An adult castrated male dog was presented with persistent hematochezia. Digital rectal examination and endoscopy found multiple colorectal masses. Complete blood count and serum biochemical results were within the reference interval. Fine needle aspirate of the masses indicated a diagnosis of inflamed polyps with a primary differential of malignancy. Histopathologic examination using endoscopy-guided incisional biopsy of the masses revealed an inflamed neoplasm with ossification. A colectomy was performed to remove the tumor. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of colorectal carcinoma in situ (CiS) with immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. The immunohistochemistry confirmed intraepithelial CD3 + T cells within CiS. The flow cytometric analysis indicated tumor-infiltrating CD4 + T, CD8 + T, and CD11b + myeloid subsets. The flow cytometric analysis of circulating and tumor-infiltrating leukocytes demonstrated a preferential expansion of CD25 + FOXP3 + regulatory T cells within CiS. To the author’s knowledge, this is the first report to show clinical evidence emphasizing the immunogenicity and immune-suppressive environment of canine colorectal CiS. Our case will be valuable in providing a rationale for basic research that dissects the immune environment for canine colorectal cancers for the future development of cancer immunotherapy.

An adult female dog was presented for evaluation of rapid growth of mammary gland masses. Complete blood count, serum biochemistry, and diagnostic imaging results were unremarkable. Fine needle aspirates of the mammary masses indicated mammary carcinoma characterized by large globoid cells with finely granular eosinophilic globules or Melamed-Wolinska-like bodies. A regional mastectomy was performed on the masses. Subsequent histopathologic examination of the surgically resected masses resulted in a diagnosis of mammary comedocarcinoma with nodal metastasis and distinct perivascular immune infiltrates, which were subject to immunohistochemical and flow cytometric immunophenotyping. Immunohistochemical examination confirmed the infiltration of CD3 + T and PAX5 + B lymphocytes. Flow cytometric analysis demonstrated tumor-infiltrating CD4 + CD25 + FOXP3 + regulatory T, CD8 + T, CD11b + myeloid, and CD21 + B cells. Of note, paired flow cytometric analysis of peripheral blood and tumor tissues showed a preferential tumor infiltration of regulatory T and B cells. Approximately two months after the mastectomy, the tumor reoccurred at the surgery site. The dog died due to deteriorating conditions. We report a rare case of canine mammary comedocarcinoma, providing clinical, clinicopathologic, histologic, and immunophenotypic characteristics. Our case is valuable in providing a rationale for basic research that maps the immune landscape of mammary comedocarcinoma to identify key immune subsets for cancer progression.

Hypoxia-inducible factor 1 (HIF1) is a master transcription factor that induces the transcription of genes involved in the metabolism and behavior of stem cells. HIF1-mediated adaptation to hypoxia is required to maintain the pluripotency and survival of stem cells under hypoxic conditions. HIF1 activity is well known to be tightly controlled by the alpha subunit of HIF1 (HIF1α). Understanding the regulatory mechanisms that control HIF1 activity in stem cells will provide novel insights into stem cell biology under hypoxia. Recent research has unraveled the mechanistic details of HIF1α regulating processes, suggesting new strategies for regulating stem cells. This review summarizes recent experimental studies on the role of several regulatory factors (including calcium, 2-oxoglutarate-dependent dioxygenase, microtubule network, importin, and coactivators) in regulating HIF1α activity in stem cells.
Anoxia ; Biology ; Calcium ; Hypoxia-Inducible Factor 1 ; Karyopherins ; Metabolism ; Microtubules ; Stem Cells ; Transcription Factors

Stem cells have attracted much attention due to their distinct features that support infinite self-renewal and differentiation into the cellular derivatives of three lineages. Recent studies have suggested that many stem cells both embryonic and adult stem cells reside in a specialized niche defined by hypoxic condition. In this respect, distinguishing functional differences arising from the oxygen concentration is important in understanding the nature of stem cells and in controlling stem cell fate for therapeutic purposes. ROS act as cellular signaling molecules involved in the propagation of signaling and the translation of environmental cues into cellular responses to maintain cellular homeostasis, which is mediated by the coordination of various cellular processes, and to adapt cellular activity to available bioenergetic sources. Thus, in this review, we describe the physiological role of ROS in stem cell fate and its effect on the metabolic regulation of stem cells.
Adult Stem Cells ; Cues ; Energy Metabolism ; Glucose ; Homeostasis ; Metabolism* ; Oxygen ; Reactive Oxygen Species ; Stem Cells*