Nikolai Nikolaevich Petrov : Founder of Russian scientific oncology (on the 140th anniversary of his birth).

Nikolai Nikolaevich Petrov was a Russian surgeon, the founder of Russian oncology and the author of many important scientific publications. N. N. Petrov enriched the medical science with a number of valuable experimental studies, which significantly advanced the knowledge of the etiology and pathogenesis of malignant tumors. He discovered the carcinogenic effects of sunlight and the influence of photometrically established doses of ultraviolet (UV) rays on the occurrence of malignancies. He organized a laboratory of experimental cancer in Sukhumi, where one of the most important experiments on the production of malignant tumors in monkeys was carried out. He was one of the founders of the Institute of Oncology in St. Petersburg. He was an active participant in international congresses on surgery and oncology. Under his direction combined surgical and radiation treatment of malignant tumors, electrosurgery for cancer operations and treatment of wounds after removal of tumors were introduced into broad medical practice. Moreover, he was very much involved in ethical problems in surgery.

Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts.

The majority of human solid tumours do not metastasize when grown subcutaneously in immunocompromised mice; this includes patient-derived xenograft (PDX) models. However, orthotopic implantation of intact tumour tissue can lead to metastasis that mimics that seen in patients. These patient-derived orthotopic xenograft (PDOX) models have a long history and might better recapitulate human tumours than PDX models.

[Immunological studies at the N.N. Petrov Research Institute of Oncology (100th anniversary of birth of Prof. T.A. Korosteleva)].

Historical essay devoted to the life and work of Professor Tamara Alexandrovna Korosteleva (1913-1991), the former Head of the Laboratory of Oncoimmunology at the N.N. Petrov Research Institute of Oncology, St. Petersburg.

A historical perspective of pancreatic cancer mouse models.

Pancreatic cancer is an inherently aggressive disease with an extremely poor prognosis and lack of effective treatments. Over the past few decades, much has been uncovered regarding the pathogenesis of pancreatic cancer and the underlying genetic alterations necessary for tumour initiation and progression. Much of what we know about pancreatic cancer has come from mouse models of this disease. This review focusses on the development of genetically engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer, as well as the increasing use of patient-derived xenografts for preclinical studies and the development of personalised medicine strategies.

Carcinogenic effects of benzene: Cesare Maltoni's contributions.

Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

Chronology of asbestos cancer discoveries: experimental studies of the Saranac Laboratory.

This commentary challenges a recently published perception that Dr. Le Roy Upson Gardner had not actually discovered in 1942 that inhaled chrysotile fibers could induce malignant neoplasia in mice. The handwritten laboratory notes and some of Dr. Gardner's slides have recently been found. They verify that the tumors he saw in the mice included truly malignant neoplasms. Gardner had by then also accumulated 11 cases of human lung cancer (two mesotheliomas) derived from Quebec asbestos miners and millers. An inhalation study designed by Dr. Gardner and conducted between 1951 and 1954, using cancer-insusceptible mice, yielded neoplasia risk ratio of 5.7 compared with control animals. The studies also showed that the primary effect of chrysotile is to cause epithelial proliferation in alveoli adjacent to bronchioles. Chrysotile type asbestos bodies were shown to remain only transiently ferruginous, but even though invisible in direct light they can be visualized at high magnification through use of phase contrast and polarized light micrography.

Nutrition and carcinogenesis: historical highlights and future prospects.

Historical reviews were presented of several selected nutritional factors that are determinants of cancer incidence in laboratory experiments utilizing animals. An all-inclusive review of nutrition as it impacts cancer incidence was not done. Rather, the selection of subjects was based on a combination of several factors. (1) The efficacy of the factor as an inhibitor. (2) Current interest in the factor. (3) The extent to which the mechanisms of the inhibition is known and that knowledge may facilitate future studies. (4) The relevance to the human problem. The future of research on cancer prevention is bright. There are now mechanism-based rapid assays to detect food stuffs that prevent cancer and to assay for the active compounds therein. The list of inhibitors shown in Table 8 will continue to grow. The challenge is to achieve universal application to the human population of appropriate dietary practices that include foods that provide the protective factors shown in Table 8.

[Cancer between infection and heredity: genes, viruses and mice at National Cancer Institute (1937-1977)]. / Le cancer entre infection et hérédité: gènes, virus et souris au National Cancer Institute (1937-1977).

After World War II, in the United States,viral explanation of cancer replaced a vision of the disease emphasizing genetic factors. From the mid 1950s onwards, experimental oncologists favored the notion that cancer was initiated by infectious agents passed from one generation to the next. In order to analyze this displacement, the present paper focuses on the part played by new experimental systems, i.e. mice showing tumors induced by viruses. Since animal models are agencies which "represent" human diseases, and mediate between different social worlds, their uses often result in opposing views. Mouse models thus provided tractable resources which favored the alternation between heredity and infection. The paper describes the emergence, in the late 1930s, at the Jackson Memorial Laboratory, of an agent enhancing the formation of mammary tumors in mice. This laboratory was then involved in the production of marketable inbred mice as well as in research concerned with genetic factors that may cause cancer. After World War II, loose theories and conflicting results helped turn the agent into a virus. At the National Cancer Institute, the virus was associated with a whole range of particles causing leukemia in mice. Owing to the Virus Cancer Program, the value of mouse tumor viruses increased in the late 1960s. This research effort then aimed at finding human tumor viruses, and at crafting cancer vaccines. It was modeled after the experience of the NCI chemotherapy program stemming from war research. In addition to the fact that biomedical research became a state enterprise, the study emphasizes three parameters. First, loose practices--both theoretical and experimental--helped manage the variability of animal models. Secondly, the standardization and mass production of animals and reagents encouraged the stabilization of research programs. Thirdly, private biotechnology companies working under NCI contracts implemented preclinical work, and mediated between virology laboratories and clinical settings.