scholarly journals Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5866
Author(s):  
Minhua Chen ◽  
Yutong Li ◽  
Yu Wu ◽  
Siqi Xie ◽  
Jie Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Nk Cells ◽  
Solid Tumors ◽  
High Dose ◽  
Dependent Manner ◽  
Free Expansion ◽  
Cell Counts ◽  
Cell Immunotherapy ◽  
Wide Range ◽  
Xenograft Mice

Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 107 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.

Lessons learned from a decade of clinical trials of high-dose chemotherapy in ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 53-58 ◽  
Author(s):  
J. A. Ledermann
Keyword(s):  
Ovarian Cancer ◽  
Solid Tumors ◽  
High Dose Chemotherapy ◽  
Marrow Transplant ◽  
Lessons Learned ◽  
Phase Iii ◽  
High Dose ◽  
Phase Ii Trials ◽  
Peripheral Blood Stem Cells ◽  
Hematological Cancers

Ovarian cancer is one of the most chemosensitive solid tumors and therefore a good example to explore high-dose chemotherapy (HDC). Interest in pursuing this treatment arose in the late 1980s following the success of HDC in treating hematological cancers and improvements in supportive care with peripheral blood stem cells. Experience from phase II trials and analysis of Bone Marrow Transplant Registry data led to the launch of several randomized phase III trials in the late 1990s. Initial enthusiasm for this treatment was in part due to the preliminary positive data emerging from HDC in breast cancer. Five randomized trials of HDC in ovarian cancer have been conducted and all experienced difficulty in recruitment. Their different designs and results are reviewed, as well as some of the lessons that have been learned about HDC in solid tumors in the last decade

Intravenous administration of ALKS 4230 as monotherapy and in combination with pembrolizumab in a phase I study of patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2649-TPS2649
Author(s):  
Ulka N. Vaishampayan ◽  
Mayer N. Fishman ◽  
Daniel C. Cho ◽  
Christopher J. Hoimes ◽  
Vamsidhar Velcheti ◽  
...  
Keyword(s):  
T Cells ◽  
Phase I ◽  
Solid Tumors ◽  
High Dose ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Part C ◽  
Cell Counts ◽  
Liver And Kidney ◽  
Ecog Ps

TPS2649 Background: ALKS 4230 is a fusion protein of circularly permuted IL-2 and IL-2 Receptor (IL-2R) α designed to selectively bind the intermediate-affinity (ia) IL-2R, comprised of IL-2Rβ and γc, for activation of CD8+ T cells and NK cells, which drive antitumor immune responses. In contrast, unmodified IL-2 activates high-affinity (ha) IL-2R, driving the expansion of immunosuppressive CD4+ regulatory T cells (Tregs) at concentrations below those that activate iaIL-2R expressing cells. Binding of IL-2 to haIL-2R on endothelial cells may contribute to capillary leak syndrome seen with high-dose IL-2. Thus, selective activation of the iaIL-2R by ALKS 4230 has the potential to enhance tumor killing and improve tolerability. ALKS 4230 has previously been shown to improve antitumor activity relative to IL-2 in murine models. In this clinical study, ALKS 4230 will be assessed as monotherapy and in combination with anti-PD-1 therapy. Methods: ALKS 4230 is being studied in adults with advanced solid tumors in a phase I first-in-human trial designed primarily to assess the safety of ALKS 4230 alone and with pembrolizumab. The study will also determine a monotherapy recommended phase 2 dose (RP2D) and characterize pharmacokinetics, pharmacodynamics (PD), immunogenicity, and evidence of anti-tumor activity. It will be conducted in 3 parts: monotherapy dose escalation (Part A), monotherapy dose expansion at the RP2D (Part B), and combination therapy with pembrolizumab (Part C). ALKS 4230 is administered as a 30 minute IV infusion once daily for five days in each 14 or 21 day cycle. Part A is inpatient. Eligibility requires ECOG PS 0-1 and adequate bone marrow, liver and kidney function. Part B will enroll 21 patients each in renal cell carcinoma and melanoma cohorts. Part C will enroll up to 79 patients total into 3 cohorts based on tumor type and prior anti-PD-1 therapy; a 4th cohort will enroll patients from Part A or B who received at least 4 cycles of ALKS 4230 or experienced disease progression on monotherapy. The primary PD endpoint is change from baseline in CD8+ T, NK, and Treg cell counts. Inflammatory cytokine levels will also be measured. Parts A and C are currently enrolling. Clinical trial information: NCT02799095.

scholarly journals Therapeutic Response of Epimedium gandiflorum’s Different Doses to Restore the Antioxidant Potential and Reproductive Hormones in Male Albino Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582095956 ◽  
Author(s):  
Naveed Munir ◽  
Zahed Mahmood ◽  
Muhammad Yameen ◽  
Ghulam Mustafa
Keyword(s):  
Therapeutic Response ◽  
Reducing Power ◽  
Reproductive Hormones ◽  
Male Rats ◽  
Albino Rats ◽  
High Dose ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Wide Range ◽  
Different Doses

Current study was planned to explore the therapeutic response of different doses of hydroethanolic extract of Epimedium grandiflorum leaves in male albino rats. Phytochemical analysis, HPLC and FTIR spectroscopy results revealed the presence of wide range of phenolic compounds and functional groups, respectively. Further, extract not induced significant hemolysis (7.56 ± 1.297%) against PBS (3.65 ± 0.35%) as negative control; while have significant clot lysis (44 ± 5.2%) potential, exhibited DPPH (78.87 ± 5.427%) scavenging, H2O2 (31.82 ± 3.491%) scavenging, antioxidant and reducing power activities. In vivo experimentation in albino male rats’ revealed that administration of different doses (50, 100, 200 mg/Kg b.w.) of extract orally for 42 days after CCl4 intoxication significantly (P < 0.05) restore the selected parameters including liver enzymes, renal profiles, and stress markers and significantly (P < 0.05) increased reproductive hormones like testosterone, luteinizing hormone, follicle stimulating hormone and prolactin while significantly (P < 0.05) decreased progesterone and estradiol toward normal in dose dependent manner. Significant (P < 0.05) improvement in the structural architecture of testicular tissue particularly in high dose group (200 mg/Kg b.w.) was also observed. Results revealed E. grandiflorum has significant therapeutic response to address the healthcare problems particularly of impotency.

scholarly journals pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity

2019 ◽  
Author(s):  
Janessa Wehr ◽  
Eden L. Sikorski ◽  
Elizabeth Bloch ◽  
Mary S. Feigman ◽  
Noel J. Ferraro ◽  
...  
Keyword(s):  
Immune System ◽  
Human Serum ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Wide Range ◽  
Ph Dependent

A growing class of immunotherapeutic agents work by redirecting components of the immune system to recognize specific markers on the surface of cancer cells and initiate a selective immune response. However, such immunotherapeutic modalities will remain confined to a relatively small subgroup of patients until two major hurdles are overcome: (1) the specific targeting of cancer cells relative to healthy cells, and (2) the lack of common targetable tumor biomarkers among all patients. Here, we designed a unique class of agents that exploit the inherent acidic microenvironment of solid tumors to selectively graft the surface of cancer cells with immuno-engager epitopes for directed destruction by components of the immune system. Specifically, conjugates were assembled using an antigen that recruit antibodies present in human serum, and the pH(Low) Insertion Peptide (pHLIP), a unique peptide that selectively target tumors in vivo by anchoring onto cancer cell surfaces in a pH-dependent manner. We established that conjugates can recruit antibodies from human serum to the surface of cancer cells, and induce complement-dependent and antibody-dependent cellular cytotoxicity by peripheral blood mononuclear cells and also an engineered NK cell line. These results suggest that these agents have the potential to be applicable to treating a wide range of solid tumors and to circumvent the problem of narrow windows of selectivity.

Risk of Subsequent Solid Tumors After Non-Hodgkin's Lymphoma: Effect of Diagnostic Age and Time Since Diagnosis

2008 ◽  
Vol 26 (11) ◽  
pp. 1850-1857 ◽  
Author(s):  
Kari Hemminki ◽  
Per Lenner ◽  
Jan Sundquist ◽  
Justo Lorenzo Bermejo
Keyword(s):  
Solid Tumors ◽  
Quantitative Data ◽  
Hodgkin’S Lymphoma ◽  
Age Groups ◽  
Hodgkin's Lymphoma ◽  
Dependent Manner ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Wide Range ◽  
Diagnostic Age

Purpose Quantitative data on subsequent cancers after primary cancers provide information on treatment-related risks on second cancers, with implications for therapeutic adverse effects and human susceptibility in general. Quantitative data on solid tumors are limited. We focus on survivors of non-Hodgkin's lymphoma (NHL) because the disease is diagnosed at a wide range of ages and treated uniformly primarily with chemotherapy. Patients and Methods The nationwide Swedish Family-Cancer Database included 11.5 million individuals whose cancers were retrieved from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent neoplasms among 28,131 patients with NHL. Results The SIR for solid tumors after NHL was 1.65 (2,290 patients) and that for lymphohematopoietic neoplasms was 5.36 (369 patients). Among the 25 most common solid tumors, the SIRs were increased for all but nine sites; the highest SIR (40.8) was observed for spinal meningioma. The SIRs for solid tumors declined in an age-dependent manner from 4.52 in diagnostic age younger than 20 years to 1.12 in diagnostic age 70+ years. In the most common patient groups, the SIRs for solid tumors increased up to 30 years after NHL diagnosis. Because of the high incidence of solid tumors in these age groups, they contributed the largest numbers of therapy-related cases. Conclusion These data indicate that age at treatment determines both the magnitude of the initial relative risk and the time-dependent modulation of the response. Therapy-related damage persists at least 30 years and its toll of solid tumors is largest 21 to 30 years after diagnosis.

scholarly journals High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1981 ◽  
Author(s):  
Qiufen Mo ◽  
Aikun Fu ◽  
Lingli Deng ◽  
Minjie Zhao ◽  
Yang Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Systemic Inflammation ◽  
Body Weight Gain ◽  
High Dose ◽  
Dependent Manner ◽  
Glucose And Lipid Metabolism ◽  
Glycerol Monolaurate ◽  
Indigenous Microbiota ◽  
Anti Inflammatory ◽  
Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

scholarly journals A Bacterial Tower of Babel: Quorum-Sensing Signaling Diversity and Its Evolution

2020 ◽  
Vol 74 (1) ◽  
pp. 587-606 ◽  
Author(s):  
Nitzan Aframian ◽  
Avigdor Eldar
Keyword(s):  
Quorum Sensing ◽  
Social Interactions ◽  
Signal Molecules ◽  
Allelic Polymorphism ◽  
Dependent Manner ◽  
Tower Of Babel ◽  
Cognate Receptor ◽  
Wide Range ◽  
Family Code ◽  
Bacterial Groups

Quorum sensing is a process in which bacteria secrete and sense a diffusible molecule, thereby enabling bacterial groups to coordinate their behavior in a density-dependent manner. Quorum sensing has evolved multiple times independently, utilizing different molecular pathways and signaling molecules. A common theme among many quorum-sensing families is their wide range of signaling diversity—different variants within a family code for different signal molecules with a cognate receptor specific to each variant. This pattern of vast allelic polymorphism raises several questions—How do different signaling variants interact with one another? How is this diversity maintained? And how did it come to exist in the first place? Here we argue that social interactions between signaling variants can explain the emergence and persistence of signaling diversity throughout evolution. Finally, we extend the discussion to include cases where multiple diverse systems work in concert in a single bacterium.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huan Lu ◽  
Guanlin Zheng ◽  
Xiang Gao ◽  
Chanjuan Chen ◽  
Min Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Erk Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Sign in / Sign up

Export Citation Format

Share Document