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- NEW GENRE Volume Four: Human Reproductive System, Genomic Endocrinology and Cancer Types
Original Volume Four: Human Reproductive System, Genomic Endocrinology and Cancer Types
VOLUME 4: Human Reproductive System, Genomic Endocrinology and Cancer Types
(Series D: BioMedicine & Immunology) Kindle Edition.
On Amazon.com since February 2, 2021
http://www.amazon.com/dp/B08VTFWVKM
NEW GENRE Volume Four: Human Reproductive System, Genomic Endocrinology and Cancer Types Pharmaceutics – Series D, Volume 4
This Volume has the following three parts:
PART A: The eTOCs in Spanish in Audio format
PART B: The eTOCs in Bi-lingual format: Spanish and English in Text format
PART C: The Editorials of the original e-Books in English in Audio format
PART A:
The eTOCs in Spanish in Audio format
Serie D: Libros electrónicos de Biomedicina. Metabolómica, inmunología, enfermedades infecciosas, genómica reproductiva y endocrinología
Cuarto volumen
Sistema reproductor humano,
endocrinología genómica y tipos de cáncer
Asesor de contenidos de la serie:
Director de estrategia emérito, LPBI Group
2021
Traducción en español
Prof. Stephen J. Williams, PhD, Editor
Prof. Sudipta Saha, PhD, Editor
y
Aviva Lev-Ari, PhD, RN, Editor
Fuente de la imagen: cortesía de Google Images
Disponible en Amazon.com desde el 02/02/2021
http://www.amazon.com/dp/B08VTFWVKM
UC, Berkeley, PhD’83
Redactor jefe de la serie de libros electrónicos BioMed
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
avivalev-ari@alum.berkeley.edu
Los 18 volúmenes de los expertos, autores y escritores del LPBI Group publicados en AMAZON.COM se encuentran en el catálogo de la Kindle Store sobre Medicina y ciencias de la vida
https://lnkd.in/ekWGNqA
Lista de colaboradores y enlaces a las biografías
Dr. Larry H. Bernstein, MD, FCAP, autor y redactor
1.2, 1.3, 1.6, 3.1, 3.2, 3.3, 3.4, 4.1, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.9, 6.6, 8.1, 8.2, 8.3, 8.4, 8.5, 9.1, 9.3, 9.4, 9.5 10.1, 10.2, 10.3.1.1, 10.3.1.3, 10.3.1.4, 10.3.2.7, 10.3.3.3, 10.3.4.1, 10.3.4.2, 10.3.4.3, 10.3.4.5
Prof. Stephen J. Williams, PhD, editor
Prefacio, Introducción del volumen, 4.5, Parte 10: Introducción, 10.3.2.1, 10.3.2.2, 10.3.2.9, 10.3.2.10, 10.3.3.4, Parte 10: Resumen y EPÍLOGO
Prof. Sudipta Saha, PhD, editor
Parte 1: Introducción, 1.5, 2.2, 2.3, 2.4, 4.2, 4.4, 5.8, 5.10, 5.11,
Parte 6: Introducción, 6.1, 6.2, 6.3, 6.4, 7.1, 7.2, 7.3, 7.4, 7.7, 7.8, 7.9, 7.10, 8.6, 10.3.2.3, 10.3.3.6,
Resumen del volumen
Dra. Aviva Lev-Ari, PhD, RN, editora y redactor
Introducción del volumen, 1.1, 1.4, 4.3, 4.6, 6.5, 6.7, 7.2, 7.5, 7.6, 9.2, 9.5, 10.3.1.2, 10.3.2.4, 10.3.2.5, 10.3.3.1, 10.3.3.2, 10.3.3.5, 10.3.4.2, 10.3.3.4, 10.3.4.5
Dra. Irina Robu, PhD
Parte 2, 5, 8, 9: Introducciones, 2.1, 10.3.2.8
Prof. Marcus W. Feldman, PhD
Parte 7: Introducción, 7.2
Dr. Prabodh Kandala, PhD
Parte 10: 10.3.2.6
Cuarto volumen
Sistema reproductor humano,
endocrinología genómica y tipos de cáncer
Los enlaces indicados llevan al contenido original en inglés
| MD | Licenciado/a en medicina y cirugía (Estados Unidos) |
| PhD | Doctorado/a |
| Ph.D | Doctorado/a |
| RN | Enfermero/a titulado/a (National Board of Nursing Registration) |
| FCAP | Miembro distinguido (Fellow) del Colegio de Anatomopatólogos de los Estados Unidos |
Indice de contenidos electrónico (IDCe)
PREFACIO por el Dr. Stephen J. Williams, PhD
Introducción al volumen
Las opiniones del Dr. Stephen J. Williams, PhD y de Dr. Aviva Lev-Ari, PhD, RN
Parte 1
Temas generales sobre la reproducción humana
Introducción, Dr. Sudipta Saha, PhD
1.1 Las 10 principales innovaciones médicas de 2018, 2020 y 2021 por la Cleveland Clinic
Reportero: Aviva Lev-Ari, PhD, RN
1.2 El caso Hobby Lobby
https://pharmaceuticalintelligence.com/2014/07/08/reason-in-hobby-lobby-3/
Redactor: Larry H. Bernstein, MD, FCAP
1.3 El voto particular de la jueza Ginsberg
https://pharmaceuticalintelligence.com/2014/07/08/justice-ginsberg-written-dissent/
Editor y reportero: Larry H. Bernstein, MD, FCAP
1.4 Micronutrientes, macronutrientes y patrones dietéticos: nutrición y fertilidad
Reportero: Aviva Lev-Ari, PhD, RN
1.5 El medicamento antivírico para la hepatitis B no es útil para reducir la transmisión maternofilial
Reportero y editor: Dr. Sudipta Saha, Ph.D.
1.6 Fisiopatología neonatal
https://pharmaceuticalintelligence.com/2015/02/22/neonatal-pathophysiology/
Escritor y editor: Larry H. Bernstein, MD, FCAP
Parte 2
Innovaciones en biología celular y embriología
Introducción, Dra. Irina Robu, PhD
2.1 Células madre embrionarias obtenidas de la piel
https://pharmaceuticalintelligence.com/2019/05/08/embryo-stem-cells-out-of-skin/
Reportero: Irina Robu, PhD
2.2 La técnica de los tres progenitores para evitar las enfermedades mitocondriales en el embrión
Reportero y editor: Dr. Sudipta Saha, Ph.D.
2.3 Terapia de reemplazo mitocondrial
https://pharmaceuticalintelligence.com/2019/04/14/mitochondria-replacement-therapy/
Editor y reportero: Dr. Sudipta Saha, Ph.D.
2.4 scPopCorn: un nuevo método computacional para la detección de subpoblaciones y su análisis comparativo entre experimentos con células individuales
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Parte 3
Señalización celular
3.1 Tutorial sobre la transducción de señales
https://pharmaceuticalintelligence.com/2014/08/12/signaling-transduction-tutorial/
Reportero y editor: Larry H. Bernstein, MD, FCAP
3.2 Introducción a la señalización
https://pharmaceuticalintelligence.com/2014/10/30/introduction-to-signaling/
Redactor: Larry H. Bernstein, MD, FCAP
3.3 La señalización y las vías de señalización
https://pharmaceuticalintelligence.com/2014/08/12/signaling-and-signaling-pathways/
Redactor: Larry H. Bernstein, MD, FCAP
3.4 Resumen de la señalización y las vías de señalización
https://pharmaceuticalintelligence.com/2014/11/01/summary-of-signaling-and-signaling-pathways/
Autor y redactor: Larry H Bernstein, MD, FCAP
Parte 4
La genómica en el bienestar prenatal e infantil
Introducción, Dr. Stephen J. Williams, PhD
4.1 Genes, proteomas y su interacción
https://pharmaceuticalintelligence.com/2014/07/28/genes-proteomes-and-their-interaction/
Autor y redactor: Larry H. Bernstein, MD, FCAP
4.2 El microARN en la reproducción
https://pharmaceuticalintelligence.com/2016/11/09/microrna-in-reproduction/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
4.3 Mesa redonda: la genómica de los trastornos prenatales e infantiles
Editor y reportero: Aviva Lev-Ari, PhD, RN
4.4 La función del gen saltarín (LINE1) al descubierto
Reportero y editor: Dr. Sudipta Saha, Ph.D.
4.5 Cómo revolucionará la SMP el diagnóstico reproductivo: reunión de noviembre, Boston, MA
Reportero: Stephen J. Williams, Ph.D.
4.6 Mesa redonda sobre genómica en los trastornos prenatales y de la infancia en la 10.ª Conferencia Anual de Medicina Personalizada en la Harvard Medical School, Boston, EUA, el 13/11/2014 a la 1:00 p.m.
Reportero: Aviva Lev-Ari, PhD, RN
Parte 5
Descubrimientos en endocrinología
Introducción, Dra. Irina Robu, PhD
5.1 Premio Roy O. Greep a la Investigación destacada en endocrinología
Redactor: Larry H Bernstein, MD, FCAP
5.2 El premio Fred Conrad Koch a la trayectoria profesional, el más alto honor de la Endocrine Society, reconoce los logros de toda una vida y las contribuciones excepcionales de una persona al campo de la endocrinología
Redactor: Larry H. Bernstein, MD, FCAP
5.3 Corteza suprarrenal
https://pharmaceuticalintelligence.com/2015/02/07/adrenal-cortex/
Escritor y editor: Larry H Bernstein, MD, FCAP
5.4 Hormonas sexuales
https://pharmaceuticalintelligence.com/2015/02/07/sex-hormones/
Autor: Larry H Bernstein, MD, FCAP
5.5 Función y trastornos del tiroides
https://pharmaceuticalintelligence.com/2015/02/05/thyroid-function-and-disorders/
Escritor y editor: Larry H. Bernstein, MD, FCAP
5.6 Eje neuroendocrino hipofisario
https://pharmaceuticalintelligence.com/2015/02/04/pituitary-neuroendocrine-axis/
Escritor y editor: Larry H. Bernstein, MD, FCAP
5.7 Acción endocrina en el mesencéfalo
https://pharmaceuticalintelligence.com/2015/02/12/endocrine-action-on-midbrain/
Editor y reportero: Larry H. Bernstein, MD, FCAP
5.8 Géneros redefinidos por la biología
https://pharmaceuticalintelligence.com/2018/03/10/genders-redefined-by-biology/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
5.9 Acción farmacológica de las hormonas esteroideas
https://pharmaceuticalintelligence.com/2014/10/27/pharmacological-action-of-steroid-hormones/
Redactor: Larry H. Bernstein, MD, FCAP
5.10 Cambios en los niveles de hormonas sexuales y del péptido natriurético de tipo N-terminal pro-B como biomarcador de enfermedades cardiovasculares
Reportero y editor: Dr. Sudipta Saha, Ph.D.
5.11 Productos químicos para el cuidado personal y el inicio de la pubertad
https://pharmaceuticalintelligence.com/2018/12/16/personal-care-chemicals-and-puberty-onset/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Parte 6
Fronteras de la endocrinología femenina
Introducción, Dr. Sudipta Saha, Ph.D.
6.1 Ovario artificial en lugar de la hormonoterapia de reposición convencional
Reportero y editor: Dr. Sudipta Saha, Ph.D.
6.2 La viabilidad del nivel de hormona antimülleriana (AMH) como marcador de fertilidad
Reportero y editor: Dr. Sudipta Saha, Ph.D.
6.3 El reloj del sistema inmunitario en el embarazo
https://pharmaceuticalintelligence.com/2017/09/13/the-immune-system-clock-of-pregnancy/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
6.4 Un interruptor genético para controlar el comportamiento sexual femenino
Reportero y editor: Dr. Sudipta Saha, Ph.D.
6.5 Trastorno del deseo sexual en mujeres premenopáusicas: la FDA aprueba Addyi (flibanserina), la «Viagra femenina» para aumentar la libido
Reportero: Aviva Lev-Ari, PhD
6.6 Tratamiento hormonal
https://pharmaceuticalintelligence.com/2015/05/15/hormone-therapy-9-4/
Escritor y editor: Larry H. Bernstein, MD, FCAP
6.7 Endometriosis: diagnóstico genómico en la UCSF
https://pharmaceuticalintelligence.com/2014/11/24/endometriosis-genomics-diagnosis-ucsf/
Reportero: Aviva Lev-Ari, PhD, RN
Parte 7
Función sexual masculina y fertilidad
Introducción del Dr. Marc Feldman, PhD
7.1 Tendencias en el recuento de espermatozoides
https://pharmaceuticalintelligence.com/2017/07/27/trends-in-sperm-count/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
7.2 Disminución del número de espermatozoides: epigenética, bienestar e importancia para la evolución y la demografía de las poblaciones
- Marc Feldman, opinión de un experto sobre la importancia de la disminución del número de espermatozoides en el futuro de la evolución y la demografía de la población
- Sudipta Saha, efectos de la calidad y la cantidad de los espermatozoides en la reproducción humana
- Aviva Lev-Ari, efectos psicosociales de la pobreza, el desempleo y la epigenética en el bienestar masculino; afecciones fisiológicas que afectan a la calidad y cantidad de los espermatozoides
7.3 El consumo de cannabis ha aumentado el número de espermatozoides
https://pharmaceuticalintelligence.com/2019/02/21/cannabis-smoking-showed-increased-sperm-count/
Editor y reportero: Dr. Sudipta Saha, Ph.D.
7.4 Defectos espermatogénicos en ratones con reversión sexual
https://pharmaceuticalintelligence.com/2016/02/29/spermatogenic-defects-in-sex-reversed-mice-2/
Editor y reportero: Dr. Sudipta Saha, Ph.D.
7.5 Fertilización: arquitectura proteica de la matriz acrosómica del espermatozoide; los filamentos del orgánulo de la cabeza del espermatozoide se dirigen al óvulo
Reportero: Aviva Lev-Ari, PhD, RN
7.6 Infertilidad masculina y genómica: los hombres fértiles portaban un conjunto completo de elementos de ARN del esperma; sin embargo, la mayoría de los hombres infértiles, no
Reportero: Aviva Lev-Ari, PhD, RN
7.7 El tratamiento con testosterona mejoró principalmente la función sexual, más que la deambulación o la vitalidad en los hombres mayores con niveles bajos de testosterona
Reportero y editor: Dr. Sudipta Saha, Ph.D.
7.8 Investigación prometedora para una píldora anticonceptiva masculina
https://pharmaceuticalintelligence.com/2017/03/23/promising-research-for-a-male-birth-control-pill/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
7.9 Molécula de conmutación celular para el control de la motilidad de los espermatozoides: un nuevo objetivo para la anticoncepción masculina y los tratamientos de la infertilidad
Reportero y editor: Sudipta Saha, Ph.D.
7.10 Dispositivo anticonceptivo de por vida para hombres: interruptor mecánico para controlar la fertilidad a voluntad
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Parte 8
Metabolómica y genómica del microbioma
Introducción, Dra. Irina Robu, PhD
8.1 Genómica metabólica y farmacéutica, Vol. 1 de la serie D de BioMed, disponible en la Kindle de Store de Amazon.com
http://www.amazon.com/dp/B012BB0ZF0
Autor: Larry H. Bernstein, MD, FCAP
8.2 Introducción a la metabolómica
https://pharmaceuticalintelligence.com/2014/10/21/introduction-to-metabolomics/
Autor: Larry H. Bernstein, MD, FCAP
8.3 Resumen y perspectiva de la metabolómica
https://pharmaceuticalintelligence.com/2014/10/16/metabolomics-summary-and-perspective/
Autor y redactor: Larry H Bernstein, MD, FCAP
8.4 Resumen de la metabolómica
https://pharmaceuticalintelligence.com/2014/11/08/introduction-to-metabolomics-2/
Autor y redactor: Larry H. Bernstein, MD, FCAP
8.5 Metabolismo de los lípidos
https://pharmaceuticalintelligence.com/2014/08/15/lipid-metabolism/
Reporter and Curator: Larry H. Bernstein, MD, FCAP
8.6 Prevalece la controversia sobre si los bebés nacidos por cesárea necesitan los microbios de la madre
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Parte 9
La diabetes y el tratamiento con insulina
Introducción, Dra. Irina Robu, PhD
9.1 Adipocitos reprogramados para producir insulina
https://pharmaceuticalintelligence.com/2016/04/14/fat-cells-reprogrammed-to-make-insulin/
Redactor: Larry H. Bernstein, MD, FCAP
9.2 La diabetes está causada por canales de calcio con fugas en las células beta del páncreas: investigación en el Columbia University Medical Center: el papel de RyR2 en la regulación de la liberación de insulina y la homeostasis de la glucosa
Reportero: Aviva Lev-Ari, PhD, RN
9.3 Endocrinología gastrointestinal
https://pharmaceuticalintelligence.com/2015/02/10/gastrointestinal-endocrinology/
Escritor y editor: Larry H Bernstein, MD, FCAP
9.4 Islotes pancreáticos
https://pharmaceuticalintelligence.com/2015/02/08/pancreatic-islets/
Escritor y editor: Larry H. Bernstein, MD, FCAP
9.5 Metformina, eje hipofisario-tiroideo, diabetes de tipo 2 y metabolismo
Autor y redactor: Larry H Bernstein, MD, FCAP y Aviva Lev-Ari, PhD, RN
Parte 10
Cáncer de los sistemas reproductor y genitourinario humanos
10.1 Introducción a las disfunciones de los estados patológicos: trastornos endocrinos, hipermetabolismo del estrés y cáncer
Autor y redactor: Larry H. Bernstein, MD, FCAP
10.2 Resumen y perspectivas. Disfunciones en los estados patológicos: trastornos endocrinos, hipermetabolismo del estrés y cáncer
Autor y redactor: Larry H. Bernstein, MD, FCAP
10.3 Tipos de cáncer en los sistemas reproductor y genitourinario humanos
Introducción del Dr. Stephen J. Williams, PhD
10.3.1 Cáncer de mama
10.3.1.1 Terapia dirigida para el cáncer de mama triple negativo
Redactor: Larry H. Bernstein, MD, FCAP
10.3.1.2 No existe a largo plazo ningún riesgo significativo de cáncer de mama a causa de la estimulación ovárica de la fecundación in vitro
Reportero: Aviva Lev-Ari, PhD, RN
10.3.1.3 Nueva estratificación del riesgo de cáncer de mama
https://pharmaceuticalintelligence.com/2016/03/18/new-risk-stratification-for-breast-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
10.3.1.4 El microambiente del cáncer de mama influye en la progresión
Redactor: Larry H. Bernstein, MD, FCAP
10.3.2 Cáncer de ovario
10.3.2.1 Un estudio revela que la confusión de las mujeres y sus médicos de cabecera sobre los síntomas del cáncer de ovario puede llevar a un diagnóstico erróneo
Reportero: Stephen J. Williams, PhD
10.3.2.2 Una historia resumida de la ciencia que hay detrás del ensayo del β-bloqueante para el tratamiento del cáncer de ovario
Redactor: Stephen J. Williams, PhD
10.3.2.3 Los betabloqueantes ayudan a mejorar la supervivencia en el cáncer de ovario
Redactor: Dr. Sudipta Saha, Ph.D
10.3.2.4 La eficacia de la ovariectomía en presencia de BRCA1 en comparación con BRCA2 y el riesgo tener de cáncer de ovario
Reportero: Aviva Lev Ari, PhD, RN
10.3.2.5 Análisis de múltiples mutaciones genéticas mediante SMP para pacientes: amplios antecedentes familiares de cáncer de mama y ovario, diagnosticados a edades tempranas y con resultado negativo en la prueba de BRCA
Reportero: Aviva Lev Ari, PhD, RN
10.3.2.6 Apretando las células de cáncer de ovario para predecir el potencial metastásico: la rigidez celular como posible biomarcador
Reportero/redactor: Prabodh Kandala, PhD
10.3.2.7 PARP como diana
https://pharmaceuticalintelligence.com/2016/05/19/targeting-parp/
Redactor: Larry H. Bernstein, MD, FCAP
10.3.2.8 Eficacia de los inhibidores de PARP más allá de las mutaciones de BRCA
Reportero: Irina Robu, PhD
10.3.2.9 Notas en directo, cobertura de la conferencia en tiempo real de la Reunión Virtual de la AACR de 2020; sesión sobre nuevas dianas y tratamientos: 28 de abril de 2020 a las 2:35 p.m.
Reportero: Stephen J. Williams, PhD
10.3.2.10 Notas en directo, cobertura de la conferencia en tiempo real de la Reunión Virtual de la AACR de 2020; mini simposio sobre el tratamiento farmacológico de las dianas del cáncer no tratadas con fármacos: 27 de abril de 2020, de 1:30 p.m a 5:00 p.m.
Reportero: Stephen J. Williams, PhD
10.3.3 Cáncer cervicouterino y de endometrio
10.3.3.1 Nuevos hallazgos en el cáncer de endometrio: mutaciones, tipos moleculares y respuestas inmunitarias evocadas por los subtipos de cáncer de endometrio y ovario propensos a las mutaciones
Redactor: Aviva Lev-Ari, PhD, RN
10.3.3.2 Inactivación del gen E6 o E7 del virus del papiloma humano en células de carcinoma cervicouterino mediante un CRISPR/Cas bacteriano
Autor: Aviva Lev-Ari, PhD, RN
10.3.3.3 Virus del papiloma para el cáncer cervicouterino
https://pharmaceuticalintelligence.com/2015/10/10/papilloma-viruses-for-cervical-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
10.3.3.4 El director del National Cancer Institute, Neil Sharpless, afirma que la mortalidad derivada de los retrasos en las pruebas de detección del cáncer debido a la pandemia de COVID19 podría provocar decenas de miles de muertes adicionales en la próxima década
Reportero: Stephen J Williams, Ph.D.
10.3.3.5 Estudios sobre el cáncer de cabeza y cuello sugieren que hay marcadores alternativos, más útiles, para el pronóstico que las pruebas de ADN del VPH
Reportero: Aviva Lev-Ari, PhD, RN
10.3.3.6 La secuenciación del exoma de los tumores serosos del endometrio muestra mutaciones somáticas recurrentes en los genes del complejo de remodelación de la cromatina y la ubiquitina·ligasa
Redactor: Dr. Sudipta Saha, Ph.D
10.3.4 Cáncer de próstata
10.3.4.1 ¿Cuándo y en qué personas se deben hacer las pruebas de detección del cáncer de próstata?
https://pharmaceuticalintelligence.com/2016/01/07/who-and-when-should-we-screen-for-prostate-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
10.3.4.2 Cáncer de próstata: Diagnóstico y nuevos tratamientos. Artículos destacados en PharmaceuticalIntelligence.com
Redactores: Larry H. Bernstein, MD, FCAP y Aviva Lev-Ari, PhD, RN
10.3.4.3 PARP como diana del cáncer de próstata
https://pharmaceuticalintelligence.com/2016/06/10/targeting-parp-in-prostate-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
10.3.4.4 Cáncer de próstata: el «mecanismo patológico» impulsado por andrógenos en las formas de aparición temprana de la enfermedad
Redactor: Aviva Lev-Ari, PhD, RN
10.3.4.5 Vías de señalización del cáncer y progresión tumoral: imágenes de procesos biológicos explicadas por un patólogo experto en cáncer
Autor experto en cáncer y editor de las ilustraciones: Larry H Bernstein, MD, FCAP, y Redactor: Aviva Lev-Ari, PhD, RN
Resumen del volumen por el Dr. Sudipta Saha, PhD
EPÍLOGO por el Dr. Stephen J. Williams, PhD
Cuarto volumen
Sistema reproductor humano,
endocrinología genómica y tipos de cáncer
Asesor de contenidos de la serie:
Director de estrategia emérito, LPBI Group
Volume Four
Human Reproductive System,
Genomic Endocrinology and
Cancer Types
2021
Prof. Stephen J. Williams, PhD, Editor
Prof. Sudipta Saha, PhD, Editor
y
Aviva Lev-Ari, PhD, RN, Editor
Disponible en Amazon.com desde el 02/02/2021
http://www.amazon.com/dp/B08VTFWVKM
PART B:
The eTOCs in Bi-lingual format: Spanish and English in Text format
Cuarto volumen
Sistema reproductor humano,
endocrinología genómica y tipos de cáncer
Asesor de contenidos de la serie:
Director de estrategia emérito, LPBI Group
2021
Traducción en español
Prof. Stephen J. Williams, PhD, Editor
Prof. Sudipta Saha, PhD, Editor
y
Aviva Lev-Ari, PhD, RN, Editor
Fuente de la imagen: cortesía de Google Images
Disponible en Amazon.com desde el 02/02/2021
http://www.amazon.com/dp/B08VTFWVKM
UC, Berkeley, PhD’83
Redactor jefe de la serie de libros electrónicos BioMed
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
avivalev-ari@alum.berkeley.edu
Volume Four
Human Reproductive System,
Genomic Endocrinology and Cancer Types
Series Content Consultant:
Emeritus CSO, LPBI Group
2021
Prof. Stephen J. Williams, PhD, Editor
Prof. Sudipta Saha, PhD, Editor
and
Aviva Lev-Ari, PhD, RN, Editor
Image Source: Courtesy of Google Images
Available on Amazon.com since 2/2/2021
http://www.amazon.com/dp/B08VTFWVKM
UC, Berkeley, PhD’83
Editor-in-Chief BioMed e-Book Series
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
avivalev-ari@alum.berkeley.edu
Los 18 volúmenes de los expertos, autores y escritores del LPBI Group publicados en AMAZON.COM se encuentran en el catálogo de la Kindle Store sobre Medicina y ciencias de la vida
All the 18 volumes by LPBI Group’s Experts, Authors, Writers published on AMAZON.COM are on the Kindle Store bookshelf on Medicine and Life Sciences
https://lnkd.in/ekWGNqA
Lista de colaboradores y enlaces a las biografías
List of Contributors & Links to Bios
Dr. Larry H. Bernstein, MD, FCAP
1.2, 1.3, 1.6, 3.1, 3.2, 3.3, 3.4, 4.1, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.9, 6.6, 8.1, 8.2, 8.3, 8.4, 8.5, 9.1, 9.3, 9.4, 9.5 10.1, 10.2, 10.3.1.1, 10.3.1.3, 10.3.1.4, 10.3.2.7, 10.3.3.3, 10.3.4.1, 10.3.4.2, 10.3.4.3, 10.3.4.5
Prof. Stephen J. Williams, PhD, editor
Prof. Stephen J. Williams, PhD, Editor
Prefacio, Introducción del volumen, 4.5, Parte 10: Introducción, 10.3.2.1, 10.3.2.2, 10.3.2.9, 10.3.2.10, 10.3.3.4, Parte 10: Resumen y EPÍLOGO
PREFACE, Volume Introduction, 4.5, Part 10: Introduction, 10.3.2.1, 10.3.2.2, 10.3.2.9, 10.3.2.10, 10.3.3.4, Part 10: Summary, EPILOGUE
Prof. Sudipta Saha, PhD, editor
Prof. Sudipta Saha, PhD, Editor
Parte 1: Introducción, 1.5, 2.2, 2.3, 2.4, 4.2, 4.4, 5.8, 5.10, 5.11,
Part 1: Introduction, 1.5, 2.2, 2.3, 2.4, 4.2, 4.4, 5.8, 5.10, 5.11,
Parte 6: Introducción, 6.1, 6.2, 6.3, 6.4, 7.1, 7.2, 7.3, 7.4, 7.7, 7.8, 7.9, 7.10, 8.6, 10.3.2.3, 10.3.3.6,
Part 6: Introduction, 6.1, 6.2, 6.3, 6.4, 7.1, 7.2, 7.3, 7.4, 7.7, 7.8, 7.9, 7.10, 8.6, 10.3.2.3, 10.3.3.6,
Resumen del volumen
Volume Summary
Dra. Aviva Lev-Ari, PhD, RN, editora
Dr. Aviva Lev-Ari, PhD, RN, Editor
Introducción del volumen, 1.1, 1.4, 4.3, 4.6, 6.5, 6.7, 7.2, 7.5, 7.6, 9.2, 9.5, 10.3.1.2, 10.3.2.4, 10.3.2.5, 10.3.3.1, 10.3.3.2, 10.3.3.5, 10.3.4.2, 10.3.3.4, 10.3.4.5
Volume Introduction, 1.1, 1.4, 4.3, 4.6, 6.5, 6.7, 7.2, 7.5, 7.6, 9.2, 9.5, 10.3.1.2, 10.3.2.4, 10.3.2.5, 10.3.3.1, 10.3.3.2, 10.3.3.5, 10.3.4.2, 10.3.3.4, 10.3.4.5
Dra. Irina Robu, PhD
Parte 2, 5, 8, 9: Introducciones, 2.1, 10.3.2.8
Part 2, 5, 8, 9: Introductions, 2.1, 10.3.2.8
Prof. Marcus W. Feldman, PhD
Parte 7: Introducción, 7.2
Part 7: Introduction, 7.2
Dr. Prabodh Kandala, PhD
Parte 10: 10.3.2.6
Part 10: 10.3.2.6
Cuarto volumen
Volume Four
Los enlaces indicados llevan al contenido original en inglés
| MD | Licenciado/a en medicina y cirugía (Estados Unidos) |
| PhD | Doctorado/a |
| Ph.D | Doctorado/a |
| RN | Enfermero/a titulado/a (National Board of Nursing Registration) |
| FCAP | Miembro distinguido (Fellow) del Colegio de Anatomopatólogos de los Estados Unidos |
Indice de contenidos electrónico (IDCe)
electronic Table of Contents
PREFACIO por el Dr. Stephen J. Williams, PhD
PREFACE by Dr. Stephen J. Williams, PhD
Introducción al volumen
Volume Introduction
Las opiniones del Dr. Stephen J. Williams, PhD y de Dr. Aviva Lev-Ari, PhD, RN
Voices of Dr. Stephen J. Williams, PhD and Voice of Dr. Aviva Lev-Ari, PhD, RN
Parte 1
Temas generales sobre la reproducción humana
Part 1
General Topics on Human Reproduction
Introducción, Dr. Sudipta Saha, PhD
Introduction – Dr. Sudipta Saha, PhD
1.1 Las 10 principales innovaciones médicas de 2018, 2020 y 2021 por la Cleveland Clinic
1.1 Top 10 Medical Innovations for 2018, 2020 and 2021 by Cleveland Clinic
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
1.2 El caso Hobby Lobby
1.2 Reason in Hobby Lobby
https://pharmaceuticalintelligence.com/2014/07/08/reason-in-hobby-lobby-3/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
1.3 El voto particular de la jueza Ginsberg
1.3 Justice Ginsberg Written Dissent
https://pharmaceuticalintelligence.com/2014/07/08/justice-ginsberg-written-dissent/
Editor y reportero: Larry H. Bernstein, MD, FCAP
Curator and Reporter: Larry H. Bernstein, MD, FCAP
1.4 Micronutrientes, macronutrientes y patrones dietéticos: nutrición y fertilidad
1.4 Micronutrients, Macronutrients and Dietary Patterns: Nutrition and Fertility
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
1.5 El medicamento antivírico para la hepatitis B no es útil para reducir la transmisión maternofilial
1.5 Antiviral drug for hepatitis B not beneficial for reducing mother-to-child transmission
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
1.6 Fisiopatología neonatal
1.6 Neonatal Pathophysiology
https://pharmaceuticalintelligence.com/2015/02/22/neonatal-pathophysiology/
Escritor y editor: Larry H. Bernstein, MD, FCAP
Writer and Curator: Larry H. Bernstein, MD, FCAP
Parte 2
Innovaciones en biología celular y embriología
Part 2
Innovations in Cell Biology and Embryology
Introducción, Dra. Irina Robu, PhD
Introduction – Dr. Irina Robu, PhD
2.1 Células madre embrionarias obtenidas de la piel
2.1 Embryo Stem Cells Out of Skin
https://pharmaceuticalintelligence.com/2019/05/08/embryo-stem-cells-out-of-skin/
Reportero: Irina Robu, PhD
Reporter: Irina Robu, PhD
2.2 La técnica de los tres progenitores para evitar las enfermedades mitocondriales en el embrión
2.2 The Three Parent Technique to Avoid Mitochondrial Disease in Embryo
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
2.3 Terapia de reemplazo mitocondrial
2.3 Mitochondria Replacement Therapy
https://pharmaceuticalintelligence.com/2019/04/14/mitochondria-replacement-therapy/
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Curator and Reporter: Dr. Sudipta Saha, Ph.D.
2.4 scPopCorn: un nuevo método computacional para la detección de subpoblaciones y su análisis comparativo entre experimentos con células individuales
2.4 scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Curator or Reporter: Dr. Sudipta Saha, Ph.D.
Parte 3
Señalización celular
Part 3
Cell Signaling
3.1 Tutorial sobre la transducción de señales
3.1 Signaling transduction tutorial
https://pharmaceuticalintelligence.com/2014/08/12/signaling-transduction-tutorial/
Reportero y editor: Larry H. Bernstein, MD, FCAP
Reporter and Curator: Larry H. Bernstein, MD, FCAP
3.2 Introducción a la señalización
3.2 Introduction to Signaling
https://pharmaceuticalintelligence.com/2014/10/30/introduction-to-signaling/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
3.3 La señalización y las vías de señalización
3.3 Signaling and Signaling Pathways
https://pharmaceuticalintelligence.com/2014/08/12/signaling-and-signaling-pathways/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
3.4 Resumen de la señalización y las vías de señalización
3.4 Summary of Signaling and Signaling Pathways
https://pharmaceuticalintelligence.com/2014/11/01/summary-of-signaling-and-signaling-pathways/
Autor y redactor: Larry H Bernstein, MD, FCAP
Author and Curator: Larry H Bernstein, MD, FCAP
Parte 4
La genómica en el bienestar prenatal e infantil
Part 4
Genomics in Prenatal and Childhood Wellness
Introducción, Dr. Stephen J. Williams, PhD
Introduction – Dr. Stephen J. Williams, PhD
4.1 Genes, proteomas y su interacción
4.1 Genes, proteomes, and their interaction
https://pharmaceuticalintelligence.com/2014/07/28/genes-proteomes-and-their-interaction/
Autor y redactor: Larry H. Bernstein, MD, FCAP
Author and Curator: Larry H. Bernstein, MD, FCAP
4.2 El microARN en la reproducción
4.2 MicroRNA in Reproduction
https://pharmaceuticalintelligence.com/2016/11/09/microrna-in-reproduction/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
4.3 Mesa redonda: la genómica de los trastornos prenatales e infantiles
4.3 Panel Discussion Genomics in Prenatal and Childhood Disorders
Editor y reportero: Aviva Lev-Ari, PhD, RN
Curator or Reporter: Aviva Lev-Ari, PhD, RN
4.4 La función del gen saltarín (LINE1) al descubierto
4.4 The function of the junk jumping gene (LINE1) uncovered
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
4.5 Cómo revolucionará la SMP el diagnóstico reproductivo: reunión de noviembre, Boston, MA
4.5 How NGS Will Revolutionize Reproductive Diagnostics: November Meeting, Boston MA
Reportero: Stephen J. Williams, Ph.D.
Reporter: Stephen J. Williams, Ph.D.
4.6 Mesa redonda sobre genómica en los trastornos prenatales y de la infancia en la 10.ª Conferencia Anual de Medicina Personalizada en la Harvard Medical School, Boston, EUA, el 13/11/2014 a la 1:00 p.m.
4.6 1:00PM 11/13/2014 – Panel Discussion Genomics in Prenatal and Childhood Disorders @10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
Parte 5
Descubrimientos en endocrinología
Part 5
Discoveries in Endocrinology
Introducción, Dra. Irina Robu, PhD
Introduction – Dr. Irina Robu, PhD
5.1 Premio Roy O. Greep a la Investigación destacada en endocrinología
5.1 Roy O. Greep Award for Outstanding Research in Endocrinology
Redactor: Larry H Bernstein, MD, FCAP
Curator: Larry H Bernstein, MD, FCAP
5.2 El premio Fred Conrad Koch a la trayectoria profesional, el más alto honor de la Endocrine Society, reconoce los logros de toda una vida y las contribuciones excepcionales de una persona al campo de la endocrinología
5.2 The Fred Conrad Koch Lifetime Achievement Award—the Society’s highest honor—recognizes the lifetime achievements and exceptional contributions of an individual to the field of endocrinology
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
5.3 Corteza suprarrenal
5.3 Adrenal Cortex
https://pharmaceuticalintelligence.com/2015/02/07/adrenal-cortex/
Escritor y editor: Larry H Bernstein, MD, FCAP
Writer and Curator: Larry H Bernstein, MD, FCAP
5.4 Hormonas sexuales
5.4 Sex Hormones
https://pharmaceuticalintelligence.com/2015/02/07/sex-hormones/
Autor: Larry H Bernstein, MD, FCAP
Author: Larry H Bernstein, MD, FCAP
5.5 Función y trastornos del tiroides
5.5 Thyroid Function and Disorders
https://pharmaceuticalintelligence.com/2015/02/05/thyroid-function-and-disorders/
Escritor y editor: Larry H. Bernstein, MD, FCAP
Writer and Curator: Larry H. Bernstein, MD, FCAP
5.6 Eje neuroendocrino hipofisario
5.6 Pituitary Neuroendocrine Axis
https://pharmaceuticalintelligence.com/2015/02/04/pituitary-neuroendocrine-axis/
Escritor y editor: Larry H. Bernstein, MD, FCAP
Writer and Curator: Larry H. Bernstein, MD, FCAP
5.7 Acción endocrina en el mesencéfalo
5.7 Endocrine Action on Midbrain
https://pharmaceuticalintelligence.com/2015/02/12/endocrine-action-on-midbrain/
Editor y reportero: Larry H. Bernstein, MD, FCAP
Curator or Reporter: Larry H. Bernstein, MD, FCAP
5.8 Géneros redefinidos por la biología
5.8 Genders redefined by Biology
https://pharmaceuticalintelligence.com/2018/03/10/genders-redefined-by-biology/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
5.9 Acción farmacológica de las hormonas esteroideas
5.9 Pharmacological Action of Steroid Hormones
https://pharmaceuticalintelligence.com/2014/10/27/pharmacological-action-of-steroid-hormones/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
5.10 Cambios en los niveles de hormonas sexuales y del péptido natriurético de tipo N-terminal pro-B como biomarcador de enfermedades cardiovasculares
5.10 Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
5.11 Productos químicos para el cuidado personal y el inicio de la pubertad
5.11 Personal Care Chemicals and Puberty Onset
https://pharmaceuticalintelligence.com/2018/12/16/personal-care-chemicals-and-puberty-onset/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Parte 6
Fronteras de la endocrinología femenina
Part 6
Frontier of Female Endocrinology
Introducción, Dr. Sudipta Saha, Ph.D.
Introduction – Dr. Sudipta Saha, Ph.D.
6.1 Ovario artificial en lugar de la hormonoterapia de reposición convencional
6.1 Artificial ovary instead of conventional hormone replacement
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
6.2 La viabilidad del nivel de hormona antimülleriana (AMH) como marcador de fertilidad
6.2 The viability of Anti-Müllerian Hormone (AMH) level as fertility marker
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
6.3 El reloj del sistema inmunitario en el embarazo
6.3 The immune system clock of pregnancy
https://pharmaceuticalintelligence.com/2017/09/13/the-immune-system-clock-of-pregnancy/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
6.4 Un interruptor genético para controlar el comportamiento sexual femenino
6.4 A genetic switch to control female sexual behavior
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
6.5 Trastorno del deseo sexual en mujeres premenopáusicas: la FDA aprueba Addyi (flibanserina), la «Viagra femenina» para aumentar la libido
6.5 Sexual Desire Disorder in Pre-menopausal Women: Addyi (flibanserin) is intended to increase libido – ‘Female Viagra’ approved by FDA
Reportero: Aviva Lev-Ari, PhD
Reporter: Aviva Lev-Ari, PhD
6.6 Tratamiento hormonal
6.6 Hormone Therapy
https://pharmaceuticalintelligence.com/2015/05/15/hormone-therapy-9-4/
Escritor y editor: Larry H. Bernstein, MD, FCAP
Writer and Curator: Larry H. Bernstein, MD, FCAP
6.7 Endometriosis: diagnóstico genómico en la UCSF
6.7 Endometriosis: Genomics Diagnosis @UCSF
https://pharmaceuticalintelligence.com/2014/11/24/endometriosis-genomics-diagnosis-ucsf/
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
Parte 7
Función sexual masculina y fertilidad
Part 7
Male Sexual Function and Fertility
Introducción del Dr. Marc Feldman, PhD
Introduction by Dr. Marc Feldman, PhD
7.1 Tendencias en el recuento de espermatozoides
7.1 Trends in Sperm Count
https://pharmaceuticalintelligence.com/2017/07/27/trends-in-sperm-count/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
7.2 Disminución del número de espermatozoides: epigenética, bienestar e importancia para la evolución y la demografía de las poblaciones
7.2 Decline in Sperm Count – Epigenetics, Well-being and the Significance for Population Evolution and Demography
Dr. Marc Feldman, opinión de un experto sobre la importancia de la disminución del número de espermatozoides en el futuro de la evolución y la demografía de la población
Dr. Marc Feldman, Expert Opinion on the significance of Sperm Count Decline on the Future of Population Evolution and Demography
Dr. Sudipta Saha, efectos de la calidad y la cantidad de los espermatozoides en la reproducción humana
Dr. Sudipta Saha, Effects of Sperm Quality and Quantity on Human Reproduction
Dra. Aviva Lev-Ari, efectos psicosociales de la pobreza, el desempleo y la epigenética en el bienestar masculino; afecciones fisiológicas que afectan a la calidad y cantidad de los espermatozoides
Dr. Aviva Lev-Ari, Psycho-Social Effects of Poverty, Unemployment and Epigenetics on Male Well-being, Physiological Conditions affecting Sperm Quality and Quantity
7.3 El consumo de cannabis ha aumentado el número de espermatozoides
7.3 Cannabis smoking showed increased sperm count
https://pharmaceuticalintelligence.com/2019/02/21/cannabis-smoking-showed-increased-sperm-count/
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Curator or Reporter: Dr. Sudipta Saha, Ph.D.
7.4 Defectos espermatogénicos en ratones con reversión sexual
7.4 Spermatogenic defects in sex reversed mice
https://pharmaceuticalintelligence.com/2016/02/29/spermatogenic-defects-in-sex-reversed-mice-2/
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Curator or Reporter: Dr. Sudipta Saha, Ph.D.
7.5 Fertilización: arquitectura proteica de la matriz acrosómica del espermatozoide; los filamentos del orgánulo de la cabeza del espermatozoide se dirigen al óvulo
7.5 Fertilization: Protein Architecture of the Sperm’s Acrosomal Matrix, Filaments in Sperm Head Organelle Target the Egg
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
7.6 Infertilidad masculina y genómica: los hombres fértiles portaban un conjunto completo de elementos de ARN del esperma; sin embargo, la mayoría de los hombres infértiles, no
7.6 Male Infertility and Genomics: Fertile men carried a complete set of the sperm RNA elements; however, most of the infertile men did not
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
7.7 El tratamiento con testosterona mejoró principalmente la función sexual, más que la deambulación o la vitalidad en los hombres mayores con niveles bajos de testosterona
7.7 Testosterone treatment improved primarily sexual function than walking or vitality in older men with low testosterone levels
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
7.8 Investigación prometedora para una píldora anticonceptiva masculina
7.8 Promising research for a male birth control pill
https://pharmaceuticalintelligence.com/2017/03/23/promising-research-for-a-male-birth-control-pill/
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
7.9 Molécula de conmutación celular para el control de la motilidad de los espermatozoides: un nuevo objetivo para la anticoncepción masculina y los tratamientos de la infertilidad
7.9 Cellular switch molecule for sperm motility control: a novel target for male contraception and infertility treatments
Reportero y editor: Sudipta Saha, Ph.D.
Reporter and Curator: Sudipta Saha, Ph.D.
7.10 Dispositivo anticonceptivo de por vida para hombres: interruptor mecánico para controlar la fertilidad a voluntad
7.10 Lifelong Contraceptive Device for Men: Mechanical Switch to Control Fertility on Wish
Reportero y editor: Dr. Sudipta Saha, Ph.D.
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Parte 8
Metabolómica y genómica del microbioma
Part 8
Metabolomics and Microbiome Genomics
Introducción, Dra. Irina Robu, PhD
Introduction – Dr. Irina Robu, PhD
8.1 Genómica metabólica y farmacéutica, Vol. 1 de la serie D de BioMed, disponible en la Kindle de Store de Amazon.com
http://www.amazon.com/dp/B012BB0ZF0
8.1 Metabolic Genomics and Pharmaceutics, Vol. 1 of BioMed Series D available on Amazon.com Kindle Store
http://www.amazon.com/dp/B012BB0ZF0
Autor: Larry H. Bernstein, MD, FCAP
Author: Larry H. Bernstein, MD, FCAP
8.2 Introducción a la metabolómica
8.2 Introduction to Metabolomics
https://pharmaceuticalintelligence.com/2014/10/21/introduction-to-metabolomics/
Autor: Larry H. Bernstein, MD, FCAP
Author: Larry H. Bernstein, MD, FCAP
8.3 Resumen y perspectiva de la metabolómica
8.3 Metabolomics Summary and Perspective
https://pharmaceuticalintelligence.com/2014/10/16/metabolomics-summary-and-perspective/
Autor y redactor: Larry H Bernstein, MD, FCAP
Author and Curator: Larry H Bernstein, MD, FCAP
8.4 Resumen de la metabolómica
8.4 Summary to Metabolomics
https://pharmaceuticalintelligence.com/2014/11/08/introduction-to-metabolomics-2/
Autor y redactor: Larry H. Bernstein, MD, FCAP
Author and Curator: Larry H. Bernstein, MD, FCAP
8.5 Metabolismo de los lípidos
8.5 Lipid Metabolism
https://pharmaceuticalintelligence.com/2014/08/15/lipid-metabolism/
Reportero y editor: Larry H. Bernstein, MD, FCAP
Reporter and Curator: Larry H. Bernstein, MD, FCAP
8.6 Prevalece la controversia sobre si los bebés nacidos por cesárea necesitan los microbios de la madre
8.6 Controversy prevails on whether C-section babies need mother’s microbes
Editor y reportero: Dr. Sudipta Saha, Ph.D.
Curator or Reporter: Dr. Sudipta Saha, Ph.D.
Parte 9
La diabetes y el tratamiento con insulina
Part 9
Diabetes and the Insulin Treatment
Introducción, Dra. Irina Robu, PhD
Introduction – Dr. Irina Robu, PhD
9.1 Adipocitos reprogramados para producir insulina
9.1 Fat Cells Reprogrammed to Make Insulin
https://pharmaceuticalintelligence.com/2016/04/14/fat-cells-reprogrammed-to-make-insulin/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
9.2 La diabetes está causada por canales de calcio con fugas en las células beta del páncreas: investigación en el Columbia University Medical Center: el papel de RyR2 en la regulación de la liberación de insulina y la homeostasis de la glucosa
9.2 Diabetes is caused by Leaky Calcium Channels in Pancreatic Beta Cells – research @Columbia University Medical Center: The Role of RyR2 in Regulation of Insulin Release and Glucose Homeostasis
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
9.3 Endocrinología gastrointestinal
9.3 Gastrointestinal Endocrinology
https://pharmaceuticalintelligence.com/2015/02/10/gastrointestinal-endocrinology/
Escritor y editor: Larry H Bernstein, MD, FCAP
Writer and Curator: Larry H Bernstein, MD, FCAP
9.4 Islotes pancreáticos
9.4 Pancreatic Islets
https://pharmaceuticalintelligence.com/2015/02/08/pancreatic-islets/
Escritor y editor: Larry H. Bernstein, MD, FCAP
Writer and Curator: Larry H. Bernstein, MD, FCAP
9.5 Metformina, eje hipofisario-tiroideo, diabetes de tipo 2 y metabolismo
9.5 Metformin, thyroid pituitary axis, diabetes mellitus, and metabolism
Autor y redactor: Larry H Bernstein, MD, FCAP y Aviva Lev-Ari, PhD, RN
Author and Curator: Larry H, Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN
Parte 10
Cáncer de los sistemas reproductor y genitourinario humanos
Part 10
Cancer of the Human Reproductive and Genitourinary Systems
10.1 Introducción a las disfunciones de los estados patológicos: trastornos endocrinos, hipermetabolismo del estrés y cáncer
10.1 Introduction to Impairments in Pathological States: Endocrine Disorders, Stress Hypermetabolism and Cancer
Autor y redactor: Larry H. Bernstein, MD, FCAP
Author and Curator: Larry H. Bernstein, MD, FCAP
10.2 Resumen y perspectivas. Disfunciones en los estados patológicos: trastornos endocrinos, hipermetabolismo del estrés y cáncer
10.2 Summary and Perspectives: Impairments in Pathological States: Endocrine Disorders, Stress Hypermetabolism and Cancer
Autor y redactor: Larry H. Bernstein, MD, FCAP
Author and Curator: Larry H. Bernstein, MD, FCAP
10.3 Tipos de cáncer en los sistemas reproductor y genitourinario humanos
10.3 Cancers Types in the Human Reproductive and Genitourinary Systems
Introducción del Dr. Stephen J. Williams, PhD
Introduction by Dr. Stephen J. Williams, PhD
10.3.1 Cáncer de mama
10.3.1 Breast Cancer
10.3.1.1 Terapia dirigida para el cáncer de mama triple negativo
10.3.1.1 Targeted Therapy for Triple Negative Breast Cancer
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.1.2 No existe a largo plazo ningún riesgo significativo de cáncer de mama a causa de la estimulación ovárica de la fecundación in vitro
10.3.1.2 No Significant Long-term Risk of Breast Cancer caused by Ovarian Stimulation for in Vitro Fertilization
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
10.3.1.3 Nueva estratificación del riesgo de cáncer de mama
10.3.1.3 New Risk Stratification for Breast Cancer
https://pharmaceuticalintelligence.com/2016/03/18/new-risk-stratification-for-breast-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.1.4 El microambiente del cáncer de mama influye en la progresión
10.3.1.4 Breast Cancer Extratumor Microenvironment has Effect on Progression
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.2 Cáncer de ovario
10.3.2 Ovarian Cancer
10.3.2.1 Un estudio revela que la confusión de las mujeres y sus médicos de cabecera sobre los síntomas del cáncer de ovario puede llevar a un diagnóstico erróneo
10.3.2.1 Study Finds that Both Women and their Primary Care Physicians Confusion over Ovarian Cancer Symptoms May Lead to Misdiagnosis
Reportero: Stephen J. Williams, PhD
Reporter: Stephen J. Williams, PhD
10.3.2.2 Una historia resumida de la ciencia que hay detrás del ensayo del β-bloqueante para el tratamiento del cáncer de ovario
10.3.2.2 A Curated History of the Science Behind the Ovarian Cancer β-Blocker Trial
Redactor: Stephen J. Williams, PhD
Curator: Stephen J. Williams, PhD
10.3.2.3 Los betabloqueantes ayudan a mejorar la supervivencia en el cáncer de ovario
10.3.2.3 Beta-Blockers help in better survival in ovarian cancer
Redactor: Dr. Sudipta Saha, Ph.D
Curator: Dr. Sudipta Saha, Ph.D
10.3.2.4 La eficacia de la ovariectomía en presencia de BRCA1 en comparación con BRCA2 y el riesgo tener de cáncer de ovario
10.3.2.4 Efficacy of Ovariectomy in Presence of BRCA1 vs BRCA2 and the Risk for Ovarian Cancer
Reportero: Aviva Lev Ari, PhD, RN
Reporter: Aviva Lev Ari, PhD, RN
10.3.2.5 Análisis de múltiples mutaciones genéticas mediante SMP para pacientes: amplios antecedentes familiares de cáncer de mama y ovario, diagnosticados a edades tempranas y con resultado negativo en la prueba de BRCA
10.3.2.5 Testing for Multiple Genetic Mutations via NGS for Patients: Very Strong Family History of Breast & Ovarian Cancer, Diagnosed at Young Ages, & Negative on BRCA Test
Reportero: Aviva Lev Ari, PhD, RN
Reporter: Aviva Lev Ari, PhD, RN
10.3.2.6 Apretando las células de cáncer de ovario para predecir el potencial metastásico: la rigidez celular como posible biomarcador
10.3.2.6 Squeezing Ovarian Cancer Cells to Predict Metastatic Potential: Cell Stiffness as Possible Biomarker
Reportero/redactor: Prabodh Kandala, PhD
Reporter/curator: Prabodh Kandala, PhD
10.3.2.7 PARP como diana
10.3.2.7 Targeting PARP
https://pharmaceuticalintelligence.com/2016/05/19/targeting-parp/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.2.8 Eficacia de los inhibidores de PARP más allá de las mutaciones de BRCA
10.3.2.8 Efficiency of PARP inhibitors beyond BRCA mutations
Reportero: Irina Robu, PhD
Reporter: Irina Robu, PhD
10.3.2.9 Notas en directo, cobertura de la conferencia en tiempo real de la Reunión Virtual de la AACR de 2020; sesión sobre nuevas dianas y tratamientos: 28 de abril de 2020 a las 2:35 p.m.
10.3.2.9 Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Novel Targets and Therapies 2:35PM
Reportero: Stephen J. Williams, PhD
Reporter: Stephen J. Williams, PhD
10.3.2.10 Notas en directo, cobertura de la conferencia en tiempo real de la Reunión Virtual de la AACR de 2020; mini simposio sobre el tratamiento farmacológico de las dianas del cáncer no tratadas con fármacos: 27 de abril de 2020, de 1:30 p.m a 5:00 p.m.
10.3.2.10 Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 27, 2020 Mini symposium on Drugging Undrugged Cancer Targets 1:30 pm – 5:00PM
Reportero: Stephen J. Williams, PhD
Reporter: Stephen J. Williams, PhD
10.3.3 Cáncer cervicouterino y de endometrio
10.3.3 Cervical and Endometrial Cancer
10.3.3.1 Nuevos hallazgos en el cáncer de endometrio: mutaciones, tipos moleculares y respuestas inmunitarias evocadas por los subtipos de cáncer de endometrio y ovario propensos a las mutaciones
10.3.3.1 New Findings in Endometrial Cancer: Mutations, Molecular Types and Immune Responses Evoked by Mutation-prone Endometrial, Ovarian Cancer Subtypes
Redactor: Aviva Lev-Ari, PhD, RN
Curator: Aviva Lev-Ari, PhD, RN
10.3.3.2 Inactivación del gen E6 o E7 del virus del papiloma humano en células de carcinoma cervicouterino mediante un CRISPR/Cas bacteriano
10.3.3.2 Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells using a bacterial CRISPR/Cas
Autor: Aviva Lev-Ari, PhD, RN
Author: Aviva Lev-Ari, PhD, RN
10.3.3.3 Virus del papiloma para el cáncer cervicouterino
10.3.3.3 Papilloma viruses for cervical cancer
https://pharmaceuticalintelligence.com/2015/10/10/papilloma-viruses-for-cervical-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.3.4 El director del National Cancer Institute, Neil Sharpless, afirma que la mortalidad derivada de los retrasos en las pruebas de detección del cáncer debido a la pandemia de COVID19 podría provocar decenas de miles de muertes adicionales en la próxima década
10.3.3.4 National Cancer Institute Director Neil Sharpless says mortality from delays in cancer screenings due to COVID19 pandemic could result in tens of thousands of extra deaths in next decade
Reportero: Stephen J Williams, Ph.D.
Reporter: Stephen J Williams, Ph.D.
10.3.3.5 Estudios sobre el cáncer de cabeza y cuello sugieren que hay marcadores alternativos, más útiles, para el pronóstico que las pruebas de ADN del VPH
10.3.3.5 Head and Neck Cancer Studies Suggest Alternative Markers More Prognostically Useful than HPV DNA Testing
Reportero: Aviva Lev-Ari, PhD, RN
Reporter: Aviva Lev-Ari, PhD, RN
10.3.3.6 La secuenciación del exoma de los tumores serosos del endometrio muestra mutaciones somáticas recurrentes en los genes del complejo de remodelación de la cromatina y la ubiquitina·ligasa
10.3.3.6 Exome sequencing of serous endometrial tumors shows recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes
Redactor: Dr. Sudipta Saha, Ph.D
Curator: Dr. Sudipta Saha, Ph.D
10.3.4 Cáncer de próstata
10.3.4 Prostate Cancer
10.3.4.1 ¿Cuándo y en qué personas se deben hacer las pruebas de detección del cáncer de próstata?
10.3.4.1 Who and when should we screen for prostate cancer?
https://pharmaceuticalintelligence.com/2016/01/07/who-and-when-should-we-screen-for-prostate-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.4.2 Cáncer de próstata: Diagnóstico y nuevos tratamientos. Artículos destacados en PharmaceuticalIntelligence.com
10.3.4.2 Prostate Cancer: Diagnosis and Novel Treatment – Articles of Note @PharmaceuticalIntelligence.com
Redactores: Larry H. Bernstein, MD, FCAP y Aviva Lev-Ari, PhD, RN
Redactores: Larry H. Bernstein, MD, FCAP y Aviva Lev-Ari, PhD, RN
10.3.4.3 PARP como diana del cáncer de próstata
10.3.4.3 Targeting PARP in Prostate Cancer
https://pharmaceuticalintelligence.com/2016/06/10/targeting-parp-in-prostate-cancer/
Redactor: Larry H. Bernstein, MD, FCAP
Curator: Larry H. Bernstein, MD, FCAP
10.3.4.4 Cáncer de próstata: el «mecanismo patológico» impulsado por andrógenos en las formas de aparición temprana de la enfermedad
10.3.4.4 Prostate Cancer: Androgen-driven “Pathomechanism” in Early-onset Forms of the Disease
Redactor: Aviva Lev-Ari, PhD, RN
Curator: Aviva Lev-Ari, PhD, RN
10.3.4.5 Vías de señalización del cáncer y progresión tumoral: imágenes de procesos biológicos explicadas por un patólogo experto en cáncer
10.3.4.5 Cancer Signaling Pathways and Tumor Progression: Images of Biological Processes in the Voice of a Pathologist Cancer Expert
Autor experto en cáncer y editor de las ilustraciones: Larry H Bernstein, MD, FCAP, y Redactor: Aviva Lev-Ari, PhD, RN
Cancer Expert Author and Illustration Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN
Resumen del volumen por el Dr. Sudipta Saha, PhD
Volume Summary by Dr. Sudipta Saha, PhD
EPÍLOGO por el Dr. Stephen J. Williams, PhD
EPILOGUE by Dr. Stephen J. Williams, PhD
Cuarto volumen
Sistema reproductor humano,
endocrinología genómica y tipos de cáncer
Asesor de contenidos de la serie:
Director de estrategia emérito, LPBI Group
Volume Four
Human Reproductive System,
Genomic Endocrinology and
Cancer Types
2021
Prof. Stephen J. Williams, PhD, Editor
Prof. Sudipta Saha, PhD, Editor
y
Aviva Lev-Ari, PhD, RN, Editor
Disponible en Amazon.com desde el 02/02/2021
http://www.amazon.com/dp/B08VTFWVKM
PART C:
The Editorials of the original e-Books in English in Audio format
Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology
Volume Four
Human Reproductive System,
Genomic Endocrinology and Cancer Types
Series Content Consultant:
Emeritus CSO, LPBI Group
2021
Prof. Stephen J. Williams, PhD, Editor
Prof. Sudipta Saha, PhD, Editor
and
Aviva Lev-Ari, PhD, RN, Editor
Image Source: Courtesy of Google Images
Available on Amazon.com since 2/2/2021
http://www.amazon.com/dp/B08VTFWVKM
UC, Berkeley, PhD’83
Editor-in-Chief BioMed e-Book Series
Leaders in Pharmaceutical Business Intelligence (LPBI) Group, Boston
avivalev-ari@alum.berkeley.edu
All the 18 volumes by LPBI Group’s Experts, Authors, Writers published on AMAZON.COM are on the Kindle Store bookshelf on Medicine and Life Sciences
https://lnkd.in/ekWGNqA
List of Contributors & Links to Bios
Dr. Larry H. Bernstein, MD, FCAP, Author and Curator
1.2, 1.3, 1.6, 3.1, 3.2, 3.3, 3.4, 4.1, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.9, 6.6, 8.1, 8.2, 8.3, 8.4, 8.5, 9.1, 9.3, 9.4, 9.5 10.1, 10.2, 10.3.1.1, 10.3.1.3, 10.3.1.4, 10.3.2.7, 10.3.3.3, 10.3.4.1, 10.3.4.2, 10.3.4.3, 10.3.4.5
Prof. Stephen J. Williams, PhD, Editor
PREFACE, Volume Introduction, 4.5, Part 10: Introduction, 10.3.2.1, 10.3.2.2, 10.3.2.9, 10.3.2.10, 10.3.3.4, Part 10: Summary, EPILOGUE
Prof. Sudipta Saha, PhD, Editor
Part 1: Introduction, 1.5, 2.2, 2.3, 2.4, 4.2, 4.4, 5.8, 5.10, 5.11,
Part 6: Introduction, 6.1, 6.2, 6.3, 6.4, 7.1, 7.2, 7.3, 7.4, 7.7, 7.8, 7.9, 7.10, 8.6, 10.3.2.3, 10.3.3.6,
Volume Summary
Dr. Aviva Lev-Ari, PhD, RN, Editor
Volume Introduction, 1.1, 1.4, 4.3, 4.6, 6.5, 6.7, 7.2, 7.5, 7.6, 9.2, 9.5, 10.3.1.2, 10.3.2.4, 10.3.2.5, 10.3.3.1, 10.3.3.2, 10.3.3.5, 10.3.4.2, 10.3.3.4, 10.3.4.5
Dra. Irina Robu, PhD
Part 2, 5, 8, 9: Introductions, 2.1, 10.3.2.8
Prof. Marcus W. Feldman, PhD
Part 7: Introduction, 7.2
Dr. Prabodh Kandala, PhD
Part 10: 10.3.2.6
Volume Four
Human Reproductive System,
Genomic Endocrinology and
Cancer Types
electronic Table of Contents: All Editorials in this volume
PREFACE by Dr. Stephen J. Williams, PhD
We are Products of Our Experiences
The above statement might seem innocuous to most, however to the scientist/clinician, experiences, whether in the laboratory or clinic, establish the basis or root of a scientist’s view on subject areas as well as deepened understanding and appreciation on the discoveries and tribulations which led the disciplines of his/her work to the present state of scientific endeavors.
To explain this, I will first explain using my own experiences, and how these experiences led to my own multi-disciplinary viewpoints on biology and disease. Next, I will show how Dr. Bernstein’s vast experience over the years has formulated his overarching, multi-disciplinary viewpoint on medicine and pathology.
Being under the tutelage of such an experienced mentor with vast expertise, and getting to understand his viewpoints, has been an invaluable learning experience for me, and am truly grateful to Dr. Bernstein for his time, effort, and discourse, both scientific and nonscientific, we would have on various subjects, My scientific training started in the Toxicology program at the Philadelphia College of Pharmacy & Science (later named University of the Sciences in Philadelphia, I prefer the former name the college was the first School of Pharmacy in the United States).
This toxicology program was just initiated by Dr. Gary Lage, at the bequest of many major pharmaceutical companies to develop the first-in-nation program to train young scientists in the field of toxicology. I was in the earliest graduating classes of this newly founded program and later realized what great timing it had been. I have always seemed to gravitate to the more applied and translational fields, even at an early age. And the opportunities, especially in research, afforded to me at such a small, intimate environment helped solidify my appreciation for the multi-disciplinary nature of biomedicine. At this time, molecular biology and the fields of oncogenesis were at its infancy, and the terms translational research and precision medicine were not in existence.
The field of immune-oncology had not gained traction from the initial discoveries of James Allison. Scientific discovery was still young but soon to be very rapid and exiting. Since this new program in Toxicology was taught by pharmacologists, my appreciation and viewpoint of cancer and oncogenesis centered on the mechanism of action of chemicals to result in carcinogenesis, giving me an appreciation of the dose-effect relationship or lack thereof (No-Observed Effect Limit) of many carcinogens.
Later in my professional life, I came to the realization of the uniqueness of this mindset due to my early training, as many in my chosen field had focused on mutated proto-oncogenes as drivers of the cancer process (potentially due to a focus on molecular biology) and had largely ignored metabolic changes that occurred or precluded the oncogenic state. Later in my research efforts, I would notice that many tumors, preferentially solid tumors, may require a predisposing cellular state, or ‘priming’ for oncogenesis.
My next experiences would involve the noncanonical nature of proteins, enzymes and (in general) the whole pathologic process. This term ‘noncanonical’ would appear to follow me all through out my scientific endeavors, even to today. When the Philadelphia Eagles coach Buddy Ryan said “what comes around goes around” I hadn’t realized what a fitting phrase this could be in many situations.
At the start of my PhD thesis work under Dr. Michael Sirover, we were attempting to purify what we felt was the product of our clone of the human uracil DNA glycosylase, an enzyme critical in the base excision DNA repair process. However, at that time, GenBank was not something you easily access and had to have an appointment to scan your sequence in, as this was all on a UNIX server. It appeared our clone was 100% identical to the subunit of GAPDH (glyceraldehyde 3 phosphate dehydrogenase), however, our lab’s results suggested that GAPDH might be a multifunctional protein. This idea landed the lab in hot water of course and my thesis project on this was in essence over because of being shunned from the field. We therefore embarked on investigating nitric oxide-induced post translational modifications of GAPDH and summarily found these modifications may regulate some of GAPDH’s pleiotropic functions, eventually, GAPDH was accepted as a multifunctional protein.
As the field of cancer research was exploding, just as I entered my postdoctoral years, I felt behind the curve in my knowledge of molecular biology and the genetic basis of cancer, especially with respect to oncogenes and tumor suppressors. I was extremely fortunate though to have a great mentor, Dr. Thomas Hamilton, who over his years had vast experience in the molecular basis of ovarian oncogenesis as well as the pharmacology of its treatment and development of acquired resistance to such treatments.
Others, at Fox Chase Cancer Center, and collaborators and colleagues in the cancer field who I had the luck to associate with at international meetings, gave me much needed appreciations for the genetic basis of cancer as well as the new paradigms of translational research, the ‘omics and big data revolution, and precision medicine. These were all new and invaluable experiences, however maybe I had strayed from the older view of metabolism as a potential driver in cancer view.
Dr. Bernstein brought me back and am glad I had the opportunity to interact with him on this e-book project, which brought me back to appreciating the overall viewpoint of disease progression.
I want to discuss how Dr. Bernstein’s experiences, especially the numerous colleagues he has worked with has firmed his unique views on medicine and pathology. Dr. Bernstein’s CV and list of collaborators reads like a Who’s Who in Medicine: people like Harry Maisel, Averill Liebow. Nathan Kaplan, Johannes Everse, Norio Shioura, Percy Russel, Herschel Sidransky, Sherman Bloom, Dhristos Tsokos, Gustave Davis, Walter Pleban, Jowseph Babb, Inder Mayall, Yves Ingenbleek, Otto Warburg, Gil David, Ronald Coifmann, Larry Kaplan, as well as numerous others.
It is this vast network of medical expertise, as well as Dr. Bernstein’s own vast knowledge and expertise, that has formulated this crucial work of bringing metabolism into the ‘omics era and the new role metabolomics will have to play in the future of medical research and personalized treatment. The reader needs to read each of these volumes in its entirely to fully appreciate both the past discoveries which are leading to today’s therapies as well as gaining a wide and multi-disciplinary view of the pathologic process.
Voice of Aviva Lev-Ari, PhD, RN
Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology
Series D: is the only series in our BioMed e-Series that focus on the clinical aspects of several biological systems and biological processes in human body:
- Volume One: Metabolic Genomics & Pharmaceutics
- Series D, Volume Two & Three: The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications
- Series D, Volume Four: Human Reproductive System, Genomic Endocrinology and Cancer Types
This volume on the human reproductive system, genomic endocrinology and cancer types of the Human reproductive system would not have been possible to have been written by our Team unless we would have had completed covering the most critical biological processes to life, such as Metabolism (Volume 1), the Immune System (Volume 2), Infectious Disease (Volume 3) and the final volume to be presented below, on the Endocrine system, what is known to date in Genomics of endocrine glandes and the cardinal functions played by hormones that are affecting reproduction and infertility, as well as the occurrence and development of cancer in the organs of the reproductive system.
Volume Introduction
Voices of Dr. Stephen J. Williams, PhD and Voice of Dr. Aviva Lev-Ari, PhD, RN
Voice of Dr. Stephen J. Williams, PhD
This is the fourth volume of the Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases and Reproductive Genomic Endocrinology.
Whereas the first volume focused on a thorough didactic on the concepts behind metabolomics (the integration of the studies of metabolism but integrating ‘omics features such as big data, metabolome networks, proteomics and protein networks and genomics), the subsequent volumes, and this current one, explains the concepts in light of the clinical challenges we face today. Each of the chapters is geared for the level of a medical student and can be an excellent main source of information or supplemental material for medical school educational purposes. In addition, it can be also used as a reference for licensing board exams, and a reference source to supplement baccalaureate level biology courses.
The current volume, Volume 4, is divided on topics related to Reproductive Genomic Endocrinology and discusses how our current view in endocrinology and embryology has changed due to the advances in genomic, proteomic, and metabolomic technologies, especially in the diagnosis and treatment of diseases and conditions on a hormonal and/or endocrine basis.
First, a general discussion on issues related to human reproduction are discussed, including bioethical concerns not seen in the pre genomics era. Reproductive biology and endocrinology are presented with new knowledge obtained from metabolomic studies. Part 2 discusses embryology emerging from the knowledge we have been acquiring on the cell biology of stem cells, including medical uses of these pluripotent cell types. The book further explains new findings in endocrinology and female and male reproduction as well as new insights into cellular signaling. In the last two chapters, specific examples of new clinical breakthroughs brought on by the combination of our new knowledge of metabolomics, stem cell biology, endocrinology, genomics, and transcriptomics, especially in the areas of diabetes and cancer. New treatments for diabetes, based on reprogramming stem cells are discussed in chapter 9. Chapter 10 discusses cancers related to the endocrine system and how the knowledge of the metabolome and proteome have advanced new treatments in hormonal-based cancers.
Voice of Dr. Aviva Lev-Ari, PhD, RN
This volume is unique in covering in one book the following cardinal interrelated aspects of wellness and disease:
- Causality,
- Intermediation,
- Detection, and
- Dysfunctions, maladaptations and the pathologies of reproductive organs
CAUSALITY
This aspects is presented as Discoveries in Endocrinology: Adrenal Cortex Sex Hormones, Thyroid Function and Disorders. Pituitary Neuroendocrine Axis, Endocrine Action on Midbrain, Pharmacological Action of Steroid Hormones, Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases and
INTERMEDIATION
Intermediation covers Hypermetabolism, Nutrition and Fertility, Diabetes and Sexual Hormones, Genders redefined by Biology and Personal Care Chemicals and Puberty Onset.
DETECTION by Genomics
NGS Will Revolutionize Reproductive Diagnostics: i.e., Endometriosis: Genomics Diagnosis @UCSF and new fertility marker. Male Sexual Function and Fertility: Male Infertility and Genomics: Fertile men carried a complete set of the sperm RNA elements; however, most of the infertile men did not.
REPRODUCTIVE ORGANS: Dysfunctions and Pathologies
The book covers Impairments in Pathological States: Endocrine Disorders, Stress Hypermetabolism and Cancer. Dedicated chapters are to
- Breast Cancer,
- Ovarian Cancer,
- Cervical and Endometrial Cancer,
- Prostate Cancer.
Not covered in the book is Testicular cancer. It is encouraging to report that in 2020, 5-year relative survival rates for testicular cancer:
| SEER stage | 5-year relative survival rate |
| Localized | 99% |
| Regional | 96% |
| Distant | 73% |
| All SEER stages combined | 95% |
SOURCE:
http://www.cancer.org › cancer › detection-diagnosis-staging
Part 1
General Topics on Human Reproduction
Introduction – Dr. Sudipta Saha, PhD
A gene therapy for blood disorders, a new class of medications for cystic fibrosis, an increased access to telemedicine are some of the innovations that will enhance healing and change healthcare in the coming year according to distinguished panel of clinicians and researchers. This section initially gives a brief account of ten such innovations. Legal rights in birth control, etc. also has been discussed in details in this segment. The other discussion in this section is on female infertility which is a global medical and social condition caused by various pathophysiological alterations. While in developing countries this condition is related to preventive, diagnostic and therapeutic inadequacy, multiple ovarian endocrine dysfunctions in industrialized nations are apparently associated with improper life-styles.
Micronutrients have essential roles in fertility, and inadequate levels can have an adverse impact on the ability to conceive. It has been reported that a proportion of women of childbearing age in general, as well as those who struggle to conceive, have lower than recommended levels of certain micronutrients. Thus, there is a rationale to supplement with vitamins and minerals before conception to optimize nutritional status and perhaps have positive effect on fertility. This segment also discusses the mother-to-child transmission of hepatitis B virus in spite of use of antiviral drug taken during pregnancy and after delivery. Finally, the various types of neonatal pathophysiology has been discussed in details.
Part 2
Innovations in Cell Biology and Embryology
Introduction – Dr. Irina Robu, PhD
Embryology is a branch of science, that would require understanding the intimate relation between structures in different organs is an incredibly complicated process. The organism is first one cell, the zygote in which the cell divides and the process is repeated again. The zygote, results from the fertilization of female egg by the sperm cells. The zygote possesses half of DNA of each two parents. It is well known that at this stage, the cells are undifferentiated and they have the potential to form any part of the body. Yet, over time these cells become more and more differentiated and acquire the characteristics of a mature cell. The circulatory, excretory, and neurologic systems all begin to develop during this stage. It is amazing that in eight weeks, a single cell develops to an organism with multi-level body plan.
Research using human embryos has expanded in the recent years due to technical advances. The advancement has led researchers to develop lab models of human embryos using pluripotent stem cells or induced pluripotent stem cells. The models can be referenced based on the developmental points such as blastoids or cells that are used to create that model such as micropatterned HESC colonies. In these models, scientists can mimic aspects of the embryo developmental stages. Yet, they can’t function as a fully functional human embryo. In contrast to embryos created via fertilization, embryos created in the labs from preexisting pluripotent stem cells without crating fully develop embryos.
At the same time, human embryology varies from country to country. Each nation develops its policies and goals based on national culture, history and politics. Many nations still view the field of embryology as a way to understand how some genetic disorders occur, whereas other nations find embryology strongly challenged by religious beliefs.
Part 3
Cell Signaling
This topic is covered at length in Volume 3
-
NEW GENRE Volume Three: The Immune System and Therapeutics
Part 4
Genomics in Prenatal and Childhood Wellness
Introduction – Dr. Stephen J. Williams, PhD
This chapter discusses the genetic, epigenetic, proteomic and transcriptional aspects of reproductive and neonatal disorders. The chapter starts with a tutorial on the process of transcriptional and epigenetic control of gene expression and also explains, in detail, the process of protein translation. There have been much advances in the area of diagnostic genomics most notably technical breakthroughs in our ability to rapidly and reliably sequence genomes from patients however, over time, it has become clear that one has to look at the totality of changes, including changes in the cellular portrait of proteins, the proteome, and its concordant epigenetic or post translational modifications occurring in the proteome in a given disease, treatment, or patient cohort.
Perspectives on the clinical implications toward understanding the complexities and regulation of the proteome are presented. Technological advances in mass spectrometry have allowed us to analyze changes occurring across the spectrum of cellular protein networks in multiple disease states and proteomic responses to therapies. As discussed in the following articles, the importance of these advances is clearly seen in revolutionizing reproductive diagnostics, and currently is assisting pediatricians in diagnosing and treating multiple childhood disorders in a more personalized medicine paradigm. International experts in these clinical fields weigh in on the impact these advances in analyzing and understanding the changes in these cellular networks play in treating children and patients in a series of panel discussions from clinical conferences.
Part 5
Discoveries in Endocrinology
Introduction – Dr. Irina Robu, PhD
Endocrinology is a dynamic field, where new applications and hormones are being discovered with eh potential to influence every biomedical sphere. The endocrine system is a network of glands and organs that are located through the body by regulating a range of bodily functions through the release of hormones. Hormones can coordinate body’s internal metabolism, reproduction, growth, sensory perception and movement. It is well known that a wide range of medical problems can arise as a result of hormonal imbalance. Human have over 50 types of hormones which can exist in various amounts and have a vital impact on the body function and development. The human endocrine system consists of a number of glands. The glands release the hormones into the bloodstream and are transported to the tissues and organs.
Using the combination in the disciplines of endocrinology and molecular biology, led to an explosion of technological advances. One of the major developments includes the advancement of insulin smart pens that track the amount and timing of insulin doses, with data shared with mobile apps while making dose recommendation. The advances in the glucose monitoring pump into hybrid closed-loop systems which are able adjust insulin delivery on the basis of live glucose measurements.
These progresses show tremendous promise for patients with type 1 diabetes, as well as parents of pediatric patients. These technologies offer possible opportunity to minimize the ease with which glycemic rate can be controlled, to reduce hypoglycemia and as a result enhance quality of life.
Another advancement in the field of endocrinology, includes the discovery of the Kiss1 gene and its receptor GPR54 which is known as the human metastasis suppressor gene and has the ability to suppress melanoma and cancer metastasis. Humans with mutations of the GPR54 gene do not undergo puberty and they are usually sterile. So the discovery of the role of kisspeptin and its receptor opens thrilling possibilities in the treatment of a variety of conditions such as delayed or precocious puberty, infertility and sex hormone-dependent cancers, such as breast and prostate cancer.
Part 6
Frontier of Female Endocrinology
Introduction – Dr. Sudipta Saha, Ph.D.
Infertility is defined as the inability to conceive after one year of regular coitus without contraception. Approximately 10% to 20% of childbearing-age couples are infertile in the United States. The demand for infertility investigations has increased dramatically in recent decades. A lot of advancements have taken place in the last decade in the research of reproduction and fertility. Hormone replacement therapies in menopause are not a good solution as it has its side effects. In replacement bioengineered ovarian constructs may help in the same therapy with natural production of required hormones. Although low AMH and high FSH are general indicators of diminished egg quantity in a female but modern research showed that although these are good predictors of egg content but are not full proof predictors of fertility or pregnancy ability.
A mathematical algorithm based immunological timeline has been proposed by modern research that can predict on the maturity of the fetus. A PGF2α based genetic switch for sexual behavior in females has been identified in fish model. A female libido enhancer like Viagra in male has been identified to treat hypoactive sexual desire disorder in premenopausal women. Scientists have also identified patterns of genetic activity that could help in early detection of disorders like endometriosis that affects millions of women worldwide. Different inhibitors and enhancers of hormones are also identified for the modulation of fertility. In the following section some of these research advancements have been discussed in a concise manner.
Part 7
Male Sexual Function and Fertility
Introduction by Dr. Marc Feldman, PhD
Burnet C. and Mildred Finley Wohlford Professor of Biology, Director, Morrison Institute for Population and Resource Studies, Co-Director, Stanford Center for Computational, Evolutionary and Human Genomics
Sperm count declines have been correlated with environmental deterioration, lifestyle changes, and overall morbidity and mortality. In Western countries, an increasing proportion of men have sperm counts below the threshold for sub-fertility or infertility. Although tobacco-smoking is a risk factor for infertility, men who have smoked marijuana at some time in their lives show an increase in their sperm count over those who have never smoked it. Some mice without a Y chromosome develop into males. These XOsra are always sterile, while only a minority of XYsra males have anatomical defects and are sterile. Using the pattern of X-ray refraction, filaments of the lysozyme-like protein, SLLP1, which is believed to be involved in targeting the mammalian egg, have been visualized and their structure revealed.
Human male infertility has been shown to be associated with an incomplete set of sperm RNA elements. Testosterone therapy delivered to men aged 65 and above with reduced serum testosterone levels improved sexual function, walking performance, and mood but had no significant effect on alleviating fatigue.
Research towards a male contraceptive pill has been on a backburner for many years. Scientists at Baylor College of Medicine have found that deletion of 30 out of 2,300 genes that are active in testes of mice produces infertility. This suggests an avenue for laboratory testing of chemicals that might disable functions of these genes and suggests targets for a male contraceptive pill. Another male contraceptive target is an enzyme in sperm cells’ outer membrane that is involved in sperm motility. Blocking this enzyme, ABHD2, could produce an effective male contraceptive. A third avenue towards male contraception involves a switching device, inserted in the vas deferens that stops sperm flow through this organ. The device, made of a medical-grade polymer often used in implants, is undergoing clinical trials.
Part 8
Metabolomics and Microbiome Genomics
Introduction – Dr. Irina Robu, PhD
Biological systems can be studies at various level, from DNA up to life sustaining reactions. The most basic level is genomics, the study of DNA structure, function, and modification, because it gives insight into the DNA code and the world around us. The final level of study would be metabolomics, the analysis of small molecules within the system, the change in their presence and concentration over time. Metabolomics has in the past 10 years, become a desired experimental method in studying disease pathogenesis. Since biological systems are highly dynamic and their cellular products are influenced by a variety of factors such as genes, age, nutrition, lifestyle, disease, drugs and the environment. Metabolomics research is a treasured tool used to characterize intra- and inter-cellular, dynamic molecular changes in a metabolism of drugs or environmental toxicants and discovery and validation of disease biomarkers. Turnover of metabolites over time can occur in seconds unlike in the levels of proteins and transcripts which usually takes min or hours. Subsequently, sample collection and preparation are one of the most crucial steps in metabolomics experiments.
Even though hypothesis generating metabolomics permits in-depth analysis of complex, quantifiable sample analytes, hypothesis driven metabolomics allows for the quantification of known metabolites. As a result global untargeted metabolomics is used as a hypothesis-generating discovery application, whereas targeted metabolomics is hypothesis-driven and used to make available quantification and validation of specific metabolites of interest or metabolic pathways.
Part 9
Diabetes and the Insulin Treatment
Introduction – Dr. Irina Robu, PhD
Over the years, occurrence of diabetes has increased not only nationally and globally. It is currently, the leading cause of mortality. And the underlying cause of diabetes varies by type, but all can lead to excess sugar in the blood. Diabetes is a condition in which the body can’t regulate or properly use sugar in the blood. The pancreas plays an essential role in controlling the levels and within the pancreas hundreds of cells, known as islets of Langerhands regulate blood glucose. The beta cells inside the islets produce insulin which is then released into the blood stream. And when sugar level reaches a specific threshold, it then signals the other cells to take up sugar. And as a result, the human body is always balancing the blood sugar. But in diabetes the blood sugar is elevated because either the pancreas doesn’t produce enough insulin, type I diabetes or because the cells in the body fail to respond to the insulin ( type II diabetes)
Type 1 diabetes can develop at any age, but it is more common in childhood and adolescence, whereas type 2 diabetes is more common in people over the age of 40.
With no full cure available, the range of management options are needed such as finger pricks, blood tests, meal planning and painful injections. The current treatment for diabetes focuses more on monitoring blood glucose levels in addition to noninsulin therapies such as insulin sensitizers, alpha-glucosidase inhibitors, incretins, pramlintide, bromocriptine and insulin therapies (insulin and insulin analogues). Type I diabetes patients struggle to balance their blood sugar and are given insulin to help them control the glucose levels multiple times a day. Type II diabetes patients can control it via diet and exercise, but some of them have to take up insulin injections to control sugar levels or additional medications to deal with the complications of the disease. Despite the ability to monitor blood glucose in real time, recombinant insulins and noninsulin therapies, treatment for diabetes remains less than ideal.
Even though, cell therapy is one of the biggest hopes near emerging a cure for diabetes. One problem with transplantation of islets is that patients need to be given islets from more than one organ donor, which means the patients who receive the transplant need powerful immunosuppressants drugs to stop the immune system from attacking the new islets. Replacing the absent insulin producing cells could possibly recover normal insulin production and cure patients.
One of the best alternatives comes from the Diabetes Research Institute in US , is currently developing a bioengineered mini-organ where insulin-producing cells are encapsulated within a protective barrier. And in 2016, the institute announced that the first patient in Europe treated with this in an ongoing phase trial I/II no longer needs insulin therapy. A similar device is being developed by Viacyte, where after the phase I trial, the company is working on revamping the engraftment of insulin-producing cells. Another by Orgenesis where cells from the patient’s liver are transformed into insulin-producing cells to avoid the issues of sourcing cells from donors.
There have been countless improvements to reduce the toll from diabetes-related complications through enhancements in insulin administration and glucose monitoring, but the perfect treatment will be the replacement of the missing insulin-producing pancreatic beta cells.
Part 10
Cancer of the Human Reproductive and
Genitourinary Systems
10.3 Cancers Types in the Human Reproductive and Genitourinary Systems
Introduction
by Stephen J. Williams, PhD
The following chapter deals with hormone-related cancers, these being cancers predominantly arising in the genitourinary system and including breast cancer, as well as the thyroid and osteosarcoma. Before the mid 80’s, oncogenesis was seen the result of uncontrolled cellular proliferation, and the focus in the cancer field was on abhorrent cell cycle regulation. However, it became apparent the etiology of many cancers involved and required the presence of hormonal factors (reviewed in (Henderson & Feigelson, 2000).
These group of cancers were referred to as the hormone-related cancers, some of which are highlighted in this chapter. This new developing polygenic model of cancer predisposition ultimately led to a paradigm shift in the detection, chemoprevention, and treatment of such cancers, namely using molecular biomarkers of hormone receptors to classify tumors (detection) with the hormone antagonists like tamoxifen and raloxifene (prevention) and other Synthetic Estrogen-Modulators (or SERMS) and antiandrogens (treatment). Some details of the history and underlying discoveries which led to this paradigm shift will be discussed in the Epilogue of this Chapter.
It has become established that many risk factors for the development of cancer involves hormonal balances. For instance, estrogens unopposed to progestins are a known risk factor for endometrial cancer (Henderson, Ross, Pike, & Casagrande, 1982; Key & Pike, 1988a, 1988b). Estrogens also have been implicated as a risk in the etiology of breast cancer with evidence from both animal models and from epidemiologic data. Very compelling data from studies on menarchie (ovulatory cycle) and oral contraceptive use as well as data from the hormone replacement studies have linked estrogens and reproductive cycling to incidence of breast cancer.
With respect to risk factors in the etiology of ovarian cancer, it had been known that nulliparity, or lack of giving offspring, is a very high-risk factor for development of ovarian cancer. Conversely, use of oral contraceptives, including estrogen and high-dose progestin, is negatively correlated with ovarian cancer risk and deemed as a preventative measure. Interestingly, although treatment of breast, prostate and endometrial cancers, especially those with corresponding hormone receptor positive status have been successfully treated with anti-hormonal agents, this cannot be said for treatment regiments for ovarian cancer, where for thirty years the mainstay therapeutic regimen has been a platinum analog with a taxane. Below is a table of corresponding risk factors and protective factors related to hormones.
However, due to our new ability to genetically classify tumors, it has been identified that many high-risk breast and ovarian cancers have a genetically heritable component, although usually this is only about 10% of cancers. Although this may seem disadvantageous, our new found ability to define genetic sub-cohorts of patients, in the instance of breast, endometrial, and ovarian cancer into BRCA wild type or mutants has ushered in a new paradigm for treatment, such as the use of PARP inhibitors in these patients to produce what is termed “synthetic lethality”. Synthetic lethality happens when the cytotoxicity of a certain drug is greatly enhanced or “appears” due to a certain genetic background such as a genetic defect or gain of function. In the case of cancers exhibiting a BRCA1/2 mutation and subsequent loss of the higher fidelity homologous recombination repair of DNA lesions, the inhibition of PARP1 forces the cell into the more error prone nonhomologous repair mechanisms and subsequent increases the frequency of DNA strand breaks. For reference the reader is directed to a great review and following figures by Thomas Helleday (Helleday, 2011).
Summary of Part 10
by Stephen J. Williams, PhD
A Century of discovery to the development of estrogen-modulatory therapy – a brief history
The discovery that cancer growth could be driven by hormones
Late 19th Century
The discoveries in the later 19th century discovery laid the groundwork for the development, a century later, of tamoxifen and other selective estrogen modulators (SERMs), important today in the treatment and prevention of breast cancer. In 1878 Thomas Beatson discovered that the breasts of rabbits stopped producing milk after he removed the ovaries. His results were presented to the Edinburgh Medico-Chirurgical Society in 1896:
“This fact seemed to me of great interest, for it pointed to one organ holding control over the secretion of another and separate organ.”
Because the breast was “held in control” by the ovaries, Beatson decided to test removal of the ovaries (called oophorectomy) in advanced breast cancer and found that oophorectomy often resulted in improvement for breast cancer patients. He also suspected that “the ovaries may be the exciting cause of carcinoma” of the breast. He had discovered the stimulating effect of the female ovarian hormone (estrogen) on breast cancer, even before the hormone itself was discovered. However, it was not until 1929, by Adolf Butenandt and Edward Doisy, that the ovarian hormone in question was purified and identified as estrogen.
Mid 1900’s and the Discovery of the Estrogen Receptor: Elwood Jensen
Up to the 1950’s, most believed the mechanism of action of estrogen on tissue growth relied on the enzymatic hydroxylation at the 17-β position of estradiol utilizing NADH. However, this hypothesis did not explain the uterotropic effects of the synthetic estrogen analog diethylsilbestrol, which did not need to be hydroxylated for it growth enhancing effects. With lessons learned from a steroid chemistry fellowship in Zurich under Nobel laureate Leopold Ruzicka, Elwood Jensen went to University of Chicago as faculty under the head of Charles Huggins, who won the Nobel for his work on prostate cancer. There, Elwood, along with postdoctoral fellow Herbert Jacobson, started to investigate how small amounts of estrogen affected uterine tissue growth.
Although their initial plan to investigate potential targets of estrogen binding was hindered by the fact that, at that time Chicago did not allow experimentation with radionuclides (specifically tritiated estrogen), a local lab at Argonne National Laboratories, home of the Fermi lab notorious as a laboratory involved in the first nuclear bomb, allowed such experimentation.
They noted that an unmodified estrogen could promote uterine tissue growth. When the finding of the now debunked enzymatic theories was announced it did not receive much fanfare, and Jensen and colleagues termed the factor which bound to estrogen as “estrophilin”, later to be identified as the estrogen receptor. Subsequently, sedimentation gradient experiments by John Baxter, Pierre Chambon (who also discovered the retinoid receptors and figured out retinol signaling), Ron Evans, Bert O’Malley (a pioneer in nuclear receptor signaling and the progesterone receptor) and Keith Yamamoto led to discoveries of multiple nuclear steroid hormone receptors, ushering in a new biological cascade which could be taken advantage of for therapeutic uses. After Jack Gorski and Elwood Jensen discovered additional forms of estrogen receptors, including the cytoplasmic and nuclear forms, these additional discoveries helped Bert O’Malley’s group to show how activation of these receptors by the binding of estrogen led to activation of the transcription of multiple genes related to the cell cycle and cellular growth.
1990s: Structure/function studies of the estrogen receptor, inhibitors, and cancer therapy.
A few technologic advances such as enhanced X-ray crystallography, enzymatic radioimmunoassays, and molecular techniques developed in the 90’s allowed for the structure determination and development of specific estrogen receptor antagonists. These tools now allowed cancer researchers the ability to tease out the clinical utility and role of the estrogen receptor in hormonally sensitive cancers like breast cancer. The advances led to the discovery of one of the most impactful therapies to that date which revolutionized breast cancer treatment and led to the early push for the next era in cancer therapy, the so-called ‘precision-medicine era’. To understand this, one needs to look no further than the research of Dr. Craig Jordan, the ‘father of tamoxifen’, of which the following articles are dedicated to.
V. Craig Jordan OBE, PhD and the discovery of SERMs and Tamoxifen
Craig Jordan, OBE, PhD, has been recognized by the Endocrine Society as the 2018 Laureate of the Gerald D. Aurbach Award for Outstanding Translational Research. Dr. Jordan is the Dallas/Fort Worth Living Legend Chair of Cancer Research in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center.
Once in a while, one gets lucky enough in science to be at an institution surrounded by the greats in science. For me that was years I spent at The Fox Chase Cancer Center among great cancer researchers such as Nobel Laureates Baruch Blumberg (Hepatitis B vaccine and causality in liver cancer), Joseph Testa, Philip Tsichlis and Alfonso Bellacosa (discovery of AKT2), Nobel Laureates Erwin Rose (ubiquitin and protein degradation). There I was able to meet and interact with Dr. Jordan, who is referred to as the “father of tamoxifen,” for his work in reinventing a failed contraceptive known as ICI 46,474 as a breast cancer treatment. It always was impressive to me that such greats of science were also the most congenial, collaborative, and helpful individuals I had the pleasure to either work with or meet.
Dr. Jordan also developed the strategy of long-term adjuvant tamoxifen therapy, as well as describing and deciphering the properties of a new group of medicines called selective estrogen receptor modulators, and the first to discover the preventive abilities of both tamoxifen and the drug raloxifene.
His Laureate citation reads:
“For the discovery and development of a novel group of medicines called selective estrogen receptor modulators (SERMs) applied to address the treatment and prevention of major diseases in women. Ideally, the SERMs switch off estrogen target tissues in the breast and uterus to prevent cancer and switch on tissues to maintain bone density or lower circulating LDL to prevent coronary heart disease. The discovery that tamoxifen is metabolically activated to 4-hydroxytamoxifen (4-OHT) with a 100-fold increased affinity for the ER became the lead compound for the new SERMs raloxifene, bazedoxifene, and lasofoxifene.
Tamoxifen and raloxifene are the pioneering SERMs whose diverse applications in breast cancer treatment and prevention, as well as osteoporosis, have extended countless women’s lives. Each has scientific origins through pharmacologic discoveries in Jordan’s laboratory. Few other mechanisms-specific medicines have such broad applications. This success has stimulated all future applications for selective nuclear receptor modulators in medicine.”
Dr. Jordan has been recognized by ASCO with the American Cancer Society Award and Lecture (2006) and the David A. Karnofsky Award and Lecture (2008). In 2014, Dr. Jordan was named as one of the 50 Oncology Luminaries for his identification of the strategic applications of tamoxifen as treatment for patients with breast cancer. He has also been recognized by Queen Elizabeth and Princess Diana for his pioneering work which has saved countless lives of breast cancer patients.
An important reference on the use of SERMs such as tamoxifen and raloxifene is V. Craig Jordan. Tamoxifen or Raloxifene for Breast Cancer Chemoprevention: A Tale of Two Choices—Point. Cancer Epidemiol Biomarkers Prev November 1 2007 (16) (11) 2207-2209; DOI: 10.1158/1055-9965.EPI-07-0629
The use of SERMs now necessitated the molecular classification of Estrogen Receptor status of breast cancers and ushered in a new paradigm of precision medicine, determining clinical strategy based on molecular biomarkers specific for a given drug’s efficacy. In addition, at the same time the ongoing problem of acquired resistance to estrogen modulators, antagonists need to be dealt with. The above mentioned discoveries of the utility of PARP inhibitors, which use is also based on the identification of a mutant biomarker for its efficacy, namely loss or mutant BRCA1/2, is now a new weapon needed to combat the advent of acquired resistance to previous developed therapies. Just as discoveries a century ago had led to new paradigms of therapy, so too must today’s discoveries be translated, in the future, to therapies to circumvent the resistance developed by therapies coming to light now.
The War Will Unfortunately Go On!
Volume Summary by Dr. Sudipta Saha, PhD, Editor
Although lot of researches are going on in reproductive biology, still it is one of the less explored field in biology compared to other study areas. Infertility is one of the major modern day problems arising from occupational hazards and lifestyle and it is also a social stigma in many societies. Added to this are the related hormonal problems and cancers. We may know the basics of reproduction as in vitro fertilization is regularly in practice nowadays worldwide but much is yet to be known about sperm motility, sperm-egg interaction and fertilization in details.
This book volume deals many such researches which are trying to put some light on the area of reproductive endocrinology and related areas. The volume starts with legal matters of reproductive rights and then goes through stem cell, cell signaling, genomics and endocrinology of reproduction. It speaks about the advancements in male and reproductive endocrinology. In recent years, the development of new technologies capable of monitoring genome function has resulted in fewer hopeful estimates and increasingly solid depictions of genome output from individual samples. It is now known that rarely a single gene can cause a disease. Multiple factors including our genome and environmental factors all play a role. The Human Genome Project and subsequent genomic revolution has not only led to advances in medicine but affects many other areas of our lives, e.g. veterinary sciences and agriculture. Advances in endocrinology genomics nowadays are helping with new diagnostic and therapeutic strategies in many conditions. In the future, all clinicians will need to become increasingly comfortable with embedding genomics into the day-to-day clinical practice, to tailor patients’ management plans to deliver more personalized medical care.
Reproductive genomics is a broad topic that includes developmental aspects, male/female/transgender populations, gametes/embryo/implantation, and the impact of reproductive disorders. Presently genetic screening of an individual is also possible before the stage of implantation. This book also relates metabolomics, microbiome genomics and some other endocrine problems with reproductive biology. Then the book talks about different types of male and female cancers related to reproduction. Therefore, this book volume gives a total idea of problems related to reproductive endocrinology and modern research advancements related to the field.
EPILOGUE by Dr. Stephen J. Williams, PhD, Editor
This Volume explores ideas and discussions that have a deep human impact both in creating life and preventing human death. The material covered focuses on innovations in human reproduction from cellular biology to embryo stem cells, cell signaling, and genomics inclusive of NGS. Further topics include discoveries in general reproductive endocrinology and specifically at the frontier of female endocrinology artificial ovaries, the immune system clock during pregnancy and the genomics of endometriosis. Additional topics include advances in male sexual function and fertility, and metabolomics and microbiome genomics. The exciting parts of this Volume are the implications on clinical conditions such as, diabetes and insulin treatment, cancers types of the reproductive and genitourinary systems, breast cancer, ovarian cancer, cervical and endometrial cancer and prostate cancer. None of the topics in this Volume are theoretical; they are quite proven eloquently and in significant depth. The science in this Volume aims at genuine deep knowledge about truly complex systems that can change the real world for the sake of humankind.
However, to have a discussion on the impact that genomics is currently having or will have in clinical practice of reproductive endocrinology and precision medicine, we must look back at some of the predictions for the potential of genomics at the advent of this field. For this we go to Dr. Francis Collins, the spearhead for the Human Genome Project and his eloquent opinion piece in Nature from 2003 entitled A Vision for the Future of Genomics Research (Collins et al., 2003). As Dr. Collins notes, just as the great discoveries by Mendel, the determination of the genetic code and structure, and the establishment of high throughput sequencing techniques were critical for the success of the Human Genome Project, so will the efforts to map the whole human genome, together with the resultant technologies of genomics, be critical for the next era of precision medicine to come. The Human Genome Project’s new research strategies and experimental technologies resulted in an ever-expansive treasure trove of genetic data and insights into normal human physiology as well as pathologic diseases. Together with advanced and more powerful computing and bioinformatic algorithms, the results from this herculean effort would have, as he theorized, transform our ability to curate, analyze, and manipulate all sorts of genomic data for the purposes of treating patients in a more personalized manner.
While the HGP was starting, the initiators of this project also had the foresight to make an investment into studying the ethical, legal, and social implications of genomics research and its applications. This had resulted in policy boards comprising of scholars in bioethics, law, social science, clinical research, theology, and public policy to evaluate any ill effects of the new technologies on society. Dr. Collins, after having numerous discussions with the experts in the field, envisioned the future of genomics to be structured as a building, with the Human Genome Project as the Foundation and multiple floors or themes resting above such as:
- Genomics to biology
- Genomics to health
- Genomics to society
with each of these themes he presented with bold grand challenges centered on pillars of education, ethics, training, technological development, computational biology, and open access resources to scientists and clinicians. Collins and others understood the need for sound policy development bases on these pillars, themes, and foundation of the HGP. It was also predicted that such an effort of broad sweeping changes would only occur with public support and an “environment where traditional boundaries become ever more porous”.
This takes us to the current time and in an article Where is Genomics Going Next, Barbara Cheifet discusses the potential for even greater advances in the coming years with the journal Genome Biology Editorial Board (Cheifet, 2019). A few quotes from this paper include:
Genomics is a key underpinning for metagenomics. This is the case because reference-based approaches are dramatically faster and more accurate than reference-free approaches whenever the reference database is complete and correct. However, with a few exceptions (such as bacteria in the human gut of healthy Western adults), we are far from having adequate reference data.
—— Rob Knight, University of California San Diego
I believe that, increasingly, genomics will be integrated with other biological studies, such as studies of evolution, comparative genomics, transcriptomics and other Omics as well as large-scale functional studies.
I can suggest a few specifics:
1.
Structural genomics will increasingly involve the comparison of multiple genomes rather than single-species genomics. These comparisons can be quite comprehensive, offering insights above those that can be achieved by studies of a number of genes alone, or by synthetic analysis, or through deduction of ancestral genomes.
2.
Genome-wide analysis of evolutionary questions, such as studies of genes that are important for development or physiology or studies of the evolutionary genomics of human diseases that have a complex genetic basis, such as heart disease and diabetes.
3.
Genome biology of cis regulatory elements and of non-coding RNAs, with reference to functional studies and comparative analyses.
——— Hong Ma, Fudan University
The genomics field has matured, and the emphasis could now be shifting from methods-focused approaches to more theory-focused approaches, with stronger roles for machine learning in uncovering underlying principles. High-throughput sequencing and methods that rely on it have been the main driving force of genomics in the past decade. In the future, hypotheses that are based on genomic data could be investigated more thoroughly, for example with the use of CRISPR-Cas-based approaches.
———– Jernej Ule, Francis Crick Institute
And other studies such as whole exome sequencing and genome wide association in massive populations using the technologies and analytical methods emanating from the Human Genome Project were now feasible to utilize for precision medicine strategies in cardiovascular disease for example (Hou et al., 2020).
These technologies were also finding utility in determining genetic risk factors associated with fetal malformations and spontaneous abortion. Using whole exome sequencing Guo and others were able to identify multiple genetic risk factors involved in reproductive disorders {(Guo et al., 2018) and references within}.
In the field of genomic endocrinology, a number of novel disease related genes, for endocrine disorders such as hypogonadotropic hypogonadism, congenital hyperinsulemia, have been elucidated from genomics studies. In The Future of Genomic Endocrinology, Dattani and Martinez-Barbara, note that many of these discoveries were direct result of sequencing of the human genome and genome wide association studies of disease populations (Dattani and Martinez-Barbera, 2011). These studies have made use of the rapid advances in next generation sequencing and whole genome analysis. However they note that the major challenges will be the interpretation of vast amounts of data generated using these techniques. Additionally, a unique challenge in the area of endocrinologic disorders is the fact that many of these disorders are inherited in a dominant fashion and display variability in clinical manifestation due to differences in penetrance. Also, many diseases are polygenic, which complicates the analysis of GWAS data.
However, this brings us to the present and the challenges which exist today, particularly those challenges which have surfaced now yet issues brought up by Dr. Collins years ago, namely the social inequities which may result from genomics research and precision medicine.
Dr. Amy McGuire focuses on this unique problem in The Road Ahead in Genetics and Genomics (McGuire et al., 2020). As Dr McGuire notes,
“As we embark on the third decade of this century, we are now faced with the prospect of being able not only to more accurately predict disease risk and tailor existing treatments on the basis of genetic and non-genetic factors but also to potentially cure or even eliminate some diseases entirely with gene-editing technologies. These advances raise many ethical and policy issues …”.
In order to make genomics truly equitable requires a multifaceted approach. We have already seen the inequities in the COVID-19 pandemic with African Americans and with breast cancer treatment in the poorer parts of the Appalachia as well as in African nations. Three areas are proposed to alleviate these genomic inequities:
- Ensure equitable representation in genomics research
- There must be equitable access to that research
- Striving to achieve more equitable outcomes from genomic medicine
If we can address these three problem areas, we might come to the full realization of Dr. Collins vision for the post genomic age.
As the post genomic age evolves, investigators in this field of reproductive and endocrine genomics have found it necessary to conduct new lines in research in a more collaborative way, which fosters innovation and more rapid discovery. This is evident in places such as Cornell University’s The Center for Reproductive Genomics founded in 2006.
This team effort has produced new findings in reproductive sciences such as:
- Role of non-coding RNAs and DNA repair in reproduction and germ cell development
- Elucidation of new signaling pathways of the hypothalamic-pituitary-gonadal axis
- Use of CRSPR-Cas9 to generate single nucleotide polymorphisms that mimic human infertility
- Understanding sperm function to aid assisted reproduction in endangered species
- Determining how cancer stem cells function in ovarian, breast cancer and germ cell tumors
Volume Four
Human Reproductive System,
Genomic Endocrinology and
Cancer Types
2021
On Amazon.com since 02/02/2021
http://www.amazon.com/dp/B08VTFWVKM
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