Publications by authors named "Chiara Maura Ciniselli"

Few studies investigated the genetics of relapsed Wilms tumor (WT), suggesting the gene, the microRNA processing genes, and the MYCN network as possibly involved in a relevant percentage of relapses. We investigated 28 relapsing WT patients (10 new cases and 18 cases in which the involvement of and miRNAPG had been excluded) with a panel of ∼5000 genes. We identified variants affecting genes involved in DNA damage prevention and repair in 12/28 relapsing patients (42.

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Dysfunctions of lipid metabolism are associated with tumor progression and treatment resistance of cutaneous melanoma. BRAF/MEK inhibitor resistance is linked to alterations of melanoma lipid pathways. We evaluated whether a specific lipid pattern characterizes plasma from melanoma patients and their response to therapy.

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Lynch syndrome (LS) is an inherited condition characterized by an increased risk of developing cancer, in particular colorectal cancer (CRC). Microsatellite instability (MSI) is the main feature of (pre)cancerous lesions occurring in LS patients. Close endoscopic surveillance is the only option available to reduce CRC morbidity and mortality.

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Article Synopsis
  • Clinical trials classify HER2-low breast cancer using IHC scores of 1+ or 2+ without gene amplification, but daily practice sees variability in accuracy due to differences among observers.
  • This study aimed to identify HER2-low tumors using gene expression profiling, analyzing data from multiple datasets to establish a consistent HER2-low signature.
  • The HER2-low signature effectively distinguished between IHC categories and showed significant enrichment for pathways related to lipid metabolism, immune response, and other functions, confirming its reliability across different datasets.
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Purpose: Colorectal adenomatous polyposis is characterized by the onset of tens to thousands of adenomas in the colorectal epithelium and, if not treated, leads to a lifetime increased risk of developing colorectal cancer compared to the general population. Thus, prophylactic surgery is recommended. This study aims to investigate the quality of life of colorectal adenomatous polyposis patients following prophylactic surgery and indirectly compares these findings with those of healthy adults of the normative sample.

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Introduction: The synthesis of the periprosthetic capsule during implant-based breast reconstruction is the result of a coordinate cascade of inflammatory events ending in a fibrous tissue deposition around the expander or implant. Although the development of small volumes of fluid is one of the complications of prosthetic-based breast reconstruction, the characterization of the periprosthetic effusions coupled with the micro-textured devices, that have been recently introduced after the recall of macro-textured ones, is still lacking. The investigation of these periprosthetic effusions and paired capsules in terms of immunological content were the primary and secondary aims of the present study, respectively.

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Background: Specific studies on stage IV rectal cancer are lacking. The aim of this study is to describe the current status of rectum-first approach (RFA), liver-first approach (LFA) and simultaneous approach (SA) in these patients.

Methods: A systematic review was performed on PubMed, EMBASE and Cochrane including studies published from January 2005 to January 2021.

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Animal experimentation is a vast ecosystem that tries to make different issues such as legislative, ethical and scientific coexist. Research in animal experimentation has made many strides thanks to the 3Rs principle and the attached legislative decrees, but for this very reason, it needs to be evenly implemented both among the countries that have adhered to the decrees and among the team members who design and execute the experimental practice. In this article, we emphasize the importance of the 3Rs principle's application, with a particular focus on the concept of Reduction and related key aspects that can best be handled with the contribution of experts from different fields.

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An annual External Quality Assurance (EQA) program has been provided to processing laboratories over the last ten years, allowing them to assess the performance of their processing methods, such as nucleic acid extractions or peripheral blood mononuclear cell (PBMC) isolation and cryopreservation. The objective of this study was to perform a global analysis on almost 1000 EQA scheme/participant data in order to assess (i) the impact of critical preanalytical factors on quantitative or qualitative attributes of different types of specimens and (ii) laboratory performance pattern over time. Statistical analysis was performed within each EQA scheme based on categorized preanalytical data provided by the participants and on centralized measurements of relevant quality attributes of the produced specimens (z-scores): DNA, cell-free (cf)DNA or RNA extraction from blood, DNA or RNA extraction from formalin fixed tissue, DNA or RNA extraction from frozen tissue, DNA extraction from saliva or stool, viable PBMC isolation and cryopreservation.

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Background: Systemic immunosuppression characterizing cancer patients represents a concern regarding the efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and real-world evidence is needed to define the efficacy and the dynamics of humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines.

Methods: We conducted an observational study that included patients with solid tumors who were candidates for mRNA anti-SARS-CoV-2 vaccination at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. The primary objective was to monitor the immunologic response to the mRNA anti-SARS-CoV-2 vaccination in terms of anti-spike antibody levels.

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Background: Breast reconstruction has become a standard of care in patients undergoing mastectomy, greatly improving their quality of life. An increasing number of patients-reported outcome measurements (PROMs) have been developed over the years to better analyze patients' subjective overall experience. BREAST-Q is the PROMs for breast surgery introduced in our practice to assess patients' experiences when undergoing implant-based breast reconstruction and radiotherapy along with the use of Peak Plasma Blade and acellular dermal matrix.

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Background: Despite huge efforts to identify biomarkers associated with long-term clinical outcomes in patients with early-stage HER2-positive breast cancer (HER2+ BC) treated with (neo)adjuvant anti-HER2 therapy, no reliable predictors have been identified so far. Fatty acid uptake, a process mediated by the transmembrane transporter CD36, has recently emerged as a potential determinant of resistance to anti-HER2 treatments in preclinical HER2+ BC models.

Methods: Here, we investigated the association between baseline intratumor CD36 gene expression and event-free survival in 180 patients enrolled in the phase III trial Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO), which randomly assigned stage II-III HER2+ BC patients to receive neoadjuvant lapatinib, trastuzumab, or lapatinib-trastuzumab in combination with chemotherapy.

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The coronavirus disease 2019 pandemic still represents a global public health emergency, despite the availability of different types of vaccines that reduced the number of severe cases, the hospitalization rate and mortality. The Italian Vaccine Distribution Plan identified healthcare workers (HCWs) as the top-priority category to receive access to a vaccine and different studies on HCWs have been implemented to clarify the duration and kinetics of antibody response. The aim of this paper is to perform a literature review across a total of 44 studies of the serologic response to COVID-19 vaccines in HCWs in Italy and to report the results obtained in a prospective longitudinal study implemented at the Fondazione IRCCS Istituto Nazionale Tumori (INT) of Milan on 1565 HCWs.

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Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and rapidly lethal tumor, poorly responsive to conventional treatments. In this regards, the identification of molecular alterations underlying DMPM onset and progression might be exploited to develop novel therapeutic strategies. Here, we focused on miR-550a-3p, which we found downregulated in 45 DMPM clinical samples compared to normal tissues and whose expression levels were associated with patient outcome.

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Background: Progression to stage IV disease remains the main cause of breast cancer-related deaths. Increasing knowledge on the hematogenous phase of metastasis is key for exploiting the entire window of opportunity to interfere with early dissemination and to achieve a more effective disease control. Recent evidence suggests that circulating tumor cells (CTCs) possess diverse adaptive mechanisms to survive in blood and eventually metastasize, encouraging research into CTC-directed therapies.

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Background: The balance between quality of life and colorectal cancer risk in familial adenomatous polyposis (FAP) patients is of primary importance. A cut-off of less than 30 polyps under 1 cm of diameter in the rectum has been used as an indication for performing ileo-rectal anastomosis (IRA) in terms of lower rectal cancer risk. This study aimed to assess clinical and surgical features of FAP patients who developed cancer of the rectal stump.

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Introduction: Disease recurrence after surgery is a crucial predictor of poor prognosis in colorectal cancer, where disseminated disease at the time of intervention can also be observed in localized early-stage cases. We evaluated the ability to predict disease recurrence of miRNAs from two signatures that we have found linked to the presence of colorectal cancer (CL signature) or adenoma (HgA signature) in higher-risk subjects.

Methods: miRNAs from the signatures were studied longitudinally by quantitative real-time polymerase chain reaction in plasma from 24 patients with resectable colorectal cancer collected at the time of surgery and during scheduled follow-up across 36 months.

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Background: Implant-based breast reconstruction in the setting of radiotherapy often leads to higher complications rates (mainly capsular contracture and wound dehiscence) and poor cosmetic outcomes. We hypothesized that the combination of pulsed-electron avalanche knife (PEAK) PlasmaBlade (a pulsed radiofrequency electrosurgery) and acellular dermal matrix Veritas® in postmastectomy radiotherapy implant-based breast reconstruction could result in lower complications rate, better reconstructive results, and patient satisfaction.

Methods: A prospective observational study focused on the use of PEAK PlasmaBlade in implant-based breast reconstruction and radiotherapy was carried out in the Plastic Reconstructive Surgery Unit at Fondazione IRCCS Istituto Nazionale Tumori Milano between December 2017 and 2019 (2017-2018: enrollment; 2018-2019: follow-up).

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Purpose: To compare the reproducibility between contrast-enhanced digital mammography (CEDM) and magnetic resonance imaging (MRI) with the postsurgical pathologic examination. In addition, the applicability of the Breast Imaging-Reporting and Data System (BI-RADS) lexicon of MRI to CEDM was evaluated for mass lesions.

Methods: A total of 62 patients with a histologically proven diagnosis of breast cancer were included in this study, for a total of 67 lesions.

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Purpose: Little is known about the efficacy of HER2-targeted therapy in patients with breast cancer showing different HER2-pathway dependence and immune phenotypes. Herein, we report a NeoALTTO exploratory analysis evaluating the clinical value of 22 types of tumor-infiltrating immune cells by CIBERSORT and 5 immune-related metagenes in the overall patient population, and in subgroups defined by the TRAR classifier as HER2-addicted (TRAR-low) or not (TRAR-high).

Patients And Methods: Association of baseline TRAR, immune-related metagenes, and CIBERSORT data with pathologic complete response (pCR) and event-free survival (EFS) were assessed using logistic and Cox regression models.

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In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy.

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Purpose: The coronavirus 2019 (COVID-19) pandemic has had profound consequences also for non-infected patients. This study aimed to evaluate the impact of the pandemic on the quality of life of a population with hereditary gastrointestinal cancer predisposition syndromes and on the surveillance/oncological care program of patients enrolled in a dedicated registry.

Methods: The study was conducted by means of an online self-report survey during the first Italian national lockdown.

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Familial adenomatous polyposis (FAP) is an autosomal-dominant hereditary condition associated with germline mutations in the adenomatous polyposis coli gene. Patient management involves prophylactic surgery and intensive life-long endoscopic surveillance. Diet is a major concern for patients with FAP, who are generally free of symptoms before surgery but tend to have issues related to bowel function postoperatively.

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Background: We aimed to investigate changes in volume and MRI T2-weighted intensity in desmoid-type fibromatosis (DF) receiving methotrexate plus vinca-alkaloids (MTX-VA) at Istituto Nazionale dei Tumori, Milan.

Methods: All cases of sporadic DF treated with MTX-VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2-signal intensity (normalized to muscle) changes.

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