Metabolite profiling reveals a connection between aldehyde dehydrogenase 1A3 and GABA metabolism in breast cancer metastasis.

Introduction: Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell (CSC) marker and in breast cancer it is associated with triple-negative/basal-like subtypes and aggressive disease. Studies on the mechanisms of ALDH1A3 in cancer have primarily focused on gene expression changes induced by the enzyme; however, its effects on metabolism have thus far been unstudied and may reveal novel mechanisms of pathogenesis.

Objective: Determine how ALDH1A3 alters the metabolite profile in breast cancer cells and assess potential impacts.

Role of Myeloid Cells in Oncolytic Reovirus-Based Cancer Therapy.

Oncolytic reovirus preferentially targets and kills cancer cells via the process of oncolysis, and additionally drives clinically favorable antitumor T cell responses that form protective immunological memory against cancer relapse. This two-prong attack by reovirus on cancers constitutes the foundation of its use as an anticancer oncolytic agent. Unfortunately, the efficacy of these reovirus-driven antitumor effects is influenced by the highly suppressive tumor microenvironment (TME).

Quantitative Proteome Responses to Oncolytic Reovirus in GM-CSF- and M-CSF-Differentiated Bone Marrow-Derived Cells.

The efficacy of oncolytic viruses (OVs), such as reovirus, is dictated by host immune responses, including those mediated by the pro- versus anti-inflammatory macrophages. As such, a detailed understanding of the interaction between reovirus and different macrophage types is critical for therapeutic efficacy. To explore reovirus-macrophage interactions, we performed tandem mass tag (TMT)-based quantitative temporal proteomics on mouse bone marrow-derived macrophages (BMMs) generated with two cytokines, macrophage colony stimulating factor (M-CSF) and granulocytic-macrophage colony stimulating factor (GM-CSF), representing anti- and proinflammatory macrophages, respectively.

The NAD Salvage Pathway Supports PHGDH-Driven Serine Biosynthesis.

NAD is a key metabolic redox cofactor that is regenerated from nicotinamide through the NAD salvage pathway. Here, we find that inhibiting the NAD salvage pathway depletes serine biosynthesis from glucose by impeding the NAD-dependent protein, 3-phosphoglycerate dehydrogenase (PHGDH). Importantly, we find that PHGDH breast cancer cell lines are exquisitely sensitive to inhibition of the NAD salvage pathway.

Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy.

Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various "hallmarks" of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells.

Citral reduces breast tumor growth by inhibiting the cancer stem cell marker ALDH1A3.

Breast cancer stem cells (CSCs) can be identified by increased Aldefluor fluorescence caused by increased expression of aldehyde dehydrogenase 1A3 (ALDH1A3), as well as ALDH1A1 and ALDH2. In addition to being a CSC marker, ALDH1A3 regulates gene expression via retinoic acid (RA) signaling and plays a key role in the progression and chemotherapy resistance of cancer. Therefore, ALDH1A3 represents a druggable anti-cancer target of interest.

Core needle biopsy of breast cancer tumors increases distant metastases in a mouse model.

Introduction: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome.

Method: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice.

Research publication in pediatric surgery: a cross-sectional study of papers presented at the Canadian Association of Pediatric Surgeons and the American Pediatric Surgery Association.

Introduction: Several studies have examined predictors of publication of research presented in scientific meetings in different disciplines. A tendency toward publishing studies with positive results has been described as "publication bias." Our objective was to determine the proportion of the studies that were published, time to publication, and factors that could predict publication in pediatric surgery.

Mediastinal polyembryoma associated with Klinefelter syndrome.

A 4.5-year-old boy presented with isosexual precocious puberty and an anterior mediastinal mass. Surgical resection demonstrated a teratoma with foci of malignant mixed germ cell tumor elements of polyembryoma.

A complication associated with central line removal in the pediatric population: retained fixed catheter fragments.

Background: There are many reports on the complications that occur at the time of insertion and during the life of central venous indwelling catheters. However, there is no literature that describes the complications that occur at the time of removal of these lines.

Methods: A retrospective review of 136 central line (Broviacs [B], Port-A- Caths [PC] and Hickmans [HC]) removals during the last 5 years was undertaken.

Undifferentiated mesenchymal neoplasm of the esophagus in a child: case report and comparison with gastrointestinal stromal tumor.

Mesenchymal neoplasms of the esophagus are relatively uncommon in adults and exceedingly rare in children. Childhood tumors consist almost exclusively of smooth muscle tumors (leiomyomas). We report a case of an undifferentiated mesenchymal neoplasm occurring in the distal esophagus of a 15-year-old boy which is not a gastrointestinal stromal tumor.