다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.

https://science.sciencemag.org/content/sci/279/5350/577.full.pdf

Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.

Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains and losses, including ETS gene family fusions, PTEN loss and androgen receptor (AR) amplification, which drive prostate cancer development and progression to lethal, metastatic castration-resistant prostate cancer (CRPC). However, less is known about the role of mutations. Here we sequenced the exomes of 50 lethal, heavily pre-treated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment-naive, high-grade localized prostate cancers. We identified low overall mutation rates even in heavily treated CRPCs (2.00 per megabase) and confirmed the monoclonal origin of lethal CRPC. Integrating exome copy number analysis identified disruptions of CHD1 that define a subtype of ETS gene family fusion-negative prostate cancer. Similarly, we demonstrate that ETS2, which is deleted in approximately one-third of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation. Furthermore, we identified recurrent mutations in multiple chromatin- and histone-modifying genes, including MLL2 (mutated in 8.6% of prostate cancers), and demonstrate interaction of the MLL complex with the AR, which is required for AR-mediated signalling. We also identified novel recurrent mutations in the AR collaborating factor FOXA1, which is mutated in 5 of 147 (3.4%) prostate cancers (both untreated localized prostate cancer and CRPC), and showed that mutated FOXA1 represses androgen signalling and increases tumour growth. Proteins that physically interact with the AR, such as the ERG gene fusion product, FOXA1, MLL2, UTX (also known as KDM6A) and ASXL1 were found to be mutated in CRPC. In summary, we describe the mutational landscape of a heavily treated metastatic cancer, identify novel mechanisms of AR signalling deregulated in prostate cancer, and prioritize candidates for future study.

The mutational landscape of lethal castration-resistant prostate cancer

This article explores the social theory and consequent methodology that underpins studies of transnational migration. First, we propose a social field approach to the study of migration and distinguish between ways of being and ways of belonging in that field. Second, we argue that assimilation and enduring transnational ties are neither incompatible nor binary opposites. Third, we highlight social processes and institutions that are routinely obscured by traditional migration scholarship but that become clear when we use a transnational lens. Finally, we locate our approach to migration research within a larger intellectual project, taken up by scholars of transnational processes in many fields, to rethink and reformulate the concept of society such that it is no longer automatically equated with the boundaries of a single nationstate. Social scientists have long been interested in how immigrants are incorporated into new countries. In Germany and France, scholars’ expectations that foreigners will assimilate is a central piece of public policy. In the United States, immigration scholars initially argued that to move up the socioeconomic ladder, immigrants would have to abandon their unique customs, language, values, and homeland ties and identities. Even when remaining ethnic became more acceptable, most researchers assumed that the importance of homeland ties would eventually fade. To be Italian American or Irish American would ultimately reflect ethnic pride within a multicultural United States rather than enduring relations to an ancestral land. Now scholars increasingly recognize that some migrants and their descendants remain strongly influenced by their continuing ties to their home country or by social networks that stretch across national borders. They see

/pdf/conceptualizing-simultaneity-a-transnational-social-field-1g8zn87miw.pdf

Conceptualizing simultaneity: a transnational social field perspective on society

This article explores the social theory and consequent methodology that underpins studies of transnational migration. First, we propose a social field approach to the study of migration and distinguish between ways of being and ways of belonging in that field. Second, we argue that assimilation and enduring transnational ties are neither incompatible nor binary opposites. Third, we highlight social processes and institutions that are routinely obscured by traditional migration scholarship but that become clear when we use a transnational lens. Finally, we locate our approach to migration research within a larger intellectual project, taken up by scholars of transnational processes in many fields, to rethink and reformulate the concept of society such that it is no longer automatically equated with the boundaries of a single nation-state.

Conceptualizing Simultaneity : A Transnational Social Field Perspective on Society

Mp24-15 thermotherapy with magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model

[Endocrinological studies on pathogenesis of urolithiasis. IV. Pathophysiological studies in hypercalciuric stone formers: use of a calcium restricted test and an oral calcium tolerance test (author's transl)].

A 1-year-old boy was referred to us because of abnormal external genitalia; that is, his penis was kinked toward the perineal region. We diagnosed hypospadias. Chromosomal examination was performed on

Detection of sex-determining region in a male with chromosomal abnormality (46,X+mar) and hypospadias.

Many drugs have been used in the treatment of renal colic, but the safest and most effective drug has not yet been clearly defined. A questionnaire was used to collate the types of treatment for renal colic used by Japanese urologists. The main treatments were nonsteroidal analgesic (suppository) and anticholinergic agent. A new protocol was developed on the basis of this result, and its effect on renal colic was verified. The combination of an injection of a local anesthetic and pointillage was found to be superior to non-steroidal analgesic anti-inflammatory drugs and anticholinergic agent in terms of both duration of action and effectiveness.

Optimal treatment of urolithiasis pain

Study Type – Aetiology (individual cohort)



Level of Evidence 2b



What's known on the subject? and What does the study add?



Recent studies have implicated the involvement of various genes in early genital tubercle outgrowth and urethral development However the previous studies have never focused on preputial development in hypospadias



We have developed a rat model of hypospadias, showing proximal hypospadias in 100% of offspring We analyzed 20 500 genes of foetal penis from a rat model We identified one gene, prolactin-induced protein (Pip) This gene had never been reported about the correlation with penile development We first demonstrated the association of PIP with preputial development of rat and also human



OBJECTIVE

• 
To investigate the molecular aetiology of hypospadias during a critical developmental period by identifying differentially regulated genes in the tissues of individuals with hypospadias and comparing these genes with similar genes in the tissues of control individuals





MATERIALS AND METHODS

• 
Pregnant Sprague–Dawley rats were administered flutamide (75 mg) on gestational days 15–17 to produce hypospadiac pups Dams were killed on gestational day 17, and the genital tubercles (GTs) of male pups were harvested

• 
Gene expression of RNA isolated from the GTs was analysed using an oligonucleotide microarray containing 20 500 genes The results of microarray analysis were confirmed using quantitative real-time PCR (qPCR) Protein expression levels were studied using Western blot analysis

• 
The distribution of genes associated with GT development in rats was histologically examined

• 
Prepuces harvested from patients with hypospadias and phimosis were immunohistochemically examined for gene distribution





RESULTS

• 
Of the 20 500 genes, 23 annotated genes, including prolactin-induced protein (Pip), in the GTs of the hypospadiac rats were expressed at levels less than half of that of similar genes in the GTs of the control rats

• 
Findings from qPCR and Western blot analysis revealed significantly lower Pip/PIP expression in the GTs of the hypospadiac rats than in those of the control rats

• 
Immunohistochemical analysis revealed PIP expression in the prepuces of the GTs of the control and hypospadiac rats

• 
PIP was expressed in the human prepuces of the patients with hypospadias and phimosis





CONCLUSIONS

• 
Pip/PIP, expressed at low levels in the GTs of hypospadiac rats, may be associated with preputial development This model can be useful to elucidate the molecular mechanisms underlying penile and urethral development as well as preputial development

• 
Further studies should provide detailed information regarding the molecular aetiology of hypospadias

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-410X.2011.10467.x

Association of prolactin‐induced protein with preputial development of hypospadias

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