Patients with advanced colorectal cancer often are treated with systemic cytotoxic therapy using fluorouracil (5‐FU), oxaliplatin, irinotecan, and FOLFOX or FOLFIRI combination protocols. Additionally, signaling pathways that are active in colorectal cancer can be therapeutically targeted. Herein, we examined whether chemotherapy impacts on WNT, MAPK and NOTCH signaling pathways in xenograft models of colon cancer. Furthermore, we tested whether combining chemotherapy with MAPK and NOTCH inhibition has superior therapeutic effects. We show that colon cancer cells with high WNT, MAPK and NOTCH activity are variably affected but generally persist in xenograft tumors under different chemotherapeutic regimens, indicating limited effects of cytotoxic therapy on oncogenic signaling pathways. Although these results provided a rationale to additionally target pathway activity, we found no significant increase in therapy response when combining MAPK and NOTCH inhibition with fluorouracil chemotherapy. We attribute this finding to a decrease in tumor cell proliferation upon MAPK and NOTCH inhibition, resulting in reduced effectiveness of cytotoxic treatment. Therapeutic benefits of combining chemotherapy with targeting of oncogenic signaling pathways must therefore be critically evaluated for patients with colorectal cancer.
Introduction: We report a case of a patient with mucopolysaccharidosis (MPS) type VI disease who underwent bilateral penetrating keratoplasty. The insight into deeper ocular structures after successful keratoplasty enabled the diagnosis of glaucoma.
Case Report: A 24-year-old male patient with genetically confirmed MPS VI disease was referred for ophthalmological co-assessment to our Department of Ophthalmology. The patient presented with low visual acuity of 6/200 in both eyes, and increased corneal thickness. The bilateral intraocular pressure was difficult to evaluate in association with the corneal thickness and rigidity. Due to total corneal opacification bilateral penetrating keratoplasty was performed. The successful keratoplasty allowed proper funduscopy and further diagnostic measurements leading to the diagnosis of advanced glaucoma.
Conclusion: Although MPS VI is an orphan disease, intravenously applied enzyme replacement therapy with galsulfase has been established as a successful treatment. However, systemically administered therapy with galsulfase does not reduce or affect ocular symptoms and manifestations. The case demonstrates the high impact of early and regularly ophthalmic co-assessment in MPS VI patients, especially keeping in mind that not only corneal involvement can be present in MPS patients. Further-more, preservation of visual acuity is of high importance for participating in social and professional life.
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