Characteristics of shifting ability in children with mild intellectual disabilities: an experimental study with a task-switching paradigm.

BACKGROUND: Shifting enables flexible switch between tasks or mental sets. It is a component of the executive function that plays critical roles in human behaviour control. However, shifting ability in individuals with intellectual disability (ID) has not been well clarified because of the use of intellectually demanding tasks in previous studies. The present study invented a novel shifting task with minimal intellectual demands and aimed to clarify the characteristics of shifting in adolescents with ID. METHODS: Adolescents with ID (n = 21) and chronological-age-matched (n = 10) and mental-age-matched controls (n = 33) performed a novel shifting task with simple rule switching (i.e. change in direction). Analyses focused on the switch cost or the increase in the reaction time associated with rule switching. RESULTS: Two subtypes of adolescents with ID were found with respect to the switch cost: one that lacks it and another with an increased switch cost. The lack of a switch cost was unique to the subgroup adolescents with ID and was not indicated in the control group. CONCLUSIONS: The present study indicated that shifting in adolescents with ID does not depend solely on their intellectual function and is highly heterogeneous. This finding further implies that executive functions, including shifting, must be evaluated separately from their intellectual functions.

Two-Dimensional Superconducting Fluctuations Associated with Charge-Density-Wave Stripes in La_{1.87}Sr_{0.13}Cu_{0.99}Fe_{0.01}O_{4}.

The presence of a small concentration of in-plane Fe dopants in La_{1.87}Sr_{0.13}Cu_{0.99}Fe_{0.01}O_{4} is known to enhance stripelike spin and charge density wave (SDW and CDW) order and suppress the superconducting T_{c}. Here, we show that it also induces highly two-dimensional superconducting correlations that have been argued to be the signatures of a new form of superconducting order, the so-called pair density wave (PDW) order. In addition, using resonant soft x-ray scattering, we find that the two-dimensional superconducting fluctuation is strongly associated with the CDW stripe. In particular, the PDW signature first appears when the correlation length of the CDW stripe grows over eight times the lattice unit (∼8a). These results provide critical conditions for the formation of the PDW order.

Low-intensity pulsed ultrasound stimulation for mandibular condyle osteoarthritis lesions in rats.

OBJECTIVE: This study evaluated low-intensity pulsed ultrasound effects for temporomandibular joint osteoarthritis in adult rats. MATERIAL AND METHODS: Osteoarthritis-like lesions were induced in 24 adult rats' temporomandibular joints with low-dose mono-iodoacetate injections. The rats were divided into four groups: control and mono-iodoacetate groups, injected with contrast media and mono-iodoacetate, respectively, at 12 weeks and observed until 20 weeks; and low-intensity pulsed ultrasound and mono-iodoacetate + low-intensity pulsed ultrasound groups, injected with contrast media and mono-iodoacetate, respectively, at 12 weeks with low-intensity pulsed ultrasound performed from 16 to 20 weeks. Condylar bone mineral density, bone mineral content and bone volume were evaluated weekly with microcomputed tomography. Histological and immunohistochemical staining for matrix metalloproteinases-13 was performed at 20 weeks. RESULTS: At 20 weeks, the mono-iodoacetate + low-intensity pulsed ultrasound group showed significantly higher bone mineral density, bone mineral content and bone volume than the mono-iodoacetate group; however, these values remained lower than those in the other two groups. On histological and immunohistochemical analysis, the chondrocytes were increased, and fewer matrix metalloproteinases-13 immunopositive cells were identified in the mono-iodoacetate + low-intensity pulsed ultrasound group than mono-iodoacetate group. CONCLUSIONS: Low-intensity pulsed ultrasound for 2 weeks may have therapeutic potential for treating temporomandibular joint osteoarthritis lesions.

Risk factors contributing to the development of neutropenia in patients receiving oral trifluridine-tipiracil (TAS-102) chemotherapy for advanced/recurrent colorectal cancer.

Elucidating the factors influencing severe neutropenia could aid in earlier management of neutropenia during oral trifluridine-tipiracil (TAS-102) chemotherapy in advanced and recurrent colorectal cancer (CRC). This study was conducted to assess the risk of TAS-102-induced grade 3 or more neutropenia. Between August 2014 and July 2017, 60 patients underwent oral TAS-102 monotherapy at Ogaki Municipal Hospital, Japan. The patients were divided into two groups based on the development of grade 3 or more neutropenia (9 patients) or not (51 patients). Risk factors for grade 3 or more neutropenia were examined by univariate and multivariate analyses. Creatinine clearance rate (CrCl) before TAS-102 administration significantly correlated with the incidence of Grade 3 or more neutropenia after TAS-102 administration (odds ratio 6.5, 95% confidence interval 1.14-30.00; p = 0.02). Multivariate analysis revealed that a CrCl of lower than 57.1 mL/min before TAS-102 administration (odds ratio 54.06, 95% confidence interval 2.14-1364.2; p = 0.02) was an independent risk factor significantly contributing to the development of grade 3 or more neutropenia, induced by TAS-102. CrCl < 57.1 mL/min in patients with advanced and recurrent CRC who underwent TAS-102 chemotherapy was associated with grade 3 or more neutropenia.

Fgfr2 is integral for bladder mesenchyme patterning and function.

While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor 2 (Fgfr2) is necessary for kidney and ureter mesenchymal development. Our objective was to determine the role of Fgfr2 in bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in bladder mesenchyme (Fgfr2BM-/-). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblotting, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with controls, embryonic (E) day 16.5 (E16.5) Fgfr2BM-/- bladders have thin muscle layers with reduced α-smooth muscle actin levels and thickened lamina propria with increased collagen expression that intrudes into muscle. From postnatal (P) day 1 (P1) to P30, Fgfr2BM-/- bladders demonstrate progressive muscle loss and increased collagen expression. Postnatal Fgfr2BM-/- bladder sheets exhibit decreased contractility and increased passive stretch tension compared with controls. In vivo cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2BM-/- bladders compared with controls. Mechanistically, while Shh expression appears normal, mRNA and protein readouts of hedgehog activity are increased in E16.5 Fgfr2BM-/- bladders compared with controls. Moreover, E16.5Fgfr2BM-/- bladders exhibit higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, than controls. Fgfr2 is critical for bladder mesenchyme patterning by virtue of its role in modulation of hedgehog signaling.

MRI depiction and 3D visualization of three anterior cruciate ligament bundles.

The anterior cruciate ligament (ACL) is divided into three fiber bundles (AM-M: anteromedial-medial, AM-L: anteromedial-lateral, PL: posterolateral). We attempted to depict the three bundles of the human ACL on MRI images and to obtain 3-dimensional visualization of them. Twenty-four knees of healthy volunteers (14 males, 10 females) were scanned by 3T-MRI using the fat suppression 3D coherent oscillatory state acquisition for the manipulation of imaging contrast (FS 3D-COSMIC). The scanned images were reconstructed after the isotropic voxel data, which allows the images to be reconstructed in any plane, was acquired. We conducted statistical examination on the identification rate of the three ACL bundles by 2D planes. Segmentation and 3D visualization of the fiber bundles using volume rendering were performed. The triple-bundle ACL was best depicted in the oblique axial plane. While the AM-M and AM-L bundles were clearly depicted in all cases, the PL bundle was not clearly visualized in two knees (8%). Therefore, the three ACL bundles were depicted in 22 knees (92%). The results of 3D visualization of the fiber arrangement agreed well with macroscopic findings of previous anatomical studies. 3T-MRI and the isotropic voxel data from FS 3D-COSMIC made it possible to demonstrate the identifiable depiction of three ACL bundles in nearly all cases. 3D visualization of the bundles could be a useful tool to understand the ACL fiber arrangement. Clin. Anat. 30:276-283, 2017. 2016 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.

A novel intranuclear RNA vector system for long-term stem cell modification.

Genetically modified stem and progenitor cells have emerged as a promising regenerative platform in the treatment of genetic and degenerative disorders, highlighted by their successful therapeutic use in inherent immunodeficiencies. However, biosafety concerns over insertional mutagenesis resulting from integrating recombinant viral vectors have overshadowed the widespread clinical applications of genetically modified stem cells. Here, we report an RNA-based episomal vector system, amenable for long-term transgene expression in stem cells. Specifically, we used a unique intranuclear RNA virus, borna disease virus (BDV), as the gene transfer vehicle, capable of persistent infections in various cell types. BDV-based vectors allowed for long-term transgene expression in mesenchymal stem cells (MSCs) without affecting cellular morphology, cell surface CD105 expression or the adipogenicity of MSCs. Similarly, replication-defective BDV vectors achieved long-term transduction of human induced pluripotent stem cells, while maintaining the ability to differentiate into three embryonic germ layers. Thus, the BDV-based vectors offer a genomic modification-free, episomal RNA delivery system for sustained stem cell transduction.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

ß-Cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection.

Protection of ß cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here we employed ß-cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to overexpress an artificial PDL1-CTLA4Ig polyprotein or interleukin 10 (IL10). ß-Cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved ß-cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received major histocompatibility complex (MHC)-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus the present study demonstrates the potent immuno-suppressive effects of ß-cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity.

Fgfr2 is integral for bladder mesenchyme patterning and function.

While urothelial signals, including sonic hedgehog (Shh), drive bladder mesenchyme differentiation, it is unclear which pathways within the mesenchyme are critical for its development. Studies have shown that fibroblast growth factor receptor (Fgfr)2 is necessary for kidney and ureter mesenchymal development. The objective of the present study was to determine the role of Fgfr2 in the bladder mesenchyme. We used Tbx18cre mice to delete Fgfr2 in the bladder mesenchyme (Fgfr2(BM-/-)). We performed three-dimensional reconstructions, quantitative real-time PCR, in situ hybridization, immunolabeling, ELISAs, immunoblot analysis, void stain on paper, ex vivo bladder sheet assays, and in vivo decerebrated cystometry. Compared with control bladders, embryonic day 16.5 (E16.5) Fgfr2(BM-/-) bladders had thin muscle layers with less α-smooth muscle actin and thickened lamina propria with increased collagen type Ia and IIIa that intruded into the muscle. The reciprocal changes in mutant layer thicknesses appeared partly due to a cell fate switch. From postnatal days 1 to 30, Fgfr2(BM-/-) bladders demonstrated progressive muscle loss and increased collagen expression. Postnatal Fgfr2(BM-/-) bladder sheets exhibited decreased agonist-mediated contractility and increased passive stretch tension versus control bladder sheets. Cystometry revealed high baseline and threshold pressures and shortened intercontractile intervals in Fgfr2(BM-/-) versus control bladders. Mechanistically, whereas Shh expression appeared normal, mRNA and protein readouts of hedgehog activity were increased in E16.5 Fgfr2(BM-/-) versus control bladders. Moreover, E16.5 Fgfr2(BM-/-) bladders exhibited higher levels of Cdo and Boc, hedgehog coreceptors that enhance sensitivity to Shh, compared with control bladders. In conclusion, loss of Fgfr2 in the bladder mesenchyme leads to abnormal bladder morphology and decreased compliance and contractility.

Efficacy and Safety of Lixisenatide in Japanese Patients with Type 2 Diabetes Insufficiently Controlled with Basal Insulin±Sulfonylurea: A Subanalysis of the GetGoal-L-Asia Study.

The aim of the study was to evaluate the efficacy and safety of once-daily lixisenatide 20 µg as add-on to basal insulin with or without sulfonylurea in Asian patients with type 2 diabetes mellitus. The study as a subanalysis of the 159 Japanese patients from the 24-week double-blind GetGoal-L-Asia study (NCT00866658) who received once-daily lixisenatide or placebo. The primary endpoint was change from baseline in HbA1c evaluated using analysis of covariance. Once-daily lixisenatide significantly reduced mean HbA1c [least squares mean difference vs. placebo - 1.1% (- 12 mmol/mol); p<0.0001]. Significantly more patients in the lixisenatide group reached HbA1c targets of < 7% (53 mmol/mol; 31.4 vs. 2.3% for placebo; p<0.0001) and ≤ 6.5% (48 mmol/mol; 12.9 vs. 1.2% for placebo; p=0.0028). Lixisenatide significantly reduced 2-h postprandial plasma glucose (least squares mean difference vs. placebo-8.64 mmol/l; p<0.0001), glucose excursion (least squares mean difference vs. placebo - 7.80 mmol/l; p<0.0001) and fasting plasma glucose (least squares mean difference vs. placebo - 0.96 mmol/l; p=0.0126). Body weight was reduced with lixisenatide but with no significant difference vs. placebo. Gastrointestinal adverse events were more frequent with lixisenatide (61.1 vs. 11.5% for placebo) but were generally transient and mild-to-moderate in intensity. The incidence of symptomatic hypoglycemia was 39.0 vs. 13.5% in patients receiving sulfonylureas and 32.3 vs. 22.9% in those not receiving sulfonylureas, for lixisenatide and placebo, respectively. In Japanese patients with type 2 diabetes mellitus, once-daily lixisenatide was well tolerated and led to significant and clinically relevant improvement in glycemic control, with a pronounced effect on postprandial plasma glucose.

Role of valence fluctuations in the superconductivity of Ce122 compounds.

Pressure dependence of the Ce valence in CeCu(2)Ge(2) has been measured up to 24 GPa at 300 K and to 17 GPa at 18-20 K using x-ray absorption spectroscopy in the partial fluorescence yield. A smooth increase of the Ce valence with pressure is observed across the two superconducting (SC) regions without any noticeable irregularity. The chemical pressure dependence of the Ce valence was also measured in Ce(Cu(1-x)Ni(x))(2)Si(2) at 20 K. A very weak, monotonic increase of the valence with x was observed, without any significant change in the two SC regions. Within experimental uncertainties, our results show no evidence for the valence transition with an abrupt change in the valence state near the SC II region, challenging the valence-fluctuation mediated superconductivity model in these compounds at high pressure and low temperature.

Characteristic RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar ataxia type 36 (Asidan).

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 36 (SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and (GGCCUG)n repeat RNA foci were detected. METHODS: Hematoxylin and eosin staining, immunohistochemical staining, as well as fluorescence in situ hybridization were used to investigate the cytoplasmic inclusions of ubiquitin and p62 and the (GGCCUG)n repeat RNA foci. RESULTS: The present study showed both ubiquitin- and p62-positive inclusions in the cytoplasm of the inferior olivary nucleus of the Asidan patient, (GGCCUG)n RNA foci in neuronal nuclei of the cerebrum, cerebellum, inferior olive, spinal cord and temporal muscle, and three types of RNA foci, i.e. single small, multiple small and giant. Of interest is that the giant RNA foci, nearly 10 µm in diameter, that were detected in Purkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of Asidan. CONCLUSIONS: The present study is the first report to show neuronal cytoplasmic inclusion bodies and giant RNA foci in an Asidan patient. The relationships between the giant RNA foci and neurodegeneration have yet to be studied.

Relationship between CT features and high preoperative serum carcinoembryonic antigen levels in early-stage lung adenocarcinoma.

AIM: To assess the relationship between thin-section computed tomography (CT) features of primary tumour and high preoperative serum carcinoembryonic antigen (CEA) levels that reportedly suggest poor prognoses in early-stage lung adenocarcinoma. MATERIALS AND METHODS: Two hundred and seventy-five consecutive patients who underwent resection of pathological stage I (T1-2aN0M0) adenocarcinomas with a maximum diameter of ≤ 3 cm (144 men, 131 women; mean age 67.8 years) were enrolled. CT features of the primary tumours and clinical characteristics of these patients were statistically evaluated to identify the factors associated with high serum CEA levels (>5 ng/ml). RESULTS: Eighty-one patients (29.5%) had high serum CEA levels. In univariate analysis, lower ground-glass opacity ratio (p < 0.001), lower tumour shadow disappearance rate (TDR: the ratio of tumour area in mediastinal window to that of lung window, p < 0.001), presence of notch (p = 0.015), and coexistence with bullae or honeycomb cysts (p < 0.001) were observed more frequently in the group with high serum CEA levels than that of the group with normal levels. TDR [odds ratio (OR) 0.984; 95% confidence interval (CI): 0.976-0.993; p < 0.001] and coexistence with bullae or honeycomb cysts (OR = 3.08; 95% CI: 1.55-6.12; p = 0.001) remained significant, even after adjusting patients' age, gender, and smoking status. CONCLUSIONS: Adenocarcinomas with lower TDR and coexisting with bullae or honeycomb cysts are associated with high preoperative serum CEA levels. Although some CEA elevations may be due to benign pulmonary diseases, such tumours are suspected to have poor prognoses, even for early-stage diseases.

Association between low MCV in early pregnancy and perinatal mental health in the Japan Environment and Children's Study and the possible effect of iron deficiency.

BACKGROUND: Postpartum anemia and iron deficiency are associated with postpartum depression. This study investigated the association between a low mean corpuscular volume (MCV) without anemia (which implies early-stage iron deficiency) in early pregnancy and perinatal mental health outcomes. METHODS: The fixed data from the Japan Environment and Children's Study (JECS), a Japanese nationwide birth cohort, were used. Perinatal mental health was assessed using the Kessler 6-item psychological distress scale (K6) in mid-pregnancy and the Edinburgh Postnatal Depression Scale (EPDS) at 1- and 6-months postpartum. RESULTS: Among the 3635 women with MCVs <85 fL in early pregnancy, the proportions of women with K6 scores ≥13 in mid-pregnancy and EPDS scores ≥9 at 1- and 6-months postpartum were 2.7 %, 12.8 %, and 9.9 %, respectively, compared with the 33,242 women with MCVs ≥85 fL at 1.9 %, 11.9 %, and 9.0 %, respectively. Multivariate logistic regression models showed that an MCV <85 in early pregnancy was associated with a K6 score ≥ 13 in mid-pregnancy and an EPDS score ≥ 9 at 1- and 6-months postpartum (adjusted odds ratio (95 % confidence interval): 1.48 (1.16-1.87), 1.14 (1.01-1.28), and 1.09 (0.95-1.24), respectively). LIMITATIONS: Low MCV values do not necessarily represent iron deficiency. Ferritin, currently the best indicator of iron deficiency, was not measured in the JECS. CONCLUSIONS: This study results suggest that a low MCV without anemia in early pregnancy is associated with a slightly increased risk of perinatal mental health deterioration.

Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair.

BACKGROUND: In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair. METHODS: Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay. RESULTS: Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I-γH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency. CONCLUSION: These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell-cycle control as well as HR pathway.

Complete remission of recurrent and refractory ovarian cancers using weekly administration of bevacizumab and gemcitabine/oxaliplatin: report of two cases.

BACKGROUND: A combination therapy with gemcitabine and oxaliplatin (GEMOX) yielded a moderate activity in platinum-resistant ovarian cancers; however, frequent severe toxicities, such as thrombocytopenia and neurotoxicity, were observed. A certain modification of schedule might therefore facilitate the clinical application of the regimen. The authors report two cases that achieved complete response to a weekly administration of bevacizumab and GEMOX. MATERIALS AND METHODS: Two patients with platinum-resistant recurrent ovarian cancers received a weekly regimen of GEMOX with bevacizumab: 2 mg/kg of bevacizumab, 300 mg/m2 of gemcitabine, and 30 mg/m2 of oxaliplatin, three weeks on and one week off, Q4 weeks. Complete remission was observed after three to four courses of therapy. Hematologic and non-hematologic toxicities more than grade 2 were not observed during chemotherapy. The patients are now without tumor progression more than 12 months after initiation of therapy. CONCLUSION: Weekly administration of bevacizumab and GEMOX had potential activity in recurrent and refractory ovarian carcinomas. These findings warrant necessity of further trial in such clinical settings.

Bilateral papillary renal cell carcinoma and angiomyolipoma in the patients with autosomal dominant polycystic kidney disease: case report of two cases and literature review.

We herein report two rare cases of bilateral renal neoplasms associated with autosomal dominant polycystic kidney disease (ADPKD). Case 1: Bilateral nephrectomy was performed on bilateral renal masses in a 58-year-old man with ADPKD. Case 2: Bilateral nephrectomy was performed on bilateral renal masses in a 32-year-old man with clinically suspected ADPKD. In case 1, angiomyolipoma (AML) and papillary renal cell carcinoma (PRCC) (type 1) were detected in the bilateral kidneys. In case 2, PRCC (type 1) was detected in the bilateral kidneys.