Posts Tagged ‘androgen receptor’

Opening Ceremony and Award Presentations from the 2015 AACR Meeting in Philadelphia PA; Pennsylvania Convention Center, Sunday April 19, 2015: 8:15 AM


Reporter: Stephen J. Williams, Ph.D.

The following contain notes from the Sunday April 19, 2015 AACR Meeting (Pennsylvania Convention Center, Philadelphia PA) 8:15 AM Opening Ceremony and Awards Presentation

Ninth Annual AACR Team Science Award

Recipient: Designing Androgen Receptor (AR) Inhibitor Team

The Designing AR Inhibitors Team is a multi-institutional team that is composed of Charles Sawyers, MD, PhD, team leader, director of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center in New York, AACR past-president, and Howard Hughes Medical Institute investigator; Howard Scher, MD, chief of genitourinary oncology service and D. Wayne Calloway chair in urologic oncology at Memorial Sloan Kettering; and Michael Jung, PhD, distinguished professor in the Department of Chemistry and Biochemistry at the UCLA.

The team was honored for their collective work in discovering and developing the novel antiandrogen enzalutamide (Xtandi) for the treatment of metastatic castration-resistant prostate cancer in a collaboration that started ten years ago.

Twelfth Annual AACR Award for Lifetime Achievement in Cancer Research

Recipient: Mario R. Capecchi, Ph.D.

Dr. Capecchi is a geneticist who won the Nobel prize for creating technologies that resulted in the first knockout mouse. For this work, Capecchi won the 2007 Nobel prize for medicine or physiology, along with Martin Evans and Oliver Smithies, who also contributed.

AACR Distinguished Public Service Award

Recipient : Miri Ziv Director General of Israel Cancermiri_ziv_180_s_002

  • Instrumental in getting national Israeli mammography screening
  • Efforts led to national skin cancer screening program in Israel
  • Prevention/control programs
  • In 1995 representative to European Breast League

Ninth Annual AACR Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research

Recipient: Donald S. Coffey, Ph.D.

Dr. Coffey discovered the nuclear matrix and made pivotal discoveries understanding the process of DNA synthesis. He is the leader of the National Prostate Coalition and efforts led to the development of the Prostate Specific Antigen (PSA) as a prostate cancer biomarker. Now his lab is assessing the role of chaos, fractals and complexity in the self-organization of DNA, cells and tissue in relation to tumor biology.

In a side note, both Dr. Foti and Dr. Coffey had the same mentor, Dr. Sydney Weinhouse and Professor Leslie Helleman, who both studied the oxidation of free fatty acids and took Otto Warburg’s hypothesis a step further to understand how more complex cancer metabolism was than Otto had imagined.

Other award winners were:

Dr. Richard Pasdur of the FDA who won the Public Service Award

In memorial

Dr. Upton (M.D.) pathologist head of NCI and established EPA

Dr. Emmanuel Farber, M.D., Ph.D. – biology of tobacco control and issued the historical Surgeon

General’s report on smoking

Dr. June Biedler, Ph.D. – showed multidrug resistance and defined cytogenetics of  neuroblastoma


Other related articles on Cancer History and Social Media Coverage were published in this Open Access Online Scientific Journal, include the following:

Cancer Biology and Genomics for Disease Diagnosis

Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA

List of Breakthroughs in Cancer Research and Oncology Drug Development by Awardees of The Israel Cancer Research Fund

2013 American Cancer Research Association Award for Outstanding Achievement in Chemistry in Cancer Research: Professor Alexander Levitzki


Read Full Post »

Introduction to Signaling

Curator: Larry H. Bernstein, MD, FCAP


We have laid down a basic structure and foundation for the remaining presentations.  It was essential to begin with the genome, which changed the course of teaching of biology and medicine in the 20th century, and introduced a central dogma of translation by transcription.  Nevertheless, there were significant inconsistencies and unanswered questions entering the twenty first century, accompanied by vast improvements in technical advances to clarify these issues. We have covered carbohydrate, protein, and lipid metabolism, which function in concert with the development of cellular structure, organ system development, and physiology.  To be sure, the progress in the study of the microscopic and particulate can’t be divorced from the observation of the whole.  We were left in the not so distant past with the impression of the Sufi story of the elephant and the three blind men, who one at a time held the tail, the trunk, and the ear, each proclaiming that it was the elephant.

I introduce here a story from the Brazilian biochemist, Jose

Eduardo des Salles Rosalino, on a formativr experience he had with the Nobelist, Luis Leloir.

Just at the beginning, when phosphorylation of proteins is presented, I assume you must mention that some proteins are activated by phosphorylation. This is fundamental in order to present self –organization reflex upon fast regulatory mechanisms. Even from an historical point of view. The first observation arrived from a sample due to be studied on the following day of glycogen synthetase. It was unintended left overnight out of the refrigerator. The result was it has changed from active form of the previous day to a non-active form. The story could have being finished here, if the researcher did not decide to spent this day increasing substrate levels (it could be a simple case of denaturation of proteins that changes its conformation despite the same order of amino acids). He kept on trying and found restoration of maximal activity. This assay was repeated with glycogen phosphorylase and the result was the opposite – it increases its activity. This led to the discovery

  • of cAMP activated protein kinase and
  • the assembly of a very complex system in the glycogen granule
  • that is not a simple carbohydrate polymer.

Instead, it has several proteins assembled and

  • preserves the capacity to receive from a single event (rise in cAMP)
  • two opposing signals with maximal efficiency,
  • stops glycogen synthesis,
  • as long as levels of glucose 6 phosphate are low
  • and increases glycogen phosphorylation as long as AMP levels are high).

I did everything I was able to do by the end of 1970 in order to repeat the assays with PK I, PKII and PKIII of M. Rouxii and using the Sutherland route to cAMP failed in this case. I then asked Leloir to suggest to my chief (SP) the idea of AA, AB, BB subunits as was observed in lactic dehydrogenase (tetramer) indicating this as his idea. The reason was my “chief”(SP) more than once, had said to me: “Leave these great ideas for the Houssay, Leloir etc…We must do our career with small things.” However, as she also had a faulty ability for recollection she also used to arrive some time later, with the very same idea but in that case, as her idea.
Leloir, said to me: I will not offer your interpretation to her as mine. I think it is not phosphorylation, however I think it is glycosylation that explains the changes in the isoenzymes with the same molecular weight preserved. This dialogue explains why during the reading and discussing “What is life” with him he asked me if as a biochemist in exile, talking to another biochemist, I expressed myself fully. I had considered that Schrödinger would not have confronted Darlington & Haldane because he was in U.K. in exile. This might explain why Leloir could have answered a bad telephone call from P. Boyer, Editor of The Enzymes, in a way that suggested that the pattern could be of covalent changes over a protein. Our FEBS and Eur J. Biochemistry papers on pyruvate kinase of M. Rouxii is wrongly quoted in this way on his review about pyruvate kinase of that year (1971).


Another aspect I think you must call attention to the following. Show in detail with different colors what carbons belongs to CoA, a huge molecule in comparison with the single two carbons of acetate that will produce the enormous jump in energy yield

  • in comparison with anaerobic glycolysis.

The idea is

  • how much must have been spent in DNA sequences to build that molecule in order to use only two atoms of carbon.

Very limited aspects of biology could be explained in this way. In case we follow an alternative way of thinking, it becomes clearer that proteins were made more stable by interaction with other molecules (great and small). Afterwards, it’s rather easy to understand how the stability of protein-RNA complexes where transmitted to RNA (vibrational +solvational reactivity stability pair of conformational energy).

Millions of years later, or as soon as, the information of interaction leading to activity and regulation could be found in RNA, proteins like reverse transcriptase move this information to a more stable form (DNA). In this way it is easier to understand the use of CoA to make two carbon molecules more reactive.

The discussions that follow are concerned with protein interactions and signaling.

Read Full Post »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Genetics and Male Endocrinology

Image Source: Created by Noam Steiner Tomer 8/10/2020

Male sexual differentiation and development proceed under direct control of androgens.  Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. Mutations in the androgen receptor gene cause phenotypic abnormalities of male sexual development that range from a:

  • female phenotype (complete testicular feminization), to that of
  • under-virilized or infertile men.

Using the tools of molecular biology, it was analyzed androgen receptor gene mutations in 31 unrelated subjects with androgen resistance syndromes. Most of the defects are due to nucleotide changes that cause premature termination codons or single amino acid substitutions within the open reading frame encoding the androgen receptor, and the majority of these substitutions are localized in three regions of the androgen receptor:

Less frequently, partial or complete gene deletions have been identified. Functional studies and immunoblot assays of the androgen receptors in patients with androgen resistance indicate that in most cases the phenotypic abnormalities are the result of impairment of receptor function or decreases in receptor abundance or both.

In the X-linked androgen insensitivity syndrome, defects in the androgen receptor gene have prevented the normal development of both internal and external male structures in 46, XY individuals.

The complete form of androgen insensitivity syndrome is characterized by

  • 46, XY karyotype,
  • external female phenotype,
  • intra-abdominal testes,
  • absence of uterus and ovaries,
  • blindly ending vagina, and
  • gynecomastia.

There is also a group of disorders of androgen action that result from partial impairment of androgen receptor function. Clinical indications can be abnormal sexual development of individuals with a

  • predominant male phenotype with
  • severe hypospadias and micropenis or of individuals with a
  • predominantly female phenotype with cliteromegaly,
  • ambiguous genitalia, and
  • gynecomastia.

Complete or gross deletions of the androgen receptor gene have not been frequently found in persons with the complete androgen insensitivity syndrome, whereas point mutations at several different sites in exons 2-8 encoding the DNA- and androgen-binding domain have been reported in both partial and complete forms of androgen insensitivity, with a relatively high number of mutations in two clusters in exons 5 and 7.

The number of mutations in exon 1 is extremely low, and no mutations have been reported in the hinge region, located between the DNA-binding domain and the ligand-binding domain.

The X-linked condition of spinal and bulbar muscle atrophy (Kennedy’s disease) is characterized by a progressive motor neuron degeneration associated with signs of androgen insensitivity and infertility. The molecular cause of spinal and bulbar muscle atrophy is an expanded length (> 40 residues) of one of the polyglutamine stretches in the N-terminal domain of the androgen receptor.

Source References:



Read Full Post »

%d bloggers like this: