1.Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target
Iwao SAIKI ; Miki YARA ; Tsuyoshi YAMANAKA ; Hiroyuki UCHINO ; Masato INAZU
Biomolecules & Therapeutics 2020;28(2):195-201
Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [3H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.
2.Cerebrovascular Accident (Stroke) in Honjo-Yuri District of Akita Prefecture, Japan ---the Past and Present---
Kenji KIKUCHI ; Yoshitaka SUDA ; Hitoshi SHIOYA ; Kenjiro SHINDO ; Kenichi ASAKURA ; Tamio NISHINARI ; Jun KUROKI ; Hiroyuki GOTO ; Yasuo YAMANAKA ; Shigeki NISHIMURA ; Tohru NAKANISHI ; Satoshi MURAI
Journal of the Japanese Association of Rural Medicine 2005;54(1):37-49
A clinico-epidemiological analysis was performed of 2,414 consecutive stroke patients who were treated in our hospital during the 6-year period from 1997 through 2003. All the patients were neurologically examined and diagnostic studies were made by use of computed tomography. Cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage accounted for 68%, 22%, and 10% of the stroke cases, respectively. The incidence of these subtypes of stroke in this region during the past 20 years was characterized by a singnificant decrease in cerebral hemorrhage, and an increased proportion of cerebral infarction. Men exceeded women in the incidences of both cerebral infarction and hemorrhage, whereas characteristically women far exceeded men in subarachnoid hemorrhage. The incidence reached a peak in the 70-79 age group regardless of the subtypes of stroke, and 64% of the entire stroke patients were those 70 and older. Women were found to suffer from stroke at much older age than men. As to the site of hemorrhage, putaminal hemorrhage was the most frequent, experienced by 36% of the patients, followed by thalamic hemorrhage in 34% of the patients. Putaminal and pontine hemorrhages predominated in the age groups younger than 60;thalamic, cerebellar and subcortical hemorrhages were predominant in the age groups older than 70. The incidence of these subtypes of hemorrhage during the past 20 years was characterized by a dramatic decrease in putaminal hemorrhage in a younger population, and a significant increase in thalamic, cerebellar, and subcortical hemorrhages in an older population.
Cerebrovascular accident
;
Hemorrhage
;
seconds
;
Age Group Unspecified
;
incidence of cases
3.Molecular and Functional Characterization of Choline Transporter-Like Proteins in Esophageal Cancer Cells and Potential Therapeutic Targets.
Fumiaki NAGASHIMA ; Ryohta NISHIYAMA ; Beniko IWAO ; Yuiko KAWAI ; Chikanao ISHII ; Tsuyoshi YAMANAKA ; Hiroyuki UCHINO ; Masato INAZU
Biomolecules & Therapeutics 2018;26(4):399-408
In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [3H]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both Na+-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.
Cell Death
;
Cell Line
;
Cell Membrane
;
Cell Survival
;
Choline Deficiency
;
Choline*
;
DNA Methylation
;
Esophageal Neoplasms*
;
Humans
;
Mitochondria
;
RNA, Messenger
;
S-Adenosylmethionine
4.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
5.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
6.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
7.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
8.Lenvatinib and pembrolizumab versus platinum doublet chemotherapy as second-line therapy for advanced or recurrent endometrial cancer
Yutaka YONEOKA ; Tsukuru AMANO ; Akimasa TAKAHASHI ; Hiroki NISHIMURA ; Mari DEGUCHI ; Hiroyuki YAMANAKA ; Yuji TANAKA ; Shunichiro TSUJI ; Takashi MURAKAMI
Obstetrics & Gynecology Science 2024;67(6):534-540
Objective:
There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM.
Methods:
We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023.
Results:
During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%-40.7%) and 70.0% (95% CI, 55.5%-84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates.
Conclusion
Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.
9.Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II or III colorectal cancer
Koji NUMATA ; Yukari ONO ; Mihwa JU ; Shizune ONUMA ; Ayano TANAKA ; Taichi KAWABE ; Sho SAWAZAKI ; Akio HIGUCHI ; Kazuki YAMANAKA ; Shinsuke HATORI ; Hiroyuki SAEKI ; Hiroshi MATSUKAWA ; Yasushi RINO ; Kazuyuki TANI
Annals of Coloproctology 2024;40(2):161-168
Purpose:
This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection.
Methods:
We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II or III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined.
Results:
The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and pT factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001).
Conclusion
Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.
10.Twenty years of otsu medical stucents association since 1969.
Michiya Ohtaka ; Tsuyoshi Ikai ; Shinji Fushiki ; Kiyoaki Kitamura ; Yasuyuki Tatsugami ; Junichiro Morikawa ; Yoshio Nakamura ; Takeshi Aoyama ; Tetsuya Yoshikawa ; Akira Matsuda ; Yoshifumi Yokota ; Takuzo Nambu ; Takeshi Moridera ; Nobuki Yamaoka ; Hiroyuki Naito ; Fumikazu Ikeda ; Hiroyuki Furukawa ; Hiroshi Yakushigawa ; Hiroshi Fujimoto ; Kishiko Hayashi ; Tsuyoshi Ohtaka ; Noboru Takano ; Yoshie Ibuki ; Tsutomu Yamanaka ; Akira Matsuda
Medical Education 1991;22(2):115-120