Mehmet Alakavuklar

Dokuz Eylul University, Ismir, İzmir, Turkey

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Publications (29)63.72 Total impact

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    ABSTRACT: Pancreatic neuroendocrine tumors constitute about 2% of all gastrointestinal neoplasms. Approximately half of the pancreatic euroendocrine tumors are nonfunctional. Due to lack of specific symptoms, most patients with nonfunctional pancreatic neuroendocrine tumors present with locally advanced or metastatic disease. Second primary malignancies are seen very rarely in these patients. Colon carcinoma ranks third in frequency among primary sites of cancer in both men and women in western countries. Presence of a metachronous colon adenocarcinoma in a patient with nonfunctional pancreatic neuroendocrine tumor has not been reported before. We present a patient who had an asymptomatic mass in the head of the pancreas, detected by ultrasonography in 1996. The patient did not consent to operation. In 2002, after the diagnosis of an unresectable, nonfunctional pancreatic neuroendocrine tumor, interferon alpha- 2b and octreotide were started. A year after biological treatment, he refused further treatment. In 2004, during the evaluation of dissemination of the asymptomatic disease, positron emission tomography revealed a high uptake by the descending colon despite the failure of other imaging methods. After surgery for operable colon carcinoma, the patient received chemotherapy and biological therapy for both tumors. Since 2005, he has been doing well without any further treatment thus far. In conclusion, computerized tomography/magnetic resonance imaging and octreotide scintigraphy may be insufficient to show disseminated disease and asymptomatic second primary malignancies. Therefore, positron emission tomography is a valuable promising option for the evaluation of gastroenteropancreatic neuroendocrine tumors and concomitant or metachronous malignancies. Lifelong follow-up by a multidisciplinary oncology team is needed so that a long-term survival can be achieved with integrated multimodal systemic treatment approaches.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 09/2009; 20(3):214-9. · 0.47 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and retinoic acid receptors (RAR/RXR) belong to the nuclear steroid receptor family. In vitro studies have suggested that PPAR-gamma ligands are highly effective in preventing mammary tumours and these effects are enhanced by some retinoids. However, in vivo anti-initiator and anti-promoter efficacies of this combination are not clear. The present study aimed to investigate the chemopreventive efficacies of the PPAR-gamma ligand rosiglitazone (200 microg/kg/day), synthetic retinoid fenretinide (0.3 mg/kg/day) and their combination on a DMBA-induced rat mammary carcinogenesis model. In the rosiglitazone group, no malignant tumour developed, apart from the lowest proliferative mammary lesions. In the fenretinide group, 30% developed a malignant tumour but there were no benign tumours. Cancer incidences were 61.5% and 10% in the control and combination groups respectively. Our results showed that the PPAR-gamma ligand rosiglitazone and synthetic retinoid fenretinide have potent chemopreventive properties against in vivo mammary carcinogenesis; however, the efficacies were not enhanced by their combination.
    Clinical and Translational Oncology 05/2009; 11(4):243-9. DOI:10.1007/s12094-009-0347-5 · 1.60 Impact Factor
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    ABSTRACT: A pilot study was performed for setting up the Dokuz Eylül University Breast Tumor DNA Bank (DEUBTB) to facilitate the sharing of tumor DNA/RNA samples and related data from cases collected by collaborators specializing in the breast cancer diseases between 2004 and 2006. The pilot study aimed to provide answers for certain questions on: (1) ethical concerns (informing the volunteer for donating specimen, anonymizing the sample information, procedure on sample request), (2) obtaining and processing samples (technical issues, flowchart), (3) storing samples and their products (storing forms and conditions), (4) clinical database (which clinical data to store), (5) management organization (quality and quantity of personnel, flowchart for management relations), (6) financial issues (establishment and maintenance costs). When the bank had 64 samples, even though it is quite ready to supply samples for a research project, it revealed many questions on details that may be answered in more than one way, pointing that all biobanks need to be controlled by a higher degree of management party which develops and offers quality standards for these establishments.
    Medical Oncology 05/2008; 25(4):471-3. DOI:10.1007/s12032-008-9060-4 · 2.06 Impact Factor
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    ABSTRACT: In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.
    International Journal of Clinical Practice 07/2006; 60(6):675-82. DOI:10.1111/j.1368-5031.2006.00742.x · 2.54 Impact Factor
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    ABSTRACT: An increased incidence of thromboembolic events has been described in women receiving systemic chemotherapy for breast cancer. The effect of anthracycline-based adjuvant chemotherapy regimens on fibrinolytic system markers of plasminogen activator inhibitor-1 (PAI-1) and thrombin activitable fibrinolysis inhibitor (TAFI) was investigated in patients with operable breast cancer. Twenty-four patients with operable breast cancer (median age, 54.5 years; range, 37-72 years) enrolled in our study. Stage I-II and stage IIIA cases received EC (Epirubicin 90 mg/m(2)/d1, I.V. and cyclophosphamide 600 mg/m(2)/d1, I.V.) and FEC (5-fluorouracil 500 mg/m(2)/d1, I.V., epirubicin 100 mg/m(2)/d1, I.V., and cyclophosphamide 500 mg/m(2)/d1, I.V.) as an adjuvant chemotherapy regimen, respectively. Each group consisted of 12 patients. Blood samples were obtained at baseline and just before the third cycle of EC and fourth cycle of FEC chemotherapy regimens. Plasma TAFI antigen and PAI-1 levels did not disclose any statistical difference between basal and postchemotherapy levels within each group and between two groups. Although postchemotherapy D-dimer levels were statistically higher in the FEC group than in the EC group, results in both groups were within normal ranges. More studies concerning the role of fibrinolytic system in breast cancer patients receiving chemotherapy, probably including cases with advanced stage and with different chemotherapy regimens and dose intensities, are needed.
    Clinical and Applied Thrombosis/Hemostasis 02/2006; 12(1):9-14. DOI:10.1177/107602960601200103 · 1.58 Impact Factor
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    ABSTRACT: 7,12-Dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), has been used extensively as a tool to initiate mammary carcinogenesis and subsequent chemoprevention. On the other hand, selenium (Se) is potentially useful in oncology because this element possesses anticarcinogenic and chemopreventive properties. Se-containing enzymes such as glutathione peroxidase (GPx) play an important role in PAH metabolism and detoxification. In this study, rats were administered a single, oral dose of DMBA (12 mg). In the Se group, rats received 20 microg Se daily via gavage, starting 2 wk before the DMBA administration and continued for 1 wk. One hundred twenty days after DMBA administration the rats were sacrificed and toxicity was evaluated using histopathological and biochemical criteria. Five rats (30%) died in the DMBA group within the study period, whereas no death occurred in the DMBA-Se-treated group. Malignant tumor frequency was 33% in the DMBA group, while no malignant tumors occurred in the DMBA-Se-treated group. Some inflammatory changes rather than epithelial changes were found upon histopathological examination. GPx activity and blood urea nitrogen levels were higher and kidney GST activity was lower in the DMBA-Se-treated group compared to DMBA alone. In conclusion, Se appears to be effective in preventing some of the adverse effects associated with DMBA.
    Journal of Toxicology and Environmental Health Part A 06/2005; 68(9):693-701. DOI:10.1080/15287390590925438 · 1.83 Impact Factor
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    ABSTRACT: The pathogenetic mechanisms that regulate the aggressive behavior of pancreatic cancer still remain to be clarified. Alterations in the apoptotic pathway and proliferative activity of tumor cells as well as mechanisms contributing to the intrinsic drug resistance of pancreatic tumors have been investigated. Survivin is a recently described antiapoptotic protein, which, when overexpressed, is associated with worse prognosis in a majority of tumors. P-glycoprotein, a product of multidrug resistance gene-1 (MDR-1) was reported to be expressed in drug-resistant tumors. The purpose of this study was to investigate whether apoptosis, its regulation by survivin, tumor cell proliferation, and P-glycoprotein expression have a significant role on the biologic behavior of pancreatic adenocarcinoma. Tumors of 45 patients with pancreatic adenocarcinoma were studied for the detection of survivin, P-glycoprotein, and Ki-67 expression by immunohistochemical method and apoptotic index by TUNEL method. Immunohistochemical staining was scored and Ki-67 and apoptotic indices were expressed as percentage of stained cells. Immunohistochemistry for survivin and P-glycoprotein revealed positive staining in 7 (15.4%) and 36 (79.5%) of the 45 tumors, respectively. The mean Ki-67 proliferative index was 43.75 +/- 25.30%. The mean apoptotic index evaluated with the TUNEL method was 37.12 +/- 34.55% for the whole group. We found no significant association between apoptotic index, expressions of survivin and P-glycoprotein, and clinicopathologic variables and survival. Apoptotic activity, survivin, and P-glycoprotein expression failed to predict the disease extent and biologic behavior in pancreatic adenocarcinoma in our cases.
    Pancreas 06/2005; 30(4):343-8. · 3.01 Impact Factor
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    ABSTRACT: A 62-year-old woman being treated for stage IIIC rectal adenocarcinoma was diagnosed with primary non-Hodgkin lymphoma of the breast after a 4-year follow-up. This case illustrates the importance of close and long-term follow-up as well as of differential diagnostic procedures for second primary malignancies after the initial diagnosis and treatment of a solid tumor.
    The Breast 05/2005; 14(2):169-74. DOI:10.1016/j.breast.2004.08.013 · 2.58 Impact Factor
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    ABSTRACT: Objectives: The pathogenetic mechanisms that regulate the aggressive behavior of pancreatic cancer still remain to be clarified. Alterations in the apoptotic pathway and proliferative activity of tumor cells as well as mechanisms contributing to the intrinsic drug resistance of pancreatic tumors have been investigated. Survivin is a recently described antiapoptotic protein, which, when overexpressed, is associated with worse prognosis in a majority of tumors. P-glycoprotein, a product of multidrug resistance gene-1 (MDR-1) was reported to be expressed in drug-resistant tumors. The purpose of this study was to investigate whether apoptosis, its regulation by survivin, tumor cell proliferation, and P-glycoprotein expression have a significant role on the biologic behavior of pancreatic adenocarcinoma. Methods: Tumors of 45 patients with pancreatic adenocarcinoma were studied for the detection of survivin, P-glycoprotein, and Ki-67 expression by immunohistochemical method and apoptotic index by TUNEL method. Immunohistochemical staining was scored and Ki-67 and apoptotic indices were expressed as percentage of stained cells. Results: Immunohistochemistry for survivin and P-glycoprotein revealed positive staining in 7 (15.4%) and 36 (79.5%) of the 45 tumors, respectively. The mean Ki-67 proliferative index was 43.75 ± 25.30%. The mean apoptotic index evaluated with the TUNEL method was 37.12 ± 34.55% for the whole group. We found no significant association between apoptotic index, expressions of survivin and P-glycoprotein, and clinicopathologic variables and survival. Conclusions: Apoptotic activity, survivin, and P-glycoprotein expression failed to predict the disease extent and biologic behavior in pancreatic adenocarcinoma in our cases.
    Pancreas 04/2005; 30(4):343-348. DOI:10.1097/01.mpa.0000160285.87322.3e · 3.01 Impact Factor
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    ABSTRACT: 5-Fluorouracil (5-FU) and gemcitabine are the major active drugs in the treatment of pancreatic cancer. Twenty-two patients with advanced pancreas cancer were treated with a new chemotherapy regimen consisting of infusional 5-FU and high-dose leucovorin with gemcitabine (GEMFUFOL). A total of 200 cycles of chemotherapy were administered. The response rate was 27.3%, all responses being partial. The median survival time and 1-year survival rate were, respectively, 13 months and 60.4%. The toxicity was very low and severe hematological toxicity was exceptional. The GEMFUFOL regimen can be an active regimen for the treatment of advanced pancreatic cancer and has a low toxicity.
    Chemotherapy 07/2004; 50(3):127-32. DOI:10.1159/000077886 · 1.55 Impact Factor
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    ABSTRACT: The hyperimmunoglobulin E (HIE) (Job's) syndrome often has it onset in childhood and is characterized by markedly elevated serum IgE levels, chronic dermatitis and recurrent pyogenic infections. Lymphoid malignancies have most commonly been associated with this syndrome while the first case in the literature of carcinoma associated with HIE syndrome was a squamous cell carcinoma of the vulva, described by Clark et al. in 1998. We observed a male patient with Job's syndrome diagnosed at age three who presented with bone pain and a metastatic epithelial tumor of the bone revealed by biopsy. Diagnostic procedures aimed at detecting the primary site showed multiple mediastinal lymph nodes with lung and liver metastases on computed tomography scans and an extradural spinal metastasis at the upper thoracic level on magnetic resonance imaging. Although the patient refused a bronchoscopic procedure, a diagnosis of pulmonary adenocarcinoma was established on the basis of sputum cytology and the clinical aspects of tumor extent. Intravenous corticosteroids and palliative radiotherapy were given for the spinal metastasis. Palliative chemotherapy could not be started because of the patient's poor performance status as well as nosocomial fungal pneumonia and pseudomonal urogenital infection with bacteremia. Despite the antifungal and broad-spectrum antimicrobial treatments, the patient died of pseudomonal sepsis.
    Tumori 01/2004; 90(1):132-5. · 1.09 Impact Factor
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    ABSTRACT: Malignant neoplasms are rarely associated with glomerular changes. The glomerular lesion seen most often in patients with malignancies is membranous glomerulonephritis. We report here a case of gastric cancer associated with rapidly progressive glomerulonephritis (RPGN). A 57-year-old man was admitted to our hospital with acute renal failure. Renal biopsy was performed, and the diagnosis was RPGN. Steroid treatment was instituted, but was complicated by hematemesis, and an early-stage gastric cancer was found after endoscopic examinations. Gastric biopsy revealed gastric adenocarcinoma. The patient's renal function improved with corticosteroid treatment and hemodialysis, and total gastrectomy was performed. The improvement in renal function persisted after the removal of the gastric cancer, and the RPGN and cancer have been in remission for 3 years.
    Gastric Cancer 02/2003; 6(4):267-9. DOI:10.1007/s10120-003-0259-y · 4.83 Impact Factor
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    ABSTRACT: Early determination that breast cancer is bilateral and multifocal can change therapy strategy and, subsequently, mortality and morbidity rates. The authors present a case with bilateral, multifocal breast cancer detected only by Tc-99m sestamibi imaging. Early and delayed Tc-99m sestamibi imaging and dynamic MRI were performed in a patient with a right-sided lesion shown on mammography. Although early Tc-99m sestamibi imaging detected bilateral breast cancer foci, both dynamic MRI and mammography missed the lesion in the left breast. Additional lesions seen on delayed Tc-99m sestamibi images of the left breast, which were initially thought to be benign, completely disappeared after concomitant chemotherapy and radiotherapy, suggesting multifocal malignant lesions in the left breast. This case suggests that Tc-99m sestamibi may be useful for detecting bilateral cancer, and delayed imaging may give additional information regarding the possible multifocal nature of the disease.
    Clinical Nuclear Medicine 09/1999; 24(8):590-3. DOI:10.1097/00003072-199908000-00009 · 2.86 Impact Factor
  • L Undar, N Akkoç, M N Alakavuklar, C Cehreli
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    ABSTRACT: The hemostatic activity of blood shows a circadian variation with a higher frequency of acute coronary events in the morning. The thrombotic tendency of blood is influenced by many factors, including platelets. Diurnal changes of in vivo platelet activation were investigated by whole blood flow cytometry in 10 young healthy male volunteers using anti-GMP-140 (anti-alpha-granule membrane protein 140 kD) monoclonal antibody at 3h intervals from 06:00 to 24:00. We also studied circulating platelet aggregates to investigate whether there exists a similarity between the results of these methods. Results of flow cytometric analysis indicate that there is an increase in platelet activation during the period from 06:00 to 09:00. Platelet activation then decreases gradually during the period from noon to midnight. These changes are accompanied by a similar trend in circulating platelet aggregates. This suggests that GMP-140 expression on platelets is synchronized with or followed by platelet aggregate formation in vivo, and increased platelet activation may predispose individuals to thrombosis at this time.
    Chronobiology International 06/1999; 16(3):335-42. · 2.88 Impact Factor
  • Clinical Nuclear Medicine 10/1998; 23(9):637-8. DOI:10.1097/00003072-199809000-00026 · 2.86 Impact Factor
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    ABSTRACT: Pamidronate is an effective drug used not only in patients with tumor-associated hypercalcemia, but also in normocalcemic patients with metastatic bone disease to relieve pains. We describe a 39-year-old normocalcemic patient with subclinical hypoparathyroidism and bone metastasis due to breast carcinoma. Following parenteral administration of 60 mg pamidronate, the corrected serum level of calcium decreased from 2.12 mmol/l (=8.9 mg/dl) to 1.42 mmol/l (5.7 mg/dl), accompanied with carpal pedal spasm. The present case indicates that the hypocalcemia due to latent hypoparathyroidism was compensated by extensive osteolysis due to bone metastasis, and that overt hypocalcemia may develop after intravenous administration of pamidronate in such a patient.
    Internal Medicine 05/1998; 37(4):396-7. DOI:10.2169/internalmedicine.37.396 · 0.97 Impact Factor
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    ABSTRACT: CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. It exists as standard (CD44s) and variant (CD44v) isoforms which have been shown to be associated with metastasis in a range of tumors. Both CD44s and CD44v are found in normal respiratory epithelium and in non small cell lung cancers (NSCLCs). However, there isn't much information regarding their role in the metastatic process of NSCLCs. We examined the expression of CD44s in 30 NSCLCs using immunohistochemical techniques. Ten were non-metastatic (N0, M0), 5 were metastases to lymph nodes (N1, M0) and 15 were excised brain metastases. We found CD44s positivity in all non-metastatic tumors with varying degrees of expression, whereas 10 out of 15 metastatic tumors in brain and 3 out of 5 lymph node metastases were negative for CD44s. There was a statistically significant inverse relation between the CD44s expression and metastatic potential (P < 0.05). Our results support the hypothesis that diminished or lack of CD44s is the functional equivalent of CD44v which may be an accompaniment of enhanced metastatic potential. The value of CD44 in predicting metastatic behavior of NSCLCs remains to be established in a larger series.
    Cancer Letters 11/1997; 119(1):27-30. DOI:10.1016/S0304-3835(97)00254-1 · 5.02 Impact Factor
  • Leukemia Research 04/1997; 21(1). DOI:10.1016/S0145-2126(97)81251-9 · 2.69 Impact Factor
  • Leukemia Research 04/1997; 21(1). DOI:10.1016/S0145-2126(97)81254-4 · 2.69 Impact Factor
  • European Journal of Cancer 11/1995; 31. DOI:10.1016/0959-8049(95)95442-9 · 4.82 Impact Factor