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    ORAL ADMINISTRATION OF BACILLUS OLIGONITROPHILUS KU-1 MAY PREVENT SIDE EFFECTS OF CONVENTIONAL ANTICANCER TREATMENT

    Sergey V. Malkov1, Vladimir V. Markelov2, Gleb Y. Polozov1,
    Boris I. Barabanschikov1, Maxim V. Trushin*1, 3

    1Kazan State University, Department of Genetics 2 Kazan Municipal Rehabilitation Medical Health Center "Sanatorium Krutushka", 3Kazan Institute of Biochemistry and Biophysics, Kazan, Russia.

    mtrushin @ mail.ru

    Rev Electron Biomed / Electron J Biomed 2006;2:105-107.

    To the Editor:

    Conventional chemotherapeutic and radiotherapeutic methods provoke significant side effects in cancer patients. Most of cancer patients show development of asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia as a result of anticancer treatment1. Some cancer sufferers demonstrate acute intestinal injury that is a common and serious problem leading to disruption of morphologic mucosal integrity and normal bacterial microflora and thereby favoring the malabsorption2. Hematologic abnormalities are, unfortunately, also frequent events in cancer patients3. In this connection, a search for efficient ways for cancellation of the above-mentioned side effects of conventional anticancer treatment is of great importance. We reported previously that oral administration of Bacillus oligonitrophilus KU-1 results in cancer inhibition4. Here we report that administration of the above-mentioned strain may prevent side effects of chemotherapeutic drugs and normalize blood picture.

    Bacillus oligonitrophilus KU-1 (Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae) strain was isolated from soil of Kazan city, Russia. 300 mg of soil was re-suspended in 2 mL of modified liquid medium of Alexandrov without potassium (pH 8.0) and inoculated on the agar plates with the same content and supplemented with orthoclase (g/L: 0.5). The full-grown mucilaginous colonies were checked on growth ability on liquid Alexandrov's medium without potassium and supplemented with orthoclase. Then B. oligonitrophilus KU-1 cells were grown at 20 0C without shaking during 2 days. Stationary phase B. oligonitrophilus KU-1 culture (0.5-1.0x109 cells per mL) was used for peroral administration according to a specially developed scheme4.

    We present here two cases where administration of B. oligonitrophilus KU-1 was in parallel with chemotherapy drugs. Case 1. Female was born in 1957. In late 1999, ovary tumor with metastases into liver and abdominal cavity as well as undifferentiated rectum tumor was revealed (T4NxM1).

    In February 23, 2000, hysterectomy and resection of greater omentum were made at Government State Service "Oncology" (Kazan, Russia). Sigmostoma and rectum were not ablated. There was about 3 litres of ascitic fluid in the abdominal cavity. Right ovary was in the form of thick-walled cyst (20x18x15 cm). In the liver, there were three roundish formations (up to 3 cm in diameter). In the rectosigmoid section, there was Schnitzler's metastasis (2x3x1 cm). Urine analysis (May 5, 2000): weight - 1.010, pH 6.0, glucose and protein was absent. L. USI (March 31, 2000): liver - heterogeneous parenchyma near the edge of costal margin. There were hyperechoic formations (in SVI - 55 mm in diameter, in SVII - 41 mm in diameter). There were foci of disintegration in the center of each hyperechoic formation. In the left lobe of liver, there was hyperechoic formation (31 mm in diameter). Gall-bladder was increased. Ultrasound investigation (May 6, 2000): liver - variety of hyperechoic metastatic formations of 69 mm in diameter (some of them were with fluid inclusions). Kidneys, spleen, heart; lungs (according to X-ray examination) and pancreas were without pathology.

    In May 2000, reception of B. oligonitrophilus KU-1 culture was started. The initial level of bacteria reception was 200 mL per day; since August and October, daily reception was increased up to 400 and 600 mL, respectively. Simultaneously, topotecan was received. Ultrasound investigation of liver (February 2, 2001): numerous metastases (47-123 mm in diameter). During all this time, the patient received daily 500-700 mL of B. oligonitrophilus KU-1 culture. Due to liver failure, the patient died in July 19, 2001.

    Case 2. Female was born in 1962. In August 2002, double-sided ovary cystadenocarcinoma (4x4 and 5x7 cm) with a wide distribution into peritoneum was determined (T4NxM1). In addition, multiple metastases into the greater omentum were observed. Cystatin was received before the operation. In that period, the patient was very ill being. In August 20, 2002, hysterectomy and ablation of greater omentum were made at Samara Oncology Center (Samara, Russia). Since September 2002, until February 2003, the patient received B. oligonitrophilus KU-1 (300 mL per day). Increase in intracranial pressure was observed while blood pressure was normal. After CA125 normalization, bacteria were received with prophylactic aim (50 mL per day, a week of reception was changed by a week of interruption). In May 17, 2004, Ultrasound investigation revealed metastases into the cellular tissue of pelvis minor. Chemotherapeutic course of treatment (cystatin, 110 mg) was perceived very badly (there were retching and asthenovegetative syndrome). Since June 2004, the patient increased reception of B. oligonitrophilus KU-1 (300 mL per day). According to ultrasound investigation data, the size of metaplastic cancer in cellular tissue of pelvis minor decreased up to 30%. Now the patient continues to receive B. oligonitrophilus KU-1 (50 mL per day, a week of reception changes by a week of interruption). In January 2005, the patient was hospitalized due to relapse of thrombophlebitis. Clot was operated. The patient received antithrombin drugs. Since January 2005, reception of B. oligonitrophilus KU-1 was stopped. As a result, there was a significant increase in CA 125 level in March 2005. In April 23, 2005, reception of B. oligonitrophilus KU-1 was resumed (200 mL per day). State of health became significantly better until the middle of May 2005. In May 25, 2005, the patient died.

    Beneficial effects of probiotic microorganisms for cancer patients are under intensive investigation not. It was shown by some researchers that, for example, Lactobacillus bulgaricus could be given to prevent radiation-induced enteritis2. The similar effects were observed during application of other probiotic strain called "Acilact" 5. It is clear from the presented material that B. oligonitrophilus KU-1 may improve hematologic parameters in cancer patients (Table 1).



    Despite application of chemotherapeutic drugs and cancer itself, both patients demonstrated normal hemoglobin levels, leukogram and biochemical values. Moreover, improvement of health state was observed despite harmful effects of chemotherapy. We consider that significant delay in lethal outcome was due to administration of B. oligonitrophilus KU-1. Although we reported about possible mechanisms of B. oligonitrophilus KU-1 action6, the exact mode of the observed beneficial effects remains to be detected. Only one thing is a definite at present - B. oligonitrophilus KU-1 can be applied not only as therapeutic drug (that is more desirable) but also as adjuvant agent to suppress side effects of conventional anticancer treatments.


    REFERENCES:

      1. Martin M, Lluch A, Segui MA, Ruiz A, Ramos M, Adrover E, Rodriguez-Lescure A, Grosse R, Calvo L, Fernandez-Chacon C, Roset M, Anton A, Isla D, Del Prado PM, Iglesias L, Zaluski J, Arcusa A, Lopez-Vega JM, Munoz M, Mel JR. Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol. 2006;17:1205-12.

      2. Demirer S, Aydintug S, Aslim B, Kepenekci I, Sengul N, Evirgen O, Gerceker D, Andrieu MN, Ulusoy C, Karahuseyinoglu S. Effects of probiotics on radiation-induced intestinal injury in rats. Nutrition 2006; 22:179-186.

      3. Pujade-Lauraine E, Richard AJ, Sapede C, Hayward C. Erythropoietic agents in anaemic patients with cancer: a retrospective observational survey of epoetin alpha, epoetin beta and darbepoetin alpha use in routine clinical practice. Oncol Rep 2005; 14:1037-1044.

      4. Malkov SV, Markelov VV, Polozov GY, Sobchuk LI, Zakharova NG, Barabanschikov BI, Kozhevnikov AY, Vaphin RA, Trushin MV. Antitumor features of Bacillus oligonitrophilus KU-1 strain. J Microbiol Immunol Infect 2005; 38: 96-104.

      5. Budagov RS, Ul'ianova LP, Pospelova VV et al. The protective activity of a new variant of the probiotic Acilact in exposure to ionizing radiation and anticancer chemotherapy under experimental conditions. Vestn Ross Akad Med Nauk 2006; 2: 3-5.

      6. Malkov SV, Markelov VV, Barabanschikov BI, Trushin MV, Marotta F. Genome rejuvenation and its applications. Biomed Scientist 2006; 50: 45-47.

    Corresponding author: Dr. Maxim V. Trushin
    Kazan Institute of Biochemistry and Biophysics
    Lobachevskii str. 2/31, P.O. Box 30,
    420111, Kazan, Russia
    Tel.: +7843-2319026
    Email: mtrushin@mail.ru

    Received: July 5, 2006
    Published: July 30, 2006