Biophysical and Biomechanical Effect of Low Intensity US Treatments on Pancreatic Adenocarcinoma 3D Cultures

Current developments in medical technology have focused on therapeutic treatments that selectively and effectively address specific pathological areas, minimizing side effects on healthy tissues. In this regard, many procedures have been developed to provide non-invasive therapy, for example therapeutic ultrasound (US). In the medical field, in particular in cancer research, it has been observed how ultrasounds can cause cell death and inhibit cell proliferation of cancer cells, while preserving healthy ones with almost negligible side effects. Various studies have shown that low intensity pulse ultrasound (LIPUS) and low intensity continuous ultrasound (LICUS) regulate the proliferation, cell differentiation and cavitation phenomena. Nowadays, there are poorly known aspects of low intensity US treatment, in terms of biophysical and biomechanical effects on target cells. The aim of this study is to set up an innovative apparatus for US treatment of pancreatic ductal adenocarcinoma (PDAC) cells, monitoring parameters such as acoustic intensity, acoustic pressure, stimulation frequency and treatment protocol. To this purpose, we have developed a custom-made set up for the US stimulation at 1.2 and 3 MHz of tridimensional (3D) cultures of PDAC cells (PANC-1, Mia Paca-2 and BxPc3 cells). Images of the 3D cultures were acquired, and the Calcein/PI assay was applied to detect US-induced cell death. Overall, the setup we have presented paves the way to an innovative protocol for tumor treatment. The system can be used either alone or in combination with small molecules or recombinant antibodies in order to propose a novel combined therapeutic approach.

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Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts

Bioscience Reports ◽

10.1042/bsr20140164 ◽

2015 ◽

Vol 35 (2) ◽

Cited By ~ 15

Author(s):

Li Sui ◽

Rui-Hong Zhang ◽

Ping Zhang ◽

Ke-Li Yun ◽

Hong-Cai Zhang ◽

...

Keyword(s):

Cell Death ◽

Side Effects ◽

Therapeutic Strategy ◽

Lead Toxicity ◽

Protective Role ◽

Molecular Processes ◽

Effective Therapeutic Strategy ◽

Mtorc1 Pathway ◽

Set Up

Lead is a metal with many recognized adverse health side effects, and yet the molecular processes in cardiofibroblasts underlying lead toxicity are still poorly understood. Our current findings will help to understand the role of lead-mediated toxicity in cardiofibroblasts, indicating that autophagy serves a protective role in response to ER stress, which affords to set up an effective therapeutic strategy for the numerous diseases related to lead-toxicity.

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Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation

Biological Chemistry ◽

10.1515/hsz-2019-0413 ◽

2020 ◽

Vol 401 (10) ◽

pp. 1153-1165 ◽

Cited By ~ 2

Author(s):

Antônio F. da Silva Filho ◽

Lucas B. Tavares ◽

Maira G. R. Pitta ◽

Eduardo I. C. Beltrão ◽

Moacyr J. B. M. Rêgo

Keyword(s):

Pancreatic Cancer ◽

Cell Death ◽

Mrna Expression ◽

Cancer Cells ◽

Ductal Adenocarcinoma ◽

Reverse Transcription Pcr ◽

Pancreatic Cancer Cells ◽

Through Flow ◽

Galectin 3

AbstractPancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.

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Kinase Inhibitors of DNA-PK, ATM and ATR in Combination with Ionizing Radiation Can Increase Tumor Cell Death in HNSCC Cells While Sparing Normal Tissue Cells

Genes ◽

10.3390/genes12060925 ◽

2021 ◽

Vol 12 (6) ◽

pp. 925

Author(s):

Eva-Maria Faulhaber ◽

Tina Jost ◽

Julia Symank ◽

Julian Scheper ◽

Felix Bürkel ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Side Effects ◽

Ionizing Radiation ◽

Cell Lines ◽

Normal Tissue ◽

Kinase Inhibitors ◽

Induced Response ◽

Tumor Control ◽

Tumor Cell Death

(1) Kinase inhibitors (KI) targeting components of the DNA damage repair pathway are a promising new type of drug. Combining them with ionizing radiation therapy (IR), which is commonly used for treatment of head and neck tumors, could improve tumor control, but could also increase negative side effects on surrounding normal tissue. (2) The effect of KI of the DDR (ATMi: AZD0156; ATRi: VE-822, dual DNA-PKi/mTORi: CC-115) in combination with IR on HPV-positive and HPV-negative HNSCC and healthy skin cells was analyzed. Cell death and cell cycle arrest were determined using flow cytometry. Additionally, clonogenic survival and migration were analyzed. (3) Studied HNSCC cell lines reacted differently to DDRi. An increase in cell death for all of the malignant cells could be observed when combining IR and KI. Healthy fibroblasts were not affected by simultaneous treatment. Migration was partially impaired. Influence on the cell cycle varied between the cell lines and inhibitors; (4) In conclusion, a combination of DDRi with IR could be feasible for patients with HNSCC. Side effects on healthy cells are expected to be limited to normal radiation-induced response. Formation of metastases could be decreased because cell migration is impaired partially. The treatment outcome for HPV-negative tumors tends to be improved by combined treatment.

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Apoptosis and inflammation

Mediators of Inflammation ◽

10.1155/s0962935195000020 ◽

1995 ◽

Vol 4 (1) ◽

pp. 5-15 ◽

Cited By ~ 68

Author(s):

C. Haanen ◽

I. Vermes

Keyword(s):

Cell Death ◽

Inflammatory Reaction ◽

Inflammatory Diseases ◽

Apoptotic Cell ◽

Cell Damage ◽

Target Cells ◽

Apoptotic Bodies ◽

Accidental Injury ◽

Inflammatory Reactions ◽

Inflammatory Processes

During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972) introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases.

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On the way home: a BCI-FES hand therapy self-managed by sub-acute SCI participants and their caregivers: a usability study

Journal of NeuroEngineering and Rehabilitation ◽

10.1186/s12984-021-00838-y ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Anna Zulauf-Czaja ◽

Manaf K. H. Al-Taleb ◽

Mariel Purcell ◽

Nina Petric-Gray ◽

Jennifer Cloughley ◽

...

Keyword(s):

Computer Literacy ◽

Hand Function ◽

Training Session ◽

Transfer Of Knowledge ◽

Wrist Flexion ◽

Hand Therapy ◽

The People ◽

Custom Made ◽

Cord Injury ◽

Set Up

Abstract Background Regaining hand function is the top priority for people with tetraplegia, however access to specialised therapy outwith clinics is limited. Here we present a system for hand therapy based on brain-computer interface (BCI) which uses a consumer grade electroencephalography (EEG) device combined with functional electrical stimulation (FES), and evaluate its usability among occupational therapists (OTs) and people with spinal cord injury (SCI) and their family members. Methods Users: Eight people with sub-acute SCI (6 M, 2F, age 55.4 ± 15.6) and their caregivers (3 M, 5F, age 45.3 ± 14.3); four OTs (4F, age 42.3 ± 9.8). User Activity: Researchers trained OTs; OTs subsequently taught caregivers to set up the system for the people with SCI to perform hand therapy. Hand therapy consisted of attempted movement (AM) of one hand to lower the power of EEG sensory-motor rhythm in the 8-12 Hz band and thereby activate FES which induced wrist flexion and extension. Technology: Consumer grade wearable EEG, multichannel FES, custom made BCI application. Location: Research space within hospital. Evaluation: donning times, BCI accuracy, BCI and FES parameter repeatability, questionnaires, focus groups and interviews. Results Effectiveness: The BCI accuracy was 70–90%. Efficiency: Median donning times decreased from 40.5 min for initial session to 27 min during last training session (N = 7), dropping to 14 min on the last self-managed session (N = 3). BCI and FES parameters were stable from session to session. Satisfaction: Mean satisfaction with the system among SCI users and caregivers was 3.68 ± 0.81 (max 5) as measured by QUEST questionnaire. Main facilitators for implementing BCI-FES technology were “seeing hand moving”, “doing something useful for the loved ones”, good level of computer literacy (people with SCI and caregivers), “active engagement in therapy” (OT), while main barriers were technical complexity of setup (all groups) and “lack of clinical evidence” (OT). Conclusion BCI-FES has potential to be used as at home hand therapy by people with SCI or stroke, provided it is easy to use and support is provided. Transfer of knowledge of operating BCI is possible from researchers to therapists to users and caregivers. Trial registration Registered with NHS GG&C on December 6th 2017; clinicaltrials.gov reference number NCT03257982, url: https://clinicaltrials.gov/ct2/show/NCT03257982.

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Potentially Curative Therapeutic Activity of NEO212, a Perillyl Alcohol-Temozolomide Conjugate, in Preclinical Cytarabine-Resistant Models of Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers13143385 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3385

Author(s):

Axel H. Schönthal ◽

Steve Swenson ◽

Radu O. Minea ◽

Hye Na Kim ◽

Heeyeon Cho ◽

...

Keyword(s):

Cell Death ◽

Acute Myeloid Leukemia ◽

Side Effects ◽

Anticancer Activity ◽

Myeloid Leukemia ◽

Perillyl Alcohol ◽

Therapeutic Activity ◽

Acute Myeloid

Despite progress in the treatment of acute myeloid leukemia (AML), the clinical outcome remains suboptimal and many patients are still dying from this disease. First-line treatment consists of chemotherapy, which typically includes cytarabine (AraC), either alone or in combination with anthracyclines, but drug resistance can develop and significantly worsen prognosis. Better treatments are needed. We are developing a novel anticancer compound, NEO212, that was created by covalent conjugation of two different molecules with already established anticancer activity, the alkylating agent temozolomide (TMZ) and the natural monoterpene perillyl alcohol (POH). We investigated the anticancer activity of NEO212 in several in vitro and in vivo models of AML. Human HL60 and U937 AML cell lines, as well as different AraC-resistant AML cell lines, were treated with NEO212 and effects on cell proliferation, cell cycle, and cell death were investigated. Mice with implanted AraC-sensitive or AraC-resistant AML cells were dosed with oral NEO212, and animal survival was monitored. Our in vitro experiments show that treatment of cells with NEO212 results in growth inhibition via potent G2 arrest, which is followed by apoptotic cell death. Intriguingly, NEO212 was equally potent in highly AraC-resistant cells. In vivo, NEO212 treatment strikingly extended survival of AML mice and the majority of treated mice continued to thrive and survive without any signs of illness. At the same time, we were unable to detect toxic side effects of NEO212 treatment. All in all, the absence of side effects, combined with striking therapeutic activity even in an AraC-resistant context, suggests that NEO212 should be developed further toward clinical testing.

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A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement.

Journal of Experimental Medicine ◽

10.1084/jem.181.6.2007 ◽

1995 ◽

Vol 181 (6) ◽

pp. 2007-2015 ◽

Cited By ~ 27

Author(s):

S Matsuoka ◽

Y Asano ◽

K Sano ◽

H Kishimoto ◽

I Yamashita ◽

...

Keyword(s):

Monoclonal Antibody ◽

Cell Death ◽

T Cell ◽

B Cells ◽

Interleukin 2 ◽

Cytolytic Activity ◽

Target Cells ◽

T And B Cells ◽

Fab Fragments ◽

T Cell Clone

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.

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Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient?

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211038136 ◽

2021 ◽

pp. 107815522110381

Author(s):

Esra Özyurt ◽

Serhat Özçelik ◽

Heves Sürmeli ◽

Mehmet Çelik ◽

Murat Ayhan ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

Side Effects ◽

Programmed Cell Death ◽

Adverse Events ◽

Checkpoint Inhibitors ◽

Host Cells ◽

Immunoglobulin G4 ◽

Programmed Cell Death 1 ◽

Recurrent Renal Cell Carcinoma

Introduction Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as “immune-related adverse events.” Case report We report a case of a 66-year-old male patient who was treated with nivolumab for recurrent renal cell carcinoma presented with hepatitis and adrenalitis. Three weeks after starting nivolumab, the patient had abdominal pain and weakness, and then aspartate and alanine transaminase levels were found to be elevated. Management and outcome Hepatitis was predicted to be due to nivolumab, because other causes were excluded. He started using oral methylprednisolone and then, hepatitis improved. However, while receiving methylprednisolone treatment, fludrocortisone was started with the pre-diagnosis of adrenalitis due to the persistence of fatigue, weakness, and hyponatremia and hyperkalemia. With both treatments, the patient's symptoms and sodium and potassium level returned to normal. Discussion This case emphasizes the need for patient's education and awareness of immune-related adverse events, and the importance of understanding the management of life-threatening complications of the checkpoint inhibitors, because these side effects require prompt recognition and treatment.

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Fas ligand mediates activation-induced cell death in human T lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.181.1.71 ◽

1995 ◽

Vol 181 (1) ◽

pp. 71-77 ◽

Cited By ~ 625

Author(s):

M R Alderson ◽

T W Tough ◽

T Davis-Smith ◽

S Braddy ◽

B Falk ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

Fas Ligand ◽

Significant Proportion ◽

Cell Receptor ◽

Target Cells ◽

Activated T Cells ◽

Activation Induced Cell Death ◽

Fas L

A significant proportion of previously activated human T cells undergo apoptosis when triggered through the CD3/T cell receptor complex, a process termed activation-induced cell death (AICD). Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in cytolysis. We demonstrate that these two pathways of apoptosis are causally related. Stimulation of previously activated T cells resulted in the expression of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell lines. The data indicate AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions.

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Optimization and evaluation of a blue light photoinitiating system for textile inkjet printing

Textile Research Journal ◽

10.1177/0040517518783346 ◽

2018 ◽

Vol 89 (10) ◽

pp. 1964-1974

Author(s):

Yi Huang ◽

Guangdong Sun ◽

Yating Ji ◽

Dapeng Li ◽

Qinguo Fan ◽

...

Keyword(s):

Blue Light ◽

Light Emitting Diode ◽

Absorption Efficiency ◽

Polymerization Rate ◽

Nozzle Clogging ◽

Light Emitting ◽

Custom Made ◽

Light Curing ◽

Set Up ◽

Pigment Ink

A blue light curing process was developed to solve the nozzle clogging challenge commonly encountered in conventional textile pigment printing, by using camphorquinone (CQ) and ethyl-4-dimethylaminobenzoate (EDMAB) as a photoinitiator combination and substituting oligomers and monomers for a polymeric binder. High light absorption efficiency was insured by closely matching the spectrum of the photoinitiator with a custom-made blue light light-emitting diode set-up. Kinetic analyses of such a CQ/EDMAB system indicated that the maximum polymerization rate of the monomer was proportional to [PI]0.5 and [I0]0.5, while excessive high photoinitiator concentration (>1 wt%) will decrease the polymerization rate because of the “filter effect.” With optimized blue light curable pigment ink formula and irradiation conditions, the photocurable pigment printed fabrics exhibited uniform and vibrant colors, clear outlines, and excellent wet and dry rubbing fastness of grades 4 and 4–5, respectively.

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