title: Potential of sulfasalazine as a therapeutic sensitizer for CD44 splice variant 9-positive urogenital cancer.
abstract: Cancer stem-like cells (CSCs) with high expression of CD44 splice variant (CD44v) have an enhanced capacity for intracellular reduced glutathione synthesis and defense against reactive oxygen species, resulting in resistance to various therapeutic stresses. Sulfasalazine (SSZ), a drug used in the treatment of rheumatoid arthritis (RA), inhibits glutamate-cystine transport, and suppressed CD44v-dependent tumor growth and increased sensitivity to cytotoxic drugs in an in vivo study. Here, we present two cases of CD44v9-positive urogenital cancer with concomitant treatment with SSZ for RA. Patient 1 was a 62-year-old man who had received SSZ for RA beginning 2 months before the diagnosis of urinary bladder cancer. Although he had multiple metastases to the bladder, abdominal, left cervical and left axillary lymph nodes, and brain, complete response with multidisciplinary therapy was maintained for more than 2 years. Patient 2 was a 74-year-old man with castration-resistant prostate cancer who was diagnosed with RA during chemotherapy and a gradual increase in prostate-specific antigen (PSA) level. When SSZ was added, his PSA value (ng/mL) decreased from 12.93 to 5.58 in only 2 weeks and then quickly rebounded, whereas levels of neuron-specific enolase, a neuroendocrine differentiator and CSC marker, remained almost unchanged. We therefore speculate that SSZ treatment may represent a new adjuvant treatment option for patients with CD44v9-positive urogenital cancer.
authors.affiliation: Department of Urology, Jichi Medical University, Tochigi, 329-0498, Japan. ttakayam@jichi.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Department of Urology, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Urology, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Morikawa
authors.affiliation: Department of Urology, Jichi Medical University, Tochigi, 329-0498, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Morita
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-Ku, 160-8582, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagano
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-Ku, 160-8582, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics; D022821:RNA Splice Sites; D012460:Sulfasalazine / Q000008:administration & dosage / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D022821:RNA Splice Sites; D012460:Sulfasalazine
keywords: Bladder cancer; CD44; CD44 splice variant; Cancer stem-like cells; Glutamate–cystine transporter; Prostate cancer; Sulfasalazine; Urogenital cancer; xCT