CPSI Biotech

Owego, NY, United States

CPSI Biotech

Owego, NY, United States

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Baust J.G.,Binghamton University State University of New York | Gage A.A.,State University of New York at Buffalo | Bjerklund Johansen T.E.,University of Oslo | Baust J.M.,CPSI Biotech
Cryobiology | Year: 2014

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, which 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. © 2013 Elsevier Inc.


PubMed | Binghamton University State University of New York and CPSI Biotech
Type: | Journal: Advances in experimental medicine and biology | Year: 2015

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, todays 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. No longer are samples providing for high immediate post-thaw viability adequate. Researchers are now requiring samples where not only is there high cell recovery but that the product recovered is physiologically and biochemically identical to its pre-freeze state at the genominic, proteomic, structural, functional and reproductive levels. Given this, biobanks are now facing the challenge of adapting strategies and protocols to address these needs moving forward. Recent studies have shown that the control and direction of the molecular response of cells to cryopreservation significantly impacts final outcome. This chapter provides an overview of the molecular stress responses of cells to cryopreservation, the impact of the apoptotic and necrotic cell death continuum and how studies focused on the targeted modulation of common and/or cell specific responses to freezing temperatures provide a path to improving sample quality and utility. This line of investigation has provided a new direction and molecular-based foundation guiding new research, technology development and procedures. As the use of and the knowledge base surrounding cryopreservation continues to expand, this path will continue to provide for improvements in overall efficacy and outcome.


PubMed | University of Oslo, State University of New York at Buffalo, Binghamton University State University of New York and CPSI Biotech
Type: Letter | Journal: Cryobiology | Year: 2014

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, which 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.


PubMed | University of Connecticut, Binghamton University State University of New York and CPSI Biotech
Type: | Journal: Advances in experimental medicine and biology | Year: 2016

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. While the adoption has been slow, discoveries including molecular control and buffering of cell stress response to CP as well as the development of new devices for improved sample freezing and thawing are providing for improved CP from both the processing and sample quality perspectives. Numerous studies have described the impact, mechanisms and points of control of cryopreservation-induced delayed-onset cell death (CIDOCD). In an effort to limit CIDOCD, efforts have focused on CP agent and freeze media formulation to provide a solution path and have yielded improvements in survival over traditional approaches. Importantly, each of these areas, new technologies and cell stress modulation, both individually and in combination, are now providing a new foundation to accelerate new research, technology and product development for which CP serves as an integral component. This chapter provides an overview of the molecular stress responses of cells to cryopreservation, the impact of the hypothermic and cell death continuums and the targeted modulation of common and/or cell specific responses to CP in providing a path to improving cell quality.


Baust J.G.,Binghamton University State University of New York | Bischof J.C.,University of Minnesota | Jiang-Hughes S.,University of Minnesota | Polascik T.J.,Duke University | And 3 more authors.
Prostate Cancer and Prostatic Diseases | Year: 2015

It is now recognized that the tumor microenvironment creates a protective neo-tissue that isolates the tumor from the various defense strategies of the body. Evidence demonstrates that, with successive therapeutic attempts, cancer cells acquire resistance to individual treatment modalities. For example, exposure to cytotoxic drugs results in the survival of approximately 20-30% of the cancer cells as only dividing cells succumb to each toxic exposure. With follow-up treatments, each additional dose results in tumor-associated fibroblasts secreting surface-protective proteins, which enhance cancer cell resistance. Similar outcomes are reported following radiotherapy. These defensive strategies are indicative of evolved capabilities of cancer to assure successful tumor growth through well-established anti-tumor-protective adaptations. As such, successful cancer management requires the activation of multiple cellular 'kill switches' to prevent initiation of diverse protective adaptations. Thermal therapies are unique treatment modalities typically applied as monotherapies (without repetition) thereby denying cancer cells the opportunity to express defensive mutations. Further, the destructive mechanisms of action involved with cryoablation (CA) include both physical and molecular insults resulting in the disruption of multiple defensive strategies that are not cell cycle dependent and adds a damaging structural (physical) element. This review discusses the application and clinical outcomes of CA with an emphasis on the mechanisms of cell death induced by structural, metabolic, vascular and immune processes. The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality. Our understanding of these mechanisms now supports adjunctive therapies that can augment cell death pathways. © 2015 Macmillan Publishers Limited All rights.


Robilotto A.T.,Binghamton University State University of New York | Baust J.M.,Binghamton University State University of New York | Van Buskirk R.G.,Binghamton University State University of New York | Gage A.A.,CPSI Biotech | And 2 more authors.
Prostate Cancer and Prostatic Diseases | Year: 2013

Background:Critical to the continual improvement of cryoablation efficacy is deciphering the biochemical responses of cells to low-temperature exposure. The identification of delayed-onset cell death has allowed for the manipulation of cellular responses through the regulation of apoptosis. We hypothesized that in addition to delayed apoptotic events associated with mild subfreezing temperatures (10 to -25 °C), cells exposed to ultra-low temperatures (<-30 °C) may undergo rapid, early-onset apoptosis.Methods:Human prostate cancer model and cells (PC-3) were exposed to temperatures of -60, -30 and -15 °C to simulate a cryoablative procedure. Using a combination of flow-cytometry, fluorescent microscopy and western blot analyses, samples were assessed at various times post thaw to identify the presence, levels and the pathways involved in cell death.Results:Exposure to temperatures <-30 °C yielded a significant apoptotic population within 30 min of thawing, peaking at 90 min (∼40%), and by 6 h, only necrosis was observed. In samples only reaching temperatures >-30 °C, apoptosis was not noted until 6-24 h post thaw, with the levels of apoptosis reaching ∼10% (-15 °C) and ∼25% (-30 °C) at 6 h post thaw. Further, it was found that early-onset apoptosis progressed through a membrane-mediated mechanism, whereas delayed apoptosis progressed through a mitochondrial path.Conclusions:These data demonstrate the impact of apoptotic continuum, whereby the more severe cryogenic stress activated the extrinsic, membrane-regulated pathway, whereas less severe freezing activated the intrinsic, mitochondrial-mediated path. The rapid induction and progression of apoptosis at ultra-low temperatures provides an explanation as to why such results have not previously been identified following freezing. Ultimately, an understanding of the events and signaling pathways involved in triggering apoptosis following freezing may provide a path for selective induction of the rapid-onset and delayed programmed cell death pathways in an effort to improve the overall cryoablation efficacy. © 2013 Macmillan Publishers Limited. All rights reserved.


Corwin W.L.,CPSI Biotech | Corwin W.L.,Binghamton University State University of New York | Baust J.M.,CPSI Biotech | Baust J.M.,Binghamton University State University of New York | And 3 more authors.
Cryobiology | Year: 2014

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. In this study hMSC were exposed to cold storage (4. °C) for varying intervals in three different media. The addition of resveratrol or salubrinal was studied to determine if either could improve cell tolerance to cold. A rapid elevation in apoptosis at 1. h post-storage as well as increased levels of necrosis through the 24. h of recovery was noted in samples. The addition of resveratrol resulted in significant improvements to hMSC survival while the addition of salubrinal revealed a differential response based on the media utilized. Decreases in both apoptosis and necrosis together with decreased cell stress/death signaling protein levels were observed following modulation. Further, ER stress and subsequent unfolded protein response (UPR) stress pathway activation was implicated in response to hMSC hypothermic storage. This study is an important first step in understanding hMSC stress responses to cold exposure and demonstrates the impact of targeted molecular modulation of specific stress pathways on cold tolerance thereby yielding improved outcomes. Continued research is necessary to further elucidate the molecular mechanisms involved in hypothermic-induced hMSC cell death. This study has demonstrated the potential for improving hMSC processing and storage through targeting select cell stress pathways. © 2014 Elsevier Inc.


Patent
Cpsi Biotech | Date: 2011-02-15

A cryogenic medical device is disclosed for use in minimally invasive surgical procedures. Various configurations of cryoprobes are designed in combination with a clamp to form a cryoclamp for the treatment of damaged, diseased, cancerous or other unwanted tissues. The device is an integrated cryoablation probe with a hinged clamp that allows for single entry into the chest cavity through a thorascopic port, by surgical or other means. The integrated cryoablation probe allows for the clamping of tissue as well as freezing with a single device. The clamp acts as an outer sheath so that when closed, directional freezing of the cryoprobe is achieved on the opposing probe surface away from the clamp or on an internal surface that is between the clamp. The cryoclamp may be a removable attachment or integrated into the unitary device.


Patent
Cpsi Biotech | Date: 2011-03-31

One embodiment of the invention is a flexible cryogenic probe tip. The flexible probe tip has a linear freeze zone at a distal end of the probe that allows for its placement and precisely controlled movements. The flexible cryogenic probe tip precisely conforms to the target tissue surface to create a linear lesion. In addition, the probe tip is steerable to facilitate proper placement with minimal access points into a patients body. Various configurations of the flexible probe tip allow it to conform and ablate tissue of many sizes, shapes, and/or dimensions. Methods of utilizing the cryogenic probe tip include steps of positioning the distal end at a tissue site for at least one ablative procedure, maneuvering the distal end to the tissue site, directing a cryogen from the supply source to the distal end, controlling a flow of cryogen from the supply source to the distal end and back to the supply source, and segmenting control of the distal end mechanically or through the step of controlling the flow of cryogen.


Patent
Cpsi Biotech | Date: 2011-03-17

An embodiment of the invention is a cryo-connector, a connector that allows for the delivery and return of a cryogen in an axial configuration. In one embodiment, the connector is a tri-axial configuration allowing for the delivery and return of pressurized cryogen as well as the application of an independent vacuum in the third lumen. Various configurations, however, may accommodate any number of luminary spaces such that cryogen (or other fluids) and/or vacuum spaces may be created in a fashion complementary to the components that the connector will affix to and interconnect with. The connectors can be utilized with any low temperature, cryogenic device and at varying pressures.

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