Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat

Abstract: Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the earl...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Publication date: Available online 11 November 2019Source: Trends in Pharmacological SciencesAuthor(s): Bushu Dong, Alex M. Jaeger, Dennis J. ThieleThe ability of cancer cells to cope with stressful conditions is critical for their survival, proliferation, and metastasis. The heat shock transcription factor 1 (HSF1) protects cells from stresses such as chemicals, radiation, and temperature. These properties of HSF1 are exploited by a broad spectrum of cancers, which exhibit high levels of nuclear, active HSF1. Functions for HSF1 in malignancy extend well beyond its central role in protein quality control. While HSF1 has be...
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 12 November 2019Source: Pharmacological ResearchAuthor(s): Zhuojun Liu, Jia Liu, Tianming Zhang, Mingxia Shi, Xiaofang Chen, Yun Chen, Jian YuAbstractReceptor tyrosine kinase-like orphan receptor 1 (ROR1) is an onco-embryonic antigen presented on chronic lymphocytic leukemia (CLL), but not on normal adult tissues, which promotes CLL-cell survival. Here, ROR1 was identified as a new client of Heat Shock Protein 90 (HSP90) via a mass spectrometry-based screen for ROR1-associated partners followed by co-immunoprecipitation (co-IP) analysis. A binding motif (ELHHPNIV) on ROR1 for HSP90 was re...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 11 November 2019Source: International Journal of PharmaceuticsAuthor(s): Mahsa Shahriari, Seyed Mohammad Taghdisi, Khalil Abnous, Mohammad Ramezani, Mona AlibolandiAbstractIn the current research, the synthesis of polysaccharide-based polymersomes for targeted delivery of doxorubicin is reported. To this aim, doxorubicin was encapsulated in aqueous compartment of hyaluronan-polycaprolactone polymersomes via nanoprecipitation method. Then the therapeutic index of the prepared formulation was studied in metastatic breast cancer model in vitro and in vivo.The size of obtained polymersomes wa...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 11 November 2019Source: International Journal of PharmaceuticsAuthor(s): Anirban Jana, Pankhuri Narula, Archana Chugh, Ritu KulshreshthaAbstractThe levels of microRNAs (miRNAs) are altered in various diseases including glioblastoma (GBM) and this alteration may have widespread effects on various hallmarks of cancer cells. MiR210 is overexpressed in GBM and functions as an oncogenic miRNA. Anti-miR210 therapy holds great promise but its efficient delivery remains a major challenge. Our work here explores a novel role of Tachyplesin (Tpl), a cell-penetrating antimicrobial peptide, as a nano...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
ConclusionOur result indicated miR-195 suppresses cyclin D1 and Cdc42 to inhibit EC cell proliferation, and Cdc42 may via regulating both cyclin D1-dependent and independent pathways to control EC cell proliferation.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
ConclusionThe effects of PLB in endocrine-resistant breast cancer cells is dependent on NQO1’s activity.Graphical Abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky. Methods A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR. Results Bivariate testing showed differences (P
Source: Annals of Plastic Surgery - Category: Cosmetic Surgery Tags: Breast Surgery Source Type: research
Conclusions Although both types of flaps offer a satisfactory approach for finger reconstruction with small-to-medium defects, FDUAP flaps are more suitable for such operations because of the better sensory reconstruction and aesthetic results.
Source: Annals of Plastic Surgery - Category: Cosmetic Surgery Tags: Hand Surgery Source Type: research
This article describes ossification of the corresponding vascular pedicle after soft tissue transfer with the lateral upper arm free flap and microsurgical anastomosis in oral cancer treatment. Similar findings in the context of the lateral upper arm free flap have never been reported in the literature; however, it is important for surgeons to know that pedicle ossification can occur. This knowledge may be helpful to avoid erroneous diagnosis of the ossification as a sign of tumor relapse/recurrence as well as to anticipate potential difficulties in the surgical approach in cases requiring reentry of the reconstructed regi...
Source: Annals of Plastic Surgery - Category: Cosmetic Surgery Tags: Microsurgery Source Type: research
This study compares the postoperative pain and opioid use in patients managed for surgery with general anesthesia (GA) with patients who were given combined epidural and general anesthesia (E/GA) with continuing postoperative epidural analgesia. Methods All patients who underwent penile inversion vaginoplasty between May of 2016 and May of 2018 under the care of single surgeon were identified retrospectively, 18 patients of which met the inclusion criteria. A retrospective chart review was conducted. Outcome measures were postoperative pain using visual analog scale, type and dosage of postoperatively administered intra...
Source: Annals of Plastic Surgery - Category: Cosmetic Surgery Tags: Reconstructive Surgery Source Type: research
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