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Combined inhibition of JAK1,2/Stat3‑PD‑L1 signaling pathway suppresses the immune escape of castration‑resistant prostate cancer to NK cells in hypoxia.

Castration‑resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4‑2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP‑1, ULBP‑2 and ULBP‑3) and MHC class I chain‑related proteins A and B

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… Targeting the Vav3 oncogene enhances docetaxel-induced apoptosis through the inhibition of androgen receptor phosphorylation in LNCaP prostate cancer cells under chronic hypoxia. Mol Cancer. 2013;12:27. doi: 10.1186/1476-4598-12-27. 13. Barsoum IB, Koti M, Siemens DR, Graham CH. …

Healthcare-resource utilization associated with radiation to bone across eight European countries: Results from a retrospective study.

BackgroundBone metastases and lytic lesions due to multiple myeloma are common in advanced cancer and can lead to debilitating complications (skeletal-related events [SREs]), including requirement for radiation to bone. Despite the high frequency of radiation to bone in patients with metastatic bone disease, our knowledge of associated healthcare resource utilization (HRU) is limited.MethodsThis retrospective study estimated HRU following radiation to bone in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and Switzerland. Eligible patients were ≥ 20 years old, had bone

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… Newer antineoplastic agents have also been shown to reduce the incidence of SREs in patients with prostate cancer: the anti-androgens enzalutamide and abiraterone acetate reduced pain in placebo-controlled phase 3 trials in patients with prostate cancer who had previously received docetaxel [9] , [25 …

A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors.

The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4-18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblast

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… Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014;7:1 10.1186/1756-8722-7-1 27. Bendell JC, Nemunaitis J, Vukelja SJ, Hagenstad C, Campos LT, Hermann RC, et al. …

Bortezomib alters sour taste sensitivity in mice.

Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the co

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… Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer J. Clin. Oncol. 24 2006 5025 5033 17075122 10.1200/JCO.2006.06.1853 11 Bruna J. Udina E. Alé A. Vilches J.J. Vynckier A. Monbaliu J. Silverman L. …

Predicting tumour response.

Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm ta

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… Contractor KB, Kenny LM, Stebbing J, et al. [18F]-3′Deoxy-3′-fluorothymidine positron emission tomography and breast cancer response to docetaxel. Clin Cancer Res. 2011;17:7664–7672. doi: 10.1158/1078-0432.CCR-11-0783. doi:10.1158/1078-0432.ccr-11-0783. PMid:22028493. 19. …

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A m

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… drug | [ 102 ] SFP | ↓ | ↓ | CRC | 5-fluorouracil, Irinotecan | [ 103 ] SIVA1 | ↓ | ↑ | CRC | 5-fluorouracil | [ 104 ] G6PD, PARP1 | ↑ | ↑ | CRC | 5-fluorouracil, cisplatin | [ 105 ] LINC01134 | ↑ | ↑ | PAAD | Gemcitabine | [ 106 ] NEDD4 | ↑ | ↑ | PAAD | Gemcitabine | [ 107 ] LINC01559 | ↑ | ↑ | BC | Docetaxel … METTL1 induced WNT/β-catenin signaling pathway and EMT and promoted resistance to cisplatin and docetaxel ( a depolymerization inhibitor of microtubules). Conversely, overexpression of WNT3A inhibited METTL1 induced chemoresistance. …

Cardiovascular Considerations Before Cancer Therapy: Gaps in Evidence and JACC: CardioOncology Expert Panel Recommendations.

Baseline cardiovascular assessment before the initiation of potentially cardiotoxic cancer therapies is a key component of cardio-oncology, aiming to reduce cardiovascular complications and morbidity in patients and survivors. Recent clinical practice guidelines provide both general and cancer therapy-specific recommendations for baseline cardiovascular toxicity risk assessment and management, including the use of dedicated risk scores, cardiovascular imaging, and biomarker testing. However, the value of such interventions in altering disease trajectories has not been established, with many re

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… New biomarkers for early detection of cardiotoxicity after treatment with docetaxel, doxorubicin and cyclophosphamide. Biomarkers. 2015;20:143–148. doi: 10.3109/1354750X.2015.1040839. 42. Lemieux J., Diorio C., Côté M.-A., et al. … Correlation of HER2 codon 655 polymorphism with cardiotoxicity risk in Chinese HER2-positive breast cancer patients undergoing epirubicin/cyclophosphamide followed by docetaxel plus trastuzumab adjuvant chemotherapy. Int J Clin Exp Pathol. 2020;13:286. 44. …

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia.

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-2

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… Paclitaxel resistance | [ 119 ] Ovarian | - | ↑ Tumor cell growth ↑ Metastasis formation in vivo | [ 161 ] Colorectal | MTTP | ↓ Tumor cell ferroptosis Oxaliplatin resistance | [ 115 ] Colorectal | - | ↑ Tumor cell invasion and migration | [ 162 ] Prostate | - | ↑ Tumor cell proliferation and migration Docetaxel … Similarly, EVs released by white adipocytes could negatively impact the sensitivity of prostate cancer cells to docetaxel treatments [ 120 ] . …

Clinical Outcomes of Endoscopic Submucosal Dissection for Early Gastric Cancer Patients With Concurrent Advanced Malignancies With Expected Poor Prognosis.

AimsDespite improved outcomes for malignant tumors, evidence regarding the management of patients with multiple malignancies remains limited. We aimed to evaluate the clinical outcomes and prognosis of patients undergoing endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) complicated by advanced malignancies in other organs with a poor prognosis.Methods and resultsWe retrospectively reviewed 3703 gastric cancer patients who underwent ESD at our hospital (2005-2022), focusing on those with advanced extra-gastric malignancies with a 5-year survival rate of ConclusionsRecently,

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… Baas , et al., “ Nivolumab Versus Docetaxel in Advanced Squamous‐Cell Non‐Small‐Cell Lung Cancer ,” New England Journal of Medicine 373 ( 2015 ): 123 – 135 . 26028407 10.1056/NEJMoa1504627 PMC4681400 3 M. Davis , D. Hui , A. …

Anti-BCMA-engineered exosomes for bortezomib-targeted delivery in multiple myeloma.

AbstractExosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared with conventional drug delivery systems. In this study, we developed a delivery platform using exosomes derived from monocytes, specifically designed for targeted delivery of bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B-cell maturation antigen (anti-BCMA), because BCMA sele

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… Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2006;24(31):5025–5033. doi: 10.1200/JCO.2006.06.1853. 19. Yang CH, Gonzalez-Angulo AM, Reuben JM, et al. …

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer.

Reactive oxygen species (ROS) are a class of bioactive molecules that are the by-products of many cellular functions. These molecules are present in normal cells at homeostatic levels but have been studied extensively in cancer due to their dysregulation resulting in pro- and anti-tumorigenic environments. Completely understanding the paradoxical nature of ROS in cancer is imperative to fully realize its modulation as cancer therapy. Studies into ROS have shown far-reaching effects in cancer, including how ROS levels regulate signaling, response to treatment, drug resistance, etc. Many drugs w

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… There was a drastic increase in apoptosis of A549/D16 cells due to ROS guided p38 MAPK phosphorylation. 59 This affect was exaggerated when used in combination with Docetaxel and Vincristine with little toxicity arising upon the Cur addition, suggesting that Cur has a role in enhancing chemotherapeutic …

The Association between Pretreatment anemia and Overall Survival in Advanced Non-small Cell lung Cancer: A Retrospective Cohort Study Using Propensity Score Matching.

Background: The purpose of this study was to investigate whether pretreatment anemia was an independent risk factor for survival in patients with advanced non-small cell lung cancer (NSCLC) after adjusting for other covariates. Methods: We used propensity score matching (PSM) to minimize the influence of confounding factors and used χ2 (categorical variables), Student's t-test (normal distribution), or Mann-Whitney U test (skewed distribution) to analyze the differences among the Hb groups. Cox regression and Kaplan-Meier analyses were used to assess the association between anemia and survival

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… The Prognostic Value of Pre-Treatment Leukocytosis in Patients with Previously Treated, Stage IIIB/IV Non-Small Cell Lung Cancer Treated with the IGF-1R Pathway Modulator AXL1717 or Docetaxel; a Retrospective Analysis of a Phase II Trial. …

Clinical, economic and organizational impact of pharmacist interventions on injectable antineoplastic prescriptions: a prospective observational study.

BackgroundPharmacists play a key role in ensuring the safe use of injectable antineoplastics, which are considered as high-alert medications. Pharmaceutical analysis of injectable antineoplastic prescriptions aims to detect and prevent drug related problems by proposing pharmacist interventions (PI). The impact of this activity for patients, healthcare facilities and other health professionals is not completely known. This study aimed at describing the clinical, economic, and organizational impacts of PIs performed by pharmacists in a chemotherapy preparation unit.MethodsA prospective 10-week

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… Hands and feet paresthesia prior to paclitaxel | 1 | 1 Oncology day care unit | Supra-therapeutic dosage | Paclitaxel | Dose adjustment | Expected reduction of 80% for paclitaxel not applied Toxicity during previous treatments: Neuropathy | 1 | 1 Oncology day care unit | Supra-therapeutic dosage | Docetaxel …

Prevention of Bortezomib-Related Peripheral Neuropathy With Docosahexaenoic Acid and α-Lipoic Acid in Patients With Multiple Myeloma: Preliminary Data.

BACKGROUND AND AIMS: Peripheral neuropathy is a common complication of chemotherapy that can induce marked disability that negatively affects the quality of life in patients with multiple myeloma (MM). The aim of this study was to prevent the onset or the worsening of peripheral neuropathy in MM patients treated with bortezomib (BTZ), using a new nutritional neuroprotective compound. We report preliminary results of 18 out of 33 patients who completed the study. METHODS: We administered a tablet of Neuronorm to patients, containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C

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… In the literature, only 2 small trials have studied the therapeutic effect of ALA alone in patients with CIPN due to docetaxel and oxaliplatin, 26 observing an improvement of neuropathic symptoms. …

Minimally effective concentration of zoledronic acid to suppress osteoclasts in vitro.

Zoledronic acid is regarded as the most potent bisphosphonate and is widely used in patients with osteoporosis; however, its side effects, including acute-phase reactions, gastrointestinal complaints, renal dysfunction and bisphosphonate-associated osteonecrosis impair the safety and quality of life of patients. The present study was designed to determine the minimal effective concentration of zoledronic acid through testing the dose-dependent effects of zoledronic acid on osteoclast suppression. A primary culture of bone marrow mononuclear cells obtained from C57 mice (age, 6 weeks) was estab

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… Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (stampede): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–1177. doi: 10.1016/S0140-6736(15)01037-5. 13. …

Acceptance of health technology assessment submissions with incremental cost-effectiveness ratios above the cost-effectiveness threshold.

ObjectivesIn health technology assessment (HTA) agencies where cost-effectiveness plays a role in decision-making, an incremental cost-effectiveness ratio (ICER) threshold is often used to inform reimbursement decisions. The acceptance of submissions with ICERs higher than the threshold was assessed across different agencies and across indications, in order to inform future reimbursement submissions.MethodsAll HTA appraisals from May 2000 to May 2014 from National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (P

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… rationale provided by HTA body a PAS/risk sharing scheme b | Unmet need/lack of alternative therapeutic options | High clinical benefit c | Orphan/rare disease | End of life considerations NICE ( £ ) Abiraterone + prednisolone | Castration-resistant metastatic prostate cancer previously treated with one docetaxel-containing …

A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.

BackgroundCurrently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Methods and findingsAffymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic

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… Chang JC, Wooten EC, Tsimelzon A, Hilsenbeck SG, Gutierrez MC, et al. (2003) Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet 362: 362–369. 32. …

Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G₂ delay and mitotic defects.

The development of clinically useful histone deacetylase inhibitors has expanded greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits cell cycle progression of human head and neck squamous cell carcinoma (HNSCC) cell lines at G₂/M and an associated decrease in expression of particular genes required for passage through G₂ and mitosis. In this study we sought to analyse the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell lines were synchronised and progression through mitosis monitored. We demonstrate that panobinostat causes a marked G₂ del

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… A phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer . Cancer Chemother Pharmacol. 66 , 181 – 189 ( 2010 ). 20217089 10.1007/s00280-010-1289-x LaBonte M. J. et al. …

Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology.

Oleocanthal (OC), a secoiridoid phenolic compound exclusive to extra virgin olive oil (EVOO), has emerged as a promising nutraceutical with multifaceted anti-cancer properties. Despite its well-characterized anti-inflammatory and antioxidant effects, the mechanistic breadth and translational potential of OC in oncology remain underexplored and fragmented across the literature. This comprehensive review synthesizes and critically analyzes recent advances in the molecular, pharmacological, and translational landscape of OC's anti-cancer activities, providing an integrative framework to bridge pr

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistan