Efficient retrovirus-mediated transfer of cell-cycle control genes to transformed cells

The use of gene therapy continues to be a promising, yet elusive, alternative for the treatment of cancer. The origins of cancer must be well understood so that the therapeutic gene can be chosen with the highest chance of successful tumor regression. The gene delivery system must be tailored for optimum transfer of the therapeutic gene to the target tissue. In order to accomplish this, we study models of G1 cell-cycle control in both normal and transformed cells in order to understand the reasons for uncontrolled cellular proliferation. We then use this information to choose the gene to be delivered to the cells. We have chosen to study p16, p21, p53 and pRb gene transfer using the pCL-retrovirus. Described here are some general concepts and specific results of our work that indicate continued hope for the development of genetically based cancer treatments.

Combating oncogene activation associated with retrovirus-mediated gene therapy of X-linked severe combined immunodeficiency

A successful gene therapy clinical trial that also encountered serious adverse effects has sparked extensive study and debate about the future directions for retrovirus-mediated interventions. Treatment of X-linked severe combined immunodeficiency with an oncoretrovirus harboring a normal copy of the gc gene was applied in two clinical trials, essentially curing 13 of 16 infants, restoring a normal immune system without the need for additional immune-related therapies. Approximately 3 years after their gene therapy, tragically, 3 of these children, all from the same trial, developed leukemia as a result of this experimental treatment. The current understanding of the mechanism behind this leukemogenesis involves three critical and cooperating factors, i.e., viral integration, oncogene activation, and the function of the therapeutic gene. In this review, we will explore the causes of this unwanted event and some of the possibilities for reducing the risk of its reoccurrence.

Unidentified member of the Chapman family, Hattoon, Illinois

Unidentified studio portrait of a member of the Chapman family, taken in the Teitzell Studio, Hattoon, Illinois.

Unidentified man on the campus of California Christian College, Los Angeles

Unidentified man in cap and gown on the campus of California Christian College, Los Angeles, in the 1920s.

Photograph of Unidentified Woman by C. Arthur, Photographer, St. Catharines [n.d.]

An unidentified young woman is featured in this undated black and white studio photograph by C. Arthur, Photographer, of St. Catharines, Ontario. This small cabinet card photograph was in the possession of the Iris Sloman Bell family of St. Catharines. Relatives of the Sloman - Bell families include former African American slaves who settled in Canada.Two photographers by the name of Arthur are listed as working in St. Catharines, Ontario in the second half of the 19th century. Charles A. Arthur was a photographer from 1880 - 1883, while Charles P. Arthur (possibly a son?) is listed as a photographer in 1898. Source: Phillips, Glen C. The Ontario photographers list (1851-1900). Sarnia: Iron Gate Publishing Co., 1990.

Unidentified Sloman relative [n.d.]

This undated photograph features an unidentified Sloman family relative pictured outside of a house in an unknown location. The photograph was among the family memorabilia retrieved from the attic of Iris Sloman Bell, of St. Catharines, in the 1980s. The Sloman - Bell family has descendants who are former Black slaves from the United States who settled in southern Ontario.

Iris Sloman with unidentified woman and sister Helen Sloman [n.d.]

Iris Sloman, at left, with her sister, Helen, far right, and an unidentified woman on the beach in this undated photo. The location could possibly be Port Dalhousie or Parry Sound. This photo was among the family memorabilia retrieved by Rick Bell from his mother's attic in St. Catharines in the 1980s. The Bell - Sloman family descends from former African American slaves who settled in the London and St. Catharines areas.

Photograph of Unidentified Man by J. W. Cole, Photographer [n.d.]

This is a small cabinet card of an unidentified man, photographed by J. W. Cole, of Brampton, Ont. He is possibly a relative of the Bell - Sloman family, whose descendants include former Black slaves who settled in Canada. While this photograph is undated, it is believed to be taken between 1865 and 1884. The photographer's stamp is printed in gold lettering along the bottom of the card. This photograph was in the possession of Iris Sloman Bell, of St. Catharines.Two photographers by the name of Cole are known to have worked in Brampton, Ontario in the latter half of the 19th century. J.F. (John W.?) is listed as a photographer in 1882, while John W. Cole operated from 1865-1884. John W. Cole is also listed as a daguerrean artist, that is, he produced daguerreotypes. He also dabbled in commerce, selling fancy goods. Source: Phillips, Glen C. The Ontario photographers list (1851-1900). Sarnia: Iron Gate Publishing Co., 1990.

Tintype of Unidentified African American Woman Leaning on Chair [n.d.]

A small tintype of a young Black woman dressed in white. The date, location and name of the photographer are unknown. This tintype was among the family memorabilia belonging to Iris Sloman Bell, of St. Catharines, Ontario. Relatives of the Sloman - Bell family are descended from former American slaves."Tintypes were the invention of Prof. Hamilton Smith of Ohio. They begin as thin sheets of iron, covered with a layer of black paint. This serves as the base for the same iodized collodion coating and silver nitrate bath used in the ambrotype process. First made in 1856, millions were produced well into the twentieth century. When tintypes were finished in the same sorts of mats and cases used for ambrotypes, it can be almost impossible to distinguish which process was used without removing the image to examine the substrate." Source: American Museum of Photography http://www.photographymuseum.com/primer.html

Postcard - Photograph postcard showing two young males and one female (all unidentified)

A postcard with a photo image of two young males and a female (all unidentified). Postcard image is stamped on rear side "C.H. Arthur, 85 St. Paul St., St. Catharines, Ont."

Unidentified Photograph - Adult Male Standing

A photograph of an unidentified male dated 1864. The rear of photograph reads "From Cray's Gallery, no. 11 East Bridge Street, Oswego, New York. A two cent stamp is also on rear of photograph.

Unidentified Photograph - Female

A photograph of an unidentified female wearing a hat and necklace The photograph is stamped J.A. Mann Photo Artist, London, Ontario.

Photograph - Unidentified Male in Uniform

A photograph of a male in uniform standing in front of a horse. In background are tents and trees.

Human Endogenous Retrovirus (HERV) Insertional Polymorphisms

Human endogenous retroviruses (HERVs) are the result of ancient germ cell infections of human germ cells by exogenous retroviruses. HERVs belong to the long terminal repeat (LTR) group of retrotransposons that comprise ~8% of the human genome. The majority of the HERVs documented have been truncated and/or incurred lethal mutations and no longer encode functional genes; however a very small number of HERVs seem to maintain functional in making new copies by retrotranspositon as suggested by the identification of a handful of polymorphic HERV insertions in human populations. The objectives of this study were to identify novel insertion of HERVs via analysis of personal genomic data and survey the polymorphism levels of new and known HERV insertions in the human genome. Specifically, this study involves the experimental validation of polymorphic HERV insertion candidates predicted by personal genome-based computation prediction and survey the polymorphism level within the human population based on a set of 30 diverse human DNA samples. Based on computational analysis of a limited number of personal genome sequences, PCR genotyping aided in the identification of 15 dimorphic, 2 trimorphic and 5 fixed full-length HERV-K insertions not previously investigated. These results suggest that the proliferation rate of HERVKs, perhaps also other ERVs, in the human genome may be much higher than we previously appreciated and the recently inserted HERVs exhibit a high level of instability. Throughout this study we have observed the frequent presence of additional forms of genotypes for these HERV insertions, and we propose for the first time the establishment of new genotype reporting nomenclature to reflect all possible combinations of the pre-integration site, solo-LTR and full-length HERV alleles.

Photograph - Unidentified Female

Black and white, 7 ½ cm x 6 cm black and white photograph of unidentified woman in a gold-toned oval frame with a velvet backing.