Kazu Ueda

Hypoxia promotes glycogen synthesis and accumulation in human ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) has several significant characteristics based on molecular features that are distinct from those of ovarian high-grade serous carcinoma. Cellular glycogen accumulation is the most conspicuous feature of OCCC and in the present study its metabolic mechanism was investigated. The amount of glycogen in cells cultured under hypoxia increased significantly and approximately doubled after 48 h (P<0.01) compared to that under normoxic conditions. Periodic acid-Schiff positive staining also demonstrated intracellular glycogen storage. Western blot analysis revealed that HIF1α, which was overexpressed and stabilized under hypoxic conditions, led to an increase in the levels of cellular glycogen synthase 1, muscle type (GYS1), and conversely to a decrease in inactive phosphorylated GYS1 at serine (Ser) 641. Additional increases were observed in both protein phosphatase 1, which dephosphorylates and thereby induces GYS1 enzyme activity, and glycogen synthase kinase 3 beta (GSK3β) phosphorylated at Ser9, which is inactive on phosphorylation of GYS1 and subsequently induces its enzyme activity. By contrast, the level of PYGM-b decreased. These results indicated that the glycogen accumulation under a hypoxic environment resulted in the promotion of glycogen synthesis, but did not lead to inhibition of glycogen degradation and/or consumption. Under hypoxic conditions, HAC2 cells showed activation of the PI3K/AKT pathway caused by a mutation in exon 20 of PIK3CA, encoding the catalytic subunit p110α of PI3K. The resulting activation of AKT (phosphoSer473) also plays a role as a central enhancer in glycogen synthesis through suppression of GSK3β via phosphorylation at Ser9. Hypoxia decreased the cytocidal activity of cisplatin and doxorubicin to various degrees. In conclusion, the hypoxic conditions together with HIF1 expression and stabilization increased the intracellular glycogen contents and resistance to the anticancer drugs.

Nonpuerperal inversion of the uterus associated with endometrial cancer: a case report.

Few nonpuerperal uterine inversions have been reported, with only 101 cases during the period from 1940 to date. Moreover, uterine inversion resulting from endometrial cancer is an extremely rare condition, with only 7 reported cases. In this article, we present a case of a patient with uterine inversion caused by endometrial cancer that could be diagnosed and treated with surgery. We also discuss the mechanism of onset and present a review of the literature.

Pilot study of CD147 protein expression in epithelial ovarian cancer using monoclonal antibody 12C3

Aim:  CD147 is a membrane glycoprotein that is expressed in various cancer cells and is involved in tumor invasion and metastasis by inducing stromal fibroblastic cells to produce matrix metalloproteinases. This study was carried out to evaluate the correlation between CD147 expression and various clinicopathologic parameters, including histological grade and prognosis in a small sample set of human ovarian cancer patients.

Establishment and characterization of JHUCS-1 cell line derived from carcinosarcoma of the human uterus

The cell line designed JHUCS-1 was established from a carcinosarcoma (malignant mixed mesodermal tumor) of the uterus that was surgically removed from a 57-year-old Japanese woman. We carefully examined the histopathology of the original tumor after the cell line was established and noted differentiation into a neuroendocrine carcinoma within the tumor’s epithelial components. Immunohistochemical staining of the tumorous tissue that had been heterotransplanted was positive for Leu7. Additionally, secretary granules were observed in the grafted cells as determined by electron microscopy. These results support the existence of neuroendocrine cells within the JHUCS-1 cell line.

A case of female adnexal tumor of probable Wolffian origin: significance of MRI findings

Female adnexal tumors of probable Wolffian origin (FATWOs) are rare neoplasms that originate from remnants of the Wolffian duct. These tumors often appear in the broad ligament and para-ovarian area where such remnants exist. FATWOs have specific pathological characteristics similar to those of remnants of the Wolffian duct. Since these tumors neither have any specific tumor markers nor specific features on scanning images, there has been no case report concerning the preoperative diagnosis of FATWOs. Diagnostic imaging technology has become remarkably developed nowadays, enabling physicians to make preoperative diagnosis more precisely. We report here a case of FATWO with detailed discussion of its MR images.

PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for monitoring ovarian clear cell carcinoma

Ovarian clear cell carcinoma (OCCC) exhibits distinct phenotypes, such as resistance to chemotherapy, poor prognosis and an association with endometriosis. Biomarkers and imaging techniques currently in use are not sufficient for reliable diagnosis of this tumor or prediction of therapeutic response. It has recently been reported that analysis of somatic mutations in cell-free circulating DNA (cfDNA) released from tumor tissues can be useful for tumor diagnosis. In the present study, we attempted to detect mutations in PIK3CA and KRAS in cfDNA from OCCC patients using droplet digital PCR (ddPCR). Here we show that we were able to specifically detect PIK3CA-H1047R and KRAS-G12D in cfDNA from OCCC patients and monitor their response to therapy. Furthermore, we found that by cleaving wild-type PIK3CA using the CRISPR/Cas9 system, we were able to improve the sensitivity of the ddPCR method and detect cfDNA harboring PIK3CA-H1047R. Our results suggest that detection of mutations in cfDNA by ddPCR would be useful for the diagnosis of OCCC, and for predicting its recurrence.

Dedifferentiated endometrial carcinoma: A report of three cases and review of the literature

Dedifferentiated endometrial carcinoma, which is defined microscopically as the co-existence of undifferentiated carcinoma and grade 1 or 2 endometrioid adenocarcinoma, is an aggressive type of cancer regardless of the percentage of undifferentiated components. It is reported that undifferentiated carcinoma comprises 9% of endometrial carcinoma. The percentage of dedifferentiated endometrial carcinoma has been hypothesized to be 40% of undifferentiated carcinoma. A precise pathological diagnosis is essential for defining the appropriate therapeutic approach and prognosis. Furthermore, since there is an association between dedifferentiated endometrial carcinoma and Lynch syndrome, it is important to identify the patients genetic background. The current case report presents three cases of dedifferentiated endometrial carcinoma treated in our hospital. In immunohistochemical staining for DNA mismatch-repair (MMR) proteins in dedifferentiated endometrial carcinoma, the components of undifferentiated carcinoma demonstrated a loss of MMR protein expression, and it is suspected that there may be a germline mutation in these cases. Therefore, Lynch syndrome should be suspected and the appropriate genetic approaches in cases of dedifferentiated endometrial carcinoma should be considered.

Higuchi's transverse incision and a modification of this method for minimally invasive surgery

Study Objective: To describe Higuchi’s transverse incision and a modification of this method for reduced port surgery (RPS). Design: Descriptive study. Setting: University hospital. Patients: Those with ovarian cyst and uterine myoma. Intervention: A platform is placed in the 2–3 cm Higuchi incision just above the pubis or on the pubis. Blunt dissection of the subcutaneous adipose tissue is performed. A T incision of the rectus abdominis fascia and a longitudinal incision of the peritoneum are performed. A LAP PROTECTOR and EZ access (Hakko Medical, Nagano, Japan) are used with the platform for single-incision laparoscopic surgery. The peritoneum and fascia are closed by continuous suture, and the skin is closed using the dermostitch technique. Main Results: Higuchi’s transverse incision is 2–3 cm in length and is made at a much lower position than the conventional Pfannenstiel transverse incision. The wound is covered by pubic hair, yielding an excellent esthetic outcome. The T incision of the rectus abdominis fascia secures a more extensive surgical field than the Pfannenstiel transverse incision. Conclusion: Higuchi’s modified transverse incision ensures a sufficient visual field, yields an excellent esthetic outcome, and is safe, suggesting the potential use of this method for RPS.

Feasibility of reduced port surgery applying Higuchi's transverse incision

Objective: Higuchi’s transverse incision is made at a lower position than the Pfannenstiel transverse incision and is superior in terms of cosmetic outcomes. The purpose of this study was to examine the safety and efficacy of novel forms of reduced port surgery for ovarian cysts and uterine fibroids applying Higuchi’s transverse incision. Methods: In 33 patients with ovarian cysts who underwent low-position single-incision laparoscopic surgery (L-SILS)-modified single-port laparoscopy placed in the 2–3-cm Higuchi’s incision above the pubis, patient’s characteristics and perioperative outcomes were compared with those of patients who underwent multiport laparoscopy (n = 53). In addition, 18 patients with uterine fibroids who underwent dual-port laparoscopically assisted myomectomy without using power morcellators and conventional four-port laparoscopically assisted myomectomy were investigated. Results: There were no significant differences between L-SILS and multiport laparoscopy in tumor diameter, bleeding, hospital stay, or postoperative pain. However, the L-SILS group demonstrated significantly shorter operative and pneumoperitoneum times (p < 0.01 and p < 0.01). In comparison with cases of uterine fibroids, no significant differences were found in maximum fibroid diameter, operative time, pneumoperitoneum time, or bleeding. However, the dual-port laparoscopically assisted myomectomy group demonstrated a significantly shorter length of hospital stay than the conventional laparoscopically assisted myomectomy group (p < 0.05). Conclusion: We reported novel forms of reduced port surgery applying Higuchi’s transverse incision. It was suggested that these procedures are relatively simple, but ensure the same safety and efficacy as conventional methods. We intend to increase the number of cases and examine safety, efficacy, and patient satisfaction for these procedures.