UNLABELLED Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibit...

Nanomedicine holds great promise for fighting against malignant tumors. However, tumor elevated interstitial fluid pressure (IFP) seriously hinders convective transvascular and interstitial transport of nanomedicines and thus damages its antitumor efficacy. In this study, combretastatin-A4 phosphate (CA4P) was utilized to reduce tumor IFP, and thereby to improve the intratumoral distribution an...

A phase III trial conducted by Eastern Cooperative Oncology Group (ECOG) investigators assessed the possible impact of paclitaxel on survival, response, and toxicity in patients with advanced non-small-cell lung cancer. Three regimens were compared: cisplatin/etoposide, paclitaxel/ cisplatin/granulocyte colony-stimulating factor (G-CSF), and paclitaxel/ cisplatin. Patients were randomly assigne...

The main problem in breast cancer treatment is the recurrence of tumor growth and metastases. Previous studies have suggested that Paclitaxel is widely used to treat various cancers. The present study analyzed the potential signaling pathway of Paclitaxel-inhibited breast cancer metastasis. It was demonstrated that Paclitaxel treatment significantly inhibited growth of breast cancer cell lines ...

Paclitaxel (Taxol), a naturally occurring antimitotic agent, has shown significant cell-killing activity against human solid tumor cells through induction of apoptosis. The molecular mechanism underlying paclitaxel-induced apoptosis is not entirely clear. Using the unique inhibitory effect of glucocorticoids on paclitaxel-induced apoptosis, we recently discovered that paclitaxel-induced inhibit...

Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyper...

Taxanes are chemotherapeutic agents with a large spectrum of antitumor activity when used as monotherapy or in combination regimens. Paclitaxel and docetaxel have poor solubility and require a complex solvent system for their commercial formulation, Cremophor EL(R) (CrEL) and Tween 80(R) respectively. Both these biological surfactants have recently been implicated as contributing not only to th...

.................................................................................................... 9 POPULÄRVETENSKAPLIG SAMMANFATTNING............................. 11 PAPERS IN THE PRESENT THESIS ....................................................... 13 ABBREVIATIONS ....................................................................................... 14 INTRODUCTION.........................

Paclitaxel is a first-line chemotherapeutic for patients with breast cancer, particularly triple-negative breast cancer (TNBC). Molecular markers for predicting pathologic responses to paclitaxel treatment is thus urgently needed since paclitaxel resistance is still a clinical issue in treating TNBCs. We investigated the transcriptional profiling of consensus genes in HCC38 (paclitaxel-sensitiv...

BACKGROUND The Hedgehog pathway receptor smoothened (SMO) has critical roles in tumor progression. However, whether SMO is a key factor regulating gastric cancer chemotherapy resistance is unknown. MATERIAL AND METHODS We investigated the potential functions of SMO in inducing gastric cancer paclitaxel resistance in clinical samples, gastric cancer cell lines (424GC and AGS), and subcutaneous s...