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

Publisher Summary This chapter discusses the role of plasminogen activators in various biological processes. In specific, it describes two types of plasminogen activators—namely, the urokinase-type plasminogen activator (u-PA) and the tissue-type plasminogen activator (t-PA), which are essentially different gene products. The amino acid sequences of these activators and nucleotide sequences of the corresponding cDNAs have largely been determined, and the cDNAs have been cloned using recombinant techniques. A variety of enzymatic as well as immunological assay and detection methods have also been developed that allows a precise quantification of the activators, a distinction between u-PA and t-PA, determination of whether an activator is present in its active or zymogen form, analysis of the kinetics of different steps of the cascade reaction, and immunocytochemical identification of u-PA and t-PA in tissue sections. Much of the studies on plasminogen activators and cancer has been guided by the hypothesis that proteolysis of the components of extracellular matrix, initiated by the release of plasminogen activator from the cancer cells, plays a decisive role for the degradation of normal tissue, and thereby for invasive growth and metastases.

Plasminogen activators, tissue degradation, and cancer.

Objective—This report presents selected estimates of complementary and alternative medicine (CAM) use among U.S. adults, using data from the 2002 National Health Interview Survey (NHIS), conducted by the Centers for Disease Control and Prevention’s (CDC) National Center for Health Statistics (NCHS). Methods—Data for the U.S. civilian noninstitutionalized population were collected using computer-assisted personal interviews (CAPI). This report is based on 31,044 interviews of adults age 18 years and over. Statistics shown in this report were age adjusted to the year 2000 U.S. standard population. Results—Sixty-two percent of adults used some form of CAM therapy during the past 12 months when the definition of CAM therapy included prayer specifically for health reasons. When prayer specifically for health reasons was excluded from the definition, 36% of adults used some form of CAM therapy during the past 12 months. The 10 most commonly used CAM therapies during the past 12 months were use of prayer specifically for one’s own health (43.0%), prayer by others for one’s own health (24.4%), natural products (18.9%), deep breathing exercises (11.6%), participation in prayer group for one’s own health (9.6%), meditation (7.6%), chiropractic care (7.5%), yoga (5.1%), massage (5.0%), and diet-based therapies (3.5%). Use of CAM varies by sex, race, geographic region, health insurance status, use of cigarettes or alcohol, and hospitalization. CAM was most often used to treat back pain or back problems, head or chest colds, neck pain or neck problems, joint pain or stiffness, and anxiety or depression. Adults age 18 years or over who used CAM were more likely to do so because they believed that CAM combined with conventional medical treatments would help (54.9%) and/or they thought it would be interesting to try (50.1%). Most adults who have ever used CAM have used it within the past 12 months, although there is variation by CAM therapy.

/pdf/complementary-and-alternative-medicine-use-among-adults-37vlml3iz3.pdf

Complementary and alternative medicine use among adults: United States, 2002

The ability of carcinomas to invade and to metastasize largely depends on the degree of epithelial differentiation within the tumors, i.e., poorly differentiated being more invasive than well-differentiated carcinomas. Here we confirmed this correlation by examining various human cell lines derived from bladder, breast, lung, and pancreas carcinomas. We found that carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed the epithelium-specific cell-cell adhesion molecule E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80), as visualized by immunofluorescence microscopy and by Western and Northern blotting, whereas carcinoma cell lines with a fibroblastoid phenotype were invasive and had lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin mAbs. These findings indicate that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and they suggest further that E-cadherin acts as an invasion suppressor.

/pdf/e-cadherin-mediated-cell-cell-adhesion-prevents-invasiveness-4b3i3zcik2.pdf

E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.

Development of a comorbidity index using physician claims data.

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

A comprehensive listing of putative human breast carcinoma cell lines and the extent to which each has been characterized is presented. Criteria used to certify the human, mammary, and malignant origin of a cell line include: ( a ) a reliable histopathological diagnosis; ( b ) interspecies specificity established by human karyotype, isoenzyme profiles, and/or cell surface antigenicity; ( c ) intraspecies specificity, demonstrated by genetic evidence of a unique, human donor distinct from other cells including HeLa cells; and ( d ) organ specificity, supported by morphological evidence of epithelial structure and secretory activity, and especially by the expression of differentiated functions; these include presence of receptors for sex steroid hormones, hormone responsiveness, and production of milk proteins, fatty acids, or milk-specific antigens. Of the 47 cell lines for which data are here reported, 22 have been shown to be derived from human, non-HeLa donors and to have epithelial morphology as revealed by light or electron microscopy. Differentiated function has been recorded for 19 cell lines. Additional human breast cancer cell lines have been reported, but characterization of some of these has been insufficient to judge the legitimacy of their pedigrees. For others mammary origin is questionable. Six purported breast cell lines are in reality HeLa cells, and one is of nonhuman origin.

https://cancerres.aacrjournals.org/content/canres/38/11_Part_2/4327.full.pdf

Human breast carcinoma cells in continuous culture: a review.

The papillomaviruses, which are widely distributed in nature, typically induce benign skin tumours (warts) in their natural hosts (reviewed in ref. 1). These viruses are members of the papovavirus group, as are the polyomaviruses2. In contrast to polyomaviruses such as SV40, polyoma and BK (reviewed in ref. 3), the papillomaviruses have not been extensively studied, primarily because of the lack of a suitable tissue culture system. In general, the proliferative skin changes induced by the papillomaviruses are limited to the epidermal cells, and the viruses have a very narrow host range. However, some bovine papilloma viruses (BPV) are exceptional in that they induce fibropapillomas in their natural host (cows); these BPV can also induce cellular transformation in tissue culture4–6 and fibroblastic tumours in heterologous animals, including hamsters7, mice5 and horses8,9. BPV DNA from virions can also transform rodent cells and is tumorigenic in hamsters10. Recently, a tissue culture focus assay11 in mouse cells (NIH 3T3 and C127) has been described for those BPV which are the aetiological agents of fibropapillomas in cows. The virally transformed cells, which did not contain infectious virus, grew in soft agar and were tumorigenic in nude (nu/nu) mice. We12 have recently molecularly cloned the entire genomes of BPV-1 and BPV-2 (ref. 13) in Escherichia coli K12 using the certified plasmid vector pBR322 (ref. 14). We now demonstrate that these cloned DNAs can transform NIH 3T3 and C127 cells. Further, a molecularly cloned fragment which contains 69% of the BPV-1 genome can also induce cellular transformation.

In vitro tumorigenic transformation by a defined sub-genomic fragment of bovine papilloma virus DNA

Accuracy of certification of underlying cause of death and implications for US mortality statistics were assessed among 257 autopsied cases collected during the calendar year 1970 at a short-stay general hospital in Atlanta, GA. Clinicopathologic cause of death (CPCD) certificates, with assignment of underlying cause of death based on autopsy findings in combination with pertinent clinical data, were prepared by a pathologist and were employed as a standard of comparison against which the accuracy of the underlying cause of death on the original death certificate was measured. Results suggest that autopsy findings are not necessarily used to supplement clinical data in filling out death certificates. Improper recording of underlying cause of death was found in 42% of the autopsied cases. Malignant neoplasms were found to be underreported and vascular diseases overreported, each by approximately 10%, when original certificates were compared to CPCD certificates. The confirmation rate for original death certificate diagnoses was 89%. In the case of a confirmed diagnosis, the underlying cause of death was substantiated by postmortem findings as having existed regardless of its role in the sequence of events leading to death. The underlying cause of death as assigned by the pathologist was listed on the original death certificate among the sequence of events leading to or contributing to death at the rate of 72% (i.e., this rate measures the sensitivity of the death certificate).

Linda W. Engel

Papers

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

Human breast carcinoma cells in continuous culture: a review.

In vitro tumorigenic transformation by a defined sub-genomic fragment of bovine papilloma virus DNA

Accuracy of death certification in an autopsied population with specific attention to malignant neoplasms and vascular diseases

Activation of human breast carcinoma collagenase through plasminogen activator