New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?

Brain metastases (BM) pose a significant challenge in the management of HER2+ breast cancer since almost 50% of patients with HER2+ breast cancer develop brain tumors. The complex process of brain metastases involves genetic mutations, adaptations and mechanisms to overcome the blood-brain barrier. While radiotherapy is still fundamental in local therapy, its use is associated with cognitive adverse effects and limited long-term control, necessitating the exploration of alternative treatments. Targeted therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates, offer promising options for HER2+ breast cancer patients with BM. Clinical trials have demonstrated the efficacy of these agents in controlling tumor growth and improving patient outcomes, posing the question of whether radiotherapy is always the unique choice in treating this cancer. Ongoing research into novel anti-HER2 antibodies and innovative combination therapies holds promise for advancing treatment outcomes and enhancing patient care in this clinical scenario. This narrative review provides a comprehensive overview of traditional medical treatments, molecularly targeted therapy and investigational agents in the management of HER2+ breast cancer with BM, highlighting the evolving landscape and potential future directions in treatment strategies to improve patient survival and quality of life.

Life Experience of Survivors of Gynecologic Cancers: A Survey Conducted in Italy.

BACKGROUND: The study of health-related quality of life in survivors of gynecologic cancers is becoming increasingly important as 1.5 million survivors of gynecologic cancer in the United States and more are expected due to advances in diagnosis and treatment. This project investigated the perceived needs and lived experiences of survivors of gynecological cancer to help design supportive activities to be implemented in clinical practice. METHODS: Patients were recruited in hospitals or through social media and responded to an online survey that was addressed to patients in Italy, specifically in Sicily, Puglia, and Campania. Patients with ovarian, endometrium, or cervix cancer were recruited among women attending Cannizzaro Hospital and Alleanza Contro il Tumore Ovarico (Alliance Against Ovarian Cancer) members. RESULTS: Body image perception was changed in 82.3% of respondents, whereas familial relationships were described as changed by 27.5% of women. In 69.6% of patients, sexual habits were hindered by changes in the body, depression, pain, and awkwardness. Physicians informed patients about sexuality changes related to cancer extensively in 16.7% of cases and briefly in 19.6% of cases. The advice of a clinical sexologist was considered potentially helpful by 31.4% of patients and not potentially helpful by 47.1%, whereas 21.6% of patients had no opinion. CONCLUSIONS: Although sexual habits are often changed by cancer, women surviving gynecological cancer rarely seek medical advice in this area. Physicians should be trained to inform patients and to promote referrals to sexologists.

Homologous Recombination Deficiency (HRD) Scoring, by Means of Two Different Shallow Whole-Genome Sequencing Pipelines (sWGS), in Ovarian Cancer Patients: A Comparison with Myriad MyChoice Assay.

High-grade serous ovarian cancer (HGSOC) patients carrying the BRCA1/2 mutation or deficient in the homologous recombination repair system (HRD) generally benefit from treatment with PARP inhibitors. Some international recommendations suggest that BRCA1/2 genetic testing should be offered for all newly diagnosed epithelial ovarian cancer, along with HRD assessment. Academic tests (ATs) are continuously under development, in order to break down the barriers patients encounter in accessing HRD testing. Two different methods for shallow whole-genome sequencing (sWGS) were compared to the reference assay, Myriad. All these three assays were performed on 20 retrospective HGSOC samples. Moreover, HRD results were correlated with the progression-free survival rate (PFS). Both sWGS chemistries showed good correlation with each other and a complete agreement, even when compared to the Myriad score. Our academic HRD assay categorized patients as HRD-Deficient, HRM-Mild and HRN-Negative. These three groups were matched with PFS, providing interesting findings in terms of HRD scoring and months of survival. Both our sWGS assays and the Myriad test correlated with the patient's response to treatments. Finally, our AT confirms its capability of determining HRD status, with the advantage of being faster, cheaper, and easier to carry out. Our results showed a prognostic value for the HRD score.

Percepción de la simulación en obstetricia y ginecología en el pregrado y posgrado de una universidad privada chilena / Perception of simulation in obstetrics and gynecology at the undergraduate and postgraduate levels of a private Chilean university

INTRODUCCIÓN: La simulación es una herramienta que promueve la confianza y desarrollo de habilidades en los participantes. En la evaluación de programas formativos la percepción de utilidad se vincula a la confianza y aprendizaje, y corresponde al primer nivel de evaluación según Kirkpatrick. OBJETIVO: Evaluar la percepción de internos y residentes de obstetricia y ginecología en escenarios de simulación. MATERIAL Y MÉTODOS: Investigación descriptiva cuantitativa, en una muestra a conveniencia de internos y residentes, quienes contestaron una escala de valoración global y de preferencias sobre sus simulaciones. RESULTADOS: Se obtuvieron 63 respuestas de internos (63%) y 7 de residentes (78%). La valoración promedio de las simulaciones fue de 6,42 en los internos y de 6,64 de los residentes. El 67% de los internos y el 86% de los residentes no eliminaría ninguna simulación. Los internos repetirían todas las simulaciones, en tanto que los residentes repetirían tres simulaciones de un total de 11. CONCLUSIONES: La valoración de las simulaciones fue alta en ambos grupos, difiriendo en las actividades que prefieren repetir, lo cual puede relacionarse con las competencias inherentes al rol de especialista en comparación al rol del médico general o a las diferencias en autoconfianza de internos y residentes.

INTRODUCTION: Clinical simulation is a training tool that promotes confidence and the development of procedural skills in participants, from initial training to the training of professional teams. In the evaluation of training programs, the measurement of perceived usefulness is linked to confidence and learning and corresponds to a first level of evaluation of the quality of training according to Kirkpatricks model. OBJECTIVE: To evaluate the perception of medical interns and Obstetrics and Gynecology fellows regarding simulation scenarios. MATERIAL AND METHODS: Quantitative descriptive research, in a convenience sample of interns and fellows, who answered a scale of global assessment and preferences about simulations. RESULTS: The average score was 6.42 for the interns and 6.64 for the scholarship recipients. With odd answers about the repetition of scenarios. 67% of the interns and 86% of the fellows responded that they would not eliminate any simulation. Conclusions: The evaluation of the scenarios was excellent and satisfactory by the participants.

The Geriatric G8 Score Is Associated with Survival Outcomes in Older Patients with Advanced Prostate Cancer in the ADHERE Prospective Study of the Meet-URO Network.

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73-82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8-29.3) and OS 48.8 mo. (95% CI, 36.8-60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 (p < 0.001 and p = 0.004) and PSA decline ≥50% (p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only (p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only (p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care.

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma.

INTRODUCTION: Endometrial cancer can be characterized by high instability of microsatellites (MSI-H), a biomarker indicative of sensibility to immune checkpoint inhibitors (ICIs). The results of the KEYNOTE-158 trial led to the approval of pembrolizumab - a monoclonal, humanized IgG4 kappa anti-PD-1 antibody able to prevent T-cell PD-1/tumor cell PD-L1/2 interaction, thus restoring T-cell-mediated anti-tumor immunity - in MSI-H endometrial cancer relapsing after at least one line of chemotherapy (CT). AREAS COVERED: Ongoing trials, such as KEYNOTE-B21/ENGOT-en11, KEYNOTE-C93/ENGOT-en15/GOG-3064, and NRG/GY018, aim to move this option earlier in the algorithm, whether adjuvant or first-line, even CT-free. Combinatorial approaches associating ICIs with other target therapies blocking immunosuppressive pathways are also being studied. EXPERT OPINION: The ICI overall response rates in MSI-H patients are encouraging, but over 50% do not respond to treatment. A more thorough definition of the MSI status regarding specific missing proteins could allow better use of this biomarker and explain why specific populations may not respond to immunotherapy regardless of widely accepted predictive biomarkers. Future developments should focus on identifying who can benefit from a CT-free treatment and translational research on primary resistant MSI-H EC.

Adherence to Oral Treatments in Older Patients with Advanced Prostate Cancer, the ADHERE Study: A Prospective Trial of the Meet-URO Network.

BACKGROUND: Novel androgen receptor signaling inhibitors for prostate cancer (PC) impose the burden of self-administration on older patients overwhelmed by the requirement of many other concomitant medications. PATIENTS AND METHODS: This study evaluated the proportion of non-adherence in a 12-month follow-up period and the first 3 months to abiraterone (ABI) or enzalutamide (ENZ). In a prospective multicenter observational cohort study, patients with metastatic castration-resistant PC (mCRPC) aged ≥70 years receiving ABI or ENZ pre- or post-docetaxel were enrolled. Treatment monitoring included pill counting, a self-assessment questionnaire, and clinical diaries at each clinical visit. Non-adherence rates were based on proportions of missed/prescribed pills ratios by pill counting. RESULTS: Overall, 234 patients were recruited with median age of 78 years (range, 73-82); 86 (37%) were treated with ABI, and 148 (63%) with ENZ. The median follow-up for adherence was seven monthly cycles (IQR: 4-12). The two cohorts were well balanced for baseline characteristics. The percentage of non-adherence by pill counting was slightly higher for ABI than ENZ (5.2% vs. 4.2%, P < .001). By self-reporting, patients on ENZ tended to report more frequently than those with ABI forgetfulness as the reason for missing events (42% vs. 17%, P < .001). A lower Geriatric G8 score correlated with non-adherence (P = .004). Overall survival (OS) was 48.8 months. Patients on ABI had radiographic progression-free survival (rPFS) of 28.4 [24.2-32.5], while for ENZ patients, we reported a median rPFS of 23.1 [18.2-28.1] months. CONCLUSION: Physicians tend to treat older mCRPC patients with ENZ. Non-adherence rate is relatively low overall but can be higher with ABI than with ENZ and correlates with the Geriatric G8 score. Forgetfulness is a potential barrier for ENZ.

Ultrasound evaluation of the first finger's sesamoid bones: diagnostic value of sesamoid and subsesamoid indices.

PURPOSE: Our analysis focuses explicitly on applying two sonographic and morphological indexes (sesamoid index and subsesamoid index) to better evaluate post-traumatic consequences to the sesamoids of the first finger. METHODS: In 2 years, we enrolled 75 patients, divided into two groups: 60 without any history of trauma and 15 reporting hyperextension trauma of the first finger. We performed clinical and instrumental examinations (sonography and X-ray) on patients with one or more symptoms compatible with sesamoiditis, while an MRI scan was performed only on patients with an acute onset and severe symptomatology. We measured both the short and long-axis diameter (in mm) for each sesamoid as well as the relation between the two parameters (sesamoid index, SI and subsesamoid index, SubI). RESULTS: All 15 patients showed sonographic alterations of the SI above the reference range, while the alterations of SubI varied according to the acuteness and gravity of trauma. In all cases, the X-ray did not show any relevant alterations. MRI scans in patients with acute symptoms confirmed the sonographic findings. CONCLUSION: Sonography enabled diagnosis of micro-injuries which were invisible to X-Ray and allowed to detect possible damages to the sesamoid complex, providing a qualitative and quantitative evaluations of the post-traumatic alteration of the metacarpophalangeal joint of the 1st finger and is therefore valid, combined with clinical examination and hand X-ray, in the evaluation of sesamoiditis without the need to perform further examinations.

A multidisciplinary approach remains the best strategy to improve and strengthen the management of ovarian cancer (Review).

Ovarian cancer represents one of the most aggressive female tumors worldwide. Over the decades, the therapeutic options for the treatment of ovarian cancer have been improved significantly through the advancement of surgical techniques as well as the availability of novel effective drugs able to extend the life expectancy of patients. However, due to its clinical, biological and molecular complexity, ovarian cancer is still considered one of the most difficult tumors to manage. In this context, several studies have highlighted how a multidisciplinary approach to this pathology improves the prognosis and survival of patients with ovarian cancer. On these bases, the aim of the present review is to present recent advantages in the diagnosis, staging and treatment of ovarian cancer highlighting the benefits of a patient­centered care approach and on the importance of a multidisciplinary team for the management of ovarian cancer.

Biochemical Characterization of Traditional Varieties of Sweet Pepper (Capsicum annuum L.) of the Campania Region, Southern Italy.

Bioactive compounds of different Campania native sweet pepper varieties were evaluated. Polyphenols ranged between 1.37 mmol g-1 and 3.42 mmol g-1, ß-carotene was abundant in the red variety "Cazzone" (7.05 µg g-1). Yellow and red varieties showed a content of ascorbic acid not inferior to 0.82 mg g-1, while in some green varieties the presence of ascorbic acid was almost inconsistent. Interrelationships between the parameters analyzed and the varieties showed that ascorbic acid could represent the factor mostly influencing the antioxidant activity. Polyphenol profile was different among the varieties, with a general prevalence of acidic phenols in yellow varieties and of flavonoids in red varieties. Principal Component Analysis, applied to ascorbic acid, total polyphenols and ß-carotene, revealed that two of the green varieties ("Friariello napoletano" and "Friariello Sigaretta") were well clustered and that the yellow variety "Corno di capra" showed similarity with the green varieties, in particular with "Friariello Nocerese". This was confirmed by the interrelationships applied to polyphenol composition, which let us to light on a clustering of several red and yellow varieties, and that mainly the yellow "Corno di capra" was closer to the green varieties of "Friariello".

Obstetric outcomes in patients who have undergone excisional treatment for high-grade cervical squamous intra-epithelial neoplasia.

OBJECTIVE: To evaluate the relationships between excisional treatment for high-grade cervical intra-epithelial neoplasia (CIN2+) and obstetric outcomes in terms of preterm delivery risk, premature rupture of membrane (PROM) and type of delivery, and between pre-term delivery and the type of excisional technique (radio frequency excision, laser conization). METHODS: This was a retrospective study of the obstetric outcomes of 2316 women aged 25-45 years who underwent excisional treatment for CIN2+ at the Obstetric and Gynecological Clinic of Ospedale Maggiore della Carità in Novara and at the Obstetric and Gynecological Department of Ospedale Sant'Anna in Torino in the period 2005-2014 and were evaluated until April 2016, and 57,937 untreated women of the same age, from the same centers. RESULTS: After treatment, 320 women had at least one pregnancy leading to delivery after a mean of 3.35 years. Treatment significantly increased the risk of preterm delivery. Compared with no treatment, the risk of preterm birth was higher in women who had undergone treatment (33.13% vs. 6.60%). Techniques removing or ablating more tissue, such as large loop excision of the transformation zone, were associated with worse outcomes (OR 2.96, 95% IC 1.72-5.10). Smoking habits significantly increase the risk of preterm delivery in the treated women (OR 2.82, 95% IC 1.61-4.9). The risk of premature rupture of the membranes (PROM) (40% vs. 23.22%), the risk of preterm PROM (pPROM) (13.13% vs. 2.71%) and dystocic births (18.75% vs 4.48%) were also significantly increased after treatment. Caesarean sections were less frequent among the treated women (15.94% vs. 32.41%). CONCLUSIONS: Our findings reveal a relationship between cervical excisional treatment and pre-term delivery, PROM, and the method of delivery. In order to minimise risk and guarantee the best obstetric outcome, patient treatment and follow-up should be personalised.

Whole-genome re-sequencing of two Italian tomato landraces reveals sequence variations in genes associated with stress tolerance, fruit quality and long shelf-life traits.

Tomato is a high value crop and the primary model for fleshy fruit development and ripening. Breeding priorities include increased fruit quality, shelf life and tolerance to stresses. To contribute towards this goal, we re-sequenced the genomes of Corbarino (COR) and Lucariello (LUC) landraces, which both possess the traits of plant adaptation to water deficit, prolonged fruit shelf-life and good fruit quality. Through the newly developed pipeline Reconstructor, we generated the genome sequences of COR and LUC using datasets of 65.8 M and 56.4 M of 30-150 bp paired-end reads, respectively. New contigs including reads that could not be mapped to the tomato reference genome were assembled, and a total of 43, 054 and 44, 579 gene loci were annotated in COR and LUC. Both genomes showed novel regions with similarity to Solanum pimpinellifolium and Solanum pennellii. In addition to small deletions and insertions, 2, 000 and 1, 700 single nucleotide polymorphisms (SNPs) could exert potentially disruptive effects on 1, 371 and 1, 201 genes in COR and LUC, respectively. A detailed survey of the SNPs occurring in fruit quality, shelf life and stress tolerance related-genes identified several candidates of potential relevance. Variations in ethylene response components may concur in determining peculiar phenotypes of COR and LUC.

MDCT classification of steatotic liver: a multicentric analysis.

PURPOSE: Fatty liver disease is the most common cause of chronic liver disease in the western world. The aim of this study was to analyze steatotic liver characteristics using multidetector row computed tomography (CT) to identify reliable criteria to identify the steatosis and quantify its severity. PATIENTS AND METHODS: Multiphasic CT scans of 51 consecutive adults (36 men, mean age 57.1±9.9 years), who underwent ultrasound-guided liver biopsy, were analyzed. In all patients, the Hounsfield units (HU) value was determined for each hepatic segment and for each contrast phase. Also, the splenic attenuation was quantified and the differences in the liver-spleen (DLS). Steatosis was graded according its severity into four grades. Receiver operating characteristic (ROC) curve analysis was carried out to calculate the sensitivity and specificity for the specific HU threshold. Pearson's ρ correlation was also calculated. A P value of 0.05 was considered statistically significant. RESULTS: We found that 14 individuals (10 men, mean age 56±9.8 years) did not have hepatic steatosis. Only the nonenhanced CT scans showed a statistically significant association with liver steatosis (with the only exception of region-of-interest selected in the Couinaud segment VII, where a P value of 0.0513 was obtained). For grades 1, 2, 3, and 4, we identified 50, 45, 35, and 20 HU as thresholds. A statistically significant association was found between steatosis and DLS in the nonenhanced and the arterial phase (P=0.0192 and 0.001, respectively). CONCLUSION: The result of our study indicates that the nonenhanced value of the liver can be used to identify steatosis of the liver and to grade its severity. Moreover, the DLS in the arterial phase represents another reliable parameter.

Speciation via floral heterochrony and presumed mycorrhizal host switching of endemic butterfly orchids on the Azorean archipelago.

• Premise of the study: Most orchid species native to the Macaronesian islands reflect immigration from western Europe or North Africa followed by anagenesis. The only putative exception is the butterfly orchids (Platanthera) of the Azores, where three species apparently reflect at least one cladogenetic speciation event. This multidisciplinary study explores the origin, speciation, phenotypic, and genotypic cohesion of these Azorean species and their mainland relatives.• Methods: Plants of Platanthera from 30 localities spanning all nine Azorean islands were compared with those of four continental European relatives for 38 morphometric characters; substantial subsets were also analyzed for plastid microsatellites, and for nrITS of both the orchids and their mycorrhizae.• Key results: Although the three Azorean and four mainland species are all readily distinguished morphometrically using several floral characters, and hybridization appears rare, divergence in ITS and especially plastid sequences is small. Despite occupying similar laurisilva habitats, the Azorean species differ radically in the identities and diversity of their mycorrhizal partners; specialism apparently increases rarity.• Conclusions: Although morphological evidence suggests two invasions of the islands from NW Africa and/or SW Europe, ITS data imply only one. As the molecular data are unable to distinguish among the potential mainland ancestors, two scenarios of relationship are explored that imply different ancestors. Both scenarios require both anagenetic and cladogenetic speciation events, involving homoplastic shifts in overall flower size and (often substantial) changes in the relative dimensions of individual floral organs. Limited genotypic divergence among the three species compared with greater phenotypic divergence suggests comparatively recent speciation. Mycorrhizae may be the most critical factor dictating the respective ecological tolerances, and thus the relative frequencies, of these species. The recent IUCN Red-List amalgamation of Azorean Platanthera taxa into a single species urgently requires reappraisal, as P. micrantha is an excellent indicator species of seminatural laurisilva forest and P. azorica is arguably Europe's rarest orchid.

Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I.

Escherichia coli topoisomerase I (EcTopoI) is a type IA bacterial topoisomerase which is receiving large attention due to its potential application as novel target for antibacterial therapeutics. Nevertheless, a detailed knowledge of its mechanism of action at molecular level is to some extent lacking. This is partly due to the requirement of several factors (metal ions, nucleic acid) to the proper progress of the enzyme catalytic cycle. Additionally, each of them can differently affect the protein structure. Here we assess the role of the different components (DNA, metal ions, protein domains) in a dynamic environment as in solution by monitoring the catalytic as well as the structural properties of EcTopoI. Our results clearly indicated the interaction among these components as functionally relevant and underlined their mutual involvement. Some similarities with other enzymes of the same family emerged (for example DNA prevents divalent metal ions coordination at non selective binding sites). Interestingly, same interactions (C- and N-terminal domain interaction) appear to be peculiar of this bacterial topoisomerase which suggest they could be favorably exploited to the design of selective inhibitors for this class of enzyme.

Ungeremine effectively targets mammalian as well as bacterial type I and type II topoisomerases.

From the methanol extract of the bulbs of Pancratium illyricum L., three phenanthridine type alkaloids, ungeremine (1), (-)-lycorine (2) and (+)-vittatine (3) were isolated. For the evaluation of their anticancer and antibacterial potential, compounds 1-3 were tested against human (I, IIα) and bacterial (IA, IV) topoisomerases. Our data demonstrated that ungeremine impairs the activity of both, human and bacterial topoisomerases. Remarkably, ungeremine was found to largely increments the DNA cleavage promoted by bacterial topoisomerase IA, a new target in antimicrobial chemotherapy.

Phylogeographic patterns, genetic affinities and morphological differentiation between Epipactis helleborine and related lineages in a Mediterranean glacial refugium.

BACKGROUND AND AIMS: In the Mediterranean basin, the Italian peninsula has been suggested to be one of the most important glacial refugia for temperate tree species. The orchid genus Epipactis is widely represented in the Italian peninsula by widespread species and several endemic, localized taxa, including selfing and outcrossing taxa. Here the phylogenetic and phylogeographic relationships in a group of closely related taxa in Epipactis are investigated with the aim of understanding the role of this refugial area for cladogenesis and speciation in herbaceous species, such as terrestrial orchids. METHODS: Ribosomal DNA (rDNA) was employed to assess phylogenetic relationships, and plastid sequence variation in the rbcL-accD spacer was used to reveal phylogeographic patterns among plastid haplotypes using a parsimony network. KEY RESULTS: Low genetic variation and shared ribotypes were detected in rDNA, whereas high levels of sequence variation and a strong phylogeographic structure were found in the examined plastid region. The parsimony plastid haplotype network identified two main haplotype groups, one including E. atrorubens/microphylla/muelleri/leptochila and the other including all accessions of E. helleborine and several localized and endemic taxa, with a combination of widespread and rare haplotypes detected across the Italian peninsula. A greater genetic divergence separated the Italian and other European accessions of E. helleborine. CONCLUSIONS: Phylogenetic and phylogeographic patterns support a working hypothesis in which the Italian peninsula has only recently been colonized by Epipactis, probably during the most recent phase of the Quaternary age and, nevertheless, it acted as a remarkable centre of diversification for this orchid lineage. Changes in pollination strategy and recurrent shifts in mating system (from allogamy to autogamy) could have represented the mechanism promoting this rapid diversification and the observed high taxonomic complexity detected in the E. helleborine species complex.

Phosphate diester and DNA hydrolysis by a multivalent, nanoparticle-based catalyst.

2-nm gold nanoclusters coated with Zn(II) complexes bearing auxiliary hydrogen bond donors act as multivalent catalysts capable of promoting the hydrolysis of model phosphate diesters with exceptional activity and inducing DNA double strand cleavage.