater
9.
Hum Resour Health ; 14: 14, 2016 Apr 12.
Article in English | MEDLINE | ID: mdl-27067144

ABSTRACT

BACKGROUND: Gender discrimination and inequality in health professional education (HPE) affect students and faculty and hinder production of the robust health workforces needed to meet health and development goals, yet HPE reformers pay scant attention to these gender barriers. Gender equality must be a core value and professional practice competency for all actors in HPE and health employment systems. METHODS: Peer-review and non-peer-review literature previously identified in a review of the literature identified interventions to counter gender discrimination and inequality in HPE and tertiary education systems in North America and the Caribbean; West, East, and Southern Africa; Asia; the Middle East and North Africa; Europe; Australia; and South America. An assessment considered 51 interventions addressing sexual harassment (18), caregiver discrimination (27), and gender equality (6). Reviewers with expertise in gender and health system strengthening rated and ranked interventions according to six gender-transformative criteria. RESULTS: Thirteen interventions were considered to have transformational potential to address gender-related obstacles to entry, retention, career progression, and graduation in HPE, when implemented in core sets of interventions. The review identified one set with potential to counter sexual harassment in HPE and two sets to counter caregiver discrimination. Gender centers and equal employment opportunity units are structural interventions that can address multiple forms of gender discrimination and inequality. CONCLUSIONS: The paper's broad aim is to encourage HPE leaders to make gender-transformative reforms in the current way of doing business and commit to themselves to countering gender discrimination and inequality. Interventions to counter gender discrimination should be seen as integral parts of institutional and instructional reforms and essential investments to scale up quality HPE and recruit and retain health workers in the systems that educate and employ them. Implementation challenges spanning financial, informational, and cultural barriers need consideration. The application of core sets of interventions and a strong learning agenda should be part of ongoing HPE reform efforts.


Subject(s)
Education, Professional , Health Personnel/education , Sexism , Women's Rights , Ethnicity , Humans
10.
Chest ; 145(6): 1255-1263, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24384690

ABSTRACT

BACKGROUND: Childhood OSA is a prevalent condition associated with raised BP as documented in cross-sectional studies. This study aimed to determine whether baseline or change in OSA severity was associated with ambulatory BP at 4-year follow-up. METHODS: Children who participated in our previous OSA prevalence research were invited to undergo a repeat overnight sleep study and 24-h ambulatory BP monitoring in this 4-year follow-up study. BP parameters of subjects with differing baseline OSA severity, that is, obstructive apnea-hypopnea index (OAHI) < 1/h, 1 to 5/h, and > 5/h, were compared. Overweight and normal-weight children were analyzed separately. RESULTS: One hundred eighty-five of 306 subjects (60%) were included in the analysis, of whom 58 were overweight at baseline. Linear increasing trends of wake systolic BP (SBP), wake diastolic BP (DBP), and sleep SBP z scores at follow-up were found across groups of increasing baseline OSA severity in the normal weight but not in the overweight subgroup. After adjusting for BMI z score, baseline OAHI was independently associated with all BP z scores at follow-up but not associated with changes in BP z scores across 4 years. On the other hand, change in OAHI was independently associated with sleep SBP and DBP z scores at follow-up and with changes in sleep SBP and DBP z scores across 4 years. CONCLUSIONS: This study provides longitudinal data as additional proof that childhood OSA is associated with elevated BP independent of obesity.


Subject(s)
Blood Pressure/physiology , Hypertension/physiopathology , Sleep Apnea, Obstructive/physiopathology , Adolescent , Blood Pressure Monitoring, Ambulatory , Child , Circadian Rhythm/physiology , Comorbidity , Female , Follow-Up Studies , Hong Kong , Humans , Longitudinal Studies , Male , Obesity/physiopathology , Polysomnography , Prospective Studies , Severity of Illness Index
11.
J Biol Chem ; 288(23): 16416-16429, 2013 Jun 07.
Article in English | MEDLINE | ID: mdl-23615907

ABSTRACT

Disulfide bonds are important for the stability of many extracellular proteins, including bacterial virulence factors. Formation of these bonds is catalyzed by thiol-disulfide oxidoreductases (TDORs). Little is known about their formation in Gram-positive bacteria, particularly among facultative anaerobic Firmicutes, such as streptococci. To investigate disulfide bond formation in Streptococcus gordonii, we identified five putative TDORs from the sequenced genome. Each of the putative TDOR genes was insertionally inactivated with an erythromycin resistance cassette, and the mutants were analyzed for autolysis, extracellular DNA release, biofilm formation, bacteriocin production, and genetic competence. This analysis revealed a single TDOR, SdbA, which exhibited a pleiotropic mutant phenotype. Using an in silico analysis approach, we identified the major autolysin AtlS as a natural substrate of SdbA and showed that SdbA is critical to the formation of a disulfide bond that is required for autolytic activity. Analysis by BLAST search revealed homologs to SdbA in other Gram-positive species. This study provides the first in vivo evidence of an oxidoreductase, SdbA, that affects multiple phenotypes in a Gram-positive bacterium. SdbA shows low sequence homology to previously identified oxidoreductases, suggesting that it may belong to a different class of enzymes. Our results demonstrate that SdbA is required for disulfide bond formation in S. gordonii and indicate that this enzyme may represent a novel type of oxidoreductase in Gram-positive bacteria.


Subject(s)
Bacterial Proteins/metabolism , Disulfides/metabolism , Membrane Proteins/metabolism , Protein Disulfide Reductase (Glutathione)/metabolism , Streptococcus gordonii/enzymology , Virulence Factors/metabolism , Bacterial Proteins/genetics , Membrane Proteins/genetics , Mutation , N-Acetylmuramoyl-L-alanine Amidase/genetics , N-Acetylmuramoyl-L-alanine Amidase/metabolism , Protein Disulfide Reductase (Glutathione)/genetics , Streptococcus gordonii/genetics , Virulence Factors/genetics
12.
Cancer Lett ; 307(2): 132-40, 2011 Aug 28.
Article in English | MEDLINE | ID: mdl-21530075

ABSTRACT

Recent studies have shown that CXCR4 is associated with tumor metastasis. Elevated levels of CXCR4 are also detected in a high percentage of DCIS cases. The high frequency of CXCR4 expression in DCIS suggests that many DCIS cases are "primed" for invasiveness. In this study, we demonstrated that expression of CXCR4 reveals morphological alterations in cells, from normal acinar morphological epithelial cells to a more invasive morphology in a 3D-culture system. Ectopic expression of CXCR4 induces invasion of MCF-10A cells. Interestingly, CXCR4 is capable of orchestrating a complex alteration in signaling networks, which include upregulation of multiple receptor tyrosine kinases (RTKs), deregulation of p53/MDM2 axis, upregulation of E-cadherin and c-myc, as well as modulation of cell cycle molecules to facilitate mammary epithelia cell transformation. These findings reveal that CXCR4 expression exerts a critical role in early stages of breast lesions, which may explain the high frequency of CXCR4 expression detected in DCIS. We believe that these studies will lead to new, biologically-based therapeutic strategies for clinical intervention, prevention and treatments of breast cancer.


Subject(s)
Cell Transformation, Neoplastic , Mammary Glands, Human/pathology , Proto-Oncogene Proteins c-mdm2/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, CXCR4/physiology , Tumor Suppressor Protein p53/metabolism , Base Sequence , Cell Line, Transformed , DNA Primers , Flow Cytometry , Humans
13.
Chest ; 137(3): 529-35, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20022971

ABSTRACT

BACKGROUND: The objective of this study was to evaluate circulating adipokines concentration in children with and without obstructive sleep apnea (OSA) and to determine the effects of treatment of OSA on their plasma concentration. METHODS: Children with habitual snoring and symptoms suggestive of OSA were consecutively recruited. Their parents completed a sleep apnea symptom questionnaire, and the subjects underwent physical examination and an overnight polysomnography (PSG). OSA was diagnosed if they had an obstructive apnea index > 1. Fasting serum adiponectin, leptin, and lipid profiles were taken after overnight PSG. The subjects were divided into groups as obese, nonobese, and with and without OSA for comparison. RESULTS: One hundred forty-one children, of whom 96 were boys, with a median (interquartile range) age of 10.8 (8.5-12.8) years were recruited. Forty-three subjects had OSA. Subjects with OSA did not have significantly different adiponectin and leptin concentrations than those without OSA for both the obese and nonobese groups. Stepwise multiple linear regressions revealed that systolic BP, age, high-density lipoprotein cholesterol, and BMI z-score were independently associated with adiponectin, whereas diastolic BP, triglyceride, height, and BMI z-score were independently associated with leptin concentration. Sixteen children with OSA underwent treatment, and there was reduction in their plasma adiponectin concentration after intervention, but such change became insignificant after controlling for change in the BMI z-score. CONCLUSIONS: BMI rather than OSA was the main determinant of adipokines in children.


Subject(s)
Adipokines/blood , Continuous Positive Airway Pressure/methods , Glucocorticoids/administration & dosage , Sleep Apnea, Obstructive/blood , Tonsillectomy , Administration, Intranasal , Biomarkers/blood , Body Mass Index , Child , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Male , Polysomnography , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/therapy , Surveys and Questionnaires , Treatment Outcome
14.
Int J Cancer ; 125(8): 1805-13, 2009 Oct 15.
Article in English | MEDLINE | ID: mdl-19569230

ABSTRACT

Transducer of ErbB-2 (TOB) is a member of the TOB/Btg gene family. A role for TOB in the suppression of human tumorigenesis has been proposed, based on the observations that TOB-knockout mice spontaneously form tumors and TOB expression is lost in human lung and thyroid cancers. However, the role of TOB in human breast cancer remains unknown. To evaluate the this role, we screened a panel of breast cancer cell lines for TOB expression levels and found that they are inversely correlated with the tumorigenicity and metastatic potential of the cell lines. In addition, we demonstrated for the first time that TOB expression is inversely correlated with breast cancer progression in clinical specimens. These results strongly indicate that the loss of TOB expression plays a role in breast cancer progression. We have also provided the first evidence that TOB functions as a tumor suppressor in breast cancer MCF-7 cells, using gain-of-function and loss-of-function approaches to manipulate TOB expression. Cell-cycle analysis further revealed that TOB can prolong the G1-S phase transition by inducing arrest at G1-S phase. Moreover, upregulation of the cyclin-dependent kinase inhibitor p27 and downregulation of the antiapoptotic proteins Bcl-2 and Bcl-XL were observed in MCF7/TOB transfectants. Conversely, opposite results were observed in shRNA-TOB transfectants. Furthermore, decreased activity of Erk2, AKT, CrkL, PDK1, and Smads were observed in TOB-overexpressing cells. Taken together, these data provide evidence that TOB can function as a tumor suppressor in breast cancer through modulation and regulation of multiple signaling pathways.


Subject(s)
Breast Neoplasms/prevention & control , Genes, Tumor Suppressor/physiology , Intracellular Signaling Peptides and Proteins/physiology , Tumor Suppressor Proteins/physiology , Animals , Apoptosis , Blotting, Northern , Blotting, Western , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Adhesion , Cell Cycle/physiology , Cell Line, Tumor , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique , Humans , Immunoblotting , Immunoenzyme Techniques , Immunoprecipitation , Mice , Mice, Nude , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Transfection
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