Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.

Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC.

Intratumoral or Subcutaneous MK-2118, a Non-Cyclic Dinucleotide STING Agonist, With or Without Pembrolizumab for Advanced or Metastatic Solid Tumors or Lymphomas.

Background: We evaluated the non-cyclic dinucleotide stimulator of interferon genes agonist MK-2118 ± pembrolizumab in patients with advanced solid tumors or lymphomas.

Methods: This first-in-human study (NCT03249792) enrolled patients with refractory, advanced solid tumors or lymphomas. Patients received intratumoral (IT) MK-2118 100-20,000 µg (arm 1), IT MK-2118 900-15,000 µg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (Q3W; arm 2), or subcutaneous (SC) MK-2118 5000-150,000 µg plus IV pembrolizumab 200 mg Q3W (arm 4); arm 3 (visceral injection of MK-2118) was not pursued.

The Antioxidant, Antimicrobial, and Antitumor Proprieties of Flavonol-Rich Extracts from (Wild Garlic) Leaves: A Comparison of Conventional Maceration and Ultrasound-Assisted Extraction Techniques.

Despite the growing interest in using natural compounds for disease prevention and treatment, (wild garlic), known for its therapeutic properties, has not been extensively studied for its chemical composition and biological activities. Therefore, this study aims to explore the in vitro antioxidant, antibacterial, and antitumor activities of extracts according to their functional phytochemical profile, while assessing whether ultrasound-assisted extraction (UAE) enhances bioactive properties in comparison to conventional maceration (CM). Both extracts were characterized by spectrophotometric methods and LC-ESI+-MS.

Acalabrutinib in combination with rituximab and lenalidomide in patients with relapsed or refractory follicular lymphoma: Results of the phase 1b open-label study (ACE-LY-003).

Patients with relapsed/refractory (R/R) follicular lymphoma (FL) have limited effective treatment options. Bruton tyrosine kinase inhibitors (BTKis) increase the anti-tumoural phenotype of tumour-associated macrophages, providing rationale to combine them with rituximab and lenalidomide (R). Acalabrutinib, a second-generation BTKi, has potential to improve R efficacy without increasing T-cell-mediated toxicity due to its lack of interleukin-2-inducible T-cell kinase inhibition.

Survival and Treatment Outcomes in Gastric Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis.

Background: Brain metastases (BM) from gastric cancer (GC) are rare but associated with poor prognosis, significantly impacting patient survival and quality of life. The objective of this systematic review and meta-analysis is to consolidate existing research on BM from GC, evaluate the incidence and clinical outcomes, and explore the effectiveness of treatment options.

Methods: A systematic search was conducted across the Medline, Web of Science, and Scopus databases, following PRISMA guidelines.

In silico splicing analysis of the PMS2 gene: exploring alternative molecular mechanisms in PMS2-associated Lynch syndrome.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated.

ER + HER2- early-stage breast cancer: association of HER2 expression, tumor characteristics, and outcomes.

Purpose: To evaluate the association between the HER2 score as provided by the Oncotype DX Recurrence Score (RS) assay, tumor characteristics, and outcomes in early-stage, ER + HER2-negative breast cancer (BC).

Methods: All women insured by the Clalit Health Services, with early-stage, ER + HER2-negative BC who underwent RS testing between 2008 and 2011 were included. Patient/tumor characteristics and Kaplan-Meier estimates for distant recurrence-free survival (DRFS) and overall survival (OS) were compared by HER2 category, based on the HER2 score provided by the RS assay: lower HER2 score group representing the lower third of the HER2 score range (≤ 8.

Identification of a central network hub of key prognostic genes based on correlation between transcriptomics and survival in patients with metastatic solid tumors.

Background: Dysregulated pathways in cancer may be hub addicted. Identifying these dysregulated networks for targeting might lead to novel therapeutic options.

Objective: Considering the hypothesis that central hubs are associated with increased lethality, identifying key hub targets within central networks could lead to the development of novel drugs with improved efficacy in advanced metastatic solid tumors.

The road to overcome pancreatic cancer: Where are we?

Pancreatic cancer (PC) is an intricate malignancy with poor prognosis. In the present state of the art review paper and clinical trial trend analysis, we explore the current clinically employed state of pancreatic cancer body of knowledge and future research directions. When considering PDACs' molecular biology, we underline the role of PanIN in carcinogenesis and mutational gain, as well as the distinctive tumor microenvironment with the characteristic dense fibrotic stroma.

Efficacy of chemotherapy after progression during or following PARPi exposure in ovarian cancer.

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) improved advanced ovarian cancer treatment. Most patients progress during or following PARPi exposure, however, with concerns about sensitivity of subsequent chemotherapy.

Patients And Methods: In this international cohort study, we evaluated the efficacy of a subsequent chemotherapy following PARPi exposure in high-grade ovarian carcinoma patients.

Dynamics and predictors of hematologic toxicity during cranio-spinal irradiation.

Background: Craniospinal irradiation (CSI) is a complex radiotherapy (RT) technique required for treating specific brain tumors and some hematologic malignancies. With large volumes of hematogenous bone marrow (BM) being irradiated, CSI could cause acute hematologic toxicity, leading to treatment interruptions or severe complications. We report on the dynamics and dose/volume predictors of hematologic toxicity during CSI.

Particle tracking, recognition and LET evaluation of out-of-field proton therapy delivered to a phantom with implants.

This study aims to assess the composition of scattered particles generated in proton therapy for tumors situated proximal to some titanium (Ti) dental implants. The investigation involves decomposing the mixed field and recording Linear Energy Transfer (LET) spectra to quantify the influence of metallic dental inserts located behind the tumor.A therapeutic conformal proton beam was used to deliver the treatment plan to an anthropomorphic head phantom with two types of implants inserted in the target volume (made of Ti and plastic, respectively).

A histopathological analysis of extrapulmonary lesions in fatal coronavirus disease (COVID-19).

Introduction: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues.

Materials And Methods: The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania.

The transcriptional landscape of cancer stem-like cell functionality in breast cancer.

Background: Cancer stem-like cells (CSCs) have been extensively researched as the primary drivers of therapy resistance and tumor relapse in patients with breast cancer. However, due to lack of specific molecular markers, increased phenotypic plasticity and no clear clinicopathological features, the assessment of CSCs presence and functionality in solid tumors is challenging. While several potential markers, such as CD24/CD44, have been proposed, the extent to which they truly represent the stem cell potential of tumors or merely provide static snapshots is still a subject of controversy.

Clinical Outcome of Colorectal Cancer Patients with Concomitant Hypertension: A Systematic Review and Meta-Analysis.

Background: Arterial hypertension is regarded as a possible biomarker of treatment efficacy in colorectal cancer. Also, extended anti-angiogenic use in the metastatic treatment of the colorectal neoplasm may result in elevated blood pressure. We carried out a systematic review and meta-analysis to assess the clinical outcome of colorectal cancer patients with concomitant hypertension (HTN).

Immunohistochemical and Morphometric Analysis of Lung Tissue in Fatal COVID-19.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2.