Mathematical energy minimization model for joining boron nitride fullerene with several BN nanostructures.

Nanoscale materials have gained considerable interest because of their special properties and wide range of applications. Many types of boron nitride at the nanoscale have been realized, including nanotubes, nanocones, fullerenes, tori, and graphene sheets. The connection of these structures at the nanoscale leads to merged structures that have enhanced features and applications. Modeling the joining between nanostructures has been adopted by different methods. Namely, carbon nanostructures have been joined by minimizing the elastic energy in symmetric configurations. In other words, the only considerable curvature in the elastic energy is the axial curvature. Accordingly, because it has nanoscale structures similar to those in carbon, BN can also be joined and connected by using this method. On the other hand, different methods have been proposed to consider the rotational curvature because it has a similar size. Based on that argument, the Willmore energy, which depends on both curvatures, has been minimized to join carbon nanostructures. This energy is used to identify the joining region, especially for a three-dimensional structure. In this paper, we expand the use of Willmore energy to cover the joining of boron nitride nanostructures. Therefore, because catenoids are absolute minimizers of this energy, pieces of catenoids can be used to connect nanostructures. In particular, we joined boron nitride fullerene to three other BN nanostructures: nanotube, fullerene, and torus. For now, there are no experimental or simulation data for comparison with the theoretical connecting structures predicted by this study, which is some justification for the suggested simple model shown in this research. Ultimately, various nanoscale BN structures might be connected by considering the same method, which may be considered in future work.

Embryonal rhabdomyosarcoma of the uterus in a 35-year-old woman: case report and review of the literature.

Embryonal rhabdomyosarcoma (RMS) is a rare sarcoma that characteristically occurs in children. The current treatment protocols are based on trials performed in patients under 21 years of age. Embryonal RMS in women over 20 years of age is rare, and studies on treatments and outcomes are limited. The authors here in report a case of a 35-year-old woman with ectocervical RMS who was treated with radical hysterectomy followed by chemotherapy. She is currently disease-free. Based on a literature review, the authors recommend a surgical approach in combination with chemotherapy for treatment of embryonal RMS in adult patients.

Long-term survival of young women receiving fertility-sparing surgery for ovarian cancer in comparison with those undergoing radical surgery.

OBJECTIVES: To compare the clinical outcome of patients with stage I epithelial ovarian cancer (EOC) who received with fertility-sparing surgery (FSS) with those who underwent radical surgery (RS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 572 patients were retrospectively evaluated. All patients were divided into three groups: group A {FSS (n=74); age, ≤ 40}; groups B and C [RS; age, 40 ≥{(B), n=52}; 40<{(C), n=446}]. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 90.8% (OS)/87.9% (DFS); group B, 88.3% (OS)/84.4% (DFS); group C, 90.6% (OS)/85.3% (DFS), respectively (OS, P=0.802; DFS, P=0.765). Additionally, there was no significant difference in OS and DFS among the three groups stratified to stage IA or IC (OS (IA), P=0.387; DFS (IA), P=0.314; OS (IC), P=0.993; DFS (IC), P=0.990, respectively). Furthermore, patients with a grade 1-2 or 3 tumours in the FSS group did not have a poorer prognosis than those in the RS group. CONCLUSIONS: Stage I EOC patients treated with FSS showed an acceptable prognosis compared with those who underwent RS.

Progressive obtundation in a young woman with bilateral corpus striatum infarction: a case report.

BACKGROUND: Bilateral ischemic infarction involving the corpus striatum is a rare event which usually results from global cerebral hypoxia, intoxications, and drug abuse. CASE PRESENTATION: We report a 28 year old Caucasian woman who presented with progressive obtundation and later development of severe expressive dysphasia and Parkinsonism after sustaining ischemic stroke of both corpora striata. Hemorrhagic transformation developed on day four of admission. CONCLUSION: This is a rare case of bilateral basal ganglia infarction with hemorrhagic transformation in a young patient. Our patient's work up did not reveal any cause behind this stroke; however, advanced investigations (such as genetic testing and conventional angiography) were not done. The damage resulted in motor dysphasia and Parkinsonism. Neither dystonia nor other involuntary movements developed, and cognitive function was not assessed because of the language disorder.

Conditional knockout of Lgr4 leads to impaired ductal elongation and branching morphogenesis in mouse mammary glands.

We have analyzed the function of LGR4 in the development of various mouse epithelial tissues. Here we first report the retarded invasion of mammary ducts into the fat pad observed in Lgr4(K5 KO) mice at 4 weeks, compared with that of age-matched Lgr4(K5 ctrl). Furthermore, we demonstrate a significant decrease in mammary ductal branching in Lgr4(K5 KO) at several stages (4, 6 and 8 weeks). On the other hand, immunohistochemical analysis of the mammary gland of Lgr4(K5 KO) using anti-αSMA, anti-K18 and anti-laminin antibodies showed structures similar to those of Lgr4(K5 ctrl) mammary glands. In addition, we did not detect significant differences in the expression of ERα, which was suggested to be a downstream molecule of LGR4, and Lgr4(K5 KO) showed no retarded invasion in the response to 17ß-estradiol administration. Furthermore, the phosphorylated form of Smad1/5/8 was normally detected in the mammary gland of Lgr4(K5 KO).

Carrier cell-based delivery of replication-competent HSV-1 mutants enhances antitumor effect for ovarian cancer.

Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. We have developed replication-competent attenuated herpes simplex virus type 1 (HSV-1) mutants, named HF10 and Hh101, which have been evaluated for their oncolytic activities. However, the host immune system remains a significant obstacle to effective intraperitoneal administration of these viruses in the clinical setting. In this study, we investigated the use of these HSV-1 mutants as oncolytic agents against ovarian cancer and the use of human peritoneal mesothelial cells (MCs) as carrier cells for intraperitoneal therapy. MCs were efficiently infected with HSV-1 mutants, and MCs loaded with HSV-1 mutants caused cell killing adequately when cocultured with cancer cells in the presence or absence of HSV antibodies. In a mouse xenograft model of ovarian cancer, the injection of infected carrier cells led to a significant reduction of tumor volume and prolonged survival in comparison with the injection of virus alone. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on ovarian cancer, which may be further enhanced by the utilization of a carrier cell delivery system, based on amplification of viral load and possibly on avoidance of neutralizing antibodies.

Bilateral infarction of paramedian thalami: a report of two cases of artery of Percheron occlusion and review of the literature.

Artery of Percheron is a normal variant of the paramedian branches of posterior cerebral artery. This artery supplies the paramedian areas of the thalami and upper midbrain. Occlusion of this artery is rare and results in a multitude of neurological signs and symptoms, which might prompt the physician think of an aetiology other than vascular insults, and therefore change the management plan. The authors report two ischaemic strokes, which developed because of this arterial occlusion; their presentation differed from each other.

Fertility-sparing surgery in young women with invasive epithelial ovarian cancer.

OBJECTIVES: The purpose of this study was to clarify the clinical outcome of patients with stage IA or more advanced epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 60 stage I EOC patients treated with FSS were retrospectively evaluated in the current study. RESULTS: The median age was 30 years (range: 12-40 years). The median follow-up time was 54.7 months (range: 4.8-243.8 months). The stage was IA in 30, IB in one, and IC in 29 patients. Fifty-two patients were alive without relapse and 8 patient experienced recurrences {IA, 2; IB, 1; IC(surface involvement), 1; and IC(positive cytology), 4}. However, all patients with stage IC(capsule rupture) (n=17) were alive without recurrence. Collectively, there was no significant difference in the overall survival between the stage IA and IC groups (P=0.256). Moreover, there was no significant difference in DFS and OS between patients with stage IC(capsule rupture) and those with stage IA. In contrast, DFS and OS of the patients with stage IC(surface involvement/positive cytology) were poorer than those of patients with stage IA {OS; P=0.030, and DFS; P=0.005, respectively}. Thirteen pregnancies were observed in 9 patients. CONCLUSIONS: FSS may be considered a treatment option in women with stage I EOC, even in those with stage IC(capsule rupture) or more wishing to bear children.

The striatocapsular infarction and its aftermaths.

Ischaemic stroke syndromes in the vascular territory of middle cerebral artery may have atypical presentation and radiographic findings because of the variable anatomy of that artery. Therefore, misdiagnosis of these syndromes as neoplastic or infectious processes is not uncommon. This case describes a 69-year-old comatose woman who was referred to us as having 'a brain tumour with massive surrounding oedema.' Further work-up revealed that she had a large left-sided lenticular nuclear infarction with some extension into the surrounding areas-the striatocapsular infarction.

Effectiveness of preoperative concurrent chemoradiation therapy (CCRT) for locally advanced adenocarcinoma of cervix.

AIM: To determine the efficacy of preoperative concurrent chemoradiation therapy (CCRT) to improve the prognosis of locally advanced adenocarcinoma of the uterine cervix. METHODS: Twenty-five patients with clinical stage IB2-IVB adenocarcinoma of the cervix were received preoperative CCRT. The CCRT protocol included: external radiotherapy to the pelvis: 39.6 Gy; intra-arterial or intravenous infusion of 70 mg/m2 cisplatin, days 1 and 22; 24-h continuous intravenous infusion of 700 mg/m2 5-FU, days 1-4 and 22-25. Two weeks after the end of CCRT, patients underwent restaging followed by appropriate surgery with pelvic lymphadenectomy. RESULTS: The overall clinical response rate was 96% (24/25), with a complete response (CR) in 12/25 patients and partial response (PR) in 12/25. On pathological examination, 5 of 19 patients (26%) undergoing surgery showed a pathological CR, 13 patients showed a PR, and 1 patient no change (NC) in their disease. Grade 3 or 4 hematological toxicity was observed in 15 patients. Grade 3 gastrointestinal toxicity was observed in 8 patients. The median follow-up period was 34 months (range, 6-69). The 5-year overall survival (OS) rate was 84%, and the progression-free survival (PFS) rate was 76%. CONCLUSIONS: Preoperative CCRT improves the survival of patients with locally advanced adenocarcinoma of the cervix, with manageable toxicities.

Is there any association between retroperitoneal lymphadenectomy and survival benefit in ovarian clear cell carcinoma patients?

BACKGROUND: To estimate the survival impact of systemic retroperitoneal lymphadenectomy in patients diagnosed with International Federation of Gynecology and Obstetrics pTI-IIb clear cell carcinoma of the ovary (CCC). PATIENTS AND METHODS: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2006. Survival curves were calculated using the Kaplan-Meier method. Differences in survival rates were analyzed using the log-rank test. RESULTS: A total of 205 patients had clinical pTI-IIb CCC (median age: 52 years, range: 30-75). One hundred and four (50.7%) patients underwent systemic retroperitoneal lymphadenectomy. Lymphadenectomy was not associated with improved disease-free and overall survival in all patients (P = 0.353 and P = 0.645, respectively). Moreover, lymphadenectomy did not improve the overall survival in those with pTIc CCC (P = 0.433). Similarly, on univariate analysis, age, volume of ascites, preoperative CA 125 values, and regimen of chemotherapy were not significant factors. In addition, there was no significant difference in the ratio of positive lymph node metastases regardless of the completion of lymphadenectomy (P = 0.955). CONCLUSION: Our data suggest that patients with pTI-IIb CCC who underwent lymphadenectomy did not show a significant improvement in survival. There was no significant difference in the overall and disease-free survival rates in pTI-IIb CCC patients regardless of the completion of surgical staging lymphadenectomy.

Twist expression in patients with cervical cancer is associated with poor disease outcome.

BACKGROUND: Twist, a basic helix--loop-helix transcription factor, has been reported to be associated with the development and progression of human cancer. We examined the distribution and expression of Twist in cervical cancer to examine its clinical significance. PATIENTS AND METHODS: We examined the distribution and expression of Twist in 101 cervical cancer specimens and determined the association between their expression and the clinico-pathological features observed, including patient outcome. RESULTS: Of the 101 specimens, 55 cases were negative for Twist immuno-expression, whereas 46 were positive. When categorized into negative versus positive expression, Twist was not associated with any of the clinico-pathological parameters examined. Positive Twist expression significantly predicted poorer overall survival (OS) and progression-free survival (PFS) when compared with negative expression (P < 0.01). In the multivariate analyses, positive Twist expression was an independent prognostic factor for OS (P < 0.05). CONCLUSIONS: Our data imply that positive Twist expression seems to be a useful marker in patients with cervical cancer likely to have an unfavorable clinical outcome.

Expression of N-acetylglucosaminyltransferase V in endometrial cancer correlates with poor prognosis.

N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyses beta1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in endometrial cancer. N-acetylglucosaminyltransferase V expression was studied by immunohistochemistry in 74 surgically resected endometrial cancers, and the staining intensity was evaluated. High GnT-V expression in tumour cells was found in 43 (58.1%) of the 74 cases, and was positively correlated with advanced patient age, histological grade, and lymph vascular space involvement. Patients with high GnT-V expression had significantly impaired overall survival and progression-free survival (PFS) (P=0.0041 and P=0.0023, respectively) compared to patients with low expression of GnT-V. On multivariate analysis, GnT-V expression was an independent prognostic factor for PFS (P=0.0364). beta1-6 branching of asparagine-linked oligosaccharides was also detected in GnT-V-positive endometrial cancer cells by leukoagglutinating phytohaemagglutinin (L(4)-PHA) staining, and the molecular size of the major glycoproteins recognised by L(4)-PHA was approximately 60-200 kDa by lectin blot analysis. These results suggested that high GnT-V expression was correlated with an unfavourable clinical outcome, and that GnT-V is involved in the malignant potential of endometrial cancer by increasing the synthesis of beta1-6 branching of asparagine-linked oligosaccharides.

Oncolytic virotherapy with an HSV amplicon vector expressing granulocyte-macrophage colony-stimulating factor using the replication-competent HSV type 1 mutant HF10 as a helper virus.

Direct viral infection of solid tumors can cause tumor cell death, but these techniques offer the opportunity to express exogenous factors to enhance the antitumor response. We investigated the antitumor effects of a herpes simplex virus (HSV) amplicon expressing mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) using the replication-competent HSV type 1 mutant HF10 as a helper virus. HF10-packaged mGM-CSF-expressing amplicon (mGM-CSF amplicon) was used to infect subcutaneously inoculated murine colorectal tumor cells (CT26 cells) and the antitumor effects were compared to tumors treated with only HF10. The mGM-CSF amplicon efficiently replicated in CT26 cells with similar oncolytic activity to HF10 in vitro. However, when mice subcutaneously inoculated with CT26 cells were intratumorally injected with HF10 or mGM-CSF amplicon, greater tumor regression was seen in mGM-CSF amplicon-treated animals. Furthermore, mGM-CSF amplicon treatment prolonged mouse survival. Immunohistochemical analysis revealed increased inflammatory cell infiltration in the solid tumor in the mGM-CSF amplicon-treated animals. These results suggest that expression of GM-CSF enhances the antitumor effects of HF10, and HF10-packaged GM-CSF-expressing amplicon is a promising agent for the treatment of subcutaneous tumors.

A pure nongestational choriocarcinoma of the ovary diagnosed with short tandem repeat analysis: case report and review of the literature.

Nongestational pure choriocarcinoma of the ovary is a very rare germ cell tumor. Except in women before menarche, determination of the origin is very difficult without genetic analysis. We present a pure nongestational choriocarcinoma arising in the left ovary of a 19-year-old woman. Following surgery, pathologic findings of the tumor demonstrated pure choriocarcinoma without combination of other germ cell tumor elements. We confirmed its nongestational origin by DNA polymorphism analysis at 15 short tandem repeat loci. Multiple courses of chemotherapy with methotrexate, etoposide, and actinomycin-D were effective for this case. DNA polymorphism analysis is useful to determine genetic origin in pure choriocarcinoma of the ovary.

Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients.

Twist is a transcription factor that regulates the expression of tumour suppressors such as E-cadherin. We examined the distribution and expression of Twist in human epithelial ovarian carcinoma (EOC) to examine its clinical significance. Paraffin sections from EOC tissues (n=82) were immunostained with Twist antibody, and the staining intensity was evaluated. The clinicopathological factors examined were age, International Federation of Gynecology and Obstetrics staging, histological type, tumour grade, preoperative value of CA125, peritoneal cytology, volume of ascites and residual tumour after cytoreductive surgery. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Of the 82 carcinomas, 49 (59.8%) cases were negative for Twist immunoexpression, and 33 (40.2%) were positive immunoexpression. When categorized into negative vs positive expression, Twist was not associated with any of the clinicopathological parameters examined. However, positive Twist expression significantly predicted poorer OS and PFS when compared with negative expression (P<0.0001). In the multivariate analyses, positive Twist expression was the only independent prognostic factor for survival in this study (P<0.0001). Positive Twist expression seems to be a useful marker in patients with EOC likely to have an unfavourable clinical outcome.

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n = 80) was immunohistochemically scored as four groups (IDO-, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P = 0.002 and P = 0.001, respectively) compared to patients with no or weak expression of IDO (IDO- or 1+). The 5-year PFS for IDO-/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n = 64), the PFS for IDO2+/3+ was significantly poor (P = 0.001) compared to that for IDO-/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P = 0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.

Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival.

Angiotensin II, a main effector peptide in the renin-angiotensin system, acts as a growth-promoting and angiogenic factor via type 1 angiotensin II receptors (AT(1)R). We have recently demonstrated that angiotensin II enhanced tumour cell invasion and vascular endothelial growth factor (VEGF) secretion via AT1R in ovarian cancer cell lines in vitro. The aim of the present study was to determine whether AT1R expression in ovarian cancer is correlated with clinicopathological parameters, angiogenic factors and patient survival. Immunohistochemical staining for AT1R, VEGF, CD34 and proliferating cell nuclear antigen (PCNA) were analysed in ovarian cancer tissues (n = 67). Intratumour microvessel density (MVD) was analysed by counting the CD34-positive endothelial cells. Type 1 angiotensin II receptors were expressed in 85% of the cases examined, of which 55% were strongly positive. Type 1 angiotensin II receptors expression was positively correlated with VEGF expression intensity and MVD, but not with histological subtype, grade, FIGO stage or PCNA labelling index. In patients who had positive staining for AT1R, the overall survival and progression-free survival were significantly poor (P = 0.041 and 0.017, respectively) as compared to those in patients who had negative staining for AT1R, although VEGF, but not AT1R, was an independent prognostic factor on multivariate analysis. These results demonstrated that AT1R correlated with tumour angiogenesis and poor patient outcome in ovarian cancer, suggesting its clinical potential for a novel molecular target in strategies for ovarian cancer treatment.

Retroviral vector backbone immunogenicity: identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences.

Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B(*)4403 and -B(*)4601, respectively. Similarly, an HLA-B(*)3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.