Search results for "Axel"
showing 10 items of 257 documents
Thyroid Cancer Resistance to Chemotherapeutic Drugs via Autocrine Production of Interleukin-4 and Interleukin-10
2003
We investigated the mechanisms responsible for the widespread refractoriness to chemotherapeutic drugs observed in thyroid cancers. We show that malignant epithelial cells from papillary, follicular, and anaplastic thyroid carcinomas express high levels of Bcl-2 and Bcl-xL. Exogenous expression of either Bcl-2 or Bcl-xL in normal thyrocytes was sufficient to prevent chemotherapeutic drug-induced cytotoxicity. All of the histological thyroid cancer variants examined produced interleukin-4 (IL-4) and interleukin-10 (IL-10), which increased Bcl-2 and Bcl-xL levels and protected thyroid cells from chemotherapeutic agents. Exposure to neutralizing antibodies against IL-4 and IL-10 resulted in do…
Abstract 1423: Shikonin impairs the growth of docetaxel-resistant prostate cancer cells by necroptosis
2021
Abstract Introduction: Prostate carcinoma (PCa) is the most common malignancy in men. Androgen-targeted therapy and chemotherapy are currently the treatment of choice for advanced stages. Due to resistance towards these therapies, prognosis remains poor and new treatment options are urgently required. Shikonin (SHI) from Traditional Chinese Medicine (TCM) might be promising, since it induces anti-tumor effects in different tumor entities. However, data on PCa are few, and data on resistant PCa are not existent. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, LNCaP, and 22Rv1 were exposed to SHI [0.1 - 1.5 μM] for 24, 48, or 72 hours. Untreated…
Uncommon Synchronous Association between Ovarian Carcinoma and Gastrointestinal Stromal Tumor: A Case Study and Literature Review
2013
Background The association of gastrointestinal stromal tumors (GIST) and other cancers is well known, but its synchronous occurrence with gynecological malignancies is very uncommon. Usually, the diagnosis is accidentally established. We describe a patient with GIST and concurrent ovarian cancer and discuss the clinical implications of this finding. Case report A 64-year-old woman with a prior diagnosis of ovarian cancer developed a second recurrence after having undergone two operations and adjuvant chemotherapy. While tumor debulking was performed, a small, nonsuspicious lesion was removed from the greater curvature of the stomach. Histology revealed a GIST. Conclusion The association of …
Altered Expression of c-IAP1, Survivin, and Smac Contributes to Chemotherapy Resistance in Thyroid Cancer Cells
2006
Abstract Resistance to chemotherapy predicts an unfavorable outcome for patients with radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying this resistance, we evaluated the expression of four different inhibitor of apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that survived 48 hours of exposure to cisplatin, doxorubicin, or taxol. We found high levels of c-IAP1 after cisplatin treatment and increased expression of survivin following exposure to doxorubicin. Cells that endured treatment with taxol showed reduced expression of Smac and released minimal amounts of this protein from the mitochondria. Down-regulation of c-IAP1 and survivin in…
Mechanisms of skin toxicity of paclitaxel: An in vitro preclinical assessment.
2020
e15511 Background: Paclitaxel skin toxicity is a frequent side effect extensively evaluated in the clinical setting. However little is known about the preclinical mechanisms that lead to this toxicity. The endpoint of this study was to analyse the cutaneous mechanisms that drive paclitaxel toxicity in a preclinical model. Methods: Primary human keratinocytes were co-cultured with human dermal fibroblast in collagen gel under air-liquid interface conditions to generate a multilayered 3D epidermis. Paclitaxel was added to 3D epidermis at 0.3 µM, 3 µM and 30 µM and total RNA and protein was extracted after 24h of incubation. Markers of cell senescence (p21 and p53), anti-apoptotic mediators (…
A randomized phase II study of estramustine phosphate versus estramustine phosphate plus etoposide in hormone refractory prostate cancer (HRPC)
2008
20632 Background: Docetaxel-based regimens represent the treatment of choice of HRPC. However, in some patients toxicity may be a concern and the quality of life may be compromised. The aim of this phase II randomized study is to investigate the efficacy and safety of low-dose chemotherapy regimen adopting a combination of EMP and VP16 in patients affected by HRPC. Methods: 54 HRPC patients were randomized between: arm A, daily oral standard dose EMP (10mg/kg) and arm B, low-dose EMP (3mg/kg) plus VP16 (25mg/mq) for 2 weeks followed by 2-weeks’rest. Systemic toxicity and hematologic exams were monitored every 2 weeks. Performance status, pain and analgesic use were evaluated according to WH…
Role of the progesterone receptor for paclitaxel resistance in primary breast cancer
2007
Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) m…
Bcl-2 and glutathione depletion sensitizes B16 melanoma to combination therapy and eliminates metastatic disease.
2007
Abstract Purpose: Advanced melanoma resists all current therapies, and metastases in the liver are particularly problematic. Prevalent resistance factors include elevated glutathione (GSH) and increased expression of bcl-2 in melanoma cells. GSH has pleiotropic effects promoting cell growth and broad resistance to therapy, whereas Bcl-2 inhibits the activation of apoptosis and contributes to elevation of GSH. This study determined the in vivo efficacy of combination therapies administered while GSH and Bcl-2 were individually and simultaneously decreased in metastatic melanoma lesions. Experimental Design: Highly metastatic murine B16 melanoma (B16M-F10) cells have elevated levels of both G…
A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced o…
2019
Purpose This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity. Patients and methods This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m 2) administered intravenously on a every 3-week schedule. Adverse event (A…
Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsenti…
2014
A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G 2 /M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr 34 and to increase the cytotoxic activity of paclit…