If complete surgical resection is not possible, partial resection followed by hormone therapy using gonadotropin-releasing hormone agonists is recommended, which in this study achieved the same favorable prognosis with regard to remission.

Cervical cancer is the fourth most common cancer in women around the world. Cancer stem cells (CSCs) are responsible for cancer initiation, as well as resistance to radiation therapy, and are considered as the effective target of cancer therapy. Indoleamine 2,3-dioxygenase 1 (IDO1) mediates tryptophan metabolism and T cell suppression, but the immune-independent function of IDO1 in cancer behavior is not fully understood. Using tumorsphere cultivation for enriched CSCs, we firstly found that IDO1 was increased in HeLa and SiHa cervical cancer cells and in these two cell lines after radiation treatment. The radiosensitivity of HeLa and SiHa tumorsphere cells was increased after the inhibition of IDO1 through RNA interference or by the treatment of INCB-024360, an IDO1 inhibitor. With the treatment of kynurenine, the first breakdown product of the IDO1-mediated tryptophan metabolism, the radiosensitivity of HeLa and SiHa cells decreased. The inhibition of Notch1 by shRNA downregulated IDO1 expression in cervical CSCs and the binding of the intracellular domain of Notch (NICD) on the IDO1 promoter was reduced by Ro-4929097, a γ-secretase inhibitor. Moreover, the knockdown of IDO1 also decreased NICD expression in cervical CSCs, which was correlated with the reduced binding of aryl hydrocarbon receptor nuclear translocator to Notch1 promoter. In vivo treatment of INCB-0234360 sensitized SiHa xenograft tumors to radiation treatment in nude mice through increased DNA damage. Furthermore, kynurenine increased the tumorsphere formation capability and the expression of cancer stemness genes including Oct4 and Sox2. Our data provide a reciprocal regulation mechanism between IDO1 and Notch1 expression in cervical cancer cells and suggest that the IDO1 inhibitors may potentially be used as radiosensitizers.

ObjectivesPrevious research has shown a possible relationship between endometriosis and autoimmune diseases. However, the relationship between endometriosis and ankylosing spondylitis (AS) is lacking. Therefore, we intended to find possible associations between endometriosis and AS using ICD-9 coding data in a population-based retrospective cohort study in Taiwan.MethodData for this retrospective cohort study were collected from the Taiwan National Health Insurance Research Database (NHIRD) between 2000–2012. We collected 13,145 patients with endometriosis and a 78,870 non-endometriosis comparison cohort. Diagnoses of endometriosis and AS were defined by the International Classification of Diseases-9 (ICD-9-CM) code for at least 3 outpatients or 1 hospitalization. Propensity score matching by comorbidities, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) usage were done for baseline comparability. Cox proportional hazard models were used to evaluate crude and adjusted hazard ratios.ResultsThe cumulative incidence of AS was higher in patients with endometriosis compared to the non-endometriosis comparison cohort (log-rank test, p = 0.015). The adjusted hazard ratio (aHR) of incidental AS in patients with endometriosis was 1.61 (95% CI = 1.11 to 2.35) in comparison to the non-endometriosis comparison cohort. An increased risk of AS was also observed in subjects with major depressive disorder (aHR = 5.05, 95% CI = 1.85 to 13.78). Stratified analyses of age subgroups showed consistent results. NSAID users had a lower risk of AS than NSAID non-users (aHR 4.57 vs 1.35, p for interaction = 0.031).ConclusionsIn this retrospective population-based cohort study, we found a higher risk of AS in patients with endometriosis. We suggest that clinicians should pay attention to the occurrence of AS in patients with endometriosis.