Pulmonary metastases

G. M. Baratt, D. Nolibe, A. Yapo, J. F. Petit, and J. P. Tenu, Use of mannosylated liposomes for in vivo targeting of a macrophage activator and control of artificial pulmonary metastases, Ann. Inst. Pasteur/Immunol., 138 (1987) 437 -50. 

Whitmore MM, et al. Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune responses. Cancer Immunol Immunother 2001 50 503. 

Liposome-encapsulated immunomodulators are currently under investigation in different patient groups although this development has certainly not advanced as far as that with the liposomal anthracyclines. MLV-MTP-PE (multilamellar vesicles-muramyl tripeptide-phos-phatidylethanolamine) was studied in several clinical trials in osteosarcoma patients who developed pulmonary metastases during adjuvant chemotherapy [108], The intravenous administration of MLV-MTP-PE induced tumouricidal properties in monocytes as well as increase in serum IL-1 shortly after intravenous infusion. Furthermore elevations in C-reactive protein, 32-microglobulin and ceruloplasmin were frequently observed. Even higher anti-tumour activity was observed in combination with ifosfamide. These preliminary results suggests that liposome-encapsulated immunomodulators in combination with chemotherapy may be an appropriate treatment for recurrent disease. 

Local sarcomas occurred in rats after subcutaneous injection with lOmg/% weekly for 1 year or with a single 50mg/kg dose. Tumors occurred between 500 and 700 days after the first injection, and, in most cases, pulmonary metastases were observed. Repeated intraperi-toneal injection of 44mg/kg in mice reduced survival and caused an increased incidence of lung tumors. ... 

The same workers found the corresponding L-iduronic acid congener (87) to be a moderate inhibitor of )3-glucuronidase from human liver (K 1.3 pmol/1). The sodium salt of glucaro- lactam and strucural analogues thereof were recently reported to be potent inhibitors of pulmonary metastases and tumour cell invasion [138]. 

A group of 40 weanling outbred female Wistar rats received a single subcutaneous injection of 200 mg/kg bw 1,2-dimethylhydrazine. Four rats died within four days after the injection. Twenty-five of 36 rats that survived for more than four days and were killed within one year after 1,2-dimethylhydrazine administration developed renal tumours, nine of them bilateral. Pulmonary metastases were foimd in one animal. Twenty-five (73%) of 34 tumours examined histologically were diagnosed as nephroblastoma-like tumours similar to human Wilms tumour, three were mesenchymal tumours, three were adenomas, two were adenocarcinomas and one was unclassifiable (Sadrudin et al., 1985). 

Hewitt died, on October 19, 1973, of pulmonary metastases from a sarcoma in the leg. He was a man of character, one of the most distinguished carbohydrate chemists in the United States, and a wonderful and generous companion. He was truly an inspiration to all who knew him, and we shall miss him sorely. 

Clear cell adenocarcinomas of the vagina and cervix induced by prenatal exposure to this drug metastasize to the lungs. The secondaries generally appear within 2-3 years of the initial diagnosis. Unusually, a case has been reported in which pulmonary metastases occurred more than 15 years after presentation of the primary tumor (14). This makes it clear that patients of this type should be followed up in the very long term. 

Number in parentheses is number of mice with pulmonary metastases of hepatocellular carcinomas. 

Mouse models are critical for the discovery and development of novel therapeutics and to understand the mechanism(s) of metastasis (see Note 1). Commonly, two different models of metastasis are utilized the first is experimental or artificial metastases, in which tumor cells are injected intravenously or via the left ventricle both of which circumvent part of the metastatic process. As a generality, the first capillary bed encountered by the injected cells provides the site for experimental metastasis. Thus, following lateral tail vein injection, pulmonary metastases are observed in rodents. This contrasts with the profile of metastases observed following injection of the left ventricle which results in hepatic metastases, as well as, potentially bone marrow and brain metastases. 

Most pulmonary tumor colonies in mice are in the pleura. Therefore, pigmented colonies (such as melanomas) can be counted without lung dissection. However, it may be more facile, especially when there are extensive pulmonary metastases, to dissect the lungs into the individual four or five lobes which are then enumerated individually using a dissecting microscope. 

The assessment of the number of experimental metastases, typically pulmonary metastases, following i.v. injection of a single cell suspension of tumor cells or collagenase-digested primary tumor provides the most common outcomes. Multiple strategies may be used for this enumeration including... 

Donawho, C. K., Pride, M. W. and Kripke, M. L. (2001) Persistence of immunogenic pulmonary metastases in the presence of protective anti-melanoma immunity. Cancer Res 61,215-221. 

On examination, Mr AC is found to have a mass in his right testicle. A CT scan confirms the presence of bilateral pulmonary metastases and a large retroperitoneal mass. An orchidectomy was arranged and histology confirmed a diagnosis of non-seminomatous germ cell tumour. Based on the levels of P-HCG and AFP ... 

Liotta, L. A., Kleinerman, J. and Saidel, G. M. (1974). Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res. 34, 997-1004. 

Talmadge, J. E. and Zbar, B. (1987). Clonality of pulmonary metastases from the bladder 6 subUne of the B16 melanoma studied by southern hybridization. J. Natl. Cancer Inst. 78, 315-320. 

Figure 4.4 Example of longitudinal follow-up by plasma L-DOPA/L-tyrosine ratio. A 52-year-old male (initial melanoma right arm) was monitored by the L-DOPA/L-tyrosine ratio, SIOOB and melanoma inhibitory activity (MIA) for 21 months. Six major clinical events are reported 1, second local recurrence, 3 years after initial diagnosis 2, bone and pulmonary metastases (stage IV) 3, evolution of subcutaneous metastases 4, evolution of cutaneous and pulmonary metastases 5, metastases to axillary nodes 6, death...

Kim SY, Lee CH, Midura BY, et al. (2007) Inhibition of the CXCR4/CXCL12 chemo-kine pathway reduces the development of murine pulmonary metastases. Clin Exp Metastasis DOI 10.1007/sl0585-007-9133-3... 

Heparin causes a reduction in mitotic index and a decrease in tumour volume for Ehrlich ascites tumours in mice . Polyethylene sulphonates having molecular weights between 15,000 and 35,000, also have antineo-plastic activity in mice against ascites tumours, carcinomas and leukaemias . Heparin has been found to reduce markedly the number of pulmonary metastases in rats receiving intravenous Walker 256 carcinoma cells . Evans blue in the presence of a sulphated pectin entered tumour cells but not normal tissue cells s. The anti-immunochemical action of heparin has been used successfully for tumour heterografts Ass. 

Dactinomycin, or actinomycin D as it was called when first introduced, has shown striking curative properties in Wilms s tumour of the kidney which forms a high proportion of all malignant tumours in children. Under its influence, even pulmonary metastases caused by this tumour regress (Farber and Mitus, 1968). Forms of cancer requiring longer treatment are not suitable for this drug, which has only moderate selectivity. 

Flynn WJ (1967) The treatment of pulmonary metastases with microspheres of yttrium 90. Minerva Med 58 4498-4500... 

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