Can Cytoreductive Nephrectomy Improve Outcomes of Nivolumab Treatment in Patients with Metastatic Clear-Cell Renal Carcinoma?

Background: This study aimed to investigate the effect of cytoreductive nephrectomy (CN) on the survival outcomes of nivolumab used as a subsequent therapy after the failure of at least one anti-vascular endothelial growth factor (VEGF) agent in patients with metastatic clear-cell renal-cell carcinoma (ccRCC). Methods: We included 106 de novo metastatic ccRCC patients who received nivolumab after progression on at least one anti-VEGF agent. Multivariate Cox regression analysis was performed to investigate the factors affecting survival in patients receiving nivolumab. Results: Of the 106 de novo metastatic ccRCC patients, 83 (78.3%) underwent CN. There were no statistical differences between the two groups in terms of age, gender, Eastern Cooperative Oncology Group (ECOG) score, tumor size, International Metastatic RCC Database Consortium (IMDC) risk group, number of previous treatment lines, first-line anti-VEGF therapy, or metastasis sites (p = 0.137, p = 0.608, p = 0.100, p = 0.376, p = 0.185, p = 0.776, p = 0.350, and p = 0.608, respectively). The patients who received nivolumab with CN had a longer time to treatment discontinuation (TTD) [14.5 months, 95% confidence interval (CI): 8.6-20.3] than did those without CN 6.7 months (95% CI: 3.9-9.5) (p = 0.001). The median overall survival (OS) was 22.7 months (95% CI: 16.1-29.4). The patients with CN had a median OS of 22.9 months (95% CI: 16.3-29.4), while those without CN had a median OS of 8.1 months (95% CI: 5.6-10.5) (p = 0.104). In the multivariate analysis, CN [hazard ratio (HR): 0.521; 95% CI: 0.297-0.916; p = 0.024] and the IMDC risk score (p = 0.011) were statistically significant factors affecting TTD; however, the IMDC risk score (p = 0.006) was the only significant factor for overall survival. Conclusions: Our study showed that the TTD of nivolumab was longer in metastatic ccRCC patients who underwent cytoreductive nephrectomy.

Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce. OBJECTIVE: We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey. PATIENTS AND METHODS: This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024. RESULTS: The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n = 8), followed by NTRK3 (n = 7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months. CONCLUSIONS: In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.

Clinical significance of sarcopenia in patients undergoing treatment for gastric cancer.

OBJECTIVE: The aim of this study was to investigate the impact of sarcopenia on prognosis in patients with gastric cancer in order to explore the relationship between sarcopenia and postoperative complications as well as durations of hospital stay and intensive care unit. METHODS: A total of 175 patients who visited the oncology clinic between 2017 and 2022 with respect to their radiological images, demographic data, and laboratory parameters were perused. The OsiriX software was used to measure the skeletal muscle area that was divided by the body height in order to obtain the skeletal muscle index. RESULTS: A total of 50.28% of 175 patients (41 females and 134 males, with a mean age of 63.5 years) who met the inclusion criteria in the study were sarcopenic. Significant differences appeared between sarcopenic and non-sarcopenic patients with respect to durations of both hospital stay (p<0.01) and intensive care unit stay (p<0.01) (multivariate analysis). Furthermore, patients with sarcopenia had significantly frequent postoperative complications in comparison with those without sarcopenia. Among the patients with sarcopenia, decreased levels of hemoglobin and albumin as well as lymphocytes were encountered in terms of inflammatory markers; nevertheless, no significant differences were determined among other inflammatory markers. CONCLUSION: In patients undergoing treatment for gastric cancer, sarcopenia increases postoperative complications and prolongs hospital and intensive care stays during the treatment process.

PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study.

INTRODUCTION: In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated. MATERIALS AND METHODS: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics. RESULTS: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were ≥ 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of ≥2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity. DISCUSSION: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged ≥75 years and/or with an ECOG performance status ≥2.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Clinical significance of sarcopenia in patients undergoing treatment for gastric cancer

SUMMARY OBJECTIVE: The aim of this study was to investigate the impact of sarcopenia on prognosis in patients with gastric cancer in order to explore the relationship between sarcopenia and postoperative complications as well as durations of hospital stay and intensive care unit. METHODS: A total of 175 patients who visited the oncology clinic between 2017 and 2022 with respect to their radiological images, demographic data, and laboratory parameters were perused. The OsiriX software was used to measure the skeletal muscle area that was divided by the body height in order to obtain the skeletal muscle index. RESULTS: A total of 50.28% of 175 patients (41 females and 134 males, with a mean age of 63.5 years) who met the inclusion criteria in the study were sarcopenic. Significant differences appeared between sarcopenic and non-sarcopenic patients with respect to durations of both hospital stay (p<0.01) and intensive care unit stay (p<0.01) (multivariate analysis). Furthermore, patients with sarcopenia had significantly frequent postoperative complications in comparison with those without sarcopenia. Among the patients with sarcopenia, decreased levels of hemoglobin and albumin as well as lymphocytes were encountered in terms of inflammatory markers; nevertheless, no significant differences were determined among other inflammatory markers. CONCLUSION: In patients undergoing treatment for gastric cancer, sarcopenia increases postoperative complications and prolongs hospital and intensive care stays during the treatment process.

First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer.

Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.

Late Endobronchial Pulmonary Metastasis in a Patient with Breast Cancer.

The lung is a common location for malignant metastases. However, endobronchial metastases from nonpulmonary neoplasms are rare. Metastatic breast cancer usually occurs in 2-3 years of the disease course. A 65-year-old woman visited our hospital for the evaluation of dry cough. The patient had a history of breast cancer, which was treated with modified radical mastectomy and axillary dissection 10 years ago; she was then treated with aromatase inhibitor for 5 years. Chest X-ray revealed right hilum enlargement. Thorax computed tomography revealed a 35-mm diameter mass that was localized in the right hilum. Fiberoptic bronchoscopy was performed, and an endobronchial lesion was observed in the right main lobe carina. Pathological evaluation revealed that the mass was a metastasis of the invasive ductal carcinoma of the breast. Weekly paklitaxel chemotherapy was initiated because of the symptomatic disease. We reported the case of a patient with breast cancer who had an endobronchial metastasis. Her disease-free interval was 10 years. This case indicates that a long-term follow-up of breast cancer is necessary, and biopsies must be performed to make a final diagnosis when any suspicious hilum enlargement is observed.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population.

Serum levels of polyamine synthesis enzymes increase in diabetic patients with breast cancer.

BACKGROUND: In this study, it was aimed to investigate the relationship between diabetes and breast cancer and the detection of enzymes and ornithine levels in polyamine synthesis pathway in diabetes, breast cancer and diabetic breast cancer patients. METHODS: Ornithine, arginine decarboxylase, ornithine decarboxylase and agmatinase levels have been measured in serum of all groups. Ornithine levels were measured spectrophotometrically. Arginine decarboxylase, ornithine decarboxylase and agmatinase levels were determined by ELISA kits. RESULTS: Except for the diabetic group, the levels of enzymes in the polyamine synthesis pathway were increased in all and statistically significant (P < 0.05). The increase in the levels of agmatinase was very important among the enzymes (P < 0.001). CONCLUSIONS: Decreased levels of polyamine synthase enzymes in diabetes mellitus were found to be increased patients with breast cancer. Whether and how diabetes-based breast cancer development relates to increase activity of enzymes responsible for polyamine synthesis requires further mechanistic and prospective monitoring studies in larger patient cohorts.

Attitudes of cancer patients after diagnosis: How cancer affects social life? A Turkish Oncology Group study.

PURPOSE: Each year, 12.7 million people learn that they have cancer and 8.2 million people die of cancer worldwide. Cancer is a major public health issue which causes fundamental changes in the lives of patients and their families. The purpose of this study was to evaluate the lives of patients after diagnosis and determine the changes in their lifestyles. METHODS: Between September 2013 to December 2013, a questionnaire consisting of 22 questions was administered during a face to face interview to patients at 13 different Oncology Units in Turkey. Each patient was queried during the administration of his/her chemotherapy. Eight of the questions featured independent choices, and 14 had dependent (multiple) choices. RESULTS: A total of 1300 patients were included in the study. Of patients 9.5% were 71 years of age and older which was the oldest age group. The mean patient age was 54.6±13.8 years. Of the whole group of patients 58.5% were female and 41.5% male. After diagnosis, 64% of the patients reported that they were complying with guidelines for a healthy lifestyle and 80% said that they were eating healthier food. At the time they filled in the questionnaire, more than half of the patients (57.3%) felt optimistic about their disease. CONCLUSIONS: Diagnosis of cancer may change the patients' dietary and reading habits, social relationships, activities and more importantly, their point of life view.

The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: a retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG).

PURPOSE: To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. METHODS: A total of 121 previously untreated female patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. RESULTS: In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8±3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values <6.08 fL, in group B values ranged from 6.09 to 8.46 fL, group C included values from 8.47 to 10.05 fL, and group D included patients with MPV values >10.06 fL. MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. CONCLUSION: We concluded that MPV can be used to predict the development of isolated bone metastases.

Tendency of cancer patients and their relatives to use internet for health-related searches: Turkish Oncology Group (TOG) Study.

PURPOSE: This study aimed to reveal the habits of using internet by cancer patients and their relatives to access health-related information and services in Turkey. METHODS: An 18-item questionnaire survey was applied in cancer patients and their relatives. RESULTS: A total of 1106 patients (male, 37.3%, and female, 62.7%) and their relatives were included in the study. The responders had been using internet to obtain health information about oncological diseases, once a month (34.2%), 1-2 times a week (27.4%) or 2-3 times a month (21.9%). After diagnosis of cancer was made, participants more frequently (64.4%) investigated health-related issues, while 64.9% of them considered internet as an important search tool, and 16.7% of them had thought to give up cancer therapy under the influence of internet information. Some (33.1%) participants had used herbal medicine, and 16.7% of them had learnt these herbal products from internet. Still 12.7% of them had not questioned the accuracy of internet information, while 26.9% of them indicated that they had not shared the internet information about cancer with their physicians, and 13 % of them searched information in internet without asking their physicians. CONCLUSION: Cancer patients and their relatives showed a higher tendency to use health-related internet information which may mislead them, and can result in treatment incompliance. Health professionals should offer evidence-based information to the patients and their relatives through internet.

Retrospective analysis of the microbiological spectrum of pneumonia in Turkish patients with lung cancer.

AIM OF THE STUDY: The spectrum of pulmonary infections in patients with lung cancer is wide, and tools for target-oriented infection control measures are necessary. In this retrospective study we report the microbiological spectrum of pneumonia (based on the results of sputum culture) in a case series of Turkish patients with lung malignancies. MATERIAL AND METHODS: Between 2010 and 2011 a total of 119 patients (111 males and 8 females, mean age: 59.8 ±9.6 years) with lung cancer and pneumonia were identified at the Department of Medical Oncology of two Turkish Universities (Uludag University, Bursa and Cumhuriyet University, Sivas). Expectorated sputum samples were collected in sterile specimen containers and processed immediately in the hospital bacteriology laboratory. RESULTS: Of the 119 study patients, 92 (77.3%) had positive isolates from sputum cultures. The most frequent isolate from the sputum of lung cancer patients with pneumonia was Aspergillus fumigatus (n = 22), followed by Haemophilus influenzae (n = 13) and Pseudomonas aeruginosa (n = 12). The likelihood of having a positive Aspergillus fumigatus sputum culture was significantly and independently associated with febrile neutropaenia (OR = 1.32, 95% CI: 1.17-3.68, p < 0.05) and the development of pneumonia within the first 10 days of chemotherapy initiation (OR = 1.78, 95% CI: 1.37-4.12, p < 0.01). CONCLUSIONS: We conclude that Aspergillus fumigatus was the most frequent isolate, but the high diversity of pathogens clearly challenges the empirical use of antimicrobial drugs.

The prognostic value of UHRF-1 and p53 in gastric cancer.

BACKGROUND/AIMS: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. PATIENTS AND METHODS: Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. RESULTS: The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and fi ve (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1-110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). CONCLUSION: According to this study, UHRF-1 and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differentiating between gastric cancer and gastritis.

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.

Effect of imatinib on growth of experimental endometriosis in rats.

OBJECTIVE: Currently, medical and surgical treatment options for endometriosis are limited due to suboptimal efficacy, and also safety and tolerance issues. Long-term use of gonadotrophin-releasing hormone analogs, androgenes, and the danazol, which are widely used drugs for endometriosis, is usually not possible due to their suboptimal safety and tolerance profile. The lack of an effective, tolerable and safe treatment option for endometriosis makes animal models of experimental endometriosis necessary to study candidate drugs. The aim of this study was to investigate the efficacy of imatinib on the experimental endometriosis in a rat model. STUDY DESIGN: Endometriosis was induced by autotransplantation of uterine tissue into the peritoneal cavity. Twenty-four rats, which had visually confirmed endometriotic implants on subsequent laparotomy, were randomized into three groups to receive imatinib (25mg/kg/day, p.o.), anastrozole (0.004 mg/day, p.o.), or normal saline (0.1 mL, i.p.) for 14 days. After removal of endometriotic tissue and H & E staining, endometriosis score was determined according to a semiquantitative histological classification. Also, immunostaining with primary antibodies including VEGF, CD117, and Bax were used for immunohistochemical (IHC) examination. RESULTS: Both anastrozole and imatinib suppressed the growth of endometriotic tissue and reduced the number of ovarian follicles. Although the difference was not statistically significant, imatinib was less effective than anastrozole for treatment of endometriosis. CONCLUSION: Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation.

Significant Association Between Polymorphisms of Wnt Antagonist Genes and Lung Cancer.

Further elucidation of the molecular mechanisms underlying lung cancer (LC) is essential for the development of new effective therapeutic agents. Recently, involvement of Wnt antagonists in oncogenesis has been demonstrated in several cancers. The investigation of their contribution to lung carcinogenesis is still under investigation. We aimed to investigate whether there is a susceptibility or preventive effect of Wnt antagonist gene polymorphisms on the development and/or prognosis of LC. We investigated 110 LC patients and 160 controls. Single-nucleotide polymorphisms of Wnt antagonist genes including DKK2 (rs17037102), DKK3 (rs3206824), DKK3 intron4 G/C (rs7396187), DKK4 (rs2073664), and sFRP4 (rs1802074) were analyzed using nested polymerase chain reaction and restriction fragment length polymorphism. Results showed that patients with DKK3 AA compared with controls have a decreased risk of LC (adjusted for smoking habit, body mass index, and familial history) (P = 0.02; odds ratio [OR],0.08; 95% confidence interval [95% CI], 0.01-0.7). It was found that, for sFRP4 polymorphism, patients with GG and GA genotypes versus AA genotype controls showed a decreased risk for LC (P = 0.01; [OR, 0.19; 95% CI, 0.05-0.73 for GG genotype]; [OR = 0.18, 95% CI, 0.04-0.72 for GA genotype]). In addition, a decreased risk of LC was also found for the genotype combination of DKK3 (rs3206824) GG and sFRP4 AG + GG (P = 0.004; OR, 0.12; 95% CI, 0.02-0.58). We suggest that these 2 polymorphisms have a protective effect on LC in this study.

The negative prognostic impact of bone metastasis with a tumor mass.

OBJECTIVE: Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer. METHODS: Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001). RESULTS: According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11-1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression. CONCLUSION: Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients.