Gamze Goksel

Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors

Objective. Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. Material and methods. Sixty-seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. Results. The overall response rate was 5%. Thirty-one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression-free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status (PS) = 2, and in patients with primary tumour location in the body or tail of the pancreas (p<0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PS = 2 had worse results than the patients with PS = 0–1 (p<0.05). Conclusions. Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine.

Cancer stem cell differentiation: TGFβ1 and versican may trigger molecules for the organization of tumor spheroids.

Cancer stem cells (CSCs) have the ability to self-renew similar to normal stem cells. This process is linked with metastasis and resistance to chemotherapy and radiotherapy. In the present study, we constructed an in vitro differentiation model for CSCs. CSCs isolated and proliferated for one passage were maintained as monolayers or spheroid-forming cells with serum included media for differentiation process. Differentiation of adhesion molecules and cellular ultrastructural properties were investigated and compared in both monolayer and spheroid cultures. CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with the remaining heterogeneous cancer cell bulk population. Microarray-based gene expression analysis was applied to determine genes with differential expression and protein expression levels of candidates were analyzed by immunohistochemistry. Electron microscopy showed detailed analysis of morphology. TGFβ1 was found to be significantly upregulated in monolayer CSCs. High expression levels of VCAN, COL7A1, ITGβ3, MMP16, RPL13A, COL4A2 and TIMP1 and low expression levels of THBS1, MMP1 and MMP14 were detected when CSCs were maintained as serum-grown prostate CSC spheroids. Immunohistochemistry supported increased immunoreactivity of TGFβ1 in monolayer cultures and VCAN in spheroids. CSCs were found to possess multipotential differentiation capabilities through upregulation and/or downregulation of their markers. TGFβ1 is a triggering molecule, it stimulates versican, Col7A1, ITGβ3 and, most importantly, the upregulation of versican was only detected in CSCs. Our data support a model where CSCs must be engaged by one or more signaling cascades to differentiate and initiate tumor formation. This mechanism occurs with intracellular and extracellular signals and it is possible that CSCc themselves may be a source for extracellular signaling. These molecules functioning in tumor progression and differentiation may help develop targeted therapy.

Potential Predictive Factors for Response to Weekly Paclitaxel Treatment in Patients with Metastatic Breast Cancer

Abstract The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS.

Serum Her-2/neu and Survivin Levels and Their Relationship to Histological Parameters in Early-stage Breast Cancer

This study was conducted to investigate the serum levels of her-2/neu and survivin in patients with early-stage breast cancer and their relationship with known histological parameters. Forty-one patients with early-stage breast cancer were investigated. Serum samples were collected from patients on their first admission before adjuvant chemotherapy, and from healthy controls. Serum her-2/neu and survivin levels were determined using an enzyme-linked immunosorbent assay. There was no difference in the levels of serum her-2/neu and survivin between the breast cancer patients and the control group. Serum her-2/neu concentration showed moderate correlations with disease stage and the Ki-67 level, and the serum survivin level showed a moderate correlation with progesterone receptor concentration. Serum levels of her-2/neu and survivin were not significantly related to age and histological parameters in patients with early-stage breast cancer. However, much research continues on the prognostic value of serum her-2/neu and survivin levels, and important new knowledge may ultimately emerge.

Role of increased mean platelet volume (MPV) and decreased MPV/platelet count ratio as poor prognostic factors in lung cancer

In this study, they investigated whether mean thrombocyte volume (MPV) and MPV/platelet count ratio have a prognostic significance in advanced NSCLC or not.

Pathologic and Clinical Characteristics of Elderly Patients With Breast Cancer: A Retrospective Analysis of a Multicenter Study (Anatolian Society of Medical Oncology)

There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.

Pretreatment Serum Albumin Level is an Independent Prognostic Factor in Patients with Stage IIIB Non-Small Cell Lung Cancer: A Study of the Turkish Descriptive Oncological Researches Group

BACKGROUND Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. MATERIALS AND METHODS This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. RESULTS The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. CONCLUSIONS This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

Comparison of inflammatory breast cancer and noninflammatory breast cancer in Western Turkey.

Objective: The study was aimed at investigating the clinical and biological features and survival outcomes of patients who were treated for metastatic inflammatory and noninflammatory breast carcinoma. Subjects and Methods: One hundred and sixty-seven metastatic breast cancer patients were enrolled into this study and divided into two groups: inflammatory (n = 46) and noninflammatory (n = 121). The clinical and hormone receptor status, c-erbB-2, Ki-67, and p53 expression, based on the immunohistochemical staining patterns, were compared between the two groups. Results: The inflammatory breast carcinoma group had a younger patient population, higher rate of adjuvant anthracycline therapy, number of lymph node metastases, rates of extranodal extension and c-erbB-2 overexpression than noninflammatory breast cancer patients (p < 0.05). With regard to survival, there were slightly better outcomes in the noninflammatory breast carcinoma group (30 months) compared to the inflammatory breast carcinoma group (23 months), but the difference was not statistically significant (p = 0.08). While survival results of p53-negative inflammatory and noninflammatory breast carcinoma patients were similar, p53-positive survival was significantly worse (p < 0.05) in inflammatory breast cancer carcinoma patients. Conclusion: Because of c-erbB-2 overexpression in inflammatory breast carcinoma patients, treatment options including trastuzumab could have given better survival outcomes. Survival of inflammatory breast carcinoma patients with a low p53 immunohistochemistry staining appeared similar to that for noninflammatory breast carcinoma. For this reason, new treatment options are needed especially in inflammatory breast carcinoma patients with high p53 positivity.

The effect of the gastrectomy on survival in patients with metastatic gastric cancer: a study of ASMO

AIM To investigate the role of surgical resection of primary tumor on overall survival (OS) in advanced gastric cancer patients at the time of diagnosis. PATIENTS & METHODS The survival rates of metastatic gastric cancer patients whose gastric primary tumor was resected at time of diagnosis were compared with metastatic gastric cancer patients whose primary tumor was nonresected. RESULTS The median progression-free survival and OS in operated and nonoperated group were 10 versus 6, 14 versus 9 months, respectively (p < 0.001). In multivariate analysis, gastric resection of primary tumor, Eastern Cooperative Oncology Group performance status, second-line chemotherapy had a significant effect on OS (hazard ratio [HR]: 0.52 [95% CI: 0.38-0.71], HR: 0.57 [95% CI: 0.42-0.78], HR: 1.48 [1.09-2.01]; p ≤ 0.001, p = 0.001 and p = 0.012, respectively). CONCLUSION Subpopulations of patients with metastatic gastric cancer might benefit from surgical removal of primary tumor.

Abstract 4072: Wnt1 gene expression alters heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+prostate cancer stem cells.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Tumor mass contains a complex and heterogeneous phenotypic population including a rare group of cancer cells that are capable of serving cancer- initiating cells or cancer stem cells (CSCs). Established cancer cell lines contain CSCs, which can be propagated, to form in vitro 3D tumor spheroids. Spheroids reflect differentiation properties of CSCs in serum contained medium and more accurately reflect the complex in vitro microenvironment than simple two-dimensional monolayer. Aberrant activation of Wnt signaling is strongly implicated in the progression of cancer and controls CSCs properties. In this study we hypothesize that when cells maintained as spheroids the structure of CSCs could be show differentiation between CSCs and non- CSCs counterpart. It is possible to determine target molecules for CSCs eradication and specify a clue in therapeutic strategies of cancer. With this aim, CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with remained heterogeneous cancer cells bulk population. Wnt1, Fzd1, Adar, Apc, Axin, Btrc, Frat1 gene expression analysis was applied and protein expression levels of Wnt1, Fzd and Axin were shown by immunohistochemistry. Results show that Wnt1 expression significantly higher in non cancer stem cells compared to CSCs. Nevertheless Fzd1, Adar, Apc, Axin, Btrc, Frat1 gene expressions were higher in CSCs group than the other population. Increased Wnt1 immunoreactivity was demonstrated in the non-cancer stem cells. It is possible to assume that intracellular signaling of Wnt pathway and related molecules in the nucleus and/or cytoplasm might play an important role independent of Wnt ligand. This unexpected expression could be important for CSCs behavior and targeting of this pathway could have therapeutic value in cancer. Citation Format: Gamze Goksel, Ayhan Bilir, Ruchan Uslu, Hakan Akbulut, Ummu Guven, Gulperi Oktem. Wnt1 gene expression alters heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+ prostate cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4072. doi:10.1158/1538-7445.AM2013-4072