Ga 13 , a heterotrimeric G-protein of the Ga 12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Ga 13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Ga 13 induces epithelial-mesenchymal transition in ovarian cancer (OvCa) cells through down-regulation of large tumor suppressor kinase (LATS) 1, a critical component of the Hippo signaling pathway. A synthetic biology approach using a mutant GPCR and chimeric G-protein revealed that Ga 13 -regulated phosphorylation of LATS1 at serine 909 within its activation loop induced recruitment of the itchy E3 ubiquitin protein ligase to trigger LATS1 degradation. Our findings uncover novel mechanisms through which Ga 13 activation induces dysregulation of the Hippo signaling pathway, which leads to aggressive cancer phenotypes, and thereby identify a potential target for preventing the metastatic spread of OvCa.
HighlightsThis report shows very rare cases of small cell carcinoma of the ovary, hypercalcemic type and pulmonary type.Their chemo sensitivity is quite different. These two cases followed opposite clinical courses.The first case (SCOHT) progressed rapidly, and showed resistance to chemotherapy and radiotherapy.The second case (SCOPT) showed sensitivity to chemotherapy and radiotherapy although recurrence was repeated.
Aim Uterine leiomyosarcoma (ULMS) is a highly aggressive and lethal disease. This malignancy remains the most common type of uterine sarcoma, affecting approximately 0.4/100 000 women each year. Our aim was to assess the treatment and prognosis of ULMS patients. Methods A total of 14 patients were treated at our institution between January 2008 and July 2017. We retrospectively analyzed their clinicopathological variables, treatment and prognosis. Results The median patient age was 63 years (range, 35–83 years). The largest group of patients had stage IB disease (stage IB, n = 8; IIB, n = 2; IIIB, n = 1; IVB, n = 3) and the largest group by histological subtype was ordinary (ordinary, n = 11; myxoid, n = 2; epithelioid, n = 1). Total abdominal hysterectomy and bilateral salpingo‐oophorectomy were performed for all patients, with additional surgical procedures (e.g., tumor resection, lymphadenectomy) performed if necessary. Twelve patients received adjuvant chemotherapy (ACT) consisting of gemcitabine and docetaxel. Ten patients experienced recurrence and received multidisciplinary therapies, including tumor resection, chemotherapy, radiation and targeted therapies. The median observation period was 17 months (range, 5–75 months), and 11 patients were alive (without disease, n = 5; with disease, n = 6). Intriguingly, five of eight stage IB patients who received postoperative ACT were alive without disease. Conclusion ULMS is rare but is associated with a poor prognosis, even if multidisciplinary therapies are administered. However, ACT appears to be effective in improving the prognosis of patients with stage IB disease.
Objective: We compared the clinical outcomes of total laparoscopic radical hysterectomy (LRH) with abdominal radical hysterectomy (ARH) performed in women with cervical cancer. Methods: Between November 2015 and February 2018, 19 women with cervical cancer (Stage IB1 or IIA1) underwent LRH, and 40 women with cervical cancer (Stage IB1 or IIA1) underwent ARH in our department. Patients' background, surgical outcomes, perioperative complications, and postoperative course were retrospectively compared between the groups. Statistical analysis was performed using the Student's t-test, Wilcoxon test, and the Fisher exact test. Results: The operative time was significantly longer (587 vs. 422 min, p<0.0001) and estimated blood loss was significantly lesser (417 vs. 1077 mL, p<0.0001) in the LRH group. No statistically significant intergroup difference was observed in the number of lymph nodes removed, surgical margin, and perioperative complications. Median follow-up was 16 and 23 months, respectively, and recurrence occurred in 1 patient in each group. Conclusion: Although this study included a limited number of patients and was a short-term study, LRH was safely performed in women with cervical cancer. Notably, no intergroup difference was observed in short-term outcomes. We will continue observation to determine the long-term prognosis in these women.
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