For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.

https://cancerres.aacrjournals.org/content/canres/48/3/589.full.pdf

Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay

The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells. There is evidence for another class of oncogenes, in which tumour-predisposing mutations are recessive to wild-type alleles. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb, assigned to the q14 band of human chromosome 13. Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours, almost half of which are osteosarcomas believed to be caused by the same mutation. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13q14, all or part of which is frequently deleted in retinoblastomas and osteosarcomas.

/pdf/a-human-dna-segment-with-properties-of-the-gene-that-kc0q4f65ya.pdf

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis

Recent evidence indicates the existence of a genetic locus in chromosome region 13q14 that confers susceptibility to retinoblastoma, a cancer of the eye in children. A gene encoding a messenger RNA (mRNA) of 4.6 kilobases (kb), located in the proximity of esterase D, was identified as the retinoblastoma susceptibility (RB) gene on the basis of chromosomal location, homozygous deletion, and tumor-specific alterations in expression. Transcription of this gene was abnormal in six of six retinoblastomas examined: in two tumors, RB mRNA was not detectable, while four others expressed variable quantities of RB mRNA with decreased molecular size of about 4.0 kb. In contrast, full-length RB mRNA was present in human fetal retina and placenta, and in other tumors such as neuroblastoma and medulloblastoma. DNA from retinoblastoma cells had a homozygous gene deletion in one case and hemizygous deletion in another case, while the remainder were not grossly different from normal human control DNA. The gene contains at least 12 exons distributed in a region of over 100 kb. Sequence analysis of complementary DNA clones yielded a single long open reading frame that could encode a hypothetical protein of 816 amino acids. A computer-assisted search of a protein sequence database revealed no closely related proteins. Features of the predicted amino acid sequence include potential metal-binding domains similar to those found in nucleic acid-binding proteins. These results provide a framework for further study of recessive genetic mechanisms in human cancers.

https://science.sciencemag.org/content/sci/235/4794/1394.full.pdf

Human retinoblastoma susceptibility gene: cloning, identification, and sequence

Experimental evidence suggests that platelets contribute to metastasis through adhesive and haemostatic functions that promote cancer cell survival, immune evasion and interactions with vascular cells to assist organ colonization from the bloodstream. Extensive experimental evidence shows that platelets support tumour metastasis. The activation of platelets and the coagulation system have a crucial role in the progression of cancer. Within the circulatory system, platelets guard tumour cells from immune elimination and promote their arrest at the endothelium, supporting the establishment of secondary lesions. These contributions of platelets to tumour cell survival and spread suggest platelets as a new avenue for therapy.

Contribution of platelets to tumour metastasis.

Three continuous lines of mammary tumor cells (ZR-75-1, ZR-75-27, and ZR-75-30) have been established from malignant effusions of two women with breast cancer. Differentiated properties expressed by each cell line include: (a) epithelial morphology (by light and electron microscopy) resembling that of the parental tumors; (b) presence of receptors for estrogen and other steroid hormones; and (c) growth responsiveness to estrogen and/or progesterone. All three cell lines possess human karyotypes that differ from one another in modal chromosome number as well as in characteristic marker chromosomes. Two of the cultures (ZR-75-27 and ZR-75-30), although derived from the same patient, have stable differences in their karyotypes.

https://cancerres.aacrjournals.org/content/canres/38/10/3352.full.pdf

Establishment and Characterization of Three New Continuous Cell Lines Derived from Human Breast Carcinomas

The seroprevalence of Helicobacter pylori infection was examined in the adult US population and among different ethnic groups. Stored sera from 7465 adult participants in the first phase of the third National Health and Nutritional Examination Survey (1988-1991) were tested with a sensitive and specific IgG ELISA, to diagnose infection. Seroprevalence of H. pylori among all participants was 32. 5%. This increased with age, from 16.7% for persons 20-29 years old to 56.9% for those > or =70 years old. Age-adjusted prevalence was substantially higher among non-Hispanic blacks (52.7%) and Mexican Americans (61.6%) than among non-Hispanic whites (26.2%). After controlling for age and other associated factors, the odds ratios relative to non-Hispanic whites decreased for non-Hispanic blacks, from 3.9 (95% confidence interval [CI], 3.1-4.9) to 3.3 (95% CI, 2. 6-4.2), and for Mexican Americans, from 6.3 (95% CI, 4.8-8.3) to 2.3 (95% CI, 1.6-3.5). The high prevalence of H. pylori infection among non-Hispanic blacks and Mexican Americans is partially explained by other factors associated with infection.

https://www.jstor.org/stable/pdfplus/30109148.pdf

Seroprevalence and Ethnic Differences in Helicobacter pylori Infection among Adults in the United States

Characteristics of an established cell line of retinoblastoma.

Electron microscopic observations on formation of pulmonary metastases.

Addition to hexamethylene bisacetamide (diacetyldiaminohexane) to cultures of a malignant mesenchymal cell line derived from a human glioblastoma multiforme induces morphological changes and stimulates the synthesis of procollagen. The morphological changes include cell elongation, an increase of extracellular material with staining properties of collagen by light microscopy, and an increase in extracellular 220-A fibrils by electron microscopy. The rate of procollagen synthesis increased as much as 20-fold, and the ratio of type I:type III procollagen changed, with type I becoming the predominant form. The change in type I:type III ratio is similar to that seen in the maturation of normal fetal to adult connective tissue.

https://www.pnas.org/content/pnas/74/11/5060.full.pdf

Tommie Sue Tralka

Papers

Establishment and Characterization of Three New Continuous Cell Lines Derived from Human Breast Carcinomas

Seroprevalence and Ethnic Differences in Helicobacter pylori Infection among Adults in the United States

Characteristics of an established cell line of retinoblastoma.

Electron microscopic observations on formation of pulmonary metastases.

Hexamethylene bisacetamide induces morphologic changes and increased synthesis of procollagen in cell line from glioblastoma multiforme