The Lived Experiences of Palliative Care Professionals in Cultivating Mindfulness: A Phenomenological Study.

Purpose: The aim of this study was to explore the essence of the lived experiences of palliative care professionals in cultivating mindfulness, with a focus on the meaning of mindfulness in their lives and how mindfulness is experienced throughout their process of caring for others. Design: This was a qualitative study using a phenomenological approach. Methods: Eleven palliative care professionals (three physicians, four nurses, three psychologists, and one spiritual care provider) partook in in-depth interviews. Data were collected from the in-depth interviews and analyzed according to the method of Giorgi. Findings: Two major themes emerged from this study. First, the palliative care professionals realized the need for self-care amid emotional burden, including recognizing their feelings of guilt and self-doubt, emotional contagion of grief, reflections of others' fragility on themself, and their self-imposed limitations. Second, they noticed the transformative impact of mindfulness on them, including detecting reconnection with their body, changes in their personal values, self-acceptance, and liberation. Conclusion: Palliative care professionals can cultivate self-acceptance and facilitate entirely new life experiences through the practice of mindfulness. For them, mindfulness is not merely a self-regulation technique but an existential epiphany, offering hope for self-care and empowerment.

Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial.

AIMS: This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P < 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P < 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode. CONCLUSION: DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population.

[The Elephant in the Room: Integrative Care for Community Hospice Palliative Care in Taiwan: An Example of a Regional Teaching Hospital in Pingtung County].

Taiwan has been an aging society since 2018. As a result, long-term care, end-of-life autonomy, and hospice care have received increasing attention. The government of Taiwan promotes home-based healthcare through the National Health Insurance System to enable the efficient utilization of medical resources and reduce overall medical costs. Taiwan's community hospice and palliative care network is expected to serve as the main care model supplementing partial hospitalization and institutional care. In this article, we review the history of and policies related to hospice and palliative care in Taiwan using a literature review and examining Pingtung County as a case study. The implementation of home-based palliative care is also outlined and policy revisions are proposed. The results are intended to provide a reference for healthcare authorities and medical institutions to promote community hospice and palliative care policies. The integrated care model can enhance the capacity of community-based palliative care, support patients receiving palliative care and their family members and caregivers, and ensure physical and psychological comfort for patients. This model contributes to the realization of older adults' preference for dying at home, which is especially pronounced in cultures where traditional Chinese ideas are deeply rooted.

Unleashing the Influence of cAMP Receptor Protein: The Master Switch of Bacteriocin Export in Pectobacterium carotovorum subsp. carotovorum.

Pectobacterium carotovorum subsp. carotovorum (Pcc) is a Gram-negative phytopathogenic bacterium that produces carocin, a low-molecular-weight bacteriocin that can kill related strains in response to factors in the environment such as UV exposure or nutritional deficiency. The function of the catabolite activator protein (CAP), also known as the cyclic AMP receptor protein (CRP), as a regulator of carocin synthesis was examined. The crp gene was knocked out as part of the investigation, and the outcomes were assessed both in vivo and in vitro. Analysis of the DNA sequence upstream of the translation initiation site of carocin S3 revealed two putative binding sites for CRP that were confirmed using a biotinylated probe pull-down experiment. This study revealed that the deletion of crp inhibited genes involved in extracellular bacteriocin export via the flagellar type III secretion system and impacted the production of many low-molecular-weight bacteriocins. The biotinylated probe pull-down test demonstrated that when UV induction was missing, CRP preferentially attached to one of the two CAP sites while binding to both when UV induction was present. In conclusion, our research aimed to simulate the signal transduction system that controls the expression of the carocin gene in response to UV induction.

[Living With Cancer: Clinical Application of Mindfulness on Cancer-Related Fatigue].

Cancer-related fatigue is the most common and longest-lasting symptom of discomfort experienced by cancer patients. Its effects on patients include physical, psychological, emotional, and cognitive stress, which greatly reduce quality of life. The field of mind-body integrated medicine has improved gradually in recent years, with many evidence-based studies supporting the efficacy of mindfulness as a symptom management strategy for cancer-related fatigue. Based on a review of the literature, this paper introduces the definition of cancer-related fatigue and related assessments and treatments, describes the origin of mindfulness and related concepts, and introduces mindfulness-based empirical treatment strategies for cancer-related fatigue, including mindfulness-based stress reduction and mindfulness-based cognitive therapy, and their effects. The findings are intended to provide clinicians with a reference for the future care of patients with cancer-related fatigue.

ATMIN enhances invasion by altering PARP1 in MSS colorectal cancer.

Genomic instability is a key cancer indicator. It results from defects in the DNA damage response (DDR) and increased replication stress. Herein, we examined how ataxia-telangiectasia mutated interactor (ATMIN), a DDR pathway involved in mismatch repair-proficient (microsatellite stability [MSS]), acts in colorectal carcinoma (CRC). Firstly, ATMIN mRNA expression was detected in CRC specimens with MSS characteristics, and the effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were gauged in MSS cell lines. To understand the molecular mechanism, co-immunoprecipitation analyses in vitro were employed. Interestingly, ATMIN expression was positively correlated with advanced stages (P < .001), lymph node metastases (P = .002), and deeper invasion (P = .037) in MSS tumors; and significantly changed the cell motility in vitro. In the high-throughput analysis, ATMIN was found to act on the Wnt signaling pathway via PARP1. PAPR1 inhibition, in turn, significantly decreased invasion abilities resulting from ATMIN overexpression in cancer cell. Taken together, ATMIN, which alters the Wnt signaling pathway regulating CRC progression, plays as a crucial prognostic factor in MSS tumors.

Resuscitated Sudden Cardiac Arrest of a Neonate with Congenital LQT Syndrome-Associated Torsades de Pointes: A Case Report and Literature Review.

Sudden infant death syndrome (SIDS), the most common cause of infant death in developed countries, is attributed to diverse trigger factors. Malignant cardiac dysrhythmias are potentially treatable etiologies, and congenital long QT syndrome (LQTS) is the most common cardiac ionic channelopathy confronted. ß-Blockers or class Ib agents are the drugs of choice for the control of arrhythmias, and an implantable cardioverter defibrillator (ICD) should be considered for secondary prevention in survivors of lethal cardiac death. We report the case of a 4-day old neonate, later genetically confirmed as LQT type 3 (LQT3), who survived a pulseless torsades de pointes (TdP) attack and was successfully treated with propranolol, mexiletine, and ICD implantation.

The Antihypertensive Effects and Safety of LCZ696 in Patients with Hypertension: A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The management of hypertension remains suboptimal throughout the world. METHODS: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. RESULTS: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = -6.52 mmHg, 95% confidence interval (CI): -8.57 to -4.47; p < 0.001), msDBP (WMD = -3.32 mmHg, 95% CI: -4.57 to -2.07; p < 0.001), maSBP (WMD = -7.08 mmHg, 95% CI: -10.48 to -3.68; p < 0.001), maDBP (WMD = -3.28 mmHg, 95% CI: -4.55 to -2.02, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger's test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. CONCLUSION: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.

ATMIN Suppresses Metastasis by Altering the WNT-Signaling Pathway via PARP1 in MSI-High Colorectal Cancer.

BACKGROUND: Constant DNA damage occurs in cells, and the cells are programmed to respond constitutively. This study explored the roles of ataxia-telangiectasia mutated interactor (ATMIN), one of the impaired pathways involving the DNA damage response (DDR) in mismatch repair-deficient [microsatellite instability (MSI)-high] colorectal carcinoma (CRC). METHODS: Expression of ATMIN messenger RNA (mRNA) was detected in CRC specimens with microsatellite instability (MSI) characteristics. The effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were evaluated in MSI-high cell lines, and liver metastasis ability was investigated in vivo. Protein-protein interactions were assessed by coimmunoprecipitation analyses in vitro. RESULTS: Decreased ATMIN expression was positively correlated with advanced stage of disease (P < 0.05), lymph node metastases (P < 0.05), and deeper invasion (P < 0.05) in MSI-high tumors. Transient or stable ATMIN knockdown significantly increased cell motility. Moreover, in the high-throughput microarray and gene set enrichment analysis, ATMIN was shown to act on the Wnt-signaling pathway via PARP1. This cascade influences ß-catenin/transcription factor 4 (TCF4) binding affinity in MSI-high tumors, and PARP1 inhibition significantly decreased the number of metastases from ATMIN knockdown cancer cells. CONCLUSIONS: The results not only indicated the critical role of ATMIN, but also shed new light on PARP1 inhibitors, providing a basis for further clinical trials of MSI-high CRC.

Recognizing spatial and temporal clustering patterns of dengue outbreaks in Taiwan.

BACKGROUND: Dengue fever is the most common arboviral infection in humans, with viral transmissions occurring in more than 100 countries in tropical regions. A global strategy for dengue prevention and control was established more than 10 years ago. However, the factors that drive the transmission of the dengue virus and subsequent viral infection continue unabated. The largest dengue outbreaks in Taiwan since World War II occurred in two recent successive years: 2014 and 2015. METHODS: We performed a systematic analysis to detect and recognize spatial and temporal clustering patterns of dengue incidence in geographical areas of Taiwan, using the map-based pattern recognition procedure and scan test. Our aim was to recognize geographical heterogeneity patterns of varying dengue incidence intensity and detect hierarchical incidence intensity clusters. RESULTS: Using the map-based pattern recognition procedure, we identified and delineated two separate hierarchical dengue incidence intensity clusters that comprise multiple mutually adjacent geographical units with high dengue incidence rates. We also found that that dengue incidence tends to peak simultaneously and homogeneously among the neighboring geographic units with high rates in the same cluster. CONCLUSION: Beyond significance testing, this study is particularly desired by and useful for health authorities who require optimal characteristics of disease incidence patterns on maps and over time. Among the integrated components for effective prevention and control of dengue and dengue hemorrhagic fever are active surveillance and community-based integrated mosquito control, for which this study provides valuable inferences. Effective dengue prevention and control programs in Taiwan are critical, and have the added benefit of controlling the potential emergence of Zika.

Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. METHODS: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer. The expression of CTGF and mitochondrial biogenesis related genes was measured by real-time polymerase chain reaction or Western blot analysis. RESULTS: CTGF decreased OCR, ECAR, adenosine triphosphate (ATP) generation, mitochondrial DNA (mtDNA), and mitochondrial transcription factor A (mtTFA) protein expression in OSCC cells. Overexpression of mtTFA restored CTGF-decreased OCR, ECAR, mtDNA copy number, migration and invasion of SAS/CTGF cells. Immunoprecipitation assay showed a higher level of ubiquitinated mtTFA protein after CTGF treatment. MG132, an inhibitor of proteasomal degradation, reversed the effect of CTGF on mtTFA protein expression in SAS cells. CONCLUSION: CTGF can decrease glycolysis, mitochondrial oxidative phosphorylation, ATP generation, and mtDNA copy number by increasing mtTFA protein degradation through ubiquitin proteasome pathway and in turn reduces migration and invasion of OSCC cells. Therefore, CTGF may be developed as a potential additive therapeutic drug for oral cancer in the near future.

Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy.

Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-ß1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-ß1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

Ataxia-telangiectasia mutated interactor regulates head and neck cancer metastasis via KRas expression.

OBJECTIVES: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear. MATERIALS AND METHODS: ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided. RESULTS: ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression. CONCLUSIONS: The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine.

Hemiasterlin derivative (R)(S)(S)-BF65 and Akt inhibitor MK-2206 synergistically inhibit SKOV3 ovarian cancer cell growth.

We reported previously that a hemiasterlin derivative BF65 is a potent anticancer agent that can inhibit microtubule assembly. Here we show that a more potent stereospecific diastereomer (R)(S)(S)-BF65 can synergize with an allosteric Akt inhibitor MK-2206 to suppress the growth of SKOV3 ovarian cancer cells with constitutively active Akt. (R)(S)(S)-BF65 induced mitotic arrest and MK-2206 caused G0/G1 arrest, while the combination of both induced simultaneous G0/G1 and G2/M cell cycle arrest. (R)(S)(S)-BF65 induced phosphorylation and inactivation of Bcl-2, and downregulated Mcl-1, consequently may lead to apoptosis. (R)(S)(S)-BF65 inhibited mitogen-activated protein kinases (MAPKs), which may stimulate cell proliferation upon activation. (R)(S)(S)-BF65 also induced DNA damage after long-term treatment. MK-2206 is known to inhibit phosphorylation and activation of Akt and suppress cancer cell growth. The combination of (R)(S)(S)-BF65 and MK-2206 also inhibited the Akt pathway. Interestingly, MK-2206 upregulated Bcl-2 and induced activation of MAPKs in SKOV3 cells; however, when combined with (R)(S)(S)-BF65, these prosurvival effects were reversed. The combination also more significantly decreased Mcl-1 protein, increased PARP cleavage, and induced γ-H2AX, a DNA damage marker. Remarkably, MK-2206 enhanced the microtubule depolymerization effect of (R)(S)(S)-BF65. The combination of (R)(S)(S)-BF65 and MK-2206 also markedly inhibited cell migration. Thus, MK-2206 synergizes with (R)(S)(S)-BF65 to inhibit SKOV3 cell growth via downregulating the Akt signaling pathway, and enhancing the microtubule disruption effect of (R)(S)(S)-BF65. (R)(S)(S)-BF65 in turn suppresses Bcl-2 and MAPKs induced by MK-2206. (R)(S)(S)-BF65 and MK-2206 compensate each other leading to increased apoptosis and enhanced cytotoxicity, and may also suppress cancer cell invasion.

Suppression of fructose-bisphosphate aldolase C expression as a predictor of advanced oral squamous cell carcinoma.

BACKGROUND: Glycolysis machinery regulates cancer cell behavior. However, the roles of these glycolysis enzymes in oral squamous cell carcinoma (OSCC) progression remain unknown. METHODS: Fructose-bisphosphate aldolase C (ALDOC) expression in OSCC patients and cell lines was detected using quantitative real-time polymerase chain reaction (PCR). The functions of ALDOC in migration and invasion were determined using gain and loss of function approaches. An orthotopic OSCC animal model was performed to investigate the effects of ALDOC on metastasis and tumorigenesis in vivo. RESULTS: ALDOC expression is negatively significantly correlated with clinical outcome and cell migration in vitro and in vivo. ALDOC blocks adenosine triphosphate generation and lactate production, and mutation constructs of Arg42 and Lys146 functionally restore ALDOC-inhibited cell migration and invasion. CONCLUSION: ALDOC functions as an OSCC prognosis marker clinically, and suppresses migration and invasion by its catalytic domain of Arg42 and Lys146. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1075-E1085, 2016.

Anti-IL-20 Monoclonal Antibody Suppresses Prostate Cancer Growth and Bone Osteolysis in Murine Models.

Interleukin (IL)-20 is a proinflammatory cytokine in the IL-10 family. IL-20 is associated with tumor promotion in the pathogenesis of oral, bladder, and breast cancer. However, little is known about the role of IL-20 in prostate cancer. We hypothesize that IL-20 promotes the growth of prostate cancer cells. Immunohistochemical staining showed that IL-20 and its receptors were expressed in human PC-3 and LNCaP prostate cancer cell lines and in prostate tumor tissue from 40 patients. In vitro, IL-20 upregulated N-cadherin, STAT3, vimentin, fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF-κB signals in PC-3 cells. We investigated the effects of anti-IL-20 monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor growth, suppressed tumor-mediated osteolysis, and protected bone mineral density after intratibial injection of prostate cancer cells. We conclude that IL-20 is involved in the cell migration, colony formation, and tumor-induced osteolysis of prostate cancer. Therefore, IL-20 might be a novel target for treating prostate cancer.

Design of multifold Ge/Si/Ge composite quantum-dot heterostructures for visible to near-infrared photodetection.

We demonstrate an effective approach to grow high-quality thin film (>1 µm) of multifold Ge/Si/Ge composite quantum dots (CQDs) stacked heterostructures for near infrared photodetection and optical interconnect applications. An otherwise random, self-assembly of variable-fold Ge/Si CQDs has been grown on Si through the insertion of Si spacer layers to produce micron-scale-thick, stacked Ge/Si CQD layers with desired QD morphology and composition distribution. The high crystalline quality of these multifold Ge CQD heterostructures is evidenced by low dark current density of 3.68 pA/µm2, superior photoresponsivity of 267 and 220 mA/W under 850 and 980 nm illumination, respectively, and very fast temporal response time of 0.24 ns measured on the Ge/Si CQD photodetectors.

A Unique Approach to Generate Self-Aligned SiO2/Ge/SiO2/SiGe Gate-Stacking Heterostructures in a Single Fabrication Step.

We report a first-of-its-kind, unique approach for generating a self-aligned, gate-stacking heterostructure of Ge quantum dot (QD)/SiO2/SiGe shell on Si in a single fabrication step. The 4-nm-thick SiO2 layer between the Ge QD and SiGe shell fabricated during the single-step process is the result of an exquisitely controlled dynamic balance between the fluxes of oxygen and silicon interstitials. The high-quality interface properties of our "designer" heterostructure are evidenced by the low interface trap density of as low as 2-4 × 10(11) cm(-2) eV(-1) and superior transfer characteristics measured for Ge-based metal-oxide-semiconductor field-effect transistors (MOSFETs). Thanks to the very thin interfacial SiO2 layer, carrier storage within the Ge QDs with good memory endurance was established under relatively low-voltage programming/erasing conditions. We hope that our unique self-aligned, gate-stacking heterostructure provides an effective approach for the production of next-generation, high-performance Ge gate/SiO2/SiGe channel MOSFETs.

The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells.

Abnormalities in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway are commonly observed in human cancers and contribute to chemotherapy resistance. Combination therapy, involving the use of molecular targeted agents and traditional cytotoxic drugs, may represent a promising strategy to lower resistance and enhance cytotoxicity. Here, we demonstrate the efficacy of an Akt inhibitor, MK-2206, in increasing the cytotoxic effect of either paclitaxel (Taxol) or cisplatin against the ovarian cancer cell lines SKOV3 (with constitutively active Akt) and ES2 (with inactive Akt). Sequential treatment of Taxol or cisplatin, followed by MK-2206, induced a synergistic inhibition of cell proliferation and effectively promoted cell death, either by inhibiting the phosphorylation of Akt and its downstream effectors 4E-BP1 and p70S6K in SKOV3 cells or by restoring p53 levels, which were downregulated after Taxol or cisplatin treatment, in ES2 cells. Combination treatment also downregulated the pro-survival protein Bcl-2 in both SKOV3 and ES2 cells, which may have contributed to cell death. In addition, we discovered that Taxol/MK-2206 or cisplatin/MK-2206 combination treatment resulted in significant enhancement of intracellular reactive oxygen species (ROS) induced by MK-2206, in both SKOV3 and ES2 cells; however, MK-2206-induced growth inhibition was reversed by a ROS scavenger only in ES2 cells. MK-2206 also suppressed DNA repair, particularly in SKOV3 cells. Taken together, our results demonstrate that the Akt inhibitor MK-2206 enhances the efficacy of cytotoxic agents in both Akt-active and Akt-inactive ovarian cancer cells but through different mechanisms.