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The reaction of (Ia) with (VIII) is also performed in chlorobenzene requiring significantly shorter reaction times, but yielding slightly to significantly less product. [ABSTRACT FROM AUTHOR]

A simple and efficient procedure for the synthesis of N-substituted acryl amides has been developed using Na2CO3/SiO2 or NaHSO4/SiO2. Na2CO3/SiO2 smoothly acts as a base in the reaction between acryloyl chloride and a variety of amines to obtain their corresponding products in good to excellent yield. Additionally, NaHSO4/SiO2 catalyzed the Ritter reaction between acryl nitrile and sec-benzylic alcohols to give the expected N-substituted acryl amide product. In both reactions, Na2CO3/SiO2 and NaHSO4/SiO2 were removed from the reaction mixture using filtration. [ABSTRACT FROM AUTHOR]

A simple protocol for the synthesis of substituted olefins is reported by the cross coupling of tertiary and secondary alcohols. [ABSTRACT FROM AUTHOR]

A simple, rapid, and efficient procedure for the title reaction is developed. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to assess whether hysterectomy with wider resection could improve survival by preventing local recurrence. Methods: Medical charts of the patients with clinical stage I/II endometrial cancers treated at our hospital between 1990 and 2009 were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse effects according to the type of hysterectomy. Results: A total of 247 patients were identified: 46 patients treated with total abdominal hysterectomy (TAH group) and 201 patients with modified radical hysterectomy (mRH group). No significant differences were observed in OS (p = 0.52) and PFS (p = 0.67) between the two groups. Also, there was no significant difference in the distribution of recurrent sites between the two groups. The patients treated with mRH had a longer operation time and more frequently developed severe adverse events, such as blood loss and lymphedema. Conclusion: In our cohorts, there were no significant differences in both PFS and OS according to surgical procedures, and the mRH group more frequently developed severe adverse events. Overall, clinical benefit was not obtained by mRH in patients with clinical stage I/II endometrial carcinomas. [ABSTRACT FROM AUTHOR]

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma that selectively affects small blood vessels. We report a patient who presented with dyspnea and weight loss as well as refractory shock and multiple‐organ dysfunction. The postmortem revealed disseminated involvement of an IVL but no evidence of infection. [ABSTRACT FROM AUTHOR]

Nitrile oxides were formed from α-nitro ketones using silica gel-supported sodium hydrogen sulfate (NaHSO4 /SiO2) or Amberlyst 15 as solid acid catalyst, and then the corresponding 3-acylisoxaszoles were obtained by reacting with alkynes via the 1,3-dipolar [3+2] cyclo-addition. These heterogeneous catalysts are easily separable from the reaction mixture and reused. This synthetic method provides a facile, efficient, and reusable production of 3-acylisoxazoles. [ABSTRACT FROM AUTHOR]

Almost a quarter of a century has passed since the term sarcopenia was defined. Sarcopenia is recognized as a poor prognostic factor in a variety of cancer types. In ovarian cancer, it remains controversial whether sarcopenia affects prognosis and how it should be evaluated. The present study aimed to evaluate the association between the volume of the psoas major muscle and survival in patients with epithelial ovarian cancer. Medical charts of patients with epithelial ovarian cancer who received first-line chemotherapy with paclitaxel and carboplatin at the National Defense Medical College Hospital (Tokorozawa, Japan) between April 2010 and January 2015 were retrospectively reviewed. The bilateral psoas major muscle areas at the fifth lumbar vertebra were measured using computed tomography images. The Institutional Review Board at National Defense Medical College Hospital (Tokorozawa, Japan) approved the study protocol. A total of 72 patients with epithelial ovarian cancer who received combination therapy with paclitaxel and carboplatin were identified and enrolled. The median psoas muscle index (PMI; psoas muscle major cross-sectional area divided by height squared) was 5.4 cm2/m2 (range, 3.3-10.0). Patients with higher PMI had significantly improved overall survival (OS) compared with those with lower PMI [log-rank test P=0.014; hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.21-6.06]. Multivariate analysis for OS revealed that lower PMI was an independent unfavorable prognostic factor (HR, 3.87; 95% CI, 1.37-12.1; P=0.0098). The volume of psoas major muscle mass could be a potential biomarker for prognosis in patients with epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract: Asymmetric reduction of ketone by a microalga, Synechocystis sp. PCC 6803, smoothly afforded to the corresponding (S)-alcohol in excellent enantiomeric excess by the aid of illumination of orange and red LED lights which are more effective than other LEDs such as blue and green lights. The condition under minimum energy flux (1.0W/m2) of orange-red LEDs is enough for the reduction of ketone, and it seems that orange-red light rather effectively forwarded the regeneration of coenzyme. [Copyright &y& Elsevier]

Background: This study aimed to examine the clinical significance and risk factors of thromboembolic events (TEEs) in patients with ovarian carcinoma. Methods: Patients with ovarian carcinoma treated at our hospital between 2000 and 2017 were identified. The risk factors of TEEs, including venous TEEs and arterial TEEs, and the association between TEEs and prognosis were investigated. Patients with TEEs were classified into two groups: those with severe TEEs, defined as patients who required urgent treatment for deep vein thrombosis, massive pulmonary embolism, acute myocardial infarction, and symptomatic cerebral infarction, and those with mild TEEs. The risk factors of severe TEEs and the association between severe TEEs and prognosis were investigated. Results: A total of 369 patients were enrolled. Among them, 53 patients (14.4%) were complicated with TEEs. Clear cell carcinoma (CCC) was a greater risk factor of TEEs than serous carcinoma (hazard ratio [HR] = 2.81, p = 0.03). In multivariate analysis for survival, TEEs were a prognostic factor of poor progression-free survival (PFS; HR = 2.90, p < 0.01) and overall survival (OS; HR = 2.89, p < 0.01). Among 53 patients with TEEs, 17 (32.1%) developed severe TEEs. CCC was strongly associated with severe TEEs (HR = 42.6, p = 0.02). Multivariate analysis for survival demonstrated that severe TEEs were a risk factor of worse PFS (HR = 4.34, p < 0.01) and OS (HR = 3.30, p = 0.03). Conclusion: TEEs induced poor prognosis and was associated with CCC. A standard treatment for CCC should be included in the strategy of TEEs. [ABSTRACT FROM AUTHOR]

Objective: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. Methods: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. Results: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). Conclusion: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC. [ABSTRACT FROM AUTHOR]

Purpose: To compare a cohort of patients with platinum-resistant recurrent ovarian cancer (PROC) treated with bevacizumab and gemcitabine (Bev-Gem) to that of patients treated only with gemcitabine (Gem).Methods: Between 2011 and 2017, we identified the Bev-Gem and Gem PROC groups. The regimen included 1000 mg/m2 of Gem on days 1, 8, and 15, and 15 mg/m2 of Bev on day 1, every 4 weeks. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the administration of Bev-Gem or Gem until disease progression or death.Results: The Bev-Gem and Gem groups included 18 and 29 patients, respectively. More patients had advanced stage disease in the Bev-Gem group (p = 0.048); no other characteristics differed between the groups. The response rates [ratio of complete remission (CR) to partial remission (PR)] of Bev-Gem and Gem were 38.9 and 3.4%, respectively (p < 0.01). The clinical benefit rates [combined percentages of CR, PR, and stable disease] of the Bev-Gem and Gem groups were 88.9 and 41.4%, respectively (p = 0.04). PFS and OS of the Bev-Gem group were superior (p < 0.01, p = 0.03, respectively). Bev-Gem was the better prognostic factor of both PFS [hazard ratio (HR) 0.17, p < 0.01] and OS (HR 0.31, p = 0.01). The frequency of hematologic and non-hematologic adverse effects was similar in each group.Conclusion: Bev-Gem regimens improved PFS and OS for PROC. Furthermore, the adverse effects of Bev-Gem were tolerable. Thus, Bev-Gem could be a candidate treatment strategy for PROC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a disease with poor prognosis. Nuclear accumulation of YB-1 is closely related to the malignancy of HCC. Treatment with anticancer agents often induces translocation of YB-1 from cytoplasm to nucleus and activates the expression of multidrug resistance gene 1 (MDR1). Therefore, any effective inhibitor of this phenomenon would be useful for cancer treatment. Here we examined various indirubin derivatives and found that indirubin 3′-oxime inhibits actinomycin D-induced nuclear transport of YB-1 and suppresses the activation of MDR1 gene expression in the human hepatocellular carcinoma cell line HepG2. Furthermore, use of both indirubin 3′-oxime and actinomycin D in combination increased the anticancer effect on HepG2 cells. Indirubin 3′-oxime is a novel and efficient inhibitor of anticancer agent-induced YB-1 nuclear translocation. [ABSTRACT FROM AUTHOR]

Purpose: Low skeletal muscle mass (sarcopenia) has been reported to have an influence on survival and toxicities of chemotherapy in several solid tumors. The impact of sarcopenia on the treatment of ovarian cancers has not been determined. The present study aimed to evaluate correlation between sarcopenia and toxicities of chemotherapy in ovarian cancers.Methods: Medical charts of the ovarian cancer patients that received chemotherapy with paclitaxel and carboplatin at our hospital between 2010 and 2015 were retrospectively reviewed. Muscle areas of bilateral psoas major muscles at the fifth lumbar vertebra were measured using images obtained by computed tomography. The volume of muscle and clinicopathological factors were evaluated for toxicities of chemotherapy. The protocol of the present study was approved by the institutional review board of our institution.Results: A total of 76 patients with ovarian cancers were identified, and enrolled in the present study. Median psoas index (PI, the psoas muscle major cross-sectional area divided by the height squared) was 583 mm2/m2 (range 326-999). The patients with low PI developed peripheral neuropathy more frequently compared with those with high PI (32 vs. 11%; P = 0.047). PI value was not associated with other toxicities such as neutropenia and thrombocytopenia. PI value was associated with grade 2 or higher peripheral neuropathy in univariate analysis (OR = 3.92; 95% CI 1.21-15.32; P = 0.02) and multivariate analysis (OR = 3.93; 95% CI 1.17-15.87; P = 0.03).Conclusions: PI value was significantly associated with peripheral neuropathy induced by combination therapy with paclitaxel and carboplatin in ovarian cancer patients. Although further studies are needed to confirm the results, the volume of skeletal muscle mass could be a potential biomarker to predict toxicities in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Objective: Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Methods: Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Results: Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. Conclusion: The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. [ABSTRACT FROM AUTHOR]

Abstract: Reaction of electron-rich arenes with acetyl bromide and aldehydes in the presence of silica gel-supported zinc bromide was carried out in benzene to give selectively the corresponding triarylmethanes or 9,10-diarylanthracenes in high yields depending upon the ratio of an arene and an aldehyde. The mild conditions employed are especially noteworthy. [Copyright &y& Elsevier]

[Display omitted] • Sunlight induced C C bond formation reaction proceeded efficiently. • Addition of alcohols/ethers/acetals to olefins proceeded using t -Bu 2 O 2. • The reactions are completed mostly within 3–4 h at room temperature in > 95 % yield. • Gram-scale reactions proceeded efficiently without large extention of reaction time. A sunlight-induced C C bond formation reactions upon the addition of alcohols/ethers/acetals to olefins proceeded efficiently using di- tert -butyl peroxide (DTBP). The reactions proceeded faster than many of the previously reported sunlight and many conventional lamp photolyses, typically in 3–4 h under irradiation with sunlight, in excellent yield using olefins bearing two electron withdrawing groups (EWGs) (product yield > 95 %) and in good to fair yield with olefins bearing one EWG. The yields observed for some products were ∼20 % higher than those obtained using a conventional Xe lamp as the light source, which was confirmed to be due to a light intensity effect. Gram-scale experiments showed similar yields to those observed in their corresponding small-scale experiments. [ABSTRACT FROM AUTHOR]

A fast photochemical C–C bond formation between cyclic ethers/acetals and olefins using di- tert -butyl peroxide (DTBP) was developed. This method provides easy access to 2-substituted cyclic ethers, and 2- or 4-substituted cyclic acetals. Acyl/formyl groups or diols can be obtained by the hydrolysis of the 2- or 4-substituted cyclic acetals, respectively. The reactions proceeded at room temperature and gave the expected products in good to excellent yields; efficient reactions were completed within 0.5 h at room temperature in >95% yield. Image 1 • Photochemical addition of cyclic ethers/acetals to olefins proceeded efficiently. • Efficient reactions are completed within 0.5 h at room temperature in > 95% yield. • The reaction is a synthesis of masked ketones/aldehydes and diols. [ABSTRACT FROM AUTHOR]

Aim: To examine the clinicopathological features of ovarian seromucinous borderline tumors (SMBTs) and compare them with those of mucinous borderline/atypical proliferative mucinous tumors (MB/APMTs)., Patients and Methods: Patients with SMBT between 2014 and 2018 and those with MB/APMT between 1988 and 2018 who underwent surgery at our Institution were identified. Pathological review was conducted using the 2014 World Health Organization criteria. Clinical features were compared retrospectively between SMBT and MB/APMT., Results: In total, 11 (12.9%) patients with SMBT and 74 (87.1%) patients with MB/APMT were included in our study. The diagnosis of six patients with SMBT and 73 patients with MB/APMT was not revised on review. SMBT was diagnosed at a younger age (p=0.04), was of smaller size (p<0.01) and bilateral (p=0.03), coexisted with endometriosis (p<0.01), and more frequently recurred than MB/APMT (p=0.04)., Conclusion: SMBT might be more aggressive than MB/APMT., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The aim of this study was to examine the associations among the haphazard invasive patterns, defined as directionless infiltration into the myometrium; expression of key proteins; tumor infiltrative lymphocytes (TILs); and the prognosis of gade-3 endometrioid carcinoma (G3EC). Between 1990 and 2013, patients with G3EC who underwent surgery at our hospital were identified. Invasive patterns were classified into either haphazard, infiltrative, or expansile patterns. The estrogen, progesterone, androgen receptor, cytokeratin 5/6, epidermal growth factor receptor, E-cadherin, snail-2, vimentin, ZEB1, chromogranin A, synaptophysin, MLH1, MSH2, MSH6, and PMS2 levels were evaluated by immunochemical analysis. The degree of strong or weak lymphocyte infiltration (LI) were evaluated using zone formation of LI at the invasive front. Haphazard, infiltrative, and expansile patterns were discovered in 8 (18%), 6 (13%), and 31 (69%) cases, respectively. Cases with the haphazard patterns were diagnosed at a more advanced stage (p < 0.01) and recurred more frequently (p < 0.01). There were statistical differences in progression-free survival (PFS) and overall survival (OS) between the three groups (PFS; p < 0.01: OS; p < 0.01). In multivariate analysis, only the haphazard pattern was found to be an independent, worse prognostic factor of PFS (Hazard ratio (HR) =10.8, p < 0.01) and OS (HR = 23.3, p < 0.01). Furthermore, the haphazard invasive pattern was related with weak LI (p < 0.01) but not with the expression of all proteins analyzed. The haphazard pattern was found to be a worse prognostic factor and was associated with weak LI in G3EC. The aggressive feature of G3EC might be associated with LI but not tumor biology.

Background/aim: This study aimed to evaluate the clinical significance of lymphocyte infiltration (LI) for patients with endometrial serous carcinoma and those with endometrioid carcinoma including serous component., Patients and Methods: Patients who underwent surgery at our hospital between 1990 and 2013 were identified. LI was classified into strong LI, defined as a continuous thick zone of LI, and weak LI, defined as the lack of zone or scattered small foci of LI at the invasive front., Results: Out of a total of 51 patients, 38 cases had weak LI and 13 had strong LI. The progression-free survival of patients with weak LI was worse (p=0.02). No significant difference of overall survival according to the status of LI was noted (p=0.054). Multivariate analysis revealed that LI was a prognostic factor of poorer progression-free survival (hazard ratio(HR)=5.05, p<0.01) and overall survival (HR=6.93, p=0.01)., Conclusion: LI might be a new biomarker of such conditions., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The pretreatment neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported to be useful as markers for prognostic factors and metastasis in several cancers. The aim of this study was to identify the predictor of lymph node (LN) metastasis by pretreatment NLR and PLR in patients with endometrial cancer., Methods: Medical charts of the patients with endometrial cancers that received primary surgery at our hospital between 2007 and 2013 were retrospectively analyzed. The cutoff value was calculated from the receiver operating characteristics (ROC) curve. Clinicopathological parameters including inflammatory markers were evaluated for LN metastasis using multiple logistic regression analysis., Results: Among 197 patients enrolled in the study, LN metastasis was observed in 25 patients (13%). ROC curves demonstrated that the best cutoff value of NLR for predicting LN metastasis was 2.18 and that of PLR was 206. In univariate analysis, several pathological factors, NLR, and PLR were identified as predictors of LN metastasis. In multiple logistic regression analysis, lymphovascular invasion and NLR were found to be significantly correlated with LN metastasis (p = 0.002, 0.039)., Conclusion: A higher pretreatment NLR was identified as a predictor of LN metastasis in endometrial cancers. Although further study is needed to confirm the results, NLR could be a candidate clinical marker for detection of LN metastasis., (© 2019 S. Karger AG, Basel.)

Background/aim: The purpose of this study was to compare the clinical behavior of several grades of endometrioid carcinoma (EC) compared to high-grade serous carcinoma (HGSC), based on World Health Organization 2014 criteria., Materials and Methods: Clinicopathological features were compared between all grades of EC and HGSC, and between HGSC and either grade 1/2 or grade 3 EC., Results: Sixty-five patients with EC and 214 with HGSC were identified. Among patients with EC, 56 displayed 1/2 EC and nine had grade 3 EC. The progression-free (PFS) and overall (OS) survival of patients with grade 1/2 EC were better than of those of patients with HGSC; however, PFS and OS did not statistically differ between patients with grade 3 EC and those with HGSC. Grade 1/2 EC, but not grade 3, was a better prognostic factor compared with HGSC., Conclusion: A grading system for EC would be beneficial for the accurate prognosis of ovarian cancer., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro . The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.

Background: Spinal cord ischemic injury is the most devastating sequela of descending and thoracoabdominal aortic surgery. Motor-evoked potentials (MEPs) have been used to intraoperatively assess motor tract function, but it remains unclear whether MEP monitoring can decrease the incidence of postoperative motor deficits. Therefore, we reviewed multicenter medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open surgery and endovascular repair) to assess the association of MEP monitoring with postoperative motor deficits., Methods: Patients included in the study underwent descending or thoracoabdominal aortic repair at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery between 2000 and 2013. Using multivariable mixed-effects logistic regression analysis, we investigated whether intraoperative MEP monitoring was associated with postoperative motor deficits at discharge after open and endovascular aortic repair., Results: We reviewed data from 1214 patients (open surgery, 601 [49.5%]; endovascular repair, 613 [50.5%]). MEP monitoring was performed in 631 patients and not performed in the remaining 583 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. Multivariable logistic regression analysis revealed that postoperative motor deficits at discharge did not have a significant association with MEP monitoring (adjusted odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69-1.88; P = .624), but with other factors: history of neural deficits (adjusted OR, 6.08; 95% CI, 3.10-11.91; P < .001), spinal drainage (adjusted OR, 2.14; 95% CI, 1.32-3.47; P = .002), and endovascular procedure (adjusted OR, 0.45; 95% CI, 0.27-0.76; P = .003). The sensitivity and specificity of MEP <25% of control value for motor deficits at discharge were 37.8% (95% CI, 26.5%-49.5%) and 95.5% (95% CI, 94.7%-96.4%), respectively., Conclusions: MEP monitoring was not significantly associated with motor deficits at discharge.

Objective: In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but "seromucinous carcinoma" was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients., Methods: Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013., Results: Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049)., Conclusion: Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Aim: To determine whether CD44, which is associated with tumor growth and metastasis, is related to carcinogenesis and prognosis in ovarian mucinous carcinomas (MACs)., Materials and Methods: Tissue blocks from 71 patients with benign mucinous ovarian tumors were used in the study: 35 were from patients with borderline mucinous ovarian tumors, and 60 from patients with MACs. Immunochemical analysis was performed to evaluate the expression of CD44 and examine its association with tumorigenesis and survival., Results: Compared to benign tumors, borderline tumors had high CD44 expression levels (p=0.047). Conversely, MACs had lower expression than borderline tumors (p=0.032). Progression-free and overall survival of patients with MAC with low CD44 expression were worse than those of patients with high expression (p=0.04 and p=0.02, respectively)., Conclusion: Malignant transformation of mucinous tumors is associated with changes in CD44 expression, with low expression level being a prognostic factor in MAC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A highly efficient and simple method for the synthesis of 2-alkylbenzothiazoles through the condensation of 2-aminothiophenol and aliphatic aldehydes in the presence of active carbon/silica gel is described. The reaction proceeded under solvent-free and microwave irradiation to afford 2-alkylbenzothiazoles in high yields. This method was extended to the synthesis of bile acid derivatives containing a benzothiazole ring and obtained the desired products in high yields. The anti-inflammatory activity and cytotoxicity of the newly synthesized benzothiazole derivatives of bile acid were tested; the results showed that anti-inflammatory activities of all tested compounds tested were higher than that of standard drugs, such as indomethacin.

Background/aim: To investigate whether XIAP down-regulation and autophagy inhibition sensitize ovarian clear cell cancer cells to cisplatin., Materials and Methods: The ovarian clear cancer cell line KK was used for in vitro analysis. Hydroxychloroquine (HCQ) and phenoxodiol (PXD) or embelin were used as autophagy and XIAP inhibitors, respectively. Non-specific and XIAP-specific siRNAs were transfected using Lipofectamine. Cytotoxicity was assessed by MTT assays. Protein expression was confirmed by western blotting., Results: In KK, down-regulation of XIAP using specific siRNAs together with HCQ treatment enhanced the anti-tumor effect of cisplatin. Although embelin sensitized KK to cisplatin through XIAP down-regulation, it induced autophagy. However, PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition. Expression of Atg7, Atg12, and Beclin 1 was decreased after PXD treatment., Conclusion: PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition and could be a new candidate for ovarian clear cell carcinoma treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The clinical significance of coexistence of endometriosis (EM) in ovarian clear cell carcinoma (CCC) has not yet been determined. The aim of the present study was to analyze the correlation of endometriosis with clinicopathological factors in CCC. The cases with CCC that received primary debulking surgery at the present hospital between 1990 and 2013 were identified. Retrospective analysis was conducted to evaluate the association between complications with EM and clinicopathological features in CCC. Of the 105 cases enrolled in the study, 45 cases were complicated with EM, and 60 cases did not have EM (non-EM). The patients with EM were diagnosed at a younger age (P=0.03), and at earlier stages (P<0.01) compared with non-EM cases. Although there was no significant difference of progression-free survival (P=0.36), complications with EM were identified as an independent prognostic factor for overall survival (OS; P<0.01) by multivariate analysis. A total of 48 patients (45.7%) developed recurrence: 18 patients in EM-group and 30 patients in non-EM group. There were no significant differences of clinicopathological factors in the treatment at recurrence between both groups. Recurrent cases in EM had significantly worse post-progression survival (PPS) compared with recurrent non-EM group (P<0.01). Multivariate analysis for PPS demonstrated that complications with EM (P<0.01) were identified as a worse prognostic factor. In CCC, the complication with EM was identified as a significant worse prognostic factor for PPS in recurrent cases. Additionally, EM was significantly associated with OS in all cases with CCC. Novel treatment strategies are therefore necessary for recurrent CCC, particularly for cases exhibiting EM.

High-temperature-required protein A2 (HtrA2) is one of the serine proteases related to apoptosis. HtrA2 protein expression has been associated with cisplatin resistance and poor prognosis in ovarian serous adenocarcinoma (SAC). The aim of this study was to understand the influence of HtrA2 on repeated treatment with cisplatin. The change in HtrA2 expression in 31 ovarian cancers was investigated by immunohistochemical analysis, before and after cisplatin-based chemotherapy, and the association between HtrA2 expression after chemotherapy and prognosis was analyzed. The association between the change in HtrA2 and proteins associated with LATS1 in ovarian serous cancer cell lines after repeated treatment with cisplatin was evaluated in vitro. In immunohistochemical analysis, repeated cisplatin treatment induced downregulation of HtrA2 protein expression, before and after cisplatin-based chemotherapy in SAC. Progression-free survival and overall survival of SAC with low expression of HtrA2 were worse than those with high expression. In vitro analysis using cisplatin-sensitive ovarian cancer cell lines, KF28, and cisplatin-resistant cancer cell lines, KFr13, obtained from KF28 by repeated cisplatin treatment, showed that HtrA2 protein expression was lower in KFr13 than in KF28. Furthermore, KFr13 had a higher invasive capacity than KF28. Next, downregulation of HtrA2 transfected with an HtrA2-specific siRNA in KF28 had not only cisplatin resistance, but also more invasive capacity than those with non-specific siRNA. Repeated treatment with cisplatin downregulated the HtrA2 protein, which led to cisplatin resistance and increased invasive capacity. Thus, HtrA2 might be a biomarker of response to cisplatin treatment and prognosis, after cisplatin-based chemotherapy.

Purpose: Recently, generic drugs of paclitaxel have been commonly used mainly by economic reasons; however, predictive factors for toxicities are not fully determined. Hypersensitivity reaction (HSR) is one of the most important adverse events in the paclitaxel-based therapy, and sometimes leads to lethal condition. The aim of the study was to identify predictors for HSR in patients treated with paclitaxel-based regimens., Methods: All the patients treated with chemotherapy including paclitaxel at our hospital between 1998 and 2013 were retrospectively evaluated. Clinicopathological factors of the patients that developed HSR and those without HSR were compared, and predictive factors for HSR were identified., Results: Among 414 patients enrolled in the study, 26 patients (6.3%) developed HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1) were identified as predictive factors for HSR. There was no significant difference in the incidence of HSR between original paclitaxel and generic drug. The incidence of HSR was higher as the number of these predictors was accumulated., Conclusions: Three factors were identified as predictive factors for HSR: younger age, a history of allergy, and short-course premedication. Accumulation of these factors increased the incidence of HSR; however, the use of generic drug was not associated HSR in gynecologic cancer patients.

Non-platinum single agents are usually used for patients with platinum-resistant recurrent ovarian cancers (ROC). However, the efficacy of these drugs is limited. The aim of the present study was to evaluate the efficacy and adverse events (AE) of combination therapy with irinotecan and platinum (CPT-Pt) for ROC. A total of 28 platinum-resistant or refractory patients with ROC treated with CPT-Pt at the National Defense Medical College Hospital institution between 2002 and 2012 were identified. All patients received taxane and carboplatin (TC) as a first-line treatment and relapsed within 6 months after completion of TC, or progressed during TC therapy. The median age was 59 years (range, 16-78), and median number of CPT-Pt therapy cycles was 5.5 (range, 2-16). The overall response rate was 14%, with a complete response (CR) in 2 patients and partial response (PR) in 2 patients. Stable disease (SD) for >3 months was observed in 15 patients (54%), resulting in a clinical benefit rate (CBR = CR + PR + SD) of 68%. The median progression-free survival and overall survival were 8 and 15 months, respectively. Fifteen cases (68%) developed grade 3/4 hematological AE and 3 cases (11%) developed non-hematological grade 3/4 AE, which were resolved by conservative management or dose reduction. Platinum re-treatment with irinotecan for platinum refractory or resistant ROC may be a candidate in such clinical settings.

The aim of the present study was to identify clinicopathological factors in long-term survivors following ovarian cancer recurrence. The patients who achieved longer survival after recurrence (n=18) and those who succumbed to the disease earlier (n=47) were identified and analyzed. There were no significant differences in age, performance status, stage distribution or histology between the two groups. Additionally, no significant difference was observed in progression-free survival after primary therapy. Multivariate analyses revealed that the predictive factors for long-term survival were i) secondary debulking surgery (OR=13.3; 95% CI: 1.39-226.7), ii) favourable response rate of second-line chemotherapy (OR=46.5; 95% CI: 1.84-313-4), and iii) ≥3 regimens after first recurrence (OR=9.01; 95% CI: 1.28-117.7). This study revealed that prolonged post-progression survival was associated with post-recurrence treatment. Therefore, appropriate selection of secondary debulking surgery and better chemotherapeutic response may lead to prolonged post-progression survival in recurrent ovarian cancer patients.

Objective: Ovarian clear cell carcinoma (CCC) is one of histological subtypes showing poor prognosis due to chemoresistance. The association of autophagy-related proteins and clinical implementation in CCC has not been determined., Methods: The present study investigated whether expression of autophagy-related protein, light chain 3A (LC3A), was related with prognoses in the patients with CCC using immuno-histochemical stainings, and whether inhibition of autophagy modified the sensitivity to cisplatin in CCC cells in vitro., Results: High expression of autophagy-related protein, LC3A, was detected in 78 cases (78%) in all CCC cases. The patients with high LC3A expression showed significantly lower response rate to primary chemotherapy (17% vs. 100%, p<0.010), and had worse progression-free survival (PFS) and overall survival (OS) compared with those with LC3A low expression. Furthermore, multivariate analyses revealed that high expression of LC3A was identified as independent worse prognostic factors for PFS and OS. Inhibition of autophagy protein LC3A using hydroxychloroquine (HCQ) increased sensitivity to cisplatin in CCC cells in vitro., Conclusion: High expression of LC3A proteins was associated with lower response to platinum therapy, leading to worse prognoses in CCC. Although further studies are needed to confirm the results, inhibition of autophagy by HCQ was associated with platinum sensitivity. Autophagy protein LC3A could be a promising target for treatment for CCC., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.