Aim: Endocrine therapy (ET) plus cyclin-dependent kinase (CDK) 4/6 inhibitors is a standard treatment for hormone receptor (HR) positive HER-2-negative metastatic breast cancer patients. In this study, we aimed to investigate the effect of body mass index (BMI) on progression-free survival (PFS) in patients receiving ET plus CDK 4/6 inhibitors.Materials & methods: Patients with metastatic HR-positive breast cancer receiving CDK 4/6 inhibitors were included in the study. A total of 116 patients were retrospectively evaluated. Patients were divided into three groups according to BMI level: normal weight (group 1) 18.5-24.9 kg/m2, overweight (group 2) 25-29.9 kg/m2 and obese (group 3): ≥30 kg/m2. Median follow-up was 10.83 months. Comparisons of PFS and BMI categories were performed by Kaplan-Meier curve and log-rank test.Results: PFS was 9.3 (5.3-13.4) months in normal weight patients and 11.1 (9.7-12.56) months in obese patients and was not reached in overweight patients. This difference was statistically significant (p = 0.02).Conclusion: Low BMI has been shown to have a negative prognostic effect on survival in patients with metastatic breast cancer and overweight patients had a longer PFS.

OBJECTIVE:In this study, we aimed to evaluate the effect of tumor size and tumor sidedness on prognosis in patients with stage 2 colon cancer.PATIENTS AND METHODS:Data of 501 patients diagnosed with stage 2 colon cancer were evaluated retrospectively. It was evaluated whether the patients' age, gender, tumor differentiation, tumor node metastasis (TNM) stage, overall survival rate, and disease-free survival rate had any correlation with horizontal tumor diameter and tumor sidedness. In the ROC analysis performed to determine the cut-off value for the tumor diameter, which we think will predict survival, no significant results were obtained with maximum sensitivity and specificity. Therefore, the median value of the tumor diameter, which is 5 cm, was accepted as the cut-off value.  Kaplan-Meier method and Cox regression analysis were used for survival analysis and determination of prognostic factors.RESULTS:When the patients were evaluated in terms of tumor localization, 189 (37.7%) patients had right colon tumors and 312 (62.3%) patients had left colon tumors. There was no statistically significant difference in terms of disease-free survival and overall survival according to tumor localization. When the patients were analyzed by dividing them into two groups according to the horizontal tumor size (<5 cm and ≥5 cm), no statistically significant difference was found between the groups in terms of disease-free survival (DFS) and overall survival (OS) p=0.085, p=0.699, respectively.CONCLUSIONS:Our results suggest that the management of patients with stage 2 colon cancer requires a better understanding of tumor biology rather than features such as tumor size and localization.

To assess the prognostic value of 18F-FDG PET SUVmax in adult Hodgkin lymphoma (HL) patients. Twenty-seven adult HL patients with pre-treatment 18F-FDG PET/CT images were included retrospectively. Female/male ratio was 9 (33%)/18 (67%). Median age was 35 (19-63). Pathologic subgroups were NLP: 1, NS: 12, LR: 2, MC: 9, Classical: 3. Clinical stages (Ann Arbor Staging System) were IA: 4, IB: 1, IIA: 11, IIB: 4, IIIB: 2, IVA: 2, IVB: 3. Two patients had extra-nodal involvement. All patients received chemotherapy (3-8 cycles ABVD) and/or radiation therapy (20-36 Gy). The ability of SUVmax to predict prognosis was analyzed by a Receiver Operating Characteristics (ROC) curve analysis. While evaluating the area under the curve, a 5% type-1 error level was accepted a statistically significant predictive value of the test variables. The relation between SUVmax and development of recurrence was analyzed using Fisher's exact test. The disease free survival (DFS) and overall survival (OS) were calculated with the Kaplan-Meier survival estimates. A separate long rank test was used to identify the independent effect of SUVmax on DFS and OS. Median follow-up time was 20 months (6-46 months). Twenty-six patients were alive at last follow-up. Area under the ROC curve was 0.549, and the best cut-off SUVmax to predict prognosis was 9. Recurrence rate was significantly higher in patients with pre-treatment SUVmax≥9 compared to SUVmax <9 (3/18 vs 1/9, p = 0.001). Median survival was 38.64±2.96 months and three-year disease free survival was 78.3% for all patients. There was no difference of OS or DFS between patients with SUVmax≥9 and SUVmax <9. Pre-treatment SUVmax may predict recurrence in adult HL patients. 18F-FDG PET/CT uptake before the treatment may be a valuable tool to evaluate prognosis in HL patients. Patients with a higher FDG uptake may be considered at increased risk of failure and may benefit from more aggressive treatment approaches.

Glioblastoma multiforme (GBM) is an aggressive brain malignancy characterized by high heterogeneity and invasiveness. It is increasingly accepted that the refractory feature of GBM to current therapies stems from the existence of few tumorigenic cells that sustain tumor growth and spreading, the so-called glioma-initiating cells (GICs). Previous studies showed that cytokines of the bone morphogenetic protein (BMP) family induce differentiation of the GICs, and thus act as tumor suppressors. Molecular pathways that explain this behavior of BMP cytokines remain largely elusive. Here, we show that BMP signaling induces Smad-dependent expression of the transcriptional regulator Snail in a rapid and sustained manner. Consistent with its already established promigratory function in other cell types, we report that Snail silencing decreases GBM cell migration. Consequently, overexpression of Snail increases GBM invasiveness in a mouse xenograft model. Surprisingly, we found that Snail depletes the GBM capacity to form gliomaspheres in vitro and to grow tumors in vivo, both of which are important features shared by GICs. Thus Snail, acting downstream of BMP signaling, dissociates the invasive capacity of GBM cells from their tumorigenic potential.

PURPOSE:Hormone receptor (HR) status is a prognostic factor in women with breast cancer and differs among different ethnic groups. HR status among Turkish, Kurdish and Arabic women with breast cancer living in Turkey is unknown and in this study we investigated the relationship between HR and HER2 status and race.METHODS:FA total of 648 women with breast cancer (Turkish 438, Kurdish 174, Arabic 35 and Armenian 1) living in southeastern Turkey and referred to the Department of Radiation Oncology between July 2006-July 2012 were included in the study. Patients were categorized into 4 groups according to their HR status. Estrogen receptor (ER) and progesterone receptor (PR) positive (ER+/PR+), ER positive and PR negative (ER+/PR-), ER negative and PR positive (ER-/PR+) and ER and PR negative (ER-/PR-). Human epidermal growth factor receptor 2 (HER2) status was recorded immunohistochemically (IHC) as negative (0 and 1+), and positive (3+). Statistical analysis included ER, PR, HER2, triple subtypes (combination of ER, PR and HER2), and race.RESULTS:The median age at diagnosis was 48 years (range 20-83). ER+, PR+ and HER2+ patients were 453 (70%), 470 (72.6%) and 206 (32.1%), respectively. ER+/PR+ rates among Turkish and Arabic patients were similar, but were higher than Kurdish patients (p<0.002). Triple-negative (ER-/PR-/HER2-) rates among Kurdish and Arabic patients were similar, but were higher than Turkish patients (p=0.04).CONCLUSION:Turkish, Kurdish and Arabic women with breast cancer in southeastern Turkey differed by HR status. Compared to Turkish and Arabic patients, Kurdish patients had more unfavorable prognostic factors.

Material and Methods: Recombinant adenoviral vectors with RGD-modified fiber (rAdRGD) and a p53-responsive promoter (PG) were constructed containing genes of p19Arf, IFN or the combination of both.Evaluation of in vitro antiproliferative effect of transgenes in B16F10 cells (B16, mouse melanoma, p53 wt) was done by annexin/PI staining and MTT assays.Bystander effect was revealed by cell cycle analysis of populations transduced with different proportions of the viruses.Antitumor effect in vivo was observed by treatment of established LLC1 tumors (mouse lung carcinoma, p53 wt) with intratumoral injection of rAdRGD in C57BL/6 mice.Involvement of immune response was revealed by second tumor challenge at contralateral flank of mice with a developed and treated first tumor.Results and Discussion: Cell death was resulted from the p19Arf and IFN combined transference (74% subG0), yet single gene transfer yielded only half the number of subG0 cells.A similar result was seen by measurement of cell viability with MTT.Evidence on a bystander effect was revealed when approximately 50% subG0 cells were observed, even though only 10% of the cells had been transduced with IFN.In a population of cells transduced with p19Arf, when 10% of them also expressed IFN, the number of subG0 cells increased to 68%, compared to transduction of p19Arf alone, which results in 45% subG0 cells.This indicates that p19Arf can sensitize cells to death by IFN bystander effect.In vivo assays with the LLC1 model have shown that in situ gene therapy of p19Arf and IFN combination was more effective to inhibit tumor progression and increase survival than application of a single gene.These animals were then challenged with the implantation of a second tumor, revealing greater retardation of growth at the secondary tumor site in mice treated with the combined gene therapy at the primary tumor locus as compared to animals that received single gene treatment. Conclusion:The use of p53-responsive vectors to express p19Arf and IFN represents a potential strategy for melanoma and lung carcinoma tumor suppression.We have shown that complementation of the p53/Arf and interferon pathways in the primary tumor may generate a strong bystander effect as well as immune stimulation.