Dual direct oral anticoagulant therapy in challenging thrombosis: a case series.

Background: While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. Objectives: We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. Methods: A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). Results: Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. Conclusion: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.

Rosai-Dorfman-Destombes disease in adults: a single center experience.

Recent advances in Rosai-Dorfman-Destombes disease (RDD), notably molecular testing, targeted therapy, and PET-CT imaging, hold promise for better recognition and improved outcomes. This study presents patients diagnosed and treated in a "real world" setting, where navigating limited resources must be considered. This retrospective single-center review includes 15 adult patients diagnosed with RDD at Vancouver General Hospital between November 2015 and October 2023. The cohort comprised five males and ten females with a median age 53 years (range 19-80 years). All 15 patients had extra-nodal disease; 11 patients exclusively had extra-nodal disease, and four patients also had lymph node involvement. Seven patients had tissue next-generation sequencing, identifying MAP2K1 mutations in four cases and a KRAS p.K117N mutation in one case that was treated with targeted therapy using trametinib. PET-CT was used for disease staging in four cases. Six patients with refractory disease tolerated lenalidomide and dexamethasone without significant toxicity; three patients achieved complete response, and three had partial response. This study highlights RDD's diverse extra-nodal manifestations. Lenalidomide combined with dexamethasone is an effective and well-tolerated treatment option for select patients, especially those with refractory disease. Broad utilization of NGS and PET-CT can positively influence management decisions.

Maternal Postpartum Depression Screening and Early Intervention in the Neonatal Intensive Care Unit.

Families with infants admitted to the neonatal intensive care unit (NICU) are at a markedly increased risk of developing postpartum depression (PPD) because of the stressors they experience by having an infant in this intensive setting. Routine screening for PPD is not regularly performed for these families because many NICUs do not offer it and well-child visits are missed while the infant is hospitalized. Because the identification and treatment of PPD is often missed in these families, screening needs to be administered in the NICU to ensure improved outcomes.

Reading instruction causes changes in category-selective visual cortex.

Education sculpts specialized neural circuits for skills like reading that are critical to success in modern society but were not anticipated by the selective pressures of evolution. Does the emergence of brain regions that selectively process novel visual stimuli like words occur at the expense of cortical representations of other stimuli like faces and objects? "Neuronal Recycling" predicts that learning to read should enhance the response to words in ventral occipitotemporal cortex (VOTC) and decrease the response to other visual categories such as faces and objects. To test this hypothesis, and more broadly to understand the changes that are induced by the early stages of literacy instruction, we conducted a randomized controlled trial with pre-school children (five years of age). Children were randomly assigned to intervention programs focused on either reading skills or oral language skills and magnetoencephalography (MEG) data collected before and after the intervention was used to measure visual responses to images of text, faces, and objects. We found that being taught reading versus oral language skills induced different patterns of change in category-selective regions of visual cortex, but that there was not a clear tradeoff between the response to words versus other categories. Within a predefined region of VOTC corresponding to the visual word form area (VWFA) we found that the relative amplitude of responses to text, faces, and objects changed, but increases in the response to words were not linked to decreases in the response to faces or objects. How these changes play out over a longer timescale is still unknown but, based on these data, we can surmise that high-level visual cortex undergoes rapid changes as children enter school and begin establishing new skills like literacy.

Need for Gastrostomy Tube in Periviable Infants.

OBJECTIVE: We sought to identify clinical and demographic factors associated with gastrostomy tube (g-tube) placement in periviable infants. STUDY DESIGN: We conducted a single-center retrospective cohort study of live-born infants between 22 and 25 weeks' gestation. Infants not actively resuscitated and those with congenital anomalies were excluded from analysis. RESULTS: Of the 243 infants included, 158 survived until discharge. Of those that survived to discharge, 35 required g-tube prior to discharge. Maternal race/ethnicity (p = 0.006), intraventricular hemorrhage (p = 0.013), periventricular leukomalacia (p = 0.003), bronchopulmonary dysplasia (BPD; p ≤ 0.001), and singleton gestation (p = 0.009) were associated with need for gastrostomy. In a multivariable logistic regression, maternal Black race (Odds Ratio [OR] = 2.88; 95% confidence interval [CI]: 1.11-7.47; p = 0.029), singleton gestation (OR = 3.99; 95% CI: 1.28-12.4; p = 0.017) and BPD (zero g-tube placement in the no BPD arm; p ≤ 0.001) were associated with need for g-tube. CONCLUSION: A high percentage of periviable infants surviving until discharge require g-tube at our institution. In this single-center retrospective study, we noted that maternal Black race, singleton gestation, and BPD were associated with increased risk for g-tube placement in infants born between 22 and 25 weeks' gestation. The finding of increased risk with maternal Black race is consistent with previous reports of racial/ethnic disparities in preterm morbidities. Additional studies examining factors associated with successful achievement of oral feedings in preterm infants are necessary and will inform future efforts to advance equity in newborn health. KEY POINTS: · BPD, singleton birth, and Black race are associated with need for g-tube in periviable infants.. · Severe intraventricular hemorrhage is associated with increased mortality or g-tube placement in periviable infants.. · Further investigation into the relationship between maternal race and g-tube placement is warranted..

Antitumor active trans­platinum complexes through metabolic stability and enhanced cellular accumulation.

Utilizing isoquinoline as a carrier ligand, we have evaluated the reactivity of selected trans­platinum planar amine (TPA) carboxylate compounds by varying the leaving carboxylate group (acetate, hydroxyacetate, and lactate) in an effort to optimize the cytotoxic and metabolic efficiency. To measure the pharmacological properties of these compounds, a combination of systematic biophysical and biological studies were carried out mainly involving substitution reaction with NAM (N-acetyl-methionine), effects on DNA structural perturbation, cytotoxicity, cellular accumulation, metabolic stability, and cell cycle effects. TPA compounds showed minimal losses in cytotoxic efficacy and outperformed cisplatin after pre-incubation with serum, while displaying a distinct micromolar cytotoxic activity with minimal DNA binding and unaltered cell cycle. Monitoring the TPA compounds with NAM suggests the following trend for the reactivity: hydroxyacetate > lactate > acetate. The same trend was seen for the cytotoxicity in tumor cells and DNA binding, while the rate of drug inactivation/protein binding in cells was not significantly different among these leaving groups. Thus, our results show superior cellular efficacy of TPA compounds and distinct micromolar cytotoxic activities different than cisplatin. Moreover, we found the TPA compounds had prolonged survival and decreased tumor burden compared to the control mice in a relevant human ovarian cancer mouse model with A2780 cells expressing luciferase. Therefore, we propose that further optimization of the basic TPA structure can give further enhanced in vivo activity and may eventually be translated into the development of clinically relevant non-traditional platinum drugs.

Microscale visualization of cellular features in adult macaque visual cortex.

Expansion microscopy and light sheet imaging enable fine-scale resolution of intracellular features that comprise neural circuits. Most current techniques visualize sparsely distributed features across whole brains or densely distributed features within individual brain regions. Here, we visualize dense distributions of immunolabeled proteins across early visual cortical areas in adult macaque monkeys. This process may be combined with multiphoton or magnetic resonance imaging to produce multimodal atlases in large, gyrencephalic brains.

A Comparison of Di- and Trinuclear Platinum Complexes Interacting with Glycosaminoglycans for Targeted Chemotherapy.

Heparan sulfate proteoglycans (HSPGs) and their associated proteins aid in tumor progression through modulation of biological events such as cell invasion, angiogenesis, metastasis, and immunological responses. Metalloshielding of the anionic heparan sulfate (HS) chains by cationic polynuclear platinum complexes (PPCs) prevents the HS from interacting with HS-associated proteins and thus diminishes the critical functions of HSPG. Studies herein exploring the PPC-HS interactions demonstrated that a series of PPCs varying in charge, nuclearity, distance between Pt centers, and hydrogen-bonding ability influence HS affinity. We report that the polyamine-linked complexes have high HS affinity and display excellent in vivo activity against breast cancer metastases and those arising in the bone and liver compared to carboplatin. Overall, the PPC-HS niche offers an attractive approach for targeting HSPG-expressing tumor cells.

Glycosaminoglycan-directed cobalt complexes.

The biological activity of the 6+ Co containing Werner's Complex has been described and mechanistic considerations suggest that the highly anionic glycosaminoglycans (heparan sulfate, HS, GAGs) are implicated in this activity [Paiva et al. 2021]. To examine in detail the molecular basis of Werner's Complex biological properties we have examined a selection of simple mononuclear Co3+ compounds for their interactions with HS and Fondaparinux (FPX). FPX is a highly sulfated synthetic pentasaccharide used as a model HS substrate [Mangrum et al. 2014, Peterson et al. 2017]. The Co complexes were chosen to be formally substitution-inert and/or have the potential for covalent binding to the biomolecule. Using both indirect competitive inhibition assays and direct mass spectrometric assays, formally substitution-inert complexes bound to FPX with protection from multiple sulfate loss in the gas phase through metalloshielding. Covalent binding of Co-Cl complexes as in [CoCl(NH3)5]2+ and cis-[CoCl2(en)2]+ was confirmed by mass spectrometry. Interestingly, the former complex was shown to be an effective inhibitor of bacterial heparinase enzyme activity and to inhibit heparanase-dependent cellular invasion through the extracellular matrix (ECM). Pursuing the theme of metalloglycomics, we have observed the hitherto unappreciated biological activity of the simple [CoCl(NH3)5]2+ compound, a staple of most inorganic chemistry lab curricula.

Radiation induces ESCRT pathway dependent CD44v3+ extracellular vesicle production stimulating pro-tumor fibroblast activity in breast cancer.

Despite recent advances in radiotherapeutic strategies, acquired resistance remains a major obstacle, leading to tumor recurrence for many patients. Once thought to be a strictly cancer cell intrinsic property, it is becoming increasingly clear that treatment-resistance is driven in part by complex interactions between cancer cells and non-transformed cells of the tumor microenvironment. Herein, we report that radiotherapy induces the production of extracellular vesicles by breast cancer cells capable of stimulating tumor-supporting fibroblast activity, facilitating tumor survival and promoting cancer stem-like cell expansion. This pro-tumor activity was associated with fibroblast production of the paracrine signaling factor IL-6 and was dependent on the expression of the heparan sulfate proteoglycan CD44v3 on the vesicle surface. Enzymatic removal or pharmaceutical inhibition of its heparan sulfate side chains disrupted this tumor-fibroblast crosstalk. Additionally, we show that the radiation-induced production of CD44v3+ vesicles is effectively silenced by blocking the ESCRT pathway using a soluble pharmacological inhibitor of MDA-9/Syntenin/SDCBP PDZ1 domain activity, PDZ1i. This population of vesicles was also detected in the sera of human patients undergoing radiotherapy, therefore representing a potential biomarker for radiation therapy and providing an opportunity for clinical intervention to improve treatment outcomes.

Improving Localization Accuracy of Neural Sources by Pre-processing: Demonstration With Infant MEG Data.

We discuss specific challenges and solutions in infant MEG, which is one of the most technically challenging areas of MEG studies. Our results can be generalized to a variety of challenging scenarios for MEG data acquisition, including clinical settings. We cover a wide range of steps in pre-processing, including movement compensation, suppression of magnetic interference from sources inside and outside the magnetically shielded room, suppression of specific physiological artifact components such as cardiac artifacts. In the assessment of the outcome of the pre-processing algorithms, we focus on comparing signal representation before and after pre-processing and discuss the importance of the different components of the main processing steps. We discuss the importance of taking the noise covariance structure into account in inverse modeling and present the proper treatment of the noise covariance matrix to accurately reflect the processing that was applied to the data. Using example cases, we investigate the level of source localization error before and after processing. One of our main findings is that statistical metrics of source reconstruction may erroneously indicate that the results are reliable even in cases where the data are severely distorted by head movements. As a consequence, we stress the importance of proper signal processing in infant MEG.

Infant brain imaging using magnetoencephalography: Challenges, solutions, and best practices.

The excellent temporal resolution and advanced spatial resolution of magnetoencephalography (MEG) makes it an excellent tool to study the neural dynamics underlying cognitive processes in the developing brain. Nonetheless, a number of challenges exist when using MEG to image infant populations. There is a persistent belief that collecting MEG data with infants presents a number of limitations and challenges that are difficult to overcome. Due to this notion, many researchers either avoid conducting infant MEG research or believe that, in order to collect high-quality data, they must impose limiting restrictions on the infant or the experimental paradigm. In this article, we discuss the various challenges unique to imaging awake infants and young children with MEG, and share general best-practice guidelines and recommendations for data collection, acquisition, preprocessing, and analysis. The current article is focused on methodology that allows investigators to test the sensory, perceptual, and cognitive capacities of awake and moving infants. We believe that such methodology opens the pathway for using MEG to provide mechanistic explanations for the complex behavior observed in awake, sentient, and dynamically interacting infants, thus addressing core topics in developmental cognitive neuroscience.

The Impact of Mode of Delivery on Maternal and Neonatal Outcomes during Periviable Birth (22-25 Weeks).

OBJECTIVE: The objective of our study was to compare the maternal and neonatal complications of periviable birth by the delivery route. STUDY DESIGN: A retrospective cohort study of periviable deliveries (220/7-256/7weeks) from 2013 to 2020 at a tertiary teaching institution was conducted. Deliveries were grouped by the mode of delivery. Excluded deliveries included pregnancy termination, anomaly, or undesired neonatal resuscitation. The primary composite maternal outcome included death, intensive care admission, sepsis, surgical site infection, unplanned operation, or readmission. Secondary outcomes included maternal blood loss, length of stay, neonatal survival, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP). Outcomes were compared using Student's t-test, Wilcoxon-Mann-Whitney and Chi-squared tests. Relative risk (RR) and 95% confidence intervals were calculated with log-binomial regression. p-Values <0.05 were considered significant. Demographic and intervention variables associated with the outcome and the exposure were included in an adjusted relative risk (aRR) model. Subgroup analyses of singleton pregnancies and 220/7 to 236/7 weeks deliveries were conducted. RESULTS: After exclusion, 230 deliveries were included in the cohort. Maternal characteristics were similar between cohorts. For the primary outcome, cesarean delivery was associated with a trend toward increased maternal morbidity (22.6 vs. 10.7%, RR = 2.11 [1.03-4.43], aRR = 1.95 [0.94-4.03], p-value 0.07). Administration of magnesium sulfate, antenatal corticosteroids, and tocolytics were similar between cohorts. Neonatal survival to discharge was not different between the groups (54/83, 65.1% vs. 118/191, 61.8%, aRR = 0.93 [0.77-1.13]). Among the 172 neonates discharged alive, there was no difference in BPD, IVH, NEC, PDA, ROP, or intact survival. CONCLUSION: Periviable birth has a high rate of maternal morbidity with a trend toward the highest risk among women undergoing cesarean delivery. These risks should be included in shared decision-making. KEY POINTS: · Periviable birth has high maternal morbidity (19%) and is highest after cesarean delivery (23%).. · Route of delivery does not impact neonatal survival or intact neonatal survival.. · Head entrapment is rare during vaginal breech delivery..

Clinical care pathway for the evaluation of patients with suspected VITT after ChAdOx1 nCoV-19 vaccination.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical care pathway was developed to guide clinicians in evaluating for VITT among patients who present with thrombocytopenia or thrombosis symptoms within 4 to 28 days after adenoviral vector vaccine exposure. All patients had enzyme-linked immunosorbent assay (ELISA) testing for platelet factor 4 (PF4) antibodies, and all cases with positive PF4-ELISA or d-dimer levels ≥2.0 mg/L fibrinogen equivalent units (FEU) had further testing for platelet-activating PF4 antibodies using a modified serotonin release assay (SRA). Between 1 May and 30 June 2021, 37% of 68 patients investigated for VITT had thrombosis, but only 3 had VITT confirmed by PF4-ELISA and SRA. Platelet counts, d-dimer levels, and ELISA optical density values were significantly different between those with and without VITT. Three patients had thrombocytopenia and thrombosis with d-dimer levels >4.0 mg/L FEU but had negative PF4-ELISA and SRA results. Patients with VITT were treated successfully with IV immunoglobulin, nonheparin anticoagulants, and corticosteroids. Our pathway demonstrated that thrombosis is common among patients investigated for VITT and that PF4-ELISA testing is necessary to confirm VITT in those presenting with thrombosis and thrombocytopenia.

Exploitation of Sulfated Glycosaminoglycan Status for Precision Medicine of Triplatin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking targetable biomarkers. TNBC is known to be most aggressive and when metastatic is often drug-resistant and uncurable. Biomarkers predicting response to therapy improve treatment decisions and allow personalized approaches for patients with TNBC. This study explores sulfated glycosaminoglycan (sGAG) levels as a predictor of TNBC response to platinum therapy. sGAG levels were quantified in three distinct TNBC tumor models, including cell line-derived, patient-derived xenograft (PDX) tumors, and isogenic models deficient in sGAG biosynthesis. The in vivo antitumor efficacy of Triplatin, a sGAG-directed platinum agent, was compared in these models with the clinical platinum agent, carboplatin. We determined that >40% of TNBC PDX tissue microarray samples have high levels of sGAGs. The in vivo accumulation of Triplatin in tumors as well as antitumor efficacy of Triplatin positively correlated with sGAG levels on tumor cells, whereas carboplatin followed the opposite trend. In carboplatin-resistant tumor models expressing high levels of sGAGs, Triplatin decreased primary tumor growth, reduced lung metastases, and inhibited metastatic growth in lungs, liver, and ovaries. sGAG levels served as a predictor of Triplatin sensitivity in TNBC. Triplatin may be particularly beneficial in treating patients with chemotherapy-resistant tumors who have evidence of residual disease after standard neoadjuvant chemotherapy. More effective neoadjuvant and adjuvant treatment will likely improve clinical outcome of TNBC.

On the Biology of Werner's Complex.

Werner's Complex, as a cationic coordination complex (CCC), has hitherto unappreciated biological properties derived from its binding affinity to highly anionic biomolecules such as glycosaminoglycans (GAGs) and nucleic acids. Competitive inhibitor and spectroscopic assays confirm the high affinity to GAGs heparin, heparan sulfate (HS), and its pentasaccharide mimetic Fondaparinux (FPX). Functional consequences of this affinity include inhibition of FPX cleavage by bacterial heparinase and mammalian heparanase enzymes with inhibition of cellular invasion and migration. Werner's Complex is a very efficient condensing agent for DNA and tRNA. In proof-of-principle for translational implications, it is demonstrated to display antiviral activity against human cytomegalovirus (HCMV) at micromolar concentrations with promising selectivity. Exploitation of non-covalent hydrogen-bonding and electrostatic interactions has motivated the unprecedented discovery of these properties, opening new avenues of research for this iconic compound.

Inexpensive Near-Infrared Fluorimeters: Enabling Translation of nIR-Based Assays to the Field.

The practical impact of analytical probes that transduce in the near-infrared (nIR) has been dampened by the lack of cost-effective and portable nIR fluorimeters. Herein, we demonstrate straightforward designs for an inexpensive microplate reader and a portable fluorimeter. These instruments require minimally complex machining and fabrication and operate with an open-source programming language (Python). Complete wiring diagrams, assembly diagrams, and scripts are provided. To demonstrate the utility of these two instruments, we performed high-throughput and field-side measurements of soil samples to evaluate the effect of soil management strategies on extracellular proteolytic, cellulolytic, and lignin-modifying activities. This was accomplished with fluorescent enzyme probes that utilized uniquely sensitive transducers exclusive to the nIR spectrum, single-walled carbon nanotubes. We also used the portable fluorimeter to evaluate spatial variations of proteolytic activity within individual field plots, while minimizing the effects of soil storage and handling. These demonstrations indicate the utility of these fluorimeters for translating analytical probes that operate in the nIR beyond the laboratory and into actual use.

Conformational Modulation of Iduronic Acid-Containing Sulfated Glycosaminoglycans by a Polynuclear Platinum Compound and Implications for Development of Antimetastatic Platinum Drugs.

1 H NMR spectroscopic studies on the 1:1 adduct of the pentasaccharide Fondaparinux (FPX) and the substitution-inert polynuclear platinum complex TriplatinNC show significant modulation of geometry around the glycosidic linkages of the FPX constituent monosaccharides. FPX is a valid model for the highly sulfated cell signalling molecule heparan sulfate (HS). The conformational ratio of the 1 C4 :2 S0 forms of the FPX residue IdoA(2S) is altered from ca. 35:65 (free FPX) to ca. 75:25 in the adduct; the first demonstration of a small molecule affecting conformational changes on a HS oligosaccharide. Functional consequences of such binding are suggested to be inhibition of HS cleavage in MDA-MB-231 triple-negative breast cancer (TNBC) cells. We further describe inhibition of metastasis by TriplatinNC in the TNBC 4T1 syngeneic tumour model. Our work provides insight into a novel approach for design of platinum drugs (and coordination compounds in general) with intrinsic anti-metastatic potential.

The leaving group in Au(I)-phosphine compounds dictates cytotoxic pathways in CEM leukemia cells and reactivity towards a Cys2His2 model zinc finger.

Gold(i)-phosphine "auranofin-like" compounds have been extensively explored as anticancer agents in the past decade. Although potent cytotoxic agents, the lack of selectivity towards tumorigenic vs. non-tumorigenic cell lines often hinders further application. Here we explore the cytotoxic effects of a series of (R3P)AuL compounds, evaluating both the effect of the basicity and bulkiness of the carrier phosphine (R = Et or Cy), and the leaving group L (Cl-vs. dmap). [Au(dmap)(Et3P)]+ had an IC50 of 0.32 µM against the CEM cell line, with good selectivity in relation to HUVEC. Flow cytometry indicates reduced G1 population and slight accumulation in G2, as opposed to auranofin, which induces a high population of cells with fragmented DNA. Protein expression profile sets [Au(dmap)(Et3P)]+ further apart from auranofin, with proteolytic degradation of caspase-3 and poly(ADP-ribose)-polymerase (PARP), DNA strand-break induced phosphorylation of Chk2 Thr68 and increased p53 ser15 phosphorylation. The cytoxicity and observable biological effects correlate directly with the reactivity trend observed when using the series of gold(i)-phosphine compounds for targeting a model zinc finger, Sp1 ZnF3.

Ru(II)-Naphthoquinone complexes with high selectivity for triple-negative breast cancer.

Six new ruthenium(ii) complexes with lapachol (Lap) and lawsone (Law) with the general formula [Ru(L)(P-P)(bipy)]PF6, where L = Lap or Law, P-P = 1,2'-bis(diphenylphosphino)ethane (dppe), 1,4'-bis(diphenylphosphino)butane (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppf) and bipy = 2,2'-bipyridine, were synthesized, fully characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis, IR spectroscopies and three of them by X-ray crystallography. All six complexes were active against breast (MCF-7 and MDA-MB-231) and prostate (DU-145) cancer cell lines with lower IC50 values than cisplatin. Complex [Ru(Lap)(dppe)(bipy)]PF6 (1a) showed significant selectivity for MDA-MB-231, a model of triple-negative breast cancer (TNBC), as compared to the "normal-like" human breast epithelial cell line, MCF-10A. Complex (1a) inhibited TNBC colony formation and induced loss of cellular adhesion. Furthermore, the complex (1a) induced mitochondrial dysfunction and generation of ROS, as is involved in the apoptotic cell death pathway. Preferential cellular uptake of complex (1a) was observed in MDA-MB-231 cells compared to MCF-10A cells, consistent with the observed selectivity for tumorigenic vs. non-tumorigenic cells. Taken together, these results indicate that ruthenium complexes containing lapachol and lawsone as ligands are promising candidates as chemotherapeutic agents.