Cancer

BACKGROUND: High-precision detection for individual and clustered microcalcifications in mammograms is important for the early diagnosis of breast cancer. Large-scale differences between the two types and low-contrast images are major difficulties faced by radiologists when performing diagnoses. OBJECTIVE: Deep learning-based methods can provide end-to-end solutions for efficient detection. However, multicenter data bias, the low resolution of network inputs, and scale differences between microcalcifications lead to low detection rates...

Increased utilization of chemotherapy in breast cancer patients has led to improved survival outcomes but it has also resulted in rising incidence of adverse effects. Occurrence of new/unreported side effect poses challenge in front of clinicians. We report the case of a 53-year lady with locally advanced, hormone receptor-positive, and human epidermal growth factor-2 (HER-2) negative right breast carcinoma. She was started on neoadjuvant chemotherapy (NACT) (doxorubicin and cyclophosphamide), to facilitate breast-conserving surgery...

BACKGROUND: ErbB/PI3K signaling is widely recognized as a critical modulator of malignancy and miRNAs have been found to play a crucial role in the regulation of this pathway. OBJECTIVE: This study aimed to identify novel miRNAs related to the ErbBs loci and investigate the functional effects of these miRNAs on ErbB/PI3K signaling in cancer progression. MATERIALS AND METHODS: Bioinformatics tools and RNA-seq data were used to discover novel miRNAs in breast and colon cancer cells...

BACKGROUND AND OBJECTIVES: In recent years, considerable insight has been gained into the pathogenesis, diagnosis and treatment of cutaneous sarcomas, including atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Both entities have shown increasing incidence rates in the last decade. This study was initiated to evaluate how these new insights impact the number of diagnoses of AFX/PDS compared to other cutaneous sarcoma entities. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, all histopathological reports of cutaneous sarcomas (AFX, PDS, dermatofibrosarcoma protuberans, cutaneous leiomyosarcoma, angiosarcoma, and Kaposi sarcoma) confirmed by board-certified dermatopathologists were analyzed during a time-period of seven years (2013-2019)...

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models...

Human leukocyte antigen (HLA) molecules present small peptide antigens to T cells, thereby allowing them to recognize pathogen-infected and cancer cells. A central dogma over the last 50+ y is that peptide binding to HLA molecules is mediated by the docking of side chains of particular amino acids in the peptide into pockets in the HLA molecules in a conserved N- to C-terminal orientation. Whether peptides can be presented in a reversed C- to N-terminal orientation remains unclear. Here, we performed large-scale identification of peptides bound to HLA-DP molecules and observed that in addition to peptide binding in an N- to C-terminal orientation, in 9 out of 14 HLA-DP allotypes, reverse motifs are found, compatible with C- to N-terminal peptide binding...

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7)...

Glioma is a deadly form of brain cancer, and the difficulty of treating glioma is exacerbated by the chemotherapeutic resistance developed in the tumor cells over the time of treatment. siRNA can be used to silence the gene responsible for the increased resistance, and sensitize the glioma cells to drugs. Here, iron oxide nanoparticles functionalized with peptides (NP-CTX-R10 ) were used to deliver siRNA to silence O6-methylguanine-DNA methyltransferase (MGMT) to sensitize tumor cells to alkylating drug, Temozolomide (TMZ)...

BACKGROUND: Lifestyle factors place those who experience incarceration at increased risk of morbidity and mortality from a range of preventable diseases, including cancer. METHODS: Two nurses were employed for a period of 6months to facilitate bowel and breast cancer screening of prisoners across four correctional centres in Queensland. We identify factors impacting on cancer screening in prisons and document the outcomes for those screened. RESULTS: Both screening programs produced a positivity rate of ∼17% in those screened, with 23 individuals returning a positive faecal occult blood test and five women requiring further investigations following breast screening...

BACKGROUND: The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. PURPOSE: To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports. DATA SOURCES: MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022...

PURPOSE: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues. METHODS: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005...

Taking advantage of the remarkable processivity and membrane penetrability, the gold nanoparticle (AuNP)-based three-dimensional (3D) DNA walking nanomachine has induced tremendous promise in molecular diagnostics and cancer therapy, whereas the executive ability of this nanomachine was eventually limited because of the disordered assembly between the walker and the track. Therefore, we developed a well-directed 3D DNA walking nanomachine by employing a DNA dendrimer as the track for intracellular imaging with high directionality and controllability...

Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state in the tumor microenvironment (TME), the therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB therapy to kill tumors efficiently. The tumor cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnO x ) nanozyme termed [email protected] showed intrinsic peroxidase and oxidase-like activities in an acidic TME...

The E. E. Just Award commemorates the great African-American cell biologist Dr. Ernest Everett Just, who was a successful pioneer in an era of systemic exclusion of minorities in science and academia. Receiving this award is not only an honor but a recognition of my long-standing commitment to helping Persons Excluded due to Ethnicity or Race (PEERS) to achieve success in biomedical careers. As a proud member of this group, I have devoted most of my career to training underrepresented undergraduate and graduate students to pursue scientific careers...

Immune checkpoint inhibitors (ICI) have become an essential part of cancer treatment. Anti-programmed cell death receptor-1 (PD-1) is a monoclonal antibody that targets PD-1. For patients with inoperable cutaneous squamous cell carcinoma, anti-PD-1 ICI treatment has been approved as monotherapy or in adjunct with other treatment modalities. A patient primarily treated with PD-1 inhibition for local advanced moderately differentiated cutaneous squamous cell carcinoma involving the parotid and the neck is presented...

PURPOSE: Leukemia inhibitory factor (LIF) is a multifunctional cytokine with numerous reported roles in cancer and is thought to drive tumor development and progression. Characterization of LIF and clinical-stage LIF inhibitors would increase our understanding of LIF as a therapeutic target. EXPERIMENTAL DESIGN: We first tested the association of LIF expression with transcript signatures representing multiple processes regulating tumor development and progression...

PURPOSE: TTo identify associations of biological signatures and stromal tumor infiltrating lymphocytes (sTILs) with pathological complete response (pCR, ypT0 ypN0) and survival in the phase II WSG-ADAPT HER2+/HR- trial (NCT01817452). EXPERIMENTAL DESIGN: Patients with cT1-cT4c, cN0-3 HER2+/HR- early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n=92) or P+T+paclitaxel (n=42). Gene expression signatures were analyzed in baseline (BL) biopsies using NanoString Breast Cancer 360 panel (n=117); BL and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively...

PURPOSE: Poly(ADP-ribose) polymerase enzyme inhibitors (PARPi) have become the standard-of-care treatment for homologous recombination deficient (HRD) high-grade serous ovarian cancer (HGSOC). However, not all HRD tumors respond to PARPi. Biomarkers to predict response are needed. [18F]FluorThanatrace ([18F]FTT) is a PARPi-analog PET radiotracer that non-invasively measures PARP-1 expression. Herein, we evaluate [18F]FTT as a biomarker to predict response to PARPi in patient-derived xenograft (PDX) models and subjects with HRD HGSOC...

Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis-time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome...

PURPOSE: Our goal was to evaluate the effect of focal vs extended irreversible electroporation on side effects, patient-reported quality of life, and early oncologic control for localized low-intermediate risk prostate cancer patients. MATERIALS AND METHODS: Men with localized low-intermediate risk prostate cancer were randomized to receive focal or extended irreversible electroporation ablation. Quality of life was measured by International Index of Erectile Function, Expanded Prostate Cancer Index Composite questionnaire, and International Prostate Symptom Score...