a-syngeneic-orthotopic-osteosarcoma-sprague-dawley-rat-model-with

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate

The most recent advance in the treatment of osteosarcoma (OS) occurred in the 1980s when multi-agent chemotherapy was shown to improve overall survival ...

non-invasive-ultrasound-assessment-endometrial-cancer-progression

Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors <em>Arid1a</em> and <em>Pten</em> in Mice

Uterine cancers can be studied in mice due to the ease of handling and genetic manipulation in these models. However, these studies are often limited to ...

The Johns Hopkins University School of Medicine

Johns Hopkins University

Johns Hopkins University School of Medicine

Juntendo University Faculty of Medicine

Juntendo University School of Medicine

Children born to women who experience stress during pregnancy have an increased risk of cancer in later life, but no previous animal studies have tested such a link. We questioned whether prenatal stress in A/J mice affected the development of lung tumors after postnatal response to tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Timed-bred A/J mice were randomly assigned on gestation day 12.5 to prenatal stress (PS) by restraint for 5 consecutive days or control (no restraint). Adult offspring of control and stressed pregnancies were all treated with three NNK injections (50 mg/kg every other day) and euthanized 16 weeks later to examine their lungs. Compared to controls, PS dams exhibited significantly increased levels of plasma corticosterone, increased adrenal weights, and decreased fetus weights without fetal loss. Prenatally stressed litters had a significantly higher neonatal death rate within first week of life, and surviving male and female offspring developed lung epithelial proliferations with increase multiplicity, increased area, and aggressive morphology. Prenatal stress also induced more advanced atypical adenomatous hyperplasia (AAH) lesions. We found no difference in lung NNK-derived methyl DNA adducts, but prenatal stress did significantly enhance CD3+ T cell and Foxp3+ T cell tumor infiltration. Prenatal stress significantly increases multiplicity, area of NNK-induced lung tumors and advanced morphology. Prenatal stress did not affect production of NNK-derived methyl DNA adducts but did increase lymphocytic infiltration of lung tumors. To our knowledge, this is the first animal model of prenatal stress with evaluation of cancer development in offspring.

Prenatal stress enhances NNK-induced lung tumors in A/J mice.

Spontaneous disappearance of a giant colonic lipoma after endoscopic biopsy.

This case involved an 80-year-old man who was seen for melena. Further testing revealed a tubular adenocarcinoma 50 mm in size in the rectum. In addition, an anal fistula was noted behind the anus along with induration. A biopsy of tissue from the external (secondary) opening of the fistula also revealed adenocarcinoma. Nodules suspected of being metastases were noted in both lung fields. The patient was diagnosed with rectal cancer, a cancer arising from an anal fistula, and a metastatic pulmonary tumor, and neoadjuvant chemotherapy was begun. A laparoscopic abdominoperineal resection was performed 34 days after 6 cycles of mFOLFOX-6 therapy. Based on pathology, the rectal cancer was diagnosed as moderately differentiated adenocarcinoma, and this adenocarcinoma had lymph node metastasis (yp T3N2aM1b). There was no communication between the rectal lesion and the anal fistula, and a moderately differentiated tubular adenocarcinoma resembling the rectal lesion was noted in the anal fistula. Immunohistochemical staining indicated that both the rectal lesion and anal fistula were cytokeratin 7 (CK7) (-) and cytokeratin 20 (CK20) (+), and the patient's condition was diagnosed as implantation of rectal cancer in an anal fistula.In instances where an anal fistula develops in colon cancer, cancer implantation in that fistula must also be taken into account, and further testing should be performed prior to surgery. 

A case of metastatic carcinoma of anal fistula caused by implantation from rectal cancer.

Cell surface receptors including the epidermal growth factor receptor (EGFR) family and G-protein coupled receptors (GPCRs) play quintessential roles in physiology, and in diseases, including cardiovascular diseases. While downstream signaling from these individual receptor families has been well studied, the cross-talk between EGF and GPCR receptor families is still incompletely understood. Including members of both receptor families, the number of receptor and ligand combinations for unique interactions is vast, offering a frontier of pharmacologic targets to explore for preventing and treating disease. This molecular cross-talk, called receptor transactivation, is reviewed here with a focus on the cardiovascular system featuring the well-studied GPCR receptors, but also discussing less-studied receptors from both families for a broad understanding of context of expansile interactions, repertoire of cellular signaling, and disease consequences. Attention is given to cell type, level of chronicity, and disease context given that transactivation and comorbidities, including diabetes, hypertension, coronavirus infection, impact cardiovascular disease and health outcomes.

GPCR-ErbB transactivation pathways and clinical implications.

Children born to women who experience stress during pregnancy have an increased risk of atherosclerosis in later life, but few animal models have explored mechanisms. To study this phenomenon, timed-bred ApoE knockout mice were determined pregnant with ultrasound and randomly assigned on  to either a control (no stress) or prenatal stress (PS) group using 2 h of restraint for five consecutive days. PS significantly increased plasma corticosterone levels in pregnant mice. The litters from PS mice showed increased neonatal mortality within the first week of life. Body weights (at euthanasia) of adult offspring at 25 wk from the PS group were significantly increased compared with weights of controls. Adult offspring from these pregnancies were serially imaged with ultrasound to measure plaque thickness and were compared with plaque macroscopic and microscopic pathology. PS groups had increased plaque thickness determined by ultrasound, gross, histological evaluation and increased aortic root and valve macrophage infiltration at 25 wk. Five-week-old mice from PS group had significant decrease in mean arterial pressure, yet blood pressure normalized by 10 wk. As prenatal stress induced increased atherosclerosis, and telomeres are susceptible to stress, aortas from 10-wk-old mice were compared for telomere lengths and were found to be significantly shorter in PS mice compared with control mice. These studies support future investigation of how stress impacts telomere shortening in animal models and human aortas. This model could be further used to investigate the role of prenatal stress, telomere biology, and atherosclerosis pathogenesis in adults.

ArticleTotal : 2	Year
Publication title Cited by 6	2021
Publication title Cited by 1	2023

Article	Year
Prenatal stress enhances NNK-induced lung tumors in A/J mice. Carcinogenesis\| PubMed ID: 32249286	2020
Spontaneous disappearance of a giant colonic lipoma after endoscopic biopsy. Endoscopy\| PubMed ID: 21271519	2011
A case of metastatic carcinoma of anal fistula caused by implantation from rectal cancer. Surgical case reports\| PubMed ID: 26943447	2015
GPCR-ErbB transactivation pathways and clinical implications. Cellular signalling\| PubMed ID: 34303814	2021
Prenatal stress enhances atherosclerosis and telomere shortening in ApoE knockout mouse offspring. American journal of physiology. Regulatory, integrative and comparative physiology\| PubMed ID: 35411811	2022

Shun Ishiyama

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