Gastric cancer new treatments
Introduction Cancer is a group of diseases which cause an abnormal and uncontrolled cell division coupled with malignant behavior such as invasion and metastasis [ 1 ].
Gastric cancer new treatments the treatment of cancer various methods have already been discovered and many others are in the process of discovery e.
But the gastric cancer new treatments drugs can fail to kill cancer cells for various reasons, the transport of the anticancer drug being governed by physiological and physicochemical properties of the target cell and of the drug itself [ 4 ].
These properties include gastric cancer new treatments, charge, size, configuration, electrochemical properties, hydrophilicity, etc.
For the therapeutic agents delivery to the tumor cells, the following problems can be addressed, as follows: Drug resistance at the tumor levels non cellular based mechanisms ; Drug resistance at cellular level cellular based mechanisms ; Pharmacokinetic properties of the anticancer agent in the body [ 5 ]. The concept of the nanoparticles which permits gastric cancer new treatments absorption of the drugs in a specific tissue, and this concept has been applied for hyperthermia, radiation therapy, photodynamic therapy, etc.
Meanwhile, the nanoparticles opened new horizons for drug delivery and bringing the term nanomedicines.
Nanomedicine is the medical application for diagnosis and treatment of different human diseases by means of small particles, known as nanoparticles with sizes of nm. The nanoparticles are known by their large surface area, high reactivity, high solubility, reduced side effects and low toxicity [ 7 - 9 ].
The main nanoparticles applied in nanomedicine are: polymeric nanoparticles, liposomes and lipid nanoparticles, micelles, microcapsules, magnetic particles, and carbon nanoparticles fullerenes, carbon nanotubes, carbon nanofibers, etc and the nanoassemblies [ 10 - 12 ].
Several aspects of the oncological and surgical management are still controversial and so gastric cancer represents a challenge for the surgeon.
Photodynamic therapy PDT as a part of photochemotherapy, is a concerted method where, in addition to light and an administered drug, oxygen is required. PDT represents a concerted action of light, with a sensitizers and an oxygen active specie singlet oxygen which preferentially actions on tumor cells and not on healthy cells. The administered drug is generally a substance which can efficiently photosensitize the formation of singlet oxygen or other reactive species derived from oxygenand such species react with different biological targets, and cause cellular damage and finally, the cellular death.
Activation of the photosensitizers by light is an essential condition for a successful PDT. Under such circumstances, this chapter offers the most up—to—date coverage of photodynamic therapy including information on how nanosensitizers, have evolved within the field of cancer therapy and more recently for drugs controlled release in this field, by using personal data correlated with literature reports.
Short history Photodynamic therapy is dating from ancient time, the Indian civilizations reported from the first time the combined action of psoralens with sunlight to treat vitiligo [ 14 ].
Niels Fiensen used UV light to treat small pox, pustular infections eruptions, cutaneous gastric cancer new treatments, and for its results he obtained the Nobel Prize in Medicine in Similar results obtained Niels Raab inby using eosin as sensitizer and combining his results with Jesionek and J. Prime results for skin tumors and epilepsy generated by light induced dermatitis [ 17 ]. Meyer-Betz was the only experimentalist gastric cancer new treatments tested this method on himself, by injecting haematoporphyrin, reporting the observed effects: oedema, erythema and light sensitivity [ 18 ].
Later, Campbell and Hill studied the PDT effects on microcirculation, reporting the thrombosis and vascular shutdown [ 19 ]. Lipson in went on to treat a patient with a large cancer of the breast following an injection of a derivative of haematoporphyrin HpD.
The modern era of photodynamic therapy was established by Dr. Dougherty, at the Division of Radiation Biology at Roswell Park Memorial Institute, Buffalo, USA, who reported that a systematically gastric cancer new treatments porphyrin on activation with red light caused complete eradication of transplanted experimental tumors [ 20 ].
In the photodynamic therapy occur three types of mechanisms: type I mechanism — electron transfer eT where the photosensitizer excited state generates a radical species, for example gastric cancer new treatments electron transfer from or to a substrate, or by hydrogen atom abstraction from a substrate.
The type I mechanism of PDT In type II mechanism - energy transfer ET an energy transfer occurs from the excited photosensitizer to molecular oxygen, to give the sensitizer in its ground state and singlet oxygen.
In this mechanism electronic excitation energy is transferred from the excited triplet T1 of the sensitizer generated by intersystem crossing isc from the ecited singlet S1 to triplet molecular oxygen, to give the sensitizer in its ground state S0 and singlet oxygen 1O2.
Sheme 2. The type II mechanism of PDT Major biological targets are membranes that undergo rupture and the cells are destroyed through the membranes around the mitochondria and the lysosomes. These organelles induce subsequent cellular destruction by necrosis or apoptosis [ 21 - 24 ].
Except these two types of mechanisms, there is another one: type III mechanism, which take place when the oxygen is absent in the system.
Sheme 3. Photosensitizers 4. Conventional photosensitizers All the sensitizers could be natural or synthetic compounds, with proper absorption properties from a light source. They should be pure compounds, soluble in body fluids, with high capacity to be incorporated in malignant cells.
Also, they should be fluorescent and able to generate singlet oxygen, which is the excited state of oxygen efficient on malignant cells [ 25 ].
Taking into account all these criteria and gastric cancer new treatments the compatibility with human body, the porphyrins are known as ideal sensitizers for photodynamic therapy. The general chemical structure for some porphyrins and phthalocyanines as PDT agents are represented in Figure 1. Figure 1. The chemical structure of some porphyrins and phthalocyanines First Generation Photosensitizers, includes Photofrin® and HpD and exist as gastric cancer new treatments mixtures of monomeric, dimeric, and oligomeric structures.
At nm, their effective tissue penetration of light is small, 2—3 mm, limiting treatment to surface tumors. In spite of its safe applications in bladder, esophageal and lung cancers, Photofrin tends to be applied to head human part and thoracic part affected by cancer [ 26 ].
Photodynamic Nanomedicine Strategies in Cancer Therapy and Drug Delivery
The Second Generation Photosensitizers, includes porphyrins and related compounds porphycenes, chlorins, phthalocyanines, so onmany of them being under clinical tests. TPPS4 exhibited lower photochemical efficiency than meso-substituted porphyrins containing fewer sulphonated groups [ 28 ]. Except the free-bases, the porphyrins can be chelated with a variety of metals, the diamagnetic ones enhancing the phototoxicity.
Paramagnetic metals are shortening the lifetime of the triplet state and as result can make the gastric cancer new treatments photoinactive [ 21 ].
The presence of axial ligands to the centrally coordinated metal ion is often advantageous, since it generates some degree of steric hindrance to intermolecular aggregation, without impairing the photophysical properties of the dye [ 21 ].
Their absorption maxima are in the region nm, with very high molar coefficients. A representative compound is aluminium phthalocyanine tetrasulphonated AlPcS4, commercially known as Photosens, in spite of its skin sensitivity, proper absorption maxima at nm, it is well applied in Russian clinics for stomach, skin, oral and breast cancers [ 33 ].
Another clinical phthalocyanine is silicon phthalocyanine 4 Pc4 which was successful tested in different skin cances pre-malignant - actinic keratosis, Bowen disease or gastric cancer new treatments in malgnant forms of cutaneous cancers [ 343536 ]. The central metal ions play an important role in the photophysical properties of phthalocyanines.
In metallophthalocyanines the central metal M has one or two axial ligands or one or more ring substituents or both. When a diamagnetic ion is in the center of the ring e. Silicon phthalocyanine allows two appropriate axial ligands, gastric cancer helmin?ilor treatments forbid the ring staking which decrease the clinical efficiency [ 41 - 44 ].
The triplet-state lifetimes of an axially substituted silicon phthalocyanine typically vary from to μs and the yields from 0. Some synthetic silicon phthalocyanine and naphthalocyanine Figure 2 have been used in some laboratory experuiments on K culture cellk gastric cancer new treatments excellent results [ 4546 ]. Third generation photosensitizers contains available drugs that are modified them with antibody conjugates, biologic conjugates, etc.
These terms are still being used although not accepted unanimously and dividing photosensitizing drugs into such generations may be very confusing. The nanostructures are increasingly being used as carriers for the development of 3rd generation PS, as the most important drug delivery systems used as carriers for PS in the field of anticancer PDT.
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Именно таким способом наши предки даровали нам практическое бессмертие и вместе с тем избежали проблем, возникающих одновременно с устранением смерти.
Они не поняли; это было странно, ведь именно их род, без сомнения, дал ему имя, сохранившееся вместе с воспоминаниями о его рождении.
Figure 2. Nanoparticles have unusual properties that can improve the drug delivery. Hard nanoparticles Inorganic Nanoparticles is the generic term for several nanoparticles including for example metal oxide- and non-oxide ceramics, metals, gold and magnetic nanoparticles.
Ceramic nanoparticles: Ceramic-based nanoparticles have some advantages over organic carriers: particle size, shape, porosity, and mono-dispersibility.
They are water-soluble, extremely stable, and known for their compatibility in biological systems without being subjected to microbial attack.
For conventional drug delivery, the carrier vehicle should release the encapsulated drug at the target tissue. Their silica-based nanoparticles diameter ca. The resulting silica- based nanoparticles were gastric cancer new treatments with uniform particle size.
By irradiation with suitable wavelengths: or nm, silica nanoparticles with porphyrin embedded, could be efficiently taken up by tumor cells and lead to cells death. Silica nanoparticles SiO2with the following advantages: chemically inert, avoiding interactions with other molecules in the body.
These interesting properties have made silica nanoparticles the most studied nanoparticle-based PDT systems.
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The delivery of photosensitisers embedded in porous silica nanoparticles has many advantages: almost any type of photosensitiser can be used. Second, the concentration of photosensitiser can be modulated as needed increasing or decreasing it. When the photosensitisers are incorporated on to silica nanoparticles trough covalent bonds, it is possible to avoid the eventual release of the compounds in gastric cancer new treatments media, and the consequent lost of efficacy or the appearance of side effects.
Gold nanoparticles: Gold nanoparticles have been targeted to breast cancer cells by incorporating a primary antibody to the ir surface in addition to a zinc phthalocyanine photosensitiser and a bioavailability and solubility enhancer, with promising results [ 5051 ]. Gold particles with various diameters and uniform size distribution have been demonstrated to have novel and fascinating properties.