Pancreatic cancer is one of the lethal types of cancer due to its ability to metastasize throughout the body. Despite recent advances in pancreatic cancer research, all the current cancer therapies have severe limitations in treating metastatic pancreatic cancer. Therefore, there is a need for a treatment regimen that can both break the immunosuppressive nature of the tumor and control cancer metastasis. We used a novel localized ablative immunotherapy, a combination of interstitial photothermal therapy (iPTT) and intratumoral administration of immunostimulant, to treat pancreatic tumors in mouse model. Here, we investigated the effects of iPTT on the tumor microenvironment or orthotopic mouse model to determine the optimal ablative effects. This treatment regimen will later be combined with an immunostimulant for a synergistic approach to provide an effective treatment modality for metastatic pancreatic cancers.
Localized ablative immunotherapy (LAIT) combines targeted photothermal therapy (PTT) and immunotherapy to ablate the primary tumor site using laser irradiation while inducing systemic and specific anti-tumor immune responses for the treatment of metastatic cancers. The therapeutic efficiency of LAIT synergized with nanomedicine has been proven to be safe and effective for cancer treatment. Here, graphene oxide (GO) is used as a light-absorbing agent to enhance the generation of heat caused by PTT and increase its tumoricidal effect. GO is also a nanocarrier for drug delivery of the immune-stimulating biopolymer N-dihydrogalactochitosan (GC). GC is an innovative and effective immunostimulant/adjuvant with surfactant properties that was used to functionalize GO nanosheets. This work was designed to determine the main properties of GO/GC nanoparticles (NPs) when used in combination with PTT. The therapeutic efficacy of the treatment is being assessed on a highly aggressive and poorly immunogenic pancreatic tumor model in mice. Overall, GO/GC shows promising properties as a stable, safe, and effective photothermal agent and immunostimulant for nano-ablative immunotherapy for cancer.
A novel biopolymer, N-dihydrogalactochitosan (GC), is developed for inducing immune responses. GC stimulates innate and adaptive antitumor and antiviral immunities. In this study, we investigated the mechanism of GC-induced immune responses through in vitro and in vivo studies. We find that GC drives type I IFN production and IFN responses in antigen presenting cells (APCs). Furthermore, GC drives alternative activation of STING leading to inflammatory cell death that enhances dendritic cell (DC) activation. In vivo, GC induced a potent response of type I IFN and upregulated genes associated with STING signaling within the tumor microenvironment (TME). Because of its potent immunological stimulation ability and its unique mechanism in inducing the immune responses, GC has been used in combination with laser photothermal (PTT) for the treatment of cancers. We find that PTT+GC induced specific modulation of immune cells, positively corresponding to long-term survival of cancer patient.
Common two-dimensional (2D) models are ineffective in mimicking solid tumors. Additionally, fibrotic stroma is one of the major characteristics of pancreatic tumors and it is often missing in in vitro models. Therefore, there is a need for a better in vitro model to accurately mimic the characteristics of tumor and to detect the progression of fibrosis within the tumor model. Here, we utilized polarization-sensitive optical coherence tomography (PS-OCT) to longitudinally detect the collagen progression within multicellular pancreatic tumor spheroids in vitro. Spheroids were scanned by PS-OCT every two days, and progression of fibrosis within the spheroids were detected.
KEYWORDS: Tumors, Optical coherence tomography, Blood vessels, Tissue optics, Surgery, Signal attenuation, Pancreatic cancer, Oncology, In vivo imaging, Cancer
We utilized optical coherence tomography (OCT) to monitor the longitudinal progression of the microenvironment and microvasculature of pancreatic tumors before and after the photothermal therapy-induced immunotherapy in vivo. The primary pancreatic tumors implanted on mouse legs and treated via the photothermal therapy-induced immunotherapy were observed every three days for 36 days. The intensity-based OCT structure, uniformity, texture, intrinsic optical attenuation contrast, and vascular structures were detected and analyzed. Our result demonstrated that the photothermal-induced immunotherapy could cause significant changes in the distribution of the tissue structure and vasculature within the microenvironment and microvasculature of the primary pancreatic tumors.
KEYWORDS: Tumors, Optical coherence tomography, Melanoma, Signal attenuation, Tissues, In vivo imaging, Angiography, Cancer, Tissue optics, Pancreatic cancer
Pancreatic tumors and melanoma are two types of cancers with high mortality. Monitoring the tumor microenvironment during growth plays an important role in studying the property of tumors. To study the progression of pancreatic tumors and melanoma in vivo, we propose to use optical coherence tomography (OCT) to monitor the tumor structure and angiogenesis in mouse in a longitudinal manner. Our results demonstrate that OCT is a promising tool to longitudinally monitor the change and progression of structure, tissue distribution, and microvasculature in pancreatic and melanoma tumor models. OCT can serve as a promising modality to provide structural and microvascular information for future anti-cancer treatment and drug development.
Pancreatic cancer is one of the deadliest types of cancer due to its ability to metastasize throughout the body. According to the Surveillance, Epidemiology, and End Results Program (SEER), the overall 5-year relative survival rate for pancreatic cancer is 10.8% but once the cancer metastasizes, this survival rate reduces to 3%. Despite recent advances in cancer research, all the current cancer therapies have severe limitations in treating pancreatic cancer. One major challenge in pancreatic cancer research is the lack of an accurate model of the pancreatic tumor and its microenvironment. The common two-dimensional (2D) models are ineffective in mimicking solid tumors. Therefore, there is a need for a better in vitro model to accurately mimic the characteristics of solid pancreatic tumor and to improve assessments for cancer therapies. Here, we generated multicellular tumor spheroids from an aggressive pancreatic cancer cell line, Panc02-H7, and monitored its growth. We also investigated the effects of photothermal therapy through irradiation of a near-infrared laser, which is used to induce immunogenic cell death (ICD) on the tumor spheroids. This three-dimensional (3D) tumor model mimics pancreatic tumors in vitro and this study can generate translatable results and, consequently, guide clinical studies.
Early assessment of sub-surface bladder tumor extension is challenging as there are no acceptable imaging modalities to determine sub-surface three-dimensional (3D) tumor extension. Current existing cystoscopy guided transurethral resection technique is limited on direct visualization of tumor surface. In this paper, a multi-modal optical imaging modality combing high-resolution optical coherence tomography (OCT) and depth-resolved high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging was developed. Bladder tissues from UPII-SV40T mice model were imaged by the multi-modal system ex vivo and sub-surface tumor extension was reconstructed. Algorithm was developed to further quantified 3D bladder tumor morphology and molecular alterations.
Three-dimensional (3D) cell culture models are developed as a promising platform to screen anticancer therapeutics and treatments. However, current imaging techniques cannot provide 3D structures of tumor spheroids in situ. In this study, we employed label-free and noninvasive optical coherence tomography (OCT) for imaging and quantifying the 3D structures of tumor spheroids. We imaged ovarian cancer spheroids with OVCAR-8 cell line over a period of 10 days with 5,000 and 50,000 initial cell numbers. We successfully reconstructed the 3D necrotic regions via label-free intrinsic scattering attenuation contrast and evaluated the effect of Cisplatin treatment on tumor spheroids.
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