EXPRESSION OF ALU REPEAT IN BLOOD PLASMA OF PATIENTS WITH BREAST CANCER DURING NEOADJUVANT CHEMOTHERAPY: AN EXPLORATORY STUDY.

BACKGROUND: Locally advanced breast cancer (LABC) rates are unusually high in developing countries. There is a need for the identification of predictive biomarkers for the selection of patients who could benefit from neoadjuvant chemotherapy (NAC). AIM: As the expression of ALU repeat is increased in cancer and has not been assessed in liquid biopsy of cancer patients, our goal was to assess ALU expression in the blood plasma of LABC patients during NAC. PATIENTS AND METHODS: Plasma samples drawn at baseline and at the end of the fourth cycle of chemotherapy were used to determine the plasma levels of ALU-RNA by quantitative real-time PCR. RESULTS: ALU expression from baseline to the fourth cycle of NAC increased from a median relative level of 1870 to 3370 in the whole group (p = 0.03). The increase in ALU-RNA levels in the course of NAC was more pronounced in premenopausal women and in patients with hormone-positive tumors. In patients with complete response to NAC, baseline ALU expression was higher than that in those with partial response. CONCLUSION: This exploratory study provides evidence that plasma ALU-RNA levels are modulated by the menopausal status and hormone receptor status of breast cancer patients and pre-therapeutic ALU-RNA levels might be useful in predicting the response to chemotherapy in a neoadjuvant setting.

Chemical and microbiological properties of Lake Aygir in Turkey and usage of drinking, fisheries, and irrigation / Propriedades químicas e microbiológicas do lago Aygir na Turquia e uso de bebidas, pescarias e irrigação

Abstract Since water is one of the essentials for life, the presence and quality of water in the habitat is extremely important. Therefore, water quality change and management of Lake Aygır was investigated in this study. For this, water samples collected from the lake and the irrigation pool between May 2015 and May 2016 were analyzed monthly. Spectrophotometric, titrimetric and microbiological methods were used to determine the water quality. According to some water quality regulations, HCO3, NH4, Cu, Mo, Br, fecal coliform and total suspended solid (TSS) values were found above the limit values. The other 29 parameters comply with Turkish national and international legislations. Lake Aygır was negatively affected by the surrounding settlements and agricultural activities. It is thought that the water resource should be monitored periodically and remedial studies should be done to prevent parameters exceeding the limits. However, Lake Aygır was generally suitable for drinking, use, fishing and irrigation.

Resumo Como a água é um dos elementos essenciais para a vida, a presença e a qualidade da água no habitat são extremamente importantes. Portanto, a mudança da qualidade da água e a gestão do lago Aygır foram investigadas neste estudo. Para isso, amostras de água coletadas no lago e na piscina de irrigação entre maio de 2015 e maio de 2016 foram analisadas mensalmente. Métodos espectrofotométricos, titulométricos e microbiológicos foram usados para determinar a qualidade da água. De acordo com alguns regulamentos de qualidade da água, os valores de HCO3, NH4, Cu, Mo, Br, coliformes fecais e total sólido suspenso (TSS) foram encontrados acima dos valores limite. Os outros 29 parâmetros estão em conformidade com as legislações nacionais e internacionais turcas. O lago Aygır foi afetado negativamente pelos assentamentos e atividades agrícolas ao redor. Pensa-se que o recurso hídrico deve ser monitorado periodicamente e estudos corretivos devem ser feitos para evitar que os parâmetros ultrapassem os limites. No entanto, o lago Aygır era geralmente adequado para beber, usar, pescar e irrigar.

An investigation on systematic history and distribution areas of tarek (Alburnus tarichi (Güldenstädt, 1814)) / Uma investigação sobre a história sistemática e as áreas de distribuição de tarek (Alburnus tarichi (Güldenstädt, 1814))

Abstract This study aimed to determine the distribution area of tarek (Alburnus tarichi (Güldenstädt, 1814)) and to define how it must be called according to the scientific name by evaluating its previous studies made by various systematisers and their reports on its distribution, and by comparing literature knowledge. The taxonomic characteristics of the collected samples were evaluated and several measurements and counts were taken on the samples; analfin origin 0-4 scales behind dorsal fin-base; 72-91 lateral line scales; 21-29 gill rakers; 7½-10 branched dorsal-fin rays and 10-12½ branched anal-fin rays. Body and caudal peduncle was moderately compressed. Body was covered by overlapping scales. Tarek has five different populations in the Basin. They are Van, Erçek, Nazik and Aygır Lakes and Koçköprü Dam Lake populations. The main living area of the tarek population is Lake Van; however, between May and June, mature individuals of tarek enter to tributaries of Van Lake. Some of them are Karasu, Bendimahi, Deliçay, Zilan, Karmuç, Sapur, Yanıkçay, Gevaş, Engil, Kurubaş and Akköprü Streams. At the end of study, it was concluded that tarek should be called as Alburnus tarichi (Güldenstädt, 1814) and it is an endemic fish species distributed only in Van Lake Basin.

Resumo Este estudo teve como objetivo determinar a área de distribuição de tarek (Alburnus tarichi) (Güldenstädt, 1814) e definir como deve ser chamado de acordo com o nome científico, avaliando estudos anteriores feitos por vários sistematizadores e seus relatórios sobre sua distribuição, e comparando o conhecimento da literatura. As características taxonômicas das amostras coletadas foram avaliadas e várias medições e contagens foram realizadas nas amostras, como origem analfin 0-4 escalas atrás da base da barbatana dorsal; 72-91 escalas de linha lateral; 21-29 rakers branquiais; 7½-10 raios da nadadeira dorsal ramificada, e 10-12½ raios da nadadeira anal ramificados. Pedúnculo caudal e corporal foram moderadamente comprimidos. O corpo estava coberto por escamas sobrepostas. Tarek tem cinco populações diferentes na bacia estudada. São as populações dos lagos Van, Erçek, Nazik e Aygır, e Koçköprü barragem. A principal área de presença da população tarek é o Lago Van; no entanto, entre maio e junho, indivíduos maduros de tarek entram nos afluentes do lago Van. Alguns deles são os fluxos Karasu, Bendimahi, Deliçay, Zilan, Karmuç, Sapur, Yanıkçay, Gevaş, Engil, Kurubaş e Akköprü. No final do estudo, concluiu-se que tarek deveria ser chamado Alburnus tarichi (Güldenstädt, 1814) e que é uma espécie de peixe endêmica distribuída apenas na Bacia do Lago Van.

An investigation on systematic history and distribution areas of tarek (Alburnus tarichi (Güldenstädt, 1814))

Abstract This study aimed to determine the distribution area of tarek (Alburnus tarichi (Güldenstädt, 1814)) and to define how it must be called according to the scientific name by evaluating its previous studies made by various systematisers and their reports on its distribution, and by comparing literature knowledge. The taxonomic characteristics of the collected samples were evaluated and several measurements and counts were taken on the samples; analfin origin 0-4 scales behind dorsal fin-base; 72-91 lateral line scales; 21-29 gill rakers; 7½-10 branched dorsal-fin rays and 10-12½ branched anal-fin rays. Body and caudal peduncle was moderately compressed. Body was covered by overlapping scales. Tarek has five different populations in the Basin. They are Van, Erçek, Nazik and Aygr Lakes and Koçköprü Dam Lake populations. The main living area of the tarek population is Lake Van; however, between May and June, mature individuals of tarek enter to tributaries of Van Lake. Some of them are Karasu, Bendimahi, Deliçay, Zilan, Karmuç, Sapur, Yankçay, Geva, Engil, Kuruba and Akköprü Streams. At the end of study, it was concluded that tarek should be called as Alburnus tarichi (Güldenstädt, 1814) and it is an endemic fish species distributed only in Van Lake Basin.

Resumo Este estudo teve como objetivo determinar a área de distribuição de tarek (Alburnus tarichi) (Güldenstädt, 1814) e definir como deve ser chamado de acordo com o nome científico, avaliando estudos anteriores feitos por vários sistematizadores e seus relatórios sobre sua distribuição, e comparando o conhecimento da literatura. As características taxonômicas das amostras coletadas foram avaliadas e várias medições e contagens foram realizadas nas amostras, como origem analfin 0-4 escalas atrás da base da barbatana dorsal; 72-91 escalas de linha lateral; 21-29 rakers branquiais; 7½-10 raios da nadadeira dorsal ramificada, e 10-12½ raios da nadadeira anal ramificados. Pedúnculo caudal e corporal foram moderadamente comprimidos. O corpo estava coberto por escamas sobrepostas. Tarek tem cinco populações diferentes na bacia estudada. São as populações dos lagos Van, Erçek, Nazik e Aygr, e Koçköprü barragem. A principal área de presença da população tarek é o Lago Van; no entanto, entre maio e junho, indivíduos maduros de tarek entram nos afluentes do lago Van. Alguns deles são os fluxos Karasu, Bendimahi, Deliçay, Zilan, Karmuç, Sapur, Yankçay, Geva, Engil, Kuruba e Akköprü. No final do estudo, concluiu-se que tarek deveria ser chamado Alburnus tarichi (Güldenstädt, 1814) e que é uma espécie de peixe endêmica distribuída apenas na Bacia do Lago Van.

Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome.

BACKGROUND: The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. MATERIALS AND METHODS: 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. RESULTS: The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7-18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06-0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. CONCLUSIONS: Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins.

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma.

OBJECTIVE: We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc). METHODS: The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test. RESULTS: Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan-Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non-clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001). CONCLUSIONS: Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.

Impaired coronary flow reserve in metastatic cancer patients treated with sunitinib.

PURPOSE: Hypertension is one of the major side effects of sunitinib, an angiogenesis inhibitor used in the treatment of metastatic renal cell carcinomas (mRCC) and gastrointestinal stromal tumors (GIST). Endothelial dysfunction, an early and reversible event in the pathogenesis of atherosclerosis, is suggested to be one of the possible underlying mechanisms of hypertension caused by angiogenesis inhibitors. Coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in mRCC and GIST patients under sunitinib treatment. METHODS: Eighteen metastatic cancer patients (16 mRCC and 2 GIST) on sunitinib treatment and 27 healthy subjects were enrolled in this cross-sectional study. Thyroid stimulating hormone (TSH), lipid profile, creatinine, hemoglobin, glucose, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anthropometric and physical parameters of patients were recorded. CFR recordings were performed by the Vivid 7 echocardiography device. RESULTS: CFR was significantly lower in patients when compared with controls (1.82±0.4 vs 2.71±0.8, respectively; p < 0.001). Impaired CFR was found in 13 (72%) patients whereas all controls had normal CFR values. CFR was inversely correlated with the duration of sunitinib treatment (r=-0.36, p =0.01), high sensitivite (hs) CRP (r = -0.574, p =0.01) and ESR (r = - 0.5, p = 0.02). CONCLUSION: Our findings indicate that CFR is significantly impaired in cancer patients on sunitinib treatment. There is an inverse correlation between CFR and duration of sunitinib treatment and inflammation markers.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Oral etoposide as first-line therapy in the treatment of patients with advanced classic Kaposi's sarcoma (CKS): a single-arm trial (oral etoposide in CKS).

BACKGROUND: Classic Kaposi's sarcoma (CKS) affects an elderly population; it is important to have effective treatment options with high activity and relatively low toxicity, and availability to be used for long periods. OBJECTIVE: We investigated the activity and safety of single-agent etoposide with an oral administration schedule in patients with advanced CKS. METHODS: Histologically confirmed, CKS patients were eligible for study. All had a negative test for HIV and good performance status. All patients received oral etoposide 50 mg twice daily for 10 days every 3 weeks. RESULTS: Thirty patients (median age 66 and 22 males) were enrolled into the study. The majority of them had non-metastatic, local advanced disease and symptoms in nearly half of patients. Complete and partial responses were observed in 10% and 77% of patients, respectively, giving an overall response rate of 87%. Stable disease occurred in the other 13% of patients. Treatment was well tolerated. Grade IV toxicity was not observed. Haematological toxicity was the principal dose-limiting side effect. Severe leucopaenia and neutropaenia were observed in 7% and 10% of patients respectively. No patient was complicated by febrile neutropaenia. Mild-moderate anaemia observed frequently, but only 3% of patients had severe anaemia and severe thrombocytopaenia was not observed. The 5-year overall survival rate was 92%. CONCLUSIONS: Single-agent oral etoposide is an effective treatment option and is acceptably toxic and easily administered. Therefore, we recommend the single agent of oral etoposide as the first-line chemotherapy for advanced CKS.

Modified DCF (mDCF) regimen seems to be as effective as original DCF in advanced gastric cancer (AGC).

PURPOSE: The aim of this retrospective study (from January 2007 to December 2011) was to investigate the efficacy and tolerability of mDCF schedule for chemotherapy-naïve AGC patients. PATIENTS: Patients (n = 54) with locally inoperable or distant metastasis and performance status of 0-2 were eligible. The triplet combination chemotherapy consisting of docetaxel 60 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and 5-fluorouracil 600 mg/m(2) for 5 days of continuous infusion were administered every 21 days, up to nine cycles. Prophylactic G-CSF was not allowed. RESULTS: In all, 36 (67 %) patients were male and 18 (33 %) were female; median age was 59 years. The majority of patients (n = 46, 85 %) had metastatic disease and 8 (15 %) of them had locally advanced disease. Liver metastasis and peritonitis carcinomatosa were found in 20 (43 %) and 18 (39 %) of the 46 cases, respectively. The median cycle of chemotherapy was 6. In assessing 50 patients for response evaluation, one had complete response. Partial response was achieved in 27 (54 %) patients. Seventeen patients (34 %) had stable disease and 5 (10 %) had progressive disease, while 4 % (n = 2) and 11 % (n = 6) of the patients developed severe (grade 3-4) neutropenia and anemia, respectively. During the median follow-up time (6.9 months, range 0.4-24), 28 (52 %) patients died. The overall and progression-free survival were 10.7 [95 % CI 8.9-12.4] and 6.8 [95 % CI 5.8-7.8] months, respectively. CONCLUSIONS: Although this was not a prospective comparative study, the mDCF regimen seems to be as effective as the original DCF in AGC with acceptable and manageable side effects.

Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients.

PURPOSE: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients. METHODS: Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves. RESULTS: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease. CONCLUSION: No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.

Transient atypical monocytosis mimic acute myelomonocytic leukemia in post-chemotherapy patients receiving G-CSF: report of two cases.

Granulocyte colony-stimulating factor (G-CSF) is now widely used in patients with malignant disorders receiving intensive chemotherapy to increase leukocyte count and to upregulate phagocyte function during neutropenia. Monocytosis associated with G-CSF has been reported in anecdotal literature. We report two cases of pseudoleukemia secondary to G-CSF administration. Both patients initially presented with myelodysplastic syndrome with chromosome 7 abnormalities that evolved into acute myeloid leukemia. Case one had deletion 7q while case two initially had monosomy 7 and subsequently developed a balanced translocation between the short (p) arm of chromosome 1 and long (q) arm of chromosome 15. Following the induction chemotherapy and G-CSF administration, both of these patients developed pseudoleukemia. Patient 1 had white blood cell (WBC) count of 26 x 10(9)/l with 72% monocytes, while patient two had WBC of 14.1 x 10(9)/l with 30% monocytes. In both patients the monocytosis resolved after the discontinuation of G-CSF therapy. In summary, patients treated with G-CSF should be followed closely. In those cases with pseudoleukemia discontinuation of the drug with no supplemental chemotherapy is probably enough to control the atypical monocytosis.

Increased incidence of trisomy 8 in acute myeloid leukemia with skin infiltration (leukemia cutis).

Anecdotal literature reports and the authors' own observations suggest an association between chromosome 8 aneuploidy and leukemia cutis. The authors investigated this potential association by using fluorescence in situ hybridization (FISH) directly on skin infiltrates in a series of 11 patients with acute monocytic leukemia (AML). Seven of the 11 patients were aneuploid for chromosome 8 by FISH which was confirmed by dual color hybridization. Six of these seven patients were AML-M4 or M5 and one was M1. The majority of the cases with leukemia cutis expressed CD4 (90% of cases), CD14 (60%), and/or CD56 (50%) in bone marrow leukemic cells. The data show the utility of examination of skin infiltrates by FISH for the detection of trisomy 8 in leukemia cutis. They also suggest the importance of trisomy 8 as a factor in predisposition to skin infiltration in AML.

Combined carcinoid tumor of the lung: a combination of carcinoid and adenocarcinoma.

Combined small cell carcinoma is an uncommon but well described diagnostic category of neuroendocrine lung tumors. The prognosis of these tumors appears to be similar to that of pure small cell carcinoma, although it is believed that the non-small cell components of these tumors are less chemo-responsive than the small cell components. We report a case of a 60-year-old male smoker with a 2-cm nodule that, on subsequent lobectomy, was a combination of carcinoid and adenocarcinoma. A lymph node metastasis to an ipsilateral hilar node was comprised of only the well differentiated adenocarcinoma component. The biologic behavior of such tumors is not well described and their place within, what may be described as, a spectrum of combined neuroendocrine tumors is discussed.

Comparison of sonograms and liver histologic findings in patients with chronic hepatitis C virus infection.

Gray scale ultrasonographic images of the liver were correlated with histologic findings in patients with chronic hepatitis C virus infection. The gray scale patterns of 64 livers with chronic hepatitis C virus infection were categorized as normal, fatty, fibrofatty, fibrotic, or inflammatory and were graded as mild, moderate, or severe. Liver biopsy specimens also were analyzed for the presence of fat, inflammation, and fibrosis and graded similarly. No correlation was found between fatty and fibrofatty sonographic findings with any of the three histologic patterns. Correlations were found between fibrotic sonographic findings and both fibrotic and inflammatory histologic findings (r = 0.27; P = 0.03). Although some pathologic features of liver disease were detected by ultrasonography, no useful correlation was noted between results of sonography and histologic examination.