A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study.

BACKGROUND: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated. METHODS: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year. RESULTS: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively. CONCLUSIONS: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).

Sorafenib with TACE improves the survival of hepatocellular carcinoma patients with more than 10 cm tumor: a single-center retrospective study.

PURPOSE: Sorafenib, a multikinase inhibitor, is effective in patients with advanced hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is an important palliative treatment for unresectable HCC, but TACE-induced ischemic injury can upregulate angiogenic factors and it might be associated with poor prognosis. The purpose of this study was to evaluate the efficacy of conventional TACE with or without sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage A-B HCC. METHODS: Thirty patients with BCLC stage A or B HCC who had undergone TACE were enrolled in this retrospective study. Child-Pugh score, BCLC staging classification, size and number of lesions were recorded. Sorafenib was given 1 month after TACE to some patients who responded to TACE. Repeated TACE was performed on demand. Tumor response was assessed every 12 weeks. The primary objective of this trial was the progression free survival (PFS). Secondary objectives were overall survival (OS), disease control rate (DCR) and total number of TACE interventions. Kaplan-Meier method was used for the estimation of survival and survival curves were compared with Log-rank test. RESULTS: Twenty-five (83.3%) patients had Child-Pugh A and 5 (16.7%) Child-Pugh B, and 24 (80%) patients had BCLC stage B disease and remanining had stage A disease. Lesion size >10 cm was found in 6 patients and 16/7/7 patients had single/two/multiple lesions, respectively. Mean number of TACE was 2.10±1.369. Seventeen (56.7%) patients used sorafenib after TACE whereas 13 (43.3%) patients were followed without any treatment but received consequent TACEs if needed. PFS of all patients was 10 months (range 3-48); it was 13 months for TACE plus sorafenib group and 9 months for TACE group (p=0.081). In subgroup analysis, TACE plus sorafenib group had better PFS (36 vs 12 months) in patients with tumor size > 10 cm (p=0.025). In the analysis of Child- Pugh A cases, PFS of TACE plus sorafenib group was 23 months while it was 10 months in TACE group (p=0.007). CONCLUSION: Concurrent treatment in Child-Pugh A group HCC with conventional TACE and sorafenib demonstrates a significant efficacy in patients having tumor size >10 cm. In Child-Pugh A group, PFS was superior in the sorafenib plus TACE group than in TACE alone group.

Comparison of FOLFIRINOX Chemotherapy with Other Regimens in Patients with Biliary Tract Cancers: a Retrospective Study.

PURPOSE: The aim of this retrospective study was to compare the different treatment options of patients with advanced biliary tract carcinoma (BTC) who were treated with platinum-gemcitabine (CG) or platinum-5-fluorouracil (CF) or 5-Fluorouracil-oxaliplatin-irinotecan (FOLFIRINOX) chemotherapy. METHODS: We included the patients with advanced BTC who were registered at the Department of Oncology in Gaziantep University between January 2008 and January 2016. The following data were analyzed: disease control rate (DCR), progression free survival (PFS) of first and second-line of chemotherapy, and overall survival (OS). Kaplan-Meier method and Log-rank test was used to compare two survival curves, and hazard regression model was used to evaluate risk factors for PFS. RESULT: Ninety-two patients were recruited. 53 (57.6 %), 27 (29.3 %), and 12 (13 %) patients received CG, CF, and FOLFIRINOX regimen as first-line chemotherapy, respectively. Median PFS and DCR of CG group were 22 weeks and 56.6 %, and these were 12 weeks and 44.4 % for CF group, and 9 weeks and 41.7 % for FOLFIRINOX group. Median OS of CG, CF, and FOLFIRINOX groups was 28, 21,and 23.5 weeks, respectively (p = 0.497). Second-line PFS of fluoropyrimidine-based chemotherapy group and gemcitabine-based chemotherapy group was 12 vs. 14 weeks (p = 0.988). Second-line PFS of FOLFIRINOX was 20 weeks, whereas it was 14 weeks for other fuoropyrimidine-based chemotherapies (p = 0.190). CONCLUSIONS: This was the first study evaluating the FOLFIRINOX regimen in BTC. Cisplatin-gemcitabine therapy still provides better survival in BCT. However, FOLFIRINOX can be an option in the second-line treatment of BTC patients who are eligible for chemotherapy.

Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients.

PURPOSE: The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms. PATIENTS AND METHODS: Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor-node-metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model. RESULTS: Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47 years (range: 21-79 years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR =4.271; 95% CI 1.515-12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047-10.125; P=0.041). CONCLUSION: MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer.

Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel.

BACKGROUND: Interindividual variability of pharmacogenetics may account for unpredictable neurotoxicities of taxanes. METHODS: From March 2011 to June 2015, female patients with operable breast cancer who had received docetaxel- or paclitaxel-containing adjuvant chemotherapy were included in this study. All patients were treated with single-agent paclitaxel intravenously (IV) 175 mg/m(2) every 3 weeks for four cycles, or IV 80 mg/m(2) weekly for 12 cycles, and IV 100 mg/m(2) docetaxel for four cycles as adjuvant treatment. We evaluated the relationship between neurotoxicity of taxanes and single-nucleotide polymorphisms of ABCB1, CYP3A4, ERCC1, ERCC2, FGFR4, TP53, ERBB2, and CYP2C8 genes. Taxane-induced neurotoxicity during the treatment was evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.03 prior to each cycle. Chi-squared tests were used to compare the two groups, and multivariate binary logistic regression models were used for determining possible risk factors of neuropathy. RESULTS: Pharmacogenetic analysis was performed in 219 females. ABCB1 3435 TT genotype had significantly higher risk for grade ≥2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172-6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade ≥2 neurotoxicity (OR: 2.259, 95% CI: 1.033-4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001-3.525, P: 0.048) compared to AA genotype with regard to any grade of neuropathy risk. We could not find any other association of other genotypes with neurotoxicity grades. CONCLUSION: ABCB1 3435 TT genotype and CYP3A4 392 AA/AG genotypes may be used as predictors of neurotoxicity during taxane chemotherapy.

Collision tumor consisting of primary follicular lymphoma and adenocarcinoma in the cecum: A case report and literature review.

The present study reports the case of a collision tumor consisting of follicular lymphoma (FL) and adenocarcinoma in the cecum of a 73-year-old man. To the best of our knowledge, the present study is the 11th case of a collision tumor consisting of colon adenocarcinoma and lymphoma to be reported in the literature, and the first case of cecum adenocarcinoma with low grade FL in the same segment of the cecum and the same regional lymph node to be reported. The present study reviewed the literature to determine treatment options for patients with collision tumors. The present patient was administered with adjuvant chemotherapy for T3N1M0 colon cancer following surgery, due to the dominance of colon adenocarcinoma in the collision tumor. Following the completion of treatment, progression of the untreated FL was observed. In the literature, patients with collision tumors are administered with chemotherapy for stage IV FL, and following the completion of treatment patients have presented with a recurrence of early stage colon adenocarcinoma. The recommended treatment for collision tumors is dependent on the dominant tumor; however, the treatment options for collision tumors in the literature appeared to exacerbate the other tumor. The characteristics of the tumors altered following chemotherapy, and immunological alterations in the tumors due to chemotherapy appear to have contributed to the exacerbation of the tumors. Therefore, patients with early-stage tumors should be considered at risk of recurrence of other malignancies, which are present in collision tumors.

Survival analysis in second-line and third-line chemotherapy with irinotecan followed by topotecan or topotecan followed by irinotecan for extensive-stage small-cell lung cancer patients: a single-center retrospective study.

PURPOSE: The number of patients who make it to receive third-line chemotherapy is increasing owing to the improvements in adverse-event management of chemotherapy for small-cell lung cancer (SCLC). Sequencing of optimal treatment for SCLC is still a challenge for oncologists. In this paper, we aim to present a different approach to the treatment of SCLC. METHODS: Between January 2008 and July 2014, all patients diagnosed with extensive-stage SCLC and treated with third-line chemotherapy at Gaziantep University Oncology Hospital were analyzed retrospectively. Disease control rates and progression-free survival (PFS) for first-, second-, and third-line chemotherapy, and overall survival (OS) were recorded. Survival analysis was calculated by using Kaplan-Meier method. RESULTS: A total of 255 SCLC patients were screened, and 25 of those patients who received third-line chemotherapy were included in this study. Median age was 57±10.131 years (range: 39-74 years). Disease control rates at first-, second-, and third-line chemotherapy were 92%, 68%, and 44%, respectively. Fourteen patients received irinotecan followed by topotecan, and eleven patients received topotecan followed by irinotecan. Second-line median PFS was statistically better in patients treated with irinotecan at second-line compared with those treated with topotecan (21 vs 12 weeks, P=0.018). Comparison of third-line median PFS of the two groups was not statistically significant (14 vs 12 weeks, P=0.986). Median OS was not statistically significant in patients who received irinotecan followed by topotecan vs those who received topotecan followed by irinotecan (18 vs 14 months, P=0.112). CONCLUSION: Sequential monotherapy with topotecan and irinotecan provides a considerable contribution to OS, and second-line irinotecan showed a better PFS, despite a similar OS, compared with topotecan.

High-throughput screening of Sirtuin family of genes in breast cancer.

Mammalian Sirtuins have been shown to perform distinct cellular functions and deregulated expression of these genes was reported to be involved in the development of various malignancies including breast cancer. An increasing number of evidence indicates that Sirtuins have both tumor promoter and tumor suppressor functions. However, the roles of Sirtuins have not been well-reported in breast cancer. In the present study, quantitative expression levels of Sirtuins (SIRT1-7) in breast cancer patients and breast cancer cell lines (MCF-7 and SKBR3) and control cell line (CRL-4010) were assessed by using a high-throughput real-time PCR method. As a result, Sirtuins were found to be differentially expressed in breast cancer tissues and cancer cell lines. Particularly, expressions of SIRT1 and SIRT4 were found to be significantly down-regulated in breast cancer tissues and SKBR3 breast cancer cells. In contrast, SIRT2, SIRT3, and SIRT5 genes were shown to be up-regulated in our study. Although SIRT6 and SIRT7 were also up-regulated in breast cancer tissues, these expression changes were statistically insignificant. Additionally, SIRT2, SIRT3, SIRT5, SIRT6 and SIRT7 were found to be differentially expressed in breast cancer cell lines. Yet, these changes were not well-correlated with tissue expression levels. In conclusion, Sirtuin family of genes shows differential expressions in breast cancer tissues and cells and SIRT1 and SIRT4 seem to play key tumor suppressor roles in breast cancer development. Herein, we report expression levels of Sirtuin family of genes in both breast cancer tissues and cancer cell lines simultaneously.

Tyrosine kinase inhibitors improve parenchymal findings of liver cirrhosis in a patient exhibiting concomitant hepatocellular carcinoma and renal cell cancer.

Hepatocellular carcinoma (HCC) and renal cell cancer (RCC) are malignancies, which are chemotherapy resistant and fatal at the advanced stages. Previously developed tyrosine kinase inhibitors are used in the treatment of advanced stage disease. In the present case study, a patient using sunitinib for stage IV RCC presented with HCC following 2 years of treatment. A patient who exhibited Child-Pugh class C cirrhosis initially, exhibited a marked improvement of hepatocellular parenchyma findings following treatment with sunitinib. Sunitinib is suggested to have preventive effects on the pathogenesis of liver fibrosis and cirrhosis in vitro, via an anti-vascular endothelial growth factor and anti-platelet-derived growth factor mechanism. However, no clinical supportive study has been performed until now. Improvement of liver functions may be explained in this manner. Therefore, investigations are required with different doses of sunitinib and other tyrosine kinase inhibitors in order to evaluate the efficacy on treatment of cirrhosis progression.

Efficacy of venlafaxine for the relief of taxane and oxaliplatin-induced acute neurotoxicity: a single-center retrospective case-control study.

BACKGROUND: Oxaliplatin and taxane-induced neurosensory toxicity is dose-limiting and mostly presents with acute symptoms that affect the activities of daily living and overall quality of life. The objective of the present study is to assess the relief of acute neuropathy with venlafaxine treatment during the chemotherapy period. PATIENTS AND METHODS: In this retrospective case-control study, from January 2010 to February 2015, patients who experienced treatment with oxaliplatin and taxane-induced acute neurotoxicity were evaluated according to the NCI-CTCAE v. 4.03 grading scale. Neurotoxicity was evaluated using a numeric rating scale (NRS) for pain intensity and experienced relief under the treatment of venlafaxine and using a neuropathic pain symptom inventory scale (NPSI) for the style of complaints. Patients who were diagnosed as mildly depressed according to the HOST anxiety and depression scale and who had grade 1 to 3 sensory neurotoxicity based on the NCI-CTCAE v. 4.03 grading scale, and who also reported ≥ 4/10 on a NRS were eligible. The primary end point was the rate of more than 75 % symptomatic relief under venlafaxine treatment. RESULTS: Two hundred six patients were included (82 % female, median age: 52.7 years). Most patients had breast, gynecologic, and colon cancer (93.4 %). Ninety-one patients who received venlafaxine and 115 patients as the control group were assessed for neurotoxicity every 3 weeks. Based on the NRS, a rate of more than 75 % symptomatic relief was 53.5, 58.3, and 45.2 % in venlafaxine arm versus 0, 0, and 0 % in the control arm in the first, second, and third visits, respectively. Side-effects of venlafaxine (n = 7) were grade 1-2 nausea/vomiting (3.2 %) and asthenia/somnolence (3.2 %) without grade 3-4 events. CONCLUSION: Venlafaxine has a significant clinical activity against taxane-oxaliplatin-induced acute neurosensory toxicity.

Taxane-induced peripheral sensorial neuropathy in cancer patients is associated with duration of diabetes mellitus: a single-center retrospective study.

PURPOSE: The purpose of this study was to determine whether the presence of diabetes mellitus (DM) influences the incidence and severity of peripheral sensory neuropathy (PSN) in patients using taxane therapy. METHODS: A retrospective single-center analysis was conducted: Patients with PSN at baseline were excluded. The incidence of PSN was evaluated retrospectively in patient subgroups who received taxane arm and taxane-plus-platinum-agents combination arm with or without known DM at baseline. RESULTS: Three hundred seventy-four patients were enrolled in this study, 81 (21.6%) of patients had DM at baseline. The incidence of grade 1 PSN (non-DM/DM) in patients receiving taxane-based chemotherapy was 33.4/25.9% and more than grade 2 PSN (non-DM/DM) was 15/34.6%. The rate of neuropathy of non-diabetic patients was 48.8%, while the rate of diabetic patients was 52.8 and 75% in DM duration below 5 years and above 5 years group, respectively. CONCLUSIONS: This retrospective analysis indicates that taxane-based therapy in DM patients whose disease duration is above 5 years appears to affect the incidence and severity of PSN without known baseline neuropathy. The probability of PSN with taxane-based therapy was similar in DM duration below 5 years and non-DM patients.

Could erlotinib treatment lead to acute cardiovascular events in patients with lung adenocarcinoma after chemotherapy failure?

Erlotinib, an epidermal growth factor receptor and tyrosine kinase inhibitor, is a targeted drug that was approved for the treatment of non-small-cell lung cancers and pancreatic cancers. Targeted tyrosine kinase inhibitors are known to have cardiotoxic effects. However, erlotinib does not have a statistically proven effect of increasing acute cardiovascular event (ACE) risk. Preclinical studies showed that beta agonist stimulation among rats that were administered erlotinib led to cardiovascular damage. Thus, there would be an aggregate effect of erlotinib on ACE, although it is not thought to be a cardiotoxic drug itself. In this paper, we present two non-small-cell lung cancer cases that developed ACE under erlotinib treatment.

Atypical presentation of disseminated intravascular coagulation with synchronous peripheral venous thromboembolism and arterial gangrene in a pancreatic cancer patient: a case report.

CONTEXT: Cancer is a prothrombotic state and anticancer therapies are often complicated by vascular events. The risk of developing thromboembolic events is substantially increased in patients with pancreatic cancer. One possible presentation of vascular events in pancreatic cancer is disseminated intravascular coagulation (DIC). CASE REPORT: In our case a patient with a diagnosis of pancreatic cancer initially presented with thrombosis and received low molecular weight heparin (LMWH) in addition to standard chemotherapy regimen. He was thought to have DIC by assessment of clinical and laboratory findings. CONCLUSION: Clinically, thrombosis was first located in the left femoral vein and encountered at right femoral artery after three weeks. This pattern was an unusual presentation of DIC. Subclinical DIC is common in patients presenting with pancreatic cancer and is considered a 'poor' prognostic factor. Acute DIC, on the other hand is a potentially mortal condition.

Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature.

The present case report defines a rare case of a liposarcoma with bone metastasis resulting in a complete remission (CR) following trabectedin treatment. The patient was referred with abdominal swelling and pain. A retroperitoneal mass was detected and described as dedifferentiated liposarcoma (DDLS). The mass was surgically removed and consequently adjuvant chemotherapy was administered. Three months after the completion of chemotherapy, patient presented with bone metastasis in thoracic and lumbar vertebrae. Vertebroplasty and radiotherapy (RT) was performed. After these therapies, bone pain persisted and bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae. Zoledronic acid was added to trabectedin treatment. CR has been detected on bone scintigraphy and positron emission tomography-computed tomography (PET-CT) after 18 weeks. Previous cases about liposarcoma treated with trabectedin were mostly about the myxoid/round cell type (former name, currently known as myxoid liposarcoma (MLS)) and mostly reported partial responses. In this study, trabectedin was used for the treatment of a metastatic retroperitoneal DDLS and a CR was achieved.

Prognostic impact of initial maximum standardized uptake value of (18)F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib.

PURPOSE: To investigate whether the initial maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has a prognostic significance in metastatic lung adenocarcinoma. PATIENTS AND METHODS: Sixty patients (24 females, mean age: 57.9±12 years) with metastatic stage lung adenocarcinoma who used erlotinib and underwent (18)F-FDG PET/CT at the time of diagnosis between May 2010 and May 2014 were enrolled in this retrospective study. The patients were stratified according to the median SUVmax value, which was found as 11. Progression-free survival (PFS) rates for 3, 6, and 12 months were examined for SUVmax values and epidermal growth factor receptor (EGFR) mutation status. RESULTS: The number of EGFR-sensitizing mutation positive/negative/unknown was 26/17/17, respectively, and the number of patients using erlotinib at first-line, second-line, and third-line therapy was 15, 31, and 14 consecutively. The PFS rates of EGFR mutation positive, negative, and unknown patients for 3 months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45-13.26), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6 months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82-6.96), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12 months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42-5.26), respectively. Thirty-one of 60 patients had SUVmax values ≤11. The PFS rates for 3, 6, and 12 months were 70.5%/28% (P=0.001, OR=9.0; 95% CI: 2.79-29.04), 61.7%/8% (P<0.001, OR=28.35; 95% CI: 5.5-143), and 52.9%/8% (P<0.001, OR=18.69; 95% CI: 3.76-92.9) for low SUVmax (≤11) group/high SUVmax (>11) group, respectively. CONCLUSION: Initial SUVmax value on (18)F-FDG PET/CT is found to be a prognostic factor anticipating the response to erlotinib for 3, 6, and 12-month rates of PFS in both EGFR-sensitizing mutation and wild-type tumor group.

The relationship between urotensin II and its receptor and the clinicopathological parameters of breast cancer.

BACKGROUND: Urotensin II is a vasoactive polypeptide. It is known that some vasoactive polypeptides are produced and secreted by tumor cells, and act as a paracrine growth stimulant. The aim of this study was to examine the relationship between urotensin II and its receptor's messenger RNA expression in breast cancer. MATERIAL/METHODS: Fifty-nine women with breast cancer were included in this study. The median age was 48 years. The relationships between urotensin II and urotensin II receptor mRNA expressions, which were derived from fresh breast cancer tissues and adjacent normal breast tissues, and clinical and pathological parameters, were assessed. RESULTS: We found expressions of urotensin II mRNA and its receptor in 55 of 59 breast cancer tissues and in 55 of 59 normal breast tissues. We found a positive significant correlation between urotensin II and its receptor (p=0.001, r=0.632), and found a negative, but insignificant, correlation between urotensin II and age (p=0.038, r=-0.281). Urotensin II levels were higher in the premenopausal group compared to the postmenopausal group (p<0.05). The mean urotensin II receptor expression was higher in the premenopausal group (p<0.05) compared to the postmenopausal group, and its expression was also higher in the group without extra-nodal invasion compared to that of the group with extra-nodal invasion (p=0.001). Urotensin II levels were higher in the group without lymphatic invasion compared to the group with lymphatic invasion (p=0.048). CONCLUSIONS: This study is the first in the English medical literature to determine the urotensin II and its receptor mRNA expressions in breast cancer tissues. Consequently, urotensin II seems be associated with menopausal status, and extra-nodal and lymphatic invasion.

Do fasudil and Y-27632 affect the level of transient receptor potential (TRP) gene expressions in breast cancer cell lines?

Breast cancer (BC) is the most frequent cancer type in women, and the mortality rate is high especially in metastatic disease. Ion channels such as the transient receptor potential (TRP) channels correlate with malignant growth and cancer progression. Hence, some authors have suggested that the expression levels of TRP channels may be used as a marker in the diagnosis and predicting the prognosis of BC. Also, in some recent studies, targeting TRP channels are suggested as a novel treatment strategy in BC. The aim of this study was to investigate the effect of two Rho-kinase (ROCK) inhibitors, fasudil and Y-27632, on the expression levels of TRP channel genes in breast cancer cell lines (ZR-75-1, MCF7, and MDA-MB-231) and breast epithelial cell line (hTERT-HME1). The expression levels of TRP genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that fasudil had reduced the TRPC1, TRPV2 expression levels in the ZR-75-1, MCF7, and MDA-MB-231 cell lines. On the other hand, fasudil and Y-27632 had reduced TRPM6 expression levels in all cell lines. Y-27632 increased the expression levels of TRPC7 in all cell lines. In conclusion, this is the first study demonstrating that the inhibition of ROCK pathway changes the expression levels of some TRP genes. Also, our study has firstly shown that the expression levels of the TRP genes which are suggested as a diagnostic and prognostic biomarker in BC, were changed with the treatment of fasudil and Y-27632.

Depression, anxiety and quality of life through the use of complementary and alternative medicine among breast cancer patients in Turkey.

BACKGROUND AND AIM: Breast cancer is the most common type of cancer amongst women today. The aim of this study was to examine the association between complementary and alternative medicine (CAM) and the quality of life (QoL), anxiety and depression and demographic characteristics of women with breast cancer. MATERIALS AND METHODS: QoL was measured by the European Organization for Treatment and Research of Cancer quality of life core questionnaire (QLQ-C30, version 3.0) and anxiety and depression was measured by the hospital anxiety and depression scale. RESULTS: In total, 122 patients with breast cancer were enrolled in the study and 50% (n=61) of them reported that they were using CAM. The most commonly used CAM methods were stinging nettle (57%) and prayer and spiritual healing (49%). No relationship was found between the use of CAM and the patient's age, time to diagnosis, cancer stage, chemotherapy use, smoking and residence. However, the analyses showed a positive association between CAM and role functioning (P=0.014) and financial difficulties (P=0.011); and a negative association between CAM and emotional functioning (P=0.033). CONCLUSIONS: Based on the previous studies, 20-83.3% of breast cancer patients among different countries and cultures used CAM. Our results suggested that the use of CAM among women is quite popular, but they showed no correlation between CAM usage and anxiety and depression. In addition, CAM usage was more common in breast cancer patients with a poor emotional and financial status.

Intrapleural hyperthermic perfusion chemotherapy in subjects with metastatic pleural malignancies.

OBJECTIVES: Malignant pleural effusion (MPE) means poor prognosis in the majority of cases. Intrapleural Hyperthermic perfusion chemotherapy (HIPEC) looks promising approach for these patients. We aimed to investigate whether cytoreductive surgery followed by HIPEC provides any survival benefit in cases with metastatic MPEs. METHODS: Between January 2009 and December 2011, 19 patients with metastatic MPEs were treated with HIPEC following surgical interventions such as pleurectomy/decortication and/or lung resection (group 1). Comparison was done with historical control groups consisted of patients who received either talc pleurodesis or pleurectomy/decortication followed by systemic treatment for the management of metastatic MPEs between June 2007 and June 2008 (group 2 and 3). Statistical analyses including overall survival, disease free interval were done for the group comparisons. RESULTS: Median survival in group 1, 2 and 3 were 15.4, 6, 8 months, respectively. One year survival was 54.7% in group 1 where it was 0.6% and 0.8% in group 2 and 3, respectively. There was no operative mortality. Morbidity was occurred in 1 patient in group 1 (5.3%). CONCLUSIONS: HIPEC combined with cytoreductive surgery seems to be a promising treatment option for subjects with metastatic MPEs. Further studies are needed for the optimization of HIPEC method, drug of choice, and the best combination therapy for the multimodal treatment.

Role of rho-kinase gene polymorphisms and protein expressions in colorectal cancer development.

OBJECTIVE: The aim of this study was to investigate a possible association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and colorectal cancer (CRC) development. METHODS: Eighty-five patients operated due to CRC and 178 healthy controls with similar age and sex were included to this study. Genomic DNA from the patients and the healthy control cases was analyzed by a BioMark 96.96 dynamic array system. The protein expressions of ROCK1, ROCK2 and p53 were determined by immunohistochemical staining. RESULTS: There were significant associations between ROCK1 (rs73963110 and rs35996865) and ROCK2 gene polymorphisms (rs2290156, rs10178332, rs35768389, rs10929732 and rs34945852) with CRC development. However, no marked associations were found between ROCK2 gene rs965665, rs2230774, rs6755196 and rs1515219 polymorphisms and the risk of developing CRC. Rho-kinase and p53 immunohistochemical stainings were markedly elevated in the tumor tissue. There were significant correlations between vascular and perineural invasions with ROCK2 or p53 protein expressions. CONCLUSIONS: These results are the first to demonstrate the contribution of Rho-kinase in CRC development in patients. Our data showed that the ROCK1 and ROCK2 genes might be a risk factor for CRC development and that genetic polymorphisms in these genes may modify individual susceptibility to CRC in the Turkish population.