Ruthenium, copper and ruthenium-copper complexes of an unsymmetrical phosphino pyridyl 1,8-naphthyridine PNNN ligand.

A new unsymmetrical dinucleating phosphino pyridyl 1,8-naphthyridine ligand PNNN is reported. Reaction with CuCl gave the dicopper complex [Cu(μ-Cl)(PNNN)] (1). In contrast, complexation of [RuCl(cymene)] yielded a monometallic species [RuCl(cymene)(PNNN)]Cl ([2]Cl) in which the Ru is bound to the κ-N,N, rather than κ-P,N, binding pocket.

Expedient Decagram-Scale Synthesis of Robust Organic Cages That Bind Sulfate Strongly and Selectively in Water.

Selective anion recognition remains a key challenge in supramolecular chemistry: only a very small number of systems that can function in water are known, and these nearly always preferentially bind hydrophobic anions. In this work, we report three robust hexa-cationic cages that can be prepared on scales up to 14 g in two simple and high-yielding steps from commercially available materials. One of these cages displays unusually strong sulfate binding in water ( = 12,000 M), and demonstrates high selectivity for this anion over HPO/HPO in DMSO/buffer mixtures.

The Effect of Neoadjuvant Systemic Therapy on Surgical Outcomes After Lymph Node Dissections for Stage III Melanoma; An Australian Cohort.

Background: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes.

Methods: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database.

Utilising a Proton-Responsive 1,8-Naphthyridine Ligand for the Synthesis of Bimetallic Palladium and Platinum Complexes.

We present four proton-responsive palladium and platinum complexes, [MCl ( PONNHO)] (M=Pd, Pt; R= Pr, Bu) synthesised by complexation of PdCl or PtCl (COD) with the 1,8-naphthyridine ligand PONNHO. Deprotonation of [MCl ( PONNHO)] switches ligand coordination from mono- to dinucleating, offering a synthetic pathway to bimetallic Pd and Pt complexes [M Cl ( PONNO) ]. Two-electron reduction gives planar M -M complexes [M ( PONNO) ] (M=Pd, Pt) containing a metal-metal bond.

A one-pot reduction route to bimetallic manganese 1,8-naphthyridine complexes.

Reaction of the dinucleating ligand 2,7-bis(6-methyl-2-pyridyl)-1,8-naphthyridine (L) with the Mn and Mn precursors MnBr(CO) and MnCl resulted in the formation of the monometallic complexes [MnBr(CO)(L)] (1) and [MnCl(L)] (3). In both cases, formation of bimetallic manganese complexes could be achieved by reduction with KC, yielding the carbonyl-bridged complex [Mn(CO)(L)] (2) and the helicate complex [Mn(L)] (4), respectively. EPR results demonstrate that 4 represents a novel, weakly antiferromagnetically coupled homovalent dimer ( = -0.

Oxidative Addition and β-Hydride Elimination by a Macrocyclic Dinickel Complex: Observing Bimetallic Elementary Reactions.

The dinickel(I) complex Ni ( PONNOPONNO), featuring a planar macrocyclic diphosphoranide ligand PONNOPONNO, offers a unique architectural platform for observing bimetallic elementary reactions. Oxidative addition reactions of alkyl halides produce dinickel(II) complexes of the type Ni (μ-R)(μ-X)( PONNOPONNO). However, when R=Et β-hydride elimination is observed to form a dinickel monohydride, with the rate dependent on the nature of X.

Inter-rater concordance of basal cell carcinoma subtypes: influences on reporting format and opportunities for further classification modifications.

Diagnosis of basal cell carcinoma (BCC) higher risk subtypes influences management strategies because of their propensity to recur locally. Subtyping is prone to inter-observer variability, and subtyping definitions are inconsistently applied. This study sought to compare the interobserver reproducibility of individual BCC subtypes using the 4th edition World Health Organization (WHO) Classification of Skin Tumours (CoST) definitions, with classification into lower and higher risk histological subtype groups.

NTRK fusions in solid tumours: what every pathologist needs to know.

Fusions involving the Neurotrophic tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2 and NTRK3) are targetable oncogenic alterations that are found in a diverse range of tumours. There is an increasing demand to identify tumours which harbour these fusions to enable treatment with selective tyrosine kinase inhibitors such as larotrectinib and entrectinib. NTRK fusions occur in a wide range of tumours including rare tumours such as infantile fibrosarcoma and secretory carcinomas of the salivary gland and breast, as well as at low frequencies in more common tumours including melanoma, colorectal, thyroid and lung carcinomas.

Highly Adaptive Nature of Group 15 (quinolyl) Ligands─Studies with Coinage Metals.

The substitution of heavier, more metallic atoms into classical organic ligand frameworks provides an important strategy for tuning ligand properties, such as ligand bite and donor character, and is the basis for the emerging area of main-group supramolecular chemistry. In this paper, we explore two new ligands [E(2-Me-8-qy)] [E = Sb (), Bi (); qy = quinolyl], allowing a fundamental comparison of their coordination behavior with classical (2-pyridyl) ligands of the type [E'(2-py)] (E = a range of bridgehead atoms and groups, py = pyridyl). A range of new coordination modes to Cu, Ag, and Au is seen for and , in the absence of steric constraints at the bridgehead and with their more remote N-donor atoms.

Biology and genetics of acquired and congenital melanocytic naevi.

Acquired and congenital melanocytic naevi are common benign neoplasms. Understanding their biology and genetics will help clinicians and pathologists correctly diagnose melanocytic tumours, and generate insights into naevus aetiology and melanomagenesis. Genomic data from published studies analysing acquired and congenital melanocytic naevi, including oncogenic driver mutations, common melanoma associated mutations, copy number aberrations, somatic mutation signature patterns, methylation profile, and single nucleotide polymorphisms, were reviewed.

Bimetallic Nickel Complexes Supported by a Planar Macrocyclic Diphosphoranide Ligand.

Metal-metal cooperativity is emerging as an important strategy in catalysis. This requires appropriate ligand scaffolds that can support two metals in close proximity. Here we report nickel-promoted formation of a dinucleating planar macrocyclic ligand that can support bimetallic dinickel(II) and dinickel(I) complexes.

Copper and Zinc Complexes of 2,7-Bis(6-methyl-2-pyridyl)-1,8-naphthyridine─A Redox-Active, Dinucleating Bis(bipyridine) Ligand.

The ligand 2,7-bis(6-methyl-2-pyridyl)-1,8-naphthyridine () acts as a dinucleating analogue of ubiquitous 2,2'-bipyridine ligands. Coordination of to [Cu(NCMe)]PF and Zn(OAc) led to isolation of monometallic [Zn(OAc)()], homobimetallic [Cu()][PF], and heterobimetallic [CuZn(μ-OAc)()]PF complexes. The redox-active nature of the ligand enables access to four redox states of the complex [Cu()][PF].

Comparative Genomics Provides Etiologic and Biological Insight into Melanoma Subtypes.

Unlabelled: Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma is associated with skin exposed to ultraviolet radiation; uveal melanoma occurs in the eyes; mucosal melanoma occurs in internal mucous membranes; and acral melanoma occurs on the palms, soles, and nail beds. Here, we present the largest whole-genome sequencing study of melanoma to date, with 570 tumors profiled, as well as methylation and RNA sequencing for subsets of tumors.

Higher proportions of CD39+ tumor-resident cytotoxic T cells predict recurrence-free survival in patients with stage III melanoma treated with adjuvant immunotherapy.

Background: Adjuvant immune checkpoint inhibitor (ICI) immunotherapies have significantly reduced the recurrence rate in high-risk patients with stage III melanoma compared with surgery alone. However, 48% of anti-PD-1-treated patients will develop recurrent disease within 4 years. There is a need to identify biomarkers of recurrence after adjuvant ICI to enable identification of patients in need of alternative treatment strategies.

Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial.

Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg and nivolumab 3 mg kg.

Comprehensive Clinical, Histopathologic, and Molecular Analysis and Long-term Follow-up of Patients With Nodal Blue Nevi.

Blue nevi are benign, melanocytic neoplasms that show a range of clinical and morphologic patterns and include common/dendritic, cellular, and atypical cellular subtypes. Like other nevi, they most commonly occur in skin but can occasionally involve lymph nodes where they may be misinterpreted as representing metastatic melanoma. Moreover, whether benign blue nevi can metastasize to lymph nodes and their natural history and prognostic significance has been the subject of great controversy.

Pathologist initiated reflex BRAF mutation testing in metastatic melanoma: experience at a specialist melanoma treatment centre.

Testing for BRAF mutations in metastatic melanoma is pivotal to identifying patients suitable for targeted therapy and influences treatment decisions regarding single agent versus combination immunotherapy. Knowledge of BRAF V600E immunohistochemistry (IHC) results can streamline decisions during initial oncology consultations, prior to DNA-based test results. In the absence of formal guidelines that require pathologist initiated ('reflex') BRAF mutation testing, our institution developed a local protocol to perform BRAF V600E IHC on specimens from all stage III/IV melanoma patients when the status is otherwise unknown.

Elevated non-coding promoter mutations are associated with malignant transformation of melanocytic naevi to melanoma.

Evolution from a benign naevus to a melanoma results principally from the stepwise accumulation of mutations. We used a custom next generation sequencing (NGS) panel targeting specific melanoma associated genes to analyse and compare differences between melanomas and their precursor naevi in coding and non-coding mutations and copy number aberrations, with a view to implementing this technique as an ancillary test to assist in the interpretation of difficult to diagnose melanocytic tumours. Fifteen cases of cutaneous melanoma with an adjacent morphologically benign (presumed precursor) naevus were selected.

Cooperative approaches in catalytic hydrogenation and dehydrogenation.

Metal-ligand cooperativity (MLC) is an established strategy for developing effective hydrogenation and dehydrogenation catalysts. Metal-metal cooperativity (MMC) in bimetallic complexes is not as well understood, and to date has had limited implementation in (de)hydrogenation. Herein we use (de)hydrogenation processes as a platform to examine modes of cooperativity, with a particular focus on catalytic mechanisms.

Clinicopathological characteristics of new primary melanomas in patients receiving immune checkpoint inhibitor therapy for metastatic melanoma.

Background: Immune checkpoint inhibitors have improved survival in advanced stage melanoma patients. Rates of new primary melanomas (NPM) in patients with prior melanoma have been reported to be as high as 12%. Little is currently known regarding the frequency or characteristics of NPMs occurring in melanoma patients treated with immune checkpoint inhibitors.

Representativeness of the Index Lymph Node for Total Nodal Basin in Pathologic Response Assessment After Neoadjuvant Checkpoint Inhibitor Therapy in Patients With Stage III Melanoma.

Importance: Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection (TLND) can be safely omitted when a major pathologic response in the largest lymph node metastasis at baseline (index lymph node; ILN) is obtained is currently being investigated. A previous small pilot study (n = 12) showed that the response in the ILN may be representative of the pathologic response in the entire TLND specimen.

BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia.