Browsing by Subject "metastasis"

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    Endobronchial metastasis from primary anorectal melanoma.
    (The American journal of case reports, 2013-01) Heyman, Benjamin M; Chung, Matthew M; Lark, Amy L; Shofer, Scott
    PATIENT: Male, 64 FINAL DIAGNOSIS: Metastatic anorectal melanoma with endotracheal metastasis Symptoms: Fatigue • weight loss • hematochezia • cough MEDICATION: None Clinical Procedure: Biopsy of anal mass • rigid bronchoscopy Specialty: Internal medicine • oncology • pulmonology. OBJECTIVE: Rare disease. BACKGROUND: Anorectal melanoma is a rare cancer with a poor prognosis. The mean survival after diagnosis is 15-25 months. At the time of diagnosis, 61% of patients have local regional lymph node metastases, and 21% have distant metastases. The lungs are a common site for metastasis for all tumors including melanoma. However endobronchial metastasis is a rare phenomenon. Endotracheal metastases are even rarer, occurring in only 5% of patients with extrapulmonary endobronchial metastases. It is most commonly seen in breast, colorectal, and kidney cancers. It is extremely rare for cutaneous melanoma. The mean survival after diagnosis is only 15 months and treatment options are limited. CASE REPORT: We report the case of a 64 year-old gentleman with newly diagnosed metastatic anorectal melanoma. A 3 cm by 3 cm bluish-black, oval-shaped, exophytic mass protruding from his anus was found on physical exam. Endobronchial and endotracheal metastasis to the trachea were discovered on computed tomography and he was subsequently taken to the operating room for argon plasma coagulation laser recanalization of his trachea via rigid bronchoscopy, and resection of his anal mass. CONCLUSIONS: We have presented the first known case of anorectal melanoma with endobronchial metastasis. Palliative APC laser recanalization was used to prevent asphyxiation from the endotracheal mass. Endobronchial metastasis is uncommon and can be easily mistaken for primary bronchogenic carcinoma. It should always be considered when evaluating patients with new lung masses.
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    Snail promotes resistance to enzalutamide through regulation of androgen receptor activity in prostate cancer.
    (Oncotarget, 2016-08-02) Ware, Kathryn E; Somarelli, Jason A; Schaeffer, Daneen; Li, Jing; Zhang, Tian; Park, Sally; Patierno, Steven R; Freedman, Jennifer; Foo, Wen-Chi; Garcia-Blanco, Mariano A; Armstrong, Andrew J
    Treatment with androgen-targeted therapies can induce upregulation of epithelial plasticity pathways. Epithelial plasticity is known to be important for metastatic dissemination and therapeutic resistance. The goal of this study is to elucidate the functional consequence of induced epithelial plasticity on AR regulation during disease progression to identify factors important for treatment-resistant and metastatic prostate cancer. We pinpoint the epithelial plasticity transcription factor, Snail, at the nexus of enzalutamide resistance and prostate cancer metastasis both in preclinical models of prostate cancer and in patients. In patients, Snail expression is associated with Gleason 9-10 high-risk disease and is strongly overexpressed in metastases as compared to localized prostate cancer. Snail expression is also elevated in enzalutamide-resistant prostate cancer cells compared to enzalutamide-sensitive cells, and downregulation of Snail re-sensitizes enzalutamide-resistant cells to enzalutamide. While activation of Snail increases migration and invasion, it is also capable of promoting enzalutamide resistance in enzalutamide-sensitive cells. This Snail-mediated enzalutamide resistance is a consequence of increased full-length AR and AR-V7 expression and nuclear localization. Downregulation of either full-length AR or AR-V7 re-sensitizes cells to enzalutamide in the presence of Snail, thus connecting Snail-induced enzalutamide resistance directly to AR biology. Finally, we demonstrate that Snail is capable of mediating-resistance through AR even in the absence of AR-V7. These findings imply that increased Snail expression during progression to metastatic disease may prime cells for resistance to AR-targeted therapies by promoting AR activity in prostate cancer.