Colorectal cancer (CRC) is the third most diagnosed form of cancer and second most deadly cancer worldwide. Introduction of better screening has improved both incidence and mortality. However, as the coronavirus disease 2019 (COVID-19) pandemic began, healthcare resources were shunted away from cancer screening services resulting in a sharp decrease in CRC screening and a backlog of patients awaiting screening tests. This may have significant effects on CRC cancer mortality, as delayed screening may lead to advanced cancer at diagnosis. Strategies to overcome COVID-19 related disruption include utilizing stool-based cancer tests, developing screening protocols based on individual risk factors, expanding telehealth, and increasing open access colonoscopies. In this review, we will summarize the effects of COVID-19 on CRC screening, the potential long-outcomes, and ways to adapt CRC screening during this global pandemic.

Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia. The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition, as well as by xerostomia. In the pharyngeal phase of swallowing, pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance. The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility. However, it can also be affected by obstruction from chronic reflux changes, pill-induced esophagitis, or Candida esophagitis. Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis. Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.

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Introduction: Alpha-fetoprotein (AFP) functions in utero to inhibit estrogen-mediated growth in fetal tissue. AFPep is a 9-amino acid cyclized form of the active site in AFP that impedes phosphorylation and activation of ERα. Recent studies demonstrate that AFPep inhibits estrogen-dependent growth in MCF-7 and T47D xenografts and decreases mammary tumor burden in estrogen-exposed ACI rats. It is important to identify biomarkers that predict the efficacy of AFPep. Dimerized, phosphorylated ERα (pERα) transcribes TRIM25, which is associated with breast cancer metastasis and decreased survival. KLF5 is a transcription factor downstream of pERα and is associated with breast and cervical cancer proliferation, invasiveness, and migration. We hypothesize that treatment with AFPep inhibits expression of TRIM25 and KLF5 and that these are predictive biomarkers for AFPep-mediated inhibition of estrogen-dependent growth. Methods: Expression of ERα, pERα, TRIM25, and KLF5 were assessed in three estrogen-sensitive models: immature mouse uterus, MCF7 xenografts, and canine breast tumors. Immature mice were treated with saline only, AFPep (100 μg) only, estrogen, or estrogen plus AFPep (100 μg). Twenty-four hours post treatment, uteri were removed, weighed, and blotted for biomarkers. Mice bearing MCF7 xenografts were treated with estrogen or estrogen with AFPep and biopsied after 14 days. Finally, two dogs, one with a simple tubular mammary adenoma and the other with a grade II mixed mammary carcinoma, were treated with AFPep for seven days. Results: Immature mice treated with estrogen had greater uterine-to-body weight ratio, increased ratio of pERα to total ERα, and increased KLF5 and TRIM25 expression compared to mice treated with saline alone or AFPep alone. Uteri from mice treated with estrogen and AFPep showed decreased uterine-to-body weight ratio, decreased ratio of pERα to total ERα, and decreased KLF5 and TRIM25 expression compared to uteri treated with estrogen alone. MCF7 xenografts from mice treated with estrogen and AFPep showed decreased ratio of pERα to total ERα compared to mice treated with estrogen alone. AFPep treatment of xenograft-bearing mice decreased expression of TRIM25 and KLF5 in the tumor. In the clinical canine mammary tumor study, a mixed carcinoma expressed pERα and treatment of that dog with AFPep decreased the expression of both KLF5 and TRIM25 in that tumor. A dog with a simple tubular adenoma did not express pERα, and treatment of that dog with AFPep had little impact on the expression of TRIM25 and KLF5 in the tumor. Conclusion: We conclude that AFPep inhibits estrogen-mediated growth and the ratio of pERα to total ERα. KLF5 and TRIM25 also serve as predictive markers for the efficacy of AFPep in uterus and breast tissue respectively. Citation Format: Kanthi J. Bommareddy, Anusri Kadakuntla, Michael Kuna, Priya Shivraj, Roman Ginnan, Ann Hohenhaus, James Bennett, Thomas Andersen. Trim25 and KLF5 expression predict AFPep-mediated inhibition of estrogen-dependent growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2968.

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