scholarly journals Effect of Isolated Serum from Breast Cancer Patients with Pectoral Nerves Block on Breast Cancer Cell Line (MDA-MB-231) Apoptosis Index

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Davar Amani ◽  
Elham Memary ◽  
Majid Samsami ◽  
Malihe Zangoue ◽  
Sadegh Shirian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Group Analysis ◽  
Control Group ◽  
Anesthetic Drugs ◽  
Apoptosis Index ◽  
Post Operation ◽  
Tumoral Cell ◽  
Late Apoptosis ◽  
The Mean

Background: Breast cancer (BC) is the most frequent cause of cancer death in women. The thoracic pectoral nerve (PECS) block has been described as the gold standard analgesic modality for BC surgery. It has been previously reported that PECS is associated with decreased BC recurrence post-mastectomy. Although several anesthetic drugs and techniques are used in surgical oncology, their effects on the behavior of cancer cells are yet to be known and the key question of whether the anesthetic technique affects cancer outcome remains unresolved. Objectives: Since anesthetic drugs and techniques and post-operative pain may affect BC recurrence, this study aimed to determine whether the anesthetic choice and technique, PECS II block, affects in vitro apoptosis of the MDA-MB-231 BC cell line. Methods: Twenty-two female BC patients, 20 to 75-years-old, with the same pathologic grades were included in this study. The patients were randomly divided into two groups. The first group received propofol general anesthesia (PGA) associated with PECS and the second group received standard PGA. Blood was sampled pre and post-operation from all patients. The sera were isolated and then exposed to the MDA-MB-231 human BC cell line. The mean percentage of apoptosis indices was analyzed by flow cytometry using Annexin V-fluorescein isothiocyanate 24 hours after treatment with patients’ sera. Results: A significant decrease was seen in the mean viability percentage of BC cell line in the PECS group, besides a significant increase in the mean percentage of necrosis and late apoptosis indices compared to the control group after exposure to sera collected from patients post-operation. Intra-group analysis of the control group showed that the exposure of the tumoral cell to post-operation sera resulted in a significant increase in the mean percentage of necrosis and late apoptosis index compared to pre-operation sera exposure. In the PECS group, the exposure of the tumoral cell to post-operation sera resulted in a significant increase in the mean percentage of cell viability and late apoptosis index compared to pre-operation sera exposure. Conclusions: In conclusion, anesthesia and BC surgery may induce apoptosis indices in the MDA-MB-231 human BC cell line. We also found that sera collected from PECS II block patients with BC could induce more apoptosis in the MDA-MB-231 cell line compared to collected sera from systemic analgesia alone after BC surgery.

scholarly journals The Effect of Health Literacy Counselling on Self-Care in Women after Mastectomy: a Randomized Clinical Trial

2020 ◽  
Vol 9 (1) ◽  
pp. 39-45
Author(s):  
Masoume Rastegar ◽  
Zohreh Mahmoodi ◽  
Sara Esmaelzadeh Saeieh ◽  
Nasibeh Sharifi ◽  
Kourosh Kabir
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Health Literacy ◽  
Intervention Group ◽  
Self Care ◽  
Essential Element ◽  
World Health ◽  
Control Group ◽  
Fars Province ◽  
The Mean

Introduction: Breast cancer has a high prevalence, constituting a major cause of mortality in women around the world. Health literacy has a vital role in the self-care of chronic diseases such as cancer and is an essential element in the ability of each person to engage with health promotion. The aim of this study was to determine effect of health literacy counselling on selfcare in women after mastectomy. Methods: This study is a randomized, controlled, clinical trial carried out on 72 women with breast cancer after mastectomy in Fars province. The eligible women entered the study using convenience sampling and were then divided into an intervention and a control group through randomized blocks of four. Health literacy questionnaire and self-care questionnaire were distributed among the participants before, immediately after and three weeks following the intervention. Data analysis was performed in SPSS ver.13. Results: The results showed no significant differences between the two groups in terms of their health literacy and self-care scores before the intervention (P=0.299 and 0.059). A comparison of the mean values showed a greater increase in the mean score of health literacy and score of selfcare immediately and three weeks after the intervention in the intervention group compared to the control group. Also, the mean score of the dimensions of self-care in chemotherapy increased over time in the intervention group. Conclusion: The findings of this study confirm the higher effectiveness of counseling with a health literacy approach on overall self-care in chemotherapy and all its dimensions.

scholarly journals Effect of Self-care Training on Upper Limb Function and Pain After Breast Cancer Surgery

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Somyye Noura ◽  
Fatemeh Kiani ◽  
Nezarali Moulaei ◽  
Mojtaba Tasbandi ◽  
Ebrahim Ebrahimi Tabas
Keyword(s):  
Breast Cancer ◽  
Upper Limb ◽  
Intervention Group ◽  
Self Care ◽  
Control Group ◽  
Limb Function ◽  
Upper Limb Function ◽  
Care Training ◽  
The Mean ◽  
And Control

Background: Breast cancer patients who undergo mastectomy encounter numerous problems, the most annoying of which is lymphedema followed by pain and decreased function in the affected limb. Objectives: This study examined the effect of self-care training on upper limb function and pain after breast surgery. Methods: This quasi-experimental study was performed on two groups of 60 patients with breast cancer in the Oncology Ward of Zahedan University of Medical Sciences in 2021. The patients were selected based on the inclusion criteria and through convenience sampling and were then randomly divided into intervention and control groups. The patients in the intervention group attended self-care training and exercise programs implemented in five sessions in addition to the routine care. One and three months after the intervention, upper limb function and pain were measured with DASH and McGill pain questionnaires. The repeated measures analysis of variance (ANOVA) and Bonferroni test were used to compare the pre-, and post-intervention mean scores and mean differences in the two groups. Results: The mean scores of upper limb function one and three months after the training program in the intervention group were lower than the mean scores of the control group. In other words, the quality of upper limb function was not significantly different despite the changes in the first month, but upper limb function significantly improved three months after the intervention (P < 0.001 vs. P = 0.06). The mean pain scores before, one month, and three months after the intervention in the intervention group were 10.4, 35.7, and 6.26, respectively, and the corresponding values in the control group were 10.8, 41.7, and 21.1, respectively, showing significant differences between the two groups, with the intervention group having lower pain scores than the control group (P = 0.001). Conclusions: Since lymphedema and its consequences, including decreased upper limb function and pain, are very serious issues, medical staff can give priority to this training program and implement it to prevent and control these complications.

scholarly journals A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Li-Quan Zhao ◽  
Jin-Wei Cheng
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Treatment Group ◽  
Cataract Surgery ◽  
Comparative Studies ◽  
Group Analysis ◽  
Control Group ◽  
Anti Vegf ◽  
The Mean ◽  
Agent Treatment

Aims. To examine possible benefits of intravitreal anti-vascular endothelial growth factor (VEGF) agent treatment immediately after cataract surgery for patients with diabetic retinopathy (DR). Methods. A comprehensive literature search was performed using the Cochrane collaboration methodology to identify randomized controlled trials (RCTs) and comparative studies of cataract surgery with or without anti-VEGF agent treatment for any diabetic retinopathy. Meta-analyses were performed for clinical outcome parameters including changes in macular thickness (MT), best-corrected visual acuity (BCVA), incidence of diabetic retinopathy and maculopathy progression, laser treatment rate, and other complications. Results. Nine RCTs and 3 nonrandomized comparative studies were identified and used for comparing cataract surgery with intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) treatment (338 eyes, intervention group) to cataract surgery alone (329 eyes, control group). Analysis of all data showed that the mean BCVA at 1 week postoperatively had no statistically significant difference in the two groups, but at 1, 3, and 6 months postoperatively, the mean BCVA was statistically significantly better in the anti-VEGF treatment group than that in cataract surgery alone group. Analysis of all data showed that the mean MT was statistically significantly less in the anti-VEGF treatment group at 1 week and 1, 3, and 6 months postoperatively (P=0.05, P=0.006, P=0.0001, and P=0.0001, respectively); but postoperative clinical outcomes were differentiated from the type of anti-VEGF agents, IVB or IVR, and the existing macular edema preoperatively. Intravitreal anti-VEGF agent treatment statistically significantly reduced the incidence of diabetic retinopathy progression and maculopathy progression compared to the control group (P=0.0003, P<0.00001, respectively). Conclusion. IVB or IVR treatment immediately after cataract surgery may represent a safe and effective strategy to prevent postoperative macular thickening or reduce macular edema and result in greater mean improvements in visual acuity for diabetic patients.

The effect of acupressure application on chemotherapy-induced nausea, vomiting, and anxiety in patients with breast cancer

2014 ◽  
Vol 13 (2) ◽  
pp. 275-284 ◽  
Author(s):  
Fatma Genç ◽  
Mehtap Tan
Keyword(s):  
Breast Cancer ◽  
Experimental Model ◽  
Patient Information ◽  
Acupuncture Point ◽  
Beck Anxiety Inventory ◽  
Control Group ◽  
Quasi Experimental ◽  
The Mean ◽  
Experimental Group

AbstractObjective:The purpose of this study was to determine the effect of acupressure applied to the pericardium 6 (P6 or neiguan) acupuncture point on chemotherapy-induced nausea, vomiting, and anxiety in patients with breast cancer.Method:The study was conducted using a quasi-experimental model with a control group. It included a total of 64 patients with stages 1–3 breast cancer who received cycle two and more advanced chemotherapy in an ambulatory chemotherapy unit. There were 32 patients in the experimental group and 32 patients in the control group. Acupressure was applied to the P6 acupuncture point of patients in the experimental group with the help of a wristband. A Patient Information Form, the Beck Anxiety Inventory, and the Index of Nausea, Vomiting and Retching were employed to collect the data.Results:It was determined that the mean nausea, vomiting, and retching scores, the total (experience, occurrence, and distress) scores, and the mean anxiety scores for patients to whom acupressure was applied at the P6 acupuncture point were statistically significantly lower compared with the scores of patients in the control group.Significance of Results:The efficacy of applying acupressure was demonstrated. We determined that applying acupressure at the P6 point is effective in decreasing chemotherapy-induced nausea, vomiting, and anxiety in patients with breast cancer. Further research with more subjects is needed.

Cytotoxicity Assessment of Quassinoids Neosergeolide and Isobrucein B toward Hematopoietic and Solid Malignancies Identifies STAT3 Activation To Be Predictive of Antitumor Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1394-1394
Author(s):  
Mitsuteru Hiwatari ◽  
Jingqiu Dai ◽  
Wei Liu ◽  
Yu-Dong Zhou ◽  
Dale G. Nagle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Strong Support ◽  
Luciferase Reporter ◽  
Control Group ◽  
Antitumor Effects ◽  
Protein Levels ◽  
Ic50 Values

Abstract Quassinoids are natural product compounds known to possess tumor cytotoxicity and antimalarial activity. Neosergiolide and isobrucein B are two quassinoids previously isolated from roots and stems of Picrolemma sprucei. In screening studies to identify inhibitors that target STAT3, we discovered neosergeolide and isobrucein B as active compounds. Approximately 5000 plant-derived extracts were screened using a cell line that stably expresses a STAT3-dependent luciferase reporter and NPM-ALK, which constitutively induces STAT3 transcriptional activity. Of 25 total hits, a P. sprucei extract was potent and selective for STAT3 inhibition, and bioassay-guided isolation identified neosergeolide and isobrucein B as the inhibitory compounds. Western blot analysis confirmed that neosergeolide and isobrucein B not only inhibit the tyrosine phosphorylation and activation of STAT3 but also decrease total STAT3 protein levels via a mechanism due in part to enhanced proteasome-mediated degradation. Small-molecule proteasome inhibitors such as MG132 and ALLN reversed the ability of the two quassinoids to decrease STAT3 protein levels; furthermore, simultaneous incubation of various hematopoietic malignancy cell lines with either neosergeolide or isobrucein B and MG132 or ALLN antagonized the cytotoxic activity of the quassinoids. Assessment of neosergiolide and isobrucein B antitumor effects using an XTT assay revealed both compounds to possess potent cytotoxic activity across a broad spectrum of hematopoietic malignancies, with T-leukemias/lymphomas being especially responsive. For example, mycosis fungoides (MF)- and Sezary syndrome (SS)-derived cell lines, as well as non-MF/SS cutaneous T-cell lymphoma (CTCL) lines, were potently inhibited by both quassinoids (neosergiolide IC50 values: MAC-1, 11.6 nM; MAC-2A, 6.9 nM; Hut-78, 6.6 nM; HH, 4.3 nM; MJ, 7.0 nM; isobrucein B IC50 values: MAC-1, 31.9 nM; MAC-2A, 72.3 nM; Hut-78, 23.5 nM; HH; 20.3 nM; MJ, 13.5 nM). Non-hematopoietic cell lines representing various solid tumors also exhibited potent cytotoxic responses to the quassinoids (e.g., gastric carcinoma line AGS [neosergiolide IC50: 16.9 nM; isobrucein B IC50: 114.9 nM]). With rare exceptions, the cytotoxicity of the quassinoids against a specific tumor cell line correlated with STAT3 activation status; for example, breast cancer line MCF7 with inactive STAT3 was resistant to both quassinoids even at the maximum concentration tested (6.25 μM), whereas breast cancer lines MDA-MB-468 and MDA-MB-435s with activated STAT3 were inhibited by both compounds at low concentrations (neosergiolide IC50: MDA-MB-435s, 31.3 nM; MDA-MB-468, 29.9 nM; isobrucein B IC50: MDA-MB-435s, 209.3 nM; MDA-MB-468, 356.8 nM). The in vitro antitumor activity of the two quassinoids could also be demonstrated in vivo. For example, isobrucein B (1.0 mg/kg IP once q 3d x 5 doses) could be safely administered and potently inhibited the growth in SCID mice of the CD30+ primary CTCL MAC-1 cell line; mice at treatment day 16 showed average subcutaneous tumor volumes of 3839 ± 863 (s.e.) mm3 in the vehicle-control group and 913 ± 349 (s.e.) mm3 in the isobrucein B group (P=0.008, t-test). These results provide strong support for STAT3 targeting in antitumor drug discovery and suggest that quassinoids may have utility in such an approach.

Biomarker correlation to clinical response in phase I/II trials of the adjuvant breast cancer vaccine neuvax (nelipepimut-S or E75).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS3126-TPS3126
Author(s):  
John S. Berry ◽  
Alfred F Trappey ◽  
Alan K. Sears ◽  
Timothy J Vreeland ◽  
Guy T. Clifton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Peptide Vaccine ◽  
Clonal Expansion ◽  
Mean Difference ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Clinical Recurrence ◽  
The Mean

TPS3126 Background: We completed phase I/II clinical trials with NeuVax (nelipepimut-S), a HLA-A2/A3-restricted, HER2-derived peptide vaccine. The vaccine was administered in the adjuvant setting to prevent recurrence in breast cancer patients rendered disease-free with standard-of-care therapy. Here, we examine the relationship between in vitro immunologic response (IR) and clinical recurrence (CR) after 5-year follow-up. Methods: The phase I/II trials were performed as dose-escalation/schedule-optimization trials enrolling node positive and high-risk, node-negative patients (pts) with tumors expressing any level of HER2 (IHC 1+,2+,or 3+). HLA-A2/A3+ pts were enrolled in the vaccine group (VG) while HLA-A2/A3- pts were followed prospectively as an untreated control group (CG). The VG was given 4-6 monthly intradermal inoculations of nelipepimut-S+GMCSF (immunoadjuvant) during the primary vaccine series (PVS). In vitro IR was assessed for E75-specific, cytotoxic T lymphocyte clonal expansion by HLA-A2:IgG dimer assay and expressed as mean dimer index (mdi) at baseline, after PVS (R6), and six months after the PVS. HER2 under-expression was defined as an IHC 1/2, and a FISH < 2.2. VG and CG pts were followed for CR over 60 months. P-values were calculated using the Fisher’s exact test. Results: Of the 195 pts enrolled, 8 withdrew, leaving 187 evaluable pts; 108 in the VG and 79 in the CG. R6 dimer assays were available for 86 pts in the VG. The mean R6 dimer in the VG is 0.63 mdi+.08. Of the 30 pts with an R6 dimer above the mean, only one recurred, compared to eight of the 56 below the mean (p=.09). The difference between baseline and maximum mdi was available in 56 HER2 under-expressing VG pts. Of the 26 pts above the mean difference (1.08 mdi +.17), one recurred, compared to six CR in the 30 pts below the mean (p=.06). There were no CR in pts with HER2 under expression with a mean difference ranked in the top third. Conclusions: In prospective, completed phase I/II trials of NeuVax (nelipepimut-S), patients who exhibit robust in vitro IR have lower recurrence rates. This finding suggests that nelipepimut-specific CTL clonal expansion is a valid biomarker for CR in pts treated with NeuVax. Clinical trial information: NCT00841399.

Relationship of peripheral neuropathy grades with increase of skin perfusion by compression therapy for breast cancer patients.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 182-182
Author(s):  
Tsuyoshi Ohno ◽  
Takashi Mine ◽  
Hiroki Yoshioka ◽  
Mikiko Kosaka ◽  
Sadayuki Matsuda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Peripheral Neuropathy ◽  
Healthy Volunteers ◽  
Compression Therapy ◽  
Cytotoxic Agents ◽  
Control Group ◽  
Skin Perfusion ◽  
Medication Therapy ◽  
Significant Difference ◽  
The Mean

182 Background: Chemotherapy-induced peripheral neuropathy (CIPN) has become a substantial problem because of specific cytotoxic agents such as nab-paclitaxel, oxaliplatin, and eribulin. In addressing CIPN-related side effects caused by nab-PTX, we previously reported better CTCAE v4.0 grades and superior nab-PTX dose maintenance in breast cancer treatment adopting our 3S approach. Our 3S approach combines compression therapy (stockings and sleeves applied 24 hours from the beginning of nab-PTX administration) with medication therapy (selected prophylactic medications goshajinkigan, lafutidine, and mecobalamin applied over the course of treatment). In revisiting how stocking use restored skin perfusion levels decreased by nab-PTX chemotherapy, we examined whether the skin perfusion increases differ by CIPN grade. Methods: Using a laser Doppler blood flow meter with integrated probe (NL-101 Nahri Nexis Japan), we measured the skin perfusion of the lower limbs before and after stocking use across four groups: three groups of 3S prophylactics-treated nab-PTX patients divided by CIPN grade (Grade 0 [G0, n=12], Grade 1 [G1, n=20], Grades 2 and 3 combined [G2+3, n=12]), and one control group of healthy volunteers (GH, n=50). Results: In the control group (GH), the mean increase in skin perfusion level (mL/min/100g) after wearing stockings was 0.90 (SD= 3.36). For the 3S prophylactic treatment patients, the mean increase was 4.25 (4.98) in the G0 group, 2.11 (4.93) in the G1 group, and 2.69 (2.53) in the G2+3 group. ANOVA analysis indicated a significant difference in skin perfusion increase among the groups (p=0.0493). Analysis between the groups indicated significance in the G0 group increase over the control group increase (p=0.0255). Conclusions: CIPN was previously shown to decrease skin perfusion; in the current study skin perfusion responsiveness to stockings differed significantly between chemotherapy patients and healthy volunteers. Restorative skin perfusion increase is potentially related with alleviating CIPN grade, for which further evaluation is needed.

Effects of exercise on cancer-related fatigue and muscular strength in patients with breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11507-11507
Author(s):  
Po-Ju Lin ◽  
Kah Poh Loh ◽  
Julia Ellen Inglis ◽  
Richard Francis Dunne ◽  
Ian Kleckner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Muscular Strength ◽  
Daily Activities ◽  
Control Group ◽  
Lower Body ◽  
Post Intervention ◽  
Cancer Related Fatigue ◽  
Body Strength ◽  
The Mean ◽  
Lower Body Strength

11507 Background: Cancer-related fatigue (CRF) is a persistent daily lack of energy commonly experienced by breast cancer (BC) patients. Due to CRF, BC patients have difficulties carrying out daily activities, become less active and consequently reduce muscular strength. Exercise can improve muscular strength and increase energy level; therefore it may alleviate CRF. This phase II RCT assessed the effects of exercise on CRF and muscular strength in BC patients. Methods: Ninety BC patients (55.5±9.6 years, 79% white, 48% and 46% under radiation or hormone therapy) were randomized into two arms: a 6-week Exercise for Cancer Patients (EXCAP) program or standard care (Control). EXCAP is a home-based, personalized, progressive exercise program combining aerobic walking and resistance band training. The Brief Fatigue Inventory was used to assess CRF and CRF interference with daily activities and a 7-10 repetition maximum chest press and leg extension strength test was used to assess upper- and lower-body strength at pre- and post-intervention. T-tests and ANCOVA with pre-intervention as the covariate were used to analyze within- and between-group changes, respectively. Results: Participants in the EXCAP group decreased CRF (-0.9±0.3, p = 0.01) and CRF interference with daily activities (-1.1±0.3, p < 0.01) from pre- to post-intervention while participants in the Control group did not. The mean improvement (from pre- to post-intervention) in CRF and CRF interference of daily activities for the EXCAP group were significantly higher than the change in the Control group (both p < 0.01). Participants in the EXCAP group increased upper- (3.9±1.4, p < 0.01) and lower-body strength (6.4±1.3, p < 0.01) from pre- to post-intervention, while participants in the Control group did not. The mean increase (from pre- to post-intervention) in lower-body strength for the EXCAP group was significantly higher than the change in the Control group (p = 0.01). Conclusions: Exercise combining aerobic walking and resistance band training reduces CRF and CRF interference with daily activities and improves muscular strength in BC patients. Results from this study provide further evidence of the benefits of exercise for supportive cancer care. Clinical trial information: NCT00851812.

Ansprechen auf eine Docetaxel-therapie im LNCaP-Prostata-karzinom-Xenograft-Mausmodell

2013 ◽  
Vol 52 (04) ◽  
pp. 141-147 ◽  
Author(s):  
M. Souvatzoglou ◽  
T. Schuster ◽  
R. Nawroth ◽  
G. Weirich ◽  
U. Treiber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Small Animal ◽  
Small Animal Pet ◽  
Control Group ◽  
Choline Uptake ◽  
Animal Pet ◽  
Choline Pet ◽  
Pet Ct ◽  
The Mean

SummaryThe aim of this study was to determine whether [11C]choline can be used for docetaxel therapy response assessment in a LNCaPprostate cancer xenograft mouse model using [11C]choline small-animal PET/CT. Animals, methods: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4–6 weeks after xenograft implantation with 37 MBq [11C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [11C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [11C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/ muscle (T/M) ratios (ROIT/ROIM = T/M ratio). Results: All LNCaP tumours could be visualized by [11C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [11C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/Mmean ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [11C]choline uptake in the control group. Conclusion: Our results show that [11C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

scholarly journals Heat Shock Protein 70 Inhibitor, Alone or in Combination with Bortezomib, Prevented Plasmacytoma Development in Immunodeficient Mice Transplanted with Myeloma Cell Lines

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5658-5658
Author(s):  
Mariana Bleker de Oliveira ◽  
Angela Isabel Eugenio ◽  
Veruska Lia Fook Alves ◽  
Daniela Zanatta ◽  
Mihoko Yamamoto ◽  
...  
Keyword(s):  
Cell Line ◽  
Tumor Cells ◽  
Cell Lines ◽  
Proteasome Inhibitor ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Immunodeficient Mice ◽  
Late Apoptosis

Abstract Introduction: HSP70 has an integrative role in protein degradation due to the interaction with many pathways, such as ubiquitin proteasome (UPS), unfolded protein response (UPR) and autophagy. In multiple myeloma (MM) HSP70 is overexpressed and helps to prevent proteotoxic stress and cell death caused by overload of unfolded/misfolded proteins produced by tumor cells. Aims: To explore the role of HSP70 inhibition, isolated or in association with proteasome inhibitor, as therapeutic strategy for MM through in vitro and in vivo analyses. Methods: RPMI8226-LUC-PURO and U266-LUC-PURO bioluminescent cell lines were treated with HSP70 inhibitor (VER155008- 50 μM or 80μM) and proteasome inhibitor (bortezomib 100nM) for evaluation of apoptosis induction by flow cytometry using annexin V and propidium iodide. NOD.Cg-rkdcscid Il2rgtm1Wjl/SzJ immunodeficient mice were used for plasmacytoma xenograft model and treated with intravenous VER155008 (40mg/kg) and bortezomib (1mg/kg), immediately after transplant of RPMI8226-LUC-PURO and U266-LUC-PURO bioluminescent cell lines (N=3 for each group, including controls, bortezomib, VER155008, and combination of bortezomib and VER155008). Bioluminescence was measured in IVIS Kinetic (Capiler Life Science) once a day for seven days. Results: Bortezomib used as single treatment was able to induce apoptosis in RPMI8226-LUC-PURO cell line: the best result for in vitro studies RPMI8226-LUC-PURO was 65% of late apoptosis after treatment with bortezomib. On the other hand, U266-LUC-PURO cell line presented higher percentage of apoptosis when treated with bortezomib and VER155008 combination: U266-LUC-PURO cell line presented more than 60% of late apoptosis after VER155008 (80μM) combined with bortezomib, showing that inhibition of HSP70 could overcome U266-LUC-PURO resistance to bortezomib alone. Mice treated with VER155008, alone or in combination with bortezomib, showed complete inhibition of tumor growth (absence of bioluminescence) for both cell lines when compared with control group after one week of treatment (p<0.001, Two-way ANOVA). Therefore, in vivo studies using mice treated with VER155008, alone or in combination with bortezomib, prevented tumor development after one week of treatment, independent of the cell line used in the xenotransplant. Conclusion: Our study shows that HSP70 and proteasome inhibitors combination induced apoptosis in tumor cells in vivo for both MM cell lines. Since HSP70 is overexpressed in MM and connects several signaling pathways that maintain cell survival, such as UPS, UPR and autophagy, it can represent a key role to establish a new approach for the treatment of MM. Financial support: FAPESP 2010/17668-6 and CNPq (155272/2013-6). UNIFESP Ethics Committee (0219/12). Disclosures No relevant conflicts of interest to declare.

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