BRCA testing in metastatic castration-resistant prostate cancer: successes and troubles in a real world setting. An Italian Multicentric study.

Objective: Prostate cancer (PCa) is the most common cause of cancer-related deaths in men worldwide. BRCA1/2 genes are reported altered in approximately 1% and 8% of PCa cases, respectively. To date, formalin-fixed paraffin-embedded (FFPE) tissues have a consolidate use in the clinical practice, but with a significant drawback related to DNA/RNA degradation during the pre-analytical process.

The role of surgery in recurrent local cerebral metastases: a multi-institutional retrospective analysis.

Background: Local recurrent brain metastases are defined as lesions that recur in the brain at the same site after a previous local therapy. In patients already submitted to surgery, a second operation may be potentially challenging due to scar formation, infiltration of cerebral vessels or eloquent brain areas and local effect of previous radiotherapy. The aim of this study is to retrospectively review the results and complications of a second surgical treatment in a series of local recurrent lesions and to review the literature on this topic.

Second surgery for relapsed glioblastoma: an observational study on criteria for patient selection in real life.

There is little consensus on salvage management of glioblastoma after recurrence, for lack of evidence. A retrospective study of treatments in patients with recurrent glioblastoma. Surgery at recurrence was related to better overall survival (OS) and progression-free survival (PFS).

DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.

17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione.

The Molecular Tumor Board of the Regina Elena National Cancer Institute: from accrual to treatment in real-world.

Background: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options.

Methods: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe.

HSF-1/miR-145-5p transcriptional axis enhances hyperthermic intraperitoneal chemotherapy efficacy on peritoneal ovarian carcinosis.

Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) increases local drug concentrations and reduces systemic side effects associated with prolonged adjuvant intraperitoneal exposure in patients affected by either peritoneal malignancies or metastatic diseases originating from gastric, colon, kidney, and ovarian primary tumors. Mechanistically, the anticancer effects of HIPEC have been poorly explored. Herein we documented that HIPEC treatment promoted miR-145-5p expression paired with a significant downregulation of its oncogenic target genes c-MYC, EGFR, OCT4, and MUC1 in a pilot cohort of patients with ovarian peritoneal metastatic lesions.

The Glioma-IRE project - Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach.

Background: This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment.

Methods: Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions.

A diagnostic circulating miRNA signature as orchestrator of cell invasion via TKS4/TKS5/EFHD2 modulation in human gliomas.

Background: Altered microRNA profiles have been observed not only in tumour tissues but also in biofluids, where they circulate in a stable form thus representing interesting biomarker candidates. This study aimed to identify a microRNA signature as a non-invasive biomarker and to investigate its impact on glioma biology.

Methods: MicroRNAs were selected using a global expression profile in preoperative serum samples from 37 glioma patients.

Targeting tumor-stroma communication by blocking endothelin-1 receptors sensitizes high-grade serous ovarian cancer to PARP inhibition.

PARP inhibitors (PARPi) have changed the treatment paradigm of high-grade serous ovarian cancer (HG-SOC). However, the impact of this class of inhibitors in HG-SOC patients with a high rate of TP53 mutations is limited, highlighting the need to develop combinatorial therapeutic strategies to improve responses to PARPi. Here, we unveil how the endothelin-1/ET-1 receptor (ET-1/ET-1R) axis, which is overexpressed in human HG-SOC and associated with poor prognosis, instructs HG-SOC/tumor microenvironment (TME) communication via key pro-malignant factors and restricts the DNA damage response induced by the PARPi olaparib.

Overexpression in metastatic breast cancer supports Syndecan-1 as a marker of invasiveness and poor prognosis.

Background: Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to investigate and compare syndecan-1 tissue expression and localization in primary and secondary BC, focusing on brain metastases.

Breast cancer metastasis: Is it a matter of OMICS and proper ex-vivo models?

Genomics has greatly increased the understanding of the study of breast cancer (BC) and has shaped the concept of intra-tumor heterogeneity, currently recognized as a propelling force for cancer progression. In this context, knowledge and understanding of metastatic breast cancer (mBC) has somehow lagged behind that of primary breast cancer. This may be explained by the relative scarcity of matched mBC samples, however it is possible that the mutation spectrum obtained from primary BC does not capture the full complexity of the metastatic disease.

Definition of the Prognostic Role of MGMT Promoter Methylation Value by Pyrosequencing in Newly Diagnosed IDH Wild-Type Glioblastoma Patients Treated with Radiochemotherapy: A Large Multicenter Study.

Background. O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) methylation status is a predictive factor for alkylating treatment efficacy in glioblastoma patients, but its prognostic role is still unclear. We performed a large, multicenter study to evaluate the association between MGMT methylation value and survival.

Circulating cell free DNA and citrullinated histone H3 as useful biomarkers of NETosis in endometrial cancer.

Background: Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC).

Identification of novel COX-2 / CYP19A1 axis involved in the mesothelioma pathogenesis opens new therapeutic opportunities.

Background: Based on previous studies highlighting that the induction of cyclooxygenase-2 (COX-2) and high prostaglandin E2 (PGE2) levels contribute to the pathogenesis of malignant pleural mesothelioma (MPM), and that aromatase (CYP19A1), an enzyme that plays a key role in estrogen biosynthesis, along with estradiol (E2) were expressed in MPM, this study aimed to investigate the possible interplay between COX-2 and CYP19A1 in the pathogenesis of mesothelioma, as well as the underlying mechanism.

Methods: The interaction between COX-2 and CYP19A1 was first investigated on different MPM lines upon PGE2, and COX-2 inhibitor (rofecoxib) treatment by western blot, RT-PCR. The key regulatory pathways involved in the COX-2 and CYP19A1 axis were further studied in MPM cells, after rofecoxib and exemestane (CYP19A1 inhibitor) treatment in monotherapy and in combination, by cell cycle distribution, western blot, and combination index analysis.

Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors.

Background: The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins.

Schwannomas of the sciatic nerve: A rare and neglected diagnosis. A review of the literature with two illustrative cases.

Objective: Schwannomas of the sciatic nerve, which is the largest nerve of the human body, are very rare accounting for ≤ 1% of all schwannomas. They often may raise confusion with other more common causes of sciatica, such as lumbar degenerative and inflammatory diseases or spinal tumors, which may often lead to a late correct diagnosis.

Patients And Methods: We present two cases of sciatic nerve schwannomas that were recently treated at our Institution, and we review the pertinent English literature on this topic over the last 15 years, yielding twenty three cases to analyze.

Sister Mary Joseph's nodule in endometrial cancer: A case report and review of the literature.

Sister Mary Joseph's nodule (SMJN) is an umbilical mass referring to an intraabdominal and/or pelvic tumor's metastasis. SMJN is frequently associated with gynecological malignancies, but only 30 cases of SMJN originated from endometrial cancer have been described in the literature. We reported a case of SMJN detected within the primary diagnosis of endometrial cancer, in which a 1-year vaginal relapse occurs.

The effect of CELLFOOD on radiotherapy or combined chemoradiotherapy: preclinical evidence.

Background: Based on previous observations that the nutraceutical CELLFOOD™ (CF), the 'physiological modulator' that aimed to make oxygen available 'on demand', inhibits the growth of cancer cells, this study was designed to investigate the role of CF in the regulation of hypoxia-inducible factor 1 alpha (HIF1α) and its correlated proteins, phosphoglycerate kinase 1 and vascular endothelial growth factor. Our idea was that CF, acting on HIF1α, in combination with current anticancer therapies could improve their effectiveness.

Methods: To evaluate the effect of CF in association with radiotherapy and chemotherapy, different human cancer cell lines and mice with mesothelioma were analysed by tumour growth, clonogenic assay, western blot and immunohistochemical analysis.

Correction to: Phase II study of weekly carboplatin in pretreated adult malignant gliomas.

In the original article, the names of authors Mariantonia Carosi and Tatiana Koudriavtseva were incorrectly captured, and author Francesco Cognetti's affiliation was incorrect. The information is correctly shown here.

Neurocognitive evaluation in older adult patients affected by glioma.

Background: Glioblastoma (GBM) has an increasing incidence and dismal prognosis in older adults. This study evaluated neurocognitive status of an older adult population with GBM and its correlation with clinical and demographical variables.

Methods: Each patient underwent an extended neuropsychological evaluation by means of a battery of standardized tests describing eight cognitive domains: global function; verbal learning; short- and long-term memory (LTM); executive functions (EFs); abstract reasoning (AR); attention; and visuo-constructional abilities (CA).

Phase II study of weekly carboplatin in pretreated adult malignant gliomas.

Purpose: Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas.

Methods: This was a single-arm, phase II study.

A multicenter real-world study of bevacizumab in heavily pretreated malignant gliomas: clinical benefit is a plausible end point?

This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG).  The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. We collected data of 197 RG patients.