CN101112398A - Application of typhoid fever and paratyphoid fever salmonella in the aspect of fast anti-tumor - Google Patents

Application of typhoid fever and paratyphoid fever salmonella in the aspect of fast anti-tumor Download PDF

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CN101112398A
CN101112398A CNA2007101455061A CN200710145506A CN101112398A CN 101112398 A CN101112398 A CN 101112398A CN A2007101455061 A CNA2007101455061 A CN A2007101455061A CN 200710145506 A CN200710145506 A CN 200710145506A CN 101112398 A CN101112398 A CN 101112398A
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罗舒仓
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/74Bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/522Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/523Bacterial cells; Fungal cells; Protozoal cells expressing foreign proteins
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract

The present invention discloses an application of typhoid and paratyphoid salmonella in the anti-tumor aspect, which is invented to solve the problems of great side effects and poor effects of the prior art in the treatment of tumors. The present invention provides the application of the typhoid and paratyphoid salmonella in the rapid anti-tumor aspect. Wherein, the tumors are one or more of gastric cancer, lung cancer, liver cancer, tongue squamous cancer, breast cancer, colon cancer, leukemia, brain tumor and sarcoma. The invention makes use of the rapid combination of the typhoid and paratyphoid salmonella with the mononuclear cells after entering into the human body, the strong endotoxin and bacteremia are released and the temperature reaches highly around 40 DEG C to 42 DEG C, so as to affect and inhibit the growth and the life cycle of the tumor cells, furthermore, the large mononuclear cells-macrophages in the reticuloendothelial system are proliferated greatly, thus enhancing the ability of the macrophages in vivo to swallow the cancer cells, so the invention has very significant inhibiting and killing effects of a variety of tumors.

Description

The application of typhoid fever, bacillus paratyphosus fast anti-tumor aspect
Technical field
The present invention relates to the application of typhoid fever, bacillus paratyphosus fast anti-tumor aspect.
Background technology
Malignant tumor (cancer) is a class serious threat human life and healthy disease.According to up-to-date statistics, the annual New Development cancer patient about about 1,600,000 of China, dead about 1,300,000, seize about 6,000,000 people's life every year in global cancer, and 1,000 ten thousand people are placed dead edge, along with going from bad to worse of environment for human survival, the incidence rate of tumor is ascendant trend year by year.World Health Organization's prediction 21 century cancer will become human dead " first killer ".Modern medicine mainly is that the operative treatment cooperation is put, chemotherapy to tumor treatment at present.Though operation can be removed primary lesion, but can not fundamentally stop the regeneration and the breeding of tumor cell, and this root of tumor recurrence and transfer in the future just, though put, chemotherapy can kill cancerous cell, but also make a large amount of normal tissue cells be subjected to grievous injury simultaneously, bring out gastrointestinal reaction, bone marrow depression and Liver and kidney, impairment of cardiac function, make the various internal organs of health seriously depleted, be difficult to accept further treatment, finally cause patient death.
We select and utilize typhoid fever, bacillus paratyphosus to the powerful inhibition of cancerous cell pointedly for this reason
Typhoid fever is to be by paratyphoid fever, second, the third three kinds of acute infectiouss disease of the digestive tract of whole body that Salmonella causes through alimentary infection by Salmonella typhi, paratyphoid fever.In the early days of foundation, because people's sanitary condition is relatively poor, its M ﹠ M is higher, once once caused serious injury to people, but along with progress of science and technology and antibiotic use, the mortality rate of typhoid fever is approximately (comprising infant and old people, in addition, between twenty and fifty mortality rate will reduce greatly) between the 0.5-1% now.Its pathogeny is: Salmonella typhi is invaded intestinal mucosa after entering small intestinal with water that pollutes or food, and the part pathogenic bacteria breeds by macrophage phagocytic and in its endochylema; Part enters the ileum aggregated lymphatic follicles through lymphatic vessel, breeds in solitary lymphatic follicles and the mesenteric lymph node, enters blood flow by thoracic duct then and causes of short duration bacteremia.This stage is equivalent to incubation period clinically.Salmonella typhi enters liver, spleen and other reticuloendothelial systems with blood flow and continues a large amount of breedings, enters blood flow once more, causes for the second time serious bacteremia, and discharges intensive endotoxin, causes clinical onset.The main pathological characteristic of typhoid fever is the hypertrophy of large mononuclear cell-macrophage in the whole body reticuloendothelial system, and its phagocyte ability is very active.
Summary of the invention
For overcoming above-mentioned defective, the object of the invention is to provide the application at anti-tumor aspect of a kind of typhoid fever, bacillus paratyphosus
For achieving the above object, the present invention proposes the application of typhoid fever, bacillus paratyphosus fast anti-tumor aspect.Wherein, above-mentioned tumor is a kind of in gastric cancer, hepatocarcinoma, pulmonary carcinoma, breast carcinoma, tongue squamous cell carcinoma, colon cancer, leukemia, the cerebral tumor and the sarcoma.
After utilizing typhoid fever, bacillus paratyphosus in entering human body, can promptly combine with mononuclear cell, and discharge high temperature about intensive endotoxin, bacteremia and 40-42 ℃, growth and life cycle with influence and containment tumor cell, and make the hypertrophy in large quantities of large mononuclear cell-macrophage in the whole body reticuloendothelial system, strengthen the ability of engulfing cancerous cell of macrophage in the body, therefore various tumors have been had containment and killing action very significantly.
The specific embodiment
The present invention proposes the application of typhoid fever, bacillus paratyphosus fast anti-tumor aspect, below with comparatively representative severally be further described as experimental example in the tumor.
Test the application of 1 Salmonella typhi in anti-hepatocarcinoma
Experiment material: injection Salmonella typhi: typhoid fever (50071)
Experimental technique: select 32 kunming mouses, female, 20g ± 2, inoculation H22, hepatoma carcinoma cell 1 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 8 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 15 ± 3 days
2 Low dose group (1250U//time) 22 ± 5 days
3 Middle dosage group (2500U//time) 27 ± 5 days
4 High dose group (5000U//time) 28 ± 3 days
From The above results, Salmonella typhi typhoid fever (50071) has fairly obvious therapeutical effect to mice H22 hepatocarcinoma.
Test the application of 2 Salmonella typhis in anti-pulmonary carcinoma
Experiment material: injection Salmonella typhi: typhoid fever (50071)
Experimental technique: select 40 C57/bl mices, male, 20g ± 2, inoculation lewis, lung carcinoma cell 2 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 10 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 20 ± 4 days
2 Low dose group (1250U//time) 21 ± 5 days
3 Middle dosage group (2500U//time) 25 ± 5 days
4 High dose group (5000U//time) 30 ± 6 days
From The above results, Salmonella typhi has fairly obvious therapeutical effect to mice lewis pulmonary carcinoma.
Test the application of 3 bacillus paratyphosuses in anti-breast cancer
Experiment material: bacillus paratyphosus: paratyphoid A (50001)
Experimental technique: select 40 Balb/c mices, female, 20g ± 2, inoculation EMT-6, breast cancer cell 5 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 10 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 18 ± 5 days
2 Low dose group (1250U//time) 20 ± 4 days
3 Middle dosage group (2500U//time) 22 ± 6 days
4 High dose group (5000U//time) 30 ± 5 days
From The above results, paratyphoid A (50001) has fairly obvious therapeutical effect to mice EMT-6 breast carcinoma.
Test the application of 4 bacillus paratyphosuses in leukemia
Experiment material: bacillus paratyphosus: paratyphoid A (50001)
Select 20 615 inbred mouses, female, 20g ± 2, inoculation L-615, the leukaemia 5 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 5 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 8 ± 4 days
2 Low dose group (1250U//time) 10 ± 4 days
3 Middle dosage group (2500U//time) 15 ± 6 days
4 High dose group (5000U//time) 19 ± 7 days
From The above results, paratyphoid A (50001) has fairly obvious therapeutical effect to mice L-615 leukemia.
Test the application of 5 bacillus paratyphosuses in resistive connection intestinal cancer
Experiment material: bacillus paratyphosus: paratyphoid B (50094)
Experimental technique: select 20 C57/bl inbred mouses, female, 20g ± 2, inoculation Z-38, colon cancer cell 5 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 5 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 30 ± 5 days
2 Low dose group (1250U//time) 35 ± 4 days
3 Middle dosage group (2500U//time) 39 ± 5 days
4 High dose group (5000U//time) 44 ± 7 days
From The above results, paratyphoid B (50094) has fairly obvious therapeutical effect to mice Z-38 colon cancer.
Test the application of 6 bacillus paratyphosuses in anti-gastric cancer
Experiment material: bacillus paratyphosus: paratyphoid B (50094)
Experimental technique: select 28 BALB/C-NU nude mices, female, 20g ± 2, inoculation BGC803, stomach cancer cell 2 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 7 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 30 ± 5 days
2 Low dose group (1250U//time) 36 ± 4 days
3 Middle dosage group (2500U//time) 40 ± 5 days
4 High dose group (5000U//time) 45 ± 7 days
From The above results, paratyphoid B (50094) has fairly obvious therapeutical effect to mice BGC803 gastric cancer.
Test the application of 7 bacillus paratyphosuses in resistive connection intestinal cancer
Experiment material: bacillus paratyphosus: paratyphoid B (50004)
Experimental technique: select 20 BALB/C-NU nude mices, female, 20g ± 2, inoculation HCT-8, colon cancer cell 2 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 5 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 25 ± 6 days
2 Low dose group (1250U//time) 29 ± 5 days
3 Middle dosage group (2500U//time) 35 ± 4 days
4 High dose group (5000U//time) 39 ± 6 days
From The above results, paratyphoid B (50004) has fairly obvious therapeutical effect to mice HCT-8 colon cancer.
Test the application of 8 bacillus paratyphosuses in anti-tongue squamous cell carcinoma
Experiment material: bacillus paratyphosus: paratyphoid B (50004)
Experimental technique: select 20 BALB/C-NU nude mices, female, 20g ± 2, inoculation TAC, tongue squamous cell carcinoma cell 2 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 5 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 35 ± 6 days
2 Low dose group (1250U//time) 40 ± 5 days
3 Middle dosage group (2500U//time) 44 ± 4 days
4 High dose group (5000U//time) 46 ± 6 days
From The above results, paratyphoid B (50004) has fairly obvious therapeutical effect to mice TAC tongue squamous cell carcinoma.
Test the application of 9 bacillus paratyphosuses in anti-tongue squamous cell carcinoma
Experiment material: bacillus paratyphosus: paratyphoid A (50443)
Experimental technique: select 32 outbreeding system kunming mices, female, 20g ± 2, inoculation TAC, cerebroma cell 5 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 8 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 16 ± 4 days
2 Low dose group (1250U//time) 19 ± 6 days
3 Middle dosage group (2500U//time) 25 ± 4 days
4 High dose group (5000U//time) 32 ± 6 days
From The above results, paratyphoid A (50443) has fairly obvious therapeutical effect to mice TAC cerebroma cell.
Test the application of 10 bacillus paratyphosuses in anti-sarcoma
Experiment material: bacillus paratyphosus: paratyphoid A (50443)
Experimental technique: select 20 outbreeding system kunming mices, female, 20g ± 2, inoculation S180, sarcoma cell 5 * 10 6/ only, the right side axillary fossa is subcutaneous.Be divided into 4 groups next day at random: matched group, low dose group (1250U/ only/time), middle dosage group (2500U/ only/time) and high dose group (5000U/ only/time), 5 every group, calculate the existence natural law of every group of mice.
Experimental result:
Sequence number Group Mean survival time (MST)
1 Matched group 10 ± 2 days
2 Low dose group (1250U//time) 15 ± 5 days
3 Middle dosage group (2500U//time) 19 ± 6 days
4 High dose group (5000U//time) 28 ± 5 days
From The above results, paratyphoid A (50443) has fairly obvious therapeutical effect to mice S180 sarcoma.
To sum up, can know that typhoid fever, bacillus paratyphosus (comprising typhoid fever behind the attenuation, bacillus paratyphosus) have direct and indirect killing action to tumor as those of ordinary skill in the art.
Above-mentioned Salmonella typhi typhoid fever (50071), paratyphoid A (50001), paratyphoid A (50443), paratyphoid B (50094), paratyphoid B (50004) are identified institute available from Beijing biological product.

Claims (10)

1. the application of typhoid fever, bacillus paratyphosus fast anti-tumor aspect.
2. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a gastric cancer.
3. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a pulmonary carcinoma.
4. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a breast carcinoma.
5. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a colon cancer.
6. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is the cerebral tumor.
7. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a sarcoma.
8. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a leukemia.
9. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is a hepatocarcinoma.
10. the application of typhoid fever as claimed in claim 1, bacillus paratyphosus fast anti-tumor aspect is characterized in that: described tumor is the tongue squamous cell carcinoma.
CNA2007101455061A 2007-08-28 2007-08-28 Application of typhoid fever and paratyphoid fever salmonella in the aspect of fast anti-tumor Pending CN101112398A (en)

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CNA2007101455061A CN101112398A (en) 2007-08-28 2007-08-28 Application of typhoid fever and paratyphoid fever salmonella in the aspect of fast anti-tumor
PCT/CN2008/001513 WO2009030103A1 (en) 2007-08-28 2008-08-22 The uses of salmonella typhi or salmonella paratyphi for preparation of medicaments for combating tumors

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009030103A1 (en) * 2007-08-28 2009-03-12 Shucang Luo The uses of salmonella typhi or salmonella paratyphi for preparation of medicaments for combating tumors
CN101485654B (en) * 2009-03-03 2010-12-08 山东大学 Application of T-2 toxin in preparing medicament for treating solid tumor
CN101984964B (en) * 2009-03-03 2012-03-07 山东大学 Application of T-2 toxin to preparing drugs for treating renal cell carcinomas
CN101669973B (en) * 2008-09-12 2013-06-19 马逸冰 Biological immunopotentiator composition for treating cancers

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6190657B1 (en) * 1995-06-07 2001-02-20 Yale University Vectors for the diagnosis and treatment of solid tumors including melanoma
US20050180985A9 (en) * 2001-10-04 2005-08-18 Vladoianu Ion R. Live attenuated salmonella strains for producing monovalent or multivalent vaccines
CN101112398A (en) * 2007-08-28 2008-01-30 罗舒仓 Application of typhoid fever and paratyphoid fever salmonella in the aspect of fast anti-tumor

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009030103A1 (en) * 2007-08-28 2009-03-12 Shucang Luo The uses of salmonella typhi or salmonella paratyphi for preparation of medicaments for combating tumors
CN101669973B (en) * 2008-09-12 2013-06-19 马逸冰 Biological immunopotentiator composition for treating cancers
CN101485654B (en) * 2009-03-03 2010-12-08 山东大学 Application of T-2 toxin in preparing medicament for treating solid tumor
CN101984964B (en) * 2009-03-03 2012-03-07 山东大学 Application of T-2 toxin to preparing drugs for treating renal cell carcinomas

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