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In vivo exploration of the functional activity of the non-coding 8q24 prostate cancer risk locus

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Asian j.urnal of Andrology 2010年第6期12卷 787-789页

作者： dolores j. lamb Mounia Tannour-Louet Scott Department of Urology Baylor College of Medicine Houston TX 77030 USA Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA

Genome-wide association studies （GWAS） have successfully identified a substantial number of risk variants for prostate cancer [1-10]. In total, more than 20 single nucleotide polymorphisms （SNPs） that predispose to prostate malignancy have been found scattered throughout the genome in coding and non-coding regions. The 8q24 chromosomal region is an intriguing locus as it harbors five independent susceptibility variants （rs10086908; rs16901979; rs620861; rs6983267; rs1447295） that span a 440-kb genomic interval devoid of genes or protein-coding transcripts.

关键词： Genomes Cancer (genus) Neoplasms Variants Prostate Genes Andean region

Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana M.López-Estévez Y.Zhang María Medel Iker Arriaga Lucía Sanj.rj. Cristian Huck-Iriart Nicola G.A.Abrescia María j.Vicent Defang Ouyang dolores Torres María j.sé Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

In vitro production of functional sperm in mice

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Asian j.urnal of Andrology 2011年第6期13卷 791-792页

作者： Kathleen Hwang dolores j.lamb Scott Department of Urology Baylor College of Medicine Houston TX 77030 USA Scott Department of Urology and Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA Laboratory for Male Reproductive Research and Testing Baylor College of Medicine Houston TX 77030 USA

Spermatogenesis refers to the process by which the production and development of the spermatozoa （the mature male gamete of most sexually reproducing species） occurs. It is a complex, stepwise process of sperm development, taking more than a month depending upon the species involving three specific functional phases： spermatogonial proliferation, meiosis and metamorphosis.1 Investigators have been successful in recreating this process in some species of fish; however, this whole process has never been reproduced in vitro in mammals.

关键词： Spermatogenesis refers production the spermatozoa

Counting your sperm before they fertilize： are sperm counts really declining？

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Asian j.urnal of Andrology 2013年第2期15卷 179-183,I0004,I0005页

作者： Alexander W Pastuszak dolores j.lamb Scott Department of Urology Baylor College of Medicine Houston TX 77030 USA Center for Reproductive Medicine Baylor College of Medicine Houston TX 77030 USA Department of Molecular Cell Biology Baylor College of Medicine Houston TX 77030 USA

Apurported global decline in sperm counts has been a source of controversy since the early 1990s. Numerous studies performed since then, as well as reanalysis of the original data, show either no changes, or even increases, in sperm concentrations over time. In this review, we discuss the 1992 meta-analysis that initiated the continuing debate on whether sperm concentrations are declining, and the com- munity discussion surrounding it over the past two decades. We also highlight studies evaluating sperm concentrations performed since the initial study that produced different results, and conclude that no definitive cause for a decrease in sperm counts has been established, and the effects of geography and environment on sperm counts are unclear.

关键词： YOUNG DANISH MEN SEMEN QUALITY DECREASING QUALITY LIFE-STYLE REGIONAL DIFFERENCES GENERAL-POPULATION MALE-INFERTILITY HEALTHY-MEN FINNISH MEN AREA

The varicocele： diagnostic dilemmas, therapeutic challenges and future perspectives

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Asian j.urnal of Andrology 2016年第2期18卷 276-281,J0007页

作者： Koj. Chiba Ranj.th Ramasamy dolores j.lamb Larry I Lipshultz Center for Reproductive Medicine Baylor College of Medicine Houston TX USA Scott Department of Urology Baylor College of Medicine Houston TX USA Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA.

A varicocele is defined as the abnormal dilation of the internal testicular vein and pampiniform venus plexus within the spermatic cord. If a semen analysis is not obtained from the adolescent male, in the absence of other symptoms, the main clinical indication used by many urologists to recommend repair is testicular atrophy. The varicocele may result in testicular damage in some males causing testicular atrophy with impaired sperm production and decreased Leydig cell function, while in other males the varicocele may seemingly cause no ill effects. In adult men, varicoceles are frequently present and surgically correctable, yet the measurable benefits of surgical repair are slight according to a Cochrane review. While occurring more commonly in infertile men than fertile men, only 20% of men with a documented varicocele will suffer from fertility problems. Most varicoceles found in adolescents are detected during a routine medical examination, and it is difficult to predict which adolescent presenting with a varicocele will ultimately show diminished testicular function in adolescence or adulthood. As in adults, the mainstay of treatment for varicocele in adolescents is surgical correction. However, unlike an adult varicocelectomy （the microsurgical approach is the most common）, treatment for an adolescent varicocele is more often laparoscopic. Nevertheless, the goals of treatment are the same in the adolescent and adult patients. Controversy remains as to which patients to treat, when to initiate the treatment, and what type of treatment is the best. This review will present the current understanding of the etiology, diagnosis and treatment of the adolescent varicocele.

关键词： adolescent adult management varicocele

Recent advances in the genetics of testicular failure

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Asian j.urnal of Andrology 2016年第3期18卷 350-355页

作者： Seung-Hun Song Koj. Chiba Ranj.th Ramasamy dolores j.lamb Center for Reproductive Medicine Baylor College of Medicine Houston Texas USA Scott Department of Urology Baylor College of Medicine Houston lexas USA Department of Urology Miller School of Medicine University of Miami FL USA.

Infertility affects approximately 15% of couples, and male factor is responsible for 30%-50% of all infertility. The most severe form of male infertility is testicular failure, and the typical phenotype of testicular failure is severely impaired spermatogenesis resulting in azoospermia or severe oligozoospermia. Although the etiology of testicular failure remains poorly understood, genetic factor typically is an underlying cause. Modern assisted reproductive techniques have revolutionized the treatment of male factor infertility, allowing biological fatherhood to be achieved by many men who would otherwise have been unable to become father to their children through natural conception. Therefore, identifying genetic abnormalities in male is critical because of the potential risk of transmission of genetic abnormalities to the offspring. Recently, along with other intense researches ongoing, whole-genome approaches have been used increasingly in the genetic studies of male infertility. In this review, we focus on the genetics of testicular failure and provide an update on the advances in the study of genetics of male *** affects approximately 15% of couples, and male factor is responsible for 30%-50% of all infertility. The most severe form of male infertility is testicular failure, and the typical phenotype of testicular failure is severely impaired spermatogenesis resulting in azoospermia or severe oligozoospermia. Although the etiology of testicular failure remains poorly understood, genetic factor typically is an underlying cause. Modern assisted reproductive techniques have revolutionized the treatment of male factor infertility, allowing biological fatherhood to be achieved by many men who would otherwise have been unable to become father to their children through natural conception. Therefore, identifying genetic abnormalities in male is critical because of the potential risk of transmission of genetic abnormalities to the offspring. Recentl

关键词： azoospermia genetics male infertility testicular failure

Sperm counts and sperm sex ratio in male infertility patients

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Asian j.urnal of Andrology 2012年第5期14卷 683-686页

作者： Michael L Eisenberg Lata Murthy Kathleen Hwang dolores j.lamb Larry I Lipshultz Department of Urology Stanford University School of Medicine Stanford CA 94305 USA Scott Department of Urology Baylor College of Medicine Houston TX 77030 USA Department of Urology Brown University Providence RI 02912 USA

In recent years, investigators have noted a trend toward a declining proportion of male births in many industrialized nations. While men bear the sex-determining chromosome, the role of the female partner as it pertains to fertilization or miscarriage may also alter the gender ratio. We attempted to determine a man＇s secondary sex ratio （F1 generation） by directly examining the sex chromosomes of his sperm. We examined our male infertility clinic database for all men who had undergone a semen fluorescence in situ hybridization （FISH）. Patient demographic and semen parameters were recorded. Chi-squared analysis was used to compare gender ratios （Y chromosomes/total chromosomes）. Multivariable logistic regression was used to predict the odds of possessing a Y-bearing sperm after accounting for demographic and semen parameters. A total of 185 men underwent sperm FISH. For the entire cohort, the proportion of Y chromosome-bearing sperm was 51.5%. Men with less than five million motile sperm had a significantly lower proportion of Y chromosome-bearing sperm （50.8%） compared to men with higher sperm counts （51.6%; P= 0.02）. After multivariable adj.stment, a higher sperm concentration, total motile sperm count and semen volume significantly increased the odds of having a Y chromosome-bearing sperm （P〈0.01）. As a man＇s sperm production declines, so does the proportion of Y chromosome-bearing sperm. Thus, a man＇s reproductive potential may predict his ability to sire male offspring.

关键词： infertility sex ratio spermatogenesis sperm chromosomes

Men with a complete absence of normal sperm morphology exhibit high rates of success without assisted reproduction

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Asian j.urnal of Andrology 2017年第1期19卷 39-42页

作者： j.son R Kovac Ryan P Smith Miguel Caj.pe dolores j.lamb Larry I Lipshultz Center of Reproductive Medicine and the Department of Molecular and Cellular Biology Scott Department of Urology Baylor College of Medicine Houston TX USA Department of Urology University of Virginia Charlottesville VA USA.

In couples with infertility, abnormal strict morphology of 0% normal forms （NF） is a criterion to proceed rapidly to in vitro fertilization （IVF）. Since no data currently exist, we investigated the outcomes for men with 0% NF to determine reproductive success without the use of assisted reproductive technologies （ART）. A cohort of 24 men with 0% NF were identified （2010-2013） with 27 randomly selected men with 〉4% NF as controls. Patient charts were reviewed with men contacted and administered an Institutional Review Board （IRB）-approved telephone questionnaire to ascertain outcomes. After a median follow-up time of 2.5 years, 29.2% of men with 0% NF did not require ART for their first pregnancy （controls = 55.6%, P〈 0.05）. When all pregnancies were analyzed together, men with 0% NF achieved twenty pregnancies of which 75% did not require IVF （controls - thirty pregnancies; 76.7% did not require IVF）. The average age of men and female partners was similar between men with 0% NF and 〉4% NF. All men had normal follicle-stimulating hormone （FSH）, testosterone, prolactin, sex hormone-binding globulin （SHBG）, and estradiol. Although, global semen parameters were worse in men with 0% NF, when a first pregnancy was a natural conception （NC）, 100% of men with 0% NF （n = 7/7） and 37.5% of controls in = 3/8） went on to have a subsequent pregnancy via NC. Men with 0% NF conceived without IVF in 29.2% of cases compared to 55.6% of controls. Strict morphology should not be used to predict fertilization, pregnancy, or live birth potential. In men with 0% NF, alternative modalities should be considered before immediate IVF.

关键词： conception infertility intrauterine insemination in vitro fertilization strict morphology success

The effects of advanced paternal age on fertility

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Asian j.urnal of Andrology 2013年第6期15卷 723-728,I0005页

作者： j.son R Kovac j.sephine Addai Ryan P Smith Robert M Coward dolores j.lamb Larry I Lipshultz Scott Department of Urology Department of Molecular and Cellular Biology The Center for Reproductive Medicine Baylor College of Medicine Houston TX 77030 USA

Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.

关键词： aging male fertility outcomes male infertility paternal age