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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.

Vemurafenib is an inhibitor of the BRAF V600E mutation which is associated with tumor responses in patients with metastatic melanoma. Although it is generally well tolerated, common side effects of vemurafenib have been reported. Arthralgia is one of the more common adverse event associated with vemurafenib. We herein report a 49-year-old woman diagnosed with metastatic melanoma harboring the BRAF V600E mutation with severe polyarthritis associated with vemurafenib after 7 days of treatment. Sonographic examination of affected joints revealed synovitis and the patient's articular symptoms were improved by analgesic and anti-inflammatory treatment, including corticosteroids. During therapy with selective BRAF inhibitors, arthritis represents a new adverse event that can require dose reduction. In case of this adverse event, treatment with anti-inflammatory drugs, such as ibuprofen and prednisone, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression.

Colorectal cancer (CRC) develops as a multi-step process which results from gradual accumulation of mutations in proto-oncogenes, tumor suppressor, and DNA repair genes. Mortality rate of CRC is very high. Therefore, development of alternative diagnostic methods which can be used in the early diagnosis is crucial. ATP2B4 gene encodes one of the four isoforms of p-type ATPase PMCA enzyme and bears critical importance in maintaining the balance of intracellular calcium homeostasis by providing the export of calcium ions out of the cell. ATP5B encodes a subunit of the mitochondrial ATP synthase which is an f-type ATPase. In this study, the relationship between ATP2B4 and ATP5B genes and CRC regarding gene expression was investigated. Study groups were constructed from a number of 50 patients (25 males, 25 females) with the mean age of 55.68 ± 9.4 and the gene expression levels in the healthy and cancerous tissues of the patients were compared by using semi-quantitative PCR and Real-Time PCR methods. As a result, in patients with rectum tumors, there was a significant relationship between ATP2B4 gene expression and the tumor location and in patients younger than 45 years, ATP5B gene expressions were detected significantly higher in tumor tissues by using RT-PCR. However, no significant relationship was detected in terms of expression differences of ATP2B4 and ATP5B genes between cancerous and healthy tissues of the CRC patients. ATP2B4 and ATP5B genes might have indirect associations in CRC pathogenesis and the investigation of their interactions with DNA repair and other related genes may help in understanding of CRC formation.

A 46-year-old man was diagnosed with brain metastasis after a two-year history of melanoma. Paliative radiotherapy was administered followed by dacarbazine, temozolamide, ipilimumab, stereotactic radiosurgery, ipilimumab reinduction and finally vemurafenib, to which the patient showed objective responses. The patient received vemurafenib for four months and died after progresive disease. Long-term follow-ups after surgery have been reported in the literature. However, in patients with unresectable metastases, outcomes are mostly detrimental. The present patient survived for 40 months after brain metastasis. The unusually long survival observed in the present case indicates the sequential effectiveness of radiotherapy, chemotherapy, ipilimumab, stereotactic radiosurgery and vemurafenib.

In lymph node-negative, hormone-positive, and Her2-negative breast cancer patients, the benefits of adding adjuvant chemotherapy to hormonal therapy continue to be debated, especially for low to intermediate grade and small tumors.Excluding patients with T4 disease, we retrospectively reviewed the records of patients with long-term follow-up at our center between 2003 and 2014. Among node-negative, hormone-positive and HER2-negative breast cancer patients, we compared two groups of patients: those given both chemotherapy (doxorubicin+cyclophosphamide) and hormonotherapy, and those prescribed hormonotherapy alone. The primary endpoints were progression-free (PFS) and overall survival (OS).Overall, no difference was observed between these two treatment groups in either DFS or OS. However, for both outcomes, there was a trend towards improved DFS and OS favoring the hormone-only group.In selected subgroups of breast cancer patients, administering adjuvant hormonal therapy alone seems to be at least as good if not better than combining hormonotherapy and chemotherapy.

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.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.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.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.

WOS: 000435353000019, PubMed ID: 29893321, Purpose: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patient's survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. Methods: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). Results: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. Conclusion: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.

To compare the effectiveness of adjuvant chemotherapy regimens in triple negative breast cancer (TNBC) for which no protocol has been determined to be treatment of choice.In this single-center retrospective trial, we analyzed the adjuvant regimens of 164 TNBC patients among 3253 breast cancer patient records. Adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), CAF (cyclophosphamide, doxorubicin, 5fluorouracil), and AC-T (doxorubicin, cyclophosphamide followed by docetaxel) regimens were compared in terms of disease free survival (DFS) and overall survival (OS).In terms of both DFS and OS TAC was significantly superior to AC-T in node positive TNBC. When node negative and positive patients were analyzed together, TAC was still significantly superior to AC-T in terms of DFS and OS. There was a trend favoring CAF over AC-T, however, it was only significant in terms of OS when all node negative and positive TNBC patients were incorporated together.In the adjuvant setting, especially in node positive patients, TAC should be the treatment of choice in TNBC patients. CAF is probably better than AC-T in TNBC.

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.

The expression differences of SCN8A (which encodes type VIII alpha subunit of voltage gated sodium channel) and NDUFC2 (which encodes C2 subunit of Complex I enzyme in oxidative phosphorylation) genes were evaluated in paired colorectal cancer (CRC) tissues which was relied on our partial transcriptome analysis data in cancer cell lines. Materials and Methods: A total of 62 paired tissues of CRC patients (34 male, 28 female) were included in the study. The mRNA levels of SCN8A and NDUFC2 genes were determined by using real-time PCR (qRT-PCR and semiquantitative PCR). Results: SCN8A gene expression level was significantly lower in tumor tissues (p = 0.0128) and in the patients with the age below 45 years (p = 0.0049). There were also meaningful relationships between the gender, grade of CRC, tumor location, histopathological classification, and SCN8A expression. There was no NDUFC2 differential expression. However, the tumors taken from right colon had significantly lower NDUFC2 expression. Conclusion: Although the voltage gated sodium channels (VGSCs) and Complex I (CI) were associated to a number of diseases including different types of cancers, the different subunits of CI and individual members of VGSCs seem to be cancer type-specific in varying proportions. Key Words: colorectal carcinoma, SCN8A, NDUFC2, Complex I, voltage gated sodium channels, gene expression.

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

PURPOSE To evaluate the clinicopathologic characteristics and treatment outcomes of young patients with colorectal cancer (CRC). METHODS Between May 2003 and June 2010, 76 patients were found eligible for this retrospective study. Age, sex, presenting symptoms, patients with acute presentation, family history, presence of polyps, histologic features, localization and stage of the tumor, treatment outcomes, time and site of recurrence, sites of metastasis, and survival outcomes were recorded from the patient files. RESULTS Seventy-six patients (55.3% male) with a median age of 23 years were evaluated. Patients were evaluated in 2 groups as follows: child-adolescent (0 to 19 y, n=20) and young adult (20 to 25 y, n=56). Sex and symptoms (abdominal pain and rectal bleeding) were significantly differed between the groups and acute presentation was close to statistical significance. Overall survival significantly increased in patients undergoing curative surgery (P

Sunitinib is a multi-targeted thyrosine kinase receptor inhibitor used in patients with advanced gastrointestinal stromal tumours (GISTs). We evaluated the efficacy and tolerability of sunitinib therapy in Turkish patients with GISTs.Between January 2001 and April 2012, 57 patients who had progressive disease or experienced unacceptable toxicity during imatinib treatment from multiple centers were investigated retrospectively.Thirty-three patients were male and 24 were female. The median age was 55 years (range; 16-84 years). Thirty-eight of the patients received imatinib for longer than 12 months, 13 patients received for 6-12 months, and 6 patients received for less than six months. The clinical benefit of sunitinib was 73.7%. Treatment-related adverse events were reported in 78% of the patients. Adverse events were generally mild to moderate in intensity. The median progression free survival (PFS) and overall survival (OS) of the patients that received sunitinib were 10.8 months and 23.9 months, respectively. The time of imatinib usage and response to sunitinib were independent prognostic factors for PFS and OS. Also, tumor size was an independent prognostic factor for PFS.Sunitinib is an effective treatment in Turkish patients with GISTs, with a clinical benefit of 73.7% and shows an acceptable tolerability.

In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis.Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34).Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02].Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.

Abdominal tuberculosis (TB) is a rare manifestation, which can be overlooked on long-lasting and non-specific findings unless a high index of suspicion is maintained. The purpose of the present study was to investigate the diagnostic features of 39 patients hospitalized with tuberculous peritonitis (TBP) in Dicle University Hospital, Turkey between January 1994 and August 2003. Twenty-two patients were male; patient age ranged between 1 and 59 years (mean: 16.2 +/- 14.4 years). There were 21 patients (54%) under 15 years of age. Thirteen children had a history of familial TB and seven adults had prior history of TB. Six (29%) of 21 pediatric cases had bacille Calmette-Guerin (BCG) scars and results of 5-tuberculin units (TU) tuberculin test were positive in seven children (18%). Of all cases, the most common presenting findings were abdominal pain (95%), ascites (92%) and abdominal distention (82%). Five of the patients had accompanying pulmonary TB, and six patients (15%) had intestinal TB who were admitted to emergency service with acute abdomen, of whom three (8%) had perforation and three (8%) had ileus. Histopathologically 20 cases (51%) were proven on abdominal ultrasonography, and computed tomography revealed most commonly ascites and thickening of peritoneum. No microbiologic evidence was obtained except three positive culture results for Mycobacterium tuberculosis. As a result, TBP should be considered for diagnosis, in patients with non-specific symptoms of abdominal pain, wasting, fever, loss of appetite, abdominal distension and even symptoms of acute abdomen, because early diagnosis and effective treatment will decrease morbidity and mortality.

Objective Risk factors of catheter-related bloodstream infection (CR-BSI) caused by central venous catheter (CVC) use at a university hospital were evaluated. Design A prospective, observational, hospital-wide study was conducted. Setting The study was conducted at a university hospital with 1050 beds. Methods Nontunneled catheters were used, and double or triple lumen was observed. Catheters were cultured by semi-quantitative method, and blood cultures were performed if necessary. All epidemiologic and clinical data were recorded without intervention during the study. Results Over a 1-year period, the study assessed 389 CVCs inserted in 367 patients (mean age 50.9 ± 18.1 years; 215 [58.6%] men, 152 [41.4%] women). Duration of catheterization was 12.0 ± 9.9 days. CVCs were inserted into either the subclavian vein (N = 263; 67.6%) or the jugular vein (N = 128; 32.4%). In 250 episodes (64.3%), antibiotics were used concomitantly. CR-BSI was found in 43 of all CVCs (11.1%). The rate of CR-BSI per 1000 catheter-days was 9.21 for the whole cohort. In multivariable analysis, only renal failure (OR 4.83; CI 1.32-17.66; P = .017) was found to be a risk factor for CR-BSI. Conclusion Renal failure was an independent risk factor for CR-BSI.

The hepatitis B virus (HBV) vaccination never lose its importance; however, we did not get immune response with vaccination in some cases at the hemodialysis (HD) units. In this research, our aim was to evaluate antibody responses that constitute with natural ways and vaccination against HBV infection in chronic HD patients. In this retrospective cohort study (between 1999 February and 2001 December), 34 patients, 19 males and 15 females that were at the HD program, were enrolled. Patients were divided into two groups: group A, vaccination group (n = 15); and group B, anti-HBc IgG (+) cases (n = 19). We injected 40 microg of recombinant HBV vaccine into the deltoid muscle at 0, 1, 2, and 6 months. The anti-HBs levels, over 10 mIU/mL, were accepted for enough immunization. In group A, after vaccination 12 of 15 (80%) patients had seroconversion but later, in five of 12 (33.3%) patients, HBs-antibody became negative and in seven of 12 (46.7%) patients the positivity of HBs-antibody continued. However, in group B, 16 of 19 (66.7%) immune patients who faced HBV infection, it was established that antibody response continued (P > 0.05). The patients in group A who had anti-HCV negativity and serum albumin levels >/=3.5g/dL (7/0; P < 0.05) had too much antibody response against the vaccine. The difference of our research was that patients under 49 years old, patients who did not respond to HBV vaccine, were proportionally higher as compared to those from other researches. In conclusion, it was realized that the immune response of the HBV vaccine was low in the HD patients and it was affected by several factors such as gender, anti-HCV positivity and nutritional status. But, in spite of getting all universal precautions, still to face with new cases emphasizes the importance of the vaccination.

Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. Material and Methods: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. Results: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. Conclusions: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues. Key Words: colorectal cancer, TRP genes family: TRPV3, TRPV4, TRPV5, TRPM4, TRPC6, mRNA expression.