Publications by authors named "MANDL A"

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death among men in the United States. The global burden of this disease is rising, placing significant strain on healthcare systems worldwide. Although definitive therapies like surgery and radiation are often effective, prostate cancer can recur and progress to castration-resistant prostate cancer in some cases.

View Article and Find Full Text PDF
Article Synopsis
  • High-dose intravenous vitamin C (HDIVC) was tested alongside docetaxel in a clinical trial for patients with advanced prostate cancer, showing no significant benefit compared to docetaxel alone.
  • The trial involved 47 participants and measured effectiveness through PSA response rates, overall survival, and quality of life, with similar outcomes in both the HDIVC and placebo groups.
  • The study was halted early due to no evidence that HDIVC improved cancer treatment results, suggesting it shouldn’t be routinely used for metastatic castration-resistant prostate cancer.
View Article and Find Full Text PDF
Article Synopsis
  • Lysine-specific demethylase 1 (LSD1) plays a key role in the progression of metastatic castration-resistant prostate cancer (mCRPC), particularly in its neuroendocrine form (NEPC), highlighting the need for effective LSD1 inhibitors like bomedemstat for treating these cancers.
  • Bomedemstat was evaluated using various scientific methods, showing it is an irreversible inhibitor of LSD1 with significantly higher specificity over monoamine oxidase enzymes, and it effectively reduces tumor growth in prostate cancer models.
  • The study found that bomedemstat accumulates well in tumors after oral administration and has an overall tolerable safety profile with manageable side effects, supporting its clinical
View Article and Find Full Text PDF
Article Synopsis
  • Lysine-specific demethylase 1 (LSD1) plays a crucial role in tumor progression in metastatic castration-resistant prostate cancer (mCRPC), particularly in the aggressive neuroendocrine subtype (NEPC) that shows resistance to typical therapies.* -
  • The study found that elevated LSD1 levels in NEPC correlate with poor clinical outcomes, and using the LSD1 inhibitor bomedemstat resulted in significant tumor regression in various cancer models.* -
  • Mechanistically, LSD1 inhibition was shown to disrupt key interactions that suppress a neuronal transcriptional program, highlighting the potential of LSD1 inhibitors as a promising treatment strategy for aggressive mCRPC types.*
View Article and Find Full Text PDF

Introduction: The bromodomain and extraterminal (BET) family of proteins are epigenetic readers of acetylated histones and are critical activators of oncogenic networks across many cancers. Therapeutic targeting of BET proteins has been an attractive area of clinical development for metastatic castration-resistant prostate cancer. In recent years, many structurally diverse BET inhibitors have been discovered and tested.

View Article and Find Full Text PDF

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs.

View Article and Find Full Text PDF

We describe two cases of acquired parathyroid hormone (PTH) resistance consequent to the development of serum PTH type 1 receptor (PTH1R) autoantibodies, which block PTH binding and signaling. Both cases were associated with other autoimmune manifestations, and one case was associated with atypical membranous glomerulonephritis. In vitro binding and signaling assays identified the presence of PTH1R-blocking IgG autoantibodies, which were not present in serum samples from patients with other renal or autoimmune disorders.

View Article and Find Full Text PDF
Article Synopsis
  • Patients with MEN1 syndrome have mutations in the MEN1 gene, making them susceptible to various tumors, including rare thymic neuroendocrine tumors (NETs), which can be lethal.
  • The study reviewed 294 MEN1 patients and found that 4.8% had thymic tumors, revealing that loss of heterozygosity (LOH) at the MEN1 gene locus contributes to these tumors' development.
  • RNA sequencing indicated that thymic NETs have a distinct gene expression profile, with KSR2 being highly expressed, suggesting it could be a target for future therapies.
View Article and Find Full Text PDF

Objective: To analyze the impact of the color of a resin composite cement (RCC) on the optical properties of different computer-aided design and computer-aided manufacturing (CAD/CAM) ceramics.

Materials And Methods: Specimens (N = 220, thickness: 0.9 ± 0.

View Article and Find Full Text PDF

Objectives: To investigate the impact of hydrothermal aging on Martens parameter (Martens hardness: HM/elastic indentation modulus: E) and biaxial flexural strength (BFS) of recently available CAD/CAM silicate ceramics.

Methods: 220 specimens (diameter: 12 mm, thickness: 0.95 mm) were fabricated from six CAD/CAM ceramics in two translucency levels (LT/HT): (a) two lithium disilicate (Amber Mill, ABM; IPS e.

View Article and Find Full Text PDF
Article Synopsis
  • MEN1 is a rare genetic disorder that can lead to the growth of tumors, and it's not clear if it usually causes blood clots.
  • A study looked at 286 MEN1 patients and found that 36 of them had blood clots, showing that MEN1 patients might have a higher risk of these clots than the general population.
  • Most patients with clots had tumors in their pancreas, and additional research is needed to understand this risk better.
View Article and Find Full Text PDF
Article Synopsis
  • * The loss of the menin protein, caused by MEN1 mutations, is a significant factor in the development of these tumors and leads to an increase in the oncogenic receptor c-MET.
  • * The review discusses clinical features, treatment options, and outcomes of GEP NETs, and highlights research on c-MET expression and potential treatments targeting c-MET as a precision-medicine strategy.
View Article and Find Full Text PDF

Summary: Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO.

View Article and Find Full Text PDF
Article Synopsis
  • Pheochromocytomas/paragangliomas (PPGLs) are rare tumors that can release norepinephrine, impacting brown adipose tissue (BAT) activation via β-adrenoceptors, which may correlate with cancer activity.
  • This study analyzed data from 342 PPGL patients, identifying 16 with BAT activation, and compared their outcomes to 36 matched controls using PET/CT imaging.
  • Results indicated that BAT activation in PPGL patients leads to significantly lower overall survival rates and is associated with higher plasma norepinephrine levels, suggesting that this activation may indicate higher mortality risk.
View Article and Find Full Text PDF

A 56-year-old woman with a history of hypothyroidism and chronic constipation presented with an acute abdomen due to colonic pseudo-obstruction. Thyroid function tests were consistent with central hypothyroidism prompting intravenous administration of stress-dose glucocorticoids and levothyroxine. The patient then underwent emergency exploratory laparotomy with sigmoid resection and end-colostomy.

View Article and Find Full Text PDF

A 36-year-old male patient initially presented with hypertension, tinnitus, bilateral carotid masses, a right jugular foramen, and a periaortic arch mass with an elevated plasma dopamine level but an otherwise normal biochemical profile. On surveillance MRI 4 years after initial presentation, he was found to have a 2.2-cm T2 hyperintense lesion with arterial enhancement adjacent to the gallbladder, which demonstrated avidity on Ga-DOTATATE PET/CT and retrospectively on F-FDOPA PET/CT but was non-avid on F-FDG PET/CT.

View Article and Find Full Text PDF

Background: Clinical practice needs a common parameter that can provide an early, reliable estimation of the outcome of sublingual immunotherapy (SLIT) in an upcoming pollen season. We investigated whether the conjunctival provocation test (CPT) can predict the beneficial outcome of SLIT in patients with allergic rhinoconjunctivitis after 4 weeks of treatment.

Methods: We conducted two separate prospective, randomized, double-blind, placebo-controlled, multicenter trials.

View Article and Find Full Text PDF

Background: The Global Allergy and Asthma European Network (GA LEN) Taskforce has requested more data on correlations between various patient-reported outcomes (PROs) in clinical trials on allergy. We compared three tools-the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Rhinitis Total Symptom Score (RTSS)-to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis.

Methods: In two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated.

View Article and Find Full Text PDF

Biomolecular assays based on the aggregation of modified gold nanoparticles (AuNPs) have been developed to provide low detection limits and rapid results with a simple one-step, wash-free procedure. However, a relatively narrow dynamic range, low sensitivity, and poor precision due to time-sensitive readout limit the application of these assay platforms. In this work we synthesized asymmetrically functionalized antibody-AuNP conjugates that are rationally designed to overcome the limitations of aggregation-based immunoassays.

View Article and Find Full Text PDF

Background: Puma (p53-upregulated modulator of apoptosis) is a proapoptotic Bcl-2 family protein that serves as a general sensor in response to pathological apoptotic stimuli. In previous work, we demonstrated that puma ablation protects the heart from reperfusion injury in a Langendorff setting. Consistent with this, downregulation of Puma in isolated cardiac myocytes prevented apoptosis induced by different proapoptotic agents.

View Article and Find Full Text PDF
Article Synopsis
  • Acute myocardial infarction is a major health issue in western countries, leading to high rates of illness and death.
  • Both apoptosis (programmed cell death) and necrosis (cell injury) of heart cells are key factors in this condition.
  • The chapter discusses methods for studying apoptosis in heart cells using isolated neonatal myocytes under conditions that simulate heart injury, with the goal of finding new treatment options for heart attacks.
View Article and Find Full Text PDF

Recent studies on cardiac hypertrophy animal model suggest that inter-domain interactions within the ryanodine receptor (RyR2) become defective concomitant with the development of hypertrophy (e.g. de-stabilization of the interaction between N-terminal and central domains of RyR2; T.

View Article and Find Full Text PDF
Article Synopsis
  • The endoplasmic reticulum (ER) plays a crucial role in protein synthesis, folding, and calcium storage, and disruptions can lead to ER stress and the unfolded protein response (UPR), which attempts to restore cellular balance.
  • Prolonged ER stress can lead to apoptosis, contributing to various diseases including brain damage, neurodegeneration, diabetes, and heart problems such as myocardial infarction and heart failure.
  • Recent studies indicate that while some UPR pathways may protect the heart, others can trigger cell death, with the protein Puma being a key player in this process, suggesting that targeting ER stress pathways could be a viable treatment strategy for heart-related diseases.
View Article and Find Full Text PDF

Phosphoinositide 3-kinase (PI3K) activation and synthesis of phosphatidylinositol-3,4-bisphosphate (PI-3,4-P2) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) lipids mediate growth factor signaling that leads to cell proliferation, migration, and survival. PI3K-dependent activation of Akt is critical for myoblast differentiation induced by serum withdrawal, suggesting that in these cells PI3K signaling is activated in an unconventional manner. Here we investigate the mechanisms by which PI3K signaling and Akt are regulated during myogenesis.

View Article and Find Full Text PDF

The announcement in January of the merger between America Online and Time Warner marked the convergence of the two most important business trends of the last five years--the rise of the Internet and the resurgence of mergers and acquisitions. M&A activity is at a fever pitch, spurred in large part by the breathtaking influx of capital into the Internet space. And all signs indicate the trend will only accelerate.

View Article and Find Full Text PDF