Clinical therapeutic effects of combined methotrexate and other chemotherapeutic agents in treating children and young patients with osteosarcoma

Glycol chitosan (GC) is the chitosan derivative that is capable of forming amphiphilic nanoparticles upon structure modifications at the reactive functional amine group on the polymer sugar backbone. Owing to the hydrophilic feature of GC and hydrophobic moieties that can be added to the GC structure, modifiable nanosystems were constructed to entrap poorly soluble drugs, mostly chemotherapeutic agents and several anti-inflammatory, anaesthetic, immunosuppressant, and antifungal drugs for more efficient delivery of the payload to the target site and improving the intended therapeutic effects. This review highlights the various hydrophobic molecules used in the chemical modification of GC to create amphiphilic nanoparticles for hydrophobic drug delivery, along with the summary of their physicochemical criteria and successful therapeutic enhancement achieved with the application of the drug-loaded amphiphiles. The biodegradable, GC-based nanoparticles particularly having the inner hydrophobic core and outer hydrophilic shell are an efficient system for drug entrapment, protection and targeting to improve the bioavailability and safety of the drug, in particular for cancer treatment purposes. The significant drug delivery enhancements achieved by these various hydrophobically-modified GC nanoparticles may provide the insights for their further use in nanomedicine.

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Mucin-1 (MUC1) as a promising molecular target in anticancer therapy

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0013.0310 ◽

2019 ◽

Vol 73 ◽

pp. 53-64

Author(s):

Agnieszka Gornowicz ◽

Anna Bielawska ◽

Bożena Popławska ◽

Krzysztof Bielawski

Keyword(s):

Tumor Cells ◽

Anticancer Agents ◽

Intracellular Signaling ◽

Current Knowledge ◽

P53 Protein ◽

Chemotherapeutic Agents ◽

Therapeutic Effects ◽

Mucin 1 ◽

Shock Proteins

Mucin 1 (MUC1) has been recognized by the National Cancer Institute as one of the most promising molecular targets in cancer therapy. Its overexpression has been demonstrated in many epithelial tumors,especially in breast cancer, whichis associated with poor prognosis. Mucin 1 is an important barrier to the penetration of drugs and takes part in the inhibition of apoptosis in tumor cells. MUC1 triggers the activation of several pathways of intracellular signaling. MUC1 interactions with ICAM-1, E-selectin, galectin-3, EGFR, ERα estrogen receptor, p53 protein, heat shock proteins HSP70 and HSP90 have been demonstrated. The MUC1 membrane subunit contributes to the activation of the ERK1 and ERK2 kinases by the induction of the Ras-Raf-Mek-Erk pathway. In addition, the role of MUC1 in the activation of the WNT/β-catenin/TCF7L2 pathway and the induction of transcription of the cyclin D1 gene was confirmed. Numerous studies have shown that blockade of MUC1 by monoclonal antibodies or small molecule inhibitors may promote therapeutic effects and contribute to increased susceptibility of tumor cells to chemotherapeutic agents. The combined effect of the anti-MUC1 antibody with novel anticancer agents may have a better therapeutic effect than monotherapy. This article reviews the current knowledge about the role of MUC1 in the development and progression of cancer as well as potential novel strategies based on mucin 1 in antineoplastic therapy.

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Targeting CXCR2 inhibits the progression of lung cancer and promotes therapeutic effect of cisplatin

Molecular Cancer ◽

10.1186/s12943-021-01355-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yuan Cheng ◽

Fei Mo ◽

Qingfang Li ◽

Xuejiao Han ◽

Houhui Shi ◽

...

Keyword(s):

Lung Cancer ◽

T Cell ◽

Therapeutic Effect ◽

Chemotherapeutic Agents ◽

Human Lung Cancer ◽

Enzyme Linked Immunosorbent Assay ◽

Therapeutic Effects ◽

Tumor Tissues ◽

Mechanistic Investigation

Abstract Background Drug-resistance and severe side effects of chemotherapeutic agents result in unsatisfied survival of patients with lung cancer. CXCLs/CXCR2 axis plays an important role in progression of cancer including lung cancer. However, the specific anti-cancer mechanism of targeting CXCR2 remains unclear. Methods Immunohistochemical analysis of CXCR2 was performed on the microarray of tumor tissues of clinical lung adenocarcinoma and lung squamous cell carcinoma patients. CCK8 test, TUNEL immunofluorescence staining, PI-Annexin V staining, β-galactosidase staining, and Western blot were used to verify the role of CXCR2 in vitro. Animal models of tail vein and subcutaneous injection were applied to investigate the therapeutic role of targeting CXCR2. Flow cytometry, qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry analysis were performed for further mechanistic investigation. Results The expression of CXCR2 was elevated in both human lung cancer stroma and tumor cells, which was associated with patients’ prognosis. Inhibition of CXCR2 promoted apoptosis, senescence, epithelial-to-mesenchymal transition (EMT), and anti-proliferation of lung cancer cells. In vivo study showed that tumor-associated neutrophils (TANs) were significantly infiltrate into tumor tissues of mouse model, with up-regulated CXCLs/CXCR2 signaling and suppressive molecules, including Arg-1 and TGF-β. SB225002, a selective inhibitor of CXCR2 showed promising therapeutic effect, and significantly reduced infiltration of neutrophils and enhanced anti-tumor T cell activity via promoting CD8+ T cell activation. Meanwhile, blockade of CXCR2 could enhance therapeutic effect of cisplatin via regulation of neutrophils infiltration. Conclusions Our finds verify the therapeutic effects of targeting CXCR2 in lung cancer and uncover the potential mechanism for the increased sensitivity to chemotherapeutic agents by antagonists of CXCR2.

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WE-AB-BRA-02: Study of the Therapeutic Effects of Pulsed Focused Ultrasound Combined with Encapsulated Chemotherapeutic Agents for Prostate Cancer in Vivo

Medical Physics ◽

10.1118/1.4957731 ◽

2016 ◽

Vol 43 (6Part38) ◽

pp. 3791-3791

Author(s):

L Chen ◽

D Cvetkovic ◽

X Chen ◽

B Wang ◽

R Gupta ◽

...

Keyword(s):

Prostate Cancer ◽

Focused Ultrasound ◽

Chemotherapeutic Agents ◽

Therapeutic Effects ◽

Pulsed Focused Ultrasound

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Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening

Cancers ◽

10.3390/cancers12123714 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3714

Author(s):

G. Lavender Hackman ◽

Meghan Collins ◽

Xiyuan Lu ◽

Alessia Lodi ◽

John DiGiovanni ◽

...

Keyword(s):

Natural Products ◽

High Throughput ◽

High Throughput Screening ◽

Cancer Therapeutics ◽

Chemotherapeutic Agents ◽

The Body ◽

Cancer Drug ◽

Therapeutic Effects ◽

Cancer Drugs ◽

Antagonistic Effects

Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effects of natural products on cancer drugs that can diminish their therapeutic efficacy and prevent cancer regression. The ability of natural products to potentially degrade or reverse the molecular activity of cancer therapeutics represents an important but highly under-emphasized area of research that is often overlooked in both pre-clinical and clinical studies. This review aims to evaluate the body of work surrounding the antagonistic interactions between natural products and cancer therapeutics and highlight applications for high-throughput screening (HTS) and deep learning techniques for the identification of natural products that antagonize cancer drug efficacy.

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Insights into Multifunctional Nanoparticle-Based Drug Delivery Systems for Glioblastoma Treatment

Molecules ◽

10.3390/molecules26082262 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2262

Author(s):

Mohd Khan ◽

Subuhi Sherwani ◽

Saif Khan ◽

Sultan Alouffi ◽

Mohammad Alam ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Therapeutic Potential ◽

Treatment Options ◽

Survival Rates ◽

Delivery Systems ◽

Chemotherapeutic Agents ◽

Membrane Receptors ◽

Therapeutic Effects ◽

Microvascular Proliferation

Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development of resistance of tumor cells to radiation in the areas of hypoxia decreases the efficiency of such treatments. Additionally, the difficulty of ensuring drugs effectively cross the natural blood–brain barrier (BBB) substantially reduces treatment efficiency. These conditions concomitantly limit the efficacy of standard chemotherapeutic agents available for GB. Indeed, there is an urgent need of a multifunctional drug vehicle system that has potential to transport anticancer drugs efficiently to the target and can successfully cross the BBB. In this review, we summarize some nanoparticle (NP)-based therapeutics attached to GB cells with antigens and membrane receptors for site-directed drug targeting. Such multicore drug delivery systems are potentially biodegradable, site-directed, nontoxic to normal cells and offer long-lasting therapeutic effects against brain cancer. These models could have better therapeutic potential for GB as well as efficient drug delivery reaching the tumor milieu. The goal of this article is to provide key considerations and a better understanding of the development of nanotherapeutics with good targetability and better tolerability in the fight against GB.

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Coupling Ifosfamide to nanoemulsion-based clove oil enhances its toxicity on malignant breast cancer and cervical cancer cells

Pharmacia ◽

10.3897/pharmacia.68.e68291 ◽

2021 ◽

Vol 68 (4) ◽

pp. 779-787

Author(s):

Sahar M. AlMotwaa

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Chemotherapeutic Agents ◽

Therapeutic Effects ◽

Dependent Manner ◽

Clove Oil ◽

Dapi Staining ◽

Cytotoxicity Studies ◽

Mcf 7

The anticancer effects of chemotherapeutic agents may be accentuated, and their side effects minimized by combining them with essential oils in nanocarrier systems. This study aimed to incorporate ifosfamide (IF) into nanoemulsion-based clove oil (IF-CLV). The nano-emulsion (NE) formulas were characterized with Zetasizer. The cytotoxicity of the formulated NEs against cervical (HeLa) and breast (MCF-7) cancer cell lines was determined using MTT assay, light microscopy, and DAPI staining. The z – average diameters of NE-CLV and IF-CLV were 63.1±1.00 and 89.4±2.64 nm, while Zeta potential values were – 4.39±0.4 and – 11.65±1.1mV, respectively. Cytotoxicity studies revealed that relative to free IF, NE-CLV and IF-CLV were highly toxic on HeLa and MCF-7cells, in a dose-dependent manner. The half-maximal inhibitory concentration (IC50) values of NE-CLV against HeLa and MCF-7 have decreased 38 and 27 folds, while the corresponding IC50 values of IF-CLV have decreased 57 and 35 folds, respectively. These results suggest that the incorporation of IF into NE-based clove oil produces potent therapeutic effects against cancer cell lines.

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Assessment of Anti-Anemic Effects of Saccharum Munja Roxb Roots Extract

10.53350/pjmhs211562159 ◽

2021 ◽

Vol 15 (6) ◽

pp. 2159-2163

Author(s):

Shaawana Aslam ◽

Komal Najam ◽

Lubna Shakir ◽

Zaka ur Rehman ◽

Nasira Saeed ◽

...

Keyword(s):

Anticancer Agents ◽

Time Course ◽

Ethanolic Extract ◽

Treated Group ◽

Chemotherapeutic Agents ◽

Therapeutic Effects ◽

Beneficial Effects ◽

Saccharum Munja ◽

Hematological Changes ◽

Rbc Count

Anticancer agents often cause bone marrow suppression resulting in progressive anemia which may influence the therapeutic effects of different cancer treatment. Objective: The objective of this study was to evaluate, effects of ethanolic extract of Saccharum munja roxb (Kaana or Sirkanda) on hemoglobin and red blood cells counts suppressed by carboplatin. Methodology: Anemia was induced in mice with a single iv dose of 50 mg/kg carboplatin. Hematological responses including, RBC and Hb was measured at 3rd, 5thand 8th day. Saccharum munja roxbethanolicextract with dose of 25mg/kg, 50mg/kg and 100mg/kg were given to different treatment groups. Results: In the low dose (R. ext 25mg/kg) group hemoglobin level was found to be 11g/dl on 8thday. However (R.ext 50mg/kg) showed more improvement in hemoglobin levels i.e11.5 g/dl at 8th day. The mice treated with higher doses of extract (R.ext100mg/kg) showed major improvement in hemoglobin levels at 8th day which was 12.6g/dl.RBC count increased after oral administration of Saccharummunja extract (R.ext 25mg/kg) to 6.4 ×106cells /mm3 on 8thday. However, in (R.ext 50mg/kg) extract treated group RBC count was found to be 6.9 × 106cells /mm3 on 8thday. In (R.ext 100mg/kg) treated group the RBC count was 7.4 × 106 /mm3 on 8thday. Conclusion: Thus, the results suggested that ethanolic-extract ofSaccharum munja roxb at different dosesshow beneficial effects in improving different parameters of blood.This study also appropriately described the time course of hematological changes after carboplatin induced anemia in mice. Therefore, this study method can be useful tool to explore potential strategies for the management of anemia caused by chemotherapeutic agents. Keywords: Carboplatin, heamoglobin, Saccharummunja

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The Physician and the Children's Cancer Center

PEDIATRICS ◽

10.1542/peds.40.3.521 ◽

1967 ◽

Vol 40 (3) ◽

pp. 521-525

Author(s):

John R. Hartmann ◽

John R. Hartmann

Keyword(s):

Prior Experience ◽

Fatal Outcome ◽

Chemotherapeutic Agents ◽

Cancer Center ◽

Therapeutic Effects ◽

Pediatric Practice ◽

Original Diagnosis ◽

Dying Children ◽

Pediatric Oncologist ◽

Specific Length

IT HAS BEEN suggested that my role in this conference be twofold: first, supposedly the confessions of a pediatric oncologist; second, the description of our program here in Seattle. The first one is rather difficult to detail concretely. Having been in general pediatric practice at one time, I think the role we oncologists have is one of the most frustrating and difficult but, at times, the most gratifying one in medicine. No one wants to take care of dying children by preference. Most of us have been hematologists and have gotten into the field of oncology because of the therapeutic effects of chemotherapeutic agents, especially in children with leukemia. I think from prior experience we recognize immediately upon original diagnosis the fatal outcome of a child with leukemia. We also try to transmit our deep compassion to the parents and to give them some ray of hope. We often look upon this area as that of a religious experience in which one has to have some beliefs to go on taking care of these children. We must believe within ourselves that a cure is possible, rarely at the present time, but hopefully in the future. I do not think this is being untruthful to the parent because we must give them some ray of hope—either control of the child's disease for a specific length of time or, aside from leukemia, more hope for potential cure. We are sometimes a little schizoid in our actions because we will treat a child with acute leukemia believing that the treatment of the child is worthwhile, while on the other hand we may cause considerable prolonged emotional conflict in the parents with repeated episodes of crises.

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Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel

Molecules ◽

10.3390/molecules25051035 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1035 ◽

Cited By ~ 7

Author(s):

Irum Naz ◽

Shanaya Ramchandani ◽

Muhammad Rashid Khan ◽

Min Hee Yang ◽

Kwang Seok Ahn

Keyword(s):

Cancer Cells ◽

Signaling Pathway ◽

Molecular Mechanisms ◽

Malignant Cell ◽

Chemotherapeutic Agents ◽

Systemic Review ◽

Parp Cleavage ◽

Therapeutic Effects ◽

Depth Study ◽

Canonical Wnt

Natural compounds extracted from plants have gained immense importance in the fight against cancer cells due to their lesser toxicity and potential therapeutic effects. Raddeanin A (RA), an oleanane type triterpenoid is a major compound isolated from Anemone raddeana Regel. As an anticancer agent, RA induces apoptosis, cell cycle arrest, inhibits invasion, migration and angiogenesis in malignant cell lines as well as in preclinical models. In this systemic review, the pharmacological effects of RA and its underlying molecular mechanisms were carefully analyzed and potential molecular targets have been highlighted. The apoptotic potential of RA can be mediated through the modulation of Bcl-2, Bax, caspase-3, caspase-8, caspase-9, cytochrome c and poly-ADP ribose polymerase (PARP) cleavage. PI3K/Akt signaling pathway serves as the major molecular target affected by RA. Furthermore, RA can block cell proliferation through inhibition of canonical Wnt/β-catenin signaling pathway in colorectal cancer cells. RA can also alter the activation of NF-κB and STAT3 signaling pathways to suppress invasion and metastasis. RA has also exhibited promising anticancer potential against drug resistant cancer cells and can enhance the anticancer effects of several chemotherapeutic agents. Overall, RA may function as a promising compound in combating cancer, although further in-depth study is required under clinical settings to validate its efficacy in cancer patients.

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