scholarly journals Effects of low intensity pulsed ultrasound on expression of B-cell lymphoma-2 and BCL2-Associated X in premature ovarian failure mice induced by 4-vinylcyclohexene diepoxide

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haopeng Xu ◽  
Yi Xia ◽  
Juan Qin ◽  
Jie Xu ◽  
Chongyan Li ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Hormone Secretion ◽  
B Cell Lymphoma ◽  
Sex Hormone ◽  
Control Group ◽  
Follicular Atresia ◽  
Pulsed Ultrasound ◽  
Vinylcyclohexene Diepoxide ◽  
Low Intensity Pulsed Ultrasound ◽  
And Control

Abstract Background Premature ovarian failure (POF) is a common disease in the field of Gynecology. Low intensity pulsed ultrasound (LIPUS) can promote tissue repair and improve function. This study was performed to determine the effects of LIPUS on granulosa cells (GCs) apoptosis and protein expression of B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) in 4-vinylcyclohexene diepoxide (VCD)-induced POF mice and investigate the mechanisms of LIPUS on ovarian function and reserve capacity. Methods The current POF mice model was administrated with VCD (160 mg/kg) by intraperitoneal injection for 15 consecutive days. The mice were divided into the POF group, LIPUS group and control group. In the LIPUS group, the right ovary of mice was treated by LIPUS (acoustic intensity was 200 mW/cm2, frequency was 0.3 MHz, and duty cycle was 20%) for 20 min, 15 consecutive days from day 16. The mice of the POF group and control group were treated without ultrasonic output. The basic observation and body weight were recorded. Hematoxylin and eosin staining (H&E staining) and enzyme-linked immunosorbent assay (ELISA) were applied to detect ovarian follicle development, ovarian morphology and sex hormone secretion. Ovarian GCs apoptosis was detected by TUNEL assay and immunohistochemistry. Results The results showed that VCD can induce estrus cycle disorder, follicular atresia, sex hormone secretion decreased and GCs apoptosis in mice to establish POF model successfully. LIPUS significantly promoted follicular development, increased sex hormone secretion, inhibited excessive follicular atresia and GCs apoptosis. The mechanism might be achieved by increasing the protein expression of Bcl-2 and decreasing the expression of Bax in ovaries. Conclusions LIPUS can improve the POF induced by VCD. These findings have the potential to provide novel methodological foundation for the future research, which help treat POF patients in the clinic.

scholarly journals Effects of Low Intensity Pulsed Ultrasound on Expression of Bax and Bcl-2 in Premature Ovarian Failure Mice Induced by 4-Vinylcyclohexene Diepoxide

2021 ◽  
Author(s):  
Haopeng Xu ◽  
Yi Xia ◽  
Juan Qin ◽  
Jie Xu ◽  
Chongyan Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Ovarian Failure ◽  
Control Group ◽  
Common Disease ◽  
Follicular Atresia ◽  
Pulsed Ultrasound ◽  
Vinylcyclohexene Diepoxide ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
And Control

Abstract BackgroundPremature ovarian failure (POF) is a common disease in the field of gynecological. This study was performed to determine the effects of low intensity pulsed ultrasound (LIPUS) on granulosa cells (GCs) apoptosis and protein expression of Bax and Bcl-2 in 4-vinylcyclohexene diepoxide (VCD)-induced POF mice. The aim of this research is to investigate the mechanisms of LIPUS on ovarian function and reserve capacity.MethodsThe current POF mice model was administrated with VCD (160 mg/kg) by intraperitoneal injection for 15 consecutive days. The mice were divided into POF group, LIPUS group and control group. In the LIPUS group, the right ovary of mice was treated by LIPUS (acoustic intensity was 200 mW/cm2, frequency was 0.3 MHz, and duty cycle was 20%) for 20 minutes, 15 consecutive days from day 16. The mice of the POF group and control group were treated without ultrasonic output. The basic observation, Hematoxylin and eosin staining (H&E staining), TUNEL assay and immunohistochemistry were applied to detect the results.ResultsThe results showed that VCD can induce estrus cycle disorder, follicular atresia and GCs apoptosis in mice to establish POF model successfully. LIPUS significantly promoted follicular development, inhibited excessive follicular atresia and GCs apoptosis. The mechanism may be achieved by increasing the protein expression of Bcl-2 and decreasing the expression of Bax in ovaries.ConclusionsThese findings have the potential to provide novel methodological foundation for the future research, which help treat POF patients in the clinic.

scholarly journals Effects of low intensity pulsed ultrasound to reduce the effusion volumes and pain with knee osteoarthritis: a randomized controlled trial

2018 ◽  
Vol 5 (1) ◽  
pp. 77
Author(s):  
P. Shanmuga Raju ◽  
Chokkarapu Ramu ◽  
N. S. Harshavardhan ◽  
K. Rajender ◽  
G. Sachin
Keyword(s):  
Randomized Controlled Trial ◽  
Knee Osteoarthritis ◽  
Controlled Trial ◽  
Control Group ◽  
Ultrasound Therapy ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Randomized Controlled ◽  
And Control

<p class="abstract"><strong>Background:</strong> The study aim was to determine the effect of low intensity pulsed ultrasound therapy to reduce the effusion volumes and pain in patients with Knee OA.</p><p class="abstract"><strong>Methods:</strong> This study design was randomized controlled trial. Total 50 patients diagnosed with Knee osteoarthritis were randomly assigned to two groups. Group I was using treatment of low intensity pulsed ultrasound therapy and group II was administered TENS with home exercise respectively. Treatments were 6 days per week and duration of 2 week. The amount of effusion volume will be measured via ultrasonograpy in knee.<strong></strong></p><p class="abstract"><strong>Results:</strong> The<strong> </strong>maximum number of cases are lying in age group &gt;60 years which is 28% and 40% in cases and control group respectively and age distribution in both the group is statistically not significant. The mean age of patients in cases and control group is 57.08±7.40 years and 58.04±9.93 years respectively.</p><p class="abstract"><strong>Conclusions:</strong> Low intensity pulsed ultrasound therapy significantly reduced the effusion volumes and pain in patients with knee osteoarthritis.</p>

Low-intensity pulsed ultrasound promotes repair of 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in SD rats

2021 ◽  
Author(s):  
Juan Qin ◽  
Junlin Chen ◽  
Haopeng Xu ◽  
Yi Xia ◽  
Wentao Tang ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Premature Ovarian Insufficiency ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Pulsed Ultrasound ◽  
Ovarian Insufficiency ◽  
Vinylcyclohexene Diepoxide ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Sd Rats

Abstract Women with premature ovarian insufficiency (POI) may be more vulnerable to a variety of health risks. To seek a new method to treat the disease, the effects of low intensity pulsed ultrasound (LIPUS) on promoting repair of ovarian injury in female SD rats induced by 4-vinylcyclohexene diepoxide (VCD) were explored in this research. A total of 24 female SD rats were subjected to intraperitoneal injection of VCD to induce POI. Successful modeling was achieved in 22 rats, which were then randomized into VCD + LIPUS group (n=13) and VCD group (n=9). The control group (n=5) was injected with equal normal saline. Hematoxylin and eosin staining (H&E staining), enzyme-linked immunosorbent assay (ELISA), western-blot analysis, scanning electron microscope (SEM), immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay were applied to detect the results. The results indicated that rats in the VCD group showed disorder in the estrous cycle, the number of atresia follicles and apoptosis granulosa cells increased (P &lt; 0.05). After the LIPUS treatment, the estrous cycle recovered, the number of follicles increased (P &lt; 0.05), the level of E2 and AMH enhanced (P &lt; 0.05) and the FSH decreased (P &lt; 0.05). The expression of NF-κB p65, TNFα, Bax, ATF4 and caspase-3 in ovarian tissue significantly decreased (P &lt; 0.05). These findings showed that LIPUS could promote the repair of the VCD induced ovarian damage in SD rats, which has the potential to be further applied in the clinic.

Abstract 12836: Low-Intensity Pulsed Ultrasound Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia -Potential Involvement of Mechanotransduction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomohiko Shindo ◽  
Kenta Ito ◽  
Kenichiro Hanawa ◽  
Kentaro Aizawa ◽  
Takashi Shiroto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Porcine Model ◽  
Left Ventricular ◽  
Control Group ◽  
Β1 Integrin ◽  
Vascular Endothelial ◽  
Pulsed Ultrasound ◽  
Caveolin 1 ◽  
Low Intensity Pulsed Ultrasound ◽  
Chronic Myocardial Ischemia

Purpose: Despite recent progress in the management of ischemic heart disease (IHD), the number of patients with severe IHD is increasing. In this study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD and to elucidate the underlying molecular mechanisms for the LIPUS-induced angiogenesis. Methods and Results: We first confirmed that the LIPUS up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle in cultured human vascular endothelial cells (HUVECs). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n=28). The heart was treated with either sham or LIPUS (32-cycle, 20 min) at 3 different short axis levels (n=14 each). Four weeks after the therapy, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05), whereas it remained unchanged in the control group. Capillary density and regional myocardial blood flow in the ischemic region were also increased in the LIPUS group but not in the control group. The protein expressions of VEGF, eNOS and bFGF in the ischemic area were enhanced in the LIPUS group compared with the control group. To further examine the signaling pathways responsible for the LIPUS-induced angiogenesis, HUVECs were transfected with siRNA or scrambled siRNA of either β1 integrin or caveolin-1. Knockdown of either β1 integrin or caveolin-1 with siRNA suppressed the LIPUS-induced up-regulation of VEGF. siRNA-mediated suppression of either focal adhesion kinase (FAK) or Fyn also inhibited the LIPUS-induced up-regulation of VEGF. Knockdown of these molecules with siRNA was confirmed with real-time PCR. Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD and that β1 integrin and caveolin-1 may be involved in underlying molecular mechanisms for the beneficial effects of the LIPUS.

scholarly journals Histological and Radiological Evaluation of Low-Intensity Pulsed Ultrasound Versus Whole Body Vibration on Healing of Mandibular Bone Defects in Rats

Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 457
Author(s):  
Milad Etemadi Sh ◽  
Nan-Chen Hsieh ◽  
Seyed Shahin Movahed Mohammadi ◽  
Shahrooz Momeni ◽  
Seyed Mohammad Razavi ◽  
...  
Keyword(s):  
Bone Density ◽  
Whole Body Vibration ◽  
Bone Defects ◽  
Whole Body ◽  
Control Group ◽  
Pulsed Ultrasound ◽  
Mandibular Bone ◽  
Body Vibration ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

Background and Objectives: Mechanical stimulation can improve the structural properties of the fracture site and induce the differentiation of different cell types for bone regeneration. This study aimed to compare the effect of low-intensity pulsed ultrasound stimulation (LIPUS) versus whole body vibration (WBV) on healing of mandibular bone defects. Materials and Methods: A mandibular defect was created in 66 rats. The rats were randomly divided into two groups of rats. Each group was subdivided randomly by three groups (n = 11) as follows: (I) control group, (II) treatment with LIPUS, and (III) treatment with WBV. The radiographic changes in bone density, the ratio of lamellar bone to the entire bone volume, the ratio of the newly formed bone to the connective tissue and inflammation grade were evaluated after 1 and 2 months. Results: LIPUS significantly increased the radiographic bone density change compared to the control group at the first and second month postoperatively (p < 0.01). WBV only significantly increased the bone density compared to the control group at the second month after the surgery (p < 0.01). Conclusions: Application of LIPUS and WBV may enhance the regeneration of mandibular bone defects in rats. Although LIPUS and WBV are effective in mandibular bone healing, the effects of LIPUS are faster and greater than WBV.

Association between Drug-Metabolizing Enzymes Polymorphisms and Diffuse Large B-Cell Lymphoma Risk in the Middle Eastern Population.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2043-2043
Author(s):  
Abdul K. Siraj ◽  
Rong Bu ◽  
Maha Al-Rasheed ◽  
Muna Ibrahim ◽  
Prashant Bavi ◽  
...  
Keyword(s):  
B Cell ◽  
Gene Polymorphisms ◽  
Cell Lymphoma ◽  
Middle Eastern ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Healthy Population ◽  
Environmental Carcinogens ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The last four decades have seen significant increase in the incidence of non-Hodgkin’s lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogens exposure related cancer risk and xenobiotic gene polymorphisms. We have undertaken a case control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1 and NQO1) were characterized in 187 individuals with DLBCL and 513 normal controls using polymerase chain reaction (PCR) based method. We chose the Saudi population as our study population because of its high consanguinity and its relative genetic homogeneity. The CYP1A1*2C, GSTT1 null and GSTP1 TT genotype were all found to be significant predictors of DLBCL risk (odds ratio 6.62, 11.94 and 3.42 respectively). None of the other alleles tested for proved to be significant indicators of DLBCL risk. These results suggest that the risk of DLBCL may indeed be associated with xenobiotics - metabolism and thus with environmental exposures. Table 1 Distribution of polymorphisms in healthy population and lymphoma patients. Polymorphism Genotype Control group Lymphoma patients p OR CYP1A1 −/− 384(76.5%) 104(78.8%) *2A −/2A 105(20.9%) 24(18.18%) 0.543 0.844 2A/2A 13(2.6%) 3(2.27%) 1.000 0.852 2A allele 13% 11.36% 0.659 0.839 CYP1A1 −/− 443(88.2%) 121(91.66%) *2B −/2B 50(10%) 10(7.58%) 0.505 0.732 2B/2B 9(1.8%) 1(0.76%) 0.697 0.407 2B allele 6.8% 4.55% 0.424 0.646 CYP1A1 −/− 497(99%) 125(94.7%) *2C −/2C 5(1%) 4(3.03%) 0.090 3.181 2C/2C 0 3(2.27%) 0.008 ND 2C allele 0.5% 3.8% 0.011 6.627 NQO1 C609T CC 295 (58.5%) 94 (62.7%) CT 177 (35.1%) 37 (24.7%) 0.051 0.656 TT 32 (6.4%) 19 (8.7%) 0.059 1.863 CT+TT 209 (41.5%) 56 (37.3%) 0.395 0.841 GSTP1 2293 CC 389 (76.3%) 113 (77.9%) CT 113 (22.2%) 24 (16.6%) 0.240 0.731 TT 8 (1.5%) 8 (5.5%) 0.017 3.422 CT+TT 121 (23.7%) 32 (22%) 0.739 0.910 GSTP1 A1578G AA 170 (33.5%) 56 (35%) AG 271 (53.5%) 96 (60%) 0.772 1.075 GG 66 (13%) 8 (5%) 0.013 0.368 AG+GG 337 (66.5%) 104 (65%) 0.774 0.937 GSTT1 P 385 (75%) 36 (20.1%) D 128 (25%) 143 (79.9%) <0.001 11.948 GSTM1 P 233 (45.4%) 91 (50%) D 280 (54.6%) 91 (50%) 0.300 0.832 Table 2 Distribution of combined GSTT1 and GSTM1 polymorphisms in case and control group. Genotype Control Case p OR Null: Complete deletion of GSTT1 and GSTM1 allele Present 423 (82.8%) 109 (60.9%) Double Null 88 (17.2%) 70 (39.1%) <0.001 3.087

STAT3 Silencing as a Novel Therapeutic Strategy for Activated B Cell-Type Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 926-926
Author(s):  
Anna Scuto ◽  
Maciej Kujawski ◽  
Claudia Kowolik ◽  
Hua Yu ◽  
Stephen Forman ◽  
...  
Keyword(s):  
B Cell ◽  
Target Genes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mrna Levels ◽  
Down Regulation ◽  
Protein Levels ◽  
Stat3 Signaling ◽  
Marrow Stroma ◽  
And Control

Abstract Abstract 926 Among the non-Hodgkin's lymphomas, the diffuse large B cell lymphoma (DLBCL) represents the most frequent (30%) of the aggressive lymphomas. Persistent STAT3 signaling contributes to malignant progression in many diverse human tumors. IL-6 and IL-10 are major activators of STAT3 signaling and are important in the pathophysiology of DLBCL. STAT3 has been found to be persistently active in activated B cells (ABC), which are non-germinal center-derived DLBCL cells. We studied the consequences of STAT3 inhibition on multiple biological functions in two representative human cell lines of this group, Ly3 and Ly10 cells. For this purpose, we established stably transduced STAT3 shRNA-expressing lentivirus Ly3 cells, control lentivirus Ly3 cells, STAT3 shRNA-expressing lentivirus Ly10 cells and control lentivirus Ly10 cells. The stable expression of STAT3 shRNA results in 40-50% reduction of total STAT3 protein levels in the STAT3 shRNA lentivirus Ly3 cells compared to the control lentivirus cells. STAT3 down-regulation induced inhibition of cell proliferation (approximately 40%). Ly3 cells respond to IL-10 more than to IL-6 in terms of proliferation; both cytokines induced less proliferation in the STAT3 shRNA lentivirus Ly3 cells compared to the control lentivirus Ly3 cells. Similar results were obtained in Ly10 cells, which respond more to IL-6 than to IL-10 in terms of proliferation. We analyzed by quantitative real-time PCR the mRNA levels of different STAT3 target genes and observed significant reduction in mRNA levels of Mcl-1, Bcl-xL and Survivin in STAT3 shRNA lentivirus Ly3 cells, as well as significant reduction of Cyclin D2 and up-regulation of STAT1 in shRNA lentivirus Ly10 cells. Comparison of these gene expression profiles with data obtained from other B-cell lymphoma cell lines revealed that silencing of STAT3 resulted in down-regulation of different STAT3 target genes in a cell-dependent manner. We also observed that both STAT3 and control lentivirus Ly3 cells have the same protein levels of c-Myc; nevertheless STAT3 silencing resulted in inhibition of IL-10-inducible upregulation of c-Myc. We next investigated the effect of STAT3 inhibition on adhesion to bone marrow stroma and chemotaxis. STAT3 shRNA lentivirus Ly3 cells adhered less to the stroma layer than control cells, and the longer they were cocultured with the stroma cells in the presence of serum-free media the more they lost the ability to adhere. Moreover, STAT3 shRNA lentivirus Ly3 cells had decreased capacity to migrate toward SDF-1 alpha, an important factor that mediates proliferation, survival, chemotaxis, migration and adhesion into bone marrow stroma. Radiation, in combination with chemotherapy, is one of the therapies used for DLBCL patients. We therefore investigated whether STAT3 down-regulation sensitized Ly3 cells to radiation. Radiation induced a higher accumulation of phospho-H2A.X (first sentinel event following DNA damage such as DSBs) and apoptosis in STAT3 shRNA lentivirus cells compared to control cells. Moreover, IL-6 and IL-10 protected the STAT3 shRNA lentivirus Ly3 cells less than the control cells from the induction of phospho-H2A.X following radiation. We further investigated the effect of STAT3 silencing in animal models of Ly3 lymphoma (Nude or NOD-SCID mice). Tumors in control lentivirus Ly3-bearing mice grew robustly, whereas tumors in STAT3 shRNA lentivirus Ly3-bearing mice regressed 5 days after injection. This tumor regression was associated with Caspase-3-dependent apoptosis, significant reduction of STAT3 target genes at the protein level such as Mcl-1, c-Myc and Survivin (approximately 40% to 60% inhibition), and reduction of cytokine production such as IL-10, IL-15, Leptin and Thrombopoietin. Taken together, these results suggest that inhibition of STAT3 is a potential promising approach in the therapy of ABC-type DLBCL. Disclosures: No relevant conflicts of interest to declare.

SNS01-T Exhibits Significant Anti-Tumoral Activity In Models Of Multiple Myeloma and Non-Hodgkins B Cell Lymphoma and Induces Cell Death In Malignant But Not Normal B Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 880-880
Author(s):  
Catherine A Taylor ◽  
Terence Tang ◽  
Sarah Francis ◽  
Zhongda Liu ◽  
Qifa Zheng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Tumor Volume ◽  
Cell Lymphoma ◽  
Xenograft Model ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Rpmi 8226

Abstract SNS01-T is a novel nanoparticle that is designed to selectively initiate apoptosis in B-cell cancers such as multiple myeloma and non-Hodgkins B-cell lymphomas. SNS01-T comprises a plasmid DNA (pExp5A) encoding a pro-apoptotic form of the eukaryotic translation initiation factor 5A (eIF5A) containing a single-point mutation that prevents hypusination, an eIF5A siRNA that inhibits expression of the pro-survival hypusine-eIF5A protein, and a polymer that serves to assemble the nucleic acids into a nanoparticle. SNS01-T is currently being investigated in a multi-site, open-label Phase1b/2a dose escalation study in subjects with relapsed or refractory multiple myeloma (MM), mantle cell lymphoma (MCL), or diffuse large B cell lymphoma (DLBCL). SNS01-T has demonstrated activity in MM xenograft models as well as in B cell lymphoma models of MCL and DLBCL, when administered twice weekly at doses ≥ 0.18 mg(nucleic acid)/kg. In this study we compared the ability of SNS01-T to transfect, regulate eIF5A expression, and kill MM, DLBCL, and MCL cell lines. Furthermore, the activity of SNS01-T in normal B cells was investigated. A previous study using a KAS-6/1 MM xenograft model demonstrated that the eIF5A siRNA and plasmid pExp5A both have anti-tumoral activity in MM but had a greater impact on tumour growth when combined together as SNS01-T. This finding was confirmed in this study in a second MM model (RPMI 8226) as well as in a DLBCL xenograft model. To determine the efficiency of SNS01-T transfection into malignant or normal B cells, the pExp5A plasmid and eIF5A siRNA were labeled with FITC and DY547, respectively, packaged into nanoparticles using polyethylenimine polymer, and used to transfect cultured cells. FACS analysis was used to determine the percent of the cell population transfected with plasmid, siRNA, or both. RT-qPCR was used to assess biological activity of SNS01-T by quantifying the expression of eIF5AK50R mRNA transgene and endogenous eIF5A mRNA in a variety of B cell lines. The IC50 of SNS01-T in a panel of MM, MCL, and DLBCL cell lines was determined by XTT assay. SCID mice bearing either RPMI 8226 MM tumours or SuDHL6 GCB DLBCL tumours were treated with pExp5A plasmid (formulated with PEI and control siRNA), eIF5A siRNA (formulated with PEI and a control plasmid), or SNS01-T at 0.375 mg/kg twice per week by intravenous injection. SNS01-T was able to transfect MM, MCL, and DLBCL cell lines, although the proportion of cells transfected with both plasmid and siRNA was higher in MM cells. Transfection of SNS01-T resulted in expression of the transgene as well as a statistically significant reduction in expression of eIF5A mRNA compared to untreated controls for all three cell types. In contrast, normal B cells were found to take up fluorescently-labeled SNS01-T with reduced efficiency compared to RPMI 8226 MM cells. Futhermore, SNS01-T was observed to induce cell death in RPMI 8226 MM cells but not in normal B cells. In the RPMI 8226 xenograft model, treatment with either the pExp5A plasmid alone or eIF5A siRNA alone resulted in a 66 % reduction (p < 0.0001) or 44 % reduction (p < 0.05) in tumor volume compared to the control group at day 24 of the study. In contrast, treatment with SNS01-T, which contains both the pExp5A plasmid and the eIF5A siRNA, resulted in an 86 % (p < 0.0001) reduction in tumor volume. A similar result was observed in the SuDHL6 model with a 14 % reduction or 27 % reduction (p < 0.05) in tumor volume compared to the control group at day 20 of the study following treatment with pExp5A plasmid or eIF5A siRNA, respectively. In contrast, treatment with SNS01-T resulted in a 79 % (p < 0.0001) reduction in tumor volume. Collectively, these preclinical studies indicate that SNS01-T therapy has significant potential against MM, MCL, and DLBCL. Disclosures: Taylor: Senesco Technologies: stock options Other. Dondero:Senesco Technologies: Employment. Thompson:Senesco Technologies: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Cilostazol Minimizes Venous Ischemic Injury in Diabetic and Normal Rats

2011 ◽  
Vol 31 (10) ◽  
pp. 2030-2040 ◽  
Author(s):  
Daisuke Wajima ◽  
Mitsutoshi Nakamura ◽  
Kaoru Horiuchi ◽  
Yasuhiro Takeshima ◽  
Fumihiko Nishimura ◽  
...  
Keyword(s):  
Infarct Size ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Doppler Flowmetry ◽  
Vessel Wall Thickness ◽  
Venous Infarcts ◽  
And Control

We evaluated the effects of cilostazol on venous infarction produced by a photothrombotic two-vein occlusion (2VO) model in diabetic and control rats. The cerebral blood flow (CBF) between the occluded veins was measured by laser Doppler flowmetry for 4 hours after 2VO. Infarct size and immunohistochemistry were evaluated 24, 48, 96, and 168 hours after 2VO. Cilostazol was administered 1 hour after 2VO, and thereafter at a continuous oral dose of 60 mg/kg per day. Cilostazol reduced the infarct size, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic and B-cell lymphoma 2-associated X protein (Bax)-positive cells, and improved the CBF in control rats. In diabetic rats, cilostazol reduced the infarct size, and the number of TUNEL-positive apoptotic and Bax-positive cells, 96 and 168 hours after 2VO, but did not improve the CBF 4 hours after 2VO. Cilostazol increased the number of B-cell lymphoma 2 (Bcl-2)-positive cells in both strains 48, 96, and 168 hours after 2VO, but did not improve vessel wall thickness or collagen deposits. Cilostazol appeared to limit venous infarcts by improving the penumbral CBF in nondiabetic rats, and inhibited pro-apoptotic changes through Bcl-2 overexpression, without improving the CBF in diabetic rats.

scholarly journals A Systematical Review of The Effect of Ketogenic Diet on Bcl-2 (B-cell lymphoma-2) Expression as An Apoptosis Marker in Cancer Treatment

2021 ◽  
Vol 4 (2) ◽  
pp. 130
Author(s):  
Vania Islamey Kusuma ◽  
Reny I’tishom ◽  
Ema Qurnianingsih ◽  
Purwo Sri Rejeki
Keyword(s):  
B Cell ◽  
Ketogenic Diet ◽  
Cancer Progression ◽  
Protein Level ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Total Sample ◽  
Control Group ◽  
P Value ◽  
High Fat

Introduction: Ketogenic diet seems to be in a great demand nowadays as a lot of people are interested in adopting it into their lifestyle. It is also found that the ketogenic diet shows several beneficial effects including cancer prevention. However, the detail mechanism still remains unknown. Therefore, this review was aimed to find out the effect of ketogenic diet on Bcl-2 (B-cell lymphoma-2) expression in cancer.Methods: We searched published literatures in PubMed through 2011-2020 using specific keywords. The literatures were filtered according to inclusion and exclusion criteria. Animal model, total sample size, underlying condition/inflammatory process occurs, details of the intervention/diet including diet contents in control group and high-fat group, and the duration of the intervention, Bcl-2 results, and p-value were extracted.Results: 7 studies were included in this review. Bcl-2 expression found decrease in 5 out of 6 studies. Similar result also obtained in Bcl-2 protein level, which measured by western blot. Bcl-2 protein level shows a decrease in 2 out of 3 studies.Conclusion: This review shows that high-fat diet that contained in ketogenic diet most likely lead to decrease in Bcl-2 expression. Therefore, indicating the ability of ketogenic diet to affect cancer progression by inducing apoptosis process.

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