Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma.

Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation.

Monitoring Over Time of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Through an Ensemble Vision Transformers-Based Model.

Background: Morphological and vascular characteristics of breast cancer can change during neoadjuvant chemotherapy (NAC). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-acquired pre- and mid-treatment quantitatively capture information about tumor heterogeneity as potential earlier indicators of pathological complete response (pCR) to NAC in breast cancer.

Aims: This study aimed to develop an ensemble deep learning-based model, exploiting a Vision Transformer (ViT) architecture, which merges features automatically extracted from five segmented slices of both pre- and mid-treatment exams containing the maximum tumor area, to predict and monitor pCR to NAC.

Self-perceived attitudes of Italian oncology nurses towards clinical trial involvement: A cohort observational study.

Background: Literature is lacking when it comes to oncology nursing attitudes in clinical trial involvement.

Objective: To assess how Italian oncology nurses perceived their attitudes in clinical trials involvement.

Methods: An on-line cohort observational study was carried out.

Nipple-Areola Complex Reconstruction Using FixNip NRI Implant after Mastectomy: An Innovative Technique.

Background: Nipple-areolar complex reconstruction is the final stage of breast reconstruction, and it improves quality of life in patients with post-mastectomy breast cancer. We present a case of a patient with breast cancer underwent breast reconstruction and subsequent nipple-areolar complex reconstruction with an innovative biocompatible smooth silicone implant specially designed for a long-lasting restoration of the nipple-areola complex called FixNip NRI. However, to our knowledge, nipple-areolar complex reconstruction with FixNip was not previously reported.

GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy.

Background: CRISPR/Cas9 system to treat human-related diseases has achieved significant results and, even if its potential application in cancer research is improving, the application of this approach in clinical practice is still a nascent technology.

Main Body: CRISPR/Cas9 technology is not yet used as a single therapy to treat tumors but it can be combined with traditional treatment strategies to provide personalized gene therapy for patients. The combination with chemotherapy, radiation and immunotherapy has been proven to be a powerful means of screening, identifying, validating and correcting tumor targets.

Assessing the cost-effectiveness of waiting list reduction strategies for a breast radiology department: a real-life case study.

Background: A timely diagnosis is essential for improving breast cancer patients' survival and designing targeted therapeutic plans. For this purpose, the screening timing, as well as the related waiting lists, are decisive. Nonetheless, even in economically advanced countries, breast cancer radiology centres fail in providing effective screening programs.

Allogeneic, donor-derived, second-generation, CD19-directed CAR-T cells for the treatment of pediatric relapsed/refractory BCP-ALL.

Autologous CD19-directed chimeric antigen receptor (CAR)-T cells have shown unprecedented efficacy in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, patients either relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or displaying profound lymphopenia and/or rapidly progressing disease often cannot access autologous products. These hurdles may be overcome by allogeneic, donor-derived CAR-T cells.

A Machine Learning Approach for Predicting Capsular Contracture after Postmastectomy Radiotherapy in Breast Cancer Patients.

In recent years, immediate breast reconstruction after mastectomy surgery has steadily increased in the treatment pathway of breast cancer (BC) patients due to its potential impact on both the morpho-functional and aesthetic type of the breast and the quality of life. Although recent studies have demonstrated how recent radiotherapy techniques have allowed a reduction of adverse events related to breast reconstruction, capsular contracture (CC) remains the main complication after post-mastectomy radio-therapy (PMRT). In this study, we evaluated the association of the occurrence of CC with some clinical, histological and therapeutic parameters related to BC patients.

PI3K/Akt Pathway: The Indestructible Role of a Vintage Target as a Support to the Most Recent Immunotherapeutic Approaches.

Pathologic activation of PI3Ks and the subsequent deregulation of its downstream signaling pathway is among the most frequent events associated with cellular transformation, cancer, and metastasis. PI3Ks are also emerging as critical factors in regulating anti-tumor immunity by either promoting an immunosuppressive tumor microenvironment or by controlling the activity and the tumor infiltration of cells involved in the immune response. For these reasons, significant pharmaceutical efforts are dedicated to inhibiting the PI3K pathway, with the main goal to target the tumor and, at the same time, to enhance the anti-tumor immunity.

Recent advances in searching c-Myc transcriptional cofactors during tumorigenesis.

Background: The mechanism by which c-Myc exerts its oncogenic functions is not completely clear and different hypotheses are still under investigation. The knowledge of the capacity of c-Myc to bind exclusively E-box sequences determined the discrepancy between, on the one hand, genomic studies showing the binding of c-Myc to all active promoters and, on the other hand, the evidence that only 60% or less of the binding sites have E-box sequences.

Main Body: In this review, we provide support to the hypothesis that the cooperation of c-Myc with transcriptional cofactors mediates c-Myc-induced cellular functions.

Promoting evaluation capacity building in a complex adaptive system.

This study provides results from an NSF funded, four year, case study about evaluation capacity building in a complex adaptive system, the Nanoscale Informal Science Education Network (NISE Net). The results of the Complex Adaptive Systems as a Model for Network Evaluations (CASNET) project indicate that complex adaptive system concepts help to explain evaluation capacity building in a network. The NISE Network was found to be a complex learning system that was supportive of evaluation capacity building through feedback loops that provided for information sharing and interaction.

Pathogen-specific B-cell receptors drive chronic lymphocytic leukemia by light-chain-dependent cross-reaction with autoantigens.

Several lines of evidence indirectly suggest that antigenic stimulation through the B-cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self-antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen-specific BCRs drive CLL development remains, however, largely unexplored.

A body-machine interface for training selective pelvis movements in stroke survivors: A pilot study.

The body-machine interfaces (BMIs) map the subjects' movements into the low dimensional control space of external devices to reach assistive and/or rehabilitative goals. This work is a first proof of concept of this kind of BMI as tool for rehabilitation after stroke. We designed an exercise to improve the control of selective movements of the pelvis in stroke survivors, increasing the ability to decouple the motion in the sagittal and frontal planes and decreasing compensatory adjustments at the shoulder girdle.

Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia.

Several chemo-resistance mechanisms including the Bcl-2 protein family overexpression and constitutive activation of the PI3K/Akt/mTOR signaling have been documented in acute lymphoblastic leukemia (ALL), encouraging targeted approaches to circumvent this clinical problem. Here we analyzed the activity of the BH3 mimetic ABT-737 in ALL, exploring the synergistic effects with the mTOR inhibitor CCI-779 on ABT-737 resistant cells. We showed that a low Mcl-1/Bcl-2 plus Bcl-xL protein ratio determined ABT-737 responsiveness.

Two types of BCR interactions are positively selected during leukemia development in the Eμ-TCL1 transgenic mouse model of CLL.

Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy characterized by a highly variable course and outcome. The disease is believed to be driven by B-cell receptor (BCR) signals generated by external antigens and/or cell-autonomous BCR interactions, but direct in vivo evidence for this is still lacking. To further define the role of the BCR pathway in the development and progression of CLL, we evaluated the capacity of different types of antigen/BCR interactions to induce leukemia in the Eμ-TCL1 transgenic mouse model.

A nonsemen copulatory fluid influences the outcome of sperm competition in Japanese quail.

Sperm competition is a powerful and widespread evolutionary force that drives the divergence of behavioural, physiological and morphological traits. Elucidating the mechanisms governing differential fertilization success is a fundamental question of sperm competition. Both sperm and nonsperm ejaculate components can influence sperm competition outcomes.

Purification and characterization of adipose-derived stem cells from patients with lipoaspirate transplant.

Techniques for medical tissue regeneration require an abundant source of human adult stem cells. There is increasing evidence that adipose stem cells contribute to restoration of tissue vascularization and organ function. The object of our study was to isolate and characterize adult adipose-derived stem cells from patients undergoing on lipoaspirate transplant with the aim to improve tissue regeneration.

Lymphoid EVA1 expression is required for DN1-DN3 thymocytes transition.

Background: Thymus organogenesis and T lymphocyte development are accomplished together during fetal life. Proper development and maintenance of thymus architecture depend on signals generated by a sustained crosstalk between developing thymocytes and stromal elements. Any maturation impairment occurring in either cellular component leads to an aberrant thymic development.

HIPK2 is involved in cell proliferation and its suppression promotes growth arrest independently of DNA damage.

Introduction/objectives: The serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) is a co-regulator of an increasing number of transcription factors and cofactors involved in DNA damage response and development. We and others have cloned HIPK2 as an interactor of the p53 oncosuppressor, and have studied the role of this interaction in cell response to stress. Nevertheless, our original cloning of HIPK2 as a p53-binding protein, was aimed at discovering partners of p53 involved in cell differentiation and development, still controversial p53 functions.

MDM2-regulated degradation of HIPK2 prevents p53Ser46 phosphorylation and DNA damage-induced apoptosis.

In response to DNA damage, p53 induces either cell-cycle arrest or apoptosis by differential transcription of several target genes and through transcription-independent apoptotic functions. p53 phosphorylation at Ser46 by HIPK2 is one determinant of the outcome because it takes place only upon severe, nonrepairable DNA damage that irreversibly drives cells to apoptosis. Here, we show that p53 represses its proapoptotic activator HIPK2 via MDM2-mediated degradation, whereas a degradation-resistant HIPK2 mutant has increased apoptotic activity.

Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis.

Galectin 3 (Gal-3), a member of the beta-galactoside binding lectin family, exhibits antiapoptotic functions, and its aberrant expression is involved in various aspects of tumor progression. Here we show that p53-induced apoptosis is associated with transcriptional repression of Gal-3. Previously, it has been reported that phosphorylation of p53 at Ser46 is important for transcription of proapoptotic genes and induction of apoptosis and that homeodomain-interacting protein kinase 2 (HIPK2) is specifically involved in these functions.

S100A2 gene is a direct transcriptional target of p53 homologues during keratinocyte differentiation.

The p53 paralogues p73, p63 and their respective truncated isoforms have been shown to be critical regulators of developmental and differentiation processes. Indeed, both p73- and p63-deficient mice exhibit severe developmental defects. Here, we show that S100A2 gene, whose transcript and protein are induced during keratinocyte differentiation of HaCaT cells, is a direct transcriptional target of p73beta and DeltaNp63alpha and is required for proper keratinocyte differentiation.

ATM is activated by default in mitosis, localizes at centrosomes and monitors mitotic spindle integrity.

We previously showed that ATM is responsible for p53 phosphorylation at Ser15 and localization at centrosomes during mitosis. When p53 centrosomal localization is prevented by inhibiting polymerization of spindle microtubules, a stabilized form of p53 is transmitted to daughter cells that arrest in the next G(1) phase of the cell cycle after exit from mitosis. AT cells are unable to both localize p53 at centrosomes in mitosis and arrest after exposure to mitotic-spindle poisons.