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Photodynamic Therapy
Published in Henry W. Lim, Nicholas A. Soter, Clinical Photomedicine, 2018
Photochemotherapy can be used for lesions accessible to light that is transmitted through the body surface or directed internally, via an optical fiber. Fibers may be inserted within tumors, permitting treatment of large masses. Thus, cutaneous, endobronchial, intra-abdominal, bladder, and central nervous system malignancies are amenable to this technique. The prototype, first-generation photosensitizer is hematoporphyrin derivative and the partially purified fraction of hematoporphyrin derivative called Photofrin II. Because hematoporphyrin derivative/Photofrin II produces singlet oxygen upon illumination (1), treatment with these compounds is appropriately called photodynamic therapy. The tumor-localizing properties of hematoporphyrin derivative were first described by Lipson (2), and subsequently by Dougherty (3). Photodynamic therapy with hematoporphyrin derivative or Photofrin II has been used on a variety of tumor types with significant clinical benefit (4–22, 35). Since 1977 about 5,000 patients have been treated with hematoporphyrin derivative or Photofrin II. Results are very encouraging with palliation of advanced tumors and cures of early disease. Phase III trials for bladder, lung, and esophageal cancers are currently underway. At our institution we have had excellent results in the treatment of several different types of cutaneous lesions including basal- and squamous-cell carcinomas (4, 14, 22, 35), recurrent or metastatic breast cancer (10), Kaposi’s sarcoma, and cutaneous T-cell lymphoma.
Spheroids in Radiobiology Research
Published in Rolf Bjerkvig, Spheroid Culture in Cancer Research, 2017
A possible explanation for the resistance of cells from large spheroids was heterogeneity in drug levels between different cells in the spheroid. This has been shown to occur in a subsequent study by West and Moore219 using a flow cytometric method for analyzing the drug content of individual cells. Mean drug uptake of single cells exposed to a fluorescent hematoporphyrin derivative was directly proportional to concentration, but at lower drug levels the heterogeneity in the population was markedly increased. Drug uptake in cells from spheroids of different sizes showed a rapid decrease between 100 to 500 u.m in diameter, with no further decrease in uptake in cells from spheroids up to 1000 µm in diameter. However, the heterogeneity in cellular drug levels increased linearly throughout the entire range of spheroids studied. The dispersal in the intracellular drug levels was 8 times greater in 1000-µm-diameter spheroids than in single cells. This group has postulated that changes in the degree of cell-cell contacts in spheroids, or alterations in the membrane composition of cells grown as spheroids, could account for the observed differences in drug uptake. Although either of these possibilities has important implications for understanding PDT, determination of the mechanism of PDT resistance in spheroids will require further experimentation.
Malignant Neoplasms of the Rectum
Published in Philip H. Gordon, Santhat Nivatvongs, Lee E. Smith, Scott Thorn Barrows, Carla Gunn, Gregory Blew, David Ehlert, Craig Kiefer, Kim Martens, Neoplasms of the Colon, Rectum, and Anus, 2007
Laser ablation is still a useful therapy for some patients, particularly when the predominant symptom is rectal bleeding. In patients with obstructing rectal carcinoma, several repeated treatment sessions may be necessary to achieve initial luminal patency and further sessions will become necessary every few months or as symptoms recur. Palliation of obstructive symptoms is achieved after two to five laser sessions in 80% to 90% patients and lasts up to six months. Complications occur in 5% of 15% of patients that are mostly minor, although perforation, sepsis, and death have been reported. Laser therapy is an important adjunct in patients with recurrent obstruction after self-expanding metal stent placement. Laser ablation is not effective in treating painful infiltration of pelvic nerves by the malignancy. Argon plasma coagulation is a cost-effective alternative to laser treatment for control of bleeding but it is less useful for treating rectal obstruction. Injection therapy of rectal carcinoma using alcohol or sclerosing agents has a great advantage of being low cost and simple. Photo-dynamic therapy, endoscopic electrocoagulation, and cryotherapy are less suitable because of side effects or complications. Photo-dynamic therapy is limited by the cutaneous photo-toxicity of the systemically administered hematoporphyrin.
Nanotechnology-based photo-immunotherapy: a new hope for inhibition of melanoma growth and metastasis
Published in Journal of Drug Targeting, 2023
Ji-Yuan Zhang, Wei-Dong Gao, Jia-Yi Lin, Shan Xu, Li-Jun Zhang, Xin-Chen Lu, Xin Luan, Jian-Qing Peng, Yi Chen
PDT effectively destruct the tumour tissue based on the PS, light with a certain wavelength, and reactive oxygen species (ROS) produced by PDT, which can not only directly destroy tumour cells at the primary site through apoptosis, necrosis or autophagy [17], but also eliminate tumour cells by destroying the tumour-associated blood vessels [18,19]. Multitudinous PSs used in PDT can be categorised into three generations. The first-generation PS (e.g. porfimer sodium and hematoporphyrin derivatives) exhibit effective photocytotoxicity, but the non-specific distribution and low light absorption limit further application [20]. The second-generation PS (e.g. the derivates of chlorins, benzoporphyrins, and phthalocyanines) possess strong absorbance in the deep red region, increasing the light penetration depth in the tissue [21–23]. The third-generation PS (e.g. phthalocyanine-lipoprotein complex) is the second-generation PSs encapsulated by biomaterials, which improve the targeting capability of PSs [24].
The structure of CLEC-2: mechanisms of dimerization and higher-order clustering
Published in Platelets, 2021
Eleyna M Martin, Malou Zuidscherwoude, Luis a Morán, Ying Di, Angel García, Steve P Watson
Hemin is structurally analogous to cobalt-hematoporphyrin, a protoporphyrin IX complexed with cobalt as displayed in Figure 5, the derived product of a high-throughput screen for inhibitors of CLEC-2[58]. Cobalt-hematoporphyrin binds directly to CLEC-2, as observed by SPR, and has been shown to inhibit the podoplanin-CLEC-2 interaction with an IC50 of 88 nM determined by ELISA, although it should be noted that platelet activation is only inhibited at low micromolar concentrations[58]. Cobalt-hematoporphyrin was also demonstrated to inhibit platelet aggregation induced by rhodocytin and podoplanin-transfected CHO cells. Given the structural similarities between hemin and cobalt-hematoporphyrin, it would suggest both molecules bind CLEC-2 in a similar manner. However, cobalt-hematoporphyrin does not induce platelet activation as seen with hemin, and is able to inhibit ligand binding[58], eluding to hemin and cobalt-hematoporphyrin interacting with CLEC-2 at distinct sites.
Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Yuyan Lin, Tao Zhou, Renren Bai, Yuanyuan Xie
As the population ages, the number of cancer cases and deaths worldwide is also rapidly growing1,2. With the continuous development of medicine, the treatment strategies for cancer are also constantly improving. Photodynamic therapy (PDT) has been considered a safer cancer therapy approach with fewer side effects3. In 1978, Dougherty first applied this technique to gastrointestinal cancer using hematoporphyrin (HPD)4,5. Clinical studies revealed that PDT has been increasingly utilised in therapy for solid tumours, including tumours of the brain, head and neck, skin, oesophagus, lung, gastrointestinal, bone, bladder, prostate, breast, cervix, and ovary and in basal cell carcinomas6,7. Porfimer sodium (Photofrin®, Figure 1) was the first photosensitiser (PS) approved worldwide for the treatment of cancer. It has no long-term side effects and can be used repeatedly without causing drug resistance8. As an effective combination therapeutic strategy, Photofrin® did not display serious toxicity. Moreover, the survival period of inoperable tumour patients was prolonged, and the quality of life improved9,10. However, patients still suffered several side effects during the treatment, including skin photosensitivity and metabolic disturbances10.