Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model

Santucci, Kimberly L.; Snyder, Kristi K.; Baust, John M.; Buskirk, Robert G. Van; Mouraviev, Vladimir; Polascik, Thomas J.; Gage, Andrew A.

doi:10.1038/pcan.2010.52

Cited by 26 publications

(33 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug resistance, however, could become an issue in vivo [60]. Previous studies from our laboratory have shown the success of adjuvants used for cryosensitization [37,57,[62][63][64][65].…”

Section: Discussionmentioning

confidence: 99%

“…In vitro and in vivo studies involving prostate cancer have shown the ability of cryosensitizing adjuvants to elevate the minimal lethal temperature for hormone refractory prostate cancer from -40°C to -20°C via pre-treatment with sub-clinical (non-toxic) doses of 5-fl uorocil, taxotere and cisplatin [65,66,71]. Other studies have demonstrated that combinatorial approaches using the active nutraceutical calcitriol (vitamin D 3 ) can result in the elevation of the minimal lethal temperature for prostate cancer to the -10 to -15°C range [57,75,76,78]. Based on these reports coupled with the identifi cation of a delayed molecular cell death response activated following freezing of C2 cells, the use of adjuvant agents, including chemotherapy and immunotherapy agents as well as RTK inhibitors, in combination with CA is an area that may also provide benefi t for treatment of MCT's and as such should be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of canine mastocytoma cell response to cryoablation

Santucci¹,

Snyder²,

Buskirk³

et al. 2020

Int J Vet Sci Res

View full text Add to dashboard Cite

IntroductionMastocytoma represents 16%-21% of all skin cancers in dogs, making it the most common form of cutaneous cancer [1]. Mast cells are generated from hematopoietic stem cells, reside in connective tissues, and comprise a necessary component of the immune response system [2]. The cause of mast cell tumors (MCT's), whether benign or malignant, is unknown. The formation of cancerous MCT's occurs frequently in dogs with median age of onset between 8-9 years [3,4].One of the most predictive factors in MCT development and subsequent aggressiveness is breed. The majority of reports agree that boxers, Labrador retrievers, pugs, golden retrievers and bulldog breeds present with the highest incidence of . Though there are a number of factors which can infl uence prognosis, including breed, c-kit mutation status and age, many veterinarians agree that the most predictive factor in MCT aggressiveness is tumor grade. Though there Abstract Introduction: Mastocytoma Tumors (MCT) represent 16%-21% of all skin cancers in dogs, making it the most common form of cutaneous cancer. Solitary MCT are typically treated with wide surgical excision margins. While effective, MCT excision can cause the release of a large amount of histamine and other cytokines resulting in complications such as systemic shock or anaphylaxis. Treatments such as chemotherapy and radiotherapy have been considered to achieve complete remission. Cryoablation also represents a potential treatment option for MCT. While studies have shown cryoablation to be benefi cial for the treatment of numerous cancers in animals and humans, few studies have described the use of cryoablation to treat MCT's. The limited use of cryoablation is due to a number of factors including a lack of basic information pertaining to dosing (minimal lethal temperature) necessary to destroy MCT cancer. As such, in this study we conducted a series of in vitro studies using the C2 cell line and a pilot ex vivo fi ne needle aspirate tissue sample in an effort to detail the effects of freezing of canine MCT.Methods: Samples were exposed to temperatures ranging from -5°C to -25°C, modeling the periphery of a cryogenic lesion for 3, 5 and 10minutes, and various markers of viability and modes of cell death were assessed daily over a 3 days recovery period. Additionally, investigation of the involvement of apoptosis in MCT cell death fl owing freezing was conducted via immunoblotting and caspase inhibition studies.Results: Viability studies revealed the -25°C isotherm as the critical minimal lethal temperature to achieve complete MCT cell death regardless of hold time. As the hold time at temperatures of -15°C and -20°C increased from 3 to 10minutes the level of cell death was also found to increase. Fluorescence microscopy, caspase inhibition and protein analysis revealed necrosis to be the primary mode of cell death following freezing. These studies, however, also revealed a signifi cant level of apoptotic cell death post-freeze. Molecular analysis suggested that freezing to -15°C to -20°C re...

show abstract

“…Drug resistance, however, could become an issue in vivo [60]. Previous studies from our laboratory have shown the success of adjuvants used for cryosensitization [37,57,[62][63][64][65].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization of canine mastocytoma cell response to cryoablation

Santucci¹,

Snyder²,

Buskirk³

et al. 2020

Int J Vet Sci Res

View full text Add to dashboard Cite

show abstract

“…Through various in vitro , in vivo , and clinical reports, improved cancer destruction at mild sub-freezing temperatures following brief low dose exposure to general or specific apoptotic inducing agents has been shown. In some cases, such as the use of vitamin D 3 as a sensitizing agent, complete prostate cancer cell death has been demonstrated following freezing to temperatures as warm as −10°C in both in vitro and in vivo models [12,61,111]. …”

Section: Adjunctive Therapymentioning

confidence: 99%

“…The diverse techniques have been broadly divided into thermal and non-thermal methods. The mechanisms of cryoablative damage are more completely described when compared to heat-based procedures [11,12,61,111]. …”

Section: Competitive Ablative Therapiesmentioning

confidence: 99%

Mechanisms of cryoablation: Clinical consequences on malignant tumors

et al. 2014

View full text Add to dashboard Cite

While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer that, while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity, we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer.

show abstract

“…We have previously reported on the ability of calcitriol to synergistically decrease postfreeze prostate cancer cell viability when combined with freezing. 19,20 To this end, investigations were conducted to determine whether this was a result of Figure 3. Asynchronous versus synchronous PC-3 cell response to freezing-alamarBlue metabolic activity data.…”

Section: Impact Of Calcitriol (Vd 3 ) and Freezing On Cell Cyclementioning

confidence: 99%