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Cancer Research Apr 2021Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of taxanes such as paclitaxel and docetaxel. Despite the high medical needs,... (Observational Study)
Observational Study
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of taxanes such as paclitaxel and docetaxel. Despite the high medical needs, insufficient understanding of the complex mechanism underlying CIPN pathogenesis precludes any endorsed causal therapy to prevent or relieve CIPN. In this study, we report that elevation of plasma galectin-3 level is a pathologic change common to both patients with taxane-treated breast cancer with CIPN and a mouse model of taxane-related CIPN. Following multiple intraperitoneal injections of paclitaxel in mice, galectin-3 levels were elevated in Schwann cells within the sciatic nerve but not in other peripheral organs or cells expressing galectin-3. Consistent with this, paclitaxel treatment of primary cultures of rat Schwann cells induced upregulation and secretion of galectin-3. migration assays revealed that recombinant galectin-3 induced a chemotactic response of the murine macrophage cell line RAW 264.7. In addition, perineural administration of galectin-3 to the sciatic nerve of naive mice mimicked paclitaxel-induced macrophage infiltration and mechanical hypersensitivity. By contrast, chemical depletion of macrophages by clodronate liposomes suppressed paclitaxel-induced mechanical hypersensitivity despite the higher level of plasma galectin-3. Deficiency ( mice) or pharmacologic inhibition of galectin-3 inhibited paclitaxel-induced macrophage infiltration and mechanical hypersensitivity. In conclusion, we propose that Schwann cell-derived galectin-3 plays a pronociceptive role via macrophage infiltration in the pathogenesis of taxane-induced peripheral neuropathy. Therapies targeting this phenomenon, which is common to patients with CIPN and mouse models, represent a novel approach to suppress taxane-related CIPN. SIGNIFICANCE: These findings demonstrate that the elevation of plasma galectin-3 is a CIPN-related pathologic change common to humans and mice, and that targeting galectin-3 is a therapeutic option to delay CIPN progression.
Topics: Animals; Antineoplastic Agents, Phytogenic; Blood Proteins; Cell Movement; Chemotaxis; Clodronic Acid; Disease Models, Animal; Docetaxel; Female; Galectins; Humans; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Paclitaxel; Pain Perception; Peripheral Nervous System Diseases; Prospective Studies; Rats; Schwann Cells; Sciatic Nerve; Up-Regulation
PubMed: 33608316
DOI: 10.1158/0008-5472.CAN-20-2799 -
The Journal of Obstetrics and... Jun 2022The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the... (Review)
Review
AIM
The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience.
METHODS
Regional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long-term.
RESULTS
An important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials.
CONCLUSIONS
Innovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Ovarian Epithelial; Cisplatin; Cytoreduction Surgical Procedures; Female; Humans; Hyperthermia, Induced; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; Pemetrexed; Peritoneal Neoplasms
PubMed: 35343033
DOI: 10.1111/jog.15224 -
Critical Reviews in Therapeutic Drug... 2020Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the... (Review)
Review
Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the development of drug resistance and severe side effects. Nanodrug delivery systems (NDDSs) such as nanoparticles and liposomes are being investigated to enhance the safety and efficacy of anticancer agents. NDDS-based delivery of a single agent is not found to be effective in long-term anticancer therapy. Codelivery of more than one anticancer agent using liposomes shows great potential since it exhibits simultaneous synergistic therapeutic manifestations at the tumor site and enhances therapeutic efficacy in terms of the low-dose requirement of each agent and diminished side effects. Liposomes are lipid vesicles arranged in concentric bilayers with an aqueous core; they are versatile nanocarriers that accommodate the diverse nature of anticancer drugs (both hydrophobic and hydrophilic) at the same time. They offer a number of advantages for combinatorial drug delivery in terms of increased blood circulation, selective accumulation at tumor tissues, and stimuli responsiveness. Various combination of drugs such as paclitaxel (PTX) and topotecan, sunitinib and irinotecan, and combretastin A-4 and doxorubicin have been reported for cancer chemotherapy using liposomes. This review focuses on recent scenarios of combinatorial drug delivery using liposomes for better chemotherapeutic outcomes. This assemblage can be of great importance to researchers looking for advances in novel drug delivery approaches for better cancer treatment.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Disease Models, Animal; Humans; Liposomes; Nanoparticles; Neoplasms; Treatment Outcome
PubMed: 32865902
DOI: 10.1615/CritRevTherDrugCarrierSyst.2019026358 -
European Journal of Cardio-thoracic... Jul 2016Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent... (Review)
Review
Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future.
Topics: Ablation Techniques; Antineoplastic Agents; Dendrimers; Drug Delivery Systems; Gene Transfer Techniques; Humans; Liposomes; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Micelles; Nanoparticles; Nanotechnology; Nanotubes, Carbon; Quantum Dots; Surgery, Computer-Assisted; Thoracic Surgical Procedures
PubMed: 26843431
DOI: 10.1093/ejcts/ezw002 -
Bulletin Du Cancer May 2017EARLY RELAPSE: Early relapse (primary or secondary) is defined by relapse of disease less than 6 months before the last infusion of chemotherapy (with a platinum...
EARLY RELAPSE: Early relapse (primary or secondary) is defined by relapse of disease less than 6 months before the last infusion of chemotherapy (with a platinum compound). There is no carcinological surgical indication. Disease should be treated with a non-platinum single agent (pegylated liposomal doxorubicin, weekly paclitaxel, gemcitabine or topotecan). Bevacizumab can be added if patients have not already received it (level of proof 1, grade A).
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Deoxycytidine; Doxorubicin; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; Topotecan; Gemcitabine
PubMed: 28625313
DOI: 10.1016/S0007-4551(17)30160-1 -
Current Pharmaceutical Design 2022Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species... (Review)
Review
Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species and is used as a chemotherapeutic agent against various cancers. The biosynthesis of paclitaxel is a complex pathway, making its total chemical synthesis commercially non-viable; hence, alternative novel sources - like plant cell culture and heterologous expression systems, are being investigated to overcome this issue. Advancements in the field of genetic engineering, microbial fermentation engineering, and recombinant techniques have significantly increased the achievable yields of paclitaxel. Indeed, paclitaxel selectively targets microtubules and causes cell cycle arrest in the G2/M phase, inducing a cytotoxic effect in a concentration and time-dependent manner. Innovative drug delivery formulations, like the development of albumin-bound nanoparticles, nano-emulsions, nano-suspensions, liposomes, and polymeric micelles, have been applied to enhance the delivery of paclitaxel to tumor cells. This review focuses on the production, biosynthesis, mechanism of action, and anticancer effects of paclitaxel.
Topics: Humans; Paclitaxel; Taxus; Antineoplastic Agents; Neoplasms; Nanoparticles
PubMed: 36330627
DOI: 10.2174/1381612829666221102155212 -
Cancer Radiotherapie : Journal de La... Jul 2021The aim of this study was to evaluate the efficacy of liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal...
PURPOSE
The aim of this study was to evaluate the efficacy of liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma (ESCC).
PATIENTS AND METHODS
Seventy-nine consecutive patients treated with liposome-paclitaxel based concurrent chemoradiotherapy between January 2015 and December 2019 at Cancer hospital of the University of Chinese Academy of Sciences (Zhejiang cancer hospital) were enrolled in this study. The overall response, toxicities, progression-free survival and overall survival were analyzed with SPSS software.
RESULTS
A total of 302 cycles of weekly chemotherapy were delivered, with a median 4 courses. After concurrent chemoradiotherapy (CCRT), the efficacy was classified as CR in 4 cases (5.1%), PR in 22 cases (28.2%) and SD in 51 cases (65.4%). The median PFS and OS time were 18.2 months and 23.4 months. The 3-year PFS and OS rates were 45.1% and 43.6%, respectively.
CONCLUSIONS
Liposome-paclitaxel and carboplatin concurrent with radiotherapy is a safe and effective modality for locally advanced ESCC. Further clinical investigation are warranted to evaluate the efficacy of this regimen.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemoradiotherapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Liposomes; Male; Middle Aged; Paclitaxel; Progression-Free Survival; Radiotherapy, Intensity-Modulated
PubMed: 33958272
DOI: 10.1016/j.canrad.2021.01.008 -
International Journal of Pharmaceutics Jun 2017In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of... (Review)
Review
In recent years, the nanotechnology has offered researchers the opportunity to solve the problems caused by the vehicle of the standard and first formulation of paclitaxel (Taxol), while maximizing the proven antineoplastic activity of the drug against many solid tumors. Hence, different types of nanocarriers have been employed to improve the efficacy, safety, physicochemical properties and pharmacokinetic/pharmacodynamic profile of this drug. To date, paclitaxel is the unique drug that is marketed in three different nanoplatforms for its parenteral delivery: polymeric nanoparticles (Abraxane), liposomes (Lipusu), and polymeric micelles (Genexol, Nanoxel and Paclical). Indeed, a fourth nanocarrier might be available soon, because phase III studies of Opaxio™, a polymeric-conjugated, are near completion. Furthermore, other several nanoformulations are currently in various stages of clinical trials. Therefore, it is only through the critical analysis of clinical evidence from these studies that we can get a more concrete idea of what has been achieved with pharmaceutical nanotechnology so far. This review attempts to summarize current information available regarding the clinical status and the physicochemical characteristic of different nanocarriers for paclitaxel delivery in cancer therapy. We present an overview of the preclinical and clinical data of these systems including their pharmacokinetics, dose and administration, adverse events and clinical efficacy.
Topics: Clinical Trials as Topic; Humans; Micelles; Nanoparticles; Nanotechnology; Paclitaxel; Polymers
PubMed: 28501439
DOI: 10.1016/j.ijpharm.2017.05.016 -
Journal of Controlled Release :... Jan 2022The combination of chemotherapy with the immune checkpoint blockade (ICB) therapy is bringing a tremendous hope in the treatment of malignant tumors. However, the...
The combination of chemotherapy with the immune checkpoint blockade (ICB) therapy is bringing a tremendous hope in the treatment of malignant tumors. However, the treatment efficacy of the existing chemo-immunotherapy is not satisfactory due to the high cost and immunogenicity of ICB antibodies, low response rate to ICB, off-target toxicity of therapeutic agents, and low drug co-delivery efficacy. Therefore, a high-efficient nanosystem combining the delivery of chemotherapeutics with small molecule ICB inhibitors may be promising for an efficient cancer therapy. Herein, a novel reactive oxygen species (ROS)-activated liposome nanoplatform was constructed by the loading of a ROS-sensitive paclitaxel derivative (PSN) into liposomes to overcome the difficulties on delivering paclitaxel mostly represented by premature drug release and a low amount accumulated into the tumor. The innovative liposomal nanosystem was rationally designed by a remote loading of BMS-202 (a small molecule PD-1/PD-L1 inhibitor) and PSN into the liposomes for a ROS-sensitive paclitaxel release and sustained BMS-202 release. The co-loaded liposomes resulted in a high co-loading ability and improved pharmacokinetic properties. An orthotopic 4 T1 breast cancer model was used to evaluate the efficiency of our nanoplatform in vivo, resulting in a superior antitumor activity. The antitumor immunity was activated by paclitaxel-mediated immunogenic cell death, while BMS-202 continuously blocked PD-L1 which could be up-regulated by paclitaxel in tumors to increase the response to ICB and further recover the host immune surveillance. These results revealed that this dual-delivery liposome might provide a promising strategy for a high-efficient chemo-immunotherapy, exhibiting a great potential for clinical translation.
Topics: Drug Delivery Systems; Drug Liberation; Immunotherapy; Paclitaxel; Photochemotherapy
PubMed: 34953979
DOI: 10.1016/j.jconrel.2021.12.023 -
European Journal of Pharmaceutics and... Nov 2023Pancreatic cancer (PC) is an incurable disease with a high death rate in the world nowadays. Gemcitabine (GEM) and Paclitaxel (PTX) are considered as references of... (Review)
Review
Pancreatic cancer (PC) is an incurable disease with a high death rate in the world nowadays. Gemcitabine (GEM) and Paclitaxel (PTX) are considered as references of chemotherapeutic treatments and are commonly used in clinical applications. Factors related to the tumor microenvironment such as insufficient tumor penetration, toxicity, and drug resistance can limit the effectiveness of these therapeutic anticancer drugs. The use of different liposomal nanostructures is a way that can optimize the drug's effectiveness and reduce toxicity. Given the development of PC therapy, this review focuses on advances in Nano-formulation, characterization, and delivery systems of loaded GEM and PTX liposomes using chemotherapy, nucleic acid delivery, and stroma remodeling therapy. As a result, the review covers the literature dealing with the applications of liposomes in PC therapy.
Topics: Humans; Gemcitabine; Paclitaxel; Liposomes; Deoxycytidine; Cell Line, Tumor; Pancreatic Neoplasms; Nanostructures; Tumor Microenvironment
PubMed: 37758121
DOI: 10.1016/j.ejpb.2023.09.014