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2.
Prev Sci ; 25(1): 31-43, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37329411

ABSTRACT

Research suggests that encounters with racism are related to depression in Black youth. However, less is known about how experienced racial discrimination can influence other aspects of well-being among Black youth including their socio-emotional development and behavior. In addition, emerging literature highlights the critical ways anticipated racial discrimination may impact the emotional well-being of Black youth. To address these gaps, the current study assessed whether experienced discrimination was associated with higher levels of internalizing problems (anxiety/depression, suicidal thoughts) and lower levels of socio-emotional development (emotion regulation, prosocial behavior). We then tested whether expected discrimination contributed to similar patterns. Lastly, this study examined how age and gender moderated this relationship. Across eight schools in three communities, 1435 Black youth (56.57% female; 56.40% 10th grade) in 10th and 12th grades responded to the Youth Experience Survey. Using a series of hierarchical linear and hierarchical binary logistic regressions, results found that those who experienced racial discrimination and expected discrimination demonstrated higher internalizing problems and lower socio-emotional development; however, expected discrimination often accounted for more variance than experienced. These findings suggest the multifaceted influence both experienced and expected racial discrimination have on the well-being of Black youth and can provide important insights to community prevention systems.


Subject(s)
Black or African American , Motivation , Psychological Well-Being , Racism , Adolescent , Female , Humans , Male , Emotions , Racism/psychology , Black or African American/psychology
3.
JNCI Cancer Spectr ; 7(6)2023 10 31.
Article in English | MEDLINE | ID: mdl-38001029

ABSTRACT

BACKGROUND: Although many human papillomavirus (HPV)-targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. METHODS: In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16-positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. RESULTS: In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7-specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. CONCLUSION: This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16-positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. TRIAL REGISTRATION: jRCT2031190034.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Human papillomavirus 16 , Human Papillomavirus Viruses , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/adverse effects , Uterine Cervical Dysplasia/prevention & control , Uterine Cervical Neoplasms/drug therapy
4.
Jpn J Compr Rehabil Sci ; 14: 39-48, 2023.
Article in English | MEDLINE | ID: mdl-37859790

ABSTRACT

Sato M, Hyakuta T. Awareness and support for post-stroke fatigue among medical professionals in the recovery phase rehabilitation ward. Jpn J Compr Rehabil Sci 2023; 14: 39-48. Objective: To clarify the level of awareness of and support for post-stroke fatigue among medical professionals working in recovery phase rehabilitation wards. Methods: We conducted a questionnaire survey targeting all medical professionals (physicians, nurses, physical therapists, occupational therapists, and speech therapists) working in recovery phase rehabilitation wards of three facilities to evaluate their awareness of post-stroke fatigue and the support they were offering to address this. Quantitative data were subjected to statistical analysis and free description data were subjected to content analysis. Results: Of the 130 participants, we obtained responses from 94 (collection rate, 72.3%; valid response rate, 100%). Those who felt that post-stroke patients are always tired or tire easily comprised 63.8%. Those who acknowledged the importance of post-stroke fatigue as a problem and that it is an issue that must be addressed comprised 70.2% and 73.4%, respectively. Issues emerging due to post-stroke fatigue were extracted as follows: "Difficulty continuing with rehabilitation," "Decreased drive," "Difficulty with emotional control/depression," "Fewer interactions with others," and "Loss of goals." Support for post-stroke fatigue was offered by 57.4% of medical professionals, most commonly as individual support such as "Ensure rest." The effects of support were described as "Cannot say either way" (44.4%), with 3.7% noting that they were not very effective. Awareness and support rates among therapists were significantly higher than those among nurses. Conclusions: Post-stroke fatigue is acknowledged by medical professionals as a critical issue that negatively influences the patient's physical, emotional, and daily living functions. Unfortunately, effective support is not currently being offered, demonstrating the need for the development of appropriate interventions.

5.
BMC Womens Health ; 23(1): 169, 2023 04 11.
Article in English | MEDLINE | ID: mdl-37041633

ABSTRACT

BACKGROUND: The purpose of this study was to develop a cervical cancer education program for students and evaluate the process for female students of an HPE teacher education university who were training to become Japanese Health and Physical Education teachers. METHODS: This study used Action Research (AR) methodology. In developing program, we analyzed the description of the teaching material development process, the lectures, and the students' report contents, which was the main activity in the program development. Thirty five third- and fourth-year students majoring in health promotion at a Health and Physical Education teacher education university, which trains Health and Physical Education teachers in Tokyo, Japan, participated in this study. RESULTS: After a review of the prototype version of the cervical cancer education material, six out of nine reviewers determined that it can be published. In the revised cervical cancer education materials, messages from students, university lecturers, and gynecologists have been added as a column in the section on 'how to prevent cervical cancer. Analysis of the contents of the texts (16,792 characters in total) of 35 student reports resulted in the generation of 51 codes, 3 categories, and 15 subcategories. CONCLUSIONS: This study reflects the intentions of female university students to contribute their knowledge to the development of educational materials on cervical cancer, which, alongside the lectures, have deepened the knowledge and awareness of cervical cancer. Based on this, the teaching material development process, lectures by experts, and students' mindset after learning about cervical cancer is reported in this study. There is a need for more educational programs on cervical cancer that are implemented through the education of female university students.


Subject(s)
Teacher Training , Uterine Cervical Neoplasms , Female , Humans , Physical Education and Training , Students , Universities
6.
J Obstet Gynaecol Res ; 49(5): 1400-1411, 2023 May.
Article in English | MEDLINE | ID: mdl-36859635

ABSTRACT

AIM: To evaluate changes of treatment strength and its impact on prognosis in older patients with ovarian cancer. METHODS: We compared relative dose intensity (RDI) as a representative of treatment strength, prognosis, and other features between older (≥65 years) and younger patients (<65 years) retrospectively. Seventy-seven older patients of 301 who received dose-dense-paclitaxel-carboplatin (dTC) and 93 older patients of 304 who received conventional-paclitaxel-carboplatin (cTC) from the Japanese Gynecologic Oncology Group (JGOG) 3016 clinical trial were analyzed. RESULTS: The RDI of older patients was lower than that of younger patients in cTC (87.4% vs. 90.8%, p = 0.009) but not in dTC (79.0% vs. 81.2%, p = 0.205). In both regimens, older patients had worse overall survival than younger patients: hazard ratio [HR] = 1.80; 95% confidence interval [CI]: 1.25-2.59; p = 0.001 for dTC, and HR = 1.59; 95% CI: 1.15-2.19; p = 0.04 for cTC. However, the RDI was not determined as a prognostic factor statistically. The prognostic factors identified by multivariate analysis for both regimens were clinical stage and residual disease; for dTC were age, performance status, and serum albumin; and for cTC was white blood cell count. There was no difference in neutropenia observed between age groups in either regimen. CONCLUSIONS: The RDI of older patients varies according to the administered schedule and is not always lower than that of younger patients. Older patients with comparable treatment strength to younger patients in the dTC group did not accomplish the same level of prognosis as younger patients. Other biologic factors attributable to aging may affect prognosis.


Subject(s)
Ovarian Neoplasms , Humans , Female , Aged , Carboplatin , Prognosis , Retrospective Studies , Ovarian Neoplasms/drug therapy , Paclitaxel/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
7.
J Reprod Immunol ; 156: 103797, 2023 03.
Article in English | MEDLINE | ID: mdl-36645984

ABSTRACT

Bacterial vaginosis due to Gardnerella vaginalis (GV) is one of the main causes of preterm birth. Antimicrobial function of the cervical glands prevents ascending pathogen infection. This study investigated the effect of GV on the cervical gland cells. We examined the correlation between GV and neutrophil elastase in the cervical mucous obtained from pregnant women's clinical samples. Culture supernatants (sup) of GV and Lactobacillus crispatus (LC) were added to human immortalized cervical gland cells (EndoCx). Quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine the effects on the production of antimicrobial peptides (AMPs), secretory leukocyte peptidase inhibitor (SLPI), and Elafin. mRNA microarray analysis revealed the expression profile of GV-exposed EndoCx. Moreover, the antimicrobial activity of Elafin against LC and GV was investigated. In the clinical samples, neutrophil elastase was increased in the GV-positive cervical mucous. In an in vitro assay, RT-qPCR and ELISA showed that GV-sup enhanced the secretion of Elafin, but not SLPI, from EndoCx, whereas LC-sup did not. mRNA microarray assay and ELISA results demonstrated that GV-sup enhanced the proinflammatory pathway and interleukin (IL)- 8 secretion from EndoCx as well as cell adhesion and tight junction pathways. Moreover, GV-sup directly enhanced Elafin and IL-8 secretion from the cervical gland cells. In the GV-abundant vaginal flora, IL-8 level increased the neutrophil elastase activity and Elafin inhibited the elastase activity to protect from tissue damage and infection. Thus, the balance of IL-8-induced neutrophil and Elafin-induced antiprotease activities may be crucial in preterm labor.


Subject(s)
Elafin , Premature Birth , Infant, Newborn , Female , Pregnancy , Humans , Elafin/metabolism , Leukocyte Elastase , Gardnerella vaginalis , Interleukin-8 , Antimicrobial Peptides , Secretory Leukocyte Peptidase Inhibitor/genetics , Epithelium , RNA, Messenger/metabolism
8.
Am J Obstet Gynecol ; 228(2): 207.e1-207.e9, 2023 02.
Article in English | MEDLINE | ID: mdl-36150519

ABSTRACT

BACKGROUND: Gonadotropin-releasing hormone agonists are used to treat premenopausal uterine leiomyomas; however, leiomyoma volume reduction is not always achieved. The reduction rate after this treatment varies for each leiomyoma, even in the same patient. Therefore, an effective method for predicting uterine leiomyoma volume reduction is required to reduce the adverse hypoestrogenic effects and drug-related economic burden related to gonadotropin-releasing hormone agonists. OBJECTIVE: This study aimed to determine the predictive use of MED12 mutations for evaluating the effect of gonadotropin-releasing hormone agonist treatment concerning reducing uterine leiomyoma volume and to predict the MED12 mutation status based on the findings of magnetic resonance imaging performed before treatment. STUDY DESIGN: MED12 exon 2 mutation and erythropoietin expression in uterine leiomyomas were evaluated concerning volume reduction, as measured using magnetic resonance imaging. We developed a system for classifying leiomyomas according to T2-weighted magnetic resonance imaging signals to noninvasively predict the presence or absence of MED12 mutations in leiomyomas. Leiomyoma samples (>5 cm) were obtained from 168 patients during surgery (hysterectomy or myomectomy) between 2005 and 2021 at Yokohama City University Hospital. To analyze the rate of leiomyoma volume reduction, 41 patients had been preoperatively administered the gonadotropin-releasing hormone agonist (leuprorelin acetate 3.75 mg, monthly subcutaneous injection) for 3 months; magnetic resonance imaging was performed before and after treatment without contrast material. RESULTS: Patients with MED12 exon 2 mutations had smaller volume reduction after treatment with the gonadotropin-releasing hormone agonist (P<.001, Mann-Whitney U test) and displayed lower signal intensity on T2-weighted images than those with leiomyomas expressing wild-type MED12 exon 2. The newly proposed magnetic resonance imaging-based classification system showed that MED12 exon 2 mutations were more frequent in the low-signal group than in the high-signal group, with nearly equal proportions of mutated and wild-type MED12 exon 2 leiomyomas noted in the intermediate group. The low-signal group had significantly lower erythropoietin expression levels than the high-signal group (P<.001, Kruskal-Wallis test with the Dunn posthoc analysis). CONCLUSION: MED12 mutation status can be a candidate marker for predicting the effect of gonadotropin-releasing hormone agonists on uterine leiomyoma reduction. Magnetic resonance imaging findings can be used to determine MED12 mutation status as a noninvasive strategy to select patients who will most likely benefit from gonadotropin-releasing hormone agonist treatment.


Subject(s)
Erythropoietin , Leiomyoma , Uterine Neoplasms , Female , Humans , Uterine Neoplasms/drug therapy , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Leiomyoma/drug therapy , Leiomyoma/genetics , Leiomyoma/pathology , Mutation , Leuprolide/therapeutic use , Erythropoietin/genetics , Gonadotropin-Releasing Hormone , Mediator Complex/genetics
9.
J Gynecol Oncol ; 34(1): e10, 2023 01.
Article in English | MEDLINE | ID: mdl-36366812

ABSTRACT

OBJECTIVE: This study aimed to assess gynecologic oncologists (GOs)' perceptions and attitudes toward cancer survivorship to help improve survivor care. METHODS: We conducted a web-based questionnaire survey about survivorship issues for the GOs belonging to the Japan Gynecologic Oncology Group. We analyzed the proactiveness of the participants toward addressing 25 survivor issues. In addition, the practice patterns and barriers to care for survivors' long-term health issues, such as second primary cancer (SPC) and lifestyle-related diseases (LSRD), and return-to-work (RTW) support were assessed. RESULTS: We received 313 responses. The respondents had a mean of 22 years of physician experience. The ratio of men to women was approximately 7:3, and 84.7% worked at facilities for multidisciplinary cancer treatment. The respondents' proactiveness for addressing psychosocial problems was significantly lower than physical and gynecological issues (p<0.01 by χ² test). However, most GOs tried to contribute to such issues according to patients' demands. Women GOs were more proactively involved in some survivorship issues than the men (p<0.05 by logistic regression analysis). The rates of the respondents who proactively discussed SPC, LSRD, and RTW were unexpectedly high (60.7%, 36.1%, and 52.4%, respectively). However, the GOs only provided verbal support for these issues in many cases. CONCLUSION: The Japanese GOs were enthusiastic about survivorship care. However, their tendency to deal with survivors' problems through their own knowledge and judgments raises concerns about the quality of care. Therefore, creating survivorship care guidelines and enhancing multidisciplinary collaboration should be prioritized.


Subject(s)
Cancer Survivors , Neoplasms, Second Primary , Neoplasms , Oncologists , Male , Humans , Female , Cancer Survivors/psychology , Survivorship , East Asian People , Practice Patterns, Physicians' , Surveys and Questionnaires , Neoplasms/therapy
10.
Placenta ; 127: 73-76, 2022 09.
Article in English | MEDLINE | ID: mdl-35973367

ABSTRACT

Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this is the first evidence directly indicating inefficient viral replication in the SARS-CoV-2-infected placenta. Additional studies are required to reveal the detailed mechanisms.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infectious Disease Transmission, Vertical , Placenta/metabolism , Pregnancy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
11.
Front Microbiol ; 13: 848439, 2022.
Article in English | MEDLINE | ID: mdl-35432235

ABSTRACT

Slaked lime (calcium hydroxide) is a commonly used disinfectant for fecal sludge. Although viruses are inactivated by lime treatment, whether RNA viruses adapt to lime treatment has not yet been determined. Here, we show that murine norovirus developed higher tolerance during serial passages with lime treatment. We compared synonymous and non-synonymous nucleotide diversities of the three open reading frames of viral genome and revealed that virus populations were subjected to enhanced purifying selection over the course of serial passages with lime treatment. Virus adaptation to lime treatment was coincident with amino acid substitution of lysine to arginine at position 345 (K345R) on the major capsid protein VP1, which accounted for more than 90% of the population. The infectious clones with the K345R produced using a plasmid-based reverse genetics system exhibited greater tolerance in a lime solution, which indicated that the specific amino acid substitution was solely involved in the viral tolerance in lime treatment.

12.
Nucl Med Biol ; 108-109: 33-43, 2022.
Article in English | MEDLINE | ID: mdl-35276446

ABSTRACT

INTRODUCTION: Theranostic applications are currently difficult to achieve owing to the limited evaluation of suitable chelators for therapeutic nuclides, such as 225Ac and 227Th. With a focus on targeted α therapy and theranostics using human IgG as a drug-delivery system (i.e., combining highly cytotoxic α-particle emitter radiation with efficient tumor targeting), we developed a recombinant humanized Nd2 (hNd2) as an anti-MUC5AC antibody since MUC5AC is highly expressed in patients with pancreatic cancer. Therefore, we aimed to evaluate the performance of 89Zr- (for diagnosis) and 225Ac- (for therapy) labeling of these antibodies using well-controlled radioisotope (RI)-labeling technology in pancreatic cancer mouse models. METHODS: 89Zr-labeled hNd2 (NMK89) and 225Ac-labeled hNd2 (NMT25) were manufactured by chemical conjugation using affinity peptides. A binding assay and the evaluation of plasma stability were performed in vitro to confirm the properties of NMK89 and NMT25. In vivo, we evaluated biodistribution, positron emission tomography (PET)/computed tomography (CT) imaging, antitumor effects, and toxicity. Moreover, the exposure dose in humans was estimated based on the biodistribution evaluation in normal mice. RESULTS: NMK89 and NMT25 showed binding specificity to MUC5AC and stability with radiochemical purity ≥90% in mice and human plasma following incubation for 168 h. NMK89 showed high accumulation in tumors and low non-specific accumulation in normal tissues. The antitumor effect of NMT25 was dose-dependent and significantly suppressed tumor growth in the NMT25 treatment groups compared with the control group (p < 0.05). NMK89 and NMT25 showed similar pharmacokinetics and biodistribution characteristics. Additionally, the human estimated exposure dose of NMK89 and NMT25 was confirmed, and the effective dose of NMK89 and NMT25 was 0.33 mSv/MBq and 177.5 mSv/MBq, respectively. CONCLUSION: NMK89 showed specific accumulation in the MUC5AC-expressing tumors, while NMT25 showed strong antitumor effects. These results suggest NMK89 and NMT25 as promising theranostic agents for pancreatic cancer.


Subject(s)
Pancreatic Neoplasms , Positron-Emission Tomography , Animals , Cell Line, Tumor , Humans , Mice , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/radiotherapy , Positron-Emission Tomography/methods , Radiometry , Tissue Distribution , Zirconium/chemistry , Pancreatic Neoplasms
14.
Mol Clin Oncol ; 14(1): 21, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33363731

ABSTRACT

Little is known about preoperative and intraoperative risk factors for postoperative complications in older patients with gynecological cancer. The present retrospective multi-institutional study included 173 older patients with primary gynecological cancer between January 2015 and December 2015 at four institutions. The cancer stage, medical history, Charlson comorbidity score, body mass index (BMI), subjective global assessment, fall risk assessment, American Society of Anesthesiologists physical status classification, surgical Apgar score (SAS), type of surgery and 1-year postoperative mortality were investigated. Multivariate analysis revealed that BMI and mental illness were risk factors for postoperative complications, and low SAS increased the risk for both postoperative complications and mortality within 1 year. Receiver operating characteristic curve analysis of postoperative complications in terms of SAS revealed that low SAS predicted high risk with a sensitivity of 85.7% and a specificity of 46.5%, and high SAS predicted low risk with a sensitivity of 21.4% and a specificity of 95%. The present results suggest that SAS, which is an intraoperative assessment, may be useful for assessing the risks of postoperative complications and mortality within 1 year. It is important to develop a preoperative assessment tool that can predict a low SAS score and reflect the postoperative prognosis of older patients with gynecological cancer.

15.
Appl Psychol Health Well Being ; 13(3): 653-676, 2021 08.
Article in English | MEDLINE | ID: mdl-32981153

ABSTRACT

BACKGROUND: Prior research observes associations between race-based stressors (e.g. stereotypes) and the compromised psychological and sociocultural adaptation of international students. METHODS: Using an explanatory sequential mixed-methods design (196 survey responses and 51 in-depth interviews), this study examined stereotypes perceived by Chinese students arriving on US college campuses after 2010, their interpretations of the new stereotypes, and the associated psychosocial adaptation challenges they had to navigate. RESULTS: Our findings suggested multiple dimensions of the stereotypes this recent wave of Chinese students perceived from their American peers, including stereotypes pertinent to their financial background (frequency effect sizes = 37.6% and 51% for quantitative and qualitative results, respectively), academic abilities (20.1% and 13.7%), personality characteristics (16.5% and 19.6%), and social attitudes and behaviors (12.9% and 9.8%). Further, this study observed that the new, prevalent stereotypes (e.g. being wealthy) might foster intergroup tension and pit Chinese students against their American peers and that some Chinese students experienced psychological issues (e.g. lower levels of collective self-esteem and feelings of shame) due to the stereotypes of wealth-flaunting Chinese students. CONCLUSIONS: This study contributes uniquely to the literature by unpacking the new stereotypes using a mixed-methods design and points to important practical implications for university services.


Subject(s)
Students , Universities , China , Humans , Self Concept , Surveys and Questionnaires , United States
16.
J Obstet Gynaecol Res ; 46(2): 328-336, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31958879

ABSTRACT

AIM: Although the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy. METHODS: Thirty-two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow-up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo-cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut-off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis. RESULTS: Cervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow-up period. CONCLUSION: Our proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.


Subject(s)
Postoperative Complications/prevention & control , Trachelectomy/adverse effects , Uterine Cervical Neoplasms/surgery , Adult , Constriction, Pathologic/etiology , Female , Humans , Incidence , Japan/epidemiology , Organ Sparing Treatments , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Pregnancy , Pregnancy Rate , Trachelectomy/methods
17.
EMBO Rep ; 20(12): e48251, 2019 12 05.
Article in English | MEDLINE | ID: mdl-31657143

ABSTRACT

Formation of primordial follicles is a fundamental, early process in mammalian oogenesis. However, little is known about the underlying mechanisms. We herein report that the RNA-binding proteins ELAVL2 and DDX6 are indispensable for the formation of quiescent primordial follicles in mouse ovaries. We show that Elavl2 knockout females are infertile due to defective primordial follicle formation. ELAVL2 associates with mRNAs encoding components of P-bodies (cytoplasmic RNP granules involved in the decay and storage of RNA) and directs the assembly of P-body-like granules by promoting the translation of DDX6 in oocytes prior to the formation of primordial follicles. Deletion of Ddx6 disturbs the assembly of P-body-like granules and severely impairs the formation of primordial follicles, indicating the potential importance of P-body-like granules in the formation of primordial follicles. Furthermore, Ddx6-deficient oocytes are abnormally enlarged due to misregulated PI3K-AKT signaling. Our data reveal that an ELAVL2-directed post-transcriptional network is essential for the formation of quiescent primordial follicles.


Subject(s)
ELAV-Like Protein 2/metabolism , Gene Regulatory Networks , Infertility, Female/genetics , Ovarian Follicle/metabolism , Animals , Cells, Cultured , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , ELAV-Like Protein 2/genetics , Female , Mice , Oogenesis , Ovarian Follicle/cytology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism
18.
Jpn J Clin Oncol ; 49(9): 877-880, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31613356

ABSTRACT

We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019.


Subject(s)
Human papillomavirus 16 , Immunotherapy , Papillomavirus E7 Proteins/immunology , Papillomavirus Infections/therapy , Papillomavirus Vaccines/therapeutic use , Squamous Intraepithelial Lesions of the Cervix/therapy , Adult , Double-Blind Method , Female , Humans , Immunity, Mucosal , Lactobacillus/genetics , Middle Aged , Squamous Intraepithelial Lesions of the Cervix/immunology , Squamous Intraepithelial Lesions of the Cervix/virology , Treatment Outcome , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/prevention & control , Uterine Cervical Dysplasia/virology
19.
Int J Clin Oncol ; 24(9): 1129-1136, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31069549

ABSTRACT

OBJECTIVE: To examine the necessity and sufficiency of different types of hysterectomy for the surgical treatment of endometrial cancer. METHODS: This was a multicenter collaborative study conducted by 11 institutions. Among patients with stage I-III endometrial cancer who underwent surgery as the initial treatment (only chemotherapy was provided if adjuvant therapy was needed) from 2001 to 2012, we retrospectively examined the type of hysterectomy, clinicopathological factors, recurrence rate over a maximum period of 5 years, and the site of recurrence. The local recurrence rate was examined by univariate and multivariate analyses. RESULTS: Among 1335 patients, 982 (73.6%) underwent simple hysterectomy (SH) and 353 (26.4%) underwent modified radical hysterectomy (mRH) and were observed for a mean duration of 51.8 months. No significant difference was observed in the rate of local recurrence between the SH and mRH groups (p = 0.928). In multivariate analysis, clinicopathological factors independently associated with localized recurrence included postmenopausal status [hazard ratio (HR) 5.036, 95% confidence interval (CI) 1.506-16.841, p = 0.009], with stages II (HR 3.337, 95% CI 1.701-6.547, p < 0.001) and III (HR 2.445, 95% CI 1.280-4.668, p = 0.007), vs stage I and histological type 2 (HR 1.610, 95% CI 0.938-2.762, p = 0.001). CONCLUSIONS: For endometrial cancer patients requiring surgery, the selection of a more extensive type of hysterectomy did not reduce the rate of local recurrence. Therefore, there is little significance in performing mRH in such cases.


Subject(s)
Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Hysterectomy/methods , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/mortality , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Treatment Outcome
20.
BMC Womens Health ; 19(1): 69, 2019 05 23.
Article in English | MEDLINE | ID: mdl-31122220

ABSTRACT

BACKGROUND: We encountered a woman with vaginal cancer that was associated with complete uterine prolapse and complicated by severe intrauterine adhesions. In this case report, we describe the clinical course and successful treatment of this rare condition. CASE PRESENTATION: A 78-year-old woman (gravida 10, para 2, abortion 8) with a 10-year history of uterine prolapse presented for evaluation of bleeding from an ulceration on the surface of the irreducibly prolapsed uterus. Biopsy of a mass on her vaginal wall led to a diagnosis of keratinizing squamous cell carcinoma. Her history of eight abortion procedures had resulted in severe intrauterine adhesions, preventing tandem insertion and intracavitary brachytherapy. She was also ineligible for surgery under general anesthesia + chemotherapy because of her advanced age and presence of arrhythmia. Therefore, we devised an extensive treatment plan involving high-dose-rate interstitial brachytherapy. This treatment successfully eliminated the squamous cell carcinoma as confirmed by biopsy with no recurrence or severe late complications. CONCLUSIONS: We found that high-dose-rate interstitial brachytherapy may be a very effective therapeutic strategy for this condition with few adverse effects.


Subject(s)
Carcinoma, Squamous Cell/surgery , Pregnancy Complications, Neoplastic/surgery , Uterine Prolapse/surgery , Vaginal Neoplasms/surgery , Aged , Brachytherapy , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/pathology , Female , Humans , Neoplasm Recurrence, Local , Pregnancy , Pregnancy Complications, Neoplastic/pathology , Uterine Prolapse/complications , Vaginal Neoplasms/complications
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