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1.
Hum Cell ; 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573494

ABSTRACT

A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient's tumour tissue. Notably, MTC-22 cells, and the patient's carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient's tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.

2.
Healthcare (Basel) ; 12(5)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38470710

ABSTRACT

Cervical cancer incidence is increasing among Japanese women, which is partly attributed to low screening rates. This study examined the implementation of opt-in human papillomavirus (HPV) self-sampling among Japanese women aged 30-39 years who had not undergone cervical cancer screening, focusing on those requiring preconception care. The responses to the opt-in approach and effectiveness in detecting cervical squamous intraepithelial neoplasia 2 or worse (CIN2+) were evaluated. Participants used the Evalyn® Brush for self-sampling, with HPV testing conducted using the Cobas 4800 system (version 2.2.0). Out of 3489 eligible, unscreened women from four municipalities in Fukui Prefecture, only 10.6% (370/3489) requested the self-sampling kit. Of these, 77.3% (286/370) returned the kit (HPV testing rate: 8.2% (286/3489)). The HPV positivity rate was 13.7% (39/285), yet only 61.5% (24/39) of those with positive HPV results proceeded to cytology testing. Subsequently, three cases of CIN2+ were detected (10.5/1000). While this study demonstrated a reasonable kit return rate and indicated the capability of opt-in HPV self-sampling to detect CIN2+ cases in unscreened women, the low ordering rate of kits and suboptimal compliance for follow-up cytology testing highlight significant challenges. The findings suggest the need for more effective strategies to enhance participation in cervical cancer screening programs.

3.
BMC Surg ; 24(1): 23, 2024 Jan 13.
Article in English | MEDLINE | ID: mdl-38218800

ABSTRACT

BACKGROUND: Placenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the "Holding-up uterus" surgical technique with a shock index (S.I.) > 1.5. METHODS: Twelve patients who underwent PAS cesarean hysterectomy were included in the study. RESULTS: Group I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5. CONCLUSIONS: The study found that the "Holding-up uterus" technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.


Subject(s)
Balloon Occlusion , Placenta Accreta , Pregnancy , Female , Humans , Placenta Accreta/surgery , Placenta Accreta/etiology , Blood Loss, Surgical , Balloon Occlusion/methods , Iliac Artery , Uterus/surgery , Hysterectomy/methods , Retrospective Studies
4.
Cancer Sci ; 114(10): 4081-4088, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37605505

ABSTRACT

The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.


Subject(s)
COVID-19 , Neoplasms , Humans , Pandemics , Early Detection of Cancer , Japan/epidemiology , COVID-19/epidemiology , Surveys and Questionnaires , Neoplasms/diagnosis , Neoplasms/epidemiology
5.
Cytopathology ; 33(3): 362-373, 2022 05.
Article in English | MEDLINE | ID: mdl-34689374

ABSTRACT

INTRODUCTION: The objective of this study was to assess the diagnostic utility of CD10 in the differential diagnosis of grade 1-endometrial endometrioid carcinoma (G1-EEC) and the metaplastic changes associated with the endometrial glandular and stromal breakdown (EGBD) on liquid-based cytological (LBC) samples. METHODS: (1) The type and distribution of CD10-positive cells in EGBD and G1-EEC patients were evaluated. (2) Based on the results from (1), histological and cytological specimens were double-immunostained with CD31 and CD10 to confirm whether CD10-positive tubular-canalicular material found in (1) was represented by fine threads of endometrial-type fibrovascular stroma. (3) Based on the results from (2), additional immunostaining of histological specimens was performed for CD146 and αSMA as markers of perivascular cells. RESULTS: (1) CD10 positive cells showed two main patterns of expression: cytoplasmic immunoreactivity in the form of dense brown granules in EGBD and tubular-canalicular branching patterns in G1-EEC. (2) The tubular-canalicular material observed in cytological specimens of G1-EEC samples co-expressed CD10 and CD31, and was interpreted as representing fine threads of endometrial fibrovascular stroma in the corresponding histological samples. Conversely, metaplastic changes in EGBD cases, only a few CD31-positive signals were found inside the condensed stromal clusters with CD10-positive. (3) Cells surrounding the CD31-positive vascular endothelial cells expressed CD146 and αSMA; moreover, some of the thin CD10-positive fibrous stromal strands also co-expressed αSMA. CONCLUSIONS: CD10 is a very useful immunomarker for distinguishing between G1-EEC and the metaplastic changes of EGBD in LBC samples.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , CD146 Antigen/metabolism , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Endometrium/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Humans , Neprilysin/metabolism , Platelet Endothelial Cell Adhesion Molecule-1
6.
BMC Cancer ; 20(1): 1056, 2020 Nov 03.
Article in English | MEDLINE | ID: mdl-33143690

ABSTRACT

BACKGROUND: In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate the efficacy of the quadrivalent HPV6/11/16/18 vaccine for persistent HPV16/18 infection in Japanese women aged 27-45 years. METHODS: This is an interventional, nonrandomized, non-double-blind prospective cohort study designed to compare the rates of persistent HPV16/18 infection between the vaccinated arm and unvaccinated arm. The subjects will consist of all women aged 27-45 years who have normal cytology results confirmed by cervical cancer screening from May 2019 to March 2021. The follow-up time is two years. The subjects will be divided into two groups: the vaccinated group and the unvaccinated group. The study will need to enroll 600 vaccinated participants (experimental arm) and 2200 unvaccinated participants (control arm). DISCUSSION: The findings of this trial (HAKUOH study) might provide the first local evidence on the subject and be significantly useful not only to medical academia but also to the Japanese Ministry of Health, Labour and Welfare. The findings could contribute to public health improvement by providing local supportive knowledge on the prevention of HPV infection through HPV vaccination in young adult women in Japan, where active recommendations have been suspended for a long time due to adverse effects. TRIAL REGISTRATION: Trial registration number: NCT04022148 . Registration began on December 1, 2019.


Subject(s)
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage , Human papillomavirus 16/isolation & purification , Human papillomavirus 18/isolation & purification , Papillomavirus Infections/diagnosis , Adult , Early Diagnosis , Female , Follow-Up Studies , Healthy Volunteers , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/pharmacology , Human papillomavirus 16/drug effects , Human papillomavirus 18/drug effects , Humans , Japan , Papillomavirus Infections/prevention & control , Prospective Studies , Research Design
7.
Int J Clin Oncol ; 25(10): 1854-1860, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32583223

ABSTRACT

BACKGROUND: To adopt HPV self-sampling in Japan, we assessed the concordance between self- and physician-collected human papillomavirus (HPV) samples from Japanese patients and examined the performance of HPV self-sampling for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Patients who had previously tested negative for intraepithelial lesions or malignancy/HPV-positive, and patients with atypical squamous cells of undetermined significance or worse (ASCUS+) cytology were eligible for this cross-sectional study. Participants performed HPV self-sampling using an Evalyn brush, which was submitted at the Fukui Prefectural Health Care Association. The Evalyn brush heads were stored in ThinPrep vials. The physician, however, performed HPV and cell sampling using an endocervical brush and immediately stored the brush heads in ThinPrep vials. All participants underwent colposcopy and biopsy. Histopathological diagnoses were made by pathologists at Fukui University Hospital. HPV infection was confirmed using a PCR-based Cobas 4800 HPV DNA test. Cytological analysis was performed at Fukui Prefectural Health Care Association. RESULTS: HPV-positive rates for physician-collected samples and self-collected samples were 51 and 50%, respectively. The perfect match rate of HPV type between the groups was 88% (κ = 0.76). HPV16/18 showed higher agreement rates than other HPVs (99%, kappa 0.96 and 89% kappa 0.77, respectively). Both groups showed 100% sensitivity to CIN2+, but specificity was 57.0 and 58.1%, respectively. CONCLUSION: For HPV typing, a good concordance rate was seen between self- and physician-collected samples. Self-sampling showed high sensitivity for CIN2+. Self-sampling using the Evalyn brush and Cobas 4800 may be feasible for screening Japanese individuals.


Subject(s)
Papillomaviridae/genetics , Papillomavirus Infections/virology , Self Care/instrumentation , Specimen Handling/instrumentation , Specimen Handling/methods , Adult , Asian People , Atypical Squamous Cells of the Cervix/pathology , Atypical Squamous Cells of the Cervix/virology , Colposcopy , Cross-Sectional Studies , Female , Human Papillomavirus DNA Tests , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Middle Aged , Papillomavirus Infections/pathology , Physicians , Polymerase Chain Reaction , Self Care/methods , Sensitivity and Specificity
8.
Diagn Cytopathol ; 46(4): 314-319, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29460481

ABSTRACT

OBJECTIVE: The introduction and establishment of a new classification system for endometrial cytology, the "New Terminology in Endometrial Cytology (NTEMC) system," which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies. METHODS: Fifty-nine cases were diagnosed as "suspicious positive" according to the three-tier reporting (TTR) system, which was adopted in Japan. The specimens were re-evaluated according to the NTEMC system. Thirty-seven of the 59 patients underwent endometrial biopsy. We correlated the pathological diagnosis with the NTEMC system category. RESULTS: The 59 cases were classified according to the NTEMC system as follows: 36 cases were classified as ATEC of undetermined significance (ATEC-US), 21 cases were classified as ATEC for which atypical endometrial hyperplasia or worse cannot be excluded (ATEC-A), and 2 cases were classified as endometrial hyperplasia. The ratio of atypical endometrial hyperplasia or malignancy in ATEC-US category was significantly lower than that in ATEC-A category. Fifteen cases in ATEC-US category did not show atypical endometrial hyperplasia lesions or malignancy after 3 months. CONCLUSIONS: These data suggest that patients with ATEC-US results can be followed up for at least three months, and the introduction of the NTEMC system decreased the number of unnecessary endometrial biopsies.


Subject(s)
Carcinoma/classification , Endometrial Neoplasms/classification , Medical Records/standards , Terminology as Topic , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged
9.
Int J Surg ; 48: 215-219, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29146268

ABSTRACT

INTRODUCTION: The aim of this study was to determine whether a preoperative health status index and intraoperative data could predict perioperative morbidity and mortality in women over the age of 65 years undergoing surgery for gynecologic disorders. METHODS: The medical records of 68 female patients who were ≥65 years of age and who underwent surgery under general anesthesia in our institute from January 2014 to December 2015 were retrospectively reviewed. Preoperative data were extracted from a database and included comorbidities, American Society of Anesthesiologists physiological status classification, the Charlson Comorbidity Index, the Subjective Global Assessment 2011 revision, the subjects' risk of falling, body mass index, and age. The intraoperative factors investigated included the type of surgery and the Surgical Apgar Score (SAS). Major postoperative complications were defined as > Grade 3 based on the Clavien-Dindo classification version 2.0. RESULTS: Of the 68 elderly gynecological patients, 6 (8.8%) developed serious Grade 3 or worse complications within 30 days of surgery. The only factor that significantly affected postoperative complications was the SAS, an index of the patient's intraoperative condition. The optimum cut-off SAS for the occurrence of complications was determined by the receiver operating characteristic curve to be ≤ 6 points; a score ≤6 points predicted the development of postoperative complications with 66.7% sensitivity and 79.0% specificity. CONCLUSION: In this study, the SAS predicted the development of serious complications in elderly gynecological patients within 30 days of surgery more accurately than did other comorbidities, preoperative assessments, and type of surgery.


Subject(s)
Decision Support Techniques , Gynecologic Surgical Procedures , Health Status Indicators , Postoperative Complications , Aged , Female , Humans , Retrospective Studies
10.
Oncotarget ; 8(14): 22581-22589, 2017 Apr 04.
Article in English | MEDLINE | ID: mdl-28186981

ABSTRACT

We investigated whether 16α-[18F]-fluoro-17ß-estradiol (18F-FES) and 18F-fluoro-deoxyglucose (FDG) uptake measured using positron emission tomography (PET) predicted prognosis in 18 patients with different histological subtypes of uterine sarcoma. Standardized uptake values (SUVs) and 18F-FDG/18F-FES SUV ratios were determined, and their correlations with progression-free (PFS) and overall survival (OS) were examined. Ten patients died from local recurrence or metastasis, and one more experienced recurrence, during the at least 36-month follow-up period. Patients with higher 18F-FDG SUVs (> 5.5) had worse OS (p = 0.007) and tended toward worse PFS (p = 0.11), while patients with lower 18F-FES SUVs (≤ 1.5) had worse PFS (p = 0.03) and tended toward worse OS (p = 0.19). Patients with 18F-FDG/18F-FES ratios > 2.6 had worse PFS (p = 0.009) and OS (p = 0.005). The 5-year PFS and OS rates were 75% and 88% for patients with lower ratios, but were only 10% and 20% for those with higher ratios. These results suggest that pretreatment tumor 18F-FDG/18F-FES ratio is useful for predicting the prognosis of uterine sarcoma patients.


Subject(s)
Estradiol/analogs & derivatives , Fluorodeoxyglucose F18/metabolism , Neoplasm Recurrence, Local/diagnostic imaging , Positron-Emission Tomography/methods , Sarcoma/diagnostic imaging , Uterine Neoplasms/diagnostic imaging , Estradiol/metabolism , Female , Humans , Image Processing, Computer-Assisted , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Radiopharmaceuticals/metabolism , Sarcoma/metabolism , Sarcoma/pathology , Survival Rate , Uterine Neoplasms/metabolism , Uterine Neoplasms/pathology
11.
Medicine (Baltimore) ; 95(9): e3017, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26945427

ABSTRACT

This study aimed to investigate whether the predictive values of intensity- and volume-based PET parameters are different between histological subtypes in patients with cervical cancer. Ninety patients, 65 with squamous cell carcinoma (SCC) and 25 with non-SCC (NSCC), who underwent pretreatment ¹8F-FDG PET/CT and pelvic MRI, were studied retrospectively. In addition to SUVmax and SUVmean, metabolic-tumor-volume (MTV) was determined by thresholding of 40% SUVmax and total-lesion-glycolysis (TLG) was calculated. Clinical factors and PET metabolic indices were compared between SCC and NSCC. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method with cut-offs determined by ROC analyses to stratify SCC and NSCC patients separately. Factors associated with survival were assessed with univariate and multivariate analyses using the Cox regression model. No significant differences were observed in clinical factors other than tumor size or ¹8F-FDG PET metabolic indices between SCC and NSCC. The Kaplan-Meier estimates of 2-year PFS and OS rates were 60% and 70% for SCC and 40% and 76% for NSCC, respectively. Multivariate analyses showed that MTV and TLG were the independent prognostic factors for PFS and OS in SCC; in contrast, SUVmax was the independent prognostic factor for PFS and OS in NSCC. Metabolic burden (MTV and TLG) could be beneficial for the prognostic prediction of cervical SCC patients; in contrast, metabolic intensity (SUVmax) could be beneficial for the prognostic prediction of NSCC patients. The different prognostic implications might be based on the differences of tissue integrity and histological heterogeneity between SCC and NSCC.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Fluorodeoxyglucose F18 , Multimodal Imaging , Positron-Emission Tomography , Radiopharmaceuticals , Tomography, X-Ray Computed , Uterine Cervical Neoplasms/diagnosis , Adult , Aged , Carcinoma, Squamous Cell/mortality , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Prognosis , ROC Curve , Retrospective Studies , Survival Analysis , Uterine Cervical Neoplasms/mortality
12.
Cancer Sci ; 105(10): 1307-12, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25154549

ABSTRACT

Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated-ERα at Ser(167) (p-Ser(167) -ERα). However, the expression of p-Ser(167) -ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p-Ser(167) -ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p-Ser(167) -ERα and for p-mTOR/p-S6K1 and p-MAPK/p-RSK. The correlation of p-Ser(167) -ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p-Ser(167) -ERα had significantly shorter relapse-free survival, and although the result was not significant, levels of nuclear p-Ser(167) -ERα tended to be higher in advanced-stage ECC patients. Nuclear p-Ser(167) -ERα was significantly positively correlated with p-MAPK and p-S6K1, and with significantly shorter relapse-free survival in EEC.


Subject(s)
Carcinoma, Endometrioid/metabolism , Endometrial Neoplasms/metabolism , Estrogen Receptor alpha/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/mortality , Endometrial Neoplasms/mortality , Female , Humans , Middle Aged , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism
13.
Oncol Lett ; 8(2): 637-641, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25009648

ABSTRACT

Advanced uterine leiomyosarcoma (LMS) is a rare and extremely aggressive disease. In patients with advanced and unresected uterine LMS, multidisciplinary therapy is the best treatment option, although no consensus exists on the efficacy of the treatment. The present study describes the case of a 41-year-old female who underwent laparotomy due to a large uterine tumor. Exploratory laparotomy revealed a large tumor that had extended from the pelvic wall to the outside of the pelvis and then invaded the colon. Large residual tumors remained present in the pelvis following suboptimal debulking surgery. Subsequent to surgery, the patient was treated with adjuvant radiotherapy, followed by chemotherapy with regional whole pelvis hyperthermia (HT). Computed tomography revealed stable disease prior and subsequent to combination treatment. While treatment was being administered for third/fourth-degree burns and subcutaneous fatty necrosis, the patient developed multi-organ failure and succumbed. The present case report describes the potential for using a combination of chemotherapy, HT and radiotherapy in patients with LMS. The development of an effective protocol is required for the administration of chemotherapy, HT and radiotherapy in patients with advanced unresected LMS.

14.
Int J Oncol ; 39(6): 1359-64, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21935568

ABSTRACT

Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Apoptosis/drug effects , Cisplatin/pharmacology , Oligopeptides/pharmacology , Ovarian Neoplasms/metabolism , Peptides/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolism , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/genetics , Cell Proliferation/drug effects , Down-Regulation/drug effects , Drug Synergism , Endothelial Cells/drug effects , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , NIH 3T3 Cells , Ovarian Neoplasms/genetics , Signal Transduction/drug effects
16.
Ann Pharmacother ; 45(10): e55, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21881031

ABSTRACT

OBJECTIVE: To report 2 cases of a probable interaction between cisplatin and warfarin. CASE SUMMARY: Two cases of transient elevation of international normalized ratio (INR) during irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 8, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3-5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles. DISCUSSION: Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin. CONCLUSIONS: Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.


Subject(s)
Anticoagulants/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/adverse effects , Warfarin/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Drug Interactions , Drug Monitoring , Female , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/drug therapy , Humans , International Normalized Ratio , Irinotecan , Middle Aged , Thromboembolism/prevention & control , Treatment Outcome , Venous Thrombosis/complications , Venous Thrombosis/drug therapy , Warfarin/administration & dosage , Warfarin/therapeutic use
17.
Eur J Cancer ; 46(18): 3445-52, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20926288

ABSTRACT

Correlations between mammalian target of rapamycin (mTOR) expression, and clinicopathological features, outcome and Akt expression in endometrial endometrioid adenocarcinoma (EEC) were investigated. Tumour samples were obtained from 82 patients with EEC who had undergone hysterectomy, and phosphorylated mTOR (p-mTOR) and Akt (p-Akt) expression in the cytoplasm and nucleus was analysed by immunohistochemical staining. Nuclear p-mTOR was significantly elevated in poorly differentiated tumours and positively correlated with lymph node involvement (P = 0.05). Nuclear p-mTOR expression was associated with significantly shorter relapse-free survival (RFS) (P<0.01) and slightly shorter overall survival (OS) (P = 0.08). Cytoplasmic expression of p-mTOR was not correlated with any clinicopathological factors. Although not significant, cytoplasmic p-mTOR expression was associated with shorter PFS and OS (P = 0.09, P = 0.283, respectively). Neither cytoplasmic nor nuclear p-Akt expression was associated with clinicopathological factors or with survival. Localisation of p-mTOR may be critical for tumour progression and outcomes in patients with EEC.


Subject(s)
Endometrial Neoplasms/metabolism , Neoplasm Proteins/metabolism , TOR Serine-Threonine Kinases/metabolism , Uterine Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Disease Progression , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Phosphorylation , Prognosis , Uterine Neoplasms/mortality , Uterine Neoplasms/pathology
18.
J Nucl Med ; 49(5): 708-12, 2008 May.
Article in English | MEDLINE | ID: mdl-18413400

ABSTRACT

UNLABELLED: The purpose of this study was to prospectively determine whether combined MRI and (18)F-FDG PET is more accurate than MRI in assessing nonbenign uterine smooth muscle tumors (USMTs). METHODS: Seventy patients (mean age, 49+/-10 y; range, 28-77 y) suspected of having nonbenign USMTs underwent both MRI and (18)F-FDG PET before surgery. Results were evaluated using receiver-operating-characteristic (ROC) analyses and the Cochran Q test. RESULTS: The area under the ROC curve for MRI with (18)F-FDG PET was significantly higher than that for MRI (0.97 vs. 0.89, P<0.05). Although multiple comparisons using the Cochran Q test were not significant, the sensitivity, specificity, and accuracy for MRI with (18)F-FDG PET with probable nonbenign USMT cases considered to be positive were higher than those for MRI (93.3% vs. 73.3%; 92.7% vs. 85.5%; and 92.9% vs. 82.9%, respectively). CONCLUSION: MRI with (18)F-FDG PET is useful in assessing nonbenign USMTs, as compared with MRI.


Subject(s)
Fluorodeoxyglucose F18 , Magnetic Resonance Imaging/methods , Myometrium/pathology , Positron-Emission Tomography/methods , Smooth Muscle Tumor/diagnostic imaging , Adult , Aged , Female , Humans , Middle Aged , Myometrium/diagnostic imaging , Sensitivity and Specificity
19.
Eur J Obstet Gynecol Reprod Biol ; 135(1): 111-5, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17293021

ABSTRACT

OBJECTIVE: The non-pregnant uterus shows wave-like activity (uterine peristalsis). This pilot study was intended to determine: (1) whether uterine peristalsis during the menstrual cycle is detectable by cine magnetic resonance imaging (MRI); (2) the effects of leiomyoma on uterine peristalsis. STUDY DESIGN: Mid-sagittal MRI was performed sequentially with T2-weighted single-shot fast spin-echo (SSFSE) in 3 normal ovulatory volunteers and 19 premenopausal women with uterine leiomyoma. Direction and frequency of movement of the junctional zone were evaluated using a cine mode display. RESULTS: Junctional zone movement was identified in all subjects. Direction of uterine peristalsis in normal volunteers was fundus-to-cervix during menstruation, cervix-to-fundus during the periovulatory phase, and isthmical during the mid- and late-luteal phases. Abnormal peristaltic patterns were detected in three of five patients with uterine leiomyoma during menstruation and in the mid-luteal phase of the cycle, respectively. CONCLUSION: Cine MRI is a novel method for evaluation of uterine peristalsis. Results of this pilot study suggest that abnormal uterine peristalsis during menstruation and the mid-luteal phase might be one of the causes of hypermenorrhea and infertility associated with uterine leiomyoma.


Subject(s)
Leiomyoma/physiopathology , Peristalsis/physiology , Uterine Neoplasms/physiopathology , Uterus/physiopathology , Adult , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging, Cine , Menstrual Cycle/physiology , Pilot Projects
20.
Gynecol Oncol ; 104(3): 764-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17156828

ABSTRACT

BACKGROUND: The positron emission tomography (PET) with F18 17beta-estradiol (FES) has good imaging for assessment of estrogen receptor in breast cancer. CASE: We report on a 30-year-old woman who desired to preserve her fertility with well-differentiated endometrial adenocarcinoma. Before hormone treatment was started, FES-PET showed increased uptake of endometrium, magnetic resonance imaging (MRI) showed thickness and F-18 fluorodeoxyglucose (FDG)-PET showed increased uptake. FES-PET after 3 months showed remaining FES uptake, but there were no abnormal findings on MRI and FDG-PET. Hysteroscopy showed remaining adenocarcinoma. After additional treatment, FES-PET showed a therapeutic response, and hysteroscopy showed no abnormal finding. CONCLUSIONS: To our knowledge, this is the first report that FES-PET has the potential to provide more useful information than did FDG-PET about the hormone therapy.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/radiotherapy , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/radiotherapy , Estradiol/analogs & derivatives , Adult , Estradiol/therapeutic use , Female , Fluorine Radioisotopes/therapeutic use , Fluorodeoxyglucose F18/therapeutic use , Humans , Positron-Emission Tomography , Radiopharmaceuticals/therapeutic use
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