Promoting Apoptosis in MCF-7 Cells via ROS Generation by Quinolino-triazoles Derived from One-Pot Telescopic Synthesis.

Inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) facilitates potent antiangiogenic and anticancer responses. In this regard, the development of effective pharmacophores, i.e.

US Food and Drug Administration Approval Summary: Eflornithine for High-Risk Neuroblastoma After Prior Multiagent, Multimodality Therapy.

On December 13, 2023, the US Food and Drug Administration (FDA) approved eflornithine (IWILFIN, US WorldMeds) to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. The approval was based on an externally controlled trial (ECT) consisting of a single-arm trial, study 3(b), compared with an external control (EC) derived from a National Cancer Institute/Children's Oncology Group-sponsored clinical trial (Study ANBL0032) and supported by confirmatory evidence. In the protocol-specified primary analysis, the event-free survival hazard ratio (HR) was 0.

Catalytic Tetrazole Synthesis via [3+2] Cycloaddition of NaN to Organonitriles Promoted by Co(II)-complex: Isolation and Characterization of a Co(II)-diazido Intermediate.

The [3+2] cycloaddition of sodium azide to nitriles to give 5-substituted 1H-tetrazoles is efficiently catalyzed by a Cobalt(II) complex () with a tetradentate ligand ,-bis(pyridin-2-ylmethyl)quinolin-8-amine. Detailed mechanistic investigation shows the intermediacy of the cobalt(II) diazido complex (), which has been isolated and structurally characterized. Complex also shows good catalytic activity for the synthesis of 5-substituted 1H-tetrazoles.

Nonheme Fe═O Complexes Supported by Four Pentadentate Ligands: Reactivity toward H- and O- Atom Transfer Processes.

Four new pentadentate N5-donor ligands, [-(1-methyl-2-imidazolyl)methyl--(2-pyridyl)-methyl--(bis-2-pyridylmethyl)-amine] (), [-bis(1-methyl-2-imidazolyl)methyl--(bis-2-pyridylmethyl)amine] (), (-(isoquinolin-3-ylmethyl)-1,1-di(pyridin-2-yl)--(pyridin-2-ylmethyl)methanamine (), and ,-bis(isoquinolin-3-ylmethyl)-1,1-di(pyridin-2-yl)methanamine (), have been synthesized based on the N4Py ligand framework, where one or two pyridyl arms of the N4Py parent are replaced by (-methyl)imidazolyl or -(isoquinolin-3-ylmethyl) moieties. Using these four pentadentate ligands, the mononuclear complexes [Fe(CHCN)()] (), [Fe(CHCN)()] (), [Fe(CHCN)()] (), and [Fe(CHCN)()] () have been synthesized and characterized. The half-wave potentials () of the complexes become more positive in the order: < < ≤ ≤ [Fe(N4Py)(CHCN)].

FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC.

On October 15, 2021, the FDA approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have programmed cell death ligand 1 (PD-L1) expression on ≥1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1,005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomly assigned 1:1 to receive atezolizumab for 16 cycles or best supportive care. The primary endpoint of disease-free survival (DFS) as assessed by investigator was tested hierarchically in the following analysis populations: stage II-IIIA NSCLC with PD-L1 expression on ≥1% of TCs (PD-L1 ≥ 1% TC); all randomly assigned patients with stage II-IIIA NSCLC; and the intent-to-treat population comprising all randomly assigned patients.

Hydrogen-atom and oxygen-atom transfer reactivities of iron(IV)-oxo complexes of quinoline-substituted pentadentate ligands.

A series of iron(II) complexes with the general formula [Fe()(L)] ( = 1, L = F, Cl; = 2, L = NCMe, HO) have been isolated and characterized. The X-ray crystallographic data reveals that metal-ligand bond distances vary with varying ligand field strengths of the sixth ligand. While the complexes with fluoride, chloride and water as axial ligand are high spin, the acetonitrile-coordinated complex is in a mixed spin state.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

Purpose: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.

Methods: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included.

Subgroup Analyses in Oncology Trials: Regulatory Considerations and Case Examples.

Subgroup analyses are assessments of treatment effects based on certain patient characteristics out of the total study population and are important for interpretation of pivotal oncology trials. However, appropriate use of subgroup analyses results for regulatory decision-making and product labeling is challenging. Typically, drugs approved by the FDA are indicated for use in the total patient population studied; however, there are examples of restriction to a subgroup of patients despite positive study results in the entire study population and also extension of an indication to the entire study population despite positive results appearing primarily in one or more subgroups.

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma.

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma-related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51-79) with at least 12 months of follow-up.

Development of novel alternative hair dyes to hazardous para-phenylenediamine.

Most of the permanent hair dye products contain p-phenylenediamine (PPD), a well-known skin sensitizer. PPD may cause cutaneous reactions and leads to allergic contact dermatitis (ACD), a condition with major medical and financial repercussions. Hair dye-induced ACD represents a growing concern both for consumers and the cosmetics industry.

Direct C-H bond halogenation and pseudohalogenation of hydrocarbons mediated by high-valent 3d metal-oxo species.

Late-stage direct functionalization of the C-H bond is synthetically desirable. Metalloenzymes having metal-oxo active sites are well known to selectively catalyze hydroxylation and halogenation reactions with high efficiency. This review highlights the recent developments in the field of direct C-H halogenation and pseudohalogenation reactions catalyzed by the functional models of metalloenzymes.

Semi-bridging σ-silyls as Z-type ligands.

The reactions of SiHPh(NCHPPh)CH-1,2 with a range of zerovalent group 10 reagents afford the homoleptic bimetallic complexes [M{μ-κ-Si,P,P'-SiPh(CHPPh)CH}] (M = Ni, Pd, Pt) in which the M-M bond is unsymmetrically bridged by two σ-silyl groups. The asymmetry of the MSi core increases from Ni through Pd to Pt and is consistent with a bonding description in which one metal acts as an electron pair donor to a trigonal bipyramidal 'Z-type' silicon centre, reminsicent of semi-bridging coordination by CO, carbynes and boryl ligands.

Structural Characterization of a Series of N5-Ligated Mn -Oxo Species.

Analysis of extended X-ray absorption fine structure (EXAFS) data for the Mn -oxo complexes [Mn (O)( N4py)] , [Mn (O)(2pyN2B)] , and [Mn (O)(2pyN2Q)] ( N4py=N,N-bis(4-methoxy-3,5-dimethyl-2-pyridylmethyl)-N-bis(2-pyridyl)methylamine; 2pyN2B=(N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2-pyridylmethyl)amine, and 2pyN2Q=N,N-bis(2-pyridyl)-N,N-bis(2-quinolylmethyl)methanamine) afforded Mn=O and Mn-N bond lengths. The Mn=O distances for [Mn (O)( N4py)] and [Mn (O)(2pyN2B)] are 1.72 and 1.

Adaptive group-sequential design with population enrichment in phase 3 randomized controlled trials with two binary co-primary endpoints.

The use of co-primary endpoints in drug development allows investigators to capture an experimental intervention's multidimensional effect more comprehensively than a single primary endpoint. We propose the theoretical basis and development of an adaptive population enrichment design with co-primary endpoints, provide stage-wise boundary values for futility and efficacy, and discuss power under different efficacy configurations, subgroup prevalence, and analysis times using a pre-specified decision criterion. We considered a two-arm, two-stage, parallel group design where population enrichment occurs at the interim analysis by dropping any non-responsive subgroups.

Mn-Oxo complex of a bis(benzimidazolyl)-containing N5 ligand reveals different reactivity trends for Mn-oxo than Fe-oxo species.

Using the pentadentate ligand (N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2-pyridylmethyl)amine, 2pyN2B), presenting two pyridyl and two (N-methyl)benzimidazolyl donor moieties in addition to a central tertiary amine, new MnII and MnIV-oxo complexes were generated and characterized. The [MnIV(O)(2pyN2B)]2+ complex showed spectroscopic signatures (i.e.

Genetic Counseling Referral Rates in Long-Term Survivors of Triple-Negative Breast Cancer.

Inherited gene mutations (pathogenic variants) cause 10% of breast cancers. pathogenic variants predispose carriers to triple-negative breast cancer (TNBC); around 30% of patients with TNBC carry pathogenic variants. The 2018 NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian recommend genetic counseling referrals for patients with TNBC diagnosed at age ≤60 years.

Volatility and Chain Length Interplay of Primary Amines: Mechanistic Investigation on the Stability and Reversibility of Ammonia-Responsive Hybrid Perovskites.

Hybrid organic-inorganic perovskites possess promising signal transduction properties, which can be exploited in a variety of sensing applications. Interestingly, the highly polar nature of these materials, while being a bane in terms of stability, can be a boon for sensitivity when they are exposed to polar gases in a controlled atmosphere. However, signal transduction during sensing induces irreversible changes in the chemical and physical structure, which is one of the major lacuna preventing its utility in commercial applications.

Determinants of Weight Gain During Adjuvant Endocrine Therapy and Association of Such Weight Gain With Recurrence in Long-term Breast Cancer Survivors.

Background: Weight gain is a negative prognostic factor in breast cancer (BC) patients. The risk factors for weight gain during adjuvant endocrine therapy (ET) and the extent to which such weight gain is associated with disease recurrence remain unclear.

Patients And Methods: We retrospectively identified a cohort of women with a diagnosis of stage I-III, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC from January 1997 to August 2008, who had received initial treatment at the MD Anderson Cancer Center, had completed 5 years of ET, and had remained free of locoregional or distant relapse or contralateral BC for ≥ 5 years after diagnosis.

Medication Regimen Complexity and Low Adherence in Older Community-Dwelling Adults With Substantiated Self-Neglect.

Objective: Determine whether medication regimen complexity predicts medication adherence levels in a sample of community-dwelling adults 65 years and older with Adult Protective Services-substantiated self-neglect.

Methods: A cross-sectional analysis of baseline data ( N = 31 participants) from a pilot intervention to increase medication adherence among the target group was performed. The Medication Regimen Complexity Index (MRCI) and the 8-item Morisky Medication Adherence Scale (MMAS-8)™ were the primary independent and dependent measures, respectively.

Larval infestation in a common Pariah Kite (Boddaert).

This paper describes a case of larval infestation in a common Pariah Kite (Boddaert). Examination on the larvae revealed that the larvae were of the family Sarcophagidae (Diptera).

Outcomes in patients with early-stage breast cancer who underwent a 21-gene expression assay.

Background: Invasive disease-free survival (IDFS) rates are excellent in patients with breast cancer (BC) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), axillary lymph node-negative (LN-) tumors with a 21-gene expression assay recurrence score (RS) of 0 to 10. However, to the authors' knowledge, the outcomes among patients with an RS of 11 to 25 who are treated with endocrine therapy alone are unknown.

Methods: In this retrospective single-institution study, the authors described the characteristics of patients with HR+, HER2-, LN- BC who underwent a 21-gene expression assay.

Inter-ligand electronic coupling mediated through a dimetal bridge: dependence on metal ions and ancillary ligands.

A series of Mo, Ru, Rh and Cu complexes with redox-active NP-R [2-(2-R)-1,8-naphthyridine; R = pyrazinyl (NP-pz, L) and thiazolyl (NP-tz, L)] ligands have been synthesized and characterized by X-ray crystallography and spectroscopic methods. Two NP-R ligands wrap the dimetal core by occupying four equatorial positions and two axial sites. The remaining four equatorial sites are engaged by bridging acetates in quadruply bonded cis-[Mo(L)(OAc)][BF] (1), cis-[Mo(L)(OAc)][BF] (1A), doubly bonded cis-[Ru(L)(OAc)][ClO] (3), cis-[Ru(L)(OAc)][ClO] (3A) and singly bonded trans-[Rh(L)(OAc)][BF] (5) and trans-[Rh(L)(OAc)][BF] (5A).

Location of Receipt of Initial Treatment and Outcomes in Long-Term Breast Cancer Survivors.

Purpose: Cancer outcomes differ depending on where treatment is received. We assessed differences in outcomes in long-term breast cancer survivors at a specialty care hospital by location of their initial treatment.

Methods: We retrospectively examined a cohort of women diagnosed with invasive early-stage breast cancer who did not experience recurrence for at least 5 years after the date of diagnosis and were evaluated at The University of Texas MD Anderson Cancer Center between January 1997 and August 2008.