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

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.

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

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.

Evaluation of a New Cystoscopic Cryocatheter and Method for the Destruction of Bladder Cancer: Preliminary Study.

To assess the ability to deliver full-thickness bladder wall cryoablation through a cystoscopic approach using a new closed-loop 6F cryocatheter and thermal dose-controlled protocol. Evaluations were conducted using a chronic porcine model wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, ureteral orifice, and distal ureter). A 6F cryocatheter was passed through the working channel of a flexible cystoscope.

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

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.

Assessment of the Impact of Post-Thaw Stress Pathway Modulation on Cell Recovery following Cryopreservation in a Hematopoietic Progenitor Cell Model.

The development and use of complex cell-based products in clinical and discovery science continues to grow at an unprecedented pace. To this end, cryopreservation plays a critical role, serving as an enabling process, providing on-demand access to biological material, facilitating large scale production, storage, and distribution of living materials. Despite serving a critical role and substantial improvements over the last several decades, cryopreservation often remains a bottleneck impacting numerous areas including cell therapy, tissue engineering, and tissue banking.

Breast Cancer Cryoablation: Assessment of the Impact of Fundamental Procedural Variables in an In Vitro Human Breast Cancer Model.

Introduction: Breast cancer is the most prominent form of cancer and the second leading cause of death in women behind lung cancer. The primary modes of treatment today include surgical excision (lumpectomy, mastectomy), radiation, chemoablation, anti-HER2/neu therapy, and/or hormone therapy. The severe side effects associated with these therapies suggest a minimally invasive therapy with fewer quality of life issues would be advantageous for treatment of this pervasive disease.

Investigation of Bladder Cancer Cell Response to Cryoablation and Adjunctive Cisplatin Based Cryo/Chemotherapy.

Due to a rising annual incidence of bladder cancer, there is a growing need for development of new strategies for treatment. In 2018, the World Cancer Research Fund and other groups reported that there were ~550,000 new cases worldwide of bladder cancer. It has been further estimated that >200,000 individuals die annually from bladder cancer worldwide.

Cryoablation: physical and molecular basis with putative immunological consequences.

Cryoablation (CA) is unique as the that impacts all cellular processes. CA is independent of cell cycle stage and degree of cellular stemness. Importantly, CA is typically applied as a non-repetitive (single session) treatment that does not support adaptative mutagenesis as do many repetitive therapies.

Assessment of a novel cryoablation device for the endovascular treatment of cardiac tachyarrhythmias.

Objectives: Cryoablation is an effective alternative treatment for cardiac arrhythmias offering shortened recovery and reduced side effects. As the use of cryoablation increases, the need for new devices and procedures has emerged. This has been driven by technological limitations including lengthy periods to generate a single lesion (3-5 min), uncertain transmurality, and differential efficacy.

Defeating Cancers' Adaptive Defensive Strategies Using Thermal Therapies: Examining Cancer's Therapeutic Resistance, Ablative, and Computational Modeling Strategies as a means for Improving Therapeutic Outcome.

Background: Diverse thermal ablative therapies are currently in use for the treatment of cancer. Commonly applied with the intent to cure, these ablative therapies are providing promising success rates similar to and often exceeding "gold standard" approaches. Cancer-curing prospects may be enhanced by deeper understanding of thermal effects on cancer cells and the hosting tissue, including the molecular mechanisms of cancer cell mutations, which enable resistance to therapy.

Dose Escalation of Vitamin D Yields Similar Cryosurgical Outcome to Single Dose Exposure in a Prostate Cancer Model.

Vitamin D (VD) is an effective adjunctive agent, enhancing the destructive effects of freezing in prostate cancer cryoablation studies. We investigated whether dose escalation of VD over several weeks, to model the increase in physiological VD levels if an oral supplement were prescribed, would be as or more effective than a single treatment 1 to 2 days prior to freezing. PC-3 cells in log phase growth to model aggressive, highly metabolically active prostate cancer were exposed to a gradually increasing dose of VD to a final dose of 80 nM over a 4-week period, maintained for 2 weeks at 80 nM, and then exposed to mild sublethal freezing temperatures.

Best practices for cryopreserving, thawing, recovering, and assessing cells.

Long-term storage of cell stocks insures that cells are available for use whenever needed. Cryopreservation of cells is the method of choice for preservation of important or rare cell stocks. There are several factors to consider when establishing a protocol for freezing, thawing, and recovery of cells after storage.

Best practices in cell culture: an overview.

This overview describes a series of articles to provide an unmet need for information on best practices in animal cell culture. The target audience primarily consists of entry-level scientists with minimal experience in cell culture. It also include scientists, journalists, and educators with some experience in cell culture, but in need of a refresher in best practices.

Assessment of Cryosurgical Device Performance Using a 3D Tissue-Engineered Cancer Model.

As the clinical use of cryoablation for the treatment of cancer has increased, so too has the need for knowledge on the dynamic environment within the frozen mass created by a cryoprobe. While a number of factors exist, an understanding of the iceball size, critical isotherm distribution/penetration, and the resultant lethal zone created by a cryoprobe are critical for clinical application. To this end, cryoprobe performance is typically characterized based on the iceball size and temperature penetration in phantom gel models.

Integrating Molecular Control to Improve Cryopreservation Outcome.

Cryopreservation (CP) is a critical component in enabling on-demand access to biological material (macromolecules, cells, and tissues), yet CP has evolved little over the last several decades. Today's CP processes often yield a suboptimal "product," which has slowed progression in areas such as cell therapy and stem cell research. Recent discoveries focusing on molecular control and buffering of cell stress responses to CP as well as the development of new devices that improve sample freezing and thawing are now providing a path to improve sample quality.

Cryopreservation: Evolution of Molecular Based Strategies.

Cryopreservation (CP) is an enabling process providing for on-demand access to biological material (cells and tissues) which serve as a starting, intermediate or even final product. While a critical tool, CP protocols, approaches and technologies have evolved little over the last several decades. A lack of conversion of discoveries from the CP sciences into mainstream utilization has resulted in a bottleneck in technological progression in areas such as stem cell research and cell therapy.

Characterization of Pancreatic Cancer Cell Thermal Response to Heat Ablation or Cryoablation.

One of the most lethal carcinomas is pancreatic cancer. As standard treatment using chemotherapy and radiation has shown limited success, thermal regimens (cryotherapy or heat ablation) are emerging as viable alternatives. Although promising, our understanding of pancreatic cancer response to thermal ablation remains limited.

Investigation of the Impact of Cell Cycle Stage on Freeze Response Sensitivity of Androgen-Insensitive Prostate Cancer.

Background: Cryoablation, an effective means of ablating cancer, is often used in conjunction with adjuvants that target cancer cells in a specific cell cycle stage to increase treatment efficacy. The objective of this study was to investigate the impact of cell cycle stage on cancer freeze response as well as investigate the potential cellular kinetic effect of calcitriol, the active metabolic of vitamin D3, when used as a cryosensitizing adjuvant in order to maximize prostate cancer cell death.

Methods: Cell cycle distribution of PC-3 cells was analyzed via flow cytometry to compare gap 1, synthesis, and gap 2/mitosis phase subpopulations pre- and postfreeze as well as changes elicited by calcitriol pretreatment.

Biobanking: The Future of Cell Preservation Strategies.

With established techniques cryopreservation is often viewed as an "old school" discipline yet modern cryopreservation is undergoing another scientific and technology development growth phase. In this regard, today's cryopreservation processes and cryopreserved products are found at the forefront of research in the areas of discovery science, stem cell research, diagnostic development and personalized medicine. As the utilization of cryopreserved cells continues to increase, the demands placed on the biobanking industry are increasing and evolving at an accelerated rate.

Characterization and modulation of human mesenchymal stem cell stress pathway response following hypothermic storage.

Human mesenchymal stem cell (hMSC) research has grown exponentially in the last decade. The ability to process and preserve these cells is vital to their use in stem cell therapy. As such, understanding the complex, molecular-based stress responses associated with biopreservation is necessary to improve outcomes and maintain the unique stem cell properties specific to hMSC.

Implications of differential stress response activation following non-frozen hepatocellular storage.

Hepatocytes are critical for numerous cell therapies and in vitro investigations. A limiting factor for their use in these applications is the ability to process and preserve them without loss of viability or functionality. Normal rat hepatocytes (NHEPs) and human hepatoma (C3A) cells were stored at either 4°C or 37°C to examine post-processing stress responses.

Vitamin D(3) cryosensitization increases prostate cancer susceptibility to cryoablation via mitochondrial-mediated apoptosis and necrosis.

Objectives: To investigate the effect and molecular mechanisms of action of Vitamin D(3) (VD(3) ) as a neo-adjunctive agent before cryosurgery in an effort to increase treatment efficacy for prostate cancer (CaP). To eliminate the potential for disease recurrence that exists at the periphery of the freeze lesion, where temperatures may be insufficient to destroy both androgen-sensitive (AS) and androgen-insensitive (AI) CaP.

Methods: Human CaP cells, LNCaP, were each genetically altered to express the AS and AI phenotypes and subjected to VD(3) treatment and freezing in an in vitro and tissue-engineered model.

The unfolded protein response in human corneal endothelial cells following hypothermic storage: implications of a novel stress pathway.

Human corneal endothelial cells (HCEC) have become increasingly important for a range of eye disease treatment therapies. Accordingly, a more detailed understanding of the processing and preservation associated stresses experienced by corneal cells might contribute to improved therapeutic outcomes. To this end, the unfolded protein response (UPR) pathway was investigated as a potential mediator of corneal cell death in response to hypothermic storage.