[Show abstract][Hide abstract] ABSTRACT: The central nervous system (CNS) is an important area of involvement for both high-grade, aggressive primary and secondary lymphomas. Although follicular lymphoma represents a low-grade histology, it may rarely present with CNS involvement. Here, we describe a patient diagnosed with follicular lymphoma who was presented with cerebellar involvement.
Cancer Research and Treatment 09/2013; 45(3):234-8. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Osteosarcoma (OS) is the primary malignant tumor of bone, with an incidence rate of 19% among all cancer types. The vast majority of patients have pulmonary metastases at diagnosis, and about half develop lung disease later, which leads to poor prognosis and increased death rate. It is therefore essential to investigate molecular markers responsible for pulmonary metastasis of osteosarcoma.In this research, a genome wide association study (GWAS) using formalin fixed paraffin embedded (FFPE) samples from lung tissue of 9 patients with pulmonary metastatic OS was performed.
Among 358 associated SNPs, rs6499861, rs10884554 and rs12154602 were found to be associated with metastatic OS most significantly. Moreover, second wave analysis of GWAS results provided the significant genes and pathways associated with metastatic OS, including genes related to metabolic and skeletal development pathways. The present study also demonstrates a feasible approach in using archival FFPE samples for GWAS.
7th International Symposium on Health Informatics and Bioinformatics 2012; 04/2012
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Formalin fixed paraffin embedded (FFPE) tissues are the most available material for routine diagnostics in pathology laboratories worldwide. They can be used for both microscopic examinations and molecular diagnostic assays after microscopy. Molecular assays, such as PCR and high throughput microarrays, have the potential to be used as routine diagnostic and prognostic tests. Those assays require high quality DNA. However, DNA extracted from FFPE material is problematic due to chemical modifications caused by formalin and continued degradation over time.In this research, FFPE samples from lung tissue of 10 patients with pulmonary metastatic osteosarcoma was used in order to provide a microarray data analysis workflow for application of FFPE-derived DNA samples in reliable copy number and loss of heterozygosity (LOH) predictions.
The present study demonstrates a feasible approach to use archival FFPE samples for the assessment of copy number aberration and LOH.
7th International Symposium on Health Informatics and Bioinformatics 2012; 04/2012
[Show abstract][Hide abstract] ABSTRACT: Selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 (Y-90) microspheres is also known as radioembolization and delivers high doses of radiation to hepatic tumors with minimum healthy liver exposure. The aim of this study was to present our preliminary experience in the role of liver directed radiotherapy with Y-90 microspheres for the treatment of unresectable hepatic metastases from neuroendocrine tumors (NET).
The results of SIRT in 10 patients (5 males, 5 females; mean age 48.7 years; age range 24-73 years) with metastatic liver disease from NETs during the period from April 2008 through August 2010 were reviewed. All patients had meticulous pre- and post-imaging studies as a part of their work-up procedure, as well as serologic tests of liver function to determine the extent of liver function damage. The patients who were eligible for SIRT had pretreatment visceral angiography to define and occlude non-target arteries.
The mean +/- SD administered SIR-Spheres activity was 1.49 +/- 0.42 GBq (range 0.72-2.21 GBq) in all the patients. These treatments delivered a dose of 99.73 +/- 66.36 Gy (range 49-420.8 Gy) to the target tumors. The estimated dose to the lungs and normal liver was 4.45 +/- 1.95 Gy (range 2.4-8.5 Gy) and 26.73 +/- 14.19 Gy (range 5-58.9 Gy), respectively. Overall response rate of 90% and patient tolerance was satisfactory for most patients.
From our limited experience, we can conclude that SIRT with Y-90 microspheres is a safe and efficacious treatment option for patients with liver metastasis of NET without any serious side effects.
[Show abstract][Hide abstract] ABSTRACT: Multidrug resistance is resistance to structurally unrelated anticancer agents. Large-scale expression analysis by using high-density oligonucleotide microarrays may provide information about new candidate genes contributing to MDR. This study demonstrates alterations in expression levels of several genes related to epithelial-mesenchymal transition (EMT) in paclitaxel, docetaxel, and doxorubicin resistant MCF-7 cells.
Resistant sublines were developed from sensitive cells by selective paclitaxel, docetaxel, and doxorubicin applications in dose increments. cDNA microarray analysis was performed for sensitive and resistant cells. Genes having statistically significantly altered expression levels more than two-folds compared to the sensitive MCF-7 cells were considered. Genes encoding the determinants of the EMT were evaluated. Immunostaining was performed for relevant protein expressions.
Key elements of EMT were transcriptionally activated in paclitaxel, docetaxel and doxorubicin resistant sublines. One of the upregulated genes was Slug, a transcription factor of E-cadherin, occludin repression, and N-cadherin, vimentin activation. Decreased estrogen receptor-α (ER) levels in cells might have stimulated Slug expression. Increased expression levels of TGF-beta receptor2 (TGFBR2) together with SMAD3 might have stimulated EMT in resistant cells. Immunocytochemistry results confirmed loss of ER and E-cadherin, together with high vimentin levels.
EMT was induced in multidrug resistant MCF-7 cells indicating a relationship of this process and drug resistance. However, the relationship of each specific component of EMT with drug resistance requires further analysis.
[Show abstract][Hide abstract] ABSTRACT: Primary (AL type) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in some organs such as the kidneys, heart and bowel. Primary amyloidosis and multiple myeloma both involve clonal plasma cell proliferation. Distinctive haematological and biochemical laboratory findings may help in early diagnosis. Here we present a 60-year-old man with an exceptional clinical course of an Ig A type multiple myeloma with generalized amyloidosis, causing nephrotic syndrome, complete intestinal colitis and malabsorbtion. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL type amyloidosis. This may facilitate earlier diagnosis and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis.
[Show abstract][Hide abstract] ABSTRACT: Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N-(3-(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague-Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as serum levels of creatine phosphokinase (CK-MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH-Px activities were significantly reduced in rats with DOX- or DOX+TRAST-induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK-MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX- and DOX+TRAST-treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.
Journal of Pineal Research 11/2010; 50(1):89-96. · 7.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A yolk sac tumor is a rare malignant tumor of germ cell origin. It most commonly arises from the testes and ovaries in young adults, but extragonadal sites of origin are reported in 10% to 15% of the cases. Yolk sac tumors are malignant, tend to recur locally, and may present with widespread metastases at the time of diagnosis. Involvement of the head and neck is uncommon. In this study, we present the case of a 23-year-old man presenting with mandibular and adjacent gingival metastasis of a mediasatinal yolk sac tumor. Thus, the patient has already undergone chemotherapy; no additional treatment was provided. In this case report, clinical and histopathologic features of the oral metastases of a yolk sac tumor were briefly discussed.
The Journal of craniofacial surgery 11/2010; 21(6):1828-30. · 0.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PurposeSince multidrug resistance is a multifactorial phenomenon, a large-scale expression analysis of drug-resistant cells by using
high-density oligonucleotide microarrays may provide information about new candidate genes contributing to resistance. Extracellular
matrix (ECM) is responsible for many aspects of proliferation and invasive/metastatic behavior of tumor cells. This study
demonstrates alterations in gene expression levels of several ECM components, matrix metalloproteinases (MMPs), adamalysins
(ADAMs and ADAMTSs) and tissue inhibitors of metalloproteinases (TIMPs) in paclitaxel, docetaxel, vincristine and doxorubicin-resistant
MethodsResistant MCF-7 cells were developed by stepwise selection of cells in increasing concentrations of drugs. Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array was used for hybridizations. Statistical significance was determined by independent sample
t test. The genes having altered expression levels in drug-resistant sublines were selected and filtered by volcano plots.
ResultsGenes up/downregulated more than twofolds were selected and listed. Expression of 25 genes encoding ECM proteins (including
collagen, finronectin and syndecan) and integrin receptor subunits were found to be upregulated in drug-resistant cells. In
addition, expression levels of, 13 genes encoding MMPs, ADAMs, ADAMTSs and TIMPs (including MMP1, MMP9, ADAM9 and TIMP3) were
found to be altered in drug-resistant sublines when compared with sensitive MCF-7.
ConclusionsBased on the expression analysis profiles, this report provides a preliminary insight into the relationship between drug resistance
and ECM components, which are related to invasion and metastasis. Correlation of each specific ECM component with drug resistance
requires further analysis.
Cancer Chemotherapy and Pharmacology 02/2010; 65(3):447-455. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to investigate the efficacy of and establish a toxicity profile for a modified regimen of dexamethasone, cytarabine and cisplatin (DHAP) for lymphoma outpatients.
Fifty-one lymphoma patients, 26 with Hodgkin's disease and 25 with non-Hodgkin's lymphoma, were included. The patients' median age was 32 years (range: 17-61). Twenty had progressive/refractory disease and 31 relapsed disease. Twenty-five were in clinical stage I/II and 26 in clinical stage III/IV before the initiation of salvage chemotherapy. DHAP consisted of dexamethasone (40 mg i.v. on days 1-4), cytarabine (2 g/m(2) i.v. as 3-hour infusion on days 2 in the evening and 3 in the morning) and cisplatin (35 mg/m(2) as 2-hour infusion on days 1-3) were administered every 21 days. A total of 154 cycles of modified DHAP were administered, with a median of 3 cycles per patient (range: 2-4).
The main toxicity was myelosuppression. WHO grade III-IV neutropenia and grade III-IV thrombocytopenia were observed in 27 (52.9%) and 21 (41%) patients, respectively. The overall response rate (85% for Hodgkin's disease and 95% for non-Hodgkin's lymphoma) was 88.3% (39.2% complete response and 49.1% partial response).
The results showed that this outpatient schedule of DHAP was well tolerated and an effective salvage regimen.
Medical Principles and Practice 01/2010; 19(5):344-7. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid hematological engraftment at autologous peripheral stem cell transplantation (APSCT) is a significant factor in reduction of early transplant-related complications and costs. For this reason, it is important to determine influences on hematological recovery.
This study was designed to evaluate factors affecting leukocyte and platelet engraftment times after high dose chemotherapy following APSCT. A total of 228 patients (131 males and 97 females) were enrolled.
There were statistically significant differences between patients with CD34+ cell doses ≥ 2.5 x 10⁶/kg (n=180) and < 2.5 x 10⁶/kg (n=48), regarding leukocyte engraftment at 11 and 12 days, respectively (p<0.02), between G-CSF (n=167) and GM-CSF (n=61) posttransplant regarding median leukocyte engraftment times (p=0.005), and between with (n=75) or without (n=153) history of pretransplant radiotherapy for both leukocyte and platelet engraftment times (p<0.001).
For leukocyte engraftment, a history of pretransplant radiotherapy, type of growth factor used and number of CD34+ cells infused, and for platelet engraftment, a history of pretransplant radiotherapy were found to be independent variables on multivariate analysis with the Cox regression method.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(3):697-702. · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the potential relationship of microvascular growth patterns with survival in invasive breast carcinomas. Thirty-one invasive ductal carcinoma cases, followed up at least for 38 months, constituted our series. All cases had been studied for ER/PR and HER2/neu expression. Clinicopathological and survival data were obtained from the archives. Tissue sections from all cases were stained with CD34 antibody to highlight the microvascular network and to measure microvessel density (MVD). The cases were then classified according to the dominance of one of the five recognizable microvascular patterns. Cox proportional hazard regression model, Fisher's exact test, and multivariate general linear model (GLM) were used to uncover the effects of the variables, such as nodal status, distant metastasis, angiogenic patterns, and MVD, on survival. There was an association between only one of the microvascular patterns and aggressive clinical course. Increased blood-filled capillaries with some clustering in the tumor might be a predictor of aggressive biological behavior in invasive breast carcinomas. Similar studies investigating larger series are needed before a generalized conclusion can be made.
Pathology - Research and Practice 11/2009; 206(2):93-7. · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34(+) selection and high-dose chemotherapy in patients with Stage III breast cancer. Fifty-five patients were enrolled in this prospective cohort study. Whereas CD34(+) positive selection was not carried out in the first group (unselected group, n:31), CD34(+) positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high-dose chemotherapy. CD34(+) selection does not change survivals, but it may decrease the distant metastases.
Journal of Clinical Apheresis 10/2009; 24(5):197-204. · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 29-year-old woman with left pleural effusion and a mass in anterior mediastinum was admitted. Transthoracic needle aspiration from the mass revealed findings consistent with nodular sclerosis variety of Hodgkin's disease. The patient was in remission after six cycles of ABVD followed by mediastinal radiotherapy. Ten months later CT scan showed three hypodense masses in the right kidney. Ultrasound guided renal biopsy revealed diffuse large B cell lymphoma. Retrospective re-evaluation of the archival specimens of the mediastinal mass was also consistent with diffuse large B cell lymphoma. After induction chemotherapy (four cycles of DHAP) she underwent high dose chemotherapy (BEAM) and autologous peripheral blood stem cell transplantation. She is still in remission for 7 years after transplantation. In conclusion, renal involvement during advanced lymphoma is quite common but isolated renal relapse in NHL is a rare situation. Although renal infiltration generally shows a poor prognosis, long-term survival may be achieved with high dose chemotherapy and autologous peripheral blood stem cell transplantation.
Medical Oncology 06/2009; 27(2):434-8. · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report an unusual paraneoplastic syndrome, amyotrophic lateral sclerosis, associated with renal cell carcinoma.
A 59-year-old man presented with muscle weakness and fasciculations in the upper extremities. Neurological examination showed that the fasciculations arose spontaneously in the upper limbs. Electrodiagnostic studies revealed an active neurogenic disorder. The patient was diagnosed with a motor neuron disease mimicking amyotrophic lateral sclerosis. Urine analysis revealed microscopic hematuria. Abdominal computerized tomography scans showed a 9.5 x 8 cm renal mass in the lower pole of the right kidney. Curative right radical nephrectomy was performed. Pathologic examination showed a clear cell adenocarcinoma. After nephrectomy, the muscle weakness and fasciculations disappeared spontaneously within 2 months. The patient was disease-free for 58 months after right radical nephrectomy. He complained of muscle weakness and fasciculation at the last follow-up again. Physical examination revealed fasciculation in the upper limbs. Abdominal tomography showed a 22 x 20 mm solid mass in the lower pole of the left kidney. Kidney-saving surgery was performed and the diagnosis of renal cell carcinoma was confirmed pathologically. Following surgery, fasciculations completely disappeared and muscle weakness diminished within 3 months.
This case highlights motor neuron disease as a rare paraneoplastic syndrome in association with renal cell carcinoma and resolution after removal of the tumor.
Medical Principles and Practice 02/2009; 18(1):73-5. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was done to evaluate the frequency and severity of mucositis in the early period of stem cell transplantation (SCT) and the relation of conditioning regimens with mucositis.
Patients with hematologic or solid tumors who underwent conditioning regimen were asked to score mucositis severity daily from the first day to the tenth day of reinfusion. Patient-reported scoring was performed according to a five-grade scale (0: no symptom; 1: mild; 2: moderate; 3: severe; 4: very severe). Total mucositis score (TMS) was defined as the addition of daily mucositis scores for 10 days. A total of 68 SCT (58 autologous and 10 allogeneic) patients, 48 men (71%) and 20 women (29%) were included to the study. Median age of patients was 32.5 (range 15-78) years. The most frequent three diagnosis were non-Hodgkin's lymphoma (37%, n = 25), Hodgkin's lymphoma (12%, n = 8), and multiple myeloma (12%, n = 8). BEAM (n = 27), ICE (n = 17), melphelan 200 mg/m(2) (M200)(n = 8), and TBI+C (total body irradiation + cyclophosphamide) (n = 16) were used as conditioning regimens.
All of the patients experienced mucositis at any grade. TMS in the sixth day was higher than TMS in the first day (p < 0.05). TMS was not related to the diagnosis or gender (p > 0.05). TMS at ICE regimen in the first 5 days after transplantation was more severe than BEAM regimen. TMS at TBI+C regimen was higher than TMS at BEAM regimen from day 4 to day 10 (p < 0.05). The mean percentages of patients who scored severe or very severe mucositis in 10 days was 7.4% in BEAM, 8.9% in ICE, 12.5% in M200, and 31.2% in TBI+C groups.
Patients experience mucositis frequently following conditioning regimen and SCT. The necessity and the timing of prophylaxis for mucositis change due to the type of conditioning regimens.
Supportive Care in Cancer 02/2009; 17(10):1295-9. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The outcome of Ewing's sarcoma depends on the anatomical site of the tumor. Studies conducted in high-risk patients are limited. We evaluated the outcome of high-risk Ewing's sarcoma patients that received long-term treatment protocol. Twenty-five patients (22 males, 3 females) with poor prognostic features were treated according to long-term Ewing's sarcoma protocol. Central-axis localization, inadequacy or unavailability of surgical resection, older than 15 years of age, are accepted as high-risk factors. The median age of patients was 23 years (range, 18-55). The tumor localization was pelvis (9), femur (1), tibia (1), fibula (1), maxilla (1), clavicle (1), vertebrae (5), metatarse (1), and ribs (5). Neoadjuvant chemotherapy was applied between weeks 0 and 6, local therapy on week 9, and adjuvant maintenance chemotherapy between weeks 11 and 41. All patients received neoadjuvant and adjuvant maintenance chemotherapy. Local therapy consisted of radiotherapy (32%), surgery alone (12%), or surgery and radiotherapy (56%). The median total treatment period was 10 months. The median follow-up was 25 months (range, 7-89). Three-year cumulative OS and DFS rates were 43% (95% CI, 28.5-57.85) and 40% (95% CI 23.63-52.19), respectively. The most common grade III/IV toxicities observed during the treatment protocol were neutropenia (16%) and gastrointestinal toxicities (16%). Our study indicated that long-term multiagent combination chemotherapy may result in better outcome in adult high-risk patients undergoing adequate surgical resection of the tumor and local radiotherapy. Further randomized studies are needed to assess the efficacy of this treatment protocol in patients with adequate surgical margins.
Medical Oncology 12/2008; 26(3):276-86. · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.
CardioVascular and Interventional Radiology 11/2008; 32(2):361-4. · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hematopoetic stem cell transplantation, even from an HLA 6/6 identical family member is associated with an increased frequency of complication in fanconi anemia (FA). The increased susceptibility for chromosomal breaks has been suggested as a contributory factor for increased risk of toxicity, graft versus host disease (GVHD) and increased incidence of post-transplant solid tumors. Therefore, non-irradiation based preparative regimens usually containing fludarabine and T-cell depletion of HLA geno-identical bone marrow cells have increasingly been used in patients with FA. Here, we report three children with FA who underwent CD-34 selected HSCT from HLA-identical family donors with reduced intensity fludarabine-based regimen.
Pediatric Blood & Cancer 06/2008; 50(5):1065-7. · 2.35 Impact Factor