Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast cancer therapy approaches. The aim of the study was to investigate the functional role of PTX resistance on MCF-7 cell survival and proliferation related to PI3K/Akt and MAPK pathways. The generated PTX-resistant (PTX-res) MCF-7 cells showed enhanced cell survival, proliferation, and colony formation potential with decreased cell death compared to wt MCF-7 cells. PTX-res MCF-7 cells exhibited increased motility profile with EMT, PI3K/Akt, and MAPK pathway induction. According to the significant SAPK/JNK activation in PTX-res MCF-7 cells, specific c-Jun N-terminal kinase inhibitor, JNK-IN-8 is shown to suppress the migration potential of cells. Treatment of JNK inhibitor suppressed the p38 and SAPK/JNK and Vimentin expression. However, the JNK inhibitor further downregulated Wnt signaling members in PTX-res MCF-7 cells. Therefore, the JNK inhibitor JNK-IN-8 might be used as a potential therapy model to reverse PTX-resistance related to Wnt signaling

In Vitro Investigations of miR-33a Expression in Estrogen Receptor-Targeting Therapies in Breast Cancer Cells

Background: Increased fatty acid synthesis leads to the aggressive phenotype of breast cancer and renders efficiency of therapeutics. Regulatory microRNAs (miRNAs) on lipid biosynthesis pathways as miR-33a have potential to clarify the exact mechanism. (2) Methods: We determined miR-33a expression levels following exposure of MCF-7 and MDA-MB-231 breast cancer cells to estrogen receptor (ER) activator (estradiol-17β, E2) or anti-estrogens (ICI 182,780, Fulvestrant, FUL) at non-cytotoxic concentrations. We related miR-33a expression levels in the cells to cellular lipid biosynthesis-related pathways through immunoblotting. (3) Results: miR-33a mimic treatment led to significantly downregulation of fatty acid synthase (FASN) in MCF-7 cells but not in MDA-MB-231 cells in the presence of estradiol-17β (E2) or Fulvestrant (FUL). In contrast to the miR-33a inhibitor effect, miR-33a mimic co-transfection with E2 or FUL led to diminished AMP-activated protein kinase α (AMPKα) activity in MCF-7 cells. E2 increases FASN levels in MDA-MB-231 cells regardless of miR-33a cellular levels. miR-33a inhibitor co-treatment suppressed E2-mediated AMPKα activity in MDA-MB-231 cells. (4) Conclusions: The cellular expression levels of miR-33a are critical to understanding differential responses which include cellular energy sensors such as AMPKα activation status in breast cancer cells

Postmastectomy Pain: A Cross-sectional Study of Prevalence, Pain Characteristics, and Effects on Quality of Life

Conclusions: PMPS seriously impacts patients' emotional situation, daily activities, and social relationships and is a major economic burden for health systems. We conclude that the rate of PMPS among patients receiving breast cancer surgery in Turkey is 64.1% and that challenges to the proper treatment of these patients deserve further investigation

Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast cancer therapy approaches. The aim of the study was to investigate the functional role of PTX resistance on MCF-7 cell survival and proliferation related to PI3K/Akt and MAPK pathways. The generated PTX-resistant (PTX-res) MCF-7 cells showed enhanced cell survival, proliferation, and colony formation potential with decreased cell death compared to wt MCF-7 cells. PTX-res MCF-7 cells exhibited increased motility profile with EMT, PI3K/Akt, and MAPK pathway induction. According to the significant SAPK/JNK activation in PTX-res MCF-7 cells, specific c-Jun N-terminal kinase inhibitor, JNK-IN-8 is shown to suppress the migration potential of cells. Treatment of JNK inhibitor suppressed the p38 and SAPK/JNK and Vimentin expression. However, the JNK inhibitor further downregulated Wnt signaling members in PTX-res MCF-7 cells. Therefore, the JNK inhibitor JNK-IN-8 might be used as a potential therapy model to reverse PTX-resistance related to Wnt signaling

Progesterone receptor status in determining the prognosis of estrogen receptor positive/HER2 negative breast carcinoma patients

Purpose: To evaluate the impact of progesterone receptor (PR) status on estrogen receptor (ER)-positive and HER2-negative breast cancer

XELOX vs. FOLFOX4 as Second Line Chemotherapy in Advanced Pancreatic Cancer

Background/Aims: The efficacy and tolerability of oxaliplatin in combination with either folinic acid, fluorouracil (5-FU) (FOLFOX4 regimen) or capecitabine (XELOX regimen) was evaluated in advanced pancreatic cancer. Methodology: In this study, eighty-five patients with advanced pancreatic cancer were enrolled after failing to gemcitabine-based chemotherapy between November 2005 and August 2011. FOLFOX4 was repeated every two weeks and XELOX regimen was repeated every three weeks until either disease progression or unacceptable toxicity occurred. Results: Eighty-five patients were evaluated for tumor response. Seven patients (18%) achieved a partial response with XELOX and stable disease was observed in 16 patients (41%). Eight patients (17%) achieved a partial response with FOLFOX4 and stable disease was observed in 12 patients (26%). Disease control rates were 59% in the XELOX arm and 43% in the FOLFOX4 arm. The median time to progression was 16 weeks in both arms. The median overall survival was 21 weeks with XELOX and 25 weeks with FOLFOX4. Conclusions: Oxaliplatin-based combination therapy showed moderate clinical activity with acceptable toxicity in patients who had progressive disease after receiving gemcitabine-based chemotherapy for advanced and/or metastatic pancreatic cancer. We conclude that XELOX is similar in terms of efficacy and toxicity profile to FOLFOX4 in the second-line treatment of metastatic pancreatic cancer

Assessment of tumor characteristics and factors affecting survival in patients with primary metastatic breast carcinoma: a Multicenter Study of the Anatolian Society of Medical Oncology

Primary metastatic breast cancer (PMBC) comprises 3-10 % of all BCs. PMBC is a heterogeneous disease. To date, little is known about the tumor characteristics, treatment results, and overall survival ( OS) of patients with PMBC. Patients were considered to have PMBC if distant metastasis was evident within 3 months of the initial diagnosis of BC. Between September 2007 and April 2013, 466 PMBC patients were included in this study and analyzed retrospectively. The median age of the patients was 50 (18- 90) years. Bone/ soft tissue metastases were more frequent in the hormone receptor (HR)(+) human epidermal growth factor receptor ( HER) 2(-) group compared with the HR(-) HER2(-) and HR(-) HER2(-) groups ( p < 0.001), whereas visceral organ metastasis was more frequent in the HR(-) HER2(-) and HR(-) HER2(-) groups ( p < 0.001). The OS was affected by Eastern Cooperative Oncology Group performance status, tumor histology, receptor status, and the site of metastasis ( p < 0.001, p < 0.001, p < 0.001, and p = 0.011, respectively). According to the first-line systemic treatment choices of the patients, the longest median OS was observed in the HR(?) HER2(-) group who received hormonotherapy combined with trastuzumab after chemotherapy ( 86 months, 95 % CI 23.8-148.1) and the shortest median OS was observed in the HR(-) HER2(-) group who received chemotherapy only ( 24 months, 95 % CI 17.9-30.0) ( p < 0.001). Bisphosphonate therapy or radiotherapy had no significant effect on OS ( p = 0.733, 0.603). In multivariate analysis, hormonotherapy, chemotherapy + trastuzumab, trastuzumab + hormonotherapy following chemotherapy, and surgery were the most important prognostic factors for OS, respectively ( p < 0.001, p = 0.025, p = 0.027, p = 0.029). The general characteristics of the primary tumor are important for the prognosis and survival of patients with PMBC. Interestingly, patients who underwent primary breast tumor surgery, even those at the metastatic stage upon admission, had the longest survival

Salvage Treatment Experience in Advanced Synovial Sarcoma: a Multicenter Retrospective Analysis of the Anatolian Society of Medical Oncology

Background: We aimed to evaluate prognostic factors and response rates to various treatment approaches to patients with synovial sarcoma in an advanced setting. Materials and Methods: We retrospectively reviewed the medical records of 55 patients (18 pts; 32.7% women) diagnosed with synovial sarcomas. Twenty had metastatic disease at the time of diagnosis while the remainder of the study group consisted of patients who developed metastatic or inoperable locally advanced disease during follow up. Results: The median follow up time was 15 months (range: 1-53). Regarding outcomes for the 55 patients, 3 and 5 year overall survival rates were 26% and 14%, respectively. In univariate analyses among demographic factors female gender was associated with a better outcome (p=0.030). Patients with early progressing disease (<2 years) had a worse prognosis when compared to patient group with late relapse, but this difference did not reach statistical significance (p=0.056). According to multivariate Cox regression analysis patients who had undergone metastasectomy had a significant survival advantage (p=0.044). The overall response rate to different salvage chemotherapy regimens given as second line treatment was around 42.9-53.9% for all regimes. There were no statistically significant differences between chemotherapy regimens given in either second or third line settings in terms of overall survival. Conclusions: We observed no major differences in terms of response rate and survival between different salvage chemotherapy regimens. Although metastatic disease still carries a poor prognosis, metastasectomy was found to be associated with improved surviva

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC)