Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Performance measures of 8,169,869 examinations in the National Breast Cancer Screening Program in Taiwan, 2004-2020.

BACKGROUND: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods. METHODS: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. RESULTS: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period. CONCLUSIONS: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

Novel PEX1 mutations in fibroblasts from children with Zellweger spectrum disorders exhibit temperature sensitive characteristics.

Zellweger spectrum disorders (ZSD) are rare autosomal recessive disorders caused by defects in peroxisome biogenesis factor (PEX; peroxin) genes leading to impaired transport of peroxisomal proteins with peroxisomal targeting signals (PTS). Four patients, including a pair of homozygotic twins, diagnosed as ZSD by genetic study with different clinical presentations and outcomes as well as various novel mutations are described here. A total of 3 novel mutations, including a nonsense, a frameshift, and a splicing mutation, in PEX1 from ZSD patients were identified and unequivocally confirmed that the p.Ile989Thr mutant PEX1 exhibited temperature-sensitive characteristics and is associated with milder ZSD. The nature of the p.Ile989Thr mutant exhibited different characteristics from that of the other previously identified temperature-sensitive p.Gly843Asp PEX1 mutant. Transcriptome profiles under nonpermissive vs. permissive conditions were explored to facilitate the understanding of p.Ile989Thr mutant PEX1. Further investigation of molecular mechanisms may help to clarify potential genetic causes that could modify the clinical presentation of ZSD.

Double-contrast barium enema is no longer justified as a backup examination for colonoscopy in the population screening program: Population study in an organized fecal immunochemical test-based screening program.

BACKGROUND AND AIM: Currently, some countries still acknowledge double-contrast barium enema (DCBE) as a backup confirmatory examination when colonoscopy is not feasible or incomplete in colorectal cancer (CRC) screening programs. This study aims to compare the performance of colonoscopy and DCBE in terms of the risk of incident CRC after negative results in the fecal immunochemical test (FIT)-based Taiwan Colorectal Cancer Screening Program. METHODS: Subjects who had positive FITs and received confirmatory exams, either colonoscopy or DCBE, without the findings of neoplastic lesions from 2004 to 2013 in the screening program comprised the study cohort. Both the colonoscopy and DCBE subcohorts were followed until the end of 2018 and linked to the Taiwan Cancer Registry to identify incident CRC cases. Multivariate analysis was conducted to compare the risk of incident CRC in both subcohorts after controlling for potential confounders. RESULTS: A total of 102 761 colonoscopies and 5885 DCBEs were performed after positive FITs without neoplastic findings during the study period. By the end of 2018, 2113 CRCs (2.7 per 1000 person-years) and 368 CRCs (7.6 per 1000 person-years) occurred in the colonoscopy and DCBE subcohorts, respectively. After adjusting for major confounders, DCBE had a significantly higher risk of incident CRC than colonoscopy, with an adjusted HR of 2.81 (95% CI = 2.51-3.14). CONCLUSIONS: In the FIT screening program, using DCBE as a backup examination was associated with a nearly threefold risk of incident CRC compared with colonoscopy, demonstrating that it is no longer justified as a backup examination for incomplete colonoscopy.

Risk of colonoscopy-related complications in a fecal immunochemical test-based population colorectal cancer screening program.

BACKGROUND: The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes. METHODS: Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy. RESULTS: 319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32). CONCLUSIONS: FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.

Mass screening and eradication of Helicobacter pylori as the policy recommendations for gastric cancer prevention.

Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a three-tier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening program to maximize the population benefits and cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage in progress, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy.

Differences in self-care knowledge, self-efficacy, psychological distress and self-management between patients with early- and end-stage chronic kidney disease.

AIMS: The study compares the differences in self-care knowledge, self-efficacy, psychological distress and self-management between patients with early- and end-stage chronic kidney disease (CKD), and predicts the influential factors of self-management. DESIGN: A cross-sectional study. METHODS: A total of 185 subjects by using convenience sampling from one teaching hospital were collected. The research instruments included the Chronic Kidney Disease Self-Care Instrument Knowledge, the Chronic Kidney Disease Self-Efficacy Instrument, the Hospital Anxiety and Depression Scale, and the Chronic Kidney Disease Self-Management Instrument. Descriptive statistics is used frequency, percentage, mean and standard deviation. Inferential statistics is used independent t-test, one-way ANOVA and multiple linear regression analysis. STROBE checklist was used as the guideline for this study. RESULTS: Our results showed that a significant difference was found in the age (p = 0.005), systolic pressure (p = .006), self-care knowledge (p = .011) and depression level (p = .003) between patients with early- and end-stage CKD. Furthermore, patients with early-stage CKD have less self-care knowledge and lower depression levels compared with patients with end-stage CKD. However, self-efficacy is the most significant predictor of self-management for patients with early- and end-stage CKD. For patients with early-stage CKD, self-efficacy explained 69.1% of the variation in self-management. CONCLUSION: According to our results, the management of depression in patients with CKD may improve their outcomes. Improving self-care knowledge of patients with end-stage CKD may improve their self-management. Therefore, our findings suggest various interventions with different necessary and prioritised precision care at early- and late-stage of CKD. RELEVANCE TO CLINICAL PRACTICE: Nurses should strive to improve the self-care knowledge of patients with early-stage CKD to delay the progression of the disease to end-stage. Screening for depression among patients with end-stage CKD is relevant, and these patients should be referred to professional counsellors when necessary.

Faecal immunochemical test after negative colonoscopy may reduce the risk of incident colorectal cancer in a population-based screening programme.

OBJECTIVE: Subjects with a positive faecal immunochemical test (FIT) have a much higher likelihood of advanced neoplasms than the general population. Whether FIT-positive subjects with negative colonoscopy should receive subsequent FIT screening remain unclear. DESIGN: Subjects with a negative colonoscopy after positive FIT in the first screening in the Taiwanese Colorectal Cancer (CRC) Screening Program 2004-2009 were followed until the end of 2014. CRC incidence was compared between those who did and did not receive subsequent FIT screening. Cox regression analysis was conducted, adjusting for major confounders to investigate whether subsequent FIT was associated with lower risk of incident CRC. RESULTS: The study cohort was comprised of 9179 subjects who had negative diagnostic colonoscopy after positive FIT in 2004-2009, of whom 6195 received subsequent FIT during the study period. The CRC incidence (per 1000 person years) was 1.34 in those who received subsequent FIT and 2.69 in those who did not, with corresponding adjusted HR (aHR) of 0.47 (95% CI 0.31 to 0.71). Lower adenoma detection rate of diagnostic colonoscopy was associated with higher risk of incident CRC but became non-significant in multivariable analysis after adjustment for subsequent FIT. Higher baseline faecal haemoglobin concentration (FHbC, µg haemoglobin/g faeces) was associated with increased risk of incident CRC (reference: FHbC=20-39; aHR=1.93 (1.04-3.56), 0.95 (0.45-2.00), 2.26 (1.16-4.43) and 2.44 (1.44-4.12) for FHbC=40-59, 60-99, 100-149 and ≥150, respectively). CONCLUSION: Subsequent FIT should be scheduled after negative colonoscopy to detect missed neoplasms and reduce the risk of incident CRC in a national FIT screening programme.

Accuracy of long-form data in the Taiwan cancer registry.

The Taiwan Cancer Registry (TCR) is a nationwide population-based registry that collects the data of patients with newly diagnosed cancer from hospitals with ≥50 beds. TCR data are high quality in terms of completeness and timeliness. However, accuracy is also a crucial quality indicator. This study evaluated the accuracy rates of selected 55 major items in the long-form TCR data between 2014 and 2016 with 700 reported cases randomly selected from 25 long-form-reporting hospitals. We calculated the accuracy rates of the reported data by employing a reabstracted chart review. Among the 55 items, the accuracy rates of 38 (69%) were at least 95%, those of 10 (18%) were between 90% and 95%, those of 5 (9%) were between 85% and 90%, and the remaining 2 (4%) were between 80% and 85%. This demonstrates a high degree of accuracy in the TCR long-form data.

Unveiling the water-associated conformational mobility in the active site of ascorbate peroxidase.

We carried out comprehensive spectroscopic studies of wild type and mutants of ascorbate peroxidase (APX) to gain understanding of the conformational mobility of the active site. In this approach, three unnatural tryptophans were applied to replace the distal tryptophan (W41) in an aim to probe polarity/water environment near the edge of the heme-containing active site. 7-azatryptophan ((7-aza)Trp) is sensitive to environment polarity, while 2,7-azatryptophan ((2,7-aza)Trp) and 2,6-diazatryptophan ((2,6-aza)Trp) undergo excited-state water-catalyzed double and triple proton transfer, respectively, and are sensitive to the water network. The combination of their absorption, emission bands and the associated relaxation dynamics of these fluorescence probes, together with the Soret-band difference absorption and resonance Raman spectroscopy, lead us to unveil the water associated conformational mobility in the active site of APX. The results are suggestive of the existence of equilibrium between two different environments surrounding W41 in APX, i.e., the water-rich and water-scant forms with distinct fluorescence relaxation. Our results thus demonstrate for the first time the power of integrating multiple sensors (7-aza)Trp, (2,7-aza)Trp and (2,6-aza)Trp in probing the water environment of a specifically targeted Trp in proteins.

The azatryptophan-based fluorescent platform for in vitro rapid screening of inhibitors disrupting IKKß-NEMO interaction.

The nuclear factor-κB (NF-κB) plays an important role in inflammatory and immune responses. Aberrant NF-κB signaling is implicated in multiple disorders, including cancer. Targeting the regulatory scaffold subunit IκB kinase γ (IKKγ/NEMO) as therapeutic interventions could be promising due to its specific involvement in canonical NF-κB activation without interfering with non-canonical signaling. In this study, the use of unnatural amino acid substituted IKKß with unique photophysical activity to sense water environment changes upon interaction with NEMO provides a powerful in vitro screening platform that would greatly facilitate the identification of compounds having the potential to disrupt IKKß-NEMO interaction, and thus specifically modulate the canonical NF-κB pathway. We then utilized a competitive binding platform to screen the binding ability of a number of potential molecules being synthesized. Our results suggest that a lead compound (-)-PDC-099 is a potent agent with ascertained potency to disrupt IKKß-NEMO complex for modulating NF-κB canonical pathway.

The In Situ Tryptophan Analogue Probes the Conformational Dynamics in Asparaginase Isozymes.

Dynamic water solvation is crucial to protein conformational reorganization and hence to protein structure and functionality. We report here the characterization of water dynamics on the L-asparaginase structural homology isozymes L-asparaginases I (AnsA) and II (AnsB), which are shown via fluorescence spectroscopy and dynamics in combination with molecular dynamics simulation to have distinct catalytic activity. By use of the tryptophan (Trp) analog probe 2,7-diaza-tryptophan ((2,7-aza)Trp), which exhibits unique water-catalyzed proton-transfer properties, AnsA and AnsB are shown to have drastically different local water environments surrounding the single Trp. In AnsA, (2,7-aza)Trp exhibits prominent green N(7)-H emission resulting from water-catalyzed excited-state proton transfer. In stark contrast, the N(7)-H emission is virtually absent in AnsB, which supports a water-accessible and a water-scant environment in the proximity of Trp for AnsA and AnsB, respectively. In addition, careful analysis of the emission spectra and corresponding relaxation dynamics, together with the results of molecular dynamics simulations, led us to propose two structural states associated with the rearrangement of the hydrogen-bond network in the vicinity of Trp for the two Ans. The water molecules revealed in the proximity of the Trp residue have semiquantitative correlation with the observed emission spectral variations of (2,7-aza)Trp between AnsA and AnsB. Titration of aspartate, a competitive inhibitor of Ans, revealed an increase in N(7)-H emission intensity in AnsA but no obvious spectral changes in AnsB. The changes in the emission profiles reflect the modulation of structural states by locally confined environment and trapped-water collective motions.

Prediction of self-care behaviour on the basis of knowledge about chronic kidney disease using self-efficacy as a mediator.

AIMS AND OBJECTIVES: This study was to investigate: (1) the important factors in the self-care of chronic kidney disease (CKD) patients and (2) the mediating effects of self-efficacy on knowledge and self-care. BACKGROUND: Chronic kidney disease has become a major global health issue and is one of the top 10 leading causes of death in Taiwan where the dialysis population ranks first in the world. The number of patients with poor self-care behaviours continues to rise despite ongoing health education. Knowledge and self-efficacy are important factors that influence self-care behaviour; however, very few articles have examined the relationships among them. DESIGN: Cross-sectional and correlational design. METHODS: Subject recruitment was conducted by purposive sampling in the renal outpatient clinics and dialysis centres of two teaching hospitals in northern Taiwan. A total of 247 patients with chronic kidney disease (stages 1-5) were enrolled. RESULTS: (1) Knowledge was positively correlated with self-efficacy (r = 0·41, p < 0·01) and with self-care (r = 0·18, p < 0·01). Self-efficacy (r = 0·44, p < 0·01) as well as age (r = 0·15, p < 0·01) were positively correlated with self-care. (2) The relationship between knowledge and self-care was fully mediated by self-efficacy (z = 4·82, p < 0·001) and the effect was 50%. CONCLUSION: The results showed that self-efficacy was a crucial mediator between knowledge and self-care. In addition to providing knowledge to chronic kidney disease patients, healthcare professionals should also offer strategies that can enhance self-efficacy to increase self-care behaviours in chronic kidney disease patients and implement effective disease management. RELEVANCE TO CLINICAL PRACTICE: Incorporate self-efficacy strategies into the process of health education to improve knowledge and the effectiveness of self-care. The findings of this study provide evidence of effectiveness of the use of group activity through self-management and self-efficacy enhancement programmes and may influence the policy makers to consider adding or modifying the reimbursement criteria.

Depression and Social Support Trajectories During 1 Year Postpartum Among Marriage-Based Immigrant Mothers in Taiwan.

OBJECTIVES: This panel study examined the trajectories of depression and social support during the first year postpartum among marriage-based immigrant mothers in Taiwan, and the effect of social support on depression. METHODS: This panel study recruited South-Asia immigrant mothers (mean age: 27years) to complete structured questionnaire at 1month, 6month, and 1year postpartum. A total of 203 immigrant mothers completed structured questionnaires at 1 and 6months, and 163 completed the questionnaires at 1year postpartum. Postpartum depression was measured using the Edinburgh Postpartum Depression Scale. Social support was composed of 3 subscales, emotional, instrumental, and informational support. Hierarchical linear modeling was used to examine the relationships between trajectories and factors associated with depression. RESULTS: Depression and instrumental support followed downward curvilinear trajectories, while emotional and informational support followed upward curvilinear trajectories. Depression was highest at 1month, decreased sharply until 6months, and then leveled off between 6 and 12months. Emotional and instrumental support negatively covaried with postpartum depression over time. When the three-dimensional supports were considered together, only emotional support retained its significance. CONCLUSIONS: Our results demonstrated that depression was highest at 1month, then decreased, and then leveled off during 1year postpartum, though further study may be needed to confirm the trajectory. The 3 types of social support differed in postpartum trajectory, suggesting the needs to consider them separately in future studies. To decrease postpartum depression among immigrant mothers, strategies should be developed to increase emotional and instrumental support during postpartum period.

Induction of p53-independent growth inhibition in lung carcinoma cell A549 by gypenosides.

The objectives of this study are to investigate antiproliferative effect and mechanisms of bioactive compounds from Gynostemma pentaphyllum (G. pentaphyllum) on lung carcinoma cell A549. Saponins, carotenoids and chlorophylls were extracted and fractionated by column chromatography, and were subjected to high-performance liquid chromatography-mass spectrometry analyses. The saponin fraction, which consisted mainly of gypenoside (Gyp) XXII and XXIII, rather than the carotenoid and chlorophyll ones, was effective in inhibiting A549 cell growth in a concentration- and a time-dependent manner as evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The estimated half maximal inhibitory concentration (IC50 ) of Gyp on A549 cells was 30.6 µg/ml. Gyp was further demonstrated to induce an apparent arrest of the A549 cell cycle at both the S phase and the G2/M phase, accompanied by a concentration- and a time-dependent increase in the proportions of both the early and late apoptotic cells. Furthermore, Gyp down-regulated cellular expression of cyclin A and B as well as BCL-2, while up-regulated the expression of BAX, DNA degradation factor 35 KD, poly [ADP-ribose] polymerase 1, p53, p21 and caspase-3. Nevertheless, both the treatment of a p53 inhibitor, pifithrin-α, and the small hairpin RNA-mediated p53 knockdown in the A549 cells did not alter the growth inhibition effect induced by Gyp. As a result, the cell cycle arrest and apoptosis of A549 cells induced by Gyp would most likely proceed through p53-independent pathway(s).

Study design, rationale and methods for a population-based study of myopia in schoolchildren: the Myopia Investigation study in Taipei.

BACKGROUND: To describe the study design, rationale and methodology of the Myopia Investigation Study in Taipei (MIT). DESIGN: The MIT was a city-wide, population-based cohort study. PARTICIPANTS: Participants were grade 2 students (Fall 2013) of all 153 elementary schools in Taipei City. METHODS: The baseline data on the risk factors for myopia development was collected by parent-administered questionnaire surveys covering demographics, medical history, parental myopia, time spent on near work and outdoor activities, reading habits and eye care-seeking behaviour. Ocular examinations focused on the measurement of visual acuity (unaided and best-corrected) and refractive status (before and after cycloplegia), which will be carried out for the eligible schoolchildren biannually for 3 years consecutively. Once myopic children are identified, case manager-led telecoaching for health-care instructions and reminders will be delivered to parents or caregivers. MAIN OUTCOME MEASURES: To build a comprehensive database for prevalence, incidence and risk factors of early childhood myopia over a 3-year follow-up period. RESULTS: Of all 19 374 eight-year-old schoolchildren (10 210 [52.7%] boys) eligible for the MIT, 16 486 (85.1%) responded to the questionnaire, 12 019 (62.0%) were examined during the third quarter of 2013 and 11 590 (59.8%) (6267 [52.9%] boys) completed cycloplegic autorefraction on both eyes and were enrolled for further data analysis. There was no significant difference in terms of demographics between the analysed participants and all grade 2 students in Taipei City. CONCLUSIONS: Data from the MIT will provide population-based information concerning the prevalence, incidence and risk factors for myopia development among young schoolchildren in a metropolitan area of Taiwan.

Flavonoids from Gynostemma pentaphyllum exhibit differential induction of cell cycle arrest in H460 and A549 cancer cells.

Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to exhibit antiproliferation effects against H460 cells (IC50 = 50.2 µg/mL), although the IC50 of H460 is 2.5-fold that of A549 cells (IC50 = 19.8 µg/mL). Further investigation revealed that H460 cells are more susceptible to kaempferol than A549, whereas A549 cell growth is better inhibited by kaempferol rhamnohexoside derivatives as compared with H460. In addition, flavonoids from G. pentaphyllum induced cell cycle arrest at both S and G2/M phases with concurrent modulated expression of the cellular proteins cyclin A, B, p53 and p21 in A549 cells, but not H460. On the contrary, apoptosis and concomitant alteration in balance of BCL-2 and BAX expression as well as activation of caspase-3 were equally affected between both cells by flavonoid treatment. These observations strongly suggest the growth inhibition discrepancy between H460 and A549 following flavonoid treatment can be attributed to the lack of cell cycle arrest in H460 cells and the differences between H460 and A549 cells may serve as contrasting models for further mechanistic investigations.