Achieving a pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) is strongly associated with improved survival. This study investigates whether bilateral asymmetry of quantitative perfusion parameters in normal parenchyma from ultrafast dynamic contrast-enhanced MRI (DCE-MRI), measured using k-means clustering (KMC) before NAC, can predict pCR in breast cancer patients.

Fifty-six breast cancer patients undergoing NAC with pretreatment ultrafast DCE-MRI (3-9 s/image at 3T) were enrolled. KMC was used to classify tumor and normal parenchymal voxels into five clusters based on maximum enhancement rate (A·α). Ipsilateral-to-contralateral (I/C) ratios of background parenchymal enhancement kinetics (kBPE) and tumor kinetics (kT) were compared between pCR and nonpCR groups. Logistic regression models were developed to predict pCR. Statistical tests included bootstrapping, z-test, chi-square, and Wilcoxon rank-sum.

Patients with residual disease showed significantly higher kBPE in the normal-appearing parenchyma of the ipsilateral breast compared to the contralateral side. Parameters including enhancement rate α, A·α, area under the enhancement curve for 30 s AUC30, volume transfer constant K^{tran s}, and rate constant of contrast transfer, K_ep, were significantly higher, while extravascular extracellular space fractional volume, v_e, was significantly lower in the ipsilateral breast parenchyma versus contralateral breast parenchyma for women who have residual disease (p < 0.05). A prediction model using kBPE asymmetry alone achieved an area under the curve (AUC) of 0.83. Including tumor kinetics improved the AUC to 0.85.

Bilateral asymmetry of kBPE parameters derived from ultrafast DCE-MRI using KMC before NAC initiation can predict pCR with high accuracy, providing a new minimal-invasive biomarker for treatment response.

Piezo1 ion channels play a crucial role in apoptosis regulation in human breast cancer cells (MCF-7), and this study evaluates the effects of Piezo1 agonist (Yoda1), inhibitor (GsMTx4), and ultrasound microbubble (USMB) treatment on cellular apoptosis pathways. In this research, in vitro cultures of normal breast epithelial cells (MCF-10A) and cancer cell lines (MCF-7, MDA-MB-231) were analyzed by Western blotting to determine Piezo1 protein levels, with MCF-7 selected for further analysis. Groups included control (untreated), Yoda1, USMB, GsMTx4, and USMB+GsMTx4, and apoptosis rates were measured via flow cytometry. Levels of apoptosis-related proteins (Bcl-2, Bax), endoplasmic reticulum stress proteins (GRP-78, Caspase 12), and mitochondrial pathway proteins (Cyt-c, Caspase 3, Caspase 9) were quantified, while JC-1 and Ca2+ fluorescent probes were used to assess mitochondrial membrane potential and intracellular Ca2+ concentration. Results showed MCF-7 cells expressed the highest Piezo1 levels. Yoda1 and USMB both markedly increased apoptosis, enhanced ER stress, and induced the mitochondrial apoptosis pathway in comparison to control, while GsMTx4 had the opposite effect and USMB reversed GsMTx4's phenotype. The USMB group exhibited the lowest mitochondrial membrane potential and the highest Ca2+ fluorescence intensity. These findings indicate that USMB activates ER stress via Piezo1, induces mitochondrial dysfunction, elevates intracellular Ca2+, and thereby promotes apoptosis in breast cancer cells.​​.

This descriptive study addresses a critical research gap by examining HPV and cervical neoplasia among women who have sex with women (WSW) in Cameroon, an underserved population. WSW typically undergo less frequent cervical cancer screening. We conducted a pilot study in Douala, Cameroon, recruiting WSW through Elle Cameroon, a community organization serving underserved populations. Working within the Cameroon Baptist Convention Health Services, participants underwent HPV screening and Visual Inspection with Acetic Acid (VIA) enhanced by Digital Cervicography (DC). We ran the frequencies and determined the p-values, prevalence odds ratios (POR) and prevalence risk ratios (PRR) using STATA 17. Statistical significance was set at 0.05. Of 26 participants enrolled, 19 (73.1%) provided valid HPV results, with 57.9% (11/19) testing positive for HPV. Also 80.8 % (21/26) of the participants were screened for cervical neoplasia and 19.05% (4/19) were positive. There was no significant association between HPV cervical neoplasia. Those who were HPV positive had 1.4 and 1.3 POR and PRR respectively. Our results suggest high prevalence of oncogenic HPV and cervical neoplasia among WSW in Cameroon. An adequately powered study is needed to further elucidate these findings and address healthcare disparities in this underserved population.

Evidence is limited concerning whether and to what extent fine particulate matter pollution (particulate matter with an aerodynamic diameter less than 2.5 μm [PM_2.5]) is linked to the risk and the time to occurrence of site-specific cancers along with the key constituents of PM_2.5 and the sensitive exposure window.

By using data from 277,446 participants in the UK Biobank, the authors estimated exposures to PM_2.5 and its 15 constituents during each participant's lifetime and at different life stages using a bilinear interpolation method. The incidence and time to occurrence of 14 cancers were ascertained. Cox proportional hazard models and accelerated failure time models were applied to investigate the associations between air pollutants and incidence risk and occurrence time of 14 cancers.

During a mean follow-up of 11.15 years, 25,820 patients with incident cancer were identified. Lifetime exposure to PM_2.5 and to its constituents was associated with an increased incidence risk of 12 of 14 cancers, with hazard ratios and 95% confidence intervals ranging from 1.04 (95% confidence interval, 1.01-1.07) for breast cancer to 1.18 (95% confidence interval, 1.10-1.27) for esophageal cancer. The constituents chloride ion, ammonium, nitrate, and sodium demonstrated the most pronounced effects. The middle-aged and elderly life stage (individuals aged 45 years and older) comprised the sensitive exposure window. The time to occurrence of cancers was earlier by from 0.05 years (ovarian cancer) to 1.95 years (esophageal cancer) because of overexposure to PM_2.5 levels greater than 5 μg/m³.

Lifetime exposure to PM_2.5 and its constituents might increase the risk and accelerate the onset of various cancers. Combustion-sourced and agriculture-sourced components mainly account for this influence, with the middle-aged and elderly life stage (aged 45 years and older) a sensitive exposure window.

Fluoropyrimidines are a vital component of chemotherapy regimens. Deleterious DPYD variants reduce activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme of fluoropyrimidine catabolism, resulting in reduced fluoropyrimidine clearance and elevated risk of life-threatening toxicities. DPYD genotype-guided fluoropyrimidine therapy can mitigate the risk of severe life-threatening toxicities, but adoption of testing globally has been limited. We developed a 91-item survey investigating global DPYD implementation strategies to gain insight into common practices and successful strategies. The survey was disseminated to Pharmacogenomics Global Research Network Implementation Working Group members consisting of 54 health care sites across 15 countries. Survey responses were received from 28 sites (52%) across 9 countries. Over 80% of sites implemented, or planned to implement, a preemptive testing strategy (i.e., before a fluoropyrimidine is administered) leveraging the electronic health record (EHR) to disseminate DPYD results to providers. All sites created infrastructure to support DPYD testing (e.g., order sets, EHR decision support), but 70% of sites indicated reliance on clinicians to remember test ordering. Only 2 sites reported high DPYD testing rates (> 75%) among patients planned to receive a fluoropyrimidine. Most sites (57%) used in-house clinical laboratories that tested for the majority of DPYD Tier 1 variants. Among sites that had implemented DPYD testing, the median turnaround time was 10 days. Few sites indicated that a high percentage (> 75%) of DPYD results were returned before fluoropyrimidine administration. Our results suggest that additional implementation strategies are needed, addressing barriers and facilitators of DPYD testing.

Laryngeal lymphoid hyperplasia is an extremely rare pathology, and clinical cases of this pathology described in the literature are limited. This article presents a clinical case of a patient with nodular idiopathic reactive lymphoid hyperplasia of the vestibular larynx. Patient G., 53 years old, was admitted to the department in April 2024 complaining of tracheostomy, difficulty swallowing, hoarseness. After the examination, the diagnosis was established: neoplasm of the larynx. Laryngeal stenosis. Tracheostomy. A neoplasm removal was performed via direct laryngoscopy under general anesthesia using radiofrequency device Surgitron and an ARC TrueBlue 445 nm surgical laser. The morphological picture was similar to a lymphoproliferative disorder. However, immunohistochemical reactions with antibodies to bcl-6 (clone GI191E/A8, Cell Marque Corporation) and to bcl-2 (clone 124, Cell Marque Corporation) canceled the diagnosis of lymphoma and established the diagnosis of supraglottic submucosa nodular idiopathic reactive lymphoid hyperplasia. The patient was decannulated and fully rehabilitated. Idiopathic lymphoid hyperplasia of the larynx is an extremely rare cause of airway stenosis that requires surgical intervention. The diagnosis should be differentiated with lymphoproliferative disorders and with foci of ectopic tonsil tissue. The diagnosis should be based on a thoroughly conducted histological examination with immunohistochemical reactions.

To analyze the ADIPOQ and ADIPOR1 levels in breast tumour tissue and adjacent adipose tissue of postmenopausal women with this cancer. We hypothesized that the tumour microenvironment (TME) of the breast had lower levels of ADIPOQ and ADIPOR1 in postmenopausal women with obesity than in those with a normal BMI.

Twenty women with normal body mass index (BMI) and 20 with obesity, all of them postmenopausal and with breast cancer (BC) were included. We obtained during surgery fresh breast tumour tissue and a fragment of breast adipose tissue adjacent to the tumour and analyzed the levels of adiponectin (ADIPOQ) and its receptor ADIPOR1 by Western blot. Statistical power of the study was > 80% with a p < 0.05ADIPOR1 protein levels were higher in breast tumour tissue versus breast adipose tissue adjacent to the tumour in postmenopausal women with normal BMI and postmenopausal women with obesity (p = 0.0012 and p = 0.0001, respectively). Moreover, we observed higher ADIPOR1 levels only in breast adipose tissue adjacent to the tumour in postmenopausal women with obesity and tumour size > 2.0 cm and clinical stage II/III (p = 0.019 and p = 0.025, respectively) versus postmenopausal women with a normal BMI. We did not observe differences in ADIPOQ.

ADIPOR1 levels were higher in breast tumour tissue compared to breast adipose tissue adjacent to the tumour in both postmenopausal women with normal BMI or with obesity. Besides, ADIPOR1 levels were higher in breast adipose tissue adjacent to the tumour of postmenopausal women and obesity, with a more aggressive breast tumour.

Myxomas are tumors that occur due to the uncontrolled proliferation of mesenchymal cells. Cardiac myxomas, although very rare, are the most common primary tumors of this location, with a prevalence of 0.03% in the general population. This paper describes a clinical case of ischemic stroke (IS) in a patient with cardiac myxoma. It has been shown that non-invasive diagnostic methods, such as echocardiography and computer and magnetic resonance imaging, should be used to detect and assess cardiac tumors. Echocardiography in IS patients prevents recurrences associated with myxoma. Therefore, it is crucial to detect and remove the tumor at an early stage.

ObjectiveThe role of the tumor suppressor p53 apoptosis effector related to PMP-22 (PERP) in breast cancer metastasis remains unclear. This study investigated PERP's role in metastatic progression, its clinical significance, and the mechanisms underlying its effects.MethodsPERP expression was assessed in breast cancer cell lines, public datasets, and 142 patient samples using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry. In vitro migration and invasion assays as well as in vivo metastasis model were performed after PERP overexpression or knockdown in MDA-MB-231 and MCF-7 cells. The roles of activating transcription factor 3 (ATF3) and heat shock protein family A member 6 (HSPA6) were evaluated through small-interfering RNA-mediated modulation, RNA sequencing, western blotting, RT-qPCR, and chromatin immunoprecipitation.ResultsPERP expression was markedly reduced in breast cancer cells and tumor tissues compared with that in normal controls, and low PERP levels were associated with poor prognosis. PERP overexpression suppressed metastasis. Mechanistically, PERP upregulated ATF3 expression, and ATF3 bound to the HSPA6 promoter to activate its transcription. Knockdown of ATF3 or HSPA6 eliminated the antimetastatic effects of PERP.ConclusionsPERP suppresses breast cancer metastasis by inducing ATF3, which in turn activates HSPA6 transcription. This PERP-ATF3-HSPA6 axis represents a key regulatory pathway and serves as a potential therapeutic target in metastatic breast cancer.

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by the activation of the JAK-STAT pathway. Previous evidence showed that metformin might be a possible therapeutic option for treating JAK2-mediated myeloproliferative neoplasms. In vitro and in vivo studies demonstrated that metformin inhibits the JAK-STAT pathway, induces apoptosis in JAK2^V617F-positive cell lines and reduces tumor burden and splenomegaly in Jak2^V617F knock-in-induced mice. The FIBROMET trial, an open label phase II study, evaluated metformin effects on 10 primary myelofibrosis patients over 2 years of treatment. Primary endpoint was bone marrow fibrosis reduction. Secondary endpoints were constitutional symptoms, blood counts, spleen size modulation and exploratory evaluation of protein and gene expression. Metformin treatment reduced bone marrow collagen deposits, downregulated the STAT pathway and reduced the p85 subunit of PI3K enzymatic complex, together with endothelial maintenance genes, in PMF patients. These results raise new evidence regarding metformin, a cheap and widely available drug, as a possible adjuvant for the treatment of PMF patients.