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The phenylpropene volatiles, dillapiole and apiole, impart one of the characteristic aromas of dill (Anethum graveolens) weeds. However, very few studies have investigated the chemical composition of volatile compounds from different developmental stages and plant parts of A. graveolens. In this study, we examined the distribution of volatile phenylpropenes, including dillapiole, in dill plants at various developmental stages. We observed that young dill seedlings accumulate high levels of dillapiole and apiole, whereas a negligible proportion was found in the flowering plants and dry seeds. Based on transcriptomics and co-expression approaches with phenylpropene biosynthetic genes, we identified dill cDNA encoding S-adenosyl-L-methionine-dependent O-methyltransferase 1 (AgOMT1), an enzyme that can convert 6- and 2-hydroxymyristicin to dillapiole and apiole, respectively, via the methylation of the ortho-hydroxy group. The AgOMT1 protein shows an apparent K

O-Methyltransferases (OMTs) play important roles in antitumor lignan biosynthesis. To date, six OMTs catalyzing the methylation of dibenzylbutyrolactone lignans as biosynthetic precursors of antitumor lignans have been identified. However, there is still no systematic understanding of the diversity and regularity of the biosynthetic mechanisms among various plant lineages. Herein, we report the characterization of two OMTs from Anthriscus sylvestris and Thujopsis dolabrata var. hondae [designated as AsSecoNorYatein (SNY) OMT and TdSNYOMT] together with the six known OMTs to evaluate their diversity and regularity. Although A. sylvestris 5-O-methylthujaplicatin (SecoNorYatein) and 4-O-demethylyatein (NorYatein) OMT (AsSNYOMT) and TdSNYOMT accept 5-O-methylthujaplicatin and 4-O-demethylyatein as substrates, phylogenetic analysis indicated that these two OMTs shared low amino acid sequence identity, 33.8%, indicating a signature of parallel evolution. The OMTs and the six previously identified OMTs were found to be diverse in terms of their substrate specificity, regioselectivity and amino acid sequence identity, indicating independent evolution in each plant species. Meanwhile, two-entropy analysis detected four amino acid residues as being specifically acquired by dibenzylbutyrolactone lignan OMTs. Site-directed mutation of AsSNYOMT indicated that two of them contributed specifically to 5-O-methylthujaplicatin methylation. The results provide a new example of parallel evolution and the diversity and regularity of OMTs in plant secondary (specialized) metabolism.

Bioengineering approaches to modify lignin content and structure in plant cell walls have shown promise for facilitating biochemical conversions of lignocellulosic biomass into valuable chemicals. Despite numerous research efforts, however, the effect of altered lignin chemistry on the supramolecular assembly of lignocellulose and consequently its deconstruction in lignin-modified transgenic and mutant plants is not fully understood. In this study, we aimed to close this gap by analyzing lignin-modified rice (Oryza sativa L.) mutants deficient in 5-HYDROXYCONIFERALDEHYDE O-METHYLTRANSFERASE (CAldOMT) and CINNAMYL ALCOHOL DEHYDROGENASE (CAD). A set of rice mutants harboring knockout mutations in either or both OsCAldOMT1 and OsCAD2 was generated in part by genome editing and subjected to comparative cell wall chemical and supramolecular structure analyses. In line with the proposed functions of CAldOMT and CAD in grass lignin biosynthesis, OsCAldOMT1-deficient mutant lines produced altered lignins depleted of syringyl and tricin units and incorporating noncanonical 5-hydroxyguaiacyl units, whereas OsCAD2-deficient mutant lines produced lignins incorporating noncanonical hydroxycinnamaldehyde-derived units. All tested OsCAldOMT1- and OsCAD2-deficient mutants, especially OsCAldOMT1-deficient lines, displayed enhanced cell wall saccharification efficiency. Solid-state nuclear magnetic resonance (NMR) and X-ray diffraction analyses of rice cell walls revealed that both OsCAldOMT1- and OsCAD2 deficiencies contributed to the disruptions of the cellulose crystalline network. Further, OsCAldOMT1 deficiency contributed to the increase of the cellulose molecular mobility more prominently than OsCAD2 deficiency, resulting in apparently more loosened lignocellulose molecular assembly. Such alterations in cell wall chemical and supramolecular structures may in part account for the variations of saccharification performance of the OsCAldOMT1- and OsCAD2-deficient rice mutants.

Adoptive cancer immunotherapy can induce objective clinical efficacy in patients with advanced cancer; however, a sustained response is achieved in a minority of cases. The persistence of infused T cells is an essential determinant of a durable therapeutic response. Antitumor T cells undergo a genome-wide remodeling of the epigenetic architecture upon repeated antigen encounters, which inevitably induces progressive T-cell differentiation and the loss of longevity. In this study, we identified PR domain zinc finger protein 1 (PRDM1) ie, Blimp-1, as a key epigenetic gene associated with terminal T-cell differentiation. The genetic knockout of PRDM1 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) supported the maintenance of an early memory phenotype and polyfunctional cytokine secretion in repeatedly stimulated chimeric antigen receptor (CAR)-engineered T cells. PRDM1 disruption promoted the expansion of less differentiated memory CAR-T cells in vivo, which enhanced T-cell persistence and improved therapeutic efficacy in multiple tumor models. Mechanistically, PRDM1-ablated T cells displayed enhanced chromatin accessibility of the genes that regulate memory formation, thereby leading to the acquisition of gene expression profiles representative of early memory T cells. PRDM1 knockout also facilitated maintaining an early memory phenotype and cytokine polyfunctionality in T-cell receptor-engineered T cells as well as tumor-infiltrating lymphocytes. In other words, targeting PRDM1 enabled the generation of superior antitumor T cells, which is potentially applicable to a wide range of adoptive cancer immunotherapies.

Hemorrhage and organ injury have been frequently reported as complications associated with trocar puncture in laparoscopic surgery. This report presents a case of delayed intestinal necrosis due to mesenteric injury. A 76-year-old woman who had a history of distal gastrectomy and adrenal insufficiency was diagnosed with stage IA endometrial cancer. We performed laparoscopic total hysterectomy and bilateral salpingo-oophorectomy. The upper abdominal wall and mesentery were adhered, and bleeding from the mesentery was noted during the first trocar puncture of the umbilical region, resulting in ligation and hemostasis. Abdominal pain and fever developed on the third postoperative day, and contrast-enhanced computed tomography demonstrated transverse colon perforation. Emergency laparotomy showed necrosis in the proximal transverse colon and a defect in the marginal artery. Mesenteric injury can lead to delayed intestinal necrosis without intraoperative macroscopic findings. In laparoscopic cases where adhesion is expected, trocar placement should be carefully considered.

Background/aim Heat shock protein 105 (HSP105) is overexpressed in various cancers, but not in normal tissues. We investigated the expression levels of HSP105 in cervical cancer and the efficacy of immunotherapy targeting HSP105. Materials and methods Previously, we established human leukocyte antigen-A*02:01 (HLA-A2) restricted HSP105 peptide-specific cytotoxic T lymphocyte (CTL) clones from a colorectal cancer patient vaccinated with an HSP105 peptide. Herein, we evaluated the expression of HSP105 in cervical cancer and cervical intraepithelial neoplasia. Moreover, we tested the effectiveness of an HLA-A2-restricted HSP105 peptide-specific CTL clone against cervical cancer cell lines. Results HSP105 was expressed in 95% (19/20) of examined cervical cancer tissues. Moreover, the HSP105 peptide-specific CTL clone recognized HSP105- and HLA-A*02:01-positive cervical cancer cell lines and also showed that cytotoxicity against the cervical cancer cell lines depends on HSP105 peptide and HLA class I restricted manners. Conclusion HSP105 could be an effective target for immunotherapy in patients with cervical cancer.

The present study aimed to evaluate the dentin bond strengths of all-in-one adhesives in combination with flowable-resin-composites of different manufacturers. The materials used in this study were two all-in-one adhesives (BeautiBond Multi, BM, and Clearfil Bond SE ONE, SE) and four flowable resin composites (Clearfil Majesty ES Flow, CME; Estelite Flow Quick, EFQ; MI Flow II, MIF; and Beautifil Flow Plus F03, BFP). By combining each all-in-one adhesive and flowable resin composite, eight experimental groups were established. The shear bond strengths (SBSs) in each group were measured, and the data were statistically analyzed using one-way analysis of variance. The SBSs of the group that used SE showed no significant differences among all flowable resin composites (p>0.05), whereas those of the group that used BM showed significant differences between BFP and CME, and CME and EFQ. The combinations showed dentin bond strength ranging approximately from 20 to 30 MPa.

Cervical cancer is a human papilloma virus-related disease, whereas endometrial cancer and atypical endometrial hyperplasia (AEH) are hormone-related diseases, so co-occurrence of the two is possible. However, scientific studies about such cases are rare. We encountered a case of cervical adenocarcinoma and AEH in a 33-year-old nulliparous woman. Two fertility-sparing treatments were performed, a radical trachelectomy for the cervical cancer and high-dose medroxyprogesterone acetate treatment for the AEH. After remission of the diseases, the patient became pregnant by in vitro fertilization and delivered a baby at 36 weeks' gestation by cesarean section. Although the patient had two uterine malignancies, proper evaluation of the diseases, consultation with the patient and her husband, and appropriate management led to fertility preservation, and live birth was achieved.

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor &gt, 6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028), the corresponding five-year OS rates in patients with a tumor ≤6.9 and &gt, 6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

Background/purpose The tissue absorption laser has been clinically applied to alleviate pain in various areas. It is used for pain relief from temporomandibular disease (TMD) in dentistry. Although the facial and trigeminal nerves are distributed around the temporomandibular joint, the effects of laser irradiation and absorption on the neural functions have not been directly studied. In this study, the Nd:YAG laser was applied to an area where the facial nerve passes with photonic radiation for the treatment of TMD. Materials and methods Ten volunteers including seven males and three females were selected as subjects. Nd:YAG laser was irradiated area included several internal and external standard and associated acupuncture points. The chorda tympani nerve, a branch of facial nerve is distributed to the front two thirds of the tongue and is associated with the sense of taste. We evaluated the effect of laser irradiation and absorption on the taste function by means of an electric taste meter. Results No significant difference was identified in the values between before and after laser irradiation (Wilcoxon signed-rank test). Conclusion It was confirmed that there was no effect on taste function while applying Nd:YAG laser irradiation around the TMD joint.

Background: It remains unclear whether the end-of-life (EOL) treatment/environment impacts on survival after anticancer treatment in terminally ill women with ovarian carcinoma (OC). Objective: The...

This study was aimed to examine the effects of intensity and frequency on the cutting efficiency of the Er,Cr:YSGG laser in the enamel and dentin. The percentage of air/water in spray during laser irradiation was fixed at 85%/75% for the enamel and dentin surfaces. Nine points on flattened surfaces of the enamel and dentin were irradiated with the Er,Cr:YSGG laser for approximately 1 s using various intensities (3.0, 4.0, and 5.0 W for enamel, 2.0, 2.5, and 3.0 for dentin) and frequencies (20, 30, and 40 Hz) (n = 10). A high-speed video microscope was used to record each laser irradiation on the tooth surface. A slow video image was used to count the number of water micro-explosions yielded on the tooth surface during the laser irradiation. A surface roughness tester was used to measure the depth of the tiny dimple developed by the laser irradiation on each specimen. The value of each dimple depth was divided by the number of water micro-explosions (pulse). This allowed for the calculation of the cutting depth per pulse. Data were statistically analyzed with two-way analysis of variance. Following laser irradiation, several representative specimens were observed using a scanning electron microscope. Significant effects of both intensity and frequency of the laser irradiation on the cutting depths of the enamel and dentin surfaces were observed (p

The radioulnar ligaments are the major stabilizers of the distal radioulnar joint under dynamic loading; however, anatomical detail regarding their attachment on the middle and distal thirds of the styloid process of the ulna remains unclear. Because previous anatomical studies included only old cadavers, their anatomical findings might not reflect the morphological features of younger and healthy specimens. This study investigated the anatomical features of the distal ulna, particularly the styloid process, to determine the attachment of the radioulnar ligaments to the styloid process and verified their direction and attachment to the styloid process in younger and healthy donors using magnetic resonance imaging (MRI). We investigated the morphological features of the distal ulna of 12 cadaveric wrists using micro‐computed tomography (micro‐CT). We also visualized and measured the distribution of the cortical bone thickness. We histologically analyzed three specimens in the axial plane and macroscopically analyzed seven specimens to examine the attachment of the radioulnar ligaments to the styloid process. In addition, we evaluated five wrists from living volunteers using 3.0 Tesla MRI. The distal ulna has a ridge on the dorsoradial aspect of the styloid process that corresponds to the attachment of the radioulnar ligaments. Micro‐CT images after data processing revealed that the cortical thickness of the dorsoradial quadrant was thicker than that of the other quadrant at the proximal slice of the styloid process (p, We observed that the styloid process of the distal ulna had a ridge on its dorsoradial aspect, corresponding to the chondral‐apophyseal entheses of the radioulnar ligaments. The directions of the radioulnar ligaments were sterically intersected, which may better satisfy both slipping stability and rotational mobility.

Objective To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus-preserving surgery (UPS) in terms of survival prognosis. Methods A regional multi-institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables. Results Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6 years (range 12-87 years), and 56 (30.3%) women underwent UPS. After PS-based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence-free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non-UPS groups. Conclusion UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.

Background. Lower-limb lymphedema (LLL) is a chronic and progressive complication of gynecologic cancer treatment, including pelvic lymphadenectomy. This study aims to investigate the therapeutic effect of goreisan, a traditional Japanese medicine, which has been used for hydrostatic modulation on patients with LLL. Methods. Patients diagnosed with LLL in our hospital in 2018 were included and principally treated with complex decongestive therapy (CDT), including elastic clothing and lymph drainage. The patients who received a combination therapy of CDT and goreisan (CDT-G group) were prescribed goreisan extract granules, with a dose of 7.5 g per os daily in three doses. Patients who were not prescribed goreisan received CDT alone (CDT group). The severity of lymphedema was evaluated by the estimated limb volume calculated by limb circumferences and the ratio of extracellular water (ECW) to total body water (TBW). Results. Nineteen women with LLL after pelvic lymphadenectomy were included in the study. The number of patients in the CDT and CDT-G groups was 8 and 11, respectively. There were no statistically significant differences between the CDT and CDT-G groups in terms of patient characteristics and severity of LLL before treatment. Reduction in ECW/TBW in the CDT-G group (in the whole body and the affected lower limb) after the intervention was significantly more remarkable than that in the CDT group. Conclusions. Goreisan-based Japanese herbal therapy may be effective in patients with LLL after retroperitoneal lymphadenectomy.

We report a case of recurrent small cell carcinoma of the uterine cervix that showed a complete response to paclitaxel, carboplatin, and bevacizumab (TC + Bev) combination therapy. Small cell carcinoma of the uterine cervix is extremely rare, with an incidence of only 1.3% in Japan, and a poor outcome. The patient was a 62-year-old woman with a chief complaint of irregular vaginal bleeding. Magnetic resonance imaging showed a 10-cm irregular mass from the uterine corpus’s posterior wall to the cervix. Abdominal total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling were performed for suspected uterine sarcoma. Histopathological findings revealed small cell carcinoma with lymph node metastasis. Although 6 cycles of etoposide + cisplatin were performed, para-aortic lymph node recurrence was found 3 months after chemotherapy. Subsequently, the patient received 8 cycles of TC + Bev, which eliminated the metastases. The patient is currently alive at 24 months.

The prognostic nutritional index (PNI), which reflects preoperative malnutrition, is useful for predicting the incidence of postoperative complications and has been reported in recent years to predict the long-term prognosis of various malignancies. The purpose of this study was to clarify the significance of PNI as a prognostic factor for early-stage clear cell ovarian carcinoma. A total of 82 patients with stage I–II (FIGO 2014) ovarian clear cell carcinoma undergoing primary surgery at our hospital from January 2005 to December 2017 were enrolled. PNI was calculated using the formula: 10 × serum albumin (g/ dL) + 0.005 × peripheral blood lymphocyte count (/mm3). Preoperative PNI exhibited relatively high area under the curve value (0.709) for 5 year survival, and the optimal cutoff value was 46.5. The overall survival was significantly shorter in the PNI-low group than in the PNI-high group. Multivariate analysis showed that high PNI was a significant independent prognostic factor for favorable prognosis (hazard ratio = 0.102, p = 0.010). There was no significant difference in recurrence-free survival between the two groups (p = 0.220), but the postrecurrence survival was significantly longer in the PNI-high group than in the PNI-low group (p = 0.0383). The preoperative PNI was a useful predictor of prognosis, even in early-stage ovarian clear cell carcinoma.

ObjectiveFinancial toxicity is a financial burden of cancer care itself, which leads to worse quality of life and higher mortality and is considered an adverse effect. The COmprehensive Score for financial Toxicity (COST) tool is a patient-reported outcome measurement used to evaluate financial toxicity. We aimed to validate the internal consistency and reproducibility of the COST tool in patients with gynecologic cancer.MethodsIn this multicenter study covering the period April 2019 to July 2021, using the COST tool in Japan, patients diagnosed with ovarian, cervical, or endometrial cancer receiving systemic anti-cancer drug therapy for more than 2 months were eligible. Patients with no out-of-pocket costs for direct medical costs were excluded. The patients answered the initial test and a retest, which was completed from 2 to 14 days after the initial test. Internal consistency and reproducibility were assessed using Cronbach’s alpha and intraclass correlation coefficient (ICC), respectively. Cronbach’s alpha ≥0.8 indicates good internal consistency, and ICC ≥0.8 is highly reliable.ResultsA total of 112 patients (ovarian: 50, cervical: 26, endometrial: 36) responded to the initial test, and 89 patients answered the retest from 2 to 14 days after the initial test. The median patient age was 58 (range, 28–78) years. The median COST score was 19. Cronbach’s alpha showed good internal consistency at 0.83 (95% CI 0.78 to 0.87). The ICC at 0.850 (95% CI 0.777 to 0.900) showed high reliability.ConclusionsThe COST tool has good internal consistency and reliable reproducibility in patients with gynecologic cancer in Japan. The COST tool quantifies financial toxicity in the insurance system, where patients have limited out-of-pocket direct medical costs. The results support the use of the COST tool in patients with gynecologic cancer.

Highlights • Ewing’s sarcoma family tumors (ESFT) of the uterine cervix are uncommon disease. • Most of ESFT show the genetic change of translocation (11;22) (q24;q12). • Neoadjuvant chemotherapy (NAC) is one of the treatment methods of choice for ESFT. • We report the case of ESFT of the uterine cervix in which NAC followed by radical hysterectomy was performed., Ewing’s sarcoma family tumors of the uterine cervix are extremely rare and, thus, an optimal treatment strategy has not yet been established. To the best of our knowledge, 28 cases were reported in the English literature between 1996 and 2020, and treatments involved surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiotherapy. The vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) protocol increased the survival rate of patients with non-metastatic Ewing’s sarcoma family tumors. We herein present a case of a Ewing’s sarcoma family tumor of the cervix in a one-month postpartum woman treated with neoadjuvant chemotherapy using the VDC-IE protocol and radical hysterectomy followed by adjuvant chemotherapy, and discussed the diagnosis and treatment of this tumor through a literature review.

Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell‐to‐cell crosstalk or phenotypic alterations including the acquisition of platinum‐resistance in OvCa cells. Herein, we report how OvCa‐associated mesothelial cells (OCAMs) induce platinum‐resistance in OvCa cells through direct cell‐to‐cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF‐β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum‐sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell‐to‐cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF‐β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell‐to‐cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum‐resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination., What's new? The clinical characteristics of refractory advanced ovarian cancer suggest that the peritoneum acts as an anchoring point for metastatic tumors, enabling persistent ovarian cancer (OvCa) cell survival. This study shows that ovarian cancer‐associated mesothelial cells (OCAMs) and OvCa cells invade the extracellular matrix of the peritoneum. OCAMs were further found to directly influence persistent OvCa cell survival via FN1 signaling. FN1 on the surface of OCAMs induced activation of the Akt signaling pathway, thereby fueling platinum resistance in OvCa cells. The findings highlight the potential for targeting OCAMs as a novel therapeutic strategy for preventing peritoneal dissemination of ovarian cancer.

Background Ubiquitin-associated protein 2-like (UBAP2L) has been demonstrated to be associated with the progression of multiple types of cancer. However, the function of UBAP2L in uterine cervical cancer remains unclear. Materials and methods Between 2005 and 2015, 84 patients who underwent surgery were included in this study. The patients were stratified into two groups on the basis of immunohistochemical staining for UBAP2L, and survival analysis was performed. Moreover, loss-of-function analysis was performed using the cervical cancer cell lines CaSki and SiHa. Results Based on immunohistochemistry, the overall survival in patients with low UBAP2L expression was significantly longer than that of those with high UBAP2L expression (p=0.045). The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation in both live cell imaging and the MTS assay. Conclusion Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation.

Background The aim of this study was to investigate how much the risks of recurrence and death are increased as a consequence of selecting fertility-sparing surgery (FSS) in young women with epithelial ovarian cancer (EOC). Methods After a central pathological review and search of the medical records from 14 collaborating hospitals, a non-randomized, observational cohort study was conducted between 1987 and 2015, including 1183 women with stage I EOC. Finally, a total of 285 patients with stage I EOC at reproductive age were recruited. Oncologic outcomes were compared between the FSS (N = 101) and radical surgery (RS) group (N = 184) using a propensity score (PS)-matching technique to adjust for relevant risk factors: the age, substage, histological type, grade, CA125 values, ascites cytology, ascites volume, and chemotherapy. Results During 66.0 months (median) of follow-up, 42 patients (14.7%) developed recurrence, and 31 patients (10.9%) died. In the original cohort, there was no significant difference in overall survival (OS) or recurrence-free survival (RFS) between the FSS and RS groups {Log-rank: OS (P = 0.838), RFS (P = 0.377)}. In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in RFS or OS between the FSS and RS groups {RFS (FSS vs. RS), HR: 1.262 (95% CI: 0.559–2.852), P = 0. 575; OS (FSS vs. RS), HR: 1.206 (95% CI: 0.460–3.163), P = 0.704}. Conclusions After adjustment for clinicopathologic factors, FSS in itself may not worsen the oncologic outcome in young women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

The standard treatment for cervical cancer is chemoradiation although some patients showed treatment resistance. The purpose of this study was to investigate the clinical efficacy of surgery after chemoradiation for cervical cancer. Patients with FIGO stage IB2 to IIB cervical cancer were included in the study between 2005 and 2015. A total of 50 patients who underwent surgery after neoadjuvant chemoradiation and 76 patients who received only chemoradiation were compared. Baseline differences between the two groups were adjusted with inverse probability of treatment weighting method using propensity scores composed of the following independent variables: age, stage, tumor size, lymph node metastasis, and histological subtypes. Median follow-up was 64.8 (range 4.8–143.9) months. After adjustment with inverse probability of treatment weighting, Kaplan–Meier curves showing adjusted progression-free survival and overall survival were significantly longer in the neoadjuvant chemoradiation compared with the chemoradiation-only group (p = 0.027 and p = 0.017, respectively). Moreover, in patients with squamous cell carcinoma, recurrence in previously irradiated field and recurrence both in and out of previously irradiated field were significantly decreased in the neoadjuvant chemoradiation compared with the chemoradiation-only group (3.1% and 18.4%, respectively; OR 0.142, p = 0.001]. Adverse events of surgery after chemoradiation were acceptable, although temporary hydronephrosis was frequently observed (23.1%). Surgery after chemoradiation reduced pelvic recurrence, and as a result, patients who underwent neoadjuvant chemoradiation showed more favorable survival outcomes compared with those who only underwent chemoradiation.

Epithelial ovarian cancer (EOC) is considered to secrete various factors in order to promote peritoneal dissemination through cell-to-cell interaction between cancer and mesothelial cells. We previously revealed that TGF-β secreted from EOC induces normal human peritoneal mesothelial cells (HPMCs) to differentiate into cancer-associated mesothelial cells (CAMCs). However, the relationship between tumor cells and CAMCs in EOC is still unclear. We hypothesized that CAMCs also secrete chemokines that attract cancer cells and induce peritoneal dissemination of EOC. We examined chemokines secreted from HPMCs and CAMCs by human chemokine array, and revealed that conditioned medium of CAMCs (CAMCs-CM) included many types of chemokines. The signals of CCL2 were the highest compared with other chemokines. The secretion and relative expression of CCL2 were significantly higher in CAMCs. Recombinant CCL2 promoted trans-mesothelial migration of HPMCs and the migration and invasion by EOC cells. In addition, CCL2 secreted from CAMCs promoted invasion of EOC cells. Furthermore, the neutralizing antibody of CCL2 reduced invasion by EOC. Clinical outcomes of patients whose tissue expressed higher CCR2 were significantly poorer than in patients whose tissue expression was lower. CCL2 activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK). In addition, CAMCs-CM activated the p38 MAPK pathway. Phosphorylation of p38 MAPK reduced with the presence of neutralizing antibody of CCL2. In conclusion, these data indicate CCL2 in CAMCs-CM promoted the malignant potential of EOC. CCL2 plays a crucial role in the tumor microenvironment of EOC.

Background: Little is known about the effect of age on the prognosis of epithelial ovarian neoplasms. In the reproductive age, fertility-sparing surgery had been widely implemented. This study aimed to elucidate impact of age on the clinicopathologic characteristics and survival of epithelial ovarian neoplasms in the reproductive age. Methods: The clinical records of patients diagnosed as epithelial ovarian cancer or epithelial borderline ovarian tumor at the age of 40 years or younger at multiple institutions in the Tokai Ovarian Tumor Study Group were reviewed retrospectively. All patients were stratified into two age groups: group A (≤ 30 years) and group B (31–40 years). Univariate and multivariate analyses were performed to evaluate overall survival and disease-free survival. Results: A total of 583 patients (325 patients: cancer, 258 patients: borderline) were included. The median follow-up time was 62.0 months (range 1–270 months). Compared with group B, group A had a significantly higher rate of borderline tumor (66.7% vs. 32.7%, p, ファイル公開：2021/01/01

Aim Cancer treatment involves long-term therapy and follow-up, with mental disorders (MD) often affecting the treatment process. Hence, in this study, we retrospectively analyze cases involving gynecologic cancer with MD and clarify the relationship between psychosis and cancer prognosis. Methods Patients with both gynecologic cancer and MD from January 2003 to August 2016 were recruited in this study. Cases were limited to those whose MD had been diagnosed before their cancer. Control patients without MD were also analyzed. Both cases and controls were adjusted for age, cancer type, and cancer stage. Results A total of 54 patients with gynecologic cancer and MD, as well as 108 controls without MD, were included. The median age of the patients was 52 years. Details regarding cancer type were as follows: 11 ovarian cancers, 26 uterine corpus cancers and 17 cervical cancers. Among these, 25 schizophrenia cases, 15 depressive disorders, 4 bipolar disorders and 10 other MD were recorded. No significant differences in the 5-year survival rate were found between patients and controls. In advanced-stage cervical cancer, however, the prognosis was significantly poor given the low rate of initial treatment completion. Moreover, patients with advanced-stage cervical cancer had significantly lower chemotherapy completion rates compared to those with other gynecologic malignancies. Conclusion Mental disorders do not affect the prognosis of gynecologic cancers, except for advanced cervical cancer. Accordingly, improving the low rate of initial treatment completion seems to be a focal point for better prognosis in advanced cervical cancer.

Podophyllotoxin is a starting material of the semisynthetic anticancer medicines etoposide, teniposide, and etopophos. The major plant source of podophyllotoxin is rhizomes of Podophyllum hexandrum, which is a Himalayan endangered species; therefore, alternative sources of podophyllotoxin or bioproduction systems have been pursued to avoid exploiting this limited natural resource. In this paper, we report de novo transcriptome analysis of Thujopsis dolablata var. hondae, which accumulates the podophyllotoxin derivatives (deoxypodophyllotoxin and β-peltatin A methyl ether) in its needles. We analyzed transcriptomes of the T. dolablata var. hondae young needles to obtain the sequences that putatively encode O-methyltransferases, cytochrome P450s, and a 2-oxoglutarate dependent dioxygenase because these protein families are responsible for podophyllotoxin-related compound formation in P. hexandrum. The resulting transcriptomes contained considerable numbers of coding sequences classified into the three protein families. Our results are a genetic basis for identifying genes involved in the biosynthesis of podophyllotoxin and related compounds and also for future metabolic engineering of podophyllotoxin in heterologous hosts.

Clear-cell carcinoma (CCC) in reproductive-age women is likely to become an increasingly critical issue regarding possibilities of infertility, hormonal dysfunction, and mortality. The aim of this study was to examine the long-term oncologic outcome and its prognostic indicators based on a multicentric cohort of young patients with CCC. During the period of 1990–2015, a total of 164 patients aged 45-year-old or younger were enrolled in the study. Clinicopathologic data of these young patients with CCC collected under a centralized pathological review system were subjected to uni- and multivariable analyses to evaluate overall survival (OS). The median follow-up was 73.8 months (range 5.2–244.2) in the surviving patients. Among these patients, 104 (63.4%) had FIGO I disease, and 22 (13.4%), 31 (18.9%), and 7 (4.3%) had II, III, and IV disease, respectively. The 5-year OS rate was 74.5%. On stratification by the FIGO stage, the 5-year OS rates were as follows: stage I (90.2%), stage II (57.9%), and stage III/IV (39.3%), respectively (P

Resveratrol and its methyl ethers, which belong to a class of natural polyphenol stilbenes, play important roles as biologically active compounds in plant defense as well as in human health. Although the biosynthetic pathway of resveratrol has been fully elucidated, the characterization of resveratrol-specific O-methyltransferases remains elusive. In this study, we used RNA-seq analysis to identify a putative aromatic O-methyltransferase gene, AcOMT1, in Acorus calamus. Recombinant AcOMT1 expressed in Escherichia coli showed high 4′-O-methylation activity toward resveratrol and its derivative, isorhapontigenin. We purified a reaction product enzymatically formed from resveratrol by AcOMT1 and confirmed it as 4′-O-methylresveratrol (deoxyrhapontigenin). Resveratrol and isorhapontigenin were the most preferred substrates with apparent Km values of 1.8 μM and 4.2 μM, respectively. Recombinant AcOMT1 exhibited reduced activity toward other resveratrol derivatives, piceatannol, oxyresveratrol, and pinostilbene. In contrast, recombinant AcOMT1 exhibited no activity toward pterostilbene or pinosylvin. These results indicate that AcOMT1 showed high 4′-O-methylation activity toward stilbenes with non-methylated phloroglucinol rings.

The Kapandji score is used widely to record thumb opposition and is the only alternative to angular measurements. We aimed to verify the extent to which the Kapandji score reflects the angle of pronation. We recruited volunteers with unaffected upper limbs (33 hands) and patients with carpal tunnel syndrome (20 hands). We attached a small gyroscope to the thumb metacarpal and measured the pronation and palmar abduction angles at each position of the Kapandji score in both groups. The Kapandji score showed a strong ceiling effect, and the increase in angle size at each Kapandji score levelled off around a score of 6 in both groups. A Kapandji score greater than 6 does not necessarily reflect thumb opposition. Level of Evidence: III