Stress responses to bacterial and viral mimetics in polycystic ovary syndrome model rats.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.

New treatment strategies for uterine sarcoma using secreted frizzled­related proteins.

Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.

Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model.

Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.

Progesterone treatment reduces food intake and body weight in ovariectomized female rats.

While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.

Effects of STAT Inhibitors in Mouse Models of Endometriosis.

The signal transducer and activator of transcription (STAT) pathway, which regulates cell proliferation and immunity, has been implicated in chronic inflammatory diseases such as rheumatoid arthritis. However, few reports have described the effects of STAT inhibitors on endometriosis, another chronic inflammatory disease. Here, we investigated the intraperitoneal microenvironment and the effects of a STAT inhibitor in a mouse model of endometriosis. In the treatment group, a STAT3 inhibitor (Stattic®, 80 mg/kg) was orally administered three times per week; control animals received orally dosed phosphate-buffered saline. Endometriosis-like lesions and peritoneal lavage fluid were collected before and 1, 2, and 3 weeks after STAT3 inhibitor administration was initiated. The lesion area was significantly increased in both groups after the first week. However, in the treatment group, the lesion areas were significantly reduced at weeks 2 and 3 compared with week 1. Transforming growth factor (TGF)-ß messenger RNA (mRNA) levels in ascites cells were significantly lower at weeks 1 and 2 than at week 0. Interleukin (IL)-6 mRNA levels were significantly higher at week 1 than at week 0 but were significantly lower at weeks 2 and 3 than at week 1. Thus, STAT inhibitors appeared to reduce the extent of endometriosis in this mouse model, and may also inhibit the IL-6 signaling pathway and reduce TGF-ß levels. This study suggests that STAT inhibitors warrant further exploration for use in the treatment of endometriosis.

Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan.

The prevalence of germline BRCA1 or BRCA2 pathogenic variants (gBRCA1/2-PV) in patients with primary epithelial ovarian cancer (OC) in a rural area of Japan and their association with clinical characteristics, including treatment response and survival outcome, were investigated. A total of 123 unbiased patients with OC were tested for gBRCA1 and gBRCA2 using next-generation sequencing-based targeted amplicon sequencing. Clinical characteristics of OC patients with and without gBRCA1/2 status were compared. The overall prevalence of gBRCA1/2-PV was 15.4% (19 cases), with gBRCA2-PV (10.5%, 13 cases) being more common than gBRCA1-PV (4.9%, 6 cases). Among the observed gBRCA1/2-PV, several novel variants were included, suggesting that gBRCA1/2-PV unique to the local area exist. gBRCA1/2-PV was significantly more prevalent in OC patients at an older age, with high-grade serous carcinoma, with advanced-stage tumors, and with a family history of breast cancer or hereditary breast and ovarian cancer syndrome (HBOC)-associated cancers. Patients with advanced-stage OC with gBRCA1/2-PV showed a significantly lower recurrence rate and tended to have better progression-free and overall survival than those with wild-type gBRCA1/2. Genetic testing for gBRCA1/2 status in all OC patients is useful not only for diagnosing HBOC in patients and their relatives to assess the risk of HBOC-associated cancers, but also to estimate therapy response and outcomes in patients.

Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy.

BACKGROUND: Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. METHODS: This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. RESULTS: The patients' median age was 60 (range 33‒80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m2) before treatment had a poor prognosis (p = 0.016 and p < 0.001). CONCLUSIONS: Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

Pathological examination of a placenta leading to the diagnosis of endometrial carcinoma: A case report.

Although endometrial cancer is extremely rare during pregnancy, the placental metastasis of endometrial cancer is even rarer. The current study presents a case of endometrial carcinoma that was diagnosed through the pathological examination of the placenta. A 35-year-old primipara woman who underwent frozen-thawed embryo transfer at the Keiai Ladies Clinic in Tokushima prefecture (Japan) received regular prenatal check-ups. She was transferred to Tokushima University Hospital for perinatal management due to the preterm premature rupture of membranes at 21 weeks and 6 days gestation. The administration of antibiotics and tocolytic agents was continued; however, labor pain occurred at 23 weeks and 3 days gestation, and a female fetus weighing 524 g was delivered vaginally. The placenta weighed 262 g and had no macroscopic abnormalities. It was submitted for pathological examination, which revealed metastatic adenocarcinoma (clear cell carcinoma suspected). The patient was subsequently diagnosed with endometrial cancer (stage I suspected), and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and pelvic lymph node dissection. The final diagnosis was stage IA endometrial cancer (endometrioid carcinoma, G2). At 1 year after surgery, there was no evidence of disease. The present case highlights the importance of considering the emergence of endometrial cancer during pregnancy.

Association between salt intake and long-term mortality in hemodialysis patients: A retrospective cohort study.

BACKGROUND: The association between salt intake and clinical outcomes in hemodialysis patients has been controversial. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. METHOD: The present study included patients who underwent hemodialysis from June 1st 2016 to May 31st 2020. Corrected salt intake by ideal body weight was the main predictor of outcomes. Ideal body weight was calculated assuming that the ideal body mass index is 22 kg/m2 for the Japanese population. The multivariate Cox proportional hazards model was used to determine the association between corrected salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cumulative incidence of cardiovascular events at year 4. RESULT: A total of 492 adult patients were enrolled in the study. The mean daily salt intake and corrected salt intake at baseline were 9.5 g/day and 0.17 g/kg/day, respectively. The low corrected salt intake group (< 0.13 g/kg/day) demonstrated the highest 4-year all-cause mortality. No association was observed between corrected salt intake and the cumulative incidence of cardiovascular events. In multivariate Cox proportional hazards analysis, only the group with corrected salt intake of 0.16-0.20 g/kg/day was associated with a decreased hazard risk for all-cause death compared with the low corrected salt intake group. CONCLUSION: The present study found that a low salt intake was associated with high all-cause mortality in hemodialysis patients. Reduced long-term survival may be attributed to malnutrition resulting from excessive salt restriction.

Behavioral Therapy for Muscular Objective Tinnitus in Forceful Eyelid Closure Syndrome (FECS): A Case Report.

This report presents the case of a patient with forceful eyelid closure syndrome (FECS) who did not have an otologic history of facial paresis. The patient was an 11-year-old girl. She complained of a click noise in the left ear simultaneous with eyelid closure and was referred to our department. A microphone in the external auditory canal captured a click noise simultaneously with eye blinking. Impedance audiometry of the left ear showed a slight compliance reduction simultaneously with eye blinking, whereas a pure-tone audiogram, tympanogram, computed tomography (CT), magnetic resonance imaging (MRI), and movement of the palate and pharynx were normal. Her previous otologic history was unremarkable and did not include facial paresis. She was diagnosed with FECS due to contraction of the tensor tympanic muscle. Treatment with an anticonvulsant for 2 months showed no effects on her tinnitus and she was bothered by her drowsiness and dizziness. Behavioral therapy (BT) was started, and the tinnitus was remarkably reduced in 7 months. BT for patients with muscular tinnitus, including FECS, may be a preferred choice rather than surgical procedure and medication including an anticonvulsant and muscle relaxant.

Clinical and biological significance of EZH2 expression in endometrial cancer.

The objective of this study was to examine the clinical significance of EZH2 expression and the therapeutic efficacy of its silencing in endometrial cancer. EZH2 expression in clinical samples was evaluated using a tissue microarray and correlated with clinical outcomes. The biological roles of EZH2 were assayed in vitro and in vivo. Gene expression was examined to reveal the molecular mechanism underlying the roles of EZH2 in endometrial cancer. We found that EZH2 overexpression was significantly correlated with disease-free and overall survival of patients with endometrial cancer. EZH2 silencing resulted in decreased cell viability and invasiveness, and increased apoptosis. In addition, EZH2 silencing enhanced the cytotoxicity of taxanes and cisplatin in Hec-1A and Ishikawa endometrial cancer cells. EZH2 silencing using small-interfering RNA (siRNA) incorporated into chitosan nanoparticles (siRNA/CN) induced a significant anti-tumor effect compared with that observed in controls (66.6% reduction in Hec-1A cells and 63.2% reduction in Ishikawa cells, p < .05 for both). Moreover, EZH2 siRNA/CN in combination with taxanes produced more robust anti-tumor effects versus those induced by monotherapies (77.0% for Hec-1A cells and 57.7% for Ishikawa cells, p < .05 for both). These results were associated with decreased angiogenesis and cell proliferation, and enhanced apoptosis. Genomic analyses revealed that EZH2 silencing decreased the expression levels of many genes associated with tumor growth, including PRDX6. Collectively, these results support EZH2 as an attractive target for the therapeutic management of endometrial cancer.

Tumor characteristics and outcome of uterine carcinosarcoma in women aged ≥80 years.

OBJECTIVE: To examine clinico-pathological characteristics and outcomes of uterine carcinosarcoma (UCS) in women aged ≥80 years. METHODS: This is a secondary analysis of a previous multicenter retrospective study examining 906 women with stage I-IV UCS who underwent primary hysterectomy. Patient demographics, treatment types, tumor characteristics, and survival were examined across aged ≥80 (n = 82 [9.1%]), aged 60-79, (n = 526 [58.1%]), and aged <60 (n = 298 [32.9%]). RESULTS: Women in the aged ≥80 group were more likely to be Caucasian, undergo simple hysterectomy without lymphadenectomy, and receive no postoperative therapy (all, P < 0.05). Tumors in the aged ≥80 group were more likely to have high-grade carcinoma, heterologous sarcoma, and sarcoma dominance but less likely to have lympho-vascular space invasion (all, P < 0.05). Lymphadenectomy did not improve survival in the aged ≥80 group (P > 0.05), whereas lymphadenectomy was protective for survival in the younger groups (both, P < 0.05). Postoperative chemotherapy was associated with improved progression-free survival (PFS) in the aged ≥80 group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.89, P = 0.021). With chemotherapy treatment, women in the aged ≥80 group had PFS similar to those in the aged 60-79 group (HR 0.97, 95%CI 0.51-1.83, P = 0.92). In contrast, without chemotherapy treatment, women in the aged ≥80 group had significantly decreased PFS compared to the aged 60-79 group (HR 1.62, 95%CI 1.09-2.40, P = 0.016). Similar associations were observed for postoperative radiotherapy. CONCLUSION: Nearly 10% of women with UCS are aged ≥80 that are characterized by aggressive tumor factors. Postoperative therapy but not extensive surgery may improve survival in this age group.

Resveratrol suppresses proliferation and induces apoptosis of uterine sarcoma cells by inhibiting the Wnt signaling pathway.

Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of ß-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this ß-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3ß. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.

Circulating Aminoterminal Propeptide of Type III Procollagen as a Biomarker of Cardiovascular Events in Patients Undergoing Hemodialysis.

AIM: Type Ⅲ collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type Ⅲ procollagen (PⅢNP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis. METHODS: Serum PⅢNP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64±11 years; dialysis duration, 11.5±7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011. RESULTS: During the follow-up for 4.7±1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PⅢNP concentration (1 U/mL; hazard ratio, 1.616; P=0.0001). The median serum PⅢNP concentrations were higher in patients with cardiovascular events than in those without (2.30±0.19 U/mL vs 1.30±0.03 U/mL; P＜0.0001). When the patients were assigned to subgroups based on serum PⅢNP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P=0.0001) in the subgroup of serum PⅢNP ≥1.75 U/mL than in that of serum PⅢNP ＜1.75 U/mL (31.9% vs 88.2%). CONCLUSIONS: Serum PⅢNP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

Can systematic lymphadenectomy be omitted for low-risk endometrial cancer?

The objective of this study was to identify pathological indicators that could be used to identify a subgroup of patients with apparent stage I endometrial cancer who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer patients underwent primary surgery at Tokushima University Hospital. We retrospectively evaluated their clinical records and histopathological factors. Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade 1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty-four patients with a T1a endometrium-limited lesion did not exhibit lymph node metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph node metastasis, and these 3 cases exhibited approximately 50% myometrial invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy remain alive without recurrence. Systematic lymphadenectomy could be omitted for patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J. Med. Invest. 65:221-224, August, 2018.

Pericyte-Specific Ninjurin1 Deletion Attenuates Vessel Maturation and Blood Flow Recovery in Hind Limb Ischemia.

Objective- Angiogenesis, entire step from endothelial cells (ECs) sprouts to vascular maturation, is a critical response to ischemia. To form functional mature vessels, interactions between ECs and pericytes are essential. Ninj1 (ninjurin1) is an adhesion molecule that contributes to the pathogenesis of neuroinflammation. We recently demonstrated that Ninj1 is expressed in pericytes during angiogenesis. However, the role of Ninj1 in angiogenesis under pathophysiological ischemic conditions has not yet been elucidated. Approach and Results- Ninj1 was detected in microvessels, and its expression was enhanced in ischemic tissues after mouse hindlimb ischemia. Knockdown of Ninj1 was performed by injection of biodegradable microspheres releasing Ninj1-small interfering RNA into muscle tissues. Alternatively, pericyte-specific Ninj1 knockout was induced by tamoxifen treatment of NG2-CreERT/Ninj1-flox mice. Ninj1 knockdown/knockout reduced the formation of blood-circulating functional vessels among total CD31+ microvessels within ischemic tissues and subsequently attenuated color Doppler-assessed blood flow recovery. Ninj1 overexpression enhanced expression of Anpt (angiopoietin) 1, whereas Ninj1 knockdown enhanced the endogenous Anpt1 antagonist, Anpt2 expression in pericytes and inhibited the association of pericytes with ECs and subsequent formation of capillary-like structure, that is, EC tube surrounded with pericytes in 3-dimensional gel culture. Conclusions- Our data demonstrate that Ninj1 is involved in the formation of functional matured vessels through the association between pericytes and ECs, resulting in blood flow recovery from ischemia. These findings further the current our understanding of vascular maturation and may support the development of therapeutics for ischemic diseases.

Characterizing sarcoma dominance pattern in uterine carcinosarcoma: Homologous versus heterologous element.

OBJECTIVE: To examine significance of sarcoma dominance (SD) patterns in uterine carcinosarcoma (UCS). METHODS: This is a secondary analysis of multicenter retrospective study examining women with stages I-IV UCS who underwent primary surgery. SD was defined as >50% of sarcoma component in uterine tumor. SD patterns were grouped as homologous sarcoma without SD (homo/non-dominance, n = 351), heterologous sarcoma without SD (hetero/non-dominance, n = 174), homologous sarcoma with SD (homo/dominance, n = 175), and heterologous sarcoma with SD (hetero/dominance, n = 189), and correlated to tumor characteristics and survival. RESULTS: SD patterns were significantly associated with age, body habitus, carcinoma type, tumor size, depth of myometrial invasion, and nodal metastasis (all, P < 0.05). On univariate analysis, SD was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (both, P < 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homo/dominance 1.35-1.69, and hetero/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homo/non-dominance (all, P < 0.05). Among stage I-III disease, when tumors had SD, adding radiotherapy to chemotherapy was significantly associated with improved PFS (adjusted-HR: homo/dominance 0.49, and hetero/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P < 0.05); contrary, this association was not observed with absence of SD (all, P > 0.05). CONCLUSION: In UCS, SD impacts survival in homologous but not in heterologous type. Regardless of sarcoma types, SD was associated with decreased survival in UCS; adding radiotherapy to chemotherapy may be an effective postoperative strategy.