Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation.
View Article and Find Full Text PDFPhylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA.
View Article and Find Full Text PDFDysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites.
View Article and Find Full Text PDF: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery; it is a test of chemosensibility in vivo with significant prognostic value and may be used to tailor adjuvant treatment according to the response. : A retrospective single-institution cohort of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans, plus antiHEr2 in Her2-positive cases, was studied. Survival was calculated at 5 and 10 years.
View Article and Find Full Text PDFPathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. ( is a key target of TDP-43 regulation and aberrantly spliced mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation.
View Article and Find Full Text PDFMalignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis.
View Article and Find Full Text PDFIntroduction: Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases.
View Article and Find Full Text PDFBreast Cancer Res Treat
June 2023
Purpose: To evaluate the differences in nodal positivity if the sentinel lymph node biopsy (SLNB) is performed before or after neoadjuvant endocrine therapy (NET) in breast cancer patients, and its impact on prognosis.
Methods: A retrospective cohort study was performed in a single center including 91 postmenopausal cases with clinically node-negative and hormone receptor-positive/HER2-negative (HR + /HER2-) breast cancer, treated with NET and SLNB. SLNB was done pre-NET until 2014, and post-NET thereafter.
Objective: Gastric cancer (GC) is a leading cause of cancer mortality, with being the second most frequently mutated driver gene in GC. We sought to decipher -specific GC regulatory networks and examine therapeutic vulnerabilities arising from loss.
Design: Genomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures of inactivation across molecular subtypes.
Sepsis is a substantial healthcare burden, and its management continues to be a major challenge. Prior studies demonstrate conflicting evidence regarding the utility of vitamin C in sepsis. This systematic review and meta-analysis aim to collect data among critically ill patients (sepsis/septic shock), comparing the efficacy of parenteral vitamin C with standard care.
View Article and Find Full Text PDFThe coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator.
View Article and Find Full Text PDFUnlabelled: Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels.
View Article and Find Full Text PDFFlowers have been used for centuries in decoration and traditional medicine, and as components of dishes. In this study, carotenoids and phenolics from 125 flowers were determined by liquid chromatography (RRLC and UHPLC). After comparing four different extractants, the carotenoids were extracted with acetone: methanol (2:1), which led to a recovery of 83%.
View Article and Find Full Text PDFBreast Cancer Res Treat
August 2021
Purpose: To report the outcomes of implementing the ACOSOG Z0011 and AMAROS trials relevant to clinical practice, and to define target groups in whom to avoid or recommend axillary radiotherapy (ART). We also aimed to analyse the reduction in morbidity when axillary lymph node dissection (ALND) was omitted.
Methods: A retrospective cohort study of T1-T2 patients with macrometastases at sentinel lymph node (SLN) who were treated between 2011 and 2020.
Breast Cancer Res Treat
February 2021
Purpose: To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy.
Methods: A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present.
Background And Objective: It remains controversial whether sentinel lymph node biopsy (SLNB) should be performed before or after neoadjuvant therapy (NAT). We aimed to evaluate the feasibility and accuracy of SLNB before NAT at a single institution, and to determine its relation to patient prognosis.
Methods: A prospective study of T1c-T2-T3 N0 breast cancer patients, after ultrasound examination, who underwent SLNB prior to NAT.
Virchows Arch
September 2016
DIPNECH is characterized by neuroendocrine cell hyperplasia, tumorlets, and eventually carcinoid tumors. Although it is regarded by some authors as a preneoplastic condition, this issue is controversial. New pathologic criteria have recently been proposed for the diagnosis of DIPNECH, and a subgroup of carcinoid tumors expressing developing neural transcription factors (DNTFs), with clinicopathologic features similar to those of DIPNECH, has been recognized.
View Article and Find Full Text PDFA 58-year old woman with chronic schizophrenia developed worsening parkinsonian symptoms over the previous 6 years, and was eventually diagnosed as having Parkinson's disease. Antipsychotics were stopped because they worsened these symptoms. Antiparkinsonian treatment led to a significant increase in delusions and behavioural disorganisation.
View Article and Find Full Text PDFBackground: The need for axillary lymph node dissection (ALND) in breast cancer patients with sentinel lymph node (SLN) micrometastases remains controversial. The aims of the study were to evaluate the locoregional failure and outcome of breast cancer patients with sentinel node micrometastases who did not undergo completion ALND.
Methods: Between November 2000 and December 2006, SLN biopsy was successfully performed in 1178 patients with invasive breast carcinoma.
Objective: The aim of the study was to determine the evolution of patients with internal mammary chain (IMC) drainage whether the IMC-sentinel lymph node (IMC-SLN) was biopsied or not, as well as to determine the clinical implications of the biopsy of the IMC-SLN (IMC-SLNB) in patients with breast cancer and IMC drainage in the lymphoscintigraphy.
Methods: Eighty-two out of 914 patients included in a prospective database of sentinel node (9%) showed IMC drainage and were included in the study. Two groups were established depending on the IMC-SLN removal: group A (IMC-SLN were removed): 44 patients, mean age 48.
Objectives: To investigate particle size distribution and possible effects of colloid concentration and time after its preparation on the particle sizes of albumin nanocolloid (Nanocoll), rhenium sulfide nanocolloid (Nanocis) and tin colloid (Hepatate).
Methods: All three kits were prepared according to the manufacturers' instructions using the following volumes of decayed Tc generator eluate: 1.5 ml, 3.