METHOD FOR INDUCING MASS APOPTOSIS OF CANCER CELLS BY ENHANCING THE OVERALL ACIDITY IN THE TUMOR

Abstract

A method for inducing mass apoptosis of cancer cells by enhancing the overall acidity in the tumor. The method enhances overall acidity in tumor internal tissue to reduce overall pH in tumor tissue, last to induce mass apoptosis of cancer cells. When pH of extracellular micro-environment of cancer cells is lower than 5.0, mass apoptosis of cancer cells can be induced. Base on the same direction synergic interaction between the changes of intracellular and extracellular acidity in tumor, the method may be achieved by injecting acid directly into tumor cells, or aggravating the anaerobic respiration of cancer cells through hyperthermia and other ways to enhance overall acidity in tumor tissues. The method may effectively induce mass apoptosis of cancer cells with little damaging to the normal cells, so as to inhibit the differentiation and proliferation of cancer cells, stop the metastasis and diffusion, and realize the radical cure of tumor.

Claims

1. A method for inducing mass apoptosis of cancer cells by enhancing overall acidity in tumor, comprising reducing overall pH in tumor tissue by adopting a physical or biochemical method, so as to enhance overall acidity in tumor tissue and induce mass apoptosis of cancer cells.

2. The method according to claim 1, wherein reducing overall pH in tumor tissue comprises needing to make the pH of extracellular micro-environment of cancer cells in tumor lower than 5, in order to induce mass apoptosis of cancer cells.

3. The method according to claim 1, wherein base on the same direction synergic interaction between the changes of intracellular acidity and extracellular acidity in tumor, reducing overall pH in tumor tissue can be performed by injecting an acid directly into tumor tissue or by hyperthermia therapy aggravateing anaerobic respiration of cancer cells in order to indirectly induce the overall acidification in tumor tissue.

4. The method according to claim 3, wherein injecting an acid directly into tumor tissue comprises an acid liquid is injected directly into tumor tissue to promote the pH of extracellular micro-environment of cancer cells to be lower than 5, thus inducing mass apoptosis of cancer cells.

5. The method according to claim 3, wherein the hyperthermia therapy comprises aggravating the anaerobic respiration of cancer cells through hyperthermia therapy to a whole body or hyperthermia therapy to tumor tissue region, so as to promote the acidification of intracellularly tissues and extracellular tissues of cancer cells, intent is to promote the pH of extracellular micro-environment of cancer cells to be lower than 5, thus fully enhancing the overall acidity in tumor, in the end inducing mass apoptosis of cancer cells.

6. The method according to claim 5, wherein internal temperature of tumor tissue is 43° C.-44° C. during the hyperthermia therapy.

7. The method according to claim 6, wherein the optimal temperature range for the hyperthermia therapy is 43° C.-44° C., the hyperthermia therapy is carried out once a day, with accumulated time for each hyperthermia therapy being not less than 30 minutes, in order to intensive effect the hyperthermia therapy is repeated once the next day.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The preferred embodiments of the present disclosure are described in detail below so that the advantages and features of the present disclosure may be more easily understood by those skilled in the art so as to make a clearer and clearer definition of the protection scope of the present disclosure.

[0028] A method for inducing mass apoptosis of cancer cells by enhancing overall acidity in tumor, wherein the method comprises steps of reducing overall pH in tumor tissue by adopting a physical method or a biochemical method so as to enhance overall acidity in tumor tissue, which in turn induce mass apoptosis of cancer cells.

[0029] The physical or biochemical methods include a variety of methods, such as by injecting an acid liquid directly into the tumor tissue or by indirectly promoting the overall acidification in tumor tissue, any methods as long as that can reduce the overall pH value of the tumor tissue are all feasible.

[0030] In one embodiment, the key step of reducing the overall pH in tumor tissue includes making the pH of extracellular micro-environment of cancer cells in tumor lower than 5.

[0031] In one embodiment, base on the same direction synergic interaction between the changes of intracellular acidity and extracellular acidity in tumor (pH<6.5), reducing overall pH in tumor tissue may be performed by injecting an acid directly into tumor tissue or by aggravating anaerobic respiration of cancer cells through hyperthermia therapy to indirectly promote the overall acidification in tumor tissue.

[0032] In one embodiment, for a single tumor without metastasis and diffusion, a fashion of injecting an acid directly into tumor tissue must make the pH of extracellular micro-environment of cancer cells to be lower than 5.

[0033] In one embodiment, for a single tumor without metastasis and diffusion, a fashion of injecting a liquid of an acid substance directly into tumor tissue must make the pH of extracellular micro-environment of cancer cells to be lower than 5, thus inducing mass apoptosis of cancer cells. the acid substance described above may be any one of lactic acid, acetic acid and hydrochloric acid, etc.

[0034] In one embodiment, for promoting indirectly the tumor tissue to overall acidification, a method of hyperthermia therapy to the whole body or hyperthermia therapy to tumor tissue region can be applied to aggravate the anaerobic respiration of cancer cells, and promote the acidification of intracellularly tissues and extracellular tissues of cancer cells, thus enhancing the overall acidity in tumor, when the pH of extracellular micro-environment of cancer cells is lower than 5, mass apoptosis of cancer cells can be sure induced.

[0035] In one embodiment, for a single tumor without metastasis and diffusion, a hyperthermia therapy can also be applied to tumor tissue region, so to aggravate the anaerobic respiration of cancer cells and promote the acidification of intracellularly tissues and extracellular tissues of cancer cells, thus enhance the overall acidity inside the tumor and induce apoptosis of cancer cells. The higher the acidity in the tumor is, the higher the ratio of apoptosis of cancer cells. Only when the pH value of extracellular micro-environment of cancer cells is lower than 6.2, the apoptosis process can be initiated. Only when the pH value of extracellular micro-environment of cancer cells is reduced lower than 5.0, the mass apoptosis of cancer cells can be induced.

[0036] In one embodiment, for metastatic and diffuse tumors, a hyperthermia therapy can be applied to whole body of the patient to aggravate the anaerobic respiration of cancer cells and promote the acidification of intracellularly tissues and extracellular tissues of cancer cells, thus fully enhancing the overall acidity in tumor, when the pH of extracellular micro-environment of cancer cells is lower than 5, the mass apoptosis of cancer cells can be induced.

[0037] In one embodiment, when a hyperthermia therapy is used, the inside of tumor tissue is heated to a temperature of 43° C.-44° C., which is more conducive to promote the acidity to enhance quickly in the tumor, inducing a highest rate of apoptosis of cancer cells, so as to achieve the mass apoptosis of cancer cells.

[0038] In one embodiment, during the hyperthermia therapy, the optimal temperature range for the hyperthermia therapy is 43° C.-44° C., the hyperthermia therapy is carried out once a day, with an accumulated time for being not less than 30 minutes each hyperthermia therapy. in order to strengthen the effect, the hyperthermia therapy is repeated once the next day

[0039] The overall acidification of the tumor tissue releases a signal that the cancer cells are suffering from a severe shortage of supplies, it indicates that cancer cells can gain self-protection only when they initiate the apoptotic program to reduce the huge consumption for oxygen and nutrients. Although the apoptotic cancer cells are not thoroughly death, Protein synthesis and DNA replication of cancer cells have been inhibited through apoptosis. At this time, the cancer cells lose the function of differentiation and proliferation, and difficult to transfer and spread, it's the equivalent of castration, In effect it's equal to the cance being cured.

EXAMPLE 1

[0040] For a single tumor without metastasis and diffusion, to injecte directly acid liquid into tumor tissue may enhance the overall acidity in the tumor, thus induce mass apoptosis of cancer cells in the tumor, In the end the tumors can be cured.

[0041] The patient Li, female, 39 years old. In a health examination 2 years ago, a 3.2*2.5*1.8 cm tumor with rough edges and a little hard feeling by hand was found in her right breast by mammary gland molybdenum target device. The patient was diagnosed with invasive ductal carcinoma of the breast by puncture biopsy; Positron emission tomography-computed tomography (PET-CT) showed a single tumor, the imaging showed obviously radioactive concentration, there were not other abnormal dense shadows and swollen lymph node. The diagnosis was a single tumor without metastasis and diffusion.

[0042] Treatment process: Medical acetic acid was dissolved in sterile water for injection, and 50,000 units of penicillin sodium were added to make 20 ml of a weak acid with a pH of 2. The drainage needle was preseted at the inner edge of the tumor adventitia being used to detect the acidity of the tumor, and the infusion needle was punctured to the center of her tumor, and the weak acid solution no less than 25% of the tumor volume was slowly injected into the tumor in not less than 50 minutes through the infusion needle with the aid of an injection pump. During the injection, by controlling the speed of the injection pump, the pH of the tumor was constantly kept at 4-5, with the maximum being not more than 5. The treatment was performed once every two days, usually acid injection is done 2-3 times. Then reviewed once every half month with mammary gland molybdenum target. The first three reexaminations showed that there was no change in tumor growth. After the fourth reexaminations, the tumor began to atrophy slowly. After 3 months, hand felt original tumor had become soft. After 6 months, the PET-CT of the tumor showed a spotted streak shadow, and the spotted streak shadow area was about 40% smaller than before treatment, the radioactive concentration in that area was significantly weakened and was close to normal. One year later, no active cancer cells were detected by the biopsy.

EXAMPLE 2

[0043] For early-stage tumors without obvious metastasis and diffusion, the hyperthermia therapy is used to tumor tissue region with precise radiation in order to aggravate the anaerobic respiration of the cancer cells, to promote the acidification of intracellularly tissues and extracellular tissues of cancer cells through the accumulation of lactic acid, thus enhance the overall acidity inside the tumor and induce apoptosis of cancer cells.

[0044] Patient Liu, male, 43 years old, a black nevus about the size of a soybean was found on the left hand fifteen years ago, and the nevus grew slowly at first. Two years ago, the original nevus gradually enlarged and the pigmentation deepened. As the enlargement, the lesions area appeared nodular, and the ulceration and bleeding on the surface were difficult to heal. There were irregular pigmented halos around, but no swelling of the axillary lymph nodes was found. The diagnosis confirmed a malignant melanoma.

[0045] Treatment process: The whole left hand and left arm were sterilized, lidocaine was injected from the shoulder to the left arm for local anesthesia, and then the whole left arm and left hand were wrapped with the sterilized film, then place the entire left arm and left hand in a thermostatic water tank with the temperature of 44-45° C. for water bath. The first water bath lasted for 40 minutes, and the next day a hyperthermia therapy was repeated for reinforcement, with the hyperthermia therapy time of 35 minutes. One week later, the ulcer began to heal and scab. One month later, the scab fell off, subcutaneous mass began to soften and atrophy. One year later, the mass disappeared, light black scar formed at the nevus, and no active cancer cells were found in the puncture biopsy of the lesion.

EXAMPLE 3

[0046] For metastatic and diffuse middle-stage tumors, microbial infections were used to induce high fevers to aggravate the anaerobic respiration of the cancer cells, through the accumulation of lactic acid to promote the acidification of intracellularly tissues and extracellular tissues of cancer cells, enhance the overall acidity inside the tumor, thus induce mass apoptosis of cancer cells in the tumors, last the tumor can be cured.

[0047] The patient Zhu, male, 81 years old, was hospitalized 6 years ago due to repeated low-grade fever. At that time, a huge lump with unclear tumor borders in the upper lobe of the right lung was found by PET-CT, CT value was 40 Hu, the size was 7.3*5.5*3.8 cm, The imaging of PET showed radioactive concentration, SUV value was 18.6. The tubercle shadow lay behind the mediastinal internal vena cava, the local density was high, CT value of 48 Hu. The imaging of PET showed radioactive concentration, SUV value was 4.3, suggesting lymph node metastasis. Healing process: The result of puncture biopsy was diagnosed as mid-stage squamous cancer of the upper right lung. During hospitalization, accidental infection caused a high fever due to infusion, the body temperature was over 42° C. The fever subsided after about 40 minutes of rescue. Afterwards, due to the high age of the patient, it was not suitable for surgical therapy, radiotherapy and chemotherapy, therefore the patient gave up conventional treatment. The results was that after accidental high fever his tumor was cured without other treatment. A special emphasis on that the use of any anti-cancer drugs during his whole treatment was completely excluded. He has been symptom-free for more than 6 years. He was 81 years old at that time and very healthy. Recent PET-CT check showed: the original lump in the upper lobe of the right lung disappeared and only multiple patches were seen. The result of PET showed that the lesion region had no abnormal increase in radioactivity uptake.

EXAMPLE 4

[0048] For metastatic and diffuse advanced breast cancer, a multi-source antenna array microwave hyperthermia therapy device was used to radiate tumor tissue region with wide-area precise hyperthermia, then to promote tumor tissue acidification, so as to induce mass apoptosis of these cancer cells. Compared with the tumor without experiment of hyperthermia therapy and acidification, verified the method of enhancing the overall acidity in the tumor to induce mass apoptosis of cancer cell has a reliable effect.

[0049] The patient Xu, female, 56 years old. One year ago, two lumps of different sizes were showed in the left breast by molybdenum target mammography of breast: one lump(A) was 2.2*2*1.3 cm, and the other lump (B) was 1.5*1*0.6 cm. and the lump(C) of right breast was 2.5*2*1.8 cm in size. These three lumps had rough edges and a hand feels a little hard. There was discharge in the left nipple. It was diagnosed as invasive ductal carcinoma of the breast by puncture biopsy. PET-CT showed that multiple lumps were obviously radioactive concentration, The patient presented with lung metastasis and multiple bone metastases, and the axillary lymph nodes on both sides were obviously enlarged. The patient was diagnosed as advanced breast cancer.

[0050] Treatment process: In view of the occurrence of distant metastasis, the patient gave up surgical therapy and only received chemotherapy, local acidification and hyperthermia therapy for palliative conservative treatment. First, a course of CMF(cyclophosphamide, methotrexate and fluorouracil) regimen chemotherapy control was performed, and then the lump(A) in left breast was injected with acid for 2 times (the method was the same as in Example 1), and using the precise optical fiber temperature measurement-control technology, the right breast was irradiated by wide-area hyperthermia therapy with a multi-source antenna array microwave hyperthermia devic. Precision control temperatureis carried out with the cooperation of optical fiber temperature measurement technology during hyperthermia therapy (fiber-optic temperature measuring device was placed in the right breast through the incision). Considering that the maximum depth of microwave irradiation was only 6cm, the right breast was squashed by a plastic sheet during irradiation, it was conducive that the lump(C) of right breast was in the range of the penetration depth of the hyperthermia therapy device, and the temperature of hyperthermia therapy was controlled within the range of 43-44° C., the duration of the hyperthermia therapy was 40 minutes. Three months later, the PET-CT showed that the acid-infused the lump(A) in the left breast did not increase and slightly atrophied, and its radioactive concentration was significantly reduced; The symptoms of the lump(B) without acid injection and hyperthermia therapy did not improve, but slightly enlarged, The radioactive concentration of the lump did not reduce;The lump(C) of right breast did not enlarge and slightly shrank after the hyperthermia therapy, and its radioactive concentration was significantly reduced;The other lung metastases and multiple bone metastases were not affected by the hyperthermia therapy and acid injection, and were still in the progressive stage, all varying degrees of increase, the radioactive concentration was not improved. The patient died 9 months later before death, the acid-injected lump(A) and hyperthermia treated lump(C) did not worsen, and there was further atrophy. The lump(B) that was not subject to hyperthermia therapy and acid-injection deteriorated significantly.

[0051] In the present disclosure, for reducing the overall pH of the tumor tissue, making the overall acidity of the intracellular tissues and extracellular tissues of the cancer cells in the tumor is enhanced by adjusting the overall acid-base property in the tumor, thereby promoting the mass apoptosis of the cancer cells, in effect it's equal to the cancer being cured.

[0052] In the present disclosure, promotion of the mass apoptosis of cancer cells by enhancing the overall acidity of tumor tissues, it only requires that the pH of the extracellular micro-environment of cancer cells in the tumor should be lower than 5, and the stronger the acidity of tumor cells is, the higher the apoptosis rate of cancer cells is.

[0053] In the present disclosure, there are included a variety of methods to enhance the overall acidity in the tumor. The method of directly injecting an acid into the tumor tissue or thermal therapy measures such as physical diathermy, microbial infection and hyperthermia therapy can be all used, as long as it can enhance the overall acidity of the tumor tissue while not too enhancing the acidity of normal cells are all feasible.

[0054] In the present disclosure, for a single tumor without metastasis and diffusion, the method of directly injecting an acidic liquid into the tumor tissue or radiating tumor tissue region with wide-area hyperthermia therapy may be adopted, only the pH of the extracellular micro-environment of the cancer cells in the tumor is lower than 5 can induce mass apoptosis of cancer cells without damaging normal cells, can achiev the purpose of killing cancer cells.

[0055] In the present disclosure, for metastatic and diffuse tumors, the anaerobic respiration of all tumor tissues can be indirectly induced through hyperthermia therapy, the form of hyperthermia therapy can be physical diathermy, microbial infection and fever, etc, as long as it can enhance the overall acidity of the tumor tissue while not too enhancing the acidity of normal cells are all feasible. Only when the pH of the extracellular micro-environment of cancer cells in the tumor is lower than 5, can the mass apoptosis of cancer cells be induced. At the same time, the temperature should be controlled to ensure that normal cells are not too acidified and are not damaged.

[0056] The hyperthermia therapy to metastatic tumors must be hyperthermia therapy to the whole body, so that full coverage of all cancer cells is ensured. The temperature range for hyperthermia therapy is 43° C.-44° C., and the hyperthermia therapy is carried out once a day, with the accumulated duration of time for each hyperthermia therapy being not less than 30 minutes. in order to intensive effect the hyperthermia therapy is repeated once the next day.

[0057] The disclosure discloses a method for inducing mass apoptosis of cancer cell by enhancing the overall acidity in the tumor. The method reduces the overall pH of tumor tissue by adjusting the acidity and basicity of the tumors, so as to enhance apoptosis of cancer cell. In order to induce apoptosis of cancer cells, the pH of the extracellular micro-environment of cancer cells must be lower than 6.2. The stronger the acidity in the tumor is, the higher the apoptosis rate of cancer cells is. When the pH of the extracellular micro-environment of cancer cells in the tumor is lower than 5, the mass apoptosis of cancer cells can be induced. There are a variety of measures to enhance the acidity of the internal environment of tumor, the method of directly injecting an acid into the tumor tissue or hyperthermia therapy such as physical diathermy, microbial infection and fever may be all used, as long as it can enhance the overall acidity of the tumor while not too enhancing the acidity of normal cells. In the present disclosure, enhance of the overall acidity in the tumor to induce the mass apoptosis of cancer cells not only can realize the curing of cancer cells, but also can avoid damaging to normal cells, and is a safe and efficient method for tumor treatment.

[0058] In the present disclosure, the principle and the mechanism of treating tumor by induction of the mass apoptosis of cancer cells through the overall acidification of the tumor are simple and a scientific the technology is easy to realize and the harm to normal cells is very small. The method in the present disclosure has good effect and high safety, and has great popularization and application value.

[0059] For those skilled in the art, it is obvious that the present disclosure is not limited to the details of the embodiments, and the present disclosure can be implemented in other specific forms without departing from the spirit or basic characteristics of the present disclosure. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present disclosure is limited by the appended claims rather than the above description. Therefore, it is intended to include all changes within the meaning and scope of the equivalent elements of the claims in the present invention. Any reference signs in the claims shall not be regarded as limiting the claims concerned.

[0060] In addition, it should be understood that although the description is described according to the embodiments, it is not that every embodiment includes only an independent technical solution. This description above is only for purpose of clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in the embodiments can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.