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    65 views7 pages

    Immunocal Breast Cancer

    Uploaded by

    api-3714923

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PDF or read online from Scribd
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    ANTICANCER RESEARCH 15: 2683-2650 (1995) The Use of a Whey Protein Concentrate the Treatment of Patients with Metastatic Carcinoma: A Phase I-II Clinical Study RENEE S. KENNEDY!, GEORGE P. KONOK!, GUSTAVO BOUNOUS?, SYLVAIN BARUCHEL? and TIMOTHY D. G. LEE Department of Surgery, Dalhousie Universi, Halifx, Nova Scot; 2Depariment of Surgery, McGill Univesity, Montreah, Quebec: Department of Pediatrics and Oncology, MeGil Univers, Montreal, Quebec; ‘Department of Immunology and Microbiology, Dalhousie Universi, Half, Nova Scotia, Cenada Abstract. Gluathione (GSH) concentration is high in most ‘tumour cells and this may be an important factor in resistance to chemotherapy. Previous in-vitro and animal experiments have shown a differential response of tumour versus normal cells to various cysteine delivery systems. More specifcaly, an in-vitro ‘assay showed that at concentrations that induce GSH synthesis in normal human cells, a specially prepared whey protein concentrate, Immunocal™, caused GSH depletion and in- hibition of proliferation in human breast cancer cells. On the ‘basis ofthis information five patients with metastatic carcinoma of the breast, one of the pancreas and one ofthe liver were fed 30 ‘grams ofthis whey protein concentrate daily for six months. In sic patient the blood lymphocyte GSH levels were substantially above normal at the outset, reflecting high tumour GSH level. Two patients (#1,#3) exhibited signs of tumour regression, normalization of haemoglobin and peripheral lymphocyte Authors’ addresses: Dr. Renee $. Kennedy, Halifax Infirmary Hospital, Gerrard Hall, 4th Floor, 5303 Mortis St, Halifax, "Nova Scotia, B3) 1B6, Dr. George P. Konok, Halifax Infirmary Hospital, Gerrard Hall, 4th Floor, $303 Morris St, Halifax, Nova Scotia B3J 186. Dr. Gustavo Bounous, Immunatech Research Corporation Ltd, 2075 Rue Universite, Suite 1100, Monteeal, Quebee, Canada, HBA2L1. Dr. Syivain Baruchel, Montreal Children Hospital, Res. INST. 2300 Tupper St, Montreal, Quebec, Canada, H3H 1P3, Dr, T.D.G. Lee, Transplantation and Immunology Laboratory, oth Floor, Sir’ Charles Tupper Bldg,, Dalhousie University, Halifax, Nova Scotia, BH 4H, Correspondence to: Dt Gustavo Bounous, Immunotech Research Corporation Lid, 2075 Rue Université, Suite 1100, Montres, ‘Quebec, Canada HA 2. Key Words: Whey protein, cancer, metastatic carcinoma, hitathione, (0250-7005/95 $2.00+.40 counts and a sustained drop of lymphocyte GSH levels towards normal. Two patients (#2,#7) showed stabilisation of the ‘tumour, increased haemoglobin levels. In three patients (#4,45,#6) the disease progressed with a trend toward higher Smphocyte GSH levels. These results indicate that whey protein ‘concentrate might deplete tumour cells of GSH and render them ‘more vulnerable to chemotherapy. Feeding a specially formulated whey protein concentrate, Immunocal™, appears to exert an inhibitory effect not only on the initiation of cancer but also on its progression (1). Indeed, in vitro studies have confirmed a direct inhibitory effect of whey protein concentrate on human cancer cell replication (2,3). In other human cancer cell studies the inhibitory effect was found to be related to the serum albumin component of whey (4) and, most recently to alpha- lactalbumin, another major component of whey protein concentrate (5). Feeding lactoferrin to mice inhibited the reduced lung colonisation by melanomas (6). Serum albumin was found to exhibit, unlike other proteins, a strong antimutagenic effect in ‘an in vitro assay using hamster cells (7) A. possible explanation for these newly discovered properties of dietary whey protein may be found in recent findings on the role of glutathione (GSH) in tumour biology. GSH, (L-y-glutamyl-L-qysteinyl-glycine) isthe principal cellular antioxidant and detoxifying agent (8). ‘The whey protein concentrate used in our studies (Immunocal™) contains substrates for GSH production as it was found in normal animals to enhance cellular OSH sgmthesis (9). We have succeeded in concentrating in Immunocal™ serum albumin, alphatfactalbumin and lactoferrin containing a significant number of cystine residues, (9). Free qysteine cannot be used to deliver this necessary 2643 ANTICANCER RESEARCH 15 263-2550 (1995) substrate, as itis toric, and is rapidly metabolised. In the peptide form, however, the disulphide ostine of undenatured Immunocal™ released during gastrointestinal digestion can be effectively transfered to target eels where it is readily cleaved to eysteine for GSH synthesis Unlike commercial whey concentrates, Immunocal™ is produced using specially designed techniques aimed at preserving the bioactive cystine rich components in their tndenatured form, Recent experimental evidence revealed an intriguing differential response of tumour vs. normal ells to GSH synthesis promoting compounds. Cellular GSH levels have been found to be several times higher in human cancer cells than inthe adjacent normal cells (10), This finding is presumably related to their proliferative activity. In fact, cancer is the only condition in which an elevation ofa tightly regulated system such as GSH bas been reported. However, when a qjsteine and GSH-promoting compound such as oxothiazolidine-4-carborylate (OTZ) was added to cultured human lung cancer cels exhibiting very high levels of GSH at the outset, no intracellular GSH increase was noted, whereas GSH increased substantially in normal cells (10. This differential response is even more pronounced in vivo, In tumour bearing rats OTZ treatment ‘was found to actually deplete GSH in the tumours (11). ‘More. specifically, an in viro assay showed that at concentrations that induce GSH synthesis in normal human cells, Immunocal™ caused GSH depletion and inhibition of proliferation of human breast cancer cells (submitted for publication by Baruchel S. 1995) (On the basis ofthese experimental data a Phase 1 clinical ‘ria was undertaken to test the effect of Immunocal™ in five patients with metastatic breast cancer, one with pancreatic Cancer and another with metastatic adenocarcinoma to the liver of unknown primary. “Materials and Methods mn testing @ new approach to cancer teatment, patient selection and faccrval ae eifealt issues Te selected patents must havea reasonable Tie expectancy, and must have measurable disease. They must not be

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