CN114768091A - Colon cancer treatment system and alternating electric field generating device for colon cancer treatment - Google Patents

Colon cancer treatment system and alternating electric field generating device for colon cancer treatment Download PDF

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Publication number
CN114768091A
CN114768091A CN202210314367.5A CN202210314367A CN114768091A CN 114768091 A CN114768091 A CN 114768091A CN 202210314367 A CN202210314367 A CN 202210314367A CN 114768091 A CN114768091 A CN 114768091A
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colon cancer
electric field
alternating electric
cancer treatment
treatment system
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卢健
周单
陈迪康
熊凌志
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Hunan Antai Kangcheng Biotechnology Co ltd
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Hunan Antai Kangcheng Biotechnology Co ltd
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Priority to CN202210314367.5A priority Critical patent/CN114768091A/en
Publication of CN114768091A publication Critical patent/CN114768091A/en
Priority to PCT/CN2023/071566 priority patent/WO2023185211A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014External stimulators, e.g. with patch electrodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36002Cancer treatment, e.g. tumour

Abstract

The invention relates to the technical field of tumor medical treatment, in particular to a colon cancer treatment system and an alternating electric field generating device for colon cancer treatment. The system comprises: a patient information processing module and an output module; the sample information processing module is used for receiving information of a colon cancer patient treated by a medicament, and the information at least comprises medication information of the colon cancer patient receiving the medicament; the drug is selected from one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine; the output module is used for receiving the information output by the patient information processing module and guiding the tumor electric field treatment of the colon cancer patient.

Description

Colon cancer treatment system and alternating electric field generating device for colon cancer treatment
Technical Field
The invention relates to the technical field of tumor medical treatment, in particular to a colon cancer treatment system and an alternating electric field generating device for colon cancer treatment.
Background
Colon cancer is a common gastrointestinal malignancy and is the second leading cause of cancer-related death in humans. The principle of treating colon cancer is comprehensive treatment mainly based on surgical resection, and chemotherapy, radiotherapy and the like are combined to reduce the recurrence rate after surgery and improve the survival rate. For the colon cancer which can not be resected, neoadjuvant chemotherapy can be adopted, so that on one hand, the stage of the tumor can be reduced, and part of the tumor which can not be resected is converted into the tumor which can be resected; on the other hand, the survival time of the patient can be prolonged, and the survival quality of the patient is improved. The colon cancer gradually metastasizes to a far distance along with growth and development, 3/4 patients have metastasis already at the time of diagnosis, patients can receive radical surgical resection, and half of patients finally have distant metastasis.
Radiotherapy plays an important role in the treatment of colorectal cancer, and aims to kill tumor cells by irradiating tumors with various radioactive rays with different energies. Radiotherapy has strong killing capacity on cancer cells, can show obvious effect in a short time, kills a large number of cancer cells and controls the disease development. Clinically, many patients who undergo radiotherapy have a tumor mass which is reduced, but the effect of tumor disappearance is unlikely to be achieved. Radiotherapy is only local treatment, can relieve local stress symptoms, but has no obvious inhibition effect on cancer cells of the whole body, and the residual cancer cells still exist in the body of a patient after radiotherapy, can continue to grow and proliferate, and can be detected to a certain extent.
Therefore, radiotherapy is often combined with chemotherapy clinically to address the limitations of radiotherapy. For example, 5-Fluorouracil (5FU) is used as a common therapeutic agent for gastrointestinal malignancies, with oxaliplatin alone or in combination, to achieve good results in the clinical treatment of colorectal cancer. However, the clinical benefit of chemotherapy is often transient, and patients using chemotherapy tend to develop resistance to the chemotherapy, so that the overall efficiency is low, and the effect of chemotherapy is greatly reduced.
The tumor electric field therapy (TTfields) is a novel tumor therapy method, transmits alternating electric fields with medium frequency (100-300kHz) and low field strength (1-3Vpeak/cm) to in-vivo focuses through an in-vitro pasted electrode plate to destroy tumor cells in a rapid division state, and is a novel therapy mode with portability, effectiveness and low side reaction. TTFields represents a new therapeutic approach that has been FDA approved for newly diagnosed glioblastomas and recurrent glioblastomas, among others.
The basic principle of TTFields' action is based on the fact that the polar molecules in tumor cells are pulled by an alternating electric field of medium frequency and low intensity, mitotic activity is hindered, and finally tumor cells die, but are not affected by rapidly dividing cells and normal tissues. TTFields is a physical rather than chemical modality that is well tolerated with little or no systemic toxic side effects. The main side effect is localized contact dermatitis under the electrode, which may be the result of a combination of factors. However, the curative effect of TTFields still has a great room for improvement, and the targeted application of TTFields with specific parameters according to the medication condition of patients is an important technical path for improving the curative effect.
Disclosure of Invention
A first object of the present invention is to provide a colon cancer treatment system, the system comprising:
a patient information processing module and an output module;
the sample information processing module is used for receiving information of a colon cancer patient adopting drug therapy, and the information at least comprises medication information of the colon cancer patient receiving platinum-based chemotherapy drugs; the medicine is selected from one or more of platinum-based chemotherapeutic medicines, 5-fluorouracil and capecitabine;
the output module is used for receiving the information output by the patient information processing module and guiding the tumor electric field treatment of the colon cancer patient.
The second purpose of the invention is to provide the application of one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine in preparing colon cancer drugs;
the subject of the colon cancer medicament is a colon cancer patient treated by a tumor electric field.
The third purpose of the invention is to provide an alternating electric field generating device for colon cancer treatment, which comprises electrodes, when the electrodes act on a subject, the alternating electric field can be applied to tumor cells of the subject, the frequency of the alternating electric field is 150 kHz-250 kHz, the field intensity is more than or equal to 1.5Vpeak/cm, and the intervention time of the alternating electric field is more than or equal to 48 h; the subject is a colon cancer patient and is treated with one or more of a platinum-based chemotherapeutic drug, 5-fluorouracil, and capecitabine.
The present invention can inhibit the proliferative capacity of colon cancer cells and promote apoptosis of cancer cells by administering one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine to the colon cancer cells and applying tumor electric field therapy to the cancer cells. The data show that the combination of the medicine and the tumor electric field treatment has a synergistic effect on the proliferation inhibition of colon cancer cells, and the results prove that the combination of the medicine and the tumor electric field treatment is effective treatment of the colon cancer cells, wherein the combined use effect of the 5-fluorouracil and the electric field is optimal, and a reference basis is provided for improving the survival time of colon cancer patients.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the prior art descriptions will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 shows the effect of different frequencies of electric field on the intervention of HT29 cells according to one embodiment of the present invention;
FIG. 2 is a graph illustrating the effect of different frequencies of electric fields on the intervention of CT26 cells, according to one embodiment of the present invention;
FIG. 3 shows the effect of the electric field on the intervention of HT29 cells at different times according to one embodiment of the present invention;
FIG. 4 is a graph illustrating the effect of an electric field applied at different times on CT26 cells according to an embodiment of the present invention;
FIG. 5 shows the effect of different field strengths of the electric field on the intervention of HT29 cells according to one embodiment of the present invention;
FIG. 6 is a graph illustrating the effect of different field strengths of the electric field on the intervention of CT26 cells according to an embodiment of the present invention;
FIG. 7 is a graph showing the effect of different groups of treatment on apoptosis of colon cancer cells using flow cytometry, according to an embodiment of the present invention;
FIG. 8 is a graph showing the effect of different groups of treatments on the viability of colon cancer cells, according to an embodiment of the present invention; a is 5-fluorouracil; b is capecitabine; c is oxaliplatin.
Detailed Description
Reference will now be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, can be used on another embodiment to yield a still further embodiment.
Unless otherwise defined, all terms (including technical and scientific terms) used in disclosing the invention are to be interpreted as commonly understood by one of ordinary skill in the art to which this invention belongs. The following definitions serve to better understand the teachings of the present invention by way of further guidance. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The term "and/or", "and/or" as used herein is intended to be inclusive of any one of the two or more items listed in association, and also to include any and all combinations of the items listed in association, including any two or more of the items listed in association, any more of the items listed in association, or all combinations of the items listed in association. It should be noted that when at least three items are connected by at least two conjunctive combinations selected from "and/or", "or" and/or ", it should be understood that in this application, the technical solutions unquestionably include the technical solutions all connected by" logical and ", and also unquestionably include the technical solutions all connected by" logical or ". For example, "A and/or B" includes A, B and A + B. For example, embodiments of "a, and/or, B, and/or, C, and/or, D" include A, B, C, D (i.e., embodiments all connected by "logical or"), A, B, C, D includes any and all combinations of any two or any three of A, B, C, D, and A, B, C, D includes four combinations (i.e., embodiments all connected by "logical and").
As used herein, the terms "comprising," "including," and "comprising" are synonymous, inclusive or open-ended, and do not exclude additional, unrecited members, elements, or method steps.
The recitation of numerical ranges by endpoints of the present invention includes all numbers and fractions subsumed within that range, as well as the recited endpoint.
"patient" or "subject" in the present invention refers to a mammal, such as a cat, dog, cow, sheep, horse, etc., suffering from colon cancer, preferably a primate, more preferably a human.
In the present invention, for the purpose of distinction, the term "drug" refers exclusively to one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine.
As used herein, "treatment" means ameliorating, inhibiting or delaying the progression of tumor growth and recurrence, inhibiting metastasis, and prolonging the survival of a patient during chemotherapy.
At least one symptom or side effect has been developed, the further progression of the side effect is slowed and/or the side effect is alleviated.
The present invention relates to concentration values, which include fluctuations within a certain range. For example, it may fluctuate within a corresponding accuracy range. For example, 2%, may be allowed to fluctuate within 0.1%. For values that are larger or do not require more fine control, the meaning is also allowed to include greater fluctuations. For example, 100mM, may allow fluctuations within the range of. + -. 1%,. + -. 2%,. + -. 5%, etc. The molecular weight is referred to, allowing the meaning to include fluctuations of ± 10%.
In the present invention, the terms "plurality" and "a plurality" mean, unless otherwise specified, 2 or more in number.
In the present invention, the technical features described in the open type include a closed technical solution composed of the listed features, and also include an open technical solution including the listed features.
In the present invention, "preferably", "better" and "preferable" are only embodiments or examples with better description, and it should be understood that the scope of the present invention is not limited by them. In the present invention, "optionally", "optional" and "optional" refer to the presence or absence, i.e., to any one selected from the two juxtapositions "present" or "absent". If multiple optional parts appear in one technical scheme, if no special description exists, and no contradiction or mutual constraint relation exists, each optional part is independent.
The present invention relates to a colon cancer treatment system, the system comprising:
a patient information processing module and an output module;
the sample information processing module is used for receiving information of a colon cancer patient treated by a medicament, and the information at least comprises medication information of the colon cancer patient receiving the medicament; the drug is selected from one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine;
the output module is used for receiving the information output by the patient information processing module and guiding the tumor electric field treatment of the colon cancer patient.
The electric field treatment of tumors in the present invention is performed in a manner well known to those skilled in the art. In some embodiments, all electrodes are positioned on the subject's body; in other embodiments, all electrodes may be implanted within the body of the subject (e.g., just below the skin of the subject, or in the vicinity of the organ being treated); and in other embodiments, some of the electrodes are positioned on the skin of the subject, while the remaining electrodes are implanted within the body of the subject.
In some cases, the drug is administered directly to the cell. In other cases, the drug may be administered to the cell indirectly (e.g., in the form of a prodrug precursor that is converted to the drug in the subject's body).
In certain instances, it may be advantageous to administer a precursor, prodrug, or different drug to a subject by reducing side effects or altering pharmacokinetics in a desirable manner. Typically, an indirectly administered ingredient may be converted into the drug in the body (e.g., liver).
In some embodiments, the electric field used for electric field treatment of tumors is an alternating electric field.
In some embodiments, the output module is configured to adjust the frequency of the alternating electric field to be 150kHz to 250kHz, such as 160kHz, 170kHz, 180kHz, 190kHz, 200kHz, 210kHz, 220kHz, 230kHz, 240 kHz.
The optimal frequency may be determined for each individual's own circumstances, such as the degree of sensitivity and tolerance to frequency. Preferably, care is taken to ensure that the alternating electric field at the selected frequency does not adversely heat the part of the subject's body.
In some embodiments, the output module is configured to adjust the field strength of the alternating electric field to be greater than or equal to 1.5Vpeak/cm, such as 1.5Vpeak/cm to 2.5Vpeak/cm, such as 1.6Vpeak/cm, 1.7Vpeak/cm, 1.8Vpeak/cm, 1.9Vpeak/cm, 2.0Vpeak/cm, 2.1Vpeak/cm, 2.2 Vpeak/cm.
In some embodiments, the output module is configured to adjust the field strength of the alternating electric field to ≧ 2.2Vpeak/cm, such as 2.3Vpeak/cm, 2.4Vpeak/cm, 2.5 Vpeak/cm.
In the present invention, if not specifically emphasized, the field intensity values of the noted alternating electric field are all the maximum amplitude (E) within a single cycle of the alternating current signalp)。
Again care is preferably taken here to ensure that the alternating electric field at the selected field strength does not adversely heat the part of the subject's body.
In some embodiments, the output module is used for adjusting the intervention time of the alternating electric field to be more than or equal to 48h, such as 48h to 82h, such as 52h, 56h, 60h, 64h, 68 h.
In some embodiments, the output module is used to adjust the intervention time ≧ 72h, e.g., 76h, 80h, of the alternating electric field.
The intervention time may be continuous or intermittent (but the cumulative time should reach the intervention time). For example, when the total intervention time is 72 hours, the intervention can be performed in 6 periods having a duration of 12 hours each, with 2 hour intervals between the periods. The term "interval" refers to a time interval in which no electric field is applied. Again, care is preferably taken here to ensure that the alternating electric field at the selected intervention time does not adversely heat a part of the subject's body.
The parameters of the alternating electric field are set for the target region, in particular the region that acts on the tumor cells and the tissue in the vicinity thereof.
Platinum-based chemotherapeutic drugs (known as platinum analogs) act in a similar manner. These agents do not have alkyl groups, but nevertheless damage DNA. They permanently coordinate to DNA to interfere with DNA repair, and are therefore described as "alkylation-like". Some non-limiting examples of platinum analogs of the invention are one or more of the following: platinum, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin, and triplatin tetranitrate.
In certain instances, at least a portion of the electric field treatment of the tumor is performed after said administering of the drug and before the drug is eliminated from the body of the subject. The term "eliminated from the body of a subject" refers to, for example, (1) metabolism of one or more of the drugs in the liver or elsewhere in the body, resulting in the excretion of substantially all of the one or more drugs from the body, or (2) reduction of the concentration of one or more of the drugs in the blood stream of the subject such that the drugs no longer provide substantially all of their therapeutic effect. The term "substantially" as used herein means greater than about 50%, 60%, 70%, 80%, 90%, or 100%.
In some embodiments, the medication information includes one or more of a type of the drug, a mode of administration, a start-stop time of administration, and a side effect after administration.
The most common post-administration side effects of chemotherapy include nausea, vomiting, diarrhea or constipation, weakness, fatigue, mucositis, hair loss, respiratory and cognitive disorders. The electric field strength can be adjusted as appropriate by the severity of the side effect.
In some embodiments, the information further comprises one or more of a photograph, age, sex, height, weight, ethnicity, eating habits, medication history, mood status, time to visit with symptoms, family genetic medical history, religious belief, frequency of smoking, type of exercise, and frequency of exercise of the patient.
According to another aspect of the invention, the invention also relates to the use of one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine in the preparation of a medicament for treating colon cancer;
the subject of the colon cancer medicament is a colon cancer patient treated by a tumor electric field.
According to the other aspect of the invention, the alternating electric field generating device for treating the colon cancer comprises electrodes, when the electrodes act on a subject, an alternating electric field can be applied to tumor cells of the subject, the frequency of the alternating electric field is 150 kHz-250 kHz, the field intensity is more than or equal to 1.5Vpeak/cm, and the intervention time of the alternating electric field is more than or equal to 48 h; the subject is a colon cancer patient and is treated with one or more of a platinum-based chemotherapeutic drug, 5-fluorouracil, and capecitabine.
The present invention also relates to a method of treating colon cancer in a subject, the method comprising: administering one or more of a platinum-based chemotherapeutic agent, 5-fluorouracil, and capecitabine to the subject; and applying an alternating electric field to the target region of the subject.
The preferred frequency of the alternating electric field is 150kHz to 250 kHz.
The preferred field intensity of the alternating electric field is more than or equal to 1.5 Vpeak/cm.
The preferred intervention time of the alternating electric field is more than or equal to 48 h.
In some embodiments, the alternating electric field is as described above.
Embodiments of the present invention will be described in detail with reference to examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures for the following examples, in which specific conditions are not specified, can be performed according to the instructions given in the present invention, according to the experimental manual or the conventional conditions in the art, according to other experimental procedures known in the art, or according to the conditions suggested by the manufacturer.
In the following specific examples, the measurement parameters relating to the components of the raw materials, if not specified otherwise, may be subject to slight deviations within the accuracy of the weighing. Temperature and time parameters are involved to allow for acceptable deviation due to instrument test accuracy or operational accuracy.
Examples
1. The experimental method comprises the following steps:
the effect of electric field and treatment with 5-fluorouracil (5FU) or oxaliplatin or capecitabine, alone or in combination, was tested using a colon cancer cell line (HT-29/CT-26, purchased from Shanghai cell Bank, Zhongkobah). All cells were supplied with 5% CO2Grown in a humidified cell incubator. Cell culture medium was purchased from Gibco and was supplemented with 10% fetal bovine serum and 1% penicillin and streptomycin prior to cell culture.
Cell proliferation assay
The colon cancer cells were intervened with an alternating electric field (100-300kHz, 1-3 Vpeak/cm). Preparing cell suspension, and regulating cell concentration. Will have a diameter of
Figure BDA0003568556550000101
The slide is placed in a ceramic culture dish, and an in vitro cell experiment tumor electric field intervention device is used. 100-150ul of cell suspension was added to each slide to distribute the cell suspension evenly on the slide surface. Placing in a 37 ℃ saturated humidity incubator for 4-6h, supplementing 4ml of culture medium after the cells are completely attached to the wall, and placing in the 37 ℃ saturated humidity incubator for overnight culture. The cells were divided into two groups, one group with and one without an electric field. The electric field adding group adjusts the electric field parameters of the instrument to required frequency according to experimental conditions, and sets corresponding cell culture box temperature according to different frequency parameters so as to ensure that the temperature in the quadrilateral culture dish is always kept at 37 ℃ in the whole electrifying process. The acting time of the electric field is 24-72 h. Taking out all the glass slides after the electric field treatment is finished, adding pancreatin for digestion, and preparing cell suspensionAnd (4) performing cell counting and subsequent experiments. The experiment was repeated 3 times.
Electric field intensity measuring method
Adding culture solution into the culture dish, applying an electric field to the culture dish, randomly inserting two probes into two points at the center of the culture dish, measuring voltage signals between the probes by using an oscilloscope, reading the peak value of the voltage signal, and recording as VpMeasuring the distance between two probes by a vernier caliper, and recording the distance as d, wherein the electric field intensity of the midpoint of the central connecting line of the probe tips is Ep=VpAnd/d, repeating the measurement for multiple times by adjusting the position of the probe, and taking the average value of the multiple measurements as a final value.
CCK-8 cell viability assay
Experimental setup: the cell line HT-29, frequency 200kHz, field strength 2.2Vpeak/cm and electric field treatment time 72h are adopted. Oxaliplatin concentration is 40mg/L,5FU concentration is 10mg/L, capecitabine concentration is 200mg/L, and treatment is given simultaneously during electric field treatment.
The CCK-8 cell viability detection kit contains WST-8(2- (2-methoxy-4-nitrophenyl) -3- (4-nitrophenyl) -5- (2, 4-disulfophenyl) -2H-tetrazole monosodium salt), under the condition that an electron carrier exists, the WST-8 is oxidized and reduced by intracellular dehydrogenase to generate water-soluble orange formazan dye which can be dissolved in a tissue culture medium, and the amount of generated formazan is directly proportional to the number of living cells. The CCK-8 method is a highly sensitive, non-radioactive colorimetric assay for determining the number of viable cells in a cell assay. And (3) collecting the cell suspension, adding 10ul of CCK-8 solution into each hole, continuously incubating for 1.5-2 hours in a cell incubator, and measuring the absorbance of each hole by using an enzyme-labeling instrument at 450 nm.
Apoptosis detection (flow cytometry)
Collecting cells, and mixing 1X 105The cells were resuspended in 200. mu.L Binding Buffer, 4. mu.L of 0.5mg/mL PI and 2. mu.L of Annexin V-FITC solution were added, incubated for 15min at room temperature in the dark, and subjected to fluorescence detection using a flow cytometer.
Experimental data were statistically analyzed using Graphpad Prism software, and comparisons between groups were performed using t-test, all data are expressed as mean ± standard deviation, # P < 0.05, # P < 0.01, # P < 0.001. Represents the statistical comparison between each experimental group and the control group, and # represents the statistical comparison between each experimental group.
2. Results of the experiment
2.1 intervention of Colon cancer cell proliferation by electric field is frequency (kHz) dependent
According to the above experimental method, HT-29/CT-26 cells were treated with alternating electric field frequencies of 0kHz, 100kHz, 200kHz and 300kHz, with a control field strength of 2.2Vpeak/cm and an electric field application time of 72 hours, and cell proliferation was examined. The results of the experiments are shown in FIGS. 1 and 2, and show that the 200kHz electric field is the optimum frequency for both of the two different colon cancer cell lines.
2.2 electric field intervention in Colon cancer cell proliferation is time (h) dependent
According to the experimental method, HT-29/CT-26 cells are treated by controlling the field strength to be 2.2Vpeak/cm and the frequency of an alternating current electric field to be 200kHz respectively with the acting time of the alternating current electric field of 0h, 24h, 48h and 72h, and the proliferation condition of the cells is detected. The experimental results of fig. 3 and 4 show that the inhibition effect of the electric field on the colon cancer cell line is positively correlated with the intervention time, and the longer the electric field is, the better the inhibition effect is.
2.3 electric field intervention Colon cancer cell proliferation has field strength (V/cm) dependence
According to the above experimental method, HT-29/CT-26 cells were treated with an AC electric field of 0Vpeak/cm, 1.0Vpeak/cm, 1.5Vpeak/cm, 2.2Vpeak/cm, respectively, while controlling the AC electric field frequency at 200kHz and the electric field application time at 72 hours, and the cell proliferation was examined. The experimental results of fig. 5 and 6 show that the larger the electric field intensity is, the more remarkable the effect of inhibiting cell proliferation is.
2.4 oxaliplatin-induced apoptosis of Colon cancer cells
Experimental setup: the cell line HT-29, frequency 200kHz, field strength 2.2Vpeak/cm and electric field treatment time 24h are adopted. Oxaliplatin concentration is 40mg/L, and oxaliplatin is administered while applying an electric field.
Fig. 7 and table 1 show that the apoptosis rate of the oxaliplatin group combined with the electric field is improved from 1.54% to 8.7% compared with the control group by detecting apoptosis through flow cytometry, and the results are statistically different.
TABLE 1
Figure BDA0003568556550000121
2.5 significant differential reduction of viability of colon cancer cells by electric field in combination with oxaliplatin or 5FU or capecitabine
Experimental setup: the cell line HT-29, frequency 200kHz, field strength 2.2Vpeak/cm and electric field treatment time 24h are adopted. The medicament respectively selects oxaliplatin or 5FU or capecitabine, wherein the concentration of the oxaliplatin is 40mg/L, the concentration of the 5FU is 10mg/L, and the concentration of the capecitabine is 200 mg/L. The treatments are administered simultaneously during the electric field treatment.
The results of the experiment in fig. 8 show that the combined use of electric field and oxaliplatin or 5FU or capecitabine significantly differentially reduces the viability of colon cancer cells compared to the use of oxaliplatin or 5FU or capecitabine alone. Compared with the single use of 5FU, the cell viability is reduced from 67.78% to 28.71% after the combination of the electric field and the 5 FU; compared with capecitabine used alone, the electric field combined with capecitabine reduces the cell viability from 70.29% to 53.12%; the electric field in combination with oxaliplatin reduced cell viability from 45.73% to 24.10% compared to oxaliplatin alone.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent should be subject to the appended claims, and the description and drawings can be used to explain the contents of the claims.

Claims (11)

1. A colon cancer treatment system, the system comprising:
a patient information processing module and an output module;
the sample information processing module is used for receiving information of a colon cancer patient treated by a medicament, and the information at least comprises medication information of the colon cancer patient receiving the medicament; the drug is selected from one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine;
the output module is used for receiving the information output by the patient information processing module and guiding the tumor electric field treatment of the colon cancer patient.
2. The colon cancer treatment system of claim 1, wherein said electric field for tumor electric field treatment is an alternating electric field.
3. The colon cancer treatment system of claim 2, said output module is configured to adjust the frequency of said alternating electric field to be between 150kHz and 250 kHz.
4. The colon cancer treatment system of claim 2, wherein said output module is used for adjusting the field strength of said alternating electric field to be more than or equal to 1.5 Vpeak/cm.
5. The colon cancer treatment system of claim 4, said output module is configured to adjust the field strength of said alternating electric field to ≧ 2.2 Vpeak/cm.
6. The colon cancer treatment system according to claim 2, wherein said output module is used for adjusting the intervention time of said alternating electric field to be more than or equal to 48 h.
7. The colon cancer treatment system of claim 6, wherein said output module is used for adjusting the intervention time of said alternating electric field to be more than or equal to 72 h.
8. A colon cancer treatment system as claimed in any one of claims 1 to 7, wherein said platinum-based chemotherapeutic agent is selected from one or more of platinum, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin, triplatin tetranitrate.
9. The colon cancer treatment system according to any one of claims 1 to 7, wherein said medication information includes one or more of the type of said drug, the mode of administration, the start and stop time of administration, and the side effects after administration.
10. The application of one or more of platinum-based chemotherapeutic drugs, 5-fluorouracil and capecitabine in preparing colon cancer drugs;
the subject of the colon cancer medicament is a colon cancer patient treated by a tumor electric field.
11. An alternating electric field generating device for treating colon cancer comprises electrodes, when the electrodes act on a subject, an alternating electric field can be applied to tumor cells of the subject, the frequency of the alternating electric field is 150 kHz-250 kHz, the field intensity is more than or equal to 1.5Vpeak/cm, and the intervention time of the alternating electric field is more than or equal to 48 h; the subject is a colon cancer patient and is treated with one or more of a platinum-based chemotherapeutic drug, 5-fluorouracil, and capecitabine.
CN202210314367.5A 2022-03-28 2022-03-28 Colon cancer treatment system and alternating electric field generating device for colon cancer treatment Pending CN114768091A (en)

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