Tsuyoshi Ohta's research while affiliated with Yamagata University and other places
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Publications (67)
Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian carcinoma that responds poorly to chemotherapy. Glutathione (GSH) is a primary antioxidant, which protects cells against reactive oxygen species (ROS). High levels of GSH are related to chemotherapeutic resistance. The glutamine/cystine transporter xCT is essential for intr...
Simple Summary
Ovarian cancer cell dissemination can lead to inoperability and death in patients with advanced ovarian cancer. Honeycomb-like structured films (HCFs) are three-dimensional (3D) porous scaffolds fabricated from biodegradable polymers and have been widely used in tissue engineering. We assessed whether HCFs could be a novel strategy t...
Background:
Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit.
Patients and methods:
The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary...
Objective:
The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment.
Methods:
The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society...
Objective:
The primary objective was to investigate the association between early menopause and cardiovascular disease (CVD) prevalence in Japanese women. The secondary objective was to ascertain the association with CVD risk factors.
Methods:
In this cross-sectional study, 7,239 naturally menopausal women from the Yamagata Cohort Study who comp...
Nuclear receptor coactivator 6 (Ncoa6), a modulator of several nuclear receptors and transcription factors, is essential for the decidualization of endometrial stromal cells in mice. However, the function of Ncoa6 in the human endometrium remains unclear. We investigated its function in the decidualization of human endometrial stromal cells (HESCs)...
Background
Group A streptococcus infection during pregnancy can be concerning. It may cause toxic shock syndrome, which can be fatal. Here, we report a rare case of a pregnant woman who developed infectious sacroiliitis due to group A streptococcus infection. To the best of our knowledge, this case is the first of its kind to be reported.
Case pre...
Glutathione is an antioxidant that has an important role in chemotherapeutic drug resistance in cancer. Cysteine is synthesized from cystine and is transported into the cell via the xCT antiporter. Another pathway for synthesizing cysteine involves intracellular methionine. We determined whether targeting the xCT represents a promising strategy for...
To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecolog...
[This corrects the article DOI: 10.18632/oncotarget.25868.].
Objective
The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy.Methods
In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated wi...
Aim:
To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012.
Methods:
The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where informa...
Ovarian mature cystic teratomas (MCT) are usually benign. However, squamous cell carcinoma (SCC) develops in 0.17%–2% of MCT. Because of its low frequency, the optimal treatment for this disease is unclear. We present a case of SCC arising from MCT. Our patient was a 30-year-old nulliparous woman complaining of right lower abdominal pain, who was r...
Glutathione (GSH) is a primary antioxidant that protects cells against reactive oxygen species (ROS), and high levels of GSH promote cancer cell survival and resistance to chemotherapy. The glutamine transporter xCT is essential for the intracellular synthesis of GSH, whereby xCT determines the intracellular redox balance. However, whether xCT inhi...
Background
Granulocyte colony stimulating factor (G-CSF) is known to cause vasculitis, mainly in the small vessels. Several cases of large-vessel vasculitis (LVV) caused by G-CSF have recently been reported in the literature; we retrospectively suspect that some cases of LVV in our institution were associated with administration of G-CSF.
Purpose...
The aim of the present study was to evaluate the oncologic safety and reproductive outcome in patients with stage I epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). Women aged ≤40 years with stage I EOC who had undergone FSS between 2000 and 2010 were retrospectively reviewed. Survival was examined using the Kaplan-Meie...
Background:
Globally, cervical cancer is the fourth most common cancer in women. Here, we report a case of cutaneous lymphangitis carcinomatosa arising from cervical cancer, an extremely rare and treatment-resistant condition.
Case presentation:
A 64-year-old Japanese woman presented with genital bleeding. She was diagnosed as having stage IB1 s...
Aim:
To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2015 and the Annual Treatment Report for 2010 on the outcomes of patients who started treatment in 2010.
Methods:
The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry where informati...
Introduction
Uterine serous carcinoma (USC) is more aggressive than other subtypes of endometrial carcinoma and is associated with a poor prognosis. We analyzed the metabolomic profile of USC with acquired resistance to paclitaxel.
Results
Glutathione (GSH) concentration in PTX-1 cells was higher than in USPC-1 cells. In addition, GSH concentratio...
Introduction: Uterine serous carcinoma (USC) is more aggressive than other subtypes of endometrial carcinoma and is associated with a poor prognosis. We analyzed the metabolomic profile of USC with acquired resistance to paclitaxel.
Method: We compared metabolic profiles and reactions to paclitaxel in both a wild-type USC cell line (USPC-1) and PTX...
Tumor lysis syndrome (TLS) is an oncological life-threatening complication characterized by hyperuricemia, hyperphosphatemia, and hyperkalemia, which can lead to acute renal failure, cardiac arrhythmias, cardiac arrest and seizures. Although TLS is a rare complication in patients with non-hematological malignancy, the mortality rate of TLS in solid...
The use of paclitaxel in addition to cisplatin resulted in the improvement of ovarian cancer treatment. Based on the results of several randomized clinical trials (RCTs), the combination of paclitaxel and carboplatin administered every 3 weeks intravenously (IV) or a dose-dense regimen of weekly paclitaxel plus carboplatin demonstrates high clinica...
Objectives:
This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women and clarify the antioxidant effect of estrogen on adipocytes.
Materials and methods:
Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery...
Purpose:
We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial.
Methods:
PLD was administered intravenously at a dose of 30 mg/m(2) on day 3. CPT-11 was adminis...
Activation of Estrogen receptor (ER) alpha (α) promotes cell growth and influences the response of cancer cell to chemotherapeutic agents. However, the mechanism by which ERα activation antagonizes cells to chemotherapy-induced cytotoxicity remains unclear. Here, we investigated the effect of cisplatin on ERα activation. In addition, we examined wh...
Objective:
We conducted this study to evaluate the efficacy and safety of adjuvant chemotherapy using taxane plus carboplatin (CBDCA) for high-risk stage IB-IIB patients with uterine cervical non-squamous cell carcinoma after radical hysterectomy.
Methods:
Thirty-seven patients were eligible. Pelvic lymph node involvement and/or parametrial inva...
Objective:
The aim of this study was to compare the efficacy of nedaplatin-based concurrent chemoradiotherapy (CCRT) with that of cisplatin-based CCRT in patients with cervical cancer.
Methods:
The medical records of patients with cervical cancer who had undergone CCRT between 2003 and 2007 were retrospectively reviewed. Of these, 129 patients w...
Background/aim:
Global increase in the trimethylation of histone H3 at lysine 27 (H3K27me3) has been associated with the differentiation of normal stem cells and cancer cells, however, the role of H3K27me3 in the control of cancer stem cells (CSCs) remains poorly understood. We investigated the impact of increased H3K27me3 on CSCs using a selectiv...
Ovarian cancer is the most lethal gynecological malignancy, for which platinum- and taxane-based chemotherapy plays a major role. Chemoresistance of ovarian cancer poses a major obstacle to the successful management of this devastating disease; however, effective measures to overcome platinum and taxane resistance are yet to be established. In the...
[Objective] The objective of this study was to examine whether estrogen receptor alpha (ERα) is associated with the sensitivity to cisplatin in ovarian cancer cells.
[Methods] Using two human ovarian cancer cell lines (Caov-3, Ovcar-3) which express ERα, we investigated the effect of cisplatin on ERα activation. We evaluated the association between...
This multi-institutional study was conducted to clarify the clinicopathological features of squamous cell carcinomas of the vulva.
The medical records of vulvar cancer patients treated between 2002 and 2012 were retrospectively reviewed following approval by the Institutional Review Board of each institution.
One hundred and eleven patients with vu...
Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical ou...
The prolongation of progression-free survival (PFS) in patients with advanced ovarian cancer by anti-angiogenic therapy has been shown in several clinical trials. However, although an anti-VEGF antibody (bevacizumab) is the only option currently available, its efficacy is limited and it is not cost-effective for use in all patients. Therefore, the...
Mayer-Rokitansky-Küster-Hauser syndrome is a rare congenital anomaly characterized by congenital aplasia or hypoplasia of the uterus and vagina. We report a case of Mayer-Rokitansky-Küster-Hauser syndrome with multiple large pelvic masses diagnosed by three-dimensional computed tomography (CT) angiography.
A 40-year-old woman with Mayer-Rokitansky-...
Cancer stem cells (CSCs) are considered to contribute to the poor prognosis of ovarian cancer as a major cause of fatal recurrence. Identification of effective measures to eliminate ovarian CSCs through induction of cell death and/or loss of self-renewal capacity would, therefore, be key to successful management of ovarian cancer.
The effects of re...
Background:
This study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer.
Methods:
This was a multicenter prospective cohort study conducted in member facilities of Tohoku Gynecologic Cancer Unit. Patients with FIGO 1A-1B1 squamous cell c...
The Wilms' tumor 1 gene WT1 encodes a zinc transcription factor involved in a variety of cancer-related processes. In this study, we sought to investigate the effects of WT1 splice variants on tumorigenic activity and survival in an in vivo ovarian cancer model. To this end, we established stable ovarian cancer cell lines transduced with lentiviral...
Background/aim:
Activation of the c-JUN N-terminal kinase (JNK) signaling pathway has been associated with poor survival of ovarian cancer patients, but the role(s) and significance of JNK signaling in ovarian cancer cells remain poorly understood. In the present study, we aimed to investigate the role of JNK specifically in ovarian cancer stem ce...
Background:
The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma.
Methods:
We conducted a retrospective survey of seven medical facilities in the Tohoku Gynecologic Cancer Unit.
Results:
A total of 45 patients who had undergone hysterectomy an...
Objective:
We investigated whether the estrogen released from non-sex cord-stromal ovarian tumors has biological effects on bone and endometrial tissue in postmenopausal women.
Materials and methods:
A total of 132 patients with malignant (n = 112) or benign (n = 20) gynecological disease with normal postmenopausal ovaries were recruited as a co...
Recent RNA-sequencing studies have identified variant transcripts, fusion transcripts and novel transcripts in cancer. However, little is known about the role of these variant transcripts in tumor development. To identify a specific role of these variant transcripts in tumor development toward chemotherapy resistance, we generated a custom retrovir...
We examined the effect of gefitinib (ZD1839), a selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, on cytotoxicity to cisplatin, EGFR downstream signaling, apoptosis and the association between the inhibition of DNA repair by gefitinib and the expression of DNA-dependent protein kinase (DNA-PK) using three ovarian cancer c...
Rho, a Ras-related small GTPase, and Rho-associated coiled coil-containing protein kinase (Rho kinase, ROCK1 and ROCK2) are key regulators of focal adhesion, actomyosin contraction, and thus cell motility. Rho/ROCK kinases also play roles in proliferation, differentiation, apoptosis and oncogenic transformation. In the present study, we have shown...
Estrogen (E2) has direct in vivo and in vitro effects, such as inducing neurite outgrowth, on neurons. We investigated the morphological changes and intracellular signaling pathway induced by E2 in neuroblastoma (SH-SY5Y) cells. The effect of medroxyprogesterone acetate (MPA) or progesterone (P4) on the E2-induced neurite outgrowth was also examine...
We previously identified serine protease HtrA1 as a down-regulated gene in epithelial ovarian cancer (EOC) that modulates cisplatin-induced cytotoxicity. However, the mechanism by which HtrA1 sensitizes cells to cisplatin-induced cytotoxicity remained unknown. We have shown previously that the pan-cyclin dependent kinase inhibitor flavopiridol (FP)...
Human Sulfatase1 enzyme (HSulf-1) is down-regulated in a majority of ovarian cancer cell lines and primary tumors, but the functional consequence of this downregulation remains unclear. Here, we showed that down-regulation of HSulf-1 by RNA interference in OV202 ovarian cancer cells resulted in an elevated level of phosphorylated AKT. Conversely, o...
We investigated the effects of dienogest (DNG), which has a profile similar to that of natural progesterone (P4), on the favorable effects of estrogen in endothelial function.
(1) Human umbilical vein endothelial cells were treated with medroxyprogesterone acetate (MPA), DNG, or P4 with or without estradiol (E2), and then we examined nitric oxide (...
To investigate the phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal regulated protein kinase (ERK) activation by chemotherapy, and the relationship between the activation of them and patient outcomes. The effect of chemotherapy on the cell proliferation and apoptosis markers and their role in the biology of ovarian cancer were also...
We examined the molecular mechanisms of the antiestrogenic effects of clomiphene citrate (CC) in the endometrium using two types of cell lines, Ishikawa and EM-E6/E7/hTERT cells. CC or ICI182780 inhibited 17beta-estradiol (E2)-induced endometrial cell proliferation and transcriptional activation of the estrogen response element (ERE) gene. We direc...
Hypoxic response of endothelial cells (EC) is an important component of tumor angiogenesis. Especially, hypoxia-inducible factor-1 (HIF-1)-dependent EC-specific mechanism is an essential component of tumor angiogenesis. Recently, the Rho/Rho-associated kinase (ROCK) signaling has been shown to play a key role in HIF-1alpha induction in renal cell c...
Diverse estrogen actions are controlled via estrogen receptors (ERs). Mechanisms of action of ERs are modulated by various factors such as ER subtypes, conformation of the ER-ligand complex, and recruitment of coregulator complexes to a target gene promoter. Estrogen exerts divergent actions on vascular cells; namely it increases endothelial cell a...
To examine the effect of raloxifene on the endothelial dysfunction caused by surgical menopause.
Ten premenopausal women who underwent gynecological surgery with ovariectomy were divided into two groups. Five participants used raloxifene (60 mg/d) for 7 days staring 1 week after the surgery, and the other five participants did not use raloxifene. W...
Small cell carcinoma of the ovary is a rare type of ovarian carcinoma with a very poor prognosis.
We report here a case of a 55-year-old woman with small cell carcinoma of the left ovary. The patient underwent cytoreductive surgery with residual tumors of 6 cm at the cul-de-sac and was found to have stage IIIc disease. After six courses of irinotec...
Vascular endothelial growth factor (VEGF)-induced endothelial cell migration is an important component of tumor angiogenesis. Rho and Rho-associated kinase (ROCK) are key regulators of focal adhesion, stress fiber formation, and thus cell motility. Inhibitors of this pathway have been shown to inhibit endothelial cell motility and angiogenesis. In...
Torsion of a nongravid uterus is extremely rare. Most cases of uterine torsion occur during pregnancy. Here we report a case of nongravid uterus torsion with a large adnexal mass. A 73-year-old woman presented at the emergency room with acute abdominal pain. A preoperative diagnosis of torsion of an ovarian cyst was made and laparotomy was performe...
Vascular endothelial senescence is involved in human atherosclerosis. Telomerase activity is known to be critical in cellular senescence and its level is modulated by regulation of telomerase catalytic subunit (telomerase reverse transcriptase (TERT)) at both the transcriptional and post-transcriptional levels. Since the cardioprotective effect of...
The phosphatidylinositol 3-kinase (PI3K)/Akt cascade has an important role in the resistance of ovarian cancer cells to cisplatin in vitro; however, there have been no reports about whether blocking the PI3K/Akt cascade enhances the sensitivity to cisplatin in vivo. We investigated whether inhibition of PI3K increased the efficacy of cisplatin in a...
The mechanism of medroxyprogesterone acetate (MPA)-induced cell proliferation in human breast cancer cells remains elusive. We examined the mechanism by which MPA affects the cyclin D1 expression in progesterone receptor (PR)-positive T47D human breast cancer cells. MPA (10 nM) treatment for 48 h induced proliferation of the cells (1.6-fold inducti...
Since ovarian borderline tumor with invasive implant behaves as carcinoma, it should be managed like carcinoma. Since its characteristic features have not been reported, its preoperative diagnosis was thought to be impossible. We evaluated the features of MRI and macroscopic appearance in two cases of ovarian borderline tumor with invasive implant....
In the present study, to examine the dynamic changes in the localization of nuclear estrogen receptor (ER)alpha induced by growth factors, we used time-lapse confocal microscopy to directly visualized ERalpha fused with green fluorescent protein (GFP-ERalpha) in single living cells treated with epidermal growth factor (EGF) or IGF-I. We observed th...
Although estrogen is known to protect against β-amyloid (Aβ)-induced neurotoxicity, the mechanisms responsible for this effect are only beginning to be elucidated. In addition, the effect of raloxifene on Aβ-induced neurotoxicity remains unknown. Here we investigated whether raloxifene exhibits similar neuro-protective effects to estrogen against A...
We investigated whether inhibition of nuclear factor-kappaB (NFkappaB) increases the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Treatment of paclitaxel-sensitive Caov-3 cells with paclitaxel transiently activated the phosphorylation of Akt, the phosphorylation of IkappaB kinase (IKK), and the phosphorylation of inhibitor...
Whether or not inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models was investigated. We compared the basal levels of phosphorylation of IkappaBalpha and activity of NFkappaB between cisplatin-sensitive A2780 cells and cisplatin-resistant Caov-3 cells. The basal levels of phosphorylation of Ikappa...
The mechanism by which raloxifene acts in the chemoprevention of breast cancer remains unclear. Because telomerase activity is involved in estrogen-induced carcinogenesis, we examined the effect of raloxifene on estrogen-induced up-regulation of telomerase activity in MCF-7 human breast cancer cell line. Raloxifene inhibited the induction of cell g...
Citations
... This improvement in the response rate to bevacizumab combined with standard chemotherapy had already been reported in ICON7 (8). Regarding platinum-resistant recurrence, which has limited treatment options and thus a worse prognosis; a previous study reported that the rate of platinum-resistant recurrence in patients treated with Bev was 18.4% compared to 38.6% in patients treated with chemotherapy only (27). The results of this study (the rate of platinum-resistant recurrence in patients treated with Bev was 15.2% compared to 44.3% in patients treated with chemotherapy only) are comparable to those of the previous study. ...
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... The most widely used regimen for NECC is platinum combined with etoposide (Sundstrøm et al. 2002). The study of Seino et al. demonstrated that in patients with stage IB2 and T1N1M0 NECC, those who received surgery followed by chemotherapy had superior OS compared with those who received surgery followed by radiotherapy (Seino et al. 2023). Ishikawa's study also showed that adjuvant chemotherapy after surgery could reduce the risk of recurrence in patients with stage I-II NECC (Ishikawa et al. 2018). ...
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... In a cross-sectional study conducted in Japan, early menopause was associated with coronary heart disease, but there was no relationship between the age of menopause and the prevalence of stroke, hypertension, and diabetes. 18 A meta-analysis study found that early menopause increases the risk of developing diabetes compared to women who go through menopause after age 45. 19 In the study of Izumi et al., 15 younger age at menopause and longer postmenopausal period were associated with increased blood pressure. ...
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... In the present study, cystine was significantly increased and His, Trp, Cit, Orn, and serotonin were significantly decreased in the plasma of patients with EMC compared to healthy controls. Cystine is a source of cysteine, which is transported into cells via the xCT antiporter and is involved in the synthesis of the antioxidant glutathione [47]. Sendo et al. reported a reduced expression of the cysteine transporter xCT, in an endometrial cancer cell line [47]. ...
... The number of patients with endometrial cancer (EC) has been steadily increasing throughout Japan. Additionally, the number of adolescence and young adults with EC who desire fertility-sparing treatment has also increased [1]. ...
... In patients with invasive cervical cancer, only laparoscopic approach has been covered by the National Health Insurance in Japan. Moreover, in Japan, the oncologic safety of MIS in the treatment of cervical cancer has been evaluated only in several retrospective studies [18][19][20][21][22]. Therefore, the oncological safety of MISs over open surgery in Japanese women with early-stage cervical cancer remains unclear. ...
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... Endometrial cancer is one of the most common malignancies of the female genital tract in Japan and other developed countries (Sung et al. 2021;Cancer Information Service 2023). Its incidence rate in Japan is increasing annually, reaching more than 17,000 cases in 2019 (Shigeta et al. 2017;Nagase et al. 2021;Nagase et al. 2022;Yoshino et al. 2022;Cancer Information Service 2023). ...
... In one case, a patient with SCC and TPS of 40 % progressed with first line carboplatin, paclitaxel and pembrolizumab treatment (Martel et al., 2023). In the other, a patient with a tumor PD-L1 expression of 50-60 % showed response to pembrolizumab as a monotherapy after progressing on carboplatin, paclitaxel, and bevacizumab (Wu et al., 2021), although that regimen has been described as effective in other cases (Fukase et al., 2020) (Tamura et al., 2023), with one of those reports also describing the use of olaparib together with bevacizumab maintenance therapy for a patient with an HRD positive tumor (Tamura et al., 2023). ...
... Many chemotherapy drugs have been found to induce ferroptosis. Studies have reported that Sulfasalazine-induced ferroptosis is mediated by the inhibition of system xc-function [43]. Sorafenib inhibited the import of cystine mediated by system xc-, resulting in the accumulation of lipid ROS and induction of ferroptosis [44]. ...
... When infections or immune-mediated diseases are ruled out, imaging modalities like CT scan, magnetic resonance imaging and positron emission tomography play a major role in attaining a successful diagnosis and should be performed as early as possible when aortitis is suspected. Although the precise mechanism of G-CSF-induced aortitis remains uncertain, it has been demonstrated that CSF-producing cell lines co-produce and activate pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-23, with subsequent pathological activation of Th17 cells, antigenspecific CD4+ T cells and neutrophils, which may be involved in the development of vasculitis 8,9 . ...
