chlorophyll-a and Neoplasm-Metastasis

To observe the effects of pheophorbide a-mediated photodynamic therapy (Pa-PDT) on the in vitro proliferation, apoptosis, invasion and metastasis of human prostate cancer PC-3 cells and to investigate its possible mechanism.. Pa-PDT in gradient concentrations (0 μM, 0.25 μM, 0.5 μM, 1 μM, 2 μM, and 4 μM) were used to act on PC-3 cells; the cell proliferation in each group was detected via methyl thiazolyl tetrazolium (MTT) assay and clone formation assay, and the cell apoptosis was detected via Hochst33258 staining and Annexin V/propidium iodide (PI) double labeling. Moreover, the effects of Pa-PDT on invasion and proliferation of PC-3 cells were observed via wound healing assay and transwell chamber assay. Finally, the expressions of apoptosis-related proteins, epithelial-mesenchymal transition (EMT)-related proteins and matrix metalloproteinases (MMPs) in each group were detected after treatment by Western blotting.. MTT and clone formation assays showed that Pa-PDT could inhibit the proliferation of PC-3 cells in a dose-dependent manner. The results of apoptosis assay revealed that Pa-PDT could significantly promote the apoptosis of PC-3 cells, obviously up-regulate the expressions of pro-apoptotic proteins, such as B-cell lymphoma-2-associated X protein (BAX), Caspase-3 and poly adenosine diphosphate-ribose polymerase (PARP), and inhibit the expression of Bcl-2. Besides, the wound healing assay and Transwell chamber assay showed that Pa-PDT could inhibit the invasion and metastasis capacities of PC-3 cells, whose relevant mechanisms were related to the fact that Pa-PDT inhibited the EMT process and down-regulated the expressions of MMPs in PC-3 cells.. Pa-PDT can inhibit the proliferation and promote the apoptosis of PC-3 cells. Moreover, it can also inhibit the invasion and metastasis capacities of PC-3 cells via inhibiting the EMT process and down-regulating the expressions of MMPs.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Chlorophyll; Epithelial-Mesenchymal Transition; Humans; Male; Neoplasm Metastasis; Photochemotherapy; Prostatic Neoplasms

An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity. Furthermore, immunogenic ZnP@pyro photodynamic therapy (PDT) treatment sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the primary 4T1 breast tumor but also significantly preventing metastasis to the lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models further demonstrate that ZnP@pyro PDT treatment combined with anti-PD-L1 results in the eradication of light-irradiated primary tumors and the complete inhibition of untreated distant tumors by generating a systemic tumor-specific cytotoxic T cell response. These findings indicate that nanoparticle-mediated PDT can potentiate the systemic efficacy of checkpoint blockade immunotherapies by activating the innate and adaptive immune systems in tumor microenvironment.

Topics: Animals; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Chlorophyll; Combined Modality Therapy; Diphosphates; Humans; Immunotherapy; Light; Lipids; Lung Neoplasms; Mice; Nanoparticles; Necrosis; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Zinc

Effective therapy for advanced cancer often requires treatment of both primary tumors and systemic disease that may not be apparent at initial diagnosis. Numerous studies have shown that stimulation of the host immune system can result in the generation of anti-tumor immune responses capable of controlling metastatic tumor growth. Thus, there is interest in the development of combination therapies that both control primary tumor growth and stimulate anti-tumor immunity for control of metastatic disease and subsequent tumor growth. Photodynamic therapy (PDT) is an FDA-approved anticancer modality that has been shown to enhance anti-tumor immunity. Augmentation of anti-tumor immunity by PDT is regimen dependent, and PDT regimens that enhance anti-tumor immunity have been defined. Unfortunately, these regimens have limited ability to control primary tumor growth. Therefore, a two-step combination therapy was devised in which a tumor-controlling PDT regimen was combined with an immune-enhancing PDT regimen. To determine whether the two-step combination therapy enhanced anti-tumor immunity, resistance to subsequent tumor challenge and T cell activation and function was measured. The ability to control distant disease was also determined. The results showed that the novel combination therapy stimulated anti-tumor immunity while retaining the ability to inhibit primary tumor growth of both murine colon (Colon26-HA) and mammary (4T1) carcinomas. The combination therapy resulted in enhanced tumor-specific T cell activation and controlled metastatic tumor growth. These results suggest that PDT may be an effective adjuvant for therapies that fail to stimulate the host anti-tumor immune response.

Topics: Animals; Antineoplastic Agents; Chlorophyll; Colonic Neoplasms; Dihematoporphyrin Ether; Female; Lymphocyte Activation; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Random Allocation; T-Lymphocytes; Transfection

Photodynamic therapy (PDT) is an established therapeutic method, first approved by the FDA for certain kinds of cancer in 1998. There are also increasing data to show that a related procedure, sonodynamic therapy (SDT), is a promising new modality for cancer treatment. Here, the authors report clinical results in 3 advanced refractory breast cancer patients who were treated using a combination of sonodynamic and photodynamic therapy (SPDT), along with conventional therapies. All 3 patients had pathologically proven metastatic breast carcinoma. These widely disseminated carcinomas had ultimately failed to respond to conventional therapy. A new sensitizing agent, Sonoflora 1 (SF1) was administered sublingually; then, after a 24-hour delay, patients were treated with a combination of light and ultrasound. All patients had significant partial or complete responses. SPDT is a promising new therapeutic combination for the treatment of breast cancer.

Topics: Administration, Sublingual; Adult; Breast Neoplasms; Carcinoma; Chlorophyll; Combined Modality Therapy; Complementary Therapies; Fatal Outcome; Female; Humans; Middle Aged; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents; Positron-Emission Tomography; Treatment Outcome; Ultrasonic Therapy

Cancer is a process of acquisition of an increased variety of cell functions by originally differentiated cells due to the failure of other organs to maintain their specific functions. Cancer cells take over functions of other organs or even other systems, that are chronically decompensated. The organ specific metabolites play an essential role in this process. Cancer is a reactive mechanism of the body to compensate for functions of decompensated organs (systems), in order to try to save life. Consequently, addition of the body's own or similar cancer extracts may be of great value in cancer treatment. A philosophic view of cancer will be briefly discussed.

Topics: Cell Differentiation; Chlorophyll; Humans; Mitosis; Models, Biological; Neoplasm Metastasis; Neoplasms; Oxygen

Topics: Chlorophyll; Coloring Agents; Hypersensitivity; Iodized Oil; Lymphatic System; Lymphography; Lymphoma; Neoplasm Metastasis; Pulmonary Embolism

Topics: Adolescent; Adult; Aged; Breast Neoplasms; Chlorophyll; Contrast Media; Female; Hodgkin Disease; Humans; Iodized Oil; Lymphography; Lymphoma; Male; Middle Aged; Neoplasm Metastasis

Topics: Chlorophyll; Chylothorax; Chylous Ascites; Cineradiography; Geriatrics; Humans; Iodized Oil; Lung Neoplasms; Lymphography; Neoplasm Metastasis; Surgical Procedures, Operative; Thoracic Duct