Multitargeting Strategy Using Tetrathiomolybdate and Lenvatinib: Maximizing Anti-Angiogenesis Activity in a Preclinical Liver Cancer Model

Abstract Purpose To investigate the suppressing tumor-promoting effects via multi-anti-angiogenesis activity of the copper chelator (Ammonium Tetrathiomolybdate, TM) combined with lenvatinib for hepatocellular carcinoma. Material and methods Fifty-five C57 mice were injected subcutaneously with Hepa1-6 hepatoma cell suspensions into the right posterior thigh. Seven days later, all subcutaneous tumors were formed and the mice were randomly distributed into 5 groups: TM Group (G1), Lenvatinib Group (G2), TM+Lenvatinib Group (G3), Control Group (G4), and Copper (II) Gluconate Group (G5). And copper concentrations in serum and tumors were measured at the predetermined times. After fourteen days of treatments, tumor weight and volumes were analyzed, histology was observed, and the expressions of VEGF and microvessel density (MVD) in tumor tissues were measured by immunohistochemistry (IHC). Results Average concentration of copper in serum was 405.14 ug/L, 480.44 ug/L, and 679.80 ug/L in normal mice, in mice on 7 days after implantation, and in the control group, respectively. Similarly, intratumoral copper concentrations were greater in G4 mice (1511.90 ug/L) than mice on 7 days after implantation (852.80 ug/L) (p < 0.05). And the serum concentration of copper was 363.65 ug/L, 508.83 ug/L, 370.52 ug/L, 822.12 ug/L in G1, G2, G3, and G5 [G5 vs other Groups, all p < 0.05; (G1, G2, and G3) vs G4, p < 0.05; G1 vs G2, p = 0.013; G2 vs G3, p = 0.018; G1 vs G3, p = 0.903] while intratumoral copper concentrations was 674.31 ug/L, 988.91 ug/L, 550.52 ug/L, and 3004.95 ug/L in G1, G2, G3, and G5 And the average tumor weight was 0.55 g, 0.44 g, 0.08 g, 1.37 g, 3.11 g in the mice of G1, G2, G3, G4, and G5, respectively. [G5 vs other Groups, all p < 0.05; (G1, G2, and G3) vs G4, p < 0.05; G1 vs G3, p < 0.05; G2 vs G3, p < 0.05; G1 vs G2, p > 0.05]. Furthermore, tumors were collected for HE staining and IHC examination. The expression levels of VEGF in G1, G2, and G3 were 43.75, 32.48, and 15, and all of them were significantly lower than those in G4 (64.28) and G5 (89.03) (G4 vs G5, p < 0.05). Similarly, the trend of MVD was just like that of VEGF in the five groups whereas no significant difference occurred in G1 and G2. Conclusion The study shows that there is a significant positive correlation between tumor load and copper. Administration of copper can promote tumor progression, and copper chelating could suppress tumor growth. The combination of TM with lenvatinib can reduce tumor angiogenesis and improved the effect of antitumor treatment. These findings offer basic data support and theoretical foundation for the clinical application of the combination therapy.

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P11.01 TMZ-LEV- IFN cocktail regimen significantly inhibited the growth of glioma

Neuro-Oncology ◽

10.1093/neuonc/noz126.147 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii42-iii42

Author(s):

X Ni ◽

Y Qu ◽

J Wang ◽

F Chen ◽

H Cai ◽

...

Keyword(s):

Control Group ◽

Type I ◽

First Line ◽

Tumor Weight ◽

Significant Difference ◽

Subcutaneous Xenograft ◽

Group Control Group ◽

The Right

Abstract BACKGROUND TMZ, is the first line chemotherapeutic drug for glioma, and drug resistance is one of the most important reasons for glioma treatment failure. Our previous studies have found that: 1) Type I interferon (IFN) could reverse the resistance of TMZ by inhibiting NF-κB activity, and down-regulating the expression of MGMT in vivo and in vitro; 2) IFN-α could significantly improve chemtherapeautic effect of TMZ for GBM patients. We aim to investigate the therapeutic effect of a cocktail chemotherapy regimen combining temozolomide (TMZ)- Levetiracetam(LEV) - interferon (IFN) on human glioma U138 and U251 subcutaneous xenograft tumor. MATERIAL AND METHODS 30 xenograft tumors were established by subcutaneously injecting 1×106 glioma cells into the right flank of 4-week-old female BALB/C nude mice and then randomly divided into 5 groups (n=6/group): Control group; TMZ group; TMZ+IFN group; TMZ+LEV group; TMZ+LEV+IFN group. Anti-tumor efficacy of five regimens for tumor-bearing mice was tested after treatment with TMZ (50 mg/kg, i.p.), IFN (2×105 IU, s.c.), LEV (150 mg/kg, i.p.), while TMZ dose were reduced to 12.5 mg/kg for U251 tumors. All drugs are given once a day for five consecutive days. After therapy, the size of tumor was measured every day until the control tumors reached 2000 mm3. Mice bearing U138 tumors were sacrificed at 40 days after therapy, and mice bearing U251 tumors were killed at 26 days after therapy. RESULTS We identified that both U138 and U251 tumor growth among TMZ group, TMZ+IFN group, TMZ+LEV group and TMZ+LEV+IFN group were significantly inhibited (P<0.05), compared with the control group. Tumor weight of all treating group was lower than that of the control group (P<0.05). The tumor weight of TMZ+LEV+IFN group was the lowest and significantly lower than that of TMZ+LEV group and TMZ group (P<0.05, respectively). No significant difference was found between TMZ+LEV+IFN group and TMZ+IFN group in U251 subcutaneous xenograft tumors, although the tumor weight was lower in TMZ+LEV+IFN group (P>0.05). In the treatment of mice bearing U138 glioma, TMZ+LEV+IFN regimen was significantly superior to TMZ+IFN regimen. CONCLUSION Our data demonstrate that both IFN and LEV can sensitize TMZ effect on glioma. TMZ-LEV-IFN cocktail appears the best regimen.

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The Effect of Reflexology on Lactation in Women Who Had Cesarean Section: A Randomized Controlled Pilot Study

Complementary Medicine Research ◽

10.1159/000513924 ◽

2021 ◽

pp. 1-8

Author(s):

Sevde Aksu ◽

Pelin Palas Karaca

Keyword(s):

Pilot Study ◽

Cesarean Section ◽

Intervention Group ◽

Control Group ◽

Breast Pain ◽

Randomized Controlled ◽

Significant Difference ◽

The Right ◽

Documentation Tool ◽

And Control

Aim: The research was conducted as a randomized controlled pilot study to evaluate the effects of reflexology on lactation in mothers who delivered by cesarean section (CS). Methods: A single-blind randomized controlled experimental study was conducted with a total of 60 postpartum women in the reflexology application (n = 30) and control groups (n = 30). After the CS, the mothers in the control group were given approximately 3-h routine nursing care after recovering from the effects of anesthesia; the introductory information form was applied, and the Breastfeeding Charting System and Documentation Tool (LATCH) and visual analog scale (VAS) for the signs of the onset of lactation were implemented on the first and second days. Reflexology was applied to the women in the intervention group after an average of 3 h following the mother’s condition had become stable and she had recovered from the effects of anesthesia. Reflexology was applied a total of 20 min – 10 min for the right foot, 10 min for the left foot – twice a day with 8-h intervals on the first and second days after CS. After the last reflexology application, the LATCH and VAS for the signs of the onset of lactation were applied. Results: Of the women, 70% breastfed their babies within 60 min after delivery; 46.7% of the mothers received breastfeeding training and 81.7% needed support for breastfeeding after the CS. The LATCH breastfeeding scores of the women in the intervention group on both days were significantly higher compared to those of the women in the control group (p < 0.001). On the first day after the CS, apart from breast pain, there was no significant difference between the two groups in terms of breast heat and breast tension (p > 0.05). On the second day after the CS, apart from breast tension, there was no significant difference between the groups in terms of breast heat and breast pain (p < 0.05). In the study, women in the intervention group were found to have higher scores in terms of all three symptoms compared to the control group (p < 0.05). Conclusions: In the study, it was determined that LATCH scores and signs of the onset of breastfeeding increased in the mothers who received reflexology after CS.

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Frequency-Following Response (FFR) in Military Pilots

International Archives of Otorhinolaryngology ◽

10.1055/s-0040-1718525 ◽

2020 ◽

Author(s):

Graziela Maria Martins-Moreira ◽

Alessandra Spada Durante

Keyword(s):

Pure Tone Audiometry ◽

Control Group ◽

Study Group ◽

Aircraft Accidents ◽

Frequency Following Response ◽

Significant Difference ◽

Qualitative Variables ◽

Chi Squared ◽

The Right ◽

Military Pilots

Abstract Introduction Good hearing in pilots, including central auditory skills, is critical for flight safety and the prevention of aircraft accidents. Pure tone audiometry alone may not be enough to assess hearing in the members of this population who, in addition to high noise levels, routinely face speech recognition tasks in non-ideal conditions. Objective To characterize the frequency-following response (FFR) of a group of military pilots compared with a control group. Methods Twenty military pilots in the Study Group and 20 non-pilot military personnel, not exposed to noise in their work, in the Control Group, all with normal hearing, aged between 30 and 40 years old, completed a questionnaire to assess their hearing habits, and their FFRs were measured with a /da/ syllable (duration 40 milliseconds, speed 10.9/s), at 80 dB NA in the right ear. All procedures were approved by the ethical committee of the institution. Statistical analysis was performed using the t-Student or Mann-Whitney tests for quantitative variables, and the Fisher or chi-squared tests for qualitative variables, and a value of p < 0.05 was considered to be statistically significant. Results There was no significant difference between the groups regarding auditory habits. In the FFR, wave amplitudes A (p = 0.01) and C (p = 0.04) were significantly lower in the Study Group. Conclusion Working as a military pilot can be a crucial factor in determining an individual's typical FFR pattern, demonstrated in the present study by statistically significant reductions in the amplitudes of the A and C waves.

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Different selective dry cow therapy concepts compared to blanket antibiotic dry cow treatment

Tierärztliche Praxis Ausgabe G Großtiere / Nutztiere ◽

10.15653/tpg-170208 ◽

2017 ◽

Vol 45 (06) ◽

pp. 343-349 ◽

Cited By ~ 1

Author(s):

Nicole Wente ◽

Jan-Hendrik Paduch ◽

Doris Klocke ◽

Elisabeth Mansion-de Vries ◽

Martina Hoedemaker ◽

...

Keyword(s):

Rapid Test ◽

Study Groups ◽

Test Methods ◽

Farm Animals ◽

Control Group ◽

Dry Period ◽

Udder Health ◽

Significant Difference ◽

Group A ◽

The Right

SummaryObjective: The aim of the study was to investigate the use of somatic cell count (SCC) and aerobic bacterial counts as possible tools to choose animals for selective dry cow treatment (DCT) on cow level. Blanket antibiotic DCT is an approved and common method in Germany aimed at increasing the cure rate of existing intramammary infections (IMI) at the time of drying off and decreasing the risk of new infections during the dry period. However, not all animals benefit equally from an antibiotic DCT. Moreover, dairies, consumers and politicians demand a reduction in the use of antibiotics in farm animals. Several criteria for identifying animals which would benefit from antibiotic DCT have been described in the literature. Material and methods: Animals chosen for this investigation were divided into three study groups: Aerobic Count Petrifilm® group A (153 cows), SCC group S (160 cows) and control group C (169 cows). All quarters were treated with an internal teat sealant (ITS) no matter which group the cows belonged to. Results: Group C, in which all cows received an antibiotic DCT, achieved the best results referred to udder health, particularly regarding bacteriological dry period cure. However, the results of the two study groups A and S, in which the animals were dried off selectively, were only marginally worse. A significant difference regarding bacterial dry period cure was revealed between group S and group C (p = 0.039), whereas no significant difference concerning new IMI risk could be detected between the three study groups. Compared to a blanket antibiotic DCT of all cows in the corresponding study group, a reduction of the usage of antibiotics of 23.5 % (A) and 55 % (S) was noticed, respectively. Furthermore, it could be shown that the lactation number as well as the microorganisms present at the time of drying off influence udder health. Conclusion: Selective DCT is an alternative method to the widespread blanket antibiotic DCT. However, it has to be mentioned that selective DCT involves the described marginal decline in udder health and the additional amount of time, which might arise from the procedure of choosing the right animals and performing the applied rapid test methods.

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Multiple sclerosis and depressive manifestations: can diffusion tensor MR imaging help in the detection of microstructural white matter changes?

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-019-0033-8 ◽

2019 ◽

Vol 50 (1) ◽

Cited By ~ 2

Author(s):

Talaat A. Hassan ◽

Shaima Fattouh Elkholy ◽

Bahaa Eldin Mahmoud ◽

Mona ElSherbiny

Keyword(s):

Multiple Sclerosis ◽

Depressive Symptoms ◽

White Matter ◽

Limbic System ◽

Diffusion Tensor ◽

Control Group ◽

Uncinate Fasciculus ◽

White Matter Tracts ◽

Significant Difference ◽

The Right

Abstract Background Multiple sclerosis is one of the commonest causes of neurological disability in middle-aged and young adults. Depression in MS patients can compromise cognitive functions, lead to suicide attempts, impair relationships and reduce compliance with disease-modifying treatments. The aim of this study was to investigate and compare the microstructural changes in the white matter tracts of the limbic system in MS patients with and those without depressive manifestations using a diffusion tensor imaging (DTI) technique. Methods This study included 40 patients who were divided into three groups. Group 1 comprised of 20 patients with relapsing-remitting MS with depressive symptoms and group 2 comprised 10 MS patients without symptoms of depression. The third group is a control group that included 10 age-matched healthy individuals. All patients underwent conventional MRI examinations and DTI to compare the fractional anisotropy (FA) values in the white matter tracts of the limbic system. Results We compared the DTI findings in MS patients with and those without depressive symptoms. It was found that patients with depression and MS exhibited a significant reduction in the FA values of the cingulum (P < 0.0111 on the right and P < 0.0142 on the left), uncinate fasciculus (P < 0.0001 on the right and P < 0.0076 on the left) and the fornix (P < 0.0001 on both sides). No significant difference was found between the FA values of the anterior thalamic radiations in both groups. Conclusion Patients with depression and MS showed more pronounced microstructural damage in the major white matter connections of the limbic pathway, namely, the uncinate fasciculus, cingulum and fornix. These changes can be detected by DTI as decreased FA values in depressed MS patients compared to those in non-depressed patients.

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Analysis of the muscle tissue of Wistar rats submitted to the sciatic nerve compression model and cryotherapy

Einstein (São Paulo) ◽

10.1590/s1679-45082018ao4206 ◽

2018 ◽

Vol 16 (3) ◽

Cited By ~ 2

Author(s):

Jhenifer Karvat ◽

Camila Mayumi Martin Kakihata ◽

Lizyana Vieira ◽

José Luis da Conceição Silva ◽

Lucinéia de Fátima Chasko Ribeiro ◽

...

Keyword(s):

Sciatic Nerve ◽

Muscle Tissue ◽

Wistar Rats ◽

Nerve Compression ◽

Control Group ◽

Functional Evaluation ◽

Cross Sectional ◽

Injury Group ◽

Significant Difference ◽

The Right

ABSTRACT Objective: To evaluate the effects of right sciatic nerve compression and cryotherapy on muscle tissue. Methods: We used 42 male Wistar rats, subdivided in the following Groups Control, Injury 3, Injury 8 and Injury 15 submitted to nerve compression and euthanized in the 3rd, 8th and 15th day after surgery. The Cryotherapy Injury 3 was entailed treatment with cryotherapy by immersion of the animal in recipient for 20 minutes during 1 day, then animals were euthanized at the 3rd day after surgery, and the Cryotherapy Injury 8 and the Cryotherapy Injury 15 was treated for 6 days, and euthanized at the 8th and 15th day after surgery. Functional evaluation was performed by the grasping strength of the right pelvic limb. The right tibialis anterior muscles were evaluated for mass, smaller diameter and cross-sectional area. In the Cryotherapy Injury 8 and the Cryotherapy Injury 15 groups, the hydroxyproline was dosed in the right soles. Results: In the compression there was a significant difference in the Injury Groups compared with the Control Group (p<0.05). In the smaller diameter, the compression in Control Group was higher than Injury 8 (p=0.0094), Injury 15 (p=0.002) and Cryotherapy Injury 15 (p<0.001) groups. The comparison between groups with euthanasia in the same post-operative period, a significant difference (p=0.0363) was seen in day 8th after surgery, and this result in Cryotherapy Injury Group was greater than Injury Group. In the fiber area, Control Group was also higher than the Injury 8 (p=0.0018), the Injury 15 (p<0.001) and the Cryotherapy Injury 15 (p<0.001). In hydroxyproline, no significant difference was seen between groups. Conclusion: Nerve damage resulted in decreased muscle strength and trophism, the cryotherapy delayed hypotrophy, but this effect did not persist after cessation of treatment.

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Evaluation of effect of local exogenous application of Myrrh oil on healing of wound incisions of facial skin (Histochemical, Histological and Histomorphometrical study in rabbits)

Journal of Baghdad College of Dentistry ◽

10.26477/jbcd.v31i4.2724 ◽

2019 ◽

Vol 31 (4) ◽

Author(s):

Nawar Bahjet Kamil ◽

Nada M. Al-Ghaban

Keyword(s):

Healing Process ◽

Inflammatory Cells ◽

Control Group ◽

Facial Skin ◽

Histological Findings ◽

Control Groups ◽

Mean Values ◽

Significant Difference ◽

The Right ◽

New Zealand Rabbits

Aim of the study: Is to evaluate the effect of myrrh oil local application on the healing process of skin wounds histologically , histomorphometrically and , histochemically. Materials and methods:Twenty male white New Zealand rabbits were used in this study. An incisional wounds with full thickness depth and of 2 cm length were done on both sides of the cheek skin of each rabbit. The left sided incisions (the control group) were irrigated with distilled water (10µL). The right sided incisions (the experimental groups) were treated with myrrh oil (10µL). Each group was subdivided into 4 subgroups according to the healing interval into 1,3,7 and 14 days(5 rabbits for each group). Results: Histological findings of our current study showed a highly significant difference between the experimental and the control groups in count of the inflammatory cells which showed that mean values increased with time for the control and the experimental groups. The histomorphometrical findings had shown that the thickness of the epithelium was nearly completed at about 7 days for the experimental groups and at about 14 days for the control. The blood vessels count was recorded to have a highly significant difference between the groups at days 1 and 3 only. The histochemical findings had shown that the collagen fibers remodeling had recorded a highly significant difference between the control and the experimental groups at days 7 and 14. Conclusion: The current study had revealed that myrrh oil accelerates wounds healing in rabbits. Key word:Wound healing , Myrrh oil, Masson’s Trichrome staining.

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Evaluation of Biomechanically Corrected Intraocular Pressure Measurements in Keratoconus and Forme Fruste Keratoconus

Ophthalmic Research ◽

10.1159/000506839 ◽

2020 ◽

Vol 63 (6) ◽

pp. 541-549

Author(s):

Tomoya Nishida ◽

Takashi Kojima ◽

Takahiro Kataoka ◽

Naoki Isogai ◽

Yoko Yoshida ◽

...

Keyword(s):

Intraocular Pressure ◽

Biomechanical Properties ◽

Control Group ◽

Pressure Measurements ◽

Altman Plot ◽

Significant Difference ◽

The Difference ◽

The Right ◽

Corneal Biomechanical Properties ◽

Forme Fruste Keratoconus

Introduction: Although biomechanically corrected intraocular pressure (bIOP) is available, the effectiveness of intraocular pressure (IOP) correction in keratoconus and forme fruste keratoconus (FFK) eyes has not been investigated. Objective: Evaluation of bIOP measurements in eyes with keratoconus and FFK. Methods: Forty-two eyes in 21 patients with keratoconus in one eye and FFK in the fellow eye were examined (KC/FFK group; mean age 24.62 ± 8.6 years; 16 males and 5 females). The control group consisted of 62 eyes in 31 unaffected subjects (mean age 26.26 ± 3.64 years; 15 males and 16 females). The bIOP was determined using a Scheimpflug-based tonometer (Corvis Scheimpflug Technology [Corvis ST®]) after measuring the IOP with a conventional non-contact tonometer (NIOP). The agreement between NIOP and bIOP values was examined using the Bland-Altman plot. The difference between NIOP and bIOP (bIOP correction amount) was compared between keratoconus and FFK eyes. Results: In the control group, there were no significant differences between right and left eyes in both NIOP and bIOP values (p = 0.975 and p = 0.224, respectively). In the KC/FFK group, NIOP values were significantly lower in the keratoconus eyes (9.93 ± 1.96 mm Hg) than in the FFK eyes (12.23 ± 3.03 mm Hg; p = 0.0003). There was no significant difference in bIOP values between the right and left eyes of the KC/FFK group (p = 0.168). The bIOP correction amount was significantly increased in keratoconus eyes (3.58 ± 2.12 mm Hg) compared to in FFK eyes (1.80 ± 3.32 mm Hg; p = 0.011). Conclusions: For eyes with keratoconus and FFK, the bIOP method is effective to adjust IOP measurements based on corneal biomechanical properties.

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Correlation between limb length discrepancy and asymmetrical rearfoot position

Journal of the American Podiatric Medical Association ◽

10.7547/87507315-83-11-625 ◽

1993 ◽

Vol 83 (11) ◽

pp. 625-633 ◽

Cited By ~ 12

Author(s):

RL Blake ◽

HJ Ferguson

Keyword(s):

Limb Length Discrepancy ◽

Limb Length ◽

Control Group ◽

Vertical Angle ◽

Short Side ◽

Length Discrepancy ◽

Heel Contact ◽

Significant Difference ◽

The Right ◽

Two Sides

Ten subjects with a known limb length discrepancy were filmed with the two-dimensional Motion Analysis Foot Trak System; eight were filmed running and walking and two were filmed walking only. A control group of ten subjects with no measured limb length discrepancy was filmed in the same manner (eight walking and running and two walking only). The calcaneus-to-vertical angle was recorded for the entire stance gait cycle (heel contact to toe-off). Analysis of the data between the short and long side showed a significant difference in calcaneal position between the two sides at midstance, with the longer side being more everted by 3 degrees or greater than the short side in most cases. There was no significant difference in the calcaneus-to-vertical angle at heel contact between the long and short side. There was no significant difference between the calcaneus-to-vertical angles of the right and left sides of the ten control subjects, either walking or running.

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Prevention of Capsular Contracture with Montelukast After Insertion of Silicone Implants in Rabbits

Journal of Computational and Theoretical Nanoscience ◽

10.1166/jctn.2016.5762 ◽

2016 ◽

Vol 13 (10) ◽

pp. 7623-7627

Author(s):

Zhenyu Jin ◽

Ki Yong Hong ◽

Kyung Won Minn ◽

Hak Chang ◽

Ung Sik Jin

Keyword(s):

Breast Implant ◽

Capsular Contracture ◽

White Female ◽

Silicone Implants ◽

Control Group ◽

Tissue Samples ◽

Significant Difference ◽

Group A ◽

The Right ◽

Experimental Group

Capsular contracture is the most common complication after insertion of silicone implants during breast implant surgery. The discovery that myofibroblasts play an important role in the formation of hypertrophic scars led to the development of pharmacological drugs such as zafirlukast, which prevents capsular contracture by resisting the above mechanism. As a result, the author sought to investigate the effect of the anti-leukotriene montelukast on capsular contracture. Ten white female New Zealand rabbits, each weighing approximately 3 kg, were used as subjects. Through bilateral incision of the midback area, the prostheses were inserted on the subpanniculus carnosus plane. Once the silicone prostheses had been inserted, the right implant was injected with 10 mL of montelukast (10 µg/mL), and the left implant was injected with 10 mL of normal saline. Eight weeks after the procedure, the capsular pressure was measured via tonometry using a circular glass piece weighing 42.7 g. The tissue samples were then extracted, and their thicknesses were measured using hematoxylin-eosin stain and Masson trichrome stain. The average pressure was 4.23±0.99 mmHg in the control group and 3.71±0.51 mmHg in the experimental group, a statistically significant difference (p = 0.02). The average capsular thickness was 947.938±300 µm in the control group and 709.672±274 µm in the experimental group, a statistically significant difference (p = 0.028). The author confirmed that montelukast injections during silicone prosthesis insertion decreased the formation of capsular contracture.

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