ORGANIC GERMANIUM / GERMANIUM SESQUIOXIDE — SCIENCE WEBSITE
The Authoritative Germanium Sesquioxide Resource

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Analytical •AntimutagenicAntioxidant •Antiviral •Arthritis •Atherosclerosis •Bioavailability •CancerCataracts  •Cervix •DNA Repair •Fibrosis •Free Radical ScavengingHazards •Heart •History •Immune SystemKidneysInflammation •Liver •Osteoporosis •Pain Management Pharmacology •Reviews •Safety •Uterus

Cancer — Linked Headers

Germane facts about germanium sesquioxide: I. Chemistry and anticancer properties. J Altern Complement Med. 2004 Apr;10(2):337-44. Kaplan BJ, Parish WW, Andrus GM, Simpson JS, Field CJ.

Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.  J Korean Med Sci. 2001 Dec; 16 Suppl:S42-53. Bespalov VG, Alexandrov VA, Limarenko AY, Voytenkov BO, Okulov VB, Kabulov MK, Peresunko AP, Slepyan LI, Davydov VV.

Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest. 2000 Feb;117(2):591-3. Mainwaring MG, Poor C, Zander DS, Harman E.

[Effect of dietary selenium and germanium on the precancerous lesion in rat glandular stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine] Zhonghua Wai Ke Za Zhi. 1996 Apr;34(4):221-3. Ming X, Yin H, Zhu Z.

Questionable methods of cancer management: hydrogen peroxide and other 'hyperoxygenation' therapies. CA Cancer J Clin. 1993 Jan-Feb;43(1):47-56.

Modifying responses of allyl sulfide, indole-3-carbinol and germanium in a rat multi-organ carcinogenesis model. Carcinogenesis. 1991 Apr;12(4):691-5. Jang JJ, Cho KJ, Lee YS, Bae JH.

Antitumor mechanisms of carboxyethyl-germanium sesquioxide (Ge-132) in mice bearing Ehrlich ascites tumors. Gan To Kagaku Ryoho. 1987 Jan;14(1):127-34. Suzuki F.

Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res. 1986 Mar-Apr;6(2):177-82. Suzuki F, Brutkiewicz RR, Pollard RB.

[Antitumor effect in mice of an organic germanium compound (Ge-132) when different administration methods are used] Gan To Kagaku Ryoho. 1985 Dec;12(12):2345-51. Aso H, Shibuya E, Suzuki F, Nakamura T, Inoue H, Ebina T, Ishida N.

[Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxyethylgermanium sesquioxide (Ge-132)] Gan To Kagaku Ryoho. 1985 Nov;12(11):2122-8. Suzuki F.

Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res. 1985 Sep-Oct;5(5):479-83. Suzuki F, Brutkiewicz RR, Pollard RB.

Inhibition of tumor growth and metastasis in association with modification of immune response by novel organic germanium compounds. J Biol Response Mod. 1985 Apr;4(2):159-68. Sato I, Yuan BD, Nishimura T, Tanaka N.

Effect of carboxyethylgermanium sesquioxide on the methylcholanthrene-induced tumorigenesis in mice. Sci Rep Res Inst Tohoku Univ [Med]. 1978 Dec;25(3-4):89-95. Kumano N, Nakai Y, Ishikawa T, Koinumaru S, Suzuki S, Konno K 

DNA binding specificity and cytotoxicity of novel antitumor agent Ge132 derivatives. Bioorg Med Chem Lett. 2005 Jun 15;15(12):2962-5. Shangguan G, Xing F, Qu X, Mao J, Zhao D, Zhao X, Ren J.

Effectiveness of propagermanium treatment in multiple myeloma patients. Eur J Haematol. 2004 Dec;73(6):397-401. Tsutsumi Y, Tanaka J, Kanamori H, Musashi M, Minami H, Fukushima A, Yamato H, Ehira N, Kawamura T, Obara S, Ogura N, Asaka M, Imamura M, Masauzi N.

Interference of selenium germanium and calcium in carcinogenesis of colon cancer. Zhonghua Wai Ke Za Zhi. 1995 Mar;33(3):167-9. Yu B, Wu J, Zhou X.

Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review). In Vivo. 1987 Jul-Aug;1(4):189-203. Brutkiewicz RR, Suzuki F.

Ability of sera from mice treated with Ge-132, an organo-germanium compound, to inhibit experimental murine ascites tumors. Gan To Kagaku Ryoho. 1985 Dec;12(12):2314-21. Suzuki F.

Multidisciplinary treatment of head and neck cancer using BCG, OK-432, and GE-132 as biologic response modifiers.  Head Neck. 1994 Jan-Feb;16(1):30-8. Fukazawa H, Ohashi Y, Sekiyama S, Hoshi H, Abe M, Takahashi M, Sato T.

Experimental study on prevention of the colorectal cancer by China medical stone and the organgermanium compound.  Zhonghua Yu Fang Yi Xue Za Zhi. 1993 Sep;27(5):286-9. Song WS.

Organic germanium: its toxic effect and function in medical care.  Zhonghua Yi Xue Za Zhi. 1993 Aug;73(8):454-6. Kong X.

Effect of combination immunochemotherapy with an organogermanium compound, Ge-132, and antitumor agents on C57BL/6 mice bearing Lewis lung carcinoma (3LL).  Gan To Kagaku Ryoho. 1986 Aug;13(8):2588-93. Kobayashi H, Komuro T, Furue H.

Antitumor activity of Ge-132, a new organogermanium compound, in mice is expressed through the functions of macrophages and T lymphocytes.  Gan To Kagaku Ryoho. 1985 Jul;12(7):1445-52. Suzuki F.

Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice.  Tohoku J Exp Med. 1985 May;146(1):97-104. Kumano N, Ishikawa T, Koinumaru S, Kikumoto T, Suzuki S, Nakai Y, Konno K.

Augmentation of NK activity in peripheral blood lymphocytes of cancer patients by intermittent GE-132 administration.  Gan To Kagaku Ryoho. 1984 Jun;11(6):1303-6. [Article in Japanese] Tanaka N, Ohida J, Ono M, Yoshiwara H, Beika T, Terasawa A, Yamada J, Morioka S, Mannami T, Orita K.

Antimutagenic effect of Ge-132 on gamma-ray-induced mutations in Escherichia coli B/r WP2 trp-.  Int J Radiat Biol Relat Stud Phys Chem Med. 1982 Dec;42(6):653-9. Mochizuki H, Kada T.

Effect of NK-421 (Bestatin) and Ge-132 on the cytotoxicity of spleen cells obtained from the tumor-bearing mice.  Gan To Kagaku Ryoho. 1982 Oct;9(10):1771-7. Ono M, Oka T, Yoshihara H, Tanaka N, Miwa H, Mannami T, Konaga E, Orita K.

The inhibition of the development of experimental tumors of the cervix uteri and vagina by using tinctures of the cultured-cell biomass of the ginseng root and its germanium-selective stocks.  Biull Eksp Biol Med. 1993 Nov;116(11):534-6. Bespalov VG, Davydov VV, Limarenko AIu, Slepian LI, Aleksandrov VA.

Cancer risks for humans from exposure to the semiconductor metals.  Scand J Work Environ Health. 1993;19 Suppl 1:101-3. Fowler BA, Yamauchi H, Conner EA, Akkerman M.

Effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.  Dis Colon Rectum. 1990 Feb;33(2):99-104. Jao SW, Lee W, Ho YS.

Therapeutic effects of organic germanium.  Med Hypotheses. 1988 Jul;26(3):207-15. Goodman S.

Prevention of pulmonary metastasis of Lewis lung carcinoma and activation of murine macrophages by a novel organic germanium compound, PCAGeS.  J Biol Response Mod. 1988 Feb;7(1):1-5. Sato I, Nishimura T, Kakimoto N, Suzuki H, Tanaka N.

Effect of 3-oxygermylpropionic Acid Polymer (SK-818) on the Incidence of Spontaneous Leukemia in AKR Mice. Haruhisa Fujita,  Masayasy Kurono, Shigeshi Toyoshima

  


Reviews, History, Cancer,
Germane facts about germanium sesquioxide: I. Chemistry and anticancer properties. J Altern Complement Med. 2004 Apr;10(2):337-44.

Kaplan BJ, Parish WW, Andrus GM, Simpson JS, Field CJ.

Departments of Paediatrics, and Community Health Sciences, Faculty of Medicine, University of Calgary, and Alberta Children's Hospital, Calgary, Alberta, Canada. kaplan@ucalgary.ca

This paper reviews the history, chemistry, safety, toxicity, and anticancer effects of the organogermanium compound bis (2-carboxyethylgermanium) sesquioxide (CEGS). A companion review follows, discussing the inaccuracies in the scientific record that have prematurely terminated research on clinical uses of CEGS. CEGS is a unique organogermanium compound first made by Mironov and coworkers in Russia and, shortly thereafter, popularized by Asai and his colleagues in Japan. Low concentrations of germanium occur in nearly all soils, plants and animal life; natural occurrence of the CEGS form is postulated but not yet demonstrated. The literature demonstrating its anticancer effect is particularly strong: CEGS induces interferon-gamma (IFN-gamma), enhances natural killer cell activity, and inhibits tumor and metastatic growth--effects often detectable after a single oral dose. In addition, oral consumption of CEGS is readily assimilated and rapidly cleared from the body without evidence of toxicity. Given these findings, the absence of human clinical trials of CEGS is unexpected. Possible explanations of why the convincing findings from animal research have not been used to support clinical trials are discussed. Clinical trials on CEGS are recommended.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
15165414&query_hl=2&itool=pubmed_DocSum

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Cancer
Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.  J Korean Med Sci. 2001 Dec; 16 Suppl:S42-53.

Bespalov VG, Alexandrov VA, Limarenko AY, Voytenkov BO, Okulov VB, Kabulov MK, Peresunko AP, Slepyan LI, Davydov VV.

Group of Cancer Chemoprevention, N.N. Petrov, Research Institute of Oncology of the Ministry of Health of the Russian Federation, St. Petersburg, Russia.

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
11748376&query_hl=2&itool=pubmed_DocSum

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Cancer
Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest. 2000 Feb;117(2):591-3.

Mainwaring MG, Poor C, Zander DS, Harman E.

Department of Medicine, Divisions of Hematology and Oncology, University of Florida College of Medicine and Veterinary Affairs Medical Center, Gainesville, FL 32610, USA. mainwmg@medicine.ufl.edu

Spindle cell carcinoma (SCC) is a rare form of lung cancer representing 0.2 to 0.3% of all primary pulmonary malignancies. Even with combined surgery, chemotherapy, and radiation therapy, these tumors are associated with a poor prognosis and only 10% of patients survive 2 years after diagnosis. We describe a patient with an unresectable SCC who, following no response to conventional treatment with combined modality therapy, chose to medicate herself with daily doses of germanium obtained in a health food store. She noted prompt symptomatic improvement and remains clinically and radiographically free of disease 42 months after starting her alternative therapy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
10669709&query_hl=2&itool=pubmed_DocSum

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Cancer
[Effect of dietary selenium and germanium on the precancerous lesion in rat glandular stomach induced by N-methyl-N'-nitro-N-nitrosoguanidine] Zhonghua Wai Ke Za Zhi. 1996 Apr;34(4):221-3.

Ming X, Yin H, Zhu Z.

Department of Surgery, Ruijin Hospital Shanghai Second Medical University.

N-Methyl-N'-nitrosoguanidine (MNNG) was administered (100 mg/L) in drinking water in 100 Wistar rats for 24 weeks to induce the precancerous lesion in glandular stomach. 77 rats with the precancerous lesion in glandular stomach were divided into 3 groups randomly at the 25 thweek. Yeast selenium (Yse, 4 mg/L) and carboxyethyl germanium sesquioxide (Ge-132, 600 mg/L) in drinking water were administered respectively in the corresponding treatment groups: 100 ml/MNNG in drinking water was administered in the treatment group, and 100 ml/MNN in drinking water was administered in the treatment group and control group for another 5 weeks. The experiment ended at the end of the 37th week. The results showed that the incidence of glandular stomach cancer in the Yse group was significantly lower than that in the control group; the infiltrating depth of glandular stomach cancer in the Yse group and the Ge-132 group was remarkably shallower than that in the control group. These findings suggest that Yse and Ge-132 have some preventive effect on the precancerous lesion in rat glandular stomach induced by MNNG.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
9387686&query_hl=2&itool=pubmed_DocSum

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Cancer
Questionable methods of cancer management: hydrogen peroxide and other 'hyperoxygenation' therapies. CA Cancer J Clin. 1993 Jan-Feb;43(1):47-56.

"Hyperoxygenation" therapy--also called "oxymedicine," "bio-oxidative therapy," "oxidative therapy," and "oxidology"--is a method of cancer management based on the erroneous concept that cancer is caused by oxygen deficiency and can be cured by exposing cancer cells to more oxygen than they can tolerate. The most highly touted "hyperoxygenating" agents are hydrogen peroxide, germanium sesquioxide, and ozone. Although these compounds have been the subject of legitimate research, there is little or no evidence that they are effective for the treatment of any serious disease, and each has demonstrated potential for harm. Therefore, the American Cancer Society recommends that individuals with cancer not seek treatment from individuals promoting any form of hyperoxygenation therapy as an "alternative" to proven medical modalities.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
8422605&query_hl=2&itool=pubmed_DocSum

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Cancer
Modifying responses of allyl sulfide, indole-3-carbinol and germanium in a rat multi-organ carcinogenesis model. Carcinogenesis. 1991 Apr;12(4):691-5.

Jang JJ, Cho KJ, Lee YS, Bae JH.

Department of Anatomical Pathology, Korea Cancer Center Hospital, Seoul.

The modifying potential of allyl sulfide (AS), indole-3-carbinol (I3C) and carboxyethylgermanium sesquioxide (GE) on lesion development was examined in a wide-spectrum initiation model. Groups 1-4 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, i.p., single dose), N-methylnitrosourea (MNU) (20 mg/kg, i.p., four doses at days 2, 5, 8 and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Groups 5-7 received vehicles without carcinogens during the initiation period. Group 8 served as the untreated control. After this initiating procedure, groups 2-7 were administered a diet containing 0.5% AS or I3C and 0.05% GE. All surviving animals were killed 40 weeks after the beginning of the experiment and the target organs were examined. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with all three compounds. AS treatment significantly decreased the incidence of hepatic hyperplastic nodules, adenoma of the lung and thyroid, and papillary or nodular hyperplasia of the urinary bladder. Administration of GE also significantly inhibited the development of hepatic nodules and adenoma of the lung and thyroid. However, I3C only inhibited the hyperplastic nodules of the liver. These results demonstrated that this multi-organ initiation model could be useful in confirming organ-specific modification potential and, in addition, the inhibitory effect of AS, I3C and GE on liver, lung, thyroid and urinary bladder carcinogenesis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
2013133&query_hl=2&itool=pubmed_DocSum

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Cancer, Immune System
Antitumor mechanisms of carboxyethyl-germanium sesquioxide (Ge-132) in mice bearing Ehrlich ascites tumors. Gan To Kagaku Ryoho. 1987 Jan;14(1):127-34.

Suzuki F.

The administration of IFN-containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing or antitumor activities of the compound were detected. Cytotoxic activities were detected in peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, no antitumor activity of Ge-sera was observed. However, Ge-132 antitumor activity was observed in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell-depleted mice. Therefore, a part of the antitumor activity of Ge-132 appears to be expressed as follows: Ge-132 stimulates T-cells to produce circulating lymphokine(s) which are inactivated by anti-IFN gamma treatment; activated M phi are generated from resting M phi by these lymphokine(s); the transplanted tumors are inhibited by these M phi.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
3800401&query_hl=2&itool=pubmed_DocSum

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Cancer
Cooperation of lymphokine(s) and macrophages in expression of antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res. 1986 Mar-Apr;6(2):177-82.

Suzuki F, Brutkiewicz RR, Pollard RB.

The administration of IFN containing sera (Ge-sera) obtained from Ge-132-treated mice (Ge-mice) or the passive transfer of macrophages (M phi) to mice bearing ascites tumors resulted in the inhibition of tumor growth. The cooperative role of Ge-sera and Ge-M phi in the display of Ge-132-antitumor activity was studied. When mice were pretreated with antimouse IFN gamma antiserum, no IFN-inducing and antitumor activities of the compound were detected. Cytotoxic activities were detected on peritoneal M phi of mice treated with Ge-sera, and passive transfer of these M phi to tumor-bearing mice resulted in the inhibition of tumor growth. When tumor-bearing mice were pretreated with substances toxic to M phi, there was no antitumor activity of Ge-sera observed. However, there was antitumor activity of Ge-sera in mice depleted of T-cells, even though the antitumor effects of the compound itself were not demonstrable in T-cell depleted mice. Therefore, a part of the antitumor activity of Ge-132 may appear to be expressed as follows: (1) Ge-132 stimulated T-cells to produce circulating lymphokine(s) which were inactivated by anti-IFN gamma treatment; (2) activated M phi were generated from resting M phi by such lymphokine(s); (3) the transplanted tumors were inhibited by these M phi.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
3085573&query_hl=2&itool=pubmed_DocSum

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Cancer
[Antitumor effect in mice of an organic germanium compound (Ge-132) when different administration methods are used] Gan To Kagaku Ryoho. 1985 Dec;12(12):2345-51.

Aso H, Shibuya E, Suzuki F, Nakamura T, Inoue H, Ebina T, Ishida N.

The antitumor effect of an organic germanium compound, carboxyethylgermanium sesquioxide (Ge-132), was examined in mice using two systems: one, the ascitic form of Ehrlich carcinoma in DDI mice, and the other, the solid form of Meth-A fibrosarcoma in BALB/c mice. In the mice with Ehrlich ascitic tumors, a remarkable prolongation in life span was observed after intraperitoneal (i.p.) or per oral (p.o.) administration of Ge-132 (300 mg/kg), but not after intravenous (i.v.) injection of the same compound. Following i.p. or p.o. administration, cytotoxic macrophages (Mo) were induced in the peritoneal cavity after 48 h. although this was not the case after i.v. injections. When the in vivo effect of these in vitro active Mo was examined after adoptive transfer to mice bearing Ehrlich ascitic tumor cells, a significant antitumor effect was noted. In the mice bearing solid Meth-A tumors, i.v. injections of Ge-132 (100 mg/kg) were found to inhibit tumor growth remarkably, although i.p. and p.o. administrations did not have the same result. This inhibitory effect of Ge-132 by i.v. administration was explained by the continued augmentation of NK activity in peripheral blood, which was followed by the induction of specific killer cells appearing in the spleen. When the mice which had recovered from Meth-A tumor growth, following i.v. injections of Ge-132, were challenged with the same tumor on day 30, all mice were able to tolerate the challenge, but not a challenge of RL male 1 tumor cells. These observations may indicate that the differing antitumor effects of Ge-132 produced when different administration methods are used can be explained by the variation in effector cells induced by such different administration routes.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
4073929&query_hl=2&itool=pubmed_DocSum

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Cancer
[Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxyethylgermanium sesquioxide (Ge-132)] Gan To Kagaku Ryoho. 1985 Nov;12(11):2122-8.

Suzuki F.

In a murine model it has been shown that the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132) can be depleted by administration of macrophage (M phi) blockers. In the present study, the role that M phi play in the antitumor activity of the compound was investigated. Oral administration of Ge-132 in mice was demonstrated to be effective in activating M phi (Ge-132-cytotoxic M phi), and the cytotoxic activity of these M phi appeared in the peritoneal cavity of mice 48 hours after the oral administration of the compound. Co-cultivation of RL male-1 leukemia or Ehrlich carcinoma cells with Ge-132-cytotoxic M phi in vitro resulted in marked suppression of the growth of tumor cells. The transfer of peritoneal exudate cells (PEC), or purified M phi fractions of PEC from Ge-132-treated mice to mice bearing Ehrlich or RL male-1 ascites tumors resulted in significant protection. However, when the cytotoxic M phi were depleted by carbonyl-iron treatment in vitro, no antitumor effect was demonstrated in mice bearing Ehrlich or RL male-1 ascites tumors. Macrophage fractions obtained from PEC of Ge-132-treated mice exhibited an inhibitory effect against certain tumors both in vivo and in vitro suggesting that the antitumor effect of Ge-132 observed in vivo resulted from the activation of M phi.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
4062310&query_hl=2&itool=pubmed_DocSum

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Cancer, Immune System
Importance of T-cells and macrophages in the antitumor activity of carboxyethylgermanium sesquioxide (Ge-132). Anticancer Res. 1985 Sep-Oct;5(5):479-83.

Suzuki F, Brutkiewicz RR, Pollard RB.

The purpose of this study was to investigate the effective mechanisms of Ge-132, an organogermanium compound with immunomodulatory activity, on experimental murine ascites tumors. The antitumor effects of Ge-132 were observed when mice inoculated with Ehrlich carcinoma (allogeneic) or RL male 1 leukemia (syngeneic) cells were treated orally. However, Ge-132 had no activity on EL-4 lymphoma (syngeneic) or Meth A fibrosarcoma (syngeneic). The antitumor activity of Ge-132 was not observed when tumor-bearing mice were treated with trypan blue, carrageenan, or monoclonal anti-Thy 1.2 antibody. However, when natural killer (NK) cells were eliminated from mice bearing RL male 1 or Ehrlich ascites tumors by treatment with anti-asialo GM1 antiserum, the antitumor activity of the compound was unchanged. This suggests that Ge-132 was effective against certain ascites tumors regardless of whether the tumor was syngeneic or allogeneic. Furthermore, its effect might be expressed through host defense mechanisms, including macrophages and/or T-cells.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
3877491&query_hl=2&itool=pubmed_DocSum

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Cancer, Immune System
Inhibition of tumor growth and metastasis in association with modification of immune response by novel organic germanium compounds. J Biol Response Mod. 1985 Apr;4(2):159-68.

Sato I, Yuan BD, Nishimura T, Tanaka N.

The effects of two novel organic germanium compounds, 1-phenyl-2-carbamoylethylgermanium sesquisulfide (PCAGeS) and 1-phenyl-2-carbamoylethylgermanium sequioxide (PCAGeO), on transplantable murine tumors and immune responses were studied. Both drugs showed low toxicity for mice. In culture, neither substance displayed significant cytotoxicity against murine tumor cells L1210 leukemia, L5178Y lymphoma, or IMC carcinoma. Growth of subcutaneously transplanted IMC carcinoma or Meth-A fibrosarcoma was markedly reduced by oral administration of PCAGeS. PCAGeO exhibited a similar but smaller effect on the tumor growth. Pulmonary metastasis of Lewis lung carcinoma was inhibited by oral or intraperitoneal treatment with PCAGeS. The activity of cyclophosphamide or Adriamycin against L1210 leukemia was significantly potentiated by oral administration of PCAGeS. PCAGeS enhanced the delayed-type hypersensitivity response to sheep red blood cells (SRBC) of mice or restored the response suppressed by ascitic IMC carcinoma, but did not significantly affect the formation of antibody to SRBC. PCAGeO similarly stimulated the DTH reaction. Phagocytic activity of peritoneal macrophages was enhanced by oral treatment of mice with PCAGeS. The results suggest that PCAGeS and PCAGeO display tumor-inhibitory activity by modification of the immune mechanism.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
3998767&query_hl=2&itool=pubmed_DocSum

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Cancer
Effect of carboxyethylgermanium sesquioxide on the methylcholanthrene-induced tumorigenesis in mice. Sci Rep Res Inst Tohoku Univ [Med]. 1978 Dec;25(3-4):89-95.

Kumano N, Nakai Y, Ishikawa T, Koinumaru S, Suzuki S, Konno K 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
752926&query_hl=2&itool=pubmed_DocSum

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Cancer
DNA binding specificity and cytotoxicity of novel antitumor agent Ge132 derivatives. Bioorg Med Chem Lett. 2005 Jun 15;15(12):2962-5.

Shangguan G, Xing F, Qu X, Mao J, Zhao D, Zhao X, Ren J.

Division of Biological Inorganic Chemistry, Key Laboratory of Rare Earth Chemistry and Physics, Graduate School of the Chinese Academy of Sciences, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

A series of Ge132 derivatives have shown enhanced antitumor activity. Previous studies suggest that DNA can be their primary target. Here we show direct evidence that two newly synthesized Ge132 derivatives can intercalate into DNA. Unexpected methyl substitution effect of the novel derivatives on DNA sequence selectivity and cytotoxicity was observed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
15914003&query_hl=48&itool=pubmed_docsum

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Immune System, Cancer
Effectiveness of propagermanium treatment in multiple myeloma patients. Eur J Haematol. 2004 Dec;73(6):397-401.

Tsutsumi Y, Tanaka J, Kanamori H, Musashi M, Minami H, Fukushima A, Yamato H, Ehira N, Kawamura T, Obara S, Ogura N, Asaka M, Imamura M, Masauzi N.

Department of Internal Medicine, Hakodate Municipal Hospital, Hakodate, Japan. rtsutsu@nyc.odn.ne.jp

Interferon (IFN) is one of several drugs effective in treating multiple myeloma (MM), and propagermanium is an IFN inducer. We report on 10 MM patients who were treated with propagermanium at doses from 10 to 40 mg. Two patients achieved complete remission (CR), two patients achieved partial remission (PR), and the condition of four patients was stable (stable disease, SD). After discontinuation of propagermanium, the status of MM progressed in two patients who were in SD and in two patients who had achieved PR. The administration of propagermanium was restarted in one patient resulting in a decrease in her paraprotein.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
15522060&query_hl=48&itool=pubmed_docsum

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Cancer
Interference of selenium germanium and calcium in carcinogenesis of colon cancer. Zhonghua Wai Ke Za Zhi. 1995 Mar;33(3):167-9.

Yu B, Wu J, Zhou X.

Ruijin Hospital, Shanghai Second Medical University.

We studied DMH induced colon cancer in 120 wistar rats, which were divided into 8 groups based on different diets. They were killed and autopsied on 4 weeks after the last injection of DMH. The tumors in various organs including its characteristics, number, site, histological types and ultrastructural changes were observed. The results showed that high fat diet has a significant effect on DMH induced colon cancer. Selenium and calcium can inhibit the effect of DMH and decrease the incidence of colon cancer. Selenium can also interfere the effect of high fat diet but germanium has no effect on colon carcinogenesis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
7555387&query_hl=48&itool=pubmed_DocSum

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Immune System, Cancer, Physiology
Biological activities and antitumor mechanism of an immunopotentiating organogermanium compound, Ge-132 (review). In Vivo. 1987 Jul-Aug;1(4):189-203.

Brutkiewicz RR, Suzuki F.

Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.

The biological activities and antitumor mechanism of an immunopotentiator, Ge-132, is reviewed herein. Ge-132 exhibited antitumor activity against certain syngeneic and allogeneic experimental tumors. It was shown that T-cells and macrophages were involved when tumor-bearing mice were protected by the compound. This protective effect could be transferred to tumor-bearing mice, not treated with the compound, by a macrophage fraction and serum specimens obtained from Ge-132-treated mice. Interferon gamma (IFN gamma) was detected in the circulation of Ge-132-treated mice and when sera obtained from Ge-132-treated mice were treated with anti-IFN gamma antiserum in vitro, the antitumor activity was abolished. On the other hand, in mice treated with anti-IFN gamma antiserum, Ge-132 did not induce serum IFN and failed to protect against death due to ascites tumor progression. The in vivo administration of monoclonal anti-Thy 1.2 antibody prevented the expression of the antitumor activity of Ge-132. However, serum specimens obtained from Ge-132-treated mice effectively inhibited the tumor growth of T-cell-depleted mice bearing ascites tumors. Since it has been reported that T-lymphocytes produce IFN gamma, this suggested that Ge-132 may first stimulate T-cells to produce IFN gamma in the expression of the observed antitumor efficacy. In addition, sera obtained from Ge-132-treated mice did not show any antitumor activity in mice depleted of macrophage functions. Additionally, passive transfer of macrophages from mice treated with these serum specimens to tumor-bearing mice also resulted in the inhibition of tumor growth. Pretreatment of these serum specimens with anti-IFN gamma antiserum effectively prevented the generation of cytotoxic macrophages. Also, tumor-bearing mice treated exogenously with this antiserum did not differ significantly in survival as compared to controls, despite the administration of Ge-132. Furthermore, the antitumor activity of Ge-132 was detected in NK cell-depleted mice. Therefore, the antitumor mechanism of Ge-132 in the murine ascites tumor system may be expressed as follows: (a) Ge-132 stimulates T-cells to induce IFN gamma when mice are treated orally with the compound, (b) IFN gamma activates macrophages to become cytotoxic, and (c) the cytotoxic macrophages eliminate tumor cells.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
2979786&query_hl=48&itool=pubmed_DocSum

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Cancer
Ability of sera from mice treated with Ge-132, an organo-germanium compound, to inhibit experimental murine ascites tumors. Gan To Kagaku Ryoho. 1985 Dec;12(12):2314-21.

Suzuki F.

Serum specimens from mice treated orally with Ge-132 (100 mg/kg) exhibited antitumor activity against Ehrlich (allogeneic) and RL 1 (syngeneic) ascites tumors in BALB/c mice. Sera obtained from mice 24 hours after Ge-132 administration displayed the highest antitumor effect and the antitumor activity was dose-dependent. Sera prepared from mice 12, 36 or 48 hours after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 hours after administration. The antiviral activity of serum from Ge-132-treated mice was inactivated by treatment with trypsin, low pH, and anti-IFN-gamma antiserum. The inactivated preparations of serum IFN induced by Ge-132 did not show antitumor activity when administered to mice bearing Ehrlich ascites tumors. These results suggest that the antitumor activity in the sera of Ge-132-treated mice may have been expressed through IFN-gamma which was induced by Ge-132.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=
3935051&query_hl=48&itool=pubmed_DocSum

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Immune System, Cancer
Multidisciplinary treatment of head and neck cancer using BCG, OK-432, and GE-132 as biologic response modifiers.  Head Neck. 1994 Jan-Feb;16(1):30-8.

Fukazawa H, Ohashi Y, Sekiyama S, Hoshi H, Abe M, Takahashi M, Sato T.

2nd Department of Oral and Maxillofacial Surgery, Niigata University, School of Dentistry, Japan.

Since 1979, we have performed multidisciplinary treatment using intensive immunotherapy with biologic response modifiers (BRM) in combination with surgical treatment of oral cancer. Chemotherapy and radiotherapy were also included as part of the therapy. A historic control study was performed. Adjuvant therapy was administered by standardized methods, and the distribution of patients at various stages was similar between groups. The immunotherapy group showed a shorter treatment period, lower rates of recurrence, metastases, and side effects, greater histologic effects at the end of the first treatment, and a higher survival rate than the nonimmunotherapy group. Immunologically, immunotherapy tended to promote positive immune reactions and inhibit negative immune reactions. PMID: 7510275 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
7510275&query_hl=8&itool=pubmed_DocSum

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Cancer
Experimental study on prevention of the colorectal cancer by China medical stone and the organgermanium compound.  Zhonghua Yu Fang Yi Xue Za Zhi. 1993 Sep;27(5):286-9.

Song WS.

Pearl River Hospital, First Medical University of PLA, Guangzhou.

To compare the effect of cancer prevention of China medical stone (CMS) and Ge-132, rats were subcutaneously injected with dimethylhydrazine for 15 weeks and orally administered with 10% china medical stone soak and Ge-132 for 27 weeks. Colorectal cancer incidence in CMS was found significantly lower than in Ge-132 and controls (P < 0.05-0.01). In Ge-132 only the mean cancer foci and the mean cancer volumes/rat were found significantly less than controls (P < 0.01). It was shown by endoscopy that a precancerous lesion of the bowel resulted from carcinogen was more mild in CMS and Ge-132 than in controls. Serum gamma-interferon titer and NK activity of spleen cells were significantly elevated in CMS and Ge-132. Researches explained that the effect of cancer prevention of CMS was better than that of Ge-132. PMID: 8137660 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
8137660&query_hl=8&itool=pubmed_DocSum

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Cancer, Physiology, Safety
Organic germanium: its toxic effect and function in medical care.  Zhonghua Yi Xue Za Zhi. 1993 Aug;73(8):454-6.

Kong X.

PMID: 8111643 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
8111643&query_hl=8&itool=pubmed_DocSum

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Cancer, Lung
Effect of combination immunochemotherapy with an organogermanium compound, Ge-132, and antitumor agents on C57BL/6 mice bearing Lewis lung carcinoma (3LL).  Gan To Kagaku Ryoho. 1986 Aug;13(8):2588-93.

Kobayashi H, Komuro T, Furue H.

The antitumor effect of combination immunochemotherapy with Ge-132 and antitumor agent was studied using C57BL/6 mice bearing Lewis lung carcinoma (3LL). Ge-132 was administered orally at a daily dose of 100 mg/kg. Antitumor agents were administered intraperitoneally once a week. Initially, the effect of combination immunochemotherapy with Ge-132 and 5-fluorouracil (5-FU) was studied on 3LL local tumor growth, pulmonary metastases, survival, delayed type hypersensitivity (DTH) and body weight in tumor-bearing mice, and the following results were obtained: Inhibition of tumor growth in the combined group; Enhanced anti-metastatic effect; Prolonged survival time, and; Recovery of loss of both DTH and body weight as a result of combination therapy. These antitumor effects were also obtained by adoptive transfer of Ge-132-stimulated splenocytes in 5-FU-treated mice bearing 3LL. These results therefore suggest that the effects of Ge-132 were expressed through modification of immunocytes. Furthermore, Ge-132 enhanced the antitumor activity of bleomycin as well as that of 5-FU. These facts suggested that Ge-132 is useful for antitumor combination immunochemotherapy. PMID: 2427032 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
2427032&query_hl=8&itool=pubmed_DocSum

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Cancer, Immune System
Antitumor activity of Ge-132, a new organogermanium compound, in mice is expressed through the functions of macrophages and T lymphocytes.  Gan To Kagaku Ryoho. 1985 Jul;12(7):1445-52.

Suzuki F.

The antitumor activity of Ge-132 against a variety of allogeneic and syngeneic murine ascites tumors was first evaluated. The antitumor effects of Ge-132 were observed when mice inoculated with Ehrlich carcinoma (allogeneic) or RL male 1 leukemia (syngeneic) cells were treated orally. However, Ge-132 had no activity on a T-cell lymphoma (EL 4, syngeneic) or a methylcholanthrene-induced fibrosarcoma (Meth-A, syngeneic). The antitumor effect of Ge-132 in mice was related to the dose administered as well as the administration schedule. The antitumor activity of Ge-132 was next studied in mice pretreated with some blockers against immunocompetent cells. The antitumor efficacy of Ge-132 was not observed when tumor-bearing mice were treated with trypan blue and carrageenan or monoclonal anti-Thy 1.2 antibody. However, when natural killer cells were eliminated from mice bearing RL male 1 or Ehrlich ascites tumors by treatment with anti-asialo GM 1 antiserum, the antitumor efficacy of the compound was unchanged. These results suggest that Ge-132 is effective against certain ascites tumors regardless of whether the tumor is syngeneic or allogeneic. Further, its effect might be expressed through host defense mechanisms, including macrophages and/or T lymphocytes. PMID: 3874600 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
3874600&query_hl=8&itool=pubmed_DocSum

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Cancer, Immune System
Antitumor effect of the organogermanium compound Ge-132 on the Lewis lung carcinoma (3LL) in C57BL/6 (B6) mice.  Tohoku J Exp Med. 1985 May;146(1):97-104.

Kumano N, Ishikawa T, Koinumaru S, Kikumoto T, Suzuki S, Nakai Y, Konno K.

Effects of the organogermanium compound Ge-132 (i.p.) were examined on the 3LL local tumor (1 X 10(5)/mouse, s.c.) and its pulmonary metastases in B6 mice. A characteristic feature of its action was the preferential antimetastatic effect under strictly defined conditions. Either inhibition or facilitation was observed depending on the treatment schedules; 7 daily doses of 100 mg/kg yielded the inhibition ratio 49% when started from day 1, whereas the treatment from day 8 resulted in the ratio -99%. The maximum inhibition was obtained at 100 mg/kg. The postsurgical-adjuvant treatment with Ge-132 was of no beneficial effect. The local tumor growth was affected only marginally and temporarily. When inoculum size was minimized (1 X 10(4)), a single dose of 300 mg/kg on day 1, but not on day 8, was effective in prolonging the latency before tumor take. The antitumor action of Ge-132 was discussed with reference to its interferon (IFN)-inducing activity. PMID: 4024087 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
4024087&query_hl=8&itool=pubmed_DocSum

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Cancer, Immune System
Augmentation of NK activity in peripheral blood lymphocytes of cancer patients by intermittent GE-132 administration.  Gan To Kagaku Ryoho. 1984 Jun;11(6):1303-6. [Article in Japanese]

Tanaka N, Ohida J, Ono M, Yoshiwara H, Beika T, Terasawa A, Yamada J, Morioka S, Mannami T, Orita K.

The natural killer (NK) activity of peripheral blood lymphocytes from 18 cancer patients was studied prior to and after multiple administration of organo-germanium compound (Ge-132). In successive oral administration of Ge-132 at a dose of 1000 mg/day for 10 days, NK-activity of patients was augmented at 3 days, but by 10 days, depression of NK activity was observed in all cases. In intermittent oral administration of Ge-132, however, more than half of the patients with augmented NK activity at day 3 maintained the high activity level at day 10. This result suggests the superiority of intermittent administration of Ge-132 for clinical use. PMID: 6732257 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
6732257&query_hl=8&itool=pubmed_DocSum

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Cancer
Antimutagenic effect of Ge-132 on gamma-ray-induced mutations in Escherichia coli B/r WP2 trp-.  Int J Radiat Biol Relat Stud Phys Chem Med. 1982 Dec;42(6):653-9.

Mochizuki H, Kada T.

PMID: 6761292 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
6761292&query_hl=8&itool=pubmed_DocSum

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Cancer
Effect of NK-421 (Bestatin) and Ge-132 on the cytotoxicity of spleen cells obtained from the tumor-bearing mice.  Gan To Kagaku Ryoho. 1982 Oct;9(10):1771-7.

Ono M, Oka T, Yoshihara H, Tanaka N, Miwa H, Mannami T, Konaga E, Orita K.

The effect of NK-421(Bestatin) and Ge-132 (an organic germanium compound) on the ADCC and natural killing (NK) activities of the spleen cells of MH-134 tumor-bearing mice were studied. In the tumor-bearing mice, the ADCC activity was enhanced, and NK activity was reduced in accordance with the progress of the tumor. By oral administration of Bestatin at doses of 5, 10 and 50 mg/kg, ADCC activity was potentiated, and at a dose of 10 mg/kg, NK activity was significantly increased. Intraperitoneal administration of Ge-132 at 50 mg/kg potentiated the ADCC activity of tumor-bearing mice. A higher activity was observed in the plastic dish adherent fraction. Ge-132 also potentiated the reduced NK activity of tumor-bearing mice to higher level than normal mice. The elevated activities of ADCC and NK following Bestatin and Ge-132 administration were decreased with anti-Thy-1 antibody and complement; however, the percent reduction was lower compared to that of the control cancer animals. This result indicates that Bestatin and Ge-132 may act on non-T cells and augment ADCC and NK activities. PMID: 7184374 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
7184374&query_hl=8&itool=pubmed_DocSum

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Cancer, Cervix, Uterus
The inhibition of the development of experimental tumors of the cervix uteri and vagina by using tinctures of the cultured-cell biomass of the ginseng root and its germanium-selective stocks.  Biull Eksp Biol Med. 1993 Nov;116(11):534-6.

Bespalov VG, Davydov VV, Limarenko AIu, Slepian LI, Aleksandrov VA.

The anticarcinogenic effects of bioginseng and two germanium-selective drugs produced by cultivating cells of ginseng radix (Panax ginseng C. A. Mey) in a conventional medium or in media containing organogermanium compounds were studied. Squamous-cell carcinomas of the uterus cervix and vagina were induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene in mice. The drugs of ginseng were used orally or intravaginally during a long period of time of the postinitiation stage of carcinogenesis. All the drugs used locally effectively inhibited the development of induced carcinomas of the uterus cervix and vagina. When orally used, the drugs of ginseng exhibited only an insignificant tendency to inhibit the carcinogenesis of uterus cervix and vagina. The anticarcinogenic effects of the compared drugs were similar. PMID: 8312554 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
8312554&query_hl=1&itool=pubmed_docsum

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Safety, Toxicity, Cancer
Cancer risks for humans from exposure to the semiconductor metals.  Scand J Work Environ Health. 1993;19 Suppl 1:101-3.

Fowler BA, Yamauchi H, Conner EA, Akkerman M.

Program in Toxicology, University of Maryland, Baltimore 21227.

Of the semiconductor metals, only arsenic has been extensively studied as a human carcinogen and systemic toxicant. Recent studies have shown, however, that gallium, arsenic, and indium are capable of producing marked alterations in cellular gene products. After acute in vivo administration indium and thallium have been shown to produce decreases in the activity of some drug-metabolizing enzymes dependent on cytochrome P-450; therefore these metals would be capable of interfering with the metabolism of organic carcinogens. Selenium is essential for the activity of the enzyme glutathione peroxidase, which modulates the active intermediates generated by drug-metabolizing enzyme systems. Germanium produces toxicity in a number of organ systems. Antimony produces lung and circulatory system effects. Overall, available data suggest that these metals or metalloids are capable of biologically altering several cellular defense mechanisms involved in the carcinogenic process and that further studies are needed to determine the associated risks. PMID: 8159952 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
8159952&query_hl=1&itool=pubmed_DocSum

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Cancer, Antimutagenic
Effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.  Dis Colon Rectum. 1990 Feb;33(2):99-104.

Jao SW, Lee W, Ho YS.

Department of Surgery, National Defense Medical Center, Taipei, Taiwan,Republic of China.

Through recent research, the trace element, germanium, was found to have an anticancer effect. The purpose of this research was to determine the effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats. Ninety-six 8-week-old Sprague-Dawley male rats were divided into 4 groups, with 24 rats in each group. All received dimethylhydrazine, 20 mg/kg body weight, subcutaneously, once a week for 20 weeks. Except for one control group, the other three groups were subdivided into six groups and administered three different kinds of germanium (inorganic germanium, organic germanium, and natural organic germanium) one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment, respectively. Twenty-four weeks after carcinogen exposure, all surviving animals were sacrificed and examined for intestinal tumors. The number and location of the tumors were recorded and the pathology examined. The incidence of intestinal cancer in the control group (dimethylhydrazine only) was 91 percent; in groups provided with inorganic germanium one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only, it was 91 and 78 percent; in groups provided with organic germanium one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only, it was 64 and 64 percent; in groups provided with natural organic germanium one month before and during dimethylhydrazine treatment and during dimethylhydrazine treatment only, it was 50 and 45 percent. From these results, the authors conclude that natural organic germanium has the best prevention effect for intestinal cancer in this animal model (P less than 0.01), followed by organic germanium (P less than 0.05). Inorganic germanium has no effect. However, there is no difference in the cancer prevention effect of germanium provided one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only. PMID: 2153512 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
2153512&query_hl=1&itool=pubmed_DocSum

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Cancer, Immune System, Antiviral, Arthritis, Osteoporosis
Therapeutic effects of organic germanium.  Med Hypotheses. 1988 Jul;26(3):207-15.

Goodman S.

International Inst. of Symbiotic Studies, Brighton, Sussex, U.K.

Germanium is present in all living plant and animal matter in micro-trace quantities. Its therapeutic attributes include immuno-enhancement, oxygen enrichment, free radical scavenging, analgesia and heavy metal detoxification. Toxicological studies document Germanium's rapid absorption and elimination from the body, and its safety. Clinical trials and use in private practices for more than a decade have demonstrated Germanium's efficacy in treating a wide range of serious afflictions, including cancer, arthritis and senile osteoporosis. Germanium's anti-viral and immunological properties, including the induction of interferon, macrophages, T-suppressor cells and augmentation of natural killer cell activity, suggest its possible efficacy in treating and/or preventing AIDS. PMID: 3043151 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
3043151&query_hl=1&itool=pubmed_DocSum

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Cancer, Lung, Immune System
Prevention of pulmonary metastasis of Lewis lung carcinoma and activation of murine macrophages by a novel organic germanium compound, PCAGeS.  J Biol Response Mod. 1988 Feb;7(1):1-5.

Sato I, Nishimura T, Kakimoto N, Suzuki H, Tanaka N.

Institute of Applied Microbiology, University of Tokyo, Japan.

The pulmonary metastasis of Lewis lung carcinoma was strongly blocked by daily intraperitoneal (i.p.) treatment with 0.5 mg of PCAGeS/kg/day for 7 days after tumor implantation. The metastasis-preventive activity of PCAGeS was markedly reduced when mice were treated with carrageenan, a macrophage blocker. On the other hand, treatment with antiasialo GM1 antiserum did not significantly affect the percentage of inhibition of metastasis by the compound. These results suggest that macrophages rather than natural killer (NK) cells play an important role in the suppression of metastasis by PCAGeS. PCAGeS induced tumoristatic and tumoricidal activities in the peritoneal macrophages of mice by oral administration. The activity of NK cells was also augmented by i.p. treatment with the compound. These results suggest that PCAGeS is a useful substance for preventing pulmonary metastasis. PMID: 3373232 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=
3373232&query_hl=1&itool=pubmed_DocSum

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Cancer
Effect of 3-oxygermylpropionic Acid Polymer (SK-818) on the Incidence of Spontaneous Leukemia in AKR Mice

Haruhisa Fujita,  Masayasy Kurono, Shigeshi Toyoshima

Division of chemotherapy, Pharmaceutical Institute, School of Medicine, Keio University, Shinjyuku-ku,  Tokyo 160, Japan and Sanwa Kagaku Kenkyusyo Co. Ltd.., Mie 511-04, Japan

Received December 20, 1989

The effects of 3-oxygermylpropionic acid polymer (proxigermanium, or SK-818)  on the incidence of the spontaneous leukemia in AKR mice were examined.  The occurrence of leukemia was indicated by a greater increase of weights of the spleen, thymus, and mesenteric lymph nodes in these mice than in non-leukemic C3H mice.  Proxigermanium inhibited the increase of the organ weights accompanying leukemia.  When administered at a dose of 10 mg/kg or 100 mg/kg orally twice a week for five months between 4 and 9 months of age, proxigermanium had a marked inhibitory effect on the increase of the organ weights in AKR mice.  These results suggest that proxigermanium powerfully inhibits spontaneous leukemia from occurring in AKR mice.

Key words:  Spontaneous leukemia/Proxigermanium compound/Inhibitory effect on the incidence of leukemia.

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