Perfluorocarbons therapeutics in modern cancer nanotechnology for hypoxia-induced anti-tumor therapy

2021 ◽  
Vol 27 ◽  
Author(s):  
Saurabh Satija ◽  
Prabal Sharma ◽  
Harpreet Kaur ◽  
Daljeet Singh Dhanjal ◽  
Reena Singh Chopra ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Tumor Cells ◽  
Chronic Hypoxia ◽  
Tumor Therapy ◽  
Oxygen Species ◽  
Tumour Hypoxia ◽  
The Past ◽  
Cell Quiescence ◽  
Diffusion Mechanisms ◽  
And Diffusion

: With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.

scholarly journals Mesoporous semiconductors combined with up-conversion nanoparticles for enhanced photodynamic therapy under near infrared light

RSC Advances ◽  
2019 ◽  
Vol 9 (30) ◽  
pp. 17273-17280 ◽  
Author(s):  
Fan Yang ◽  
Jun Liu ◽  
Xue Jiang ◽  
Weiwei Wu ◽  
Zhenni Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Near Infrared ◽  
Tumor Therapy ◽  
Reactive Oxygen ◽  
Infrared Light ◽  
Oxygen Species ◽  
Near Infrared Light

Photodynamic therapy (PDT) is a promising and effective method for tumor therapy that relies on the reactive oxygen species (ROS) produced by photosensitizers at specific wavelengths to inhibit tumor cells.

scholarly journals Intramuscular Expression of Plasmid-Encoded FVII-Fc Immunoconjugate for Tumor Immunotherapy by Targeting Tumoral Blood Vessels and Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Liping Ma ◽  
Guanru Wang ◽  
Sijia Liu ◽  
Feng Bi ◽  
Ming Liu ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Continuous Production ◽  
Expression System ◽  
Tumor Therapy ◽  
Coagulation Factor ◽  
Tumor Immunotherapy ◽  
Factor Vii ◽  
Dependent Manner

Tissue factor (TF) has been confirmed to be specifically expressed by vascular endothelial cells (VECs) in solid tumors and certain types of malignant tumor cells. Coagulation factor VII (FVII) can specifically bind to TF with high affinity, so the FVII-TF interaction provides an ideal target for tumor therapy. Expression of proteins in skeletal muscles is a simple and economical avenue for continuous production of therapeutic molecules. However, it is difficult to treat solid tumors till now due to the limited number of therapeutic proteins produced by the intramuscular gene expression system. Herein, we strived to explore whether anti-tumor effects can be achieved via intramuscular delivery of a plasmid encoding a FVII-guided immunoconjugate (Icon) molecule by a previously established Pluronic L64/electropulse (L/E) technique. Our study exhibited several interesting outcomes. 1) The mouse light chain of FVII (mLFVII) molecule could guide red fluorescent protein (RFP) to accumulate predominantly at tumor sites in a TF-dependent manner. 2) Intramuscular expression of mLFVII-hFc (human IgG1 Fc) Icon could significantly inhibit the growth of both liver and lung cancers in nude mice, and the inhibition extent was proportional to the level of tumor-expressed TF. 3) The number of blood vessels and the amount of blood flow in tumors were significantly decreased in mLFVII-hFc Icon-treated mice. 4) This immunotherapy system did not display obvious side effects. Our study provided an efficient and economical system for tumor immunotherapy by targeting both blood vessels and tumor cells. It is also an open system for synergistic therapy by conveniently integrating other anticancer regimens.

The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis

2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Oxidative Damage ◽  
Tumor Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tumor Treatment ◽  
Normal Cells ◽  
Treatment And Prevention

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

Nano Technological Approach for Anti-Tumor Therapy: Opportunities and Challenges

2020 ◽  
Vol 10 ◽  
Author(s):  
Krishna Champaneria ◽  
Prajesh Prajapati
Keyword(s):  
Adverse Effects ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Blood Circulation ◽  
Review Paper ◽  
Tumor Therapy ◽  
Conventional Chemotherapy ◽  
Targeting Delivery ◽  
Tumor Accumulation ◽  
Work Done

Cancer is one of the reason for mortality and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that can destroy Tumor cells effectively. But these agents destroy healthy cells along with the tumor cells, leading to many adverse effects which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize the adverse effects, various drug delivery systems (DDSs) has been developed. Among them, nanoparticles are attractive platforms for it. So this review paper explores the recent work done on targeted delivery, enhancing tumor accumulation and longer blood circulation using more effective biomaterial that will enhance the properties of nanoparticles. Moreover, various target-specific delivery of drugs like antibody-targeted, targeting delivery through angiogenesis, mitochondria, CD44 receptor are also explained.

Penile Lymphoepithelioma-Like Carcinoma: A Rare Case With PD-L1 Expression

2021 ◽  
pp. 106689692098834
Author(s):  
Raquel Machado-Neves ◽  
Bernardo Teixeira ◽  
Elsa Fonseca ◽  
Pedro Valente ◽  
Joaquim Lindoro ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Tumor Cells ◽  
Rare Case ◽  
Malignant Tumors ◽  
Squamous Cell Carcinomas ◽  
The Third ◽  
The Past ◽  
First Case ◽  
Lymphoplasmacytic Infiltrate

Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

scholarly journals 150 GAIA-102: a new class off-the-shelf allogeneic NK-like cells that can eliminate solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A163-A163
Author(s):  
Yui Harada ◽  
Yoshikazu Yonemitsu
Keyword(s):  
Nk Cells ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Adoptive Immunotherapy ◽  
Nk Cell ◽  
Peritoneal Dissemination ◽  
Checkpoint Inhibitors ◽  
Antitumor Effects ◽  
Car T

BackgroundCancer immunotherapy has been established as a new therapeutic category since the recent success of immune checkpoint inhibitors and a type of adoptive immunotherapy, namely chimeric antigen receptor-modified T cells (CAR-T). Although CAR-T demonstrated impressive clinical results, serious adverse effects (cytokine storm and on-target off-tumor toxicity) and undefined efficacy on solid tumors are important issues to be solved. We’ve developed a cutting-edge, simple, and feeder-free method to generate highly activated and expanded human NK cells from peripheral blood (US9404083, PCT/JP2019/012744, PCT/JP2020/012386), and have been conducting further investigation why our new type of NK cells, named as GAIA-102, are so effective to kill malignant cells.MethodsCryopreserved PBMCs purchased from vendors were mixed and processed by using LOVO and CliniMACS® Prodigy (automated/closed systems). CD3+ and CD34+ cells were depleted, and the cells were cultured with high concentration of hIL-2 and 5% UltraGRO® for 14 days in our original closed system. Then, we confirmed the expression of surface markers, CD107a mobilization and cell-mediated cytotoxicity against various tumor cells and normal cells with or without monoclonal antibody drugs in vitro and antitumor effects against peritoneal dissemination model using SKOV3 in vivo.ResultsImportantly, we’ve found that our GAIA-102 exhibited CD3-/CD56bright/CD57- immature phenotype that could kill various tumor cells efficiently from various origins, including Raji cells that was highly resistant to NK cell killing. More importantly, massive accumulation, retention, infiltration and sphere destruction by GAIA-102 were affected neither by myeloid-derived suppressor cells nor regulatory T-lymphocytes. GAIA-102 was also effective in vivo to murine model of peritoneal dissemination of human ovarian cancer; thus, these findings indicate that GAIA-102 has a potential to be an ‘upward compatible’ modality over CAR-T strategy, and would be a new and promising candidate for adoptive immunotherapy against solid tumors.ConclusionsWe now just started GMP/GCTP production of this new and powerful NK cells and first-in-human clinical trials in use of GAIA-102 will be initiated on 2021.Ethics ApprovalThe animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Kyushu University (approval nos. A30-234-0 and A30-359-0).

scholarly journals Cyclic Hypoxia: An Update on Its Characteristics, Methods to Measure It and Biological Implications in Cancer

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 23
Author(s):  
Samuel B. Bader ◽  
Mark W. Dewhirst ◽  
Ester M. Hammond
Keyword(s):  
Vascular Remodeling ◽  
Intermittent Hypoxia ◽  
Chronic Hypoxia ◽  
Tumor Hypoxia ◽  
Biological Response ◽  
Therapy Response ◽  
Static Condition ◽  
Oxygen Species ◽  
Oxygen Levels ◽  
Poor Patient

Regions of hypoxia occur in most if not all solid cancers. Although the presence of tumor hypoxia is a common occurrence, the levels of hypoxia and proportion of the tumor that are hypoxic vary significantly. Importantly, even within tumors, oxygen levels fluctuate due to changes in red blood cell flux, vascular remodeling and thermoregulation. Together, this leads to cyclic or intermittent hypoxia. Tumor hypoxia predicts for poor patient outcome, in part due to increased resistance to all standard therapies. However, it is less clear how cyclic hypoxia impacts therapy response. Here, we discuss the causes of cyclic hypoxia and, importantly, which imaging modalities are best suited to detecting cyclic vs. chronic hypoxia. In addition, we provide a comparison of the biological response to chronic and cyclic hypoxia, including how the levels of reactive oxygen species and HIF-1 are likely impacted. Together, we highlight the importance of remembering that tumor hypoxia is not a static condition and that the fluctuations in oxygen levels have significant biological consequences.

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