In Silico Screening and Experimental Verification of Near-Infrared-Emissive Two-Boron-Doped Polycyclic Aromatic Hydrocarbons.

Embedding two boron atoms into a polycyclic aromatic hydrocarbon (PAH) leads to the formation of a neutral analogue that is isoelectronic to the corresponding dicationic PAH skeleton, which can significantly alter its electronic structure. Based on this concept, we explore herein the identification of near-infrared (NIR)-emissive PAHs with the aid of an in silico screening method. Using perylene as the PAH scaffold, we embedded two boron atoms and fused two thiophene rings to it. Based on this design concept, all possible structures (ca. 2500 entities) were generated using a comprehensive structure generator. Time-dependent DFT calculations were conducted on all these structures, and promising candidates were extracted based on the vertical excitation energy, transition dipole moment, and atomization energy per bond. One of the extracted dithieno-diboraperylene candidates was synthesized and indeed exhibited emission at 724 nm with a quantum yield of 0.40 in toluene, demonstrating the validity of this screening method. This modification was further applied to other PAHs, and a series of thienobora-modified PAHs was synthesized.

Abnormal Vaginal Cytology after Total Laparoscopic Hysterectomy in Patients with Cervical Intraepithelial Neoplasia.

To explore the incidence of abnormal vaginal cytology after total laparoscopic hysterectomy for the treatment of cervical intraepithelial neoplasia 3, we retrospectively analyzed the medical records of patients treated at NHO Shikoku Cancer Center (Japan) in 2014-2019. The cases of 99 patients who underwent a laparoscopic (n=36) or open (n=63) hysterectomy and postoperative follow-up were examined. Abnormal vaginal cytology was detected in 13.9% (5/36) of the laparoscopic-surgery (LS) group and 14.3% (9/63) of the open-surgery (OS) group. A vaginal biopsy was performed at the physicians' discretion; one LS patient and six OS patients were diagnosed with vaginal intraepithelial neoplasia. The cumulative incidence of abnormal vaginal cytology at 3 years post-hysterectomy was 21.4% (LS group) and 20.5% (OS group), a nonsignificant difference. A multivariate analysis showed that age > 50 years was the only independent risk factor for abnormal vaginal cytology among the covariates examined including age; body mass index; histories of vaginal delivery, abdominal surgery, and smoking; and surgical approach (hazard ratio 8.11; 95% confidence interval 1.73-37.98; p=0.01). These results suggest that the occurrence of abnormal vaginal cytology after a hysterectomy may not be influenced by the laparoscopic procedure but is associated with older age.

Handling of Germline Findings in Clinical Comprehensive Cancer Genomic Profiling.

Patients found to have presumed germline pathogenic variants (PGPVs) during comprehensive genomic profiling (CGP) require genetic counseling (GC) referrals. We retrospectively investigated the outcomes of patients with PGPVs. Among 159 patients who underwent CGP, we recommended GC for the 16 patients with PGPVs (3 with [FG group] and 13 without [G Group] a family/personal history of hereditary cancer) as well as for the 8 patients with no PGPVs, but a history (F group); 2 (67%), 5 (38%), and 3 (38%) patients received GC in the FG, G, and F groups, respectively. Germline testing results were positive in 1 and 2 patients of the FG and G groups, respectively. Among the patients recommended for GC, 58% did not receive GC due to lack of interest, poor performance status, or death. CGP contributes to the identification of germline variants in patients without a history of hereditary cancer. However, the proportion of patients who undergo GC should be improved.

Multiple resonance type thermally activated delayed fluorescence by dibenzo [1,4] azaborine derivatives.

We studied the photophysical and electroluminescent (EL) characteristics of a series of azaborine derivatives having a pair of boron and nitrogen aimed at the multi-resonance (MR) effect. The computational study with the STEOM-DLPNO-CCSD method clarified that the combination of a BN ring-fusion and a terminal carbazole enhanced the MR effect and spin-orbit coupling matrix element (SOCME), simultaneously. Also, we clarified that the second triplet excited state (T2) plays an important role in efficient MR-based thermally activated delayed fluorescence (TADF). Furthermore, we obtained a blue-violet OLED with an external EL quantum efficiency (EQE) of 9.1%, implying the presence of a pronounced nonradiative decay path from the lowest triplet excited state (T1).

Frequency and clinical features of deficient mismatch repair in ovarian clear cell and endometrioid carcinoma.

OBJECTIVE: To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). METHODS: We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. RESULTS: MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. CONCLUSION: The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

Planarized Phenyldithienylboranes: Effects of the Bridging Moieties and π-Extension on the Photophysical Properties and Lewis Acidity.

Two kinds of planarized phenyldithienylboranes, which contain (CH3 )2 C- or CH2 -bridging moieties, were synthesized. The difference of the bridging moieties affects their packing structures and photophysical properties. In particular, the (CH3 )2 C-bridged derivative exhibits a large Stokes shift, unusual for such planarized compounds, that results from a large structural relaxation in the excited state. A series of π-extended derivatives was synthesized, among which a p-(diphenylamino)phenyl-substituted derivative shows large solvatochromism in the fluorescence spectra, while maintaining high quantum yields even in polar solvents. The Lewis acidity of the phenyldithienylborane derivatives was also assessed by titration with pyridine. The Lewis acidity of the boron center is affected not only by the difference in the steric bulk of the bridging moieties, but also by the electronic effect of the substituents introduced at remote positions relative to the boron atom. These results demonstrate the characteristic features of planarized phenyldithienylboranes as building blocks for boron-based π-electron materials.

Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report.

BACKGROUND: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development. CASE PRESENTATION: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma. CONCLUSIONS: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.

Rapid modification of antibodies on the surface of liposomes composed of high-affinity protein A-conjugated phospholipid for selective drug delivery.

Antibody-modified liposomes, immuno-liposomes, can selectively deliver encapsulated drug 'cargos' to cells via the interaction of cell surface proteins with antibodies. However, chemical modification of both the antibodies and phospholipids is required for the preparation of immuno-liposomes for each target protein using conventional methods, which is time-consuming. In the present study, we demonstrated that high-affinity protein A- (Protein A-R28: PAR28) displaying liposomes prepared by the post-insertion of PAR28-conjugated phospholipid through polyethylene glycol (PEG)-linkers (PAR28-PEG-lipo) can undergo rapid modification of antibodies on their surface, and the liposomes can be delivered to cells based on their modified antibodies. Anti-CD147 and anti-CD31 antibodies could be modified with PAR28-PEG-lipo within 1 h, and each liposome was specifically taken up by CD147- and CD31-positive cells, respectively. The cellular amounts of doxorubicin delivered by anti-CD147 antibody-modified PAR28-PEG-lipo were significantly higher than those of isotype control antibody-modified liposomes. PAR28-PEG-lipo can easily and rapidly undergo modification of various antibodies on their surface, which then makes them capable of selective drug delivery dependent on the antibodies.

Regio- and Stereoselective 1,2-Carboboration of Ynamides with Aryldichloroboranes.

Catalyst-free 1,2-carboboration of ynamides is presented. Readily available aryldichloroboranes react with alkyl- or aryl-substituted ynamides in high yields with complete regio- and stereoselectivity to valuable ß-boryl-ß-alkyl/aryl α-aryl substituted enamides which belong to the class of trisubstituted alkenylboronates. The 1,2-carboboration reaction is experimentally easy to conduct, shows high functional group tolerance and broad substrate scope. Gram-scale reactions and diverse synthetic transformations convincingly demonstrate the synthetic potential of this method. The reaction can also be used to access 1-boraphenalenes, a class of boron-doped polycyclic aromatic hydrocarbons.

Electron-Deficient Heteroacenes that Contain Two Boron Atoms: Near-Infrared Fluorescence Based on a Push-Pull Effect*.

Electron-deficient heteroacenes that contain two tricoordinate boron atoms in their acene skeletons and planarized phenyl ether moieties at their periphery were synthesized via the borylation of silicon-bridged precursors. X-ray crystallographic analysis revealed quinoidal structures, which give rise to two-step reversible redox processes for both the reduction and oxidation. These compounds exhibit intense absorption and sharp fluorescence bands with vibronic structures in the near-infrared (NIR) region. These properties originate from the push-pull effect along the long axis of the molecule derived from the electron-donating ether moieties and the electron-accepting boron moieties. Of particular note is the NIR emission of the thienothiophene-centered heteroacene, which has a maximum at 952 nm with a narrow band width of 309 cm-1 in cyclohexane. A Franck-Condon analysis revealed the crucial role of the sterically less-hindered thienothiophene spacer in achieving this sharp emission band.

Twofold C-H Activation Enables Synthesis of a Diazacoronene-Type Fluorophore with Near Infrared Emission Through Isosteric Replacement.

The synthesis and photophysical properties of a soluble amide-embedded coronene is reported. The key step in this synthesis is the twofold C-H activation of diazaperylene by a rhodium(III)Cp* catalyst. This unprecedented structural motif shows intense fluorescence in the near infrared region with a small Stokes shift and a distinct vibronic structure, which exhibits a slight extent of negative solvatochromism. Comparison of this compound with some relevant compounds revealed the importance of the amide incorporation in the peripheral concave region including an angular position to retain high aromaticity reflecting that of parent coronene. Treatment of this compound with Lewis acid B(C6 F5 )3 formed a bis-adduct, which exhibited enhanced aromaticity as a consequence of the increased double bond character of the amide C-N bonds.

Uterine leiomyosarcoma well-controlled with eribulin mesylate.

Uterine leiomyosarcoma is a rare type of malignant gynecological tumor and has a poor prognosis; therefore, this tumor is often difficult to treat. Some new drugs have been approved during the past several years in Japan and are expected to be efficacious. Eribulin, one of these drugs, is a natural product of halichondrin B, which is isolated from a marine sponge. A recent clinical trial comparing eribulin with dacarbazine to target liposarcoma and leiomyosarcoma indicated that overall survival (OS) was prolonged by treatment with eribulin. We report a case of uterine progressive leiomyosarcoma that responded to eribulin. A 57-year-old woman was suspected of having leiomyosarcoma based on an endometrial biopsy and imaging examinations. Although the tumor grew toward the uterine artery on the right side of the uterine cervix, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy to obtain an outcome of no gross residual disease. However, the margin of the right side of the uterine cervix was histologically positive, so leiomyosarcoma stage IIB (pT2bcN0cM0, FIGO2008) was diagnosed. Gemcitabine and docetaxel therapy was administered postoperatively. However, after three cycles, the residual tumor progressed. Other anticancer drugs were administered but were ineffective. We administered eribulin (1.4 mg/m2) as a fourth-line regimen, and the mass decreased by 32% after four cycles. However, the residual tumor continued to grow after eight cycles. The only adverse event associated with eribulin treatment was mild, grade 2 neutropenia. For our patient, eribulin was effective for her recurrent leiomyosarcoma. In selecting chemotherapy, there are currently no fixed guidelines; we should consider the characteristics and adverse events associated with each drug and patient performance status and comorbidities. In this patient, eribulin was associated with few adverse events, an easy route of administration and a good quality of life. Therefore, eribulin is expected to be efficacious for the treatment of gynecologic sarcoma.

Planarized B,N-phenylated dibenzoazaborine with a carbazole substructure: electronic impact of the structural constraint.

A B,N-diphenyl-5,10-dihydro-dibenzo-1,4-azaborine, in which both phenyl groups on the boron and nitrogen atoms are planarized to generate a carbazole substructure, was synthesized. The structral constraint around the boron and nitrogen atoms alters the π-conjugation mode and thus the photophysical and electrochemical properties. Specifically, this structurally constrained dibenzoazaborine showed an intense blue emission with a narrow full width at half maximum. One of its derivatives exhibited near infrared absorption in the one-electron-oxidized state.

Structurally Constrained Boron-, Nitrogen-, Silicon-, and Phosphorus-Centered Polycyclic π-Conjugated Systems.

Incorporation of main group elements into the π-conjugated frameworks is a sophisticated strategy to alter the fundamental nature of the parent conjugated π-systems, giving rise to attractive electronic and photophysical properties that are otherwise inaccessible with classic carbon- or metal-based materials. Out of all π-conjugated heterocycles, those that are structurally constrained by tethered aryl substituents surrounding the main group center deserve a great deal of attention because not only do they commonly possess the maximum efficiency of π-conjugation and intermolecular interaction, but they also enjoy remarkable thermal and morphological stabilities that are especially crucial for solid-state performances. In certain cases, elucidation of the behavior of such compounds may additionally provide sufficient perspective toward graphene materials doped with main group elements, which are widely considered as potential next-generation optoelectronic materials. In this review, we will specifically focus on historical developments of structurally constrained polycyclic π-electron systems particularly of those with boron, nitrogen, silicon, or phosphorus atoms annulated directly into the center of π-conjugated systems.

Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

BACKGROUND: Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. CASE PRESENTATION: Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. CONCLUSIONS: Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

Long-term outcomes of postoperative taxane/platinum chemotherapy for early stage cervical cancer: a retrospective study.

BACKGROUND: Taxane/platinum (TP)-based combination chemotherapy is standard for the treatment of metastatic or recurrent cervical cancer. The aim of this study was to investigate the efficacy of postoperative TP therapy in early stage cervical cancer. METHODS: A retrospective review of patients with FIGO IB-IIB stage cervical cancer who were treated with radical hysterectomy and displayed surgical-pathological risk factors was performed. 122 patients were identified between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to investigate predictors of survival. RESULTS: The median follow-up period was 82.4 months. The postoperative adjuvant therapy was TP in 82 (67.2%) patients, other chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to the postoperative adjuvant therapy. The estimated 5-year overall survival was 95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT group, and 100% in the NFT group. No significant difference of survival was observed in the subgroups. However, when analyzing only patients who displayed high-risk factors, non-TP adjuvant therapy (including RT and other chemotherapies) was independently associated with shorter survival on multivariate analysis. In the TP group, multivariate analysis revealed that a positive surgical margin was a significant predictor of shorter survival. CONCLUSIONS: Postoperative TP is effective in patients with surgically treated early stage cervical cancer. In these populations, a positive surgical margin could be associated with poor prognosis.

Predictors of distant relapse in patients with FIGO stage IIB-IVA cervical cancer treated with definitive radiotherapy.

AIM: To investigate the predictors of distant relapse in International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer patients treated with definitive radiotherapy (RT). METHODS: The clinical data of 219 patients with FIGO stage IIB-IVA cervical cancer treated with definitive RT between January 1997 and December 2011 were retrospectively reviewed. The cumulative distant relapse, progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to investigate the predictors of distant relapse in patients. RESULTS: Following treatment with definitive RT, 61 of the 219 (27.9%) patients developed distant relapse with median PFS and OS rates of 9.9 and 32.8 months, and estimated five-year PFS and OS rates of 4.9% and 21.3%, respectively. Multivariate analysis revealed that pelvic node metastasis, pretreatment leukocytosis and pretreatment neutrophilia were significant predictors of distant relapse. The risk of developing distant relapse was found to be associated with the number of predictors that the patients displayed: the estimated five-year distant relapse rates of the patients with no predictors, one predictor and two predictors were 20.3%, 35.5% and 88.9%, respectively. CONCLUSIONS: Roughly 28% of patients with FIGO stage IIB-IVA cervical cancer developed distant relapse after definitive RT. Pelvic lymph node metastasis and pretreatment leukocytosis/neutrophilia are independent predictors of distant relapse.

[Safety and Efficacy of Cisplatin Treatment after Carboplatin Hypersensitivity Reactions in Gynecologic Malignancies].

To investigate the safety and efficacy of cisplatin(CDDP)treatment after carboplatin(CBDCA)hypersensitivity reactions (CHSR)in gynecologic malignancies, we retrospectively reviewed the clinical records of 544 patients who underwent paclitaxel and CBDCA therapy(TC therapy). CHSR was observed in 18 patients. Eight patients were administered weekly paclitaxel and CDDP therapy(wTP therapy)continuously, to confirm that there was no CDDP hypersensitivity followingintravenous administration of 10 mgCDDP. At the onset of CHSR, the patients had received a median of 9 TC therapy cycles, and the median number of CBDCA administrations was 14. The frequency of CHSR was significantly higher in patients who received 7 cycles or more of TC therapy and CBDCA administration(p<0.0001). The median number of wTP therapy administrations was 8. Although CDDP hypersensitivity reactions were observed in 2 patients, their symptoms were mild(Grade 2, CTCAE v4.0). Of the 6 patients who received wTP therapy and had evaluable disease sites, 1, 2, 2 and 1 patients showed CR, PR, SD, and PD, respectively. The median progression-free survival in these 6 patients was 9.5 months. For patients with the platinum- sensitive disease who have CHSR, CDDP could improve their prognosis.

Beta-agonist residues in cattle, chicken and swine livers at the wet market and the environmental impacts of wastewater from livestock farms in Selangor State, Malaysia.

Fourteen beta-agonists were quantitatively analyzed in cattle, chicken and swine liver specimens purchased at 14 wet markets in Selangor State, Malaysia, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The health risks of ractopamine and clenbuterol residues in the Malaysian population were assessed based on quantitative data and meat consumption statistics in Malaysia. Wastewater samples collected at swine farms (n = 2) and cattle/cow farms (n = 2) in the Kuala Langat district were analyzed for the presence for the 14 compounds. Wastewater in chicken farms was not collected because there was negligible discharge during the breeding period. The environmental impacts caused by beta-agonists discharged from livestock farms were spatially assessed in the Langat River basin using a geographic information system (GIS). As a result, 10 compounds were detected in the liver specimens. Ractopamine, which is a permitted compound for swine in Malaysia, was frequently detected in swine livers; also, 9 other compounds that are prohibited compounds could be illegally abused among livestock farms. The health risks of ractopamine and clenbuterol were assessed to be minimal as their hazard quotients were no more than 7.82 × 10-4 and 2.71 × 10-3, respectively. Five beta-agonists were detected in the wastewater samples, and ractopamine in the swine farm resulted in the highest contamination (30.1 µg/L). The environmental impacts of the beta-agonists in the Langat River basin were generally concluded to be minimal, but the ractopamine contamination released from swine farms was localized in coastal areas near the estuary of the Langat River basin because most swine farms were located in that region.

The potential of vitamin K3 as an anticancer agent against breast cancer that acts via the mitochondria-related apoptotic pathway.

PURPOSE: We tried to clarify the cytotoxic mechanism of VK(3) using the breast cancer cell line MCF-7. METHODS: Cytotoxicity was measured via intracellular esterase activity. DNA fragmentation was assessed by agarose gel electrophoresis. JC-1 staining was applied to measure mitochondrial dysfunction. Caspase activation and reactive oxidative species (ROS) generation were also measured. RESULTS: VK(3) exhibited cytotoxicity that caused DNA fragmentation in MCF-7 cells with an IC(50) of 14.2 microM. JC-1 staining revealed that VK(3) caused mitochondrial dysfunction including a disappearance of mitochondrial membrane potential. Additional investigation showed that the mitochondrial damage was induced by the generation of ROS and the subsequent activation of caspase-7 and -9. CONCLUSIONS: Our findings demonstrate that VK(3)-induced apoptosis is selectively initiated by the mitochondria-related pathway and might be useful in breast cancer chemotherapy.