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Introduction Refractory fistulas of the bladder are not rare, but they can rarely be closed naturally. Bladder fistulas can be treated in various ways. We report the case of an old woman who had a refractory fistula of the bladder that was able to be repaired with transurethral cystoscopic injection of N-butyl-2-cyanoacrylate. Case presentation For decades after being treated for cervical cancer in 1970s, the woman frequently suffered from fevers. A computed tomography scan showed pelvic abscess at the left side of her bladder, and cystography showed urine leakage at the wall. Thus, we diagnosed her with a pelvic abscess due to a bladder fistula after radiation. Then, we treated her with drainage, antibiotic agents, and N-butyl-2-cyanoacrylate. After that, she no longer had fevers, and cystography showed no leakage of urine. Conclusion This result indicates transurethral cystoscopic injection of N-butyl-2-cyanoacrylate may treat bladder fistulas safely, minimally invasively, and quickly.

Most human malignant tumor cells arise from epithelial tissues, which show distinctive characteristics, such as polarization, cell-to-cell contact between neighboring cells, and anchoring to a basement membrane. When tumor cells invaginate into the stroma, the cells are exposed to extracellular environments, including the extracellular matrix (ECM). Increased ECM stiffness has been reported to promote cellular biological activities, such as excessive cellular growth and enhanced migration capability. Therefore, tumorous ECM stiffness is not only an important clinical tumor feature but also plays a pivotal role in tumor cell behavior. Transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable nonselective cation channel, has been reported to be mechano-sensitive and to regulate tumorigenesis, but the underlying molecular mechanism in tumorigenesis remains unclear. The function of TRPV4 in oral squamous cell carcinoma (OSCC) is also unknown. The current study was conducted to investigate whether or not TRPV4 might be involved in OSCC tumorigenesis. TRPV4 mRNA levels were elevated in OSCC cell lines compared with normal oral epithelial cells, and its expression was required for TRPV4 agonist-dependent Ca2+ entry. TRPV4-depleted tumor cells exhibited decreased proliferation capabilities in three-dimensional culture but not in a low-attachment plastic dish. A xenograft tumor model demonstrated that TRPV4 expression was involved in cancer cell proliferation in vivo. Furthermore, loss-of-function experiments using siRNA or an inhibitor revealed that the TRPV4 expression was required for CaMKII-mediated AKT activation. Immunohistochemical analyses of tissue specimens obtained from 36 OSCC patients showed that TRPV4 was weakly observed in non-tumor regions but was strongly expressed in tumor lesions at high frequencies where phosphorylated AKT expression was frequently detected. These results suggest that the TRPV4/CaMKII/AKT axis, which might be activated by extracellular environments, promotes OSCC tumor cell growth.

Introduction Pneumatosis cystoides intestinalis is a rare condition characterized by air-filled cysts within intestinal walls. It can be caused by various factors. We report a case of pneumatosis cystoides intestinalis linked to sunitinib treatment for renal cell carcinoma. Case presentation A 67-year-old female with advanced renal cell carcinoma who had been treated with sunitinib visited our hospital complaining of abdominal pain. Computed tomography scans showed diffuse air-filled cystic formation of intestine. We treated with conservative therapy, and she recovered. However, although air-filled cysts disappeared in the images, intraoperative findings in the resection of a recurrent paracaval lymph node showed a thinning of the intestine. Conclusion It is necessary to consider pneumatosis cystoides intestinalis when a patient using a tyrosine kinase inhibitor complains of abdominal symptoms. It should also be noted that the effect of pneumatosis cystoides intestinalis may remain even if pneumatosis disappears from the image on tomography scans.

Introduction: The aim of our present study was to investigate the impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) on the antitumour effects of targeted agents in patients with metastatic renal cell carcinoma (mRCC).Methods: The NLRs in 283 cases of molecular targeted therapy for mRCC were measured before starting the prescription of the molecular targeted agent. The significance of pretreatment NLR on the site of metastatic organs and on progression-free survival (PFS)in each case was analyzed.Results: Metastases other than lung, which is defined as “extrapulmonary metastasis,” were observed in 190 cases (67.1%). The median of pretreated NLR was 2.39 (0.49‒68.7). In 97 of the 283 cases,pretreated NLR was 3.0 or higher. These cases were categorized as the high NLR group and the rest as the low NLR group. When the cases with extrapulmonary metastasis were investigated and classifiedbased on their pretreated NLR, 50% PFS in the high NLR and low NLR groups was 6.7 months and 12 months (p=0.0001), respectively. Multivariate analysis revealed that high NLR (>3.0) was an independent predictive factor for PFS in the cases with extrapulmonary metastasis (hazard ratio 2.762; p

Prostate cancer, one of the most common malignant tumors among men, is closely associated with obesity and, thus far, several studies have suggested the association between obesity and aggressive pathological characteristics in the United States. However, the effect of obesity on prostate cancer mortality is controversial, and it remains unclear whether obesity contributes to the aggressiveness of prostate cancer in Asian patients. The aim of the present study was to investigate the association between body mass index (BMI) and the clinicopathological characteristics of prostate cancer in 2,003 Japanese patients who underwent radical prostatectomy. There was a significant association between higher BMI and higher Gleason score (GS). The multivariate analysis also revealed that BMI was an independent indicator for GS ≥8 at surgery. Moreover, among patients with lower prostate-specific antigen levels, biochemical recurrence-free survival was significantly worse in those with higher BMI. These results suggest that BMI may be a classifier for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy in Japanese patients.

The loading caused by occlusion and mastication plays an important role in maintaining periodontal ligament (PDL) tissues. We hypothesized that a loading magnitude would be involved in the production of biological factors that function in the maintenance of PDL tissues. Here, we identified up-regulated gene expressions of transforming growth factor-β1 (TGF-β1), alkaline phosphatase (ALP), and angiotensinogen in human PDL fibroblastic cells (HPLFs) that were exposed to 8% stretch loading. Immunolocalization of angiotensin I/II (Ang I/II), which was converted from angiotensinogen, was detected in rat PDL tissues. HPLFs that were stimulated by Ang II also increased their gene expressions of TGF-β1 and ALP. Furthermore, the antagonist for Ang II type 2 receptor, rather than for type 1, significantly inhibited gene expressions induced by the stretch loading. Analysis of these data suggests that Ang II mediates the loading signal in stretched HPLFs to induce expressions of TGF-β1 and ALP.

Periodontal ligament stem cells (PDLSCs) have recently been proposed as a novel option in periodontal regenerative therapy. However, one of the issues is the difficulty of stably generating PDLSCs because of the variation of stem cell potential between donors. Here, we show that Semaphorin 3A (Sema3A) can induce mesenchymal-stem-like properties in human periodontal ligament (PDL) cells. Sema3A expression was specifically observed in the dental follicle during tooth development and in parts of mature PDL tissue in rodent tooth and periodontal tissue. Sema3A expression levels were found to be higher in multipotential human PDL cell clones compared with low-differentiation potential clones. Sema3A-overexpressing PDL cells exhibited an enhanced capacity to differentiate into both functional osteoblasts and adipocytes. Moreover, PDL cells treated with Sema3A only at the initiation of culture stimulated osteogenesis, while Sema3A treatment throughout the culture had no effect on osteogenic differentiation. Finally, Sema3A-overexpressing PDL cells upregulated the expression of embryonic stem cell markers (NANOG, OCT4, and E-cadherin) and mesenchymal stem cell markers (CD73, CD90, CD105, CD146, and CD166), and Sema3A promoted cell division activity of PDL cells. These results suggest that Sema3A may possess the function to convert PDL cells into mesenchymal-stem-like cells. Refereed/Peer-reviewed

Millions of people experience consequential tooth loss related to irretrievable damage of the periodontium caused by deep caries, severe periodontal diseases or irreversible trauma, resulting in a decreased quality of life. Hence, dental scientists have focused much attention on tissue engineering techniques in an effort to address this condition. The periodontium is composed mainly of two soft tissues and two hard tissues; the former includes the periodontal ligament (PDL) tissue and gingival tissue, and the latter includes alveolar bone and cementum covering the tooth root. In particular, PDL is a dynamic connective tissue that is subjected to continual adaptation to maintain tissue size and width, as well as structural integrity, including fibers and bone modeling. The main role of PDL is to anchor the tooth root to the alveolar bone socket tightly, cushioning mechanical load that proceeds from mastication. Thus, PDL tissue constitutes the bedrock of periodontium to determine the life-span of tooth. In this chapter, we describe the phenotypes of multipotent clonal human PDL progenitor/stem cell lines that we have recently established, and present a comparison with PDL stem cells (PDLSCs). PDLSCs represent typical properties of bone marrow-derived mesenchymal stem cells (BMMSCs). PDLSCs exhibit a self-renewing capacity and express cell surface markers similar to BMMSCs. PDLSCs also possess the multipotential to differentiate into various types of cells, such as osteoblast-like cells, adipocytes, chondrocytes and neurocytes, in vitro. Additionally, PDLSCs represent a distinctive potential to form cementumand PDL-like tissues in vivo, suggesting that PDLSCs might belong to a unique population of somatic stem cells. Since a very small number of stem cells are included in PDL tissue, researchers have tried to establish immortalized PDL stem cell lines for the convenience and consistency of analyses. Recently, we succeeded in establishing two clonal human PDL cell lines with multipotential by transduction with Simian Virus (SV) 40 large T-antigen and human telomerase reverse transcriptase. These clonal cell lines exhibited unique characteristics: cell line 1-11 demonstrated osteoblastic and adipocytic differentiation capabilities, and cell line 1-17 exhibited the potential to differentiate into osteoblasts, adipocytes, chondrocytes and neurocytes. Flow cytometric analysis demonstrated that the percentage of cells expressing BMMSC markers was very high in both cell lines. On the other hand, cell line 1-17 expressed embryonic stem (ES) cell marker genes at higher levels, compared with cell line 1-11. Furthermore, both cell lines expressed PDL phenotype-related molecules at equivalent levels while BMMSCs showed little expression. When transplanted into PDL defects formed

Male sex drive rhythm (MSDR) in Drosophila is a circadian behavior only observed in the social context of male-female pairs. In the presence of a female, males exhibit long periods of courtship activity with a pronounced rest phase at dusk, although isolated males exhibit an activity peak at dusk. The molecular mechanisms regulating the switch between these activity patterns are unknown. Here, we genetically manipulate the molecular clock in different subsets of neurons and find that proper oscillation of the molecular clock in ventral lateral neurons is essential for MSDR. These neurons express pigment-dispersing factor, the lack of which disrupts MSDR. Furthermore, we show that a cluster of dorsal neurons (DN1s) requires the molecular clock to synchronize the trough phase at dusk in MSDR and to establish the evening peak in single fly locomotor rhythm (SLR). Finally, we provide evidence that DN1s exert their roles in MSDR and SLR via distinct signaling pathways.

SummaryIdentification of nutritious compounds is dependent on expression of specific taste receptors in appropriate taste-cell types [1]. In contrast to mammals, which rely on a single, broadly tuned heterodimeric sugar receptor [2], the Drosophila genome harbors a small subfamily of eight, closely related gustatory receptor (Gr) genes, Gr5a, Gr61a, and Gr64a–Gr64f, of which three have been proposed to mediate sweet taste [3–6]. However, expression and function of several of these putative sugar Gr genes are not known. Here, we present a comprehensive expression and functional analysis using GrLEXA/GAL4 alleles that were generated through homologous recombination. We show that sugar Gr genes are expressed in a combinatorial manner to yield at least eight sets of sweet-sensing neurons. Behavioral investigations show that most sugar Gr mutations affect taste responses to only a small number of sugars and that effective detection of most sugars is dependent on more than one Gr gene. Surprisingly, Gr64a, one of three Gr genes previously proposed to play a major role in sweet taste [3, 4], is not expressed in labellar taste neurons, and Gr64a mutant flies exhibit normal sugar responses elicited from the labellum. Our analysis provides a molecular rationale for distinct tuning profiles of sweet taste neurons, and it favors a model whereby all sugar Grs contribute to sweet taste. Furthermore, expression in olfactory organs and the brain implies novel roles for sugar Gr genes in olfaction and internal nutrient sensing, respectively. Thus, sugar receptors may contribute to feeding behavior via multiple sensory systems.