Ex vivo recovery and activation of dysfunctional, anergic, monocyte-derived dendritic cells from patients with operable breast cancer: critical role of IFN-alpha

Background Dendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses. Results Peripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generated in vitro from adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-α+IFN-α) or 3 CCM (GM-CSF+IL-4+TNF-α) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40) in vitro (p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001). Conclusion Dysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed by ex vivo culturing of precursor adherent monocytes using a 4 CCM containing IFN-α. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-α. However, 4 CCM containing IFN-α generated-PBDCs, do not produce and secrete IL-12p70 in vitro

Human papillomavirus DNA in plasma of patients with cervical cancer

BACKGROUND: Human papillomavirus (HPV) is a crucial etiological factor for cervical cancer (CC) development. From a diagnostic view-point, the consistent presence of HPV in CC allows the viral DNA to be used as a genetic marker. The aims of this study were to evaluate the presence, physical status and clinical significant of HPV DNA in circulation of CC patients. RESULTS: Whereas 6 out of 50 (12%) HPV positive CC patients revealed plasma HPV DNA, it was detected in none of 20 normal controls or 13 HPV negative CC cases. The plasma DNA exhibited an HPV type identical to the HPV in the primary tumors and the DNA from both sources was integrated into host genome. Interestingly, several findings suggested an association between plasma HPV DNA and metastasis. First, three of the HPV DNA positive cases were CC patients with clinical stage IVB or recurrence with distance metastases (P = 0.001, RR = 15.67). Second, the amount of plasma HPV DNA from metastatic patients to be three times more than three other patients without metastases. Finally, the later cases had tendency to develop recurrence distant metastases within one year after complete treatment when compared with other HPV associated CC patients with the same stage but without the present of plasma HPV DNA. CONCLUSIONS: The plasma HPV DNA originated from the CC, was associated with metastasis and could be used as a marker representing the circulating free CC DNA

Effects on quality of life, anti-cancer responses, breast conserving surgery and survival with neoadjuvant docetaxel: a randomised study of sequential weekly versus three-weekly docetaxel following neoadjuvant doxorubicin and cyclophosphamide in women with primary breast cancer

<p>Abstract</p> <p>Background</p> <p>Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS), Disease Free Survival (DFS) and Overall Survival (OS).</p> <p>Methods</p> <p>Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m²) or four cycles of 3-weekly docetaxel (100 mg/m²). The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed.</p> <p>Results</p> <p>At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%), pathological complete response (20% vs. 27%), and breast-conserving surgery (BCS) rates (49% vs. 42%). Disease-free survival and overall survival were similar between treatment groups.</p> <p>Conclusions</p> <p>Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS) or survival outcomes in the neoadjuvant setting.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN09184069">ISRCTN09184069</a></p

Regional variation and determinants of vitamin D status in sunshine-abundant Thailand

<p>Abstract</p> <p>Background</p> <p>Vitamin D insufficiency is highly prevalent. Most of the studies concerning vitamin D status were generated from countries situated at temperate latitudes. It is less clear what the extent of vitamin D insufficiency is in countries situated in the tropics and how geographical regions within country would affect vitamin D status. In the present study, we investigated vitamin D status in Thais according to geographical regions and other risk factors.</p> <p>Methods</p> <p>Subjects consisted of 2,641 adults, aged 15 - 98 years, randomly selected from the Thai 4th National Health Examination Survey (2008-9) cohort. Serum 25 hydroxyvitamin D were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE.</p> <p>Results</p> <p>Subjects residing in Bangkok, the capital city of Thailand, had lower 25(OH)D levels than other parts of the country (Bangkok, central, northern, northeastern and southern regions: 64.8 ± 0.7, 79.5 ± 1.1, 81.7 ± 1.2, 82.2 ± 0.8 and 78.3 ± 1.3 nmol/L, respectively; <it>p </it>< 0.001). Within each region, except for the northeastern part of the country, subjects living inside municipal areas had lower circulating 25(OH)D (central, 77.0 ± 20.9 nmol/L vs 85.0 ± 22.1 nmol/L, <it>p </it>< 0.001; north 79.3 ± 22.1 nmol/L vs 86.8 ± 21.8 nmol/L, <it>p </it>< 0.001; northeast 84.1 ± 23.3 nmol/L vs 87.3 ± 20.9 nmol/L, <it>p </it>= 0.001; south, 76.6 ± 20.5 nmol/L vs 85.2 ± 24.7 nmol/L, <it>p </it>< 0.001). Overall, the prevalence of vitamin D insufficiency was 64.6%, 46.7%, and 33.5% in Bangkok, municipal areas except Bangkok, and outside municipal area in other parts of the country, respectively. In addition, the prevalence of vitamin D insufficiency according to geographical regions was 43.1%, 39.1%, 34.2% and 43.8% in the central, north, northeast and south, respectively. After controlling for covariates in multiple linear regression analysis, the results showed that low serum 25(OH)D levels were associated with being female, younger age, living in urban and Bangkok.</p> <p>Conclusions</p> <p>Vitamin D insufficiency is common and varies across geographical regions in Thailand.</p

Prevalence of chronic kidney disease in Thai adults: a national health survey

<p>Abstract</p> <p>Background</p> <p>The prevalence of patients with end stage renal disease (ESRD) who need dialysis and/or transplantation has more than doubled in Thailand during the past two decades. It has been suggested that therapeutic strategies to reduce the risk of ESRD and other complications in CKD are now available, thus the early recognition and the institution of proven therapeutic strategies are important and beneficial. We, therefore, aimed to determine the prevalence of CKD in Thai adults from the National Health Examination Survey of 2004.</p> <p>Methods</p> <p>Data from a nationally representative sample of 3,117 individuals aged 15 years and older was collected using questionnaires, physical examination and blood samples. Serum creatinine was measured by Jaffé method. GFR was estimated using the Chinese modified Modification of Diet in Renal Disease Study equation. Chronic kidney Disease (CKD) stages were classified based on Kidney Disease Outcome Quality Initiative (K/DOQI).</p> <p>Results</p> <p>The prevalence of CKD in Thai adults weighted to the 2004 Thai population by stage was 8.1% for stage 3, 0.2% and 0.15% for stage 4 and 5 respectively. Compared to non-CKD, individuals with CKD were older, had a higher level of cholesterol, and higher blood pressure. Those with cardiovascular risk factors were more likely to have CKD (stage 3-5) than those without, including hypertension (OR 1.6, 95%CI 1.1, 3.4), diabetes (OR 1.87, 95%CI 1.0, 3.4). CKD was more common in northeast (OR 2.1, 95%CI 1.3, 3.3) compared to central region. Urinalysis was not performed, therefore, we could not have data on CKD stage 1 and 2. We have no specific GFR formula for Thai population.</p> <p>Conclusion</p> <p>The identification of CKD patients should be evaluated and monitored for appropriate intervention for progression to kidney disease from this screening.</p

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was \u3c1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

An effective method for the identification and separation of Anopheles minimus, the primary malaria vector in Thailand, and its sister species Anopheles harrisoni, with a comparison of their mating behaviors

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached article is the published pdf

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as “radical cure”), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide. Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient’s G6PD status is known before deciding to administer an 8-aminoquinoline-based drug. In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure

National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.Peer reviewe