Investigation of Liver Cancer Cell Response to Cryoablation and AdjunctiveBased Cryo Chemotherapy

doi:10.31488/bjcr.153

Cited by 3 publications

(5 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar positive outcomes have been reported by Petrone et al [38] and Kovach et al [38]. These, and other, reports demonstrate the potential for cryoablation to treat PaCa [28,39,40]. Given that some PaCa tumors are poor candidates for surgical resection due to proximity to blood vessels and other organs, the precise targeting of cancerous cells with cryoablation could expand therapeutic options to more patients.…”

Section: Introductionsupporting

confidence: 76%

“…A recently completed clinical trial (NCT03695835) on the combination of cryoablation and pembrolizumab included a PaCa subgroup with initial results showing a benefit. We, as well as others, have published numerous studies on the effects of the combination of freezing with adjunctive agents, including chemotherapeutic drugs and nutraceuticals, in various cancer cell systems [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. The objective of this combinatorial adjunctive agent approach is to elevate the minimum lethal temperature necessary to fully ablate a tumor, thus ensuring complete cancer cell destruction with minimal over-freezing.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

et al. 2022

View full text Add to dashboard Cite

As the incidence of pancreatic ductal adenocarcinoma (PDAC) continues to grow, so does the need for new strategies for treatment. One such area being evaluated is cryoablation. While promising, studies remain limited and questions surrounding basic dosing (minimal lethal temperature) coupled with technological issues associated with accessing PDAC tumors and tumor proximity to vasculature and bile ducts, among others, have limited the use of cryoablation. Additionally, as chemotherapy remains the first-line of attack for PDAC, there is limited information on the impact of combining freezing with chemotherapy. As such, this study investigated the in vitro response of a PDAC cell line to freezing, chemotherapy, and the combination of chemotherapy pre-treatment and freezing. PANC-1 cells and PANC-1 tumor models were exposed to cryoablation (freezing insult) and compared to non-frozen controls. Additionally, PANC-1 cells were exposed to varying sub-clinical doses of gemcitabine or oxaliplatin alone and in combination with freezing. The results show that freezing to −10 °C did not affect viability, whereas −15 °C and −20 °C resulted in a reduction in 1 day post-freeze viability to 85% and 20%, respectively, though both recovered to controls by day 7. A complete cell loss was found following a single freeze below −25 °C. The combination of 100 nM gemcitabine (1.1 mg/m2) pre-treatment and a single freeze at −15 °C resulted in near-complete cell death (<5% survival) over the 7-day assessment interval. The combination of 8.8 µM oxaliplatin (130 mg/m2) pre-treatment and a single −15 °C freeze resulted in a similar trend of increased PANC-1 cell death. In summary, these in vitro results suggest that freezing alone to temperatures in the range of −25 °C results in a high degree of PDAC destruction. Further, the data support a potential combinatorial chemo/cryo-therapeutic strategy for the treatment of PDAC. These results suggest that a reduction in chemotherapeutic dose may be possible when offered in combination with freezing for the treatment of PDAC.

show abstract

Section: Introductionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

et al. 2022

View full text Add to dashboard Cite

show abstract

“…This prevented detailed histological characterization of the ablated tissue areas. Thirdly, while studies have shown that liver and pancreatic tissue have a similar minimal lethal temperature range (−20 °C to −25 °C) [ 26 , 68 , 70 , 71 , 91 ], extrapolation of the in vivo findings on liver tissue cryoablation to that of pancreatic tissue cryoablation using FrostBite should be with caution. To address these items, future in vivo studies will include expanded survival studies, histological analysis (H&E and trichrome staining), in vivo tumor models, and investigation of freeze duration (time and repeat freezes) on lesion size.…”

Section: Discussionmentioning

confidence: 99%

The Assessment of a Novel Endoscopic Ultrasound-Compatible Cryocatheter to Ablate Pancreatic Cancer

Baust,

Robilotto,

Raijman

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that may be treated utilizing thermal therapies. Cryoablation is an effective, minimally invasive therapy that has been utilized for the treatment of various cancers, offering patients a quicker recovery and reduced side effects. Cryoablation has been utilized on a limited basis for the treatment of PDAC. With the recent reports on the success of cryoablation, there is a growing interest in the use of cryoablation as a standalone, minimally invasive procedure to treat PDAC. While offering a promising path, the application of cryoablation to PDAC is limited by current technologies. As such, there is a need for the development of new devices to support advanced treatment strategies for PDAC. To this end, this study investigated the performance of a new endoscopic ultrasound-compatible cryoablation catheter technology, FrostBite. We hypothesized that FrostBite would enable the rapid, effective, minimally invasive delivery of ultra-cold temperatures to target tissues, resulting in effective ablation via an endoscopic approach. Thermal properties and ablative efficacy were evaluated using a heat-loaded gel model, tissue-engineered models (TEMs), and an initial in vivo porcine study. Freeze protocols evaluated included single and repeat 3 and 5 min applications. Isotherm assessment revealed the generation of a 2.2 cm diameter frozen mass with the −20 °C isotherm reaching a diameter of 1.5 cm following a single 5 min freeze. TEM studies revealed the achievement of temperatures ≤ −20 °C at a diameter of 1.9 cm after a 5 min freeze. Fluorescent imaging conducted 24 h post-thaw demonstrated a uniformly shaped ellipsoidal ablative zone with a midline diameter of 2.5 cm, resulting in a total ablative volume of 6.9 cm3 after a single 5 min freeze. In vivo findings consistently demonstrated the generation of ablative areas measuring 2.03 cm × 3.2 cm. These studies demonstrate the potential of the FrostBite cryocatheter as an endoscopic ultrasound-based treatment option. The data suggest that FrostBite may provide for the rapid, effective, controllable freezing of cancerous pancreatic and liver tissues. This ablative power also offers the potential of improved safety margins via the minimally invasive nature of an endoscopic ultrasound-based approach or natural orifice transluminal endoscopic surgery (NOTES)-based approach. The results of this pre-clinical feasibility study show promise, affirming the need for further investigation into the potential of the FrostBite cryocatheter as an advanced, minimally invasive cryoablative technology.

show abstract

“…The lethal temperature varies between cancer and tissue types, necessitating careful planning and visualization (tumor and frozen mass) to achieve maximum targeted destruction while avoiding damage to adjacent structures [ 17 , 18 ]. For instance, studies have shown that for the destruction of pancreatic and renal cancer, a minimal lethal temperature (MLT) of <−25 °C must be attained, whereas for late-stage prostate cancer, temperatures <−40 °C are necessary [ 19 , 20 , 21 , 22 , 23 ]. Application of a double freeze (providing repeat thermal insult in a finite window) has been shown to increase the MLT in the range of 5 to 10 °C [ 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, studies have shown that for the destruction of pancreatic and renal cancer, a minimal lethal temperature (MLT) of <−25 °C must be attained, whereas for late-stage prostate cancer, temperatures <−40 °C are necessary [ 19 , 20 , 21 , 22 , 23 ]. Application of a double freeze (providing repeat thermal insult in a finite window) has been shown to increase the MLT in the range of 5 to 10 °C [ 19 , 20 , 21 , 22 , 23 ]. In the case of LC, while numerous studies have demonstrated that CA can be used to effectively target NSCLC and support lethality in the −20 °C to −35 °C range [ 24 , 25 , 26 ], the definition of the MLT for LC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Lung Cancer Cell Response to Cryoablation and Adjunctive Gemcitabine-Based Cryo-Chemotherapy Using the A549 Cell Line

Santucci,

Snyder,

Van Buskirk

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Due to the rising annual incidence of lung cancer (LC), new treatment strategies are needed. While various options exist, many, if not all, remain suboptimal. Several studies have shown cryoablation to be a promising approach. Yet, a lack of basic information pertaining to LC response to freezing and requirement for percutaneous access has limited clinical use. In this study, we investigated the A549 lung carcinoma cell line response to freezing. The data show that a single 5 min freeze to −15 °C did not affect cell viability, whereas −20 °C and −25 °C result in a significant reduction in viability 1 day post freeze to <10%. These populations, however, were able to recover in culture. Application of a repeat (double) freeze resulted in complete cell death at −25 °C. Studies investigating the impact of adjunctive gemcitabine (75 nM) pretreatment in combination with freezing were then conducted. Exposure to gemcitabine alone resulted in minimal cell death. The combination of gemcitabine pretreatment and a −20 °C single freeze as well as combination treatment with a −15 °C repeat freeze both resulted in complete cell death. This suggests that gemcitabine pretreatment may be synergistically effective when combined with freezing. Studies into the modes of cell death associated with the increased cell death revealed the increased involvement of necroptosis in combination treatment. In summary, these results suggest that repeat freezing to −20 °C to −25 °C results in a high degree of LC destruction. Further, the data suggest that the combination of gemcitabine pretreatment and freezing resulted in a shift of the minimum lethal temperature for LC from −25 °C to −15 °C. These findings, in combination with previous reports, suggest that cryoablation alone or in combination with chemotherapy may provide an improved path for the treatment of LC.

show abstract

Investigation of Liver Cancer Cell Response to Cryoablation and AdjunctiveBased Cryo Chemotherapy

Cited by 3 publications

References 59 publications

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

The Assessment of a Novel Endoscopic Ultrasound-Compatible Cryocatheter to Ablate Pancreatic Cancer

Investigation of Lung Cancer Cell Response to Cryoablation and Adjunctive Gemcitabine-Based Cryo-Chemotherapy Using the A549 Cell Line

Contact Info

Product

Resources

About