Onset Of Pulmonary Metastasis Research Articles

A Single Nucleotide Change in the Mouse Genome Accelerates Breast Cancer Progression

In the growth factor receptor gene FGFR4 the presence of the common single nucleotide polymorphism Arg388 has been associated with progression of various types of cancer including breast cancer. However, a causative relationship is not readily assigned due to genetic heterogeneity in different patient cohorts. To address this issue, we compared the effects of this allele on malignant progression in the WAP-TGFalpha transgenic mouse model of breast cancer. A knock-in strain was generated to introduce an analogous Arg385 allele into the murine FGFR4 gene. Mouse embryonic fibroblasts derived from this strain displayed accelerated cell transformation, with transformed cells exhibiting greater motility and invasive behavior. In the in vivo context of TGFalpha-induced mammary carcinogenesis, tumor development and progression was significantly advanced in tumor mass, size, and onset of pulmonary metastases. Our findings definitively identify the FGFR4 Arg388 allele as a functional prognostic marker for breast cancer progression.

Radiation therapy for testicular tumors metastasizing to the lungs

Records of 63 cases of testicular tumors treated at the Hunter Radiation Therapy Center, Yale-New Haven Hospital from 1962 through 1971 were reviewed. One hundred percent cure rate was obtained in the 36 Stage I and II pure seminoma (Group I) patients. For Stage I, the para-aortic and homolateral iliac lymph nodes were irradiated to a dose of 3,000 to 3,500 rads in three to four weeks. Elective irradiation of the mediastinum and supraclavicular areas was omitted. For Stage II, such extended field irradiation was employed to a dose of 2,000 to 3,000 rads in two to three weeks. Six (or 43 percent) of the 14 embryonal carcinoma (Group II) patients are alive for a minimum of three to a maximum of eleven years. Both teratoma (Group III) patients are alive at five and seven years as well. All eight Stage I teratocarconoma (Group IV) patients are alive with no evident disease at three to ten years. Our data indicate the difference in prognosis between patients who subsequently developed localized lung metastases and those who initially presented with pulmonary disease. We conclude that intensive combined efforts of both radiation and medical oncologists can salvage a considerable number of patients with metachronous onset of pulmonary metastases.