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Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment.

The skeletal system is of paramount importance in advanced stage prostate cancer (PCa) as it is the preferred site of metastasis. Complex mechanisms are employed sequentially by PCa cells to home to and colonize the bone. Bone-resident PCa cells then recruit osteoblasts (OBs), osteoclasts (OCs), and macrophages within the niche into entities that promote cancer cell growth and survival. Since PCa is heavily reliant on androgens for growth and survival, androgen-deprivation therapy (ADT) is the standard of care for advanced disease. Although it significantly improves survival rates, ADT detrime

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… J Biol Chem ( 2002 ) 277 ( 18 ): 15813 – 8 . 10.1074/jbc.M201075200 11867640 69 Dhani NC Emmenegger U Adams L Jongstra J Tannock IF Sridhar SS Phase II study of cytarabine in men with docetaxel-refractory, castration-resistant prostate cancer with evaluation of TMPRSS2-ERG and SPINK1 as serum biomarkers …

The Osteoclast in Bone Metastasis: Player and Target.

Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenome

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… So far, there is an ongoing phase II clinical trial for the treatment of metastatic prostate cancer patients using the anti-αvβ3 integrin human monoclonal antibody, Etaracizumab, in combination with docetaxel, zoledronate and prednisone ( NCT00072930 ). …

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

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… In castration-resistant prostate cancer, Zol reduces skeletal-related events, especially when combined with docetaxel [ 143 ]. In addition, Zol has been shown to reduce skeletal-related events in multiple myeloma patients [ 143 ]. Zol has shown preclinical and clinical activity in MPM. …

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Cabazitaxel (Jextana ® ), a new microtubule-stabilizing taxane has been effective against metastatic breast- and metastatic hormone-resistant prostate cancer that acquired resistance to both paclitaxel and docetaxel [ 61 ]. …

Comprehensive review of targeted therapy for colorectal cancer.

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approa

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… Mice with human prostate cancer xenografts that express PSMA might exhibit an improved tumour response to a docetaxel nanoparticle that targets PSMA rather than to passively targeting nanoparticles [ 125 ]. …

The Cancer Antioxidant Regulation System in Therapeutic Resistance.

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cancer cells adeptly maintain elevated levels of both ROS and antioxidants through a process termed "redox reprogramming". This balance optimizes the proliferative influence of ROS while simultaneously reducing the potential for ROS to cause damage to the cell. In some cases, the adapted antioxidant machinery can hamper the efficacy of treatments for neoplastic diseases, representing a significant facet of the resistance mechanisms ob

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… In NSCLC cells, GLUD1 overexpression promoted the increased entry of glutamate into the TCA cycle, leading to the overload of the electron transport chain (ETC) and the production of significant amounts of ROS, which, in turn, promoted the EMT and resistance to docetaxel [ 260 ]. …

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one : National Harbor, MD, USA. 9-13 November 2016

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Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Potential of gamma/delta T cells for solid tumor immunotherapy.

Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis

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… radical prostatectomy | | JPRN- UMIN000006617 | | Auto-gamma/delta T cell | 2012 | Multiple myeloma | | JPRN- UMIN000007878 | | Gamma-delta T Cells | 2012 | Epithelial Ovarian Cancer IClyCO | | NCT01606358 | | Autologous gamma/delta T cell | 2012 | Esophageal cancer | | JPRN- UMIN000008097 | Docetaxel …

The Battlefield of Chemotherapy in Pediatric Cancers.

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses

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… As P-gp is the substrate of a broad range of antineoplastic agents, overexpressed P-gp has been demonstrated to lead to the development of drug resistance, including chemotherapeutic agents Vinca alkaloids (vinblastine and vincristine), Taxanes (paclitaxel and docetaxel), Anthracyclines (doxorubicin, …

Oncology biosimilars: New developments and future directions.

Biologicals have become an integral part of cancer treatment both as therapeutic agents and as supportive care agents. It is important to know that biologics are large, complex molecular entities requiring extensive immunogenicity testing and pharmacovigilance strategies to ensure no immune response is evoked in the body. Oncology's pharmacological market is dominated by biologics; however, their high development and manufacturing costs are burdensome to health care systems. Biologics being the most expensive prescription drugs on the market limit the accessibility for necessary treatment in t

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… A Study of SIBP‐01 or CN‐Trastuzumab Plus Docetaxel And Carboplatin In HER2 Positive Breast Cancer. Identifier: NCT03989037 Available from: https://clinicaltrials.gov/ct2/show/NCT03989037 . 163 National Library of Medicine (U.S.) . …

Dynamic roles of inflammasomes in inflammatory tumor microenvironment.

The inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysreg

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… Gluck S TP53 genomics predict higher clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine +/- trastuzumab Breast Cancer Res. Treat. 2012 132 781 791 10.1007/s10549-011-1412-7 21373875 121. …

Efficacy and Safety of Filgrastim and Its Biosimilars to Prevent Febrile Neutropenia in Cancer Patients: A Prospective Study and Meta-Analysis.

Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrop

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… XM02 is superior to placebo and equivalent to Neupogen™ in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer. 2008;8:332. doi: 10.1186/1471-2407-8-332. 79. …

The changing therapeutic landscape, burden of disease, and unmet needs in patients with cutaneous T-cell lymphoma.

Cutaneous T-cell lymphomas (CTCLs) have a chronic, relapsing course, and the most common subtypes are mycosis fungoides and Sézary syndrome. The disease causes visible skin alterations and can also cause alopecia, pruritus and pain, all of which can impact patients' health-related quality of life (HRQoL). The goal of treatment is to reduce symptoms and prevent disease progression. However, treatment recommendations are often based on low levels of evidence due to the lack of well-designed randomised clinical trials and treatment guidelines, and approved drugs vary considerably across different

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… Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non‐small cell lung cancer in patients previously treated with platinum‐based chemotherapy . …

Minimal Residual Disease in Multiple Myeloma: Something Old, Something New.

The game-changing outcome effect, due to the generalized use of novel agents in MM, has cre-ated a paradigm shift. Achieving frequent deep responses has placed MM among those neoplasms where the rationale for assessing MRD is fulfilled. However, its implementation in MM has raised specific questions: how might we weight standard measures against deep MRD in the emerging CAR-T setting? Which high sensitivity method to choose? Are current response criteria still useful? In this work, we address lessons learned from the use of MRD in other neoplasms, the steps followed for the harmonization of cu

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… Docetaxel Plus Prednisone or Mitoxantrone Plus Prednisone for Advanced Prostate Cancer 50 Studies Every Urologist Should Know Oxford University Press Oxford, UK 2021 83 88 10.1093/med/9780190655341.003.0015 4. Anderson K.C. Auclair D. Kelloff G.J. Sigman C.C. Avet-Loiseau H. Farrell A.T. …

Pulmonary Hypertension in an Oncologic Intensive Care Unit

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… Pericardial disease (tamponade, constrictive pericarditis) | • Amyloidosis • Carcinoid heart disease • Cardiac tumors • Radiation therapy • SVC syndrome • Anthracyclines (doxorubicin, epirubicin, idarubicin) • Anthraquinone (mitoxantrone) • Alkylating agents (cyclophosphamide, ifosfamide) • Taxanes (docetaxel …

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities

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… This phase II clinical trial aimed at evaluating whether esomeprazole improves efficacy of docetaxel and cisplatin treatment in metastatic breast cancer. The results showed that high dose PPIs proved beneficial and improved chemotherapy efficacy [ 124 ]. …

Leptomeningeal disease: current diagnostic and therapeutic strategies.

OBJECTIVES: We determined the efficacy of the use of a tension free prolene mesh to correct a grade III anterior vaginal wall prolapse recurrence. METHODS: Twelve women (mean age 65.6 years) with stress urinary incontinence (SUI) (4 type II and 1 type III) and bladder prolapse entered the study. After vaginal incision a pretailored polypropylene mesh was fixed to its four angles by absorbable sutures to the urethropelvic ligaments and pubocervical fascia anteriorly and to the cardinal ligaments and pubocervical fascia posteriorly. When present, a posterior descensus was corrected during the s

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… Phase III trials include the ASCEND4 trial, where treatment is randomized to platinum pemetrexed versus ceritinib, and the ASCEND5 trial, where patients failing crizotinib are randomized to pemetrexed, docetaxel, or ceretinib [ 131 ]. …

Pharmacogenomics and Big Data in medical oncology: developments and challenges.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient's response to various drugs with the aim to minimize tria

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… alkaloids) | Irinotecan, Topotecan Etoposide, Teniposide | Interference with enzymes that assist with DNA replication; cell arrest in the radiosensitive phases of cell cycle | Lung, ovarian, colorectal, gastrointestinal, pancreatic, leukaemias | 12 , 13 Mitotic inhibitors/Taxanes (plant alkaloids) | Docetaxel …