Catabolism of extracellular glutathione supplies amino acids to support tumor growth.

Restricting amino acids from tumors is an emerging therapeutic strategy with significant promise. While typically considered an intracellular antioxidant with tumor-promoting capabilities, glutathione (GSH) is a tripeptide of cysteine, glutamate, and glycine that can be catabolized, yielding amino acids. The extent to which GSH-derived amino acids are essential to cancers is unclear.

AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, responses are typically short lived. Thus, there is an urgent need to develop more effective treatments.

Osteosynthesis-associated infection in maxillofacial surgery by bacterial biofilms: a retrospective cohort study of 11 years.

Objectives: The aim of this retrospective cohort study was to determine risk factors for osteosynthesis-associated infections (OAI) with subsequent necessity of implant removal in oral and maxillofacial surgery.

Materials And Methods: A total of 3937 records of patients who received either orthognathic, trauma, or reconstructive jaw surgery from 2009 to 2021 were screened for osteosynthetic material removal due to infection. Treatment-intervals, volume of applied osteosynthetic material, and respective surgical procedures were also assessed.

STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer.

PARP inhibitors (PARPi) have drastically changed the treatment landscape of advanced ovarian tumors with BRCA mutations. However, the impact of this class of inhibitors in patients with advanced BRCA-mutant breast cancer is relatively modest. Using a syngeneic genetically-engineered mouse model of breast tumor driven by Brca1 deficiency, we show that tumor-associated macrophages (TAMs) blunt PARPi efficacy both in vivo and in vitro.

Spatial proteomic characterization of HER2-positive breast tumors through neoadjuvant therapy predicts response.

The addition of HER2-targeted agents to neoadjuvant chemotherapy has dramatically improved pathological complete response (pCR) rates in early-stage, HER2-positive breast cancer. Nonetheless, up to 50% of patients have residual disease after treatment, while others are likely overtreated. Here, we performed multiplex spatial proteomic characterization of 122 samples from 57 HER2-positive breast tumors from the neoadjuvant TRIO-US B07 clinical trial sampled pre-treatment, after 14-21 d of HER2-targeted therapy and at surgery.

A retrospective analysis of social media posts pertaining to COVID-19 vaccination side effects.

Objectives: With an uprising influence of social media platforms like Twitter and Instagram a multitude of worldwide accessible information is available. Since the beginning of COVID-19 pandemic the exchange of medical information about several topics related to this infectious disease and its vaccination has increased rapidly. The purpose of this investigation was to assess the content associated with COVID-19 vaccination and its side effects and evaluate its educational quality.

Long-Term Results After Head Orthosis Therapy for Early Childhood Position-Related Cranial Deformities: Stability of Treatment Outcome and Parental Satisfaction.

The purpose of this study was to determine whether different types of position-related cranial deformities show changes after completion of head orthosis therapy. We investigated how children's age at the begin of molding helmet therapy affects the duration and long-term stability of treatment. In addition, parental satisfaction with helmet therapy has been investigated.

#facialtraumasurgery: Educational Content of Instagram as a Social Media Source for Facial Trauma Surgery.

With an uprising influence of social media platforms like Instagram during the last decade, medical and healthcare related posts have accumulated majorly. In particular the head and face characterizes and signifies each individual's human character, which may be the reason why numerous posts are shared on social media platforms. The purpose of this investigation was to assess the content associated with facial trauma surgery and evaluate its educational quality.

A volumetric study of mandibular condyles in orthognathic patients by semiautomatic segmentation.

Purpose: This study was conducted to elucidate volumetric data of mandibular condyles of orthognathic patients by analyzing cone beam computed tomography images based upon semiautomatic segmentation.

Methods: Cone beam computed tomography images of 87 patients with malocclusions were analyzed in this retrospective study. Patients were between 17 and 53 years old and diagnosed with Angle class I, II, or III malocclusion.

Metabolic perturbations sensitize triple-negative breast cancers to apoptosis induced by BH3 mimetics.

Cancer cells have differential metabolic dependencies compared to their nonmalignant counterparts. However, few metabolism-targeting compounds have been successful in clinical trials. Here, we investigated the metabolic vulnerabilities of triple-negative breast cancer (TNBC), particularly those metabolic perturbations that increased mitochondrial apoptotic priming and sensitivity to BH3 mimetics (drugs that antagonize antiapoptotic proteins).

Clinical evaluation of BCL-2/XL levels pre- and post- HER2-targeted therapy.

Our previous pre-clinical work defined BCL-2 induction as a critical component of the adaptive response to lapatinib-mediated inhibition of HER2. To determine whether a similar BCL-2 upregulation occurs in lapatinib-treated patients, we evaluated gene expression within tumor biopsies, collected before and after lapatinib or trastuzumab treatment, from the TRIO-B-07 clinical trial (NCT#00769470). We detected BCL2 mRNA upregulation in both HER2+/ER- as well as HER2+/ER+ patient tumors treated with lapatinib or trastuzumab.

Comparison of two established 2D staging techniques to their appliance in 3D cone beam computer-tomography for dental age estimation.

For medicolegal purposes, orthodontic or orthognathic treatment various stomatological staging technique for age estimation with appliance of conventional radiographic images have been published. It remains uninvestigated if cone beam computer-tomography delivers comparable staging results to the conventional radiographic stages of third molar analysis. We conducted a retrospective cross-sectional study of 312 patients aged 13-21 years.

Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07).

In this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms.

Dexmedetomidine Dosing to Prevent Pediatric Emergence Delirium.

Because of the high incidence and untoward effects of emergence delirium in the pediatric population, investigating pharmacologic measures for preventing this phenomenon is important to the anesthesia provider. Dexmedetomidine, a highly selective α agonist, has been shown to prevent emergence delirium in the perioperative setting; however, recommendations for best practice regarding use of this medication are not widely available. Barriers to the use of dexmedetomidine may include side effects such as bradycardia and delayed emergence, as well as limited evidence for the best practice of timing, method, and dosing of dexmedetomidine.

Cefazolin versus ampicillin/sulbactam as an empiric antibiosis in severe odontogenic neck infection descending from the lower jaw-retrospective analysis of 350 cases.

Objectives: Odontogenic infections descending from the lower jaw may lead to severe health conditions. Commonly, a biphasic treatment of surgical drainage and antibiotic therapy is conducted. The choice of the administered empiric antibiotic agent remains debatable.

Neutralization of BCL-2/X Enhances the Cytotoxicity of T-DM1 .

One of the most recent advances in the treatment of HER2 breast cancer is the development of the antibody-drug conjugate, T-DM1. T-DM1 has proven clinical benefits for patients with advanced and/or metastatic breast cancer who have progressed on prior HER2-targeted therapies. However, T-DM1 resistance ultimately occurs and represents a major obstacle in the effective treatment of this disease.

Erratum: Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo.

[This corrects the article DOI: 10.1038/s41523-017-0020-z.].

Rapid Sequential in Situ Multiplexing with DNA Exchange Imaging in Neuronal Cells and Tissues.

To decipher the molecular mechanisms of biological function, it is critical to map the molecular composition of individual cells or even more importantly tissue samples in the context of their biological environment in situ. Immunofluorescence (IF) provides specific labeling for molecular profiling. However, conventional IF methods have finite multiplexing capabilities due to spectral overlap of the fluorophores.

Systematic three-dimensional analysis of wafer-based maxillary repositioning procedures in orthognathic surgery.

Purpose: Little is known about the three-dimensional (3D) transfer accuracy in maxillary repositioning procedures based on conventionally manufactured dental-mounted wafers. The purpose of the present study was a systematic 3D analysis for wafer-based maxillary positioning in orthognathic surgery.

Materials And Methods: A total of 92 patients underwent Le Fort I in addition to mandibular bilateral sagittal split osteotomies (BSSO).

Distance-dependent accuracy in Le Fort I maxillary repositioning procedures.

It has been hypothesised that, in maxillary repositioning procedures, longer distances correlate with less accurate transfers and particularly the repositioning forces of facial skin and muscles that increase exponentially. However, this has not to our knowledge been confirmed. The purpose of this study was to search for differences in the accuracy of transfer from maxillary repositioning procedures parallel to the three orthogonal planes and with respect to three different anatomical landmarks of the first molar left and right (M1L and M1R) and the first incisor (I).

Niche-localized tumor cells are protected from HER2-targeted therapy via upregulation of an anti-apoptotic program in vivo.

Several lines of evidence suggest that components of the tumor microenvironment, specifically basement membrane and extracellular matrix proteins, influence drug sensitivities. We previously reported differential drug sensitivity of tumor cells localized adjacent to laminin-rich extracellular matrix in three-dimensional tumor spheroid cultures. To evaluate whether differential intra-tumor responses to targeted therapy occur in vivo, we examined the sensitivity of human epidermal growth factor receptor 2-positive tumors to lapatinib using a previously described ductal carcinoma in situ-like model characterized by tumor cell confinement within ductal structures surrounded by an organized basement membrane.