scholarly journals A Therapeutic Role for Survivin in Mitigating the Harmful Effects of Ionizing Radiation

Sarcoma ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Katherine H. Carruthers ◽  
Gregory Metzger ◽  
Eugene Choi ◽  
Matthew J. During ◽  
Ergun Kocak
Keyword(s):  
Ionizing Radiation ◽  
Gait Analysis ◽  
Survivin Expression ◽  
Control Group ◽  
Treatment Protocols ◽  
Yellow Fluorescence Protein ◽  
Oncological Treatment ◽  
Normal Tissues ◽  
Negative Side Effects ◽  
Extent Of Damage

Background. Radiation therapy is a form of adjuvant care used in many oncological treatment protocols. However, nonmalignant neighboring tissues are harmed as a result of this treatment. Therefore, the goal of this study was to induce the production of survivin, an antiapoptotic protein, to determine if this protein could provide protection to noncancerous cells during radiation exposure.Methods. Using a murine model, a recombinant adenoassociated virus (rAAV) was used to deliver survivin to the treatment group and yellow fluorescence protein (YFP) to the control group. Both groups received targeted radiation. Visual inspection, gait analysis, and tissue histology were used to determine the extent of damage caused by the radiation.Results. The YFP group demonstrated ulceration of the irradiated area while the survivin treated mice exhibited only hair loss. Histology showed that the YFP treated mice experienced dermal thickening, as well as an increase in collagen that was not present in the survivin treated mice. Gait analysis demonstrated a difference between the two groups, with the YFP mice averaging a lower speed.Conclusions. The use of gene-modification to induce survivin expression in normal tissues allows for the protection of nontarget areas from the negative side effects normally associated with ionizing radiation.

Prevalence of Thyroid Diseases in an Occupationally Radiation Exposed Group: A Cross-Sectional Study in a University Hospital of Southern Italy

2019 ◽  
Vol 19 (6) ◽  
pp. 803-808 ◽  
Author(s):  
Luigi Vimercati ◽  
Luigi De Maria ◽  
Francesca Mansi ◽  
Antonio Caputi ◽  
Giovanni M. Ferri ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Healthcare Workers ◽  
Southern Italy ◽  
Cross Sectional Study ◽  
Thyroid Diseases ◽  
University Hospital ◽  
Control Group ◽  
Sectional Study ◽  
Cross Sectional ◽  
Exposed Workers

Background: Thyroid diseases occur more frequently in people exposed to ionizing radiation, but the relationship between occupational exposure to ionizing radiation and thyroid pathologies still remains unclear. Objective: To evaluate the prevalence of thyroid diseases in healthcare workers exposed to low-level ionizing radiation compared with a control group working at the University Hospital of Bari, Southern Italy, and living in the same geographical area, characterized by mild iodine deficiency. Methods: We ran a cross-sectional study to investigate whether healthcare workers exposed to ionizing radiation had a higher prevalence of thyroid diseases. Four hundred and forty-four exposed healthcare workers (241 more exposed, or “A Category”, and 203 less exposed, or “B Category”) and 614 nonexposed healthcare workers were enrolled during a routine examination at the Occupational Health Unit. They were asked to fill in an anamnestic questionnaire and undergo a physical examination, serum determination of fT3, fT4 and TSH, anti-TPO ab and anti-TG ab and ultrasound neck scan. Thyroid nodules were submitted to fine needle aspiration biopsy when indicated. Results: The prevalence of thyroid diseases was statistically higher in the exposed workers compared to controls (40% vs 29%, adPR 1.65; IC95% 1.34-2.07). In particular, the thyroid nodularity prevalence in the exposed group was approximately twice as high as that in the controls (29% vs 13%; adPR 2.83; IC95% 2.12-3.8). No statistically significant association was found between exposure to ionizing radiation and other thyroid diseases. Conclusion: In our study, mild ionizing radiation-exposed healthcare workers had a statistically higher prevalence of thyroid diseases than the control group. The results are likely due to a closer and more meticulous health surveillance programme carried out in the ionising radiation-exposed workers, allowing them to identify thyroid alterations earlier than non-exposed health staff.

Effects of LncRNA HOX Transcript Antisense RNA Targeting miRNA-761 on Cervical Cancer Cell Proliferation and Apoptosis

2021 ◽  
Vol 11 (10) ◽  
pp. 2081-2086
Author(s):  
Bin Qiu ◽  
Hui Zhong ◽  
Shenqiu Ming ◽  
Chunxia Zhu
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Control Group ◽  
Normal Tissues ◽  
Cell Clones ◽  
Cervical Cancer Cells ◽  
Set Up ◽  
Cancer Tissues ◽  
Lncrna Hotair

Abnormal LncRNA HOTAIR level is correlated with various cancers and miR-761 can inhibit cancers. LncRNA HOTAIR targets miR-761 by StarBase 2.0 analysis. Our study investigated whether LncRNA HOTAIR can affect cervical cancer cells by regulating miR-761. The control group (NC group), LncRNA HOTAIR group and LncRNA HOTAIR + miR-761 Mimics group were set up to measure LncRNA HOTAIR and miR-761 level by qRT-PCR. Dual fluorescein reporter assay assessed whether miR-761 binds LncRNA HOTAIR. Western blot was used to measure Cyclin D1, Bcl-2 and Tubulin expression and clone formation assay was to assess cell proliferation and Annexin VFITC/PI staining was to detect cell apoptosis. Compared with normal tissues, LncRNA HOTAIR level was significantly higher in cervical cancer tissues, while miR-761 was lower (P < 0.01). LncRNA HOTAIR targets miR-761. Compared with NC group, CyclinD1 and Bcl-2 in LncRNA HOTAIR group were significantly increased (P < 0.01), which were significantly lower in LncRNA HOTAIR + miR-761 Mimics group (P < 0.05). Compared to NC group, miR-761 in LncRNA HOTAIR group was significantly reduced (P < 0.01) and elevated by miR-761 Mimics. In addition, compared to NC group, the number of cell clones in LncRNA HOTAIR group was increased, cell proliferation was increased, and number of apoptotic cells was decreased, which were all reversed in the LncRNA HOTAIR + miR-761 Mimics group. LncRNA HOTAIR targets miR-761, promotes cell proliferation and reduces cell apoptosis. miR-761 mimics can partially prevent the effects of LncRNA HOTAIR.

scholarly journals Persistent Increased Frequency of Genomic Instability in Women Diagnosed with Breast Cancer: Before, during, and after Treatments

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
André Luiz Pinho Sobral ◽  
Jaqueline Nascimento Picada ◽  
Ivana Grivicich ◽  
Antonio Luiz Gomes Júnior ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Comet Assay ◽  
Peripheral Blood ◽  
Micronucleus Test ◽  
Cancer Control ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Buccal Cells ◽  
Oncological Treatment

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient’s cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.

scholarly journals Interleukin 37 Expression was Negatively Associated with Pathological Grading in Human Gliomas

2021 ◽  
Author(s):  
Sheng Liu ◽  
Ying Ba ◽  
Chenglong Li ◽  
Mengyang Xing ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Survival Time ◽  
Grade Level ◽  
Brain Injuries ◽  
Control Group ◽  
Normal Brain ◽  
Normal Tissues ◽  
Pathological Type ◽  
Tumor Tissues ◽  
Clinicopathologic Factors ◽  
Immunohistochemical Techniques

Abstract Background: Little is known about the roles of interleukin 37 (IL-37), a newly identified cytokine, in the pathogenesis of cancer. In this study, we aimed to determine the expression of IL-37 in gliomas with different pathological grades and evaluated its effects on survival. Methods: Ninety-five participants with different pathological grades of glioma were included in this study, which were classified into grade I-II (n=27), grade III (n=30), and grade IV (n=38). Ten normal brain tissues that were resected for intracranial decompression after traumatic brain injuries served as control group. The expression of IL-37 mRNA and protein in glioma tissues was determined using Real-time PCR and immunohistochemical techniques. The association between IL-37 expression and various clinicopathologic factors was evaluated. Results: IL-37 mRNA was expressed in normal tissues and tumor tissues, and the expression of IL-37 in tumor tissues were significantly higher than normal brain tissue (p<0.05). IL-37 expression showed decline with the increase of grade level. The expression of IL-37 was significantly lower in glioma tissues of a high malignancy compared with the glioma tissues of a low malignancy. Patients with low IL-37 expression showed a shorter survival time. Conclusions: Low IL-37 expression was negatively correlated with pathological grade, rather than pathological type. Low IL-37 was positively correlated with survival time. Thus, IL-37 maybe plays an inhibitory role in glioma progression.

scholarly journals Propolis Protective Effects Against Doxorubicin-Induced Multi-Organ Toxicity via Suppression of Oxidative Stress, Inflammation, Apoptosis, and Histopathological Alterations in Female Albino Rats

2021 ◽  
Vol 12 (2) ◽  
pp. 1762-1777
Keyword(s):  
Oxidative Stress ◽  
Large Scale ◽  
Protective Efficacy ◽  
Biological Activities ◽  
Female Rats ◽  
Control Group ◽  
Albino Rats ◽  
Protective Agent ◽  
Protective Effects ◽  
Treatment Protocols

Doxorubicin (DOX) is effective chemotherapy in several malignancies, but large-scale toxicities limit its clinical usefulness. Propolis has been reported to exhibit a broad spectrum of biological activities. We aim to assess the protective efficacy of propolis against DOX-induced multi-toxicity in female rats. Forty female rats were divided into four groups: control group; Group (P) were administrated oral propolis (100 mg/kg once daily for 28 days); Group (P+DOX) were injected with a single intraperitoneal dose of DOX (20 mg/kg i.p at 24th day after the propolis administration) and group (DOX) were injected with doxorubicin only. Estimation of cardiac, renal and hepatic injury markers, apoptosis and pro-inflammatory cytokines were done using sera. Also, liver and heart tissue samples were collected to determine GSH and MDA as oxidative stress markers. In addition to histopathological and immunohistochemical examination of Cytochrome-C and Connexin43 on lysed myocardium, liver, kidney and lung tissues. Doxorubicin toxicity caused marked deteriorations of measured parameters through the different mechanisms in different body organs. However, pre-treatment with propolis significantly ameliorated these alterations. Thus propolis can ameliorate the DOX-induced experimental multi-toxicity as cardiomyopathy, hepatotoxicity, nephritis and pneumonia. Thus, it could be a promising protective agent in DOX treatment protocols.

Efficacy of an antigravity treadmill on functional outcome in non-operatively treated pelvic fractures: a prospective pilot study

2019 ◽  
Vol 26 (11) ◽  
pp. 1-9
Author(s):  
Ralf Henkelmann ◽  
Michael Schäfer ◽  
Andreas Höch ◽  
Christian Leps ◽  
Martin Busse ◽  
...  
Keyword(s):  
Pilot Study ◽  
Gait Analysis ◽  
Rating Scale ◽  
Intervention Group ◽  
Training Session ◽  
Pelvic Fractures ◽  
Control Group ◽  
Gait Patterns ◽  
Prospective Pilot Study ◽  
Normal Gait

Background/Aims Treating pelvic fractures non-operatively is possible. The immobilisation stage of recovery requires different adjustment processes compared to those used in operative treatment. The aim of the present study was to prove the additional benefit an antigravity treadmill can have on patients with non-operatively treated pelvic fractures. Methods A prospective pilot study, including patients with non-operatively treated pelvic fractures as the intervention group and healthy volunteers as a control group, was undertaken. Patients of the intervention group participated in a training session with an antigravity treadmill every 3 days for a total of 40 days, in addition to physiotherapy, lymph drainage massage and manual therapy. Patients were evaluated using a dynamic gait index, and a numeric rating scale on three successive dates, to assess their pain. A standardised gait analysis was also carried out. Results The intervention group comprised 9 patients, while 33 patients made up the control group. All patients completed the protocols and experienced a significant decrease in pain and increase of mobility. Gait analysis showed that by the 40-day follow-up, patients in the intervention group had regained almost normal gait patterns when compared to the control group. At each time point, a significant improvement in patients' gait patterns could be seen. Conclusions The results concurred with previous studies, suggesting that the antigravity treadmill is safe and that recovery to almost normal gait patterns is possible, while the comparison to a healthy group strengthened the data. The present prospective study thus showed promising results regarding the efficacy of the antigravity treadmill, despite study limitations.

scholarly journals Effects of Passive Hydrotherapy WATSU (WaterShiatsu) in the Third Trimester of Pregnancy: Results of a Controlled Pilot Study

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Agnes M. Schitter ◽  
Marko Nedeljkovic ◽  
Heiner Baur ◽  
Johannes Fleckenstein ◽  
Luigi Raio
Keyword(s):  
Pilot Study ◽  
Pregnant Women ◽  
Qualitative Data ◽  
Passive Control ◽  
Intervention Group ◽  
Treatment Method ◽  
Control Group ◽  
Third Trimester ◽  
Therapeutic Benefits ◽  
Negative Side Effects

Background. WATSU (WaterShiatsu) is a complementary therapeutic treatment method comprising passive stretches and massage techniques administered in 35°C warm water. Pregnant women claim safe methods to reduce pain, stress, and fatigue. Therefore, we conducted a pilot study evaluating the effects of WATSU on pregnancy-related complaints in third trimester pregnant women.Methods. Nine healthy pregnant women at gestational week ≥34 were included in an intervention group (receiving WATSU) and compared to eight women in a passive control group (receiving no treatment). WATSU was performed on days 1 and 4 of the study, accompanied by ultrasound examinations. Outcomes include physiological and psychometric as well as qualitative data. Participants in the control group completed questionnaires only.Results. WATSU was found to significantly lower participants’ levels of stress and pain and to improve their mental health-related quality of life and mood. In comparison to the passive control group, participants in the intervention group reported reduction in perceived stress from day 1 to day 8 (P=0.036, Cohen’sf=0.57). Qualitative data indicate that WATSU was appreciated as enjoyable and deeply relaxing. No negative side effects were reported.Conclusion. Our findings support the notion that WATSU yields therapeutic benefits for pregnant women and warrant further research. This study has been registered at ClinicalTrials.gov:NCT01708018.

scholarly journals Gait Analysis and Knee Kinematics in Patients with Anterior Cruciate Ligament Rupture: Before and After Reconstruction

2020 ◽  
Vol 10 (10) ◽  
pp. 3378
Author(s):  
Dmitry Skvortsov ◽  
Sergey Kaurkin ◽  
Alexander Akhpashev ◽  
Aljona Altukhova ◽  
Alexander Troitskiy ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Gait Analysis ◽  
Acl Reconstruction ◽  
Cruciate Ligament ◽  
Surgical Reconstruction ◽  
Control Group ◽  
Cycle Duration ◽  
Post Surgery ◽  
Before And After ◽  
Anterior Cruciate

The objective of the study was to evaluate the clinical, functional, and biomechanical symptoms in patients with anterior cruciate ligament (ACL) rupture before and after ACL reconstruction. The study enrolled 20 patients and 20 healthy subjects as controls. Walking biomechanics was assessed at three time points: before surgery and three months and a year or more after surgical reconstruction. Impact loads on both sides differed significantly from the respective values before surgery (p<0.05). Walking cycle duration decreased with time after surgery. On both sides (affected and unaffected), hip movement amplitudes were significantly smaller than in control (p<0.05). They remained so in the follow-up periods after the reconstruction. Before ACL reconstruction, the amplitude of the main flexion of the knee was significantly reduced both on the affected and unaffected sides. The amplitude gradually increased after the reconstruction, and a year post-surgery, it reached, on the operated side, the same values as in the control group. Complete functional recovery of the knee joint was not achieved within a year after the ACL surgical reconstruction. The remaining changes, however, were not clinically pronounced and could only be detected by instrumental gait analysis. The compensatory processes developed bilaterally, in both the hip and knee joints.

Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2021-2021
Author(s):  
A. B. Heimberger ◽  
G. E. Archer ◽  
D. A. Mitchell ◽  
D. D. Bigner ◽  
R. J. Schmittling ◽  
...  
Keyword(s):  
Immune Responses ◽  
Phase Ii ◽  
Drug Hypersensitivity ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Keyhole Limpet Hemocyanin ◽  
Peptide Sequence ◽  
Control Group ◽  
Specific Gene ◽  
Normal Tissues

2021 Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBM and other neoplasms. The cancer vaccine CDX-110 is comprised of an EGFRvIII-specific peptide sequence linked to keyhole limpet hemocyanin (KLH). Methods: A phase II multi-center trial assessed the immunogenicity and efficacy of CDX-110 in patients with newly-diagnosed, EGFRvIII+ GBM. After resection and radiation / TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression. Sequential cohorts received CDX-110 alone [ACTIVATE (n = 18)] or in combination with TMZ (200 mg/m2 x 5/28 days [ACT II A (n = 13)]) or (100 mg/m2 x 21/28 days [ACT II B (n=10)]). Results: Reversible systemic drug hypersensitivity reactions were seen in 1 ACTIVATE and 4 ACT II patients. Two patients had non-specific changes on MRI which were possibly due to the vaccine but which resolved. Despite grade 2 or 3 lymphopenia in all ACT II patients, EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Although ACT II B patients had more severe TMZ-induced lymphopenia, they developed greater EGFRvIII-specific immune responses (p = 0.028) when compared to ACT II A. EGFRvIII-specific IgG1 also increased in avidity with vaccination (Ka>>2x109M-1) in a randomly selected subset of 4 patients (p = 0.000068). Of the 23 recurrent tumors studied, 18 lost EGFRvIII expression (p = 0.001). There are no significant differences between ACT II A and B in estimated median TTP (18.5 vs. 14.9 months, p = 0.31) and OS (23.6 vs. 19.9 months, p = 0.75). ACTIVATE TTP (14.2 months) and OS (26.0 months) and ACT II TTP (15.2 months) and OS (23.6 months) compare favorably to a TMZ-treated, matched historical control group (TTP: 6.3 months; OS: 15.0 months). Conclusions: CDX-110 vaccination in patients with GBM appears very promising. TMZ enhances immune responses despite lymphodepletion. CDX-110 with simultaneous TMZ is under further investigation in a larger phase II trial. [Table: see text]

T-cell redirected killing and cure of pancreatic and gastric cancer xenografts by targeting Trop-2.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 262-262
Author(s):  
David M. Goldenberg ◽  
Edmund A. Rossi ◽  
Diane L Rossi ◽  
Thomas M. Cardillo ◽  
Chien-Hsing Chang
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Control Group ◽  
Calcium Signal ◽  
Target Cells ◽  
Normal Tissues

262 Background: Trop-2 [also called tumor-associated calcium signal transducer 2 (TACSTD2), EGP-1 (epithelial glycoprotein-1), GA733-1, or M1S1]is a 35 kDa transmembrane glycoprotein that is overexpressed relative to normal tissues in a variety of human cancers, including pancreatic and gastric carcinomas, where increased expression correlates with poor prognosis. Trop-2 appears to be more tumor-specific than the related molecule, EpCAM (Trop-1). MT110, the EpCAM antibody x CD3 bispecific T-cell engager (BiTE), is currently undergoing a Phase I study in various solid tumors, including lung, gastric, colorectal, breast, prostate, and ovarian cancers. We produced a similar T-cell redirecting bispecific tandem scFv, E1-3, using the variable domains of hRS7 (humanized anti-Trop-2 mAb) and Okt-3 (anti-CD3 mAb). Methods: T-cell activation, cytokine induction and cytotoxicity were evaluated ex vivo using PBMCs or purified T cells with human pancreatic (Capan-1 and BxPC3) and gastric (NCI-N87) cancer cell lines as target cells. In vivo activity was assayed with NCI-N87 xenografts that were inoculated s.c. in a mixture with twice the number of human PBMCs and matrigel. Results: In the presence of target cells and PBMCs, E1-3 potently induced T-cell activation, proliferation, and dose-dependent cytokine production of IL-2 (>2 ng/mL), IL-6 (>1 ng/mL), IL-10 (>7 ng/mL), TNF-α (>1 ng/mL) and IFN-γ (>50 ng/mL). In vitro, E1-3 mediated a highly potent T-cell lysis of BxPC3 [IC50=0.09(±0.04) pM], Capan-1 [IC50=1.2(±1.1) pM] and NCI-N87 [IC50=1.2(±1.2) pM] target cells. In vivo, two 50-µg doses of E1-3 given three days apart cured all of the mice (N=8) bearing NCI-N87 xenografts (P=0.0005; Log-Rank). Tumors in the control group (PBMCs only) reached the endpoint (TV>1 cm3) with a median of 39.5 days. All mice remained tumor-free in the E1-3 group at 78 days. Conclusions: Trop-2 is an attractive target for T-cell-mediated killing of pancreatic, gastric and other epithelial cancers.

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