Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer-clinician's insight

Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the realtime feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a costeffectiveness analysis is also necessary.

Sialic acid-mediated photochemotherapy enhances infiltration of CD8^(+)T cells from tumor-draining lymph nodes into tumors of immunosenescent mice

Immunoscenescence plays a key role in the initiation and development of tumors.Furthermore,immunoscenescence also impacts drug delivery and cancer therapeutic efficacy.To reduce the impact of immunosenescence on anti-tumor therapy,this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid(SA)-modified liposomes into the tumor,kill tumor cells via SA-mediated photochemotherapy,enhance infiltration of neutrophils into the tumor,induce immunogenic death of tumor cells with chemotherapy,enhance infiltration of CD8^(+)T cells into the tumordraining lymph nodes and tumors of immunosenescent mice,and achieve SA-mediated photochemotherapy.We found that CD8^(+)T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2-and 8-month-old mice;16-month-old mice exhibited immunosenescence.The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice,and tumors recurred after scabbing.SA-mediated photochemotherapy enhanced tumor infiltration by CD8^(+)T cells and neutrophils,induced crusting and regression of tumors in 8-month-old mice,inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Intraoperative photodynamic therapy for tracheal mass in non-small cell lung cancer:A case report

BACKGROUND Tracheal neoplasms represent less than 0.1%of all malignancies and have no established treatment guidelines.Surgical resection with reconstruction is the primary treatment.This study demonstrates successful treatment of concurrent lung and tracheal tumors using surgical excision and intraoperative photodynamic therapy(PDT),highlighting the effectiveness and safety of this approach.CASE SUMMARY A 74-year-old male with a history of smoking and chronic obstructive pulmonary disease was diagnosed with tracheal squamous cell carcinoma and right lower lobe adenocarcinoma.A multidisciplinary team created a treatment plan involving tumor resection and PDT.The tracheal tumor was removed through a tracheal incision and this was followed by intraluminal PDT.The trachea was repaired and a right lower lobectomy was performed.The patient received a second PDT treatment postoperatively and was discharged 10 d after the tracheal surgery,without complications.He then underwent platinum-based chemotherapy for lymphovascular invasion of lung cancer.Three-month postoperative bronchoscopy revealed normal tracheal mucosa with a scar at the resection site and no evidence of tumor recurrence in the trachea or lung.CONCLUSION Our case of concurrent tracheal and lung cancers was successfully treated with surgical excision and intraoperative PDT which proved safe and effective in this patient.

Endoscopic ultrasound guided interventional procedures

Endoscopic ultrasound(EUS) has emerged as an important diagnostic and therapeutic modality in the field of gastrointestinal endoscopy. EUS provides access to many organs and lesions which are in proximity to the gastrointestinal tract and thus giving an opportunity to target them for therapeutic and diagnostic purposes. This modality also provides a real time opportunityto target the required area while avoiding adjacent vascular and other structures. Therapeutic EUS has found role in management of pancreatic fluid collections, biliary and pancreatic duct drainage in cases of failed endoscopic retrograde cholangiopancreatography, drainage of gallbladder, celiac plexus neurolysis/blockage, drainage of mediastinal and intra-abdominal abscesses and collections and in targeted cancer chemotherapy and radiotherapy. Infact, therapeutic EUS has emerged as the therapy of choice for management of pancreatic pseudocysts and recent innovations like fully covered removable metallic stents have improved results in patients with organised necrosis. Similarly, EUS guided drainage of biliary tract and pancreatic duct helps drainage of these systems in patients with failed cannulation, inaccessible papilla as with duodenal/gastric obstruction or surgically altered anatomy. EUS guided gall bladder drainage is a useful emergent procedure in patients with acute cholecystitis who are not fit for surgery. EUS guided celiac plexus neurolysis and blockage is more effective and less morbid vis-à-vis the percutaneous technique. The field of interventional EUS is rapidly advancing and many more interventions are being continuously added. This review focuses on the current status of evidence vis-à-vis the established indications of therapeutic EUS.

Separation and identification of the major components of Photocarcinorin and their tumor-photobiological activities

It has been shown by the results-of HPLC analysis in combination with spectrographicdeterminations that PsD-007 is composed of 7 different porphyrins,In order of the proportion inPsD-007,they are:3 （or 8）-（l-methoxyethyl）-8 （or 3）-（l-hydroxyethyl）-deuteroporphyrin Ⅸ（MHD）;3,8-di-（l-methoxyethyl）-deuteroporphyrin Ⅸ（DMD）;3（or 8）-（l-methoxyethyl）-8 （or3）-vinyl-deuteroporphyrin Ⅸ（MVD）;3（or 8）-（l-hydroxyethyl）-8（or 3）-vinyl-deuteroporphyrin Ⅸ（HVD）;hernatoporphyrin Ⅸ （Hp）;protoporphyrin Ⅸ （Pp） and 3（or 8）-（O-aceylethyl）-8（or 3）-（l-hydroxyethyl）-deuteroporphrin Ⅸ （AHD）,which presented only in crude PsD-007 and hasbeen transformed into MHD and Hp,respectively during the separation and preparing the clinicalpreparation of PsD-007.Structures of these porphyrins were further eonfirmed by the corre-sponding anthentic samples obtained by synthetic method.It was found on the basis of the experi-mental data of photosensitizing ability in cell-free systems and photoinactivation of human cancercells in vitro as well as efficacy of photodynamic therapy for sarcoma.S180 in mice of the ma-jor components MILD,DMD and MVD composed of which more over 85% of the totalamount of PsD-007,that they all exhibited comparatively high photosensitizing ability andphotodynamic effects on cancer cells and tram-planted animal tumor.

Hematoporphyrin 3-or 8-monomethyl ether:a promising candidate for tumor photodynamic therapy

Presented are methods for preparation,photosensitizing potential,photoinactivationof human cancer cells in vitro,efficacy of photodynamic therapy(PDT)of transplanted animaltumor and related data of preclinical and toxicological tests of a new single porphyrin compoundhematoporphyrin monomethyl ether(HMME).The results of experiments indicated that in com-parison with the mixed porphyrin preparation(HpD)now used in clinical practice,HMMEproved to be of higher photosensitizing potential,stronger photodynamic effects,lower toxicitynonmutagenicity and nonteratogenicity,furthermore it can be selectively uptaken into tumor tis-sue in mice.It may be considered a new ideal drug candidate for tumor photodynamic therapy.

A new photolocalizing and photochemotherapeutic agent and radiosensitizer photocarcinorin(PsD-007)

Here is presented a brief review of studies on the home-made photolocalizing andphotochemotherapeutic agent as well as radiosensitizer for human malignancies called photocarcinorin(PsD-007).Experimental data and principal research conclusions of chemistry,pharmacodynamics,preclinical pharmacology and toxicology as well as phase-Ⅰ-Ⅱ clinical trials are summarized.

SYNERGISM BETWEEN PHOTODYNAMIC THERAPY OF ALUMINUM SULFONATED PHTHALOCYANINE AND HYPERTHERMIA ON MOUSE HEPATOMA IN VIVO AND I

Mouse hepatoma ascites was inoculated sc into the footpad of right hindleg. On d 7 after inoculation the tunior site was treated by heat (44 ℃, 25 min), photodynamic therapy (PDT) of aluminum sulfonated phthalocyanine (AlSPc), and PDT plus heat. The hepatoma growth was almost completely inhibited and a high percentage of cure obtained in the combination group.The succinic dehydrogenase (SD), superoxide dismutase (SOD) and glutathione (GSH) of hepatonia cells were not affected by heat alone, but when heat was used following PDT, the SD, SOD and GSH in hepatonia calls were significantly inhibited.

Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle

The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.

Photodynamic therapy combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization

The aim of this research was to evaluate the efficacy and safety of photodynamic therapy(PDT)combined with intravitreal injection of triamcinolone acetonide(TA)in the treatment of choroidal neovascularization(CNV)secon-dary to age-related macular degeneration(AMD)and patho-logical myopia.PDT combined with intravitreal injection of TA was performed on 16 eyes of 16 patients with CNV diagnosed by visual acuity,fluorescein fundus angiography(FFA)and optical coherent tomography(OCT),including 14 eyes secondary to age-related macular degeneration and two eyes secondary to pathological myopia.TA was injected intravitreally 72 h post PDT on 12 eyes and from three months to one year(mean nine months)post PDT on four eyes respec-tively.All the patients were followed up for 3 to 18 months(mean 18.6 months).Best-corrected visual acuity,intraocular pressure,retinal thickness and FFAwere observed.The visual acuity was improved in seven eyes(43.8%)of all the 16 eyes and stable in nine eyes(56.2%),respectively.FFA revealed complete or partial closure of CNV in all patients.OCT showed that the macular edema disappeared or was allevi-ated.Transient intraocular pressure elevation occurred in one patient(6.25%)of all the 16 eyes and intraocular pressure returned to the normal after a transient treatment with anti-glaucoma medication.The mean number of PDTs during the first year was 1.1.PDT combined with intravitreal injection of TA for CNV is safe and effective.It can reduce the risk of visual loss and the treatment frequency.