Phase I trial of phIL12 plasmid intratumoral gene electrotransfer in patients with basal cell carcinoma in head and neck region.

Introduction: In the treatment of cancer, immunomodulatory approaches are developed to support the organism in fighting cancer or to enhance the immunomodulatory effects of local ablative techniques. To this end, we conducted an interventional, open-label, single-arm Phase I trial to evaluate the safety and tolerability of intratumoral phIL12 plasmid DNA gene electrotransfer as primary objectives.

Methods: The study was dose-escalating with 3 consecutive cohorts of 3 patients per phIL12 dose level (0.

Clustering Algorithm-Driven Detection of TRBC1-Restricted Clonal T-Cell Populations Produces Better Results than Manual Gating Analysis.

Flow cytometric (FC) immunophenotyping and T-cell receptor (TCR) gene rearrangement studies are essential ancillary methods for the characterisation of T-cell lymphomas. Traditional manual gating and polymerase chain reaction (PCR)-based analyses can be labour-intensive, operator-dependent, and have limitations in terms of sensitivity and specificity. The objective of our study was to investigate the efficacy of the Phenograph and t-SNE algorithms together with an antibody specific for the TCR β-chain constant region 1 (TRBC1) to identify monoclonal T-cell populations.

FoxP3 Regulatory T-Cell Quantities in Nodal T-Follicular Helper Cell Lymphomas and Peripheral T-Cell Lymphomas Not Otherwise Specified and Their Impact on Overall Survival.

Background/objectives: The tumour microenvironment (TME) plays an important role in the development and progression of cancer and it differs among lymphomas, both with respect to the composition and quantity of specific tumour-infiltrating immune cells (TICs), such as FoxP3 regulatory T cells (Tregs). The role of FoxP3 Tregs in the TME of peripheral T-cell lymphomas (PTCLs) is complex, and their impact on overall survival (OS) remains unclear. Consequently, we aim to evaluate and compare the FoxP3 cell quantity in nodal PTCLs and reactive lymph nodes (LNs), with a focus on investigating their impact on OS.

Predicting nodal response to neoadjuvant treatment in breast cancer with core biopsy biomarkers of tumor microenvironment using data mining.

Purpose: To generate a model for predicting nodal response to neoadjuvant systemic treatment (NAST) in biopsy-proven node-positive breast cancer patients (cN+) that incorporates tumor microenvironment (TME) characteristics and could be used for planning the axillary surgical staging procedure.

Methods: Clinical and pathologic features were retrospectively collected for 437 patients. Core biopsy (CB) samples were reviewed for stromal content and tumor-infiltrating lymphocytes (TIL).

Non-clinical evaluation of pmIL12 gene therapy for approval of the phase I clinical study.

Immunotherapeutic drugs are promising medicines for cancer treatment. A potential candidate for immunotherapy is interleukin-12 (IL-12), a cytokine well known for its ability to mediate antitumor activity. We developed a plasmid encoding human IL-12 devoid of an antibiotic resistance gene (phIL12).

Treatment of vulvar cancer recurrence with electrochemotherapy: a case-control study.

Background: Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used, surgery is often the only treatment option for vulvar cancer recurrence with potential resection of clitoris, vagina, urethra or anal sphincter. The unique advantage of ECT is its selectivity for cancer cells while sparing the surrounding healthy tissue.

Results from the UNITED study: a multicenter study validating the prognostic effect of the tumor-stroma ratio in colon cancer.

Background: The TNM (tumor-node-metastasis) Evaluation Committee of Union for International Cancer Control (UICC) and College of American Pathologists (CAP) recommended to prospectively validate the cost-effective and robust tumor-stroma ratio (TSR) as an independent prognostic parameter, since high intratumor stromal percentages have previously predicted poor patient-related outcomes.

Patients And Methods: The 'Uniform Noting for International application of Tumor-stroma ratio as Easy Diagnostic tool' (UNITED) study enrolled patients in 27 participating centers in 12 countries worldwide. The TSR, categorized as stroma-high (>50%) or stroma-low (≤50%), was scored through standardized microscopic assessment by certified pathologists, and effect on disease-free survival (DFS) was evaluated with 3-year median follow-up.

Do Double-Expressor High-Grade B-Cell Lymphomas Really Need Intensified Treatment? A Report from the Real-Life Series of High-Grade B-Cell Lymphomas Treated with Different Therapeutic Protocols at the Institute of Oncology Ljubljana.

High-grade B-cell lymphomas with and and/or rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with and and/or rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed.

The prognostic significance of programmed cell death protein 1 and its ligand on lymphoma cells and tumor-immune cells in diffuse large B-cell lymphoma, not otherwise specified.

Background: Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type non-Hodgkin's lymphoma, where the treatment of relapsed/refractory cases is the major challenge. Programmed cell death protein 1 (PD-1) and its ligand PD-L1 play a crucial role in the negative regulation of the immune response against the disease. The aim of the study was to analyze the expression of PD-1 and PD-L1 on lymphoma cells (LCs) and tumor-immune cells (TICs) and to investigate their correlation with outcome.

Detection performance and prognostic value of initial bone marrow involvement in diffuse large B-cell lymphoma: a single centre F-FDG PET/CT and bone marrow biopsy evaluation study.

Background: Detection of bone marrow involvement (BMI) in diffuse large B-cell lymphoma (DLBCL) typically relies on invasive bone marrow biopsy (BMB) that faces procedure limitations, while F-FDG PET/CT imaging offers a noninvasive alternative. The present study assesses the performance of F-FDG PET/CT in DLBCL BMI detection, its agreement with BMB, and the impact of BMI on survival outcomes.

Patients And Methods: This retrospective study analyzes baseline F-FDG PET/CT and BMB findings in145 stage II-IV DLBCL patients, evaluating both performance of the two diagnostic procedures and the impact of BMI on survival.

The prognostic significance of tumor-immune microenvironment in ascites of patients with high-grade serous carcinoma.

Background: High-grade serous carcinoma (HGSC) is often associated with ascites at presentation. Our objective was to quantify immune cells (ICs) in ascites prior to any treatment was given and evaluate their impact on progression-free survival (PFS) and overall survival (OS).

Patients And Methods: Forty-seven patients with primary HGSC and ascites were included.

Clear Cell Carcinoma Arising in Low-Grade Mullerian Adenosarcoma: First Reported Case with Insight into Molecular Profile.

Uterine adenosarcoma (AS) is a rare biphasic neoplasm composed of a malignant, usually low-grade stromal component and benign epithelial component, usually endometrioid. Pathogenesis is unknown; some cases are undoubtably associated with tamoxifen use. Endometrial clear cell carcinoma (CCC) is an aggressive subtype of endometrial cancer, accounting for less than 10% of all uterine carcinomas.

Morphological and Immunocytochemical Characterization of Tumor Spheroids in Ascites from High-Grade Serous Carcinoma.

Tumor spheroids in the ascites of high-grade serous carcinoma (HGSC) are poorly described. Our objective was to describe their morphological features, cellular composition, PD-1 and PD-L1 expression, and survival correlation of these parameters. The density and size of spheroids were assessed in Giemsa-stained smears; the cell composition of spheroids, including tumor cells, immune cells, capillaries, and myofibroblasts, as well as PD-1 and PD-L1 expression on tumor and immune cells was assessed in immunocytochemically stained cell block sections.

Axillary ultrasound for predicting response to neoadjuvant treatment in breast cancer patients-a single institution experience.

Background: In node-positive breast cancer patients at diagnosis (cN +) that render node-negative after neoadjuvant systemic treatment (NAST), axillary lymph node dissection (ALND) can be avoided in selected cases. Axillary ultrasound (AUS) is most often used for re-staging after NAST. We aimed to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AUS after NAST for predicting nodal response at the Institute of Oncology, Ljubljana.

Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node-positive breast cancer patients.

Purpose: To determine whether the absence of post-treatment changes in the negative sentinel lymph nodes (SLN) in the neoadjuvant setting for biopsy-proven cN + disease results in an increased regional recurrence (RR) rate in patients after SLN biopsy (SLNB) only.

Methods: Breast cancer patients with biopsy-proven cN + disease who converted to node-negative disease after neoadjuvant systemic treatment (NAST) and underwent SLNB only were included. Retrospective analysis was performed for patients diagnosed between 2008 and 2021.

Histologic changes of porcine portal vein anastomosis after electrochemotherapy with bleomycin.

Electrochemotherapy (ECT) is used for treatment of unresectable abdominal malignancies. This study aims to show that ECT of porcine portal vein anastomosis is safe and feasible in order to extend the indications for margin attenuation after resection of locally advanced pancreatic carcinoma. No marked differences were found between the control group and ECT treated groups.

Electrochemotherapy of Melanoma Cutaneous Metastases in Organ Transplant Recipients: A Systematic Review of Preclinical and Clinical Studies.

Cutaneous melanoma is a highly aggressive form of skin cancer. The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of advanced melanoma, led to durable responses, and improved overall survival. However, the success of ICIs in melanoma treatment is influenced by the tumor microenvironment (TME) which plays a critical role in regulating the immune response to the tumor.

CD56-positive diffuse large B-cell lymphoma: comprehensive analysis of clinical, pathological, and molecular characteristics with literature review.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. The expression of CD56 in DLBCL is highly unusual. Little is known about its incidence and clinical importance.

Treatment of vulvar cancer recurrences with electrochemotherapy - a detailed analysis of possible causes for unsuccessful treatment.

Background: Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported the safety and effectiveness of electrochemotherapy for palliative treatment of gynecological cancers and mostly vulvar squamous cell carcinoma. Some tumors, however, fail to respond to electrochemotherapy.

Cytokeratin and CD56 aberrant co-expression in diffuse large B-cell lymphoma, NOS misinterpreted as metastatic neuroendocrine carcinoma by FNAC.

Aberrant expression of epithelial and neuroendocrine markers is rare in diffuse large B-cell lymphoma (DLBCL) and can lead to erroneous diagnosis with inappropriate treatment. This case report describes a case of DLBCL with a co-expression of cytokeratins and CD56 that was misdiagnosed as metastatic neuroendocrine carcinoma.

Numerical mesoscale tissue model of electrochemotherapy in liver based on histological findings.

Electrochemotherapy (ECT) and irreversible electroporation (IRE) are being investigated for treatment of hepatic tumours. The liver is a highly heterogeneous organ, permeated with a network of macro- and microvasculature, biliary tracts and connective tissue. The success of ECT and IRE depends on sufficient electric field established in whole target tissue; therefore, tissue heterogeneity may affect the treatment outcome.

NUT Carcinoma: A Clinical, Morphological and Immunohistochemical Mimicker-The Role of RNA Sequencing in the Diagnostic Procedure.

NUT carcinoma is a highly aggressive and rare subset of squamous cell carcinoma with grim prognosis. It is under-recognized by both pathologists and oncologists. Recognition is challenging due to its rareness and the fact that its clinical and laboratory features as well as morphological and immunohistochemical characteristics may mimic other malignancies.

A Systematic Review about Imaging and Histopathological Findings for Detecting and Evaluating Electroporation Based Treatments Response.

Background: Imaging methods and the most appropriate criteria to be used for detecting and evaluating response to oncological treatments depend on the pathology and anatomical site to be treated and on the treatment to be performed. This document provides a general overview of the main imaging and histopathological findings of electroporation-based treatments (Electrochemotherapy-ECT and Irreversible electroporation-IRE) compared to thermal approach, such as radiofrequency ablation (RFA), in deep-seated cancers with a particular attention to pancreatic and liver cancer.

Methods: Numerous electronic datasets were examined: PubMed, Scopus, Web of Science and Google Scholar.