CN110172403A - Application under 280nm LED UV hypoxia condition in malignant tumour autotransplantation purging in vitro - Google Patents
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Abstract
This research is induced cell apoptosis with ultraviolet light and cobalt chloride simulated hypoxia as theoretical foundation, utilize CoCl2 simulated hypoxia environment, 280nm LED UV irradiates acute promyelocytic leukemia cell (HL-60 cell), inquire into proliferative conditions of the HL-60 cell under low-oxygen environment after 280nm LED UV irradiation, it was found that 280nm LED UV and hypoxemia inhibit HL-60 cell Proliferation, it induces cell apoptosis, and 280nm LED UV under normoxic condition under low oxygen conditions to the Proliferation Ability of cell and apoptotic effect compared with becoming apparent from.Graft is irradiated by 280nm LED UV under hypoxia condition, so that residual tumor Apoptosis and necrosis in graft, and normal cell can normally survive, to reach the final purpose for removing residual tumor, recurrence rate after mitigating leukaemic's autotransplantation, indicates its application prospect in leukaemia autotransplantation purging in vitro.
Description
Technical field:
The present invention relates to a kind of light emitting diode ultraviolet lamp (Light Emitting Diode Ultraviolet, LED
UV) and cobalt chloride chemical reagent, the invention discloses its effects in leukaemia autologous hematopoietic stem cell transplantation for treatment.
Background technique:
Leukaemia (AL) is the most common Malignancy of children, mainly since hematopoietic stem/progenitor is broken up
Be obstructed, and occur malignant proliferation and apoptosis it is incompetent as a result, therefore, inducing leukemia cell differentiation and (or) apoptosis be always by
It is considered the Critical policies of leukemia treating.AL is divided for acute lymphoblastic leukemia (acute according to FAB parting
Lymphoblastic leukemia, ALL) and acute myelocytic leukemia (acute myeloid leukemia, AML).Mesh
The preceding complex treatment used based on chemotherapy, therapeutic effect be improved significantly, 5 years overall survival (overall of ALL
Survival, OS) reach 90% or so, AML and is also raised to 60% or so.But nonetheless, still have 10%~15% so far
ALL and hematopoietic stem cell transplantation (hematopoietic stem cell need to be relied on close to 50% AML
Transplantation, HSCT) further treat.Autologous hematopoietic stem cell transplantation (Autologous HSCT, Auto-
HSCT) refer to the candidate stem cell in specific period acquisition infant itself, by specially treated (such as purify, transgenosis) or
Storage in vitro feeds back after infant receives high dose chemotherapy or radiotherapy, to promote its Radiation in jury or hematopoietic reconstitution, initially makees
For the replacement therapy side of the leukaemic of the no appropriate donors row Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) for the treatment of
Case can have anti-tumor effect more higher than chemotherapy, be avoided that Chemotherapy leads to the production of important organ damage and multidrug resistance
It is raw.Compared with allo-HSCT, Auto-HSCT is not limited by human leukocyte antigen (HLA) distribution type, and the anti-place of graft does not occur
Main disease, does not need immunosupress after Auto-HSCT, and transplanting associated death is reduced.It is controlled currently, auto-HSCT is widely used in
Treat Malignancy and solid tumor over much dosage put/chemotherapy after bone-marrow transplantation, it can also be used to treat serious self
Immunity disease.According to the source of candidate stem cell, auto-HSCT points are autologous bone marrow transplantation and autologous peripheral HSCT.Periphery
Candidate stem cell (peripheral blood stem cells, PBSCs) acquisition is convenient, is not required to anaesthetize, has bone marrow neoplasms or connect
It can also be acquired by the hurtful infant of radiotherapy, hematopoietic reconstitution is faster than bone-marrow transplantation, thus becomes the dry thin of auto-HSCT first choice
Born of the same parents source.The acquisition of PBSCs typically occurs in chemotherapy early stage, and normal residual tumor cell in graft, this is to lead to auto-HSCT
The main reason for recurrence and graft failure, and auto-HSCT lacks effective Graft versus leukemia effect, relapse after transplantation
Rate is compared with allo-HSCT high.Therefore, purging in vitro is the method that tumor load is effectively reduced before chemotherapy combined is transplanted, and is taken various
Effective measures reduce tumour cell pollution, increase residual tumor cells in graft and become the sensibility of chemotherapeutics to mention
The important measures of high auto-HSCT curative effect.
Ultraviolet light (UV) especially ultraviolet B radiation (UVB) is potent apoptosis inducers, short-term UVB irradiation
Apoptosis can be caused, and long-time exposure can induce the necrosis of various cell lines in vitro.UV may act on the multiple of cell
Target spot is related to different kinds of molecules approach.UV irradiation can directly result in DNA damage, generate 2,3- cyclobutane pyrimidine dimer and pyrimidine
(6-4) pyrimidone photoproduct, it can interfere the metabolism of DNA, effectively block duplication and transcription (Reichrath J,
Rass K.Ultraviolet damage, DNA repair and vitamin D in nonmelanoma skin cancer
And in malignant melanoma:an update [J] .Adv Exp Med Biol, 2014,810:208-
233.Synowiec E, Hoser G, Wojcik K, et al.UV Differentially Induces Oxidative
Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and
Resistant to Imatinib [J] .Int J Mol Sci, 2015,16 (8): 18111-18128.).It can also make intracellular
Photosensitizer molecule electronics distribution also change, generate excitation state, DNA damage can be directly resulted in.DNA damage can lead to
P53 activation, promotes cell-cycle arrest albumen p21WAF1/CIP1, DNA repair enzyme and anti-apoptotic genes expression transcription, mentioned for DNA reparation
For the time, but when DNA damage can not be repaired completely, p53 then triggers Apoptosis, and preventing damaged dna from entering cell causes to swell
Tumor occurs.UV can by way of non-ligand-dependent inducing death receptor TNF, Fas aggregation and activation, FAS-FADD-
The compound body colour of caspase-8 is formed, the initiating signal apoptosis involvement as apoptosis.UV can also stimulate ROS, RNS and free radical
Generation, cause the damage of large biological molecule, cause DNA break, protein denaturation and chromosome aberration, induce cell apoptosis,
The ROS generation of UV induction is related with mitochondria potential decline, and ROS makes mitochondrial outer membrane that lipid peroxidation injury occur, and makes film
Mobility reduce, permeability increases, the dysfunction of memebrane protein and mitochondria, then lead to Ca2+ overload, generate ATP and subtract
Less, mitochondrial membrane potential decline etc., causes early stage cytochrome c to discharge, to promote the induction of Apoptosis.It is thin in addition to inducing
Outside born of the same parents' apoptosis, UV irradiation can reduce the incidence of graft versus host disease(GVH disease) with the anti-host response of inhibition of transplant, what it was induced
Immunosupress is related with the effect of regulatory T cells (Tregs).Clinically UV will be used for the treatments of certain tumours, such as narrow spectrum
Ultraviolet B radiation has become the prefered method for the treatment of early stage Skin Cell lymthoma (IA, IB, IIA phase) at present.In recent years, LED
UV has received widespread attention as a kind of novel UV radiation source.Compared with traditional mercury lamp, UV LED has not mercurous, volume
It is small, the service life is long, snap switch, energy-efficient, attenuation is small, light output is stable, convenient for control and adjust the advantages that, may replace
Traditional mercury lamp is applied in various fields.280nm is located at DNA and nucleoprotein absorbs near the highest peak of UV, 280nm LED
UV can penetrate the shell of bacterium, the cell wall of fungi and virus, destroy the structure of nucleic acid and protein, inhibit duplication, to send out
The effect of bactericidal antiphlogistic is waved, traditional UV lamp can be substituted in many applications, such as sterilize, Water warfare and medical treatment.
Oxygen is substance necessary to aerobe and cells survival, and oxygen concentration slight change can cause biological cell inner ring
Border variation.Oxygen balance therein is not only mammal and maintains the basis of normal growth and development and physiology course and tumour thin
The necessary factor of born of the same parents' maintenance cells survival.During tumour cell copes with hypoxemia, what hypoxia inducible factor (HIF-1) mediated
The activation of hypoxia signal Signal Transduction Pathways plays an important role, and HIF-1 is heterodimer transcription factor, passes through under normoxic condition
Proteasome degradation is destroyed rapidly, but under anaerobic conditions, and slowly, the expression for eventually leading to target gene increases for degradation.
There is certain relationships for certain albumen in HIF-1 and the mitochondrial pathways, such as will promote apoptogene (Bax) to take tumour to low
Oxygen position, the apoptosis of inducing cell.Apoptotic pathways include endogenous and extrinsic pathway, and intrinsic pathway is also known as mitochondria
Approach.Apoptosis depends primarily on the type of cell and apoptotic stimulus using which kind of approach, this usual two approach there is
Close connection.Wherein, mitochondria is the key cells device for determining Apoptosis.Under low-oxygen environment, mitochondria generates excessive
ROS causes macromolecular to be damaged, such as lipid peroxidation, protein oxidation, and DNA oxidation etc. may cause cellular damage and death.
Summary of the invention:
Based on the above research situation, this experiment with ultraviolet light and cobalt chloride simulated hypoxia induce cell apoptosis for theory according to
According to utilizing CoCl2Simulated hypoxia environment, 280nm LED UV irradiate acute promyelocytic leukemia cell (HL-60 cell),
Proliferative conditions of the HL-60 cell under low-oxygen environment after 280nm LED UV irradiation are inquired into, find 280nm LED UV low
Inhibit HL-60 cell Proliferation and apoptosis-induced and downright bad, but inhibition and apoptosis-induced effect to normal cell under the conditions of oxygen
Gently, graft is irradiated by 280nm LED UV under hypoxia condition, so that residual tumor Apoptosis and necrosis in graft, and
Normal cell can normally survive, to reach the final purpose for removing residual tumor, answering after mitigating leukaemic's autotransplantation
Hair rate indicates its application prospect in leukaemia autotransplantation purging in vitro.
This application provides a kind of devices, it is characterised in that: includes light emitting diode ultraviolet lamp (Light Emitting
Diode Ultraviolet, LED UV)；And cobalt chloride.
Device as described above, it is characterised in that: light emitting diode ultraviolet lamp (Light Emitting Diode
Ultraviolet, LED UV), including lamp cap and pedestal, lamp cap can free regulating irradiation angle, the time of adjustment base carves
Degree is to adjust exposure dose.
Device as described above, it is characterised in that: light emitting diode ultraviolet lamp can discharge medium wave wavelength, and wavelength is
280nm。
Device as described above, it is characterised in that: light emitting diode ultraviolet lamp can be 280nm LED UV.
Device as described above is purging in vitro of the preparation with autologous hematopoietic stem cell transplantation for treatment leukaemia during
Application in device.
Device as described above is in preparation with the purging in vitro of autologous hematopoietic stem cell transplantation for treatment malignant neoplastic disease
Application in the device of process.
Purposes as described above, it is characterised in that the tumour or leukaemia, specifically: the white blood of acute lymphoblastic
Disease, acute myelocytic leukemia and neuroblastoma.
It is white with autologous hematopoietic stem cell transplantation for treatment in preparation that present invention also provides 280nm LED UV and/or cobalt chloride
The application in device during the purging in vitro of blood disease.
Present invention also provides 280nm LED UV and/or cobalt chloride to be disliked in preparation with autologous hematopoietic stem cell transplantation for treatment
Application in the device of the purging in vitro process of property tumor disease.
Cobalt chloride as described above, preferably CoCl2·6H2O, molecular weight 237.93g/mol, red monoclinic crystallographic system knot
Crystalline substance, it is soluble easily in water in addition to above application, present invention also provides:
A kind of light emitting diode ultraviolet lamp (Light Emitting Diode Ultraviolet, LED UV), feature
Be to include lamp cap and pedestal, lamp cap can free regulating irradiation angle, the time scale of adjustment base adjusts exposure dose.
280nm LED UV as described above, it is characterised in that release medium wave wavelength, wavelength 280nm.
280nm LED UV as described above is with the purging in vitro process of autologous hematopoietic stem cell transplantation for treatment leukaemia
In application.
280nm LED UV as described above is with the external of autologous hematopoietic stem cell transplantation for treatment malignant neoplastic disease
Application in purification process.
Application as described above, it is characterised in that the tumour, specifically: acute lymphoblastic leukemia, acute marrow
Chronic myeloid leukemia and neuroblastoma.
A kind of cobalt chloride chemical reagent, it is characterised in that molecular formula CoCl2·6H2O, molecular weight 237.93g/mol,
The crystallization of red monoclinic crystallographic system, it is soluble easily in water.
Cobalt chloride as described above is the purging in vitro of application autologous hematopoietic stem cell transplantation for treatment leukaemia during
Using.
Purging in vitro of the cobalt chloride as described above in application autologous hematopoietic stem cell transplantation for treatment malignant neoplastic disease
Application in the process.
Application as described above, it is characterised in that the tumour, specifically: acute lymphoblastic leukemia, acute marrow
Chronic myeloid leukemia and neuroblastoma.
Light emitting diode ultraviolet lamp combines cobalt chloride in the external net of application autologous hematopoietic stem cell transplantation for treatment leukaemia
Application during change.
Light emitting diode ultraviolet lamp combines cobalt chloride and is applying autologous hematopoietic stem cell transplantation for treatment malignant neoplastic disease
Purging in vitro during application.
Application as described above, it is characterised in that the tumour or leukaemia, specifically: the white blood of acute lymphoblastic
Disease, acute myelocytic leukemia and neuroblastoma.
Light emitting diode ultraviolet lamp as described above, can discharge medium wave wavelength, wavelength 280nm.Preferably 280nm
LED UV。
Above-mentioned apparatus or application can reduce remaining cells of resistant tumors in autograft.
Above-mentioned apparatus or application can remove residual tumor.
Above-mentioned apparatus or application can mitigate the recurrence rate after leukaemic's autologous hematopoietic stem cell transplantation.
Above-mentioned apparatus or apply is of great significance in leukaemia autotransplantation purging in vitro.
Detailed description of the invention
Fig. 1, HL-60 cell are grown after different condition is handled and morphological change
Fig. 2, HL-60 cell apoptosis rate after different condition is handled
Fig. 3, HL-60 cell Bcl-2 protein expression after different condition is handled change
Specific embodiment:
1, experimental group
This research uses the strain of acute promyelocytic leukemia cell standard cell (HL-60 cell).Experiment is divided into normal control
Group (control group), hypoxemia processing group (hypoxia group), ultraviolet light irradiation group (ultraviolet light group), hypoxemia+ultraviolet light is jointly processed by group are (low
Oxygen+ultraviolet light group).HL-60 cell is recovered according to a conventional method, secondary culture, for real after cell enters logarithmic growth phase
It tests.The cell for taking growth conditions good, control group row routine culture, hypoxia group give CoCl2(150 μm of ol/L of final concentration) processing,
Ultraviolet light group 30J/m2The 280nm length ultraviolet light emitting diode of energy irradiates, and hypoxemia+ultraviolet light group is giving CoCl2Processing
On the basis of use 30J/m2The 280nm length ultraviolet light emitting diode of energy irradiates.Group of cells is in 37 DEG C, 5%CO2Constant temperature training
Case culture is supported, collects cell for detecting after being incubated for 48h.The form and record of group of cells are observed under inverted microscope.
1.1 CCK-8 methods detect cell proliferation inhibition rate
Each group cell to be measured is inoculated in sterile 96 well culture plate with the density of 4 × 104 cells/wells, every hole is added
10 μ L CCK-8 solution are put into 37 DEG C, are incubated for 3h in 5%CO2 constant incubator, cell-free culture solution is added as blank pair
According to each hole absorbance value (OD) of detection, record repeat 3 as a result, experiment is independent at 450nm wavelength on enzyme-linked immunosorbent assay instrument
It is secondary.Cell proliferation inhibition rate is calculated according to following formula:
The detection of 1.2 Apoptosis by Flow Cytometries
By HL-60 cell with 1 × 106The density of a cells/well is seeded in 24 orifice plates, and carries out phase respectively according to grouping
It should handle.It is washed 2 times with PBS, with 500 μ L buffer suspension cells, is separately added into 5 μ L of AnnexinV-FITC, 5 PI μ L, keeps away
Light is incubated for 15min, flow cytomery apoptosis rate, as a result with the sum of early apoptosis and non-viable apoptotic cell ratio table
Show.Experiment is independently repeated 3 times.
The expression of 1.3 quantitative real-time PCRs detection Bcl-2 gene mRNA
By HL-60 cell with 1 × 106The density of a cells/well is seeded in 24 orifice plates, and carries out phase respectively according to grouping
It should handle.The RNA of each group cell to be measured is extracted according to the method that RNAiso Plus kit provides.It is pressed on ice bath
PrimeScriptTM RT reagent Kit Reverse Transcriptase kit specification prepares RT reaction solution, and reverse transcription synthesizes cDNA.
Specificity amplification primer designs and synthesizes (table 1) by Sangon Biotech (Shanghai) Co., Ltd..Real-time fluorescence quantitative PCR
(RT-qPCR) 10 μ L of amplification reaction system (20 μ L): SYBR Premix Ex TaqTM, upstream and downstream primer each 0.8 μ L, cDNA
2.0 6.4 μ L of μ L, dH2O of template.Reaction condition: 95 DEG C of initial denaturation 30s；95 DEG C of 5s, 60 DEG C of 34s, 40 circulations.According to survey
As a result the Ct value obtained, the relative expression quantity of the Bcl-2 of calculating indicate that Δ Δ Ct=experimental group Bcl-2 is average with 2- Δ Δ Ct
Value-experimental group GAPDH average value)-(control group Bcl-2 average value-control group GAPDH average value).Experiment is independently repeated 3 times.
The primer sequence table of table 1 Bcl-2 and GAPDH
The expression quantity of 1.4 immunoblottings (Western Blot) detection Bcl-2 albumen
By HL-60 cell with 1 × 106The density of a cells/well is seeded in 24 orifice plates, and carries out phase respectively according to grouping
It should handle.Using using Protein Extraction Reagent box to extract gross protein after RIPA lysate lytic cell, BCA method measures protein
Albumen is separated by electrophoresis using 12.5%SDS-PAGE in concentration, and protein gel is transferred on PDVF film, and Bcl-2 mono- is added after closing
Anti- (1: 1000) 4 DEG C of overnight incubations, addition secondary antibody (1: 5000) is incubated for 1h, using GAPDH protein expression as internal reference, uses
Image J software evaluation albumen relative expression quantity.
2, experimental result
The growth of 2.1 group of cells and morphologic change
Observation is as it can be seen that cellular control unit upgrowth situation is good, with the extension of incubation time, cell number under inverted microscope
Amount increases, and cellular morphology is complete, round bright, marshalling；Each experimental group cell shrinkage, bright degree reduce, are disorganized, with
The extension of incubation time, cell quantity reduce, it is the most significant with hypoxemia+ultraviolet light group, it is seen that dead cell and cell division
Aposome out.(see Fig. 1)
2.2 group of cells Proliferation Ability situations of change
The proliferation inhibition rate of control group is set as 0.Hypoxia group, ultraviolet light group, hypoxemia+ultraviolet light group HL-60 cell Proliferation
Obvious inhibiting effect is generated, inhibiting rate is respectively 20.5% ± 1.0%, 44.3% ± 2.1%, 64.7% ± 3.3%, each group
Cell proliferation inhibition rate comparing difference is statistically significant (F=267.326, P < 0.01).Ultraviolet light group cell proliferation inhibition rate
Higher than hypoxia group (P < 0.05), hypoxemia+ultraviolet light group cell proliferation inhibition rate is apparently higher than ultraviolet light group and hypoxia group (P <
0.05)。
2.3 group of cells apoptosis situations of change
Control group, hypoxia group, ultraviolet light group, hypoxemia+ultraviolet light group apoptosis rate is respectively 2.64% ± 1.16%,
10.6% ± 0.7%, 14.5% ± 1.5,31.7% ± 1.3%, the statistically significant (F of group of cells apoptosis rate comparing difference
=319.507, P < 0.01).Hypoxia group, ultraviolet light group and hypoxemia+ultraviolet light group apoptosis rate are above control group (P <
0.05), ultraviolet light group apoptosis rate is higher than hypoxia group (P < 0.05), and hypoxemia+ultraviolet light group apoptosis rate is apparently higher than low
Oxygen group and ultraviolet light group (P < 0.05).(see Fig. 2: Flow cytometry each group HL-60 Apoptosis situation AnnexinV (-)
PI (-) is living cells (Q4), and AnnexinV (-) PI (+) is mechanical damage cell (Q1), and AnnexinV (+) PI (-) is to wither early stage
Die cell (Q3), AnnexinV (+) PI (+) is non-viable apoptotic cell (Q2), with early apoptosis and non-viable apoptotic cell ratio it
(Q2+Q3) calculates apoptosis rate.)
The variation of 2.4 each group Bcl-2 mRNA expressions
Control group Bcl-2 mRNA relative expression quantity is set as 1, hypoxia group, ultraviolet light group, hypoxemia+ultraviolet light group Bcl-2
The relative expression quantity of mRNA is respectively 0.73 ± 0.01,0.62 ± 0.02,0.46 ± 0.02, the opposite table of each group Bcl-2 mRNA
It is statistically significant (F=612.602, P < 0.01) up to amount comparing difference.Hypoxia group, ultraviolet light group and hypoxemia+ultraviolet light group are thin
Born of the same parents' Bcl-2 mrna expression amount is below control group (P < 0.05), and ultraviolet light group Bcl-2 mrna expression amount is lower than hypoxia group (P
< 0.05), hypoxemia+ultraviolet light group Bcl-2 mrna expression amount is lower than hypoxia group and ultraviolet light group (P < 0.05).(see Fig. 3)
The variation of 2.5 each group Bcl-2 protein expression levels
Control group Bcl-2 albumen relative expression quantity is set as 1, hypoxia group, ultraviolet light group, hypoxemia+ultraviolet light group Bcl-2 egg
White relative expression quantity is respectively 0.75 ± 0.03,0.64 ± 0.01,0.52 ± 0.04, the relative expression of each group Bcl-2 albumen
It is statistically significant (F=523.642, P < 0.01) to measure comparing difference.Hypoxia group, ultraviolet light group and hypoxemia+ultraviolet light group cell
Bcl-2 expressing quantity is below control group (P < 0.05), and ultraviolet light group Bcl-2 expressing quantity is lower than hypoxia group (P <
0.05), hypoxemia+ultraviolet light group Bcl-2 expressing quantity is lower than hypoxia group and ultraviolet light group (P < 0.05).(see Fig. 3)
3, conclusion
The study find that 280nm LED-UV inhibits the proliferation of HL-60 cell in hypoxia condition and induces cell apoptosis,
In Leukemic Cells In Vitro cell plays the role of apoptosis-induced and dead, can be used as leukaemic's autologous hematopoietic stem cell transplantation body
A part of external purifying process reduces remaining cells of resistant tumors in autograft, removes residual tumor most to reach
Whole purpose, the recurrence rate after mitigating leukaemic's autologous hematopoietic stem cell transplantation, in leukaemia autotransplantation purging in vitro
In be with a wide range of applications.
Above description is general description of the invention.It according to circumstances or is actually needed, the variation of form can be carried out and waited
The substitution of value, although using specific term herein, these terms are intended to describe, rather than the purpose for limitation.Ability
Field technique personnel can make various changes or modifications the present invention, and such equivalent forms equally fall within the application appended claims
Within book limited range.
Claims (9)
1. a kind of device, it is characterised in that: include light emitting diode ultraviolet lamp (Light Emitting Diode
Ultraviolet, LED UV)；And cobalt chloride.
2. device as described in claim 1, it is characterised in that: light emitting diode ultraviolet lamp (Light Emitting Diode
Ultraviolet, LED UV), including lamp cap and pedestal, lamp cap can free regulating irradiation angle, the time of adjustment base carves
Degree is to adjust exposure dose.
3. device as described in claim 1, it is characterised in that: light emitting diode ultraviolet lamp can discharge medium wave wavelength, wavelength
For 280nm.
4. device as described in claim 1, it is characterised in that: light emitting diode ultraviolet lamp can be 280nm LED UV.
5. device as described in claim 1 is in preparation with the purging in vitro process of autologous hematopoietic stem cell transplantation for treatment leukaemia
In device in application.
6. device as described in claim 1 is in preparation with the external of autologous hematopoietic stem cell transplantation for treatment malignant neoplastic disease
Application in the device of purification process.
7. the purposes as described in claim 5 or 6, it is characterised in that the leukaemia or tumour, specifically: acute lymphoblastic
Chronic myeloid leukemia, acute myelocytic leukemia and neuroblastoma.
8.280nm LED UV and/or cobalt chloride are being prepared with the purging in vitro mistake of autologous hematopoietic stem cell transplantation for treatment leukaemia
The application in device in journey.
9.280nm LED UV and/or cobalt chloride are being prepared with the body of autologous hematopoietic stem cell transplantation for treatment malignant neoplastic disease
Application in the device of external purifying process.
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