Peritoneal tumor

Reddy, J.A., Abburi, C., Hofland, H., et al. (2002). Folate-targeted, cationic liposome-mediated gene transfer into disseminated peritoneal tumors. Gene ., 9(22), 1542-1550. 

Foyle A, Al-Jabi M, McGaughey WTE. Papillary peritoneal tumors in women. Am J Surg Pathol. 1981 5 241-249. 

After intraperitoneal injection into a murine disseminated peritoneal tumor model, however, folate lipoplex formulations produced an approximately 10-fold increase in tumor-associated gene expression, compared with conventional complex [68]. When gene expression was measured in tumors and various peritoneal organs after intraperitoneal administration, the highest gene expression was observed in tumor cell ascites, followed by solid tumors. Thus, intraperitoneal administration of the folate-PEG-lipid-containing liposome complex may be more suitable for peritoneal dissemination. 

To test the feasibility of this approach, earlier studies in this laboratory used methotrexate (MTX) as a model drug [2, 3], Pharmacokinetic investigations demonstrated that systemic administration of polyclonal anti-MTX Fab with i.p. administration of MTX led to a decrease in the systemic exposure of unbound MTX, while not altering peritoneal exposure [2], To facilitate further evaluation of anti-MTX antibodies on MTX induced toxicity, monoclonal anti-MTX IgG and Fab were produced and purified [4], Subsequent studies demonstrated that after this combination therapy, anti-MTX Fab could allow a fivefold increase of the maximum tolerated dose of i.p. MTX and enhance the median survival time of mice bearing peritoneal tumors [5]. 

Balthasar J P, Fung H L (1996). Inverse targeting of peritoneal tumors Selective alteration of the disposition of methotrexate through the use of anti-methotrexate antibodies and antibody fragments. J. Pharm. Sci. 85 1035-1043. 

T cells in vitro [121]. The Tat-p27 protein dose-dependently induced cell cycle arrest at Gl. Snyder et al. demonstrated that the Tat-p27 tumor suppressor protein actually inhibited tumor growth in two mouse models, such as a HI299 subcutaneous solid tumor xenograft model and a more clinical-relevant peritoneal tumor model [122]. 

Metastatic involvement of peritoneum (peritoneal carcinomatosis) is by far the most common peritoneal tumor (Walsh and Williams 1971 Bell and Scully 1990). Tumors that preferentially metastasize to the peritoneum include the following adenocarcinomas stomach intestine (colon-rectum) gallbladder or biliary tree pancreas breast lung ovary and uterus (Runyon et al. 1988) as well as lymphoma... 

Low RN, Barone RM, L.acey C et al (1997) Peritoneal tumor MR imaging with dilute oral barium and intravenous gadolinium-containing contrast agents compared with unenhanced MR imaging and CT. Radiology 204(2) 513-520... 

In an animal study of rats exposed by inhalation to ethylene oxide at 10, 33, or 100 ppm for approximately two years (245), and in a separate chronic rat study in which rats were exposed to 50 or 100 ppm of ethylene oxide (240), increased incidences of mononuclear cell leukemia, peritoneal mesothelioma, and various brain tumors have been reported. In an NTP (246) two-year inhalation study of mice at 50 and 100 ppm, alveolar/bronchiolar carcinomas and adenomas, papillary cystadenomas of the harderian gland, and malignant lymphomas, uterine adenocarcinomas, and mammary gland tumors were increased in one or both exposure groups. 

Muramyl dipeptide derivatives have also been microencapsulated in lactide/glycolide copolymers for use alone as an immuno potentiator. L-lactide/glycolide copolymers were used to deliver MDP-B30, a lipophilic compound, from very small microspheres (less than 5 pm in diameter). The amount of MDP-B30 required for tumor growth inhibitory activity of mouse peritoneal macrophages was 2000 times less for the controlled release MDP-B30 microspheres than for the unen-capsulated drug (134). 

Intraperitoneal administration of chemotherapeutic agents has been used for many years as a way of increasing the delivery of drugs to tumors (e.g., ovarian carcinoma) located in the peritoneal cavity (Markman, 1986 Howell and Zimra, 1988). Cisplatin (Casper et al., 1983 Markman et al., 1985), cytosine arabinoside (Ara-C) (King et al., 1984 Markman et al., 1985, 1986), and bleomycin (Markman et al., 1986) are examples of intraperitoneally administered drugs which were already successfully applied in clinical settings. 

Markman, M. (1986). Intraperitoneal antineoplastic agents for tumors principally confined to the peritoneal cavity. Cancer Treatm. Rev., 1, 219-242. 

Tumor involves one or both ovaries with microscopic confirmed peritoneal metastasis outside pelvis and/or regional lymph node metastasis... 

Ascites or peritoneal washings Tumor on external surfaces Ovary capsule... 

E2. Echtenacher, B Falk, W Mannel, D. N., and Krammer, P. H., Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J. Immunol. 145, 3762-3766 (1990). 

Mamede, M., Saga, T., Kobayashi, H., Ishimori, T., Higashi, T., Sato, N., Brechbiel, M.W., and Konishi, J. (2003) Radiolabeling of avidin with very high specific activity for internal radiation therapy of intra-peritoneally disseminated tumors. Clin. Cancer Res. 9, 3756-3762. 

Moos, A., Oughton, J., and Kerkvliet, N.I., The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on tumor necrosis factor (TNF) production by peritoneal cells, Toxicol. Lett., 90, 145,1997. 

Laskin, D.L., Laskin, J.D., Weinstein, I.B. and Carchman, R.A. (1981). Induction of chemotaxis in mouse peritoneal macrophages by phorbolester tumor promoters. Cancer Res. 41 1923. 

Monoclonal antibodies can be produced not only in a cell culture but also in live animals. When injected into mice (in the peritoneal cavity, the gut), the hybridoma cells produce tumors containing an antibody-rich fluid called ascites fluid. Production in cell culture is usually preferred, as the ascites technique may be very painful to the animal and if replacement techniques exist, may be considered unethical. The process of producing monoclonal antibodies described above was invented by Georges Kohler. Cesar Milstein, and Niels Kaj Jeme in 1975 they shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery (http //en.wikipedia.org/ wiki/Antibody). 

Blood vessels penetrating tumors provide malignant cells with another point at which to enter the circulation. Evidence exists that in situation where cancers disseminate predominantly by the blood, the extent of metastasis depends upon the vasculature of the primary tumor. Thin-walled capillaries, especially those newly formed, provide poor resistance to invading cancer cells. Also, data from microscopy studies show that the endothelium of tumor vessels, particularly in areas of poor oxygenation, is often abnormal (Kl). These abnormalities may permit invasion by neoplastic cells (P3). Finally, tumors can spread by direct extension into body cavities such as pleural and peritoneal spaces. An example of this is the formation of peritoneal metastases from ovarian carcinoma. 

Flahn SM, Putt ME, Metz J, Shin DB, Rickter E, Menon C, Smith D, Glatstein E, Fraker DL, Busch TM (2006) Photofrin uptake in the tumor and normal tissues of patients receiving intra-peritoneal photodynamic therapy. Clin Cancer Res 12 5464-5470. 

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