A remote mentorship model for empowering students to undertake electrocardiology research: Effects on gender equity.

Over the past years, there has been increasing awareness on female representation in cardiology, in particular senior academic ranks. Given the gender disparity in cardiology, female talents in cardiovascular academic medicine are significantly under-represented. In addition, whilst women have a slightly higher frequency of earning first authorships, it has been reported that women are 50% less likely to hold a senior authorship position. The drop in female representation in senior ranks of academic medicine may be contributed by a lack of female talent engagement, particularly during their early-career advancement, in high-impact journals and leadership roles. We present a remote, accessible-distributed research team model to help raise the female representation and tackle the challenges faced by female academics in the field of cardiovascular medicine. The group celebrates accessibility through open communication and collaboration, where mentees can seek research advice and ideas virtually from senior members and principal investigators. The decentralized system allows easy access for research guidance and inspirationand break down barriers in the lack of mentorship for early-career female talents. Students are empowered to lead their projects, and be involved in all phases- from the generation of study ideas to publication. The early development of holistic independent research skills equips students to become principal investigators and leaders in the future. The distributive element of the group is demonstrated through the decentralized research approach employed. Authorship is allocated based on intellectual contribution rather than on the acquisition of funding or seniority level.

The use of minimal fluoroscopy for cardiac electrophysiology procedures: A meta-analysis and review of the literature.

BACKGROUND: Conventional catheter ablation involves prolonged exposure to ionizing radiation, potentially leading to detrimental health effects. Minimal fluoroscopy (MF) represents a safer alternative, which should be explored. Data on the safety and efficacy of this technique are limited. HYPOTHESIS: Our hypothesis is that MF is of equal efficacy and safety to conventional catheter ablation with the use of fluoroscopy by performing a meta-analysis of both randomized controlled trials (RCTs) and real-world registry studies. METHODS: Pubmed and Embase were searched from their inception to July 2020 for RCTs, cohort and observational studies that assessed the outcomes of catheter ablation using a MF technique versus the conventional approach. RESULTS: Fifteen studies involving 3795 patients were included in this meta-analysis. There was a significant reduction in fluoroscopy and procedural time with no difference in acute success (odds ratio [OR]:0.74, 95% CI: 0.50-1.10, p = .14), long-term success (OR:0.92, 95% CI: 0.65-1.31, p = .38), arrhythmia recurrence (OR:1.24, 95% CI: 0.75-2.06, p = .97) or rate of complications. (OR:0.83, 95% CI: 0.46-1.48, p = .65). Additionally sub-group analysis for those undergoing catheter ablation for atrial fibrillation (AF) did not demonstrate a difference in success or complication rates (OR:0.86, 95% CI: 0.30-2.42, p = .77). Multivariate meta-regression did not identify the presence of moderator variables. CONCLUSION: This updated meta-analysis demonstrated an overall reduction in procedural and fluoroscopy time for those undergoing a minimal fluoroscopic approach. There was no significant difference in either acute or chronic success rates or complications between a MF approach and conventional approach for the management of all arrhythmias including those undergoing catheter ablation for AF.

Mutual Information Reveals Non-linear Relationships between Electrocardiographic Conduction or Repolarization Indices and Mechanical Dispersion by Speckle-Tracking Echocardiography in the General Population.

Electrical inhomogeneities can lead to regional heterogeneity in left ventricular contraction. We investigated the correlation between electrocardiographic parameters of conduction and/or repolarization and myocardial longitudinal strain-derived parameters in a general population. Mean and dispersion (maximum-minimum) values were calculated for the electrocardiographic indices: QT interval, Tpeak-Tend interval (Tpe), JTpeak interval (JTp), JTend interval (JTe), QTpeak interval (QTp). Mechanical dispersion was assessed using the standard deviation (SD) of time-to-peak longitudinal strains (MDSD) and the difference between the longest time and shortest time to peak strain (MDdelta) by speckle-tracking echocardiography. A total of 59 patients, 60 ± 12 y, were included. Tpe, Tpe/QT, Tpe/JTp and Tpe/JTe correlated well with MDSD and MDdelta (r ≥ 0.43, p < 0.001). Mutual information revealed significant non-linear relationships between most of the electrocardiographic indices measured and mechanical dispersion. In conclusion, there is a moderate linear correlation between electrocardiographic indices reflecting repolarization heterogeneities and speckle tracking-assessed mechanical dispersion.

Worldwide Survey of COVID-19-Associated Arrhythmias.

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Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats.

Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of both atrial fibrillation (AF) and diabetes mellitus (DM). Wenxin Keli (WXKL), an antiarrhythmic traditional Chinese medicine, has been shown to prevent cardiac arrhythmias through modulation of cardiac ion channels. This study tested the hypothesis that WXKL can improve atrial remodeling in diabetic rats by restoring mitochondrial function. Primary atrial fibroblasts of neonatal SD rats were divided into four groups: control, hydrogen peroxide (H2O2), H2O2+WXKL 1 g/L, and H2O2+WXKL 3 g/L groups. Intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial oxygen consumption were measured. SD male rats were randomly divided into three groups: control, DM, and DM+WXKL groups. Rats in the DM+WXKL group were treated with daily gavage of WXKL at 3 g/kg. After eight weeks, echocardiography, hemodynamic examination, histology, electrophysiology study, mitochondrial respiratory function, and western blots were assessed. H2O2 treatment led to increased ROS and decreased intracellular MMP and mitochondrial oxygen consumption in primary atrial fibroblasts. WXKL improved the above changes. DM rats showed increased atrial fibrosis, greater left atrial diameter, lower atrial conduction velocity, higher conduction heterogeneity, higher AF inducibility, and lower mitochondrial protein expression, and all these abnormal changes except for left atrial diameter were improved in the DM+WXKL group. WXKL improves atrial remodeling by regulating mitochondrial function and homeostasis and reducing mitochondrial ROS in diabetic rats.

Effects of ticagrelor pretreatment on electrophysiological properties of stellate ganglion neurons following myocardial infarction.

Higher sympathetic activity predisposes to malignant ventricular arrhythmias in the context of myocardial infarction (MI). This is, in part, mediated by the electrical activity of the stellate ganglion (SG). The aim of this study is to examine the effects of ticagrelor pretreatment on the electrophysiological properties of SG neurons following MI in rabbits. MI was induced by isoproterenol (ISO) of 150 mg kg-1 d-1 (twice at an interval of 24 hours). Ticagrelor pretreatment was administered at low- (10 mg kg-1 d-1) or high-dose (20 mg kg-1 d-1). Protein and RNA expression were determined by immunohistochemical analysis and real-time PCR, respectively. The activity of sodium channel current (INa), delayed rectifier potassium current (IKDR), M-type potassium current (IKM) as well as action potentials (APs) from SG neurons were measured by whole-cell patch-clamp. Intracellular calcium concentrations were measured by confocal microscopy. Compared with the control group, the MI group exhibited a greater amplitude of INa, IKDR and IKM, significantly altered activation and inactivation characteristics of INa, no significant alterations in protein or mRNA expression of sodium and M-type potassium channels, along with higher AP amplitude and frequency and intracellular calcium concentrations. Most of these abnormalities were prevented by pretreatment with low- or high-dose ticagrelor. Our data suggest that ticagrelor exerts cardioprotective effects, potentially through modulating the activity of different ion channels in SG neurons.

Restitution metrics in Brugada syndrome: a systematic review and meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death. Restitution analysis has been examined in BrS patients but not all studies have reported significant differences between BrS patients and controls. Therefore, we conducted a systematic review and meta-analysis to investigate the different restitution indices used in BrS. METHODS: PubMed and Embase were searched until April 7, 2019, identifying 20 and 27 studies. RESULTS: A total of ten studies involving 178 BrS (mean age 38 years old, 63% male) and 102 controls (mean age 31 years old, 42% male) were included in this systematic review. Pacing was carried out at the right ventricular outflow tract (RVOT)/right ventricular apex (RPA) (n = 4), RPA (n = 4), or right atrium (RA) (n = 1). Basic cycle lengths of 400 (n = 4), 500 (n = 2), 600 (n = 6) and 750 ms (n = 1) were used. Recording methods include electrograms (n = 4), monophasic action potentials (n = 5), and electrocardiograms (n = 1). Signals were obtained from the RVOT (n = 8), RVA (n = 3), RA (n = 1), or the body surface (n = 1). The maximum restitution slope for endocardial repolarization at the RVOT was 0.87 for BrS patients (n = 5; 95% confidence interval [CI] 0.68-1.07) compared with 0.74 in control subjects (n = 4; 95% CI 0.42-1.06), with a significant mean difference of 0.40 (n = 4; 95% CI 0.11-0.69; P = 0.007). CONCLUSIONS: Steeper endocardial repolarization restitution slopes are found in BrS patients compared with controls at baseline. Restitution analysis can provide important information for risk stratification in BrS.

Right ventricular outflow tract low-voltage areas identify the site of origin of idiopathic ventricular arrhythmias: A high-density mapping study.

INTRODUCTION: Electronatomical mapping allows direct and accurate visualization of myocardial abnormalities. This study investigated whether high-density endocardial bipolar voltage mapping of the right ventricular outflow tract (RVOT) during sinus rhythm may guide catheter ablation of idiopathic ventricular arrhythmias (VAs). METHODS AND RESULTS: Forty-four patients (18 males, mean age: 38.1 ± 13.8 years) with idiopathic RVOT VAs and negative cardiac magnetic resonance imaging underwent a stepwise mapping approach for the identification of the site of origin (SOO). High-density electronatomical mapping (1096.6 ± 322.3 points) was performed during sinus rhythm and identified at least two low bipolar voltage areas less than 1 mV (mean amplitude of 0.20 ± 0.10 mV) in 39 of 44 patients. The mean low-voltage surface area was 1.4 ± 0.8 cm2 . Group 1 consisted of 28 patients exhibiting low-voltage areas and high-arrhythmia burden during the procedure. Pace match to the clinical VAs was produced in one of these low-voltage areas. Activation mapping established the SOO at these sites in 27 of 28 cases. Group 2 comprised 11 patients exhibiting abnormal electroanatomical mapping, but very low-arrhythmia burden during the procedure. Pace mapping produced a near-perfect or perfect match to the clinical VAs in one of these areas in 9 of 11 patients which was marked as potential SOO and targeted for ablation. During the follow-up period, 25 of 28 patients from group 1 (89%) and 7 of 9 patients from group 2 (78%) were free from VAs. CONCLUSIONS: Small but detectable very low-voltage areas during mapping in sinus rhythm characterize the arrhythmogenic substrate of idiopathic RVOT VAs and may guide successful catheter ablation.

Is Danggui Safe to be Taken by Breast Cancer Patients?-A Skepticism Finally Answered by Comprehensive Preclinical Evidence.

Angelica sinensis (AS, Danggui) has long been regarded to stimulate breast cancer growth; hence, the use of AS in breast cancer patients remains a major concern for both patients and practitioners. Since safety studies of herbs would be unethical to carry out in patients, the present study aimed to investigate the potential unsafe effects of AS in a systematic pre-clinical approach. Human breast cancer cells, breast orthotopic tumor-bearing mouse models, as well as primary breast cancer cells from patients' tumors were used to evaluate the effect of AS hot water extract on the progression of breast tumors and/or growth of breast cancer cells. We showed that AS is not that stimulatory in breast cancer both in vitro and in vivo, though AS should still be used with caution in estrogen receptor-positive breast cancer patients. This novel approach of applying breast cancer cell lines, xenograft, and syngeneic tumors models, as well as primary breast cancer cells from patients' tumors in Chinese medicines safety evaluation was proven feasible. Our finding is important information for patients, Chinese medicine practitioners, and clinicians on the safety use of AS in breast cancer, which will affect future clinical practice.

Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer.

BACKGROUND: An increasing number of breast cancer patients in Asian countries has been found to consume dietary supplements including phytoestrogen-rich Chinese herbal medicines with an expectation to alleviate the side effects of conventional cancer therapies. PURPOSE: The question of whether estrogenic Chinese herbal medicines are beneficial or detrimental to the health of breast cancer patients remains uncertain. STUDY DESIGN: The present study aimed at establishing a systematic approach to look at the safety profiles of estrogenic Chinese herbal medicines (CHM). METHODS: The effects of estrogenic CHM on the growth of human breast cancer cells as well as the progression of breast tumors in mice have been investigated. RESULTS: Our results demonstrated that among 10 selected estrogenic CHM, the aqueous extracts of Cistanche deserticola (CD) and Dioscorea opposita (DO) at 0.4 to 1.6 mg/ml significantly stimulated cell viability in both estrogen receptor (ER)-positive (MDA-MB-361 and MCF-7) and ER-negative (SKBR3 and MDA-MB-231) breast cancer cells. However, results from animal studies showed that no significant difference was found on the size of mouse 4T1 breast tumors in CD- and DO-treated mice when compared with the control group, while the number of proliferative cells were found to be increased in DO-treated group. Besides, CD and DO treatments induced significant immunomodulatory effects on 4T1 tumor-bearing mice by increasing the production of cytokines IL-2 and IFN-γ and modulation of regulatory T-cells. Furthermore, CD and DO treatments did not stimulate, but in fact suppressed human triple-negative MDA-MB-231 breast xenografts growth in immunodeficiency mice. CONCLUSION: The considerable concerns on the use of CD and DO in breast cancer patients could be relieved to some extents upon the findings of this pre-clinical study. The potential harmful effects of estrogenic Chinese herbal medicines on breast cancer growth should be verified in both cell-based and tumor-bearing mice models.

Electrocardiographic conduction and repolarization markers associated with sudden cardiac death: moving along the electrocardiography waveform.

The QT interval along with its heart rate corrected form (QTc) are well-established ECG markers that have been found to be associated with malignant ventricular arrhythmogenesis. However, extensive preclinical and clinical investigations over the years have allowed for novel clinical ECG markers to be generated as predictors of arrhythmogenesis and sudden cardiac death. Repolarization markers include the older QTc, QT dispersion and newer Tpeak - Tend intervals, (Tpeak - Tend) / QT ratios, T-wave alternans (TWA), microvolt TWA and T-wave area dispersion. Meanwhile, conduction markers dissecting the QRS complex, such as QRS dispersion (QRSD) and fragmented QRS, were also found to correlate conduction velocity and unidirectional block with re-entrant substrates in various cardiac conditions. Both repolarization and conduction parameters can be combined into the excitation wavelength (λ). A surrogate marker for λ is the index of Cardiac Electrophysiological Balance (iCEB: QT / QRSd). Other markers based on conduction-repolarization are [QRSD x (Tpeak-Tend) / QRSd] and [QRSD x (Tpeak-Tend) / (QRSd x QT)]. Advancement in technology permitted sophisticated electrophysiological analyses such as principal component analysis and periodic repolarization dynamics to further improve risk stratification. This was closely followed by other novel indices including ventricular ectopic QRS interval, the f99 index and EntropyXQT, which integrates mathematical and physical calculations for determining the risk markers. Though proven to be effective in limited patient cohorts, more clinical studies across different cardiac pathologies are required to confirm their validity. As such, this review seeks to encapsulate the development of old and new ECG markers along with their associated utility and shortcomings in clinical practice.

How Heart Rate Should Be Controlled in Patients with Atherosclerosis and Heart Failure.

PURPOSE OF REVIEW: Resting heart rate is an independent risk factor for all-cause and cardiovascular mortality in patients with heart failure. The main objectives are to discuss the prognosis of heart rate, its association with coronary atherosclerosis, and the modalities of control of the heart rate in sinus rhythm and in the rhythm of atrial fibrillation in patients with chronic heart failure. RECENT FINDINGS: As a therapeutic option for control heart rate, medications such as beta-blockers, digoxin, and finally ivabradine have been studied. Non-dihydropyridine calcium channel blockers are contraindicated in patients with heart failure and reduced ejection fraction. The influence of the magnitude of heart rate reduction and beta-blocker dose on morbidity and mortality will be discussed. Regarding the patients with heart failure and atrial fibrillation, there are different findings in heart rate control with the use of a beta-blocker. Patients eligible for ivabradine have clinical benefits and increased ejection fraction. Vagal nerve stimulation has low efficacy for the control of heart rate. Complementary therapies such as tai chi and yoga showed no effect on heart rate. In this review, we discuss the main therapeutic options for the control of heart rate in patients with atherosclerosis and heart failure. More research is needed to examine the effects of therapeutic options for heart rate control in different population types, as well as their effects on clinical outcomes and impact on morbidity and mortality.

Depressive Symptoms, Co-Morbidities, and Glycemic Control in Hong Kong Chinese Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: Undiagnosed depression is an important comorbidity in type 2 diabetes (T2D) which can be detected using the Geriatric Depression Scale (GDS-15) questionnaire. In this cross-sectional study, we examined the associations of depression using GDS score with control of cardiometabolic risk factors and health status in elderly patients with T2D. SETTING AND PARTICIPANTS: Between February and December 2013, patients aged ≥65 years who underwent structured comprehensive assessment as a quality improvement program at the Diabetes Center of a teaching hospital were invited to complete the GDS-15 questionnaire. MAIN OUTCOME MEASURES: Depression was defined as a GDS score ≥7. Demographic data, prior history of co-morbidities, frequency of self-reported hypoglycemia, and attainment of treatment targets defined as HbA1c, <7%, blood pressure <130/80 mmHg, and LDL-C <2.6 mmol/L were documented. RESULTS: Among 325 participants (65% male, median [interquartile range] age: 69 [8] years), 42 (13%) had depression. Patients with depression had longer disease durations (mean ± SD: 15.1 ± 9.1 vs. 11.6 ± 8.1 years, P = 0.02), more frequent self-reported hypoglycemic events (17 vs. 6%, P = 0.03) and were less likely to attain all three treatment targets (0 vs. 16%, P = 0.004) than those without depression. On multivariable analysis, patients with depression had an odds ratio of 2.84 (95% confidence intervals: 1.35-6.00, P = 0.006) of reporting prior history of co-morbidities. CONCLUSION: In elderly patients with T2D, depression was not uncommon especially in those with poor control of risk factors, hypoglycemia, and co-morbidities. Inclusion of GDS-15 questionnaire during structured assessment for complications and risk factors can identify these high-risk patients for more holistic management of their physical and mental health.

Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts.

Acute effects of heptanol (0.1 to 2 mM) on atrial electrophysiology were explored in Langendorff-perfused mouse hearts. Left atrial bipolar electrogram or monophasic action potential recordings were obtained during right atrial stimulation. Regular pacing at 8 Hz elicited atrial activity in 11 out of 11 hearts without inducing atrial arrhythmias. Programmed electrical stimulation using a S1S2 protocol provoked atrial tachy-arrhythmias in 9 of 17 hearts. In the initially arrhythmic group, 2 mM heptanol exerted anti-arrhythmic effects (Fisher's exact test, P < 0.05) and increased atrial effective refractory period (ERP) from 26.0 ± 1.9 to 57.1 ± 2.5 ms (ANOVA, P < 0.001) despite increasing activation latency from 18.7 ± 1.1 to 28.9 ± 2.1 ms (P < 0.001) and leaving action potential duration at 90% repolarization (APD90) unaltered (25.6 ± 1.2 vs. 27.2 ± 1.2 ms; P > 0.05), which led to increases in ERP/latency ratio from 1.4 ± 0.1 to 2.1 ± 0.2 and ERP/APD90 ratio from 1.0 ± 0.1 to 2.1 ± 0.2 (P < 0.001). In contrast, in the initially non-arrhythmic group, heptanol did not alter arrhythmogenicity, increased AERP from 47.3 ± 5.3 to 54.5 ± 3.1 ms (P < 0.05) and activation latency from 23.7 ± 2.2 to 31.3 ± 2.5 ms and did not alter APD90 (24.1 ± 1.2 vs. 25.0 ± 2.3 ms; P > 0.05), leaving both AERP/latency ratio (2.1 ± 0.3 vs. 1.9 ± 0.2; P > 0.05) and ERP/APD90 ratio (2.0 ± 0.2 vs. 2.1 ± 0.1; P > 0.05) unaltered. Lower heptanol concentrations (0.1, 0.5 and 1 mM) did not alter arrhythmogenicity or the above parameters. The present findings contrast with known ventricular pro-arrhythmic effects of heptanol associated with decreased ERP/latency ratio, despite increased ERP/APD ratio observed in both the atria and ventricles.

Photodynamic therapy of Pheophorbide a inhibits the proliferation of human breast tumour via both caspase-dependent and -independent apoptotic pathways in in vitro and in vivo models.

Breast cancer is conventionally treated by surgery and radiotherapy, with adjuvant chemotherapy and hormonotherapy as supplementary treatments. However, such treatments are associated with adverse side effects and drug resistance. In this study, Pheophorbide a (Pa), a photosensitizer isolated from Scutelleria barbata, was analysed for its antiproliferative effect on human breast tumour cells. The IC (inhibitory concentration)(50) of the combined treatment of Pa and photodynamic therapy (Pa-PDT) on human breast tumour MCF-7 cells was 0.5 µm. Mechanistic studies in MCF-7 cells demonstrated that Pa was localized in the mitochondria, and reactive oxygen species were found to be released after Pa-PDT. Apoptosis was the major mechanism responsible for the tumour cell death, and mitochondrial membrane depolarization and cytochrome c release highlighted the role of mitochondria in the apoptotic mechanism. Up-regulation of tumour suppressor protein p53, cleavage of caspase-9 and poly (ADP-ribose) polymerase suggested that the caspase-dependent pathway was induced, while the release of apoptosis-inducing factors demonstrated that the apoptosis was also mediated by the caspase-independent mechanism. In vivo study using the mouse xenograft model showed a significant inhibition of MCF-7 tumour growth by Pa-PDT. Together, the results of this study provide a basis for understanding and developing Pa-PDT as a cure for breast cancer.

Monitoring of treatment response after chemoradiotherapy for head and neck cancer using in vivo 1H MR spectroscopy.

Elevated choline (Cho) level has been documented on proton magnetic resonance spectroscopy ((1)H MRS) in head and neck squamous cell carcinoma and therefore percentage changes in Cho levels after chemoradiotherapy may serve as a marker of residual cancer in a post-treatment mass (PTM). Forty-six patients underwent (1)H MRS before treatment and the 30 patients with a PTM underwent repeat (1)H MRS at 6 weeks post-treatment. The percentage change in Cho/creatine and Cho/water ratios were correlated with residual cancer. The mean pretreatment Cho/creatine and Cho/water ratios were 2.24 and 1.20 x 10(-3), respectively. Cho persisted in four out of nine PTMs with residual cancer. Cho was absent in five out of nine PTMs with residual cancer and 21/21 PTMs without cancer. The number of PTMs with persistent Cho was too small to allow analysis of percentage change in ratios but the presence of Cho in a PTM showed significant correlation with residual cancer (p = 0.0046), producing a sensitivity, specificity, positive predictive value and negative predictive value of 44%, 100%, 100% and 81%, respectively. Therefore, the presence of Cho in a PTM may serve as a marker of residual cancer. Furthermore since so few PTMs contain Cho, a percentage change in Cho ratios may not be a useful method for monitoring treatment response.

Comparative studies of various ganoderma species and their different parts with regard to their antitumor and immunomodulating activities in vitro.

OBJECTIVES: Ganoderma lucidum (Lingzhi or Reishi) has been commonly suggested in East Asia as a potential candidate for prevention and treatment of different diseases, including cancer. Ganoderma extracts, in particular Ganoderma lucidum (extracts or isolated components), have previously been shown to possess antitumor activities. The present study aimed at comparing three different species of Ganoderma, wildly grown versus cultivated, as well as the different parts of the fruiting body (whole fruiting body, pileus, and stipe), with regard to their antitumor effects in human breast cancer cells and immunomodulatory activities in mouse splenic lymphocytes in vitro. METHODS: The aqueous extracts (12.5-400 microg/mL) of G. lucidum, G. sinense, and G. tsugae were examined for their antiproliferative activities in human breast cancer cell lines, MCF-7 and MDA-MB-231, as well as in normal human mammary epithelial cells (primary culture). The immunomodulatory effects of the extracts were evaluated in mouse splenic lymphocytes. The proliferative responses of the mentioned cell types were determined by MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide] assay. RESULTS: The present results demonstrated that the extracts of all tested Ganoderma samples could significantly inhibit cell proliferation in human breast cancer cell lines MCF-7 and MDA-MB-231, with G. tsugae being the most potent. The extracts, however, did not exert any significant cytotoxic effect on human normal mammary epithelial cells. Within the species G. sinense, the inhibitory effects of wildly grown samples were not significantly different from those of the cultivated samples, except at 400 microg/mL. Most of the tested extracts of Ganoderma stimulated mouse splenic lymphocytes proliferation. The extracts from the stipes of the G. tsugae and wildly grown G. sinense showed much stronger inhibitory effects than the other parts of the fruiting body in both cancer cell lines, whereas the extracts from the stipes of G. lucidum and wildly grown G. sinense showed stronger immunopotentiating activities in mouse splenic lymphocytes. CONCLUSIONS: These results indicate that the aqueous extracts of these commonly available Ganoderma fruiting bodies, G. lucidum, G. sinense, and G. tsugae have antitumor activities in human breast cancer cells and immunomodulatory activities in murine lymphocytes. In addition, the present findings also suggest that the stipes of fruiting bodies of Ganoderma species should be included in the preparation of extract of these fungi in order to obtain the most comprehensive active ingredients. To the best of the authors' knowledge, this is the first detailed comparison among the different parts of the fruiting bodies of Ganoderma.