Androgen Receptor Expression in Thai Breast Cancer Patients

The aim of this study was to investigate prevalence and related factors of androgen receptor (AR) expression in Thai breast cancer patients. A descriptive study was done in 95 patients, who were admitted to Charoenkrung Pracharak Hospital, Bangkok (2011–2013). Statistical relationships were examined between AR protein expression, tumor status, and patient characteristics. Compared with those from Western countries, ethnic Thai patients were younger at age of diagnosis and had a higher proliferative index (high Ki-67 expression), which indicates unfavorable prognosis. In addition, 91% of the Thai breast tumors that were positive for any of the following receptors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) also expressed the AR protein, while in triple negative breast tumors only 33% were AR positive. ER and PR expression was positively related with AR expression, while AR expression was inversely correlated to Ki-67 expression. AR status was strongly correlated with ER and PR status in Thai patients. There is an inverse relationship between Ki-67 and AR, which suggests that AR may be a prognostic factor for breast cancer

The possible role of Androgen and selected natural chemicals effect on human breast cancer cells and the co-culture system

The majority of Thai breast cancer patients had tumors that expresses the AR (80%). These tumors are mostly hormonal and HER-2 positive in nature. Expression of the AR in triple negative breast tumors are less common (33%). When compared with data from Western studies, the Thai patients show higher in AR expression and the ratio between hormonal/HER-2 responsive and triple negative breast tumors than Western patients. According to high expression of AR, we studied the role of androgens in breast cancer model. Our results demonstrate the use of a co-culture system of breast tumor cells and BAFs for anti-aromatase assays. Two main findings in our studies are first, that androgens can induce or reduce breast cancer cell growth, depending on the ability of conversion to estradiol by aromatase in the fibroblasts of breast tissue. On the other hand, non-aromatizable androgens (DHT) may inhibited proliferation of both hormone receptors, positive or triple negative breast cancers. Second, it shows that resveratrol, melatonin, and depsidones can inhibit hormonal positive breast cancer cell growth via the anti-aromatase activity. The results show the possibility of resveratrol, melatonin, and depsidones as new candidates for anti-aromatase agents to fight against hormonal positive breast cancer. Further research is needed for possible adverse effects of these compounds at dose levels that have been found to show AI properties

The possible role of Androgen and selected natural chemicals effect on human breast cancer cells and the co-culture system

The majority of Thai breast cancer patients had tumors that expresses the AR (80%). These tumors are mostly hormonal and HER-2 positive in nature. Expression of the AR in triple negative breast tumors are less common (33%). When compared with data from Western studies, the Thai patients show higher in AR expression and the ratio between hormonal/HER-2 responsive and triple negative breast tumors than Western patients. According to high expression of AR, we studied the role of androgens in breast cancer model. Our results demonstrate the use of a co-culture system of breast tumor cells and BAFs for anti-aromatase assays. Two main findings in our studies are first, that androgens can induce or reduce breast cancer cell growth, depending on the ability of conversion to estradiol by aromatase in the fibroblasts of breast tissue. On the other hand, non-aromatizable androgens (DHT) may inhibited proliferation of both hormone receptors, positive or triple negative breast cancers. Second, it shows that resveratrol, melatonin, and depsidones can inhibit hormonal positive breast cancer cell growth via the anti-aromatase activity. The results show the possibility of resveratrol, melatonin, and depsidones as new candidates for anti-aromatase agents to fight against hormonal positive breast cancer. Further research is needed for possible adverse effects of these compounds at dose levels that have been found to show AI properties

Androgen Receptor Expression in Thai Breast Cancer Patients

The aim of this study was to investigate prevalence and related factors of androgen receptor (AR) expression in Thai breast cancer patients. A descriptive study was done in 95 patients, who were admitted to Charoenkrung Pracharak Hospital, Bangkok (2011–2013). Statistical relationships were examined between AR protein expression, tumor status, and patient characteristics. Compared with those from Western countries, ethnic Thai patients were younger at age of diagnosis and had a higher proliferative index (high Ki-67 expression), which indicates unfavorable prognosis. In addition, 91% of the Thai breast tumors that were positive for any of the following receptors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) also expressed the AR protein, while in triple negative breast tumors only 33% were AR positive. ER and PR expression was positively related with AR expression, while AR expression was inversely correlated to Ki-67 expression. AR status was strongly correlated with ER and PR status in Thai patients. There is an inverse relationship between Ki-67 and AR, which suggests that AR may be a prognostic factor for breast cancer

Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts

Targeting the estrogen pathway has been proven effective in the treatment for estrogen receptor positive breast cancer. There are currently two common groups of anti-estrogenic compounds used in the clinic; Selective Estrogen Receptor Modulators (SERMs, e.g. tamoxifen) and Selective Estrogen Enzyme Modulators (SEEMs e.g. letrozole). Among various naturally occurring, biologically active compounds, resveratrol and melatonin have been suggested to act as aromatase inhibitors, which make them potential candidates in hormonal treatment of breast cancer. Here we used a co-culture model in which we previously demonstrated that primary human breast adipose fibroblasts (BAFs) can convert testosterone to estradiol, which subsequently results in estrogen receptor-mediated breast cancer T47D cell proliferation. In the presence of testosterone in this model, we examined the effect of letrozole, resveratrol and melatonin on cell proliferation, estradiol (E2) production and gene expression of CYP19A1, pS2 and Ki-67. Both melatonin and resveratrol were found to be aromatase inhibitors in this co-culture system, albeit at different concentrations. Our co-culture model did not provide any indications that melatonin is also a selective estrogen receptor modulator. In the T47D-BAF co-culture, a melatonin concentration of 20nM and resveratrol concentration of 20μM have an aromatase inhibitory effect as potent as 20nM letrozole, which is a clinically used anti-aromatase drug in breast cancer treatment. The SEEM mechanism of action of especially melatonin clearly offers potential advantages for breast cancer treatment

Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts

Targeting the estrogen pathway has been proven effective in the treatment for estrogen receptor positive breast cancer. There are currently two common groups of anti-estrogenic compounds used in the clinic; Selective Estrogen Receptor Modulators (SERMs, e.g. tamoxifen) and Selective Estrogen Enzyme Modulators (SEEMs e.g. letrozole). Among various naturally occurring, biologically active compounds, resveratrol and melatonin have been suggested to act as aromatase inhibitors, which make them potential candidates in hormonal treatment of breast cancer. Here we used a co-culture model in which we previously demonstrated that primary human breast adipose fibroblasts (BAFs) can convert testosterone to estradiol, which subsequently results in estrogen receptor-mediated breast cancer T47D cell proliferation. In the presence of testosterone in this model, we examined the effect of letrozole, resveratrol and melatonin on cell proliferation, estradiol (E2) production and gene expression of CYP19A1, pS2 and Ki-67. Both melatonin and resveratrol were found to be aromatase inhibitors in this co-culture system, albeit at different concentrations. Our co-culture model did not provide any indications that melatonin is also a selective estrogen receptor modulator. In the T47D-BAF co-culture, a melatonin concentration of 20nM and resveratrol concentration of 20μM have an aromatase inhibitory effect as potent as 20nM letrozole, which is a clinically used anti-aromatase drug in breast cancer treatment. The SEEM mechanism of action of especially melatonin clearly offers potential advantages for breast cancer treatment

Depsidones inhibit aromatase activity and tumor cell proliferation in a co-culture of human primary breast adipose fibroblasts and T47D breast tumor cells

Naturally occurring depsidones from the marine fungus Aspergillus unguis are known to have substantial anti-cancer activity, but their mechanism of action remains elusive. The purpose of this study was to examine the anti-aromatase activity of two common depsidones, unguinol and aspergillusidone A, in a co-culture system of human primary breast adipose fibroblasts and hormonal responsive T47D breast tumor cells. Using this in vitro model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity. The IC50 values of these depisidones were compared with the aromatase inhibitors letrozole and exemestane. Letrozole and exemestane had IC50 values of respectively, 0.19 and 0.14 μM, while those for Unguinol and Aspergillusidone A were respectively, 9.7 and 7.3 μM. Our results indicate that among the depsidones there maybe aromatase inhibitors with possible pharmacotherapeutical relevance

Depsidones inhibit aromatase activity and tumor cell proliferation in a co-culture of human primary breast adipose fibroblasts and T47D breast tumor cells

Naturally occurring depsidones from the marine fungus Aspergillus unguis are known to have substantial anti-cancer activity, but their mechanism of action remains elusive. The purpose of this study was to examine the anti-aromatase activity of two common depsidones, unguinol and aspergillusidone A, in a co-culture system of human primary breast adipose fibroblasts and hormonal responsive T47D breast tumor cells. Using this in vitro model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity. The IC50 values of these depisidones were compared with the aromatase inhibitors letrozole and exemestane. Letrozole and exemestane had IC50 values of respectively, 0.19 and 0.14 μM, while those for Unguinol and Aspergillusidone A were respectively, 9.7 and 7.3 μM. Our results indicate that among the depsidones there maybe aromatase inhibitors with possible pharmacotherapeutical relevance

Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand

INTRODUCTION: Latent HIV reservoirs are rapidly established in lymphoid tissues during acute HIV infection (AHI). Sampling these tissues provides important information about HIV pathogenesis. This period is associated with viral replication and immune activation that may affect procedure-related adverse events (AEs). We examined the safety and tolerability of inguinal lymph node (LN) biopsy in research participants with AHI in Bangkok, Thailand. METHODS: Between 2013 and 2016, 67 AHI participants in the RV254/SEARCH010 study underwent at least one optional inguinal LN biopsy during AHI at the baseline visit and/or after antiretroviral therapy (median 48 weeks after antiretroviral therapy). Biopsy-related AEs were graded according to NIH Division of AIDS guidelines. Poisson regression was used to calculate incidence rate ratios and 95% confidence intervals to evaluate associations of demographic and HIV characteristics, procedure timing, and repetition with AE incidence. RESULTS: Of the 67 participants, 97% were male with a median age of 26. Among 78 LN biopsies (39 at baseline and 39 at follow-up), 10 (12.8%) AEs were reported: 6 (7.7%) grade 1 and 4 (5.1%) grade 2. The AEs were biopsy-site discomfort (n = 8, 10.2%) and hematoma (n = 2, 2.6%). No factors were significantly associated with AE incidence. All biopsy-related AEs were transient and self-limited. CONCLUSIONS: Inguinal LN biopsies were safe and well tolerated in mostly Thai men with AHI. As LN biopsies become an integral part of HIV research, this study provides information to participants, researchers, and institutional review boards that these samples can be safely obtained