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OBJECTIVE: Osteopontin (OPN), a phosphorylated sialoprotein, has been shown to overexpress in a variety of cancers and to contribute tumor progression and metastasis by increasing cell migration and adhesion. In the current study, we aimed to investigate the prognostic and predictive role of OPN in patients with advanced gastric cancer. METHODS: A total of 42 consecutive chemonaive patients with advanced gastric cancer and 29 healthy controls were included. The patients were treated with a modified DCF regimen. The blood samples were obtained before each chemotherapy cycle from the patients and once from the healthy controls. The plasma OPN is measured by ELISA. RESULTS: The overall response and disease stabilization rates were 25% and 72%, respectively. The median serum OPN level of the patient group was significantly higher compared to healthy controls (176.9 ng/ml (range: 41.5 -521.4) vs 64.3 ng/ml (range 42.1-105.3 ng/ml), p<0.0001). The median overall survival time was 7.0 ± 1.1 (95% CI: 4.9-9.2) months and 1-year overall survival rate was 20.8%. The patients who responded to mDCF had lower plasma OPN levels than the non-responding ones (110.7±29.3 ng/mL, 211.9±24.4 ng/mL respectively, p=0.002). The performance status and the plasma OPN levels were found to be significant factors for overall survival in the multivariate analysis (p=0.004 and 0.016, respectively). CONCLUSION: The serum OPN seems to be a novel significant prognostic and predictive factor in patients with advanced gastric cancer who were treated with DCF regimen.
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Osteopontina , Neoplasias Gástricas , Biomarcadores de Tumor/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Osteopontina/metabolismo , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
The combination of cytotoxic treatment modalities, including oncolytic viral gene therapies and immunotherapy, usually yields a synergistic effect. In the current study, a bicistronic adenoviral vector, Ad-CD-GMCSF, carrying the cytosine deaminase (CD) and granulocyte-macrophage colony-stimulating factor (GM-CSF) transcription units driven by a cytomegalovirus promoter was constructed, and the in vitro efficacy of the vector was tested in tumor cell lines and a syngeneic mouse model of colon cancer. The tumor cells infected with Ad-CD-GMCSF vector were found to produce a substantial amount of GM-CSF in tumor cell lines. Accordingly, the vector carrying CD and GM-CSF transcription units together induced a potent antitumor immunity with a significantly increased number of tumor-specific T cells and tumor-specific T-cell cytotoxicity (p < 0.001). The tumor growth rate of Ad-CD-GMCSF-treated mice was significantly lower when compared to the control and an adenoviral vector carrying only the CD transcription unit (Ad-CD; p < 0.05). Likewise, the median overall survival of the Ad-CD-GMCSF vector group was significantly higher than that of the control and Ad-CD groups (34.0 ± 12.8 vs. 14.0 ± 0.5 and 23.0 ± 2.8 days, respectively; p < 0.001). In conclusion, along with its cytotoxic effect, the high immunostimulatory effect of the bicistronic Ad-CD-GMCSF vector has excellent potential in the treatment of cancers.
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Adenoviridae/genética , Citosina Desaminasa/genética , Terapia Genética , Vectores Genéticos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Neoplasias/genética , Neoplasias/terapia , Transgenes , Animales , Citocinas/metabolismo , Citosina Desaminasa/metabolismo , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Expresión Génica , Orden Génico , Terapia Genética/métodos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Inmunomodulación , Ratones , Neoplasias/inmunología , Neoplasias/patología , Resultado del Tratamiento , Microambiente Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: In the present study, we investigated the prognostic and predictive role of neuroendocrine differentiation (NED) and tumor-associated macrophage (TAM) infiltration in tumor tissue from patients with advanced colorectal cancer who had received bevacizumab plus chemotherapy. PATIENTS AND METHODS: A total of 123 consecutive patients with advanced colorectal cancer who had received bevacizumab plus irinotecan/oxaliplatin-based combination chemotherapy were included in the present study. In addition to the clinicopathologic parameters, the presence of NED and the level of TAM infiltration were studied as covariates for survival analysis. RESULTS: The median patient age was 57 years (range, 30-76 years). The chemotherapy backbone was FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) for 75% of the patients. Univariate analysis showed that only NED and TAM infiltration were significant predictive factors for progression-free survival. Left-sided tumors and low TAM infiltration were favorable factors for overall survival on univariate analysis. However, the TAM level was the only independent prognostic factor for overall survival (hazard ratio, 0.301; 95% confidence interval, 0.102-0.892). CONCLUSION: Our results suggest that increased TAM infiltration in tumor tissue and NED could decrease the efficacy of bevacizumab plus combination chemotherapy in patients with advanced colorectal cancer. TAM infiltration in the tumor tissue could be used as a biomarker in patients with advanced colorectal cancer receiving bevacizumab plus chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Bevacizumab/farmacología , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Macrófagos/inmunología , Células Neuroendocrinas/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Camptotecina/farmacología , Camptotecina/uso terapéutico , Diferenciación Celular , Colon/citología , Colon/inmunología , Colon/patología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/inmunología , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Leucovorina/farmacología , Leucovorina/uso terapéutico , Persona de Mediana Edad , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Pronóstico , Supervivencia sin Progresión , Estudios Prospectivos , Recto/citología , Recto/inmunología , Recto/patologíaRESUMEN
AIM: There are inconsistent results about the effects of vitamin D level on breast cancer prognosis. We aimed to investigate the effect of vitamin D levels on the prognosis of resectable breast cancer in a patient group with highly different clothing styles. PATIENTS & METHODS: A total of 186 breast cancer patients were enrolled in the study. RESULTS: Vitamin D level was sufficient, insufficient and deficient in 17.2, 52.2 and 30.6% of patients, respectively. There was a significant relationship between clothing style and serum 25 (OH) D levels. We could not establish any relation between vitamin D level and tumor characteristics or survival. CONCLUSION: Vitamin D supplementation can be more important than diagnostic serum vitamin D level on prognosis of breast cancer.
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Neoplasias de la Mama/sangre , Recurrencia Local de Neoplasia/epidemiología , Vitamina D/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Mama/patología , Mama/cirugía , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Mastectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Pronóstico , Reproducibilidad de los Resultados , Resultado del Tratamiento , Turquía , Vitamina D/uso terapéutico , Adulto JovenRESUMEN
BACKGROUNDS: The serum leptin level (SLL) has been shown to increase in patients with nonsmall cell lung cancer (NSCLC). However, available data regarding the relation between SLL and tumor subtypes, survival, cachexia, and tumor respectability in NSCLC are still under debate. The aim of this study is to evaluate SLL in NSCLC patients with and without cachexia. MATERIALS AND METHODS: A total of 71 patients with early stage NSCLC were enrolled in this prospective study. SLL was measured by enzyme-linked immunosorbent assay. The relationship between SLL and clinicopathological factors including histopathological subtypes, weight loss, overall survival, and tumor resectability were evaluated. RESULTS: Of the 71 patients, 57 (81%) were male with a mean age of 63.3 ± 8.2 years. The rates of histological subtypes of NSCLC were as follows: Squamous cell carcinoma 60.5%, adenocarcinoma 32%, and others 7.2%. Mean SLL was 12.9 ± 38.4 pmol/mL. There was no distinctive difference between SLL, weight loss, and survival. However, when stratifying the groups according to the lung cancer histological subtypes, mean SLL was significantly higher in patients with adenocarcinoma than those with squamous cell subtype (26.9 ± 6.2 pmol/mL vs. 5.1 ± 9.1 pmol/mL, P = 0.004). CONCLUSIONS: SLL might be beneficial as a useful biomarker in preclinical setting of NSCLC to guide detecting the lung cancer subtypes as well as monitoring the patients.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Leptina/sangre , Neoplasias Pulmonares/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND/AIM: The role of angiogenic factors in gastric cancer is not clear. We aimed to assess the role of vascular endothelial growth factor A (VEGFA), angiopoietin 1 (Ang-1), and placental growth factor (PlGF) in the prognosis of patients with advanced gastric cancer. MATERIALS AND METHODS: Thirty consecutive patients treated with a modified DCF (docetaxel, cisplatin, and fluorouracil) regimen were included in the study. The plasma VEGFA, Ang-1, and PlGF levels of the patients before treatment and following two cycles of chemotherapy were measured and evaluated as prognostic factors. RESULTS: Poor performance status and lower Ang-1 levels were correlated with poor overall survival (OS). No significant correlation between VEGFA or PlGF and OS was found. An angiogenesis prognostic index (API) based on the levels of VEGFA, Ang-1, and PlGF was found to be highly correlated with OS. Performance status and API were found as independent prognostic factors for OS. Furthermore, a decrease in VEGFA by 25% from the pretreatment level was also found as a prognostic factor for OS independent of response to DCF regimen. CONCLUSION: Our results support the use of the new API including VEGFA, Ang-1, and PlGF levels in patients with advanced gastric cancer as a predictor of survival.
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Inhibidores de la Angiogénesis/administración & dosificación , Proteínas Similares a la Angiopoyetina/sangre , Proteínas de la Membrana/sangre , Neovascularización Patológica/sangre , Neoplasias Gástricas/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Proteína 1 Similar a la Angiopoyetina , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/fisiopatología , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/fisiopatología , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Optimal duration of adjuvant trastuzumab in early breast cancer is an unresolved issue. In this observational study, we compared the outcome of 9 weeks and 1 year adjuvant trastuzumab in early breast cancer patients in Turkey. METHODS: Records of 680 patients with HER2-positive early breast cancer who received adjuvant trastuzumab plus chemotherapy were obtained and patients were followed up to compare the disease-free survival (DFS) outcome of 9 weeks versus 1 year trastuzumab. RESULTS: Nine weeks and 1 year trastuzumab was given to 202 (29.7 %) and 478 (70.3 %) patients, respectively. There was a significantly lower rate of patients with negative lymph nodes in the 9-week trastuzumab group. At median 3 years of follow-up from the date of starting trastuzumab, the DFS rates were 88.6 and 85.6 %, respectively (p = 0.670). When adjusted for all the prognostic factors that were significant on univariate analysis, again there was no significant difference in DFS between the groups (HR 0.675; 95 % CI 0.370-1.231; p = 0.200). Cardiac toxicity defined as a ≥15 % decrease in LVEF was significantly higher in the 1-year trastuzumab group (1.88 % versus none for 1-year and 9-week trastuzumab groups, respectively; p = 0.050). CONCLUSION: The results of this observational study suggest that DFS outcome of 9 weeks of adjuvant trastuzumab may be comparable to 1 year adjuvant trastuzumab: this needs confirmation by randomized trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Cardiotoxicidad/etiología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversos , Resultado del Tratamiento , Turquía , Adulto JovenRESUMEN
Malignant mesothelioma (MM) is a neoplasm which originates from serous membranes. It is relatively more common in Turkey. Ninety-nine patients between 2002-2009 were evaluated for survival and patient characteristics with chest pain, dyspnea, weight loss, loss of appetite, anemia, leukocytosis, thrombocytosis and lactate dehydrogenase (LDH) elevation, retrospectively. Male/female ratio was 1.41(58/41). Median age was 53(27-88). Asbestosis exposure rate was 78.5%. Most of the patients had better ECOG-PS (88.7% for 1-2). Chest pain (47.7%), dyspnea (44.8%), weight loss (49%), loss of appetite (50%), anemia (38%), leukocytosis (37.2%), thrombocytosis (26.6%) and LDH elevation (10.1%) were found with median values such as 11.8 g/dL (5-17.1) for hemoglobin, 8,800/mm3 for WBC (2,600-38,300), 382,000/mm(3) for platelets (28,000-1,504,000) and 253 IU/L for LDH (85-1,877), respectively. The most common site was pleura (62.3%). Half of the patients were unclassified, while epitheloid histopathology (39.4%) was most common in classified ones. RT rate was 42.1% in operated patients and all had pleural MM. Median OS was 22.9 months. Eighty percent of the patients had first-line CT with a clinical benefit rate of 63.3%. Second-line CT rate was 29% with a clinical benefit rate of 44%. Most preferred CT regimen was cisplatinum and pemetrexed. Most of the patients were male in their 50 s with pleural MM. They had chest pain, dyspnea, weight loss and loss of appetite as the most common symptoms at diagnosis. Only half of the patients could be subtyped with a predominance of epitheloid histology.
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Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Dolor en el Pecho/diagnóstico , Disnea/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidad , Mesotelioma/terapia , Mesotelioma Maligno , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Pérdida de PesoRESUMEN
A survey in the year 2007 among medical students of Ankara University Medical School to assess the smoking rates showed that 25.1 % of them were smoking. Moreover, the smoking rate was 35 % at sixth grade students and 60 % of the smokers specified that they started smoking at medical school. This report provides a successful approach to decrease smoking among medical students by measures against starting smoking. An "Antismoking Group" composed of voluntary academic staff, nurses, students, psychologists, and a social worker of the medical school was established to engage in lowering the smoking rate and eliminating it eventually among our students. Several methods including regular monthly meetings, annual "Smoking or Health" symposiums, and lectures to first, second, and third grade students to increase their awareness related to harms of smoking and their role in the fight against smoking were carried out. Our surveys in the years 2009 (641 students) and 2012 (975 students) showed that total smoking rates dropped to 15.0 and 11.0 %, respectively (p < 0.0002). Moreover, the smoking rate for the sixth grade students dropped from 35.0 % in 2007 to 21.8 and 8.8 % in the years 2009 and 2012, respectively (p < 0.0002). In 2012, the smoking rates of first year and sixth year students were 7.8 and 9.0 %, respectively. These close rates of smoking at the first and last years of medical school training and the significant drop in smoking rates in 5 years confirm that our group pursued a realistic and successful strategy against smoking.
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Educación en Salud , Cese del Hábito de Fumar/psicología , Prevención del Hábito de Fumar , Estudiantes de Medicina/psicología , Adolescente , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Fumar/epidemiología , Fumar/psicología , Estudiantes de Medicina/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVE: Triple negative breast cancer (TNBC) is generally considered as a poorer prognostic subgroup, with propensity for earlier relapse and visceral involvement. The aim of this study is to evaluate the outcome of non-metastatic TNBC patients from different centers in Turkey and identify clinical and pathologic variables that may effect survival. MATERIALS AND METHODS: Between 1993-2007, from five different centers in Turkey, 316 nonmetastatic triple negative breast cancer patients were identified with follow-up of at least 12 months. The data was collected retrospectively from patient charts. The prognostic impact of several clinical variables were evaluated by the Kaplan-Meier and Cox multivariate anayses. RESULTS: Mean age at diagnosis was 49 years (range: 24-82). The majority of the patient group had invasive ductal carcinoma (n: 260, 82.3%) and stage II disease (n: 164; 51.9%). Majority of the patients (87.7%) received adjuvant chemotherapy. 5 year overall survival (OS) and disease-free survival (DFS) rates were 84.6% and 71.6%, respectively. Univariate analysis revealed locally advanced disease (p: 0.001), advanced pathological stage (p: 0.021), larger tumor size (T1&T2 vs T3&T4) (p<0.001), nodal positivity (p: 0.006), and extensive nodal involvement (p<0.001) as significant factors for DFS; whereas, advanced pathological stage (p: 0.017), extensive nodal involvement (p<0.001) and larger tumor size (p: 0,001) and presence of breast cancer-affected member in the family (p=0.05) were identified as prognostic factors with an impact on OS. Multivariate analysis revealed larger tumor size (T3&T4 vs T1&T2) and presence of lymph node metastases (node-positive vs node-negative) as significant independent prognostic factors for DFS (Hazard ratio (HR): 3.03, 95% CI: 1.71-5.35, p<0.001 and HR: 1.77, 95% CI: 1.05-3.0, p=0.03, respectively). Higher tumor stage was the only independent factor affecting overall survival (HR: 2.81; 95% CI, 1.27-6.22, p=0.01). CONCLUSION: The outcome of patients with TNBC in this cohort is comparable to other studies including TNBC patients. Tumor size and presence of lymph node metastasis are the major independent factors that have effect on DFS, however higher tumor stage was the only negative prognostic factor for OS.
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BACKGROUND: The ABO blood groups and Rh factor may affect the risk of lung cancer. MATERIALS AND METHODS: We analyzed 2,044 lung cancer patients with serologically confirmed ABO/Rh blood group. A group of 3,022,883 healthy blood donors of Turkish Red Crescent was identified as a control group. We compared the distributions of ABO/Rh blood group between them. RESULTS: The median age was 62 years (range: 17-90). There was a clear male predominance (84% vs. 16%). Overall distributions of ABO blood groups were significantly different between patients and controls (p=0.01). There were also significant differences between patients and controls with respect to Rh positive vs. Rh negative (p=0.04) and O vs. non-O (p=0.002). There were no statistically significant differences of blood groups with respect to sex, age, or histology. CONCLUSIONS: In the study population, ABO blood types were associated with the lung cancer. Having non-O blood type and Rh-negative feature increased the risk of lung cancer. However, further prospective studies are necessary to define the mechanisms by which ABO blood type may influence the lung cancer risk.
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Sistema del Grupo Sanguíneo ABO/sangre , Neoplasias Pulmonares/sangre , Sistema del Grupo Sanguíneo Rh-Hr/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Turquía/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor of mesothelial surfaces. Previous studies have observed an association between ABO blood groups and risk of certain malignancies, including pancreatic and gastric cancer; however, no information on any association with MM risk is available. The aim of this study was to investigate possible associations amoong MM clinicopathological features and ABO blood groups and Rh factor. MATERIALS AND METHODS: In 252 patients with MM, the ABO blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with various clinicopathological features were also evaluated in the patient group. RESULTS: The median age was 55 (range: 27-86) and 61.5% of patients were male. While 82.8% of patients had a history of exposure to asbestos, 60.7% of patients had a smoking history. Epithelioid (65.1%) was the most common histology and 18.7% of patients had mixed histology. Overall, the ABO blood group distribution of the 252 patients with MM was comparable with the general population. The median overall survival (OS) was 14 months (95% confidence interval, 11.3-16.6 months). The median OS for A, B, AB, and O were 11, 15, 16, and 15 months respectively (p=0.396). First line chemotherapy was administered to 118 patients. The median OS of patients on pemetrexed or gemcitabine was longer than patient who was not administered chemotherapy [17 months (95%CI, 11.7-22.2) vs. 9 months (95%CI, 6.9-11.0); p<0.001]. CONCLUSIONS: The results of this study suggest that patients with MM can benefit from treatment with pemetrexed or gemcitabine in combination with cisplatin. We did not observe a statistically significant association between ABO blood group and risk of MM.
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Sistema del Grupo Sanguíneo ABO/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mesotelioma/sangre , Mesotelioma/tratamiento farmacológico , Sistema del Grupo Sanguíneo Rh-Hr/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Cisplatino/administración & dosificación , Intervalos de Confianza , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Masculino , Mesotelioma/patología , Persona de Mediana Edad , Pemetrexed , Estudios Retrospectivos , Turquía , GemcitabinaRESUMEN
BACKGROUND: An association between the ABO blood group and the risk of certain malignancies, including pancreatic and gastric cancer, has been reported previously. However, it is unclear whether this association is valid for gastrointestinal stromal tumors (GIST). In this study, ABO blood groups and the Rh factor were investigated in a series of GIST cases. MATERIAL AND METHODS: In 162 patients with GIST, blood group and Rh factor were examined and compared with a control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with tumor size, mitotic activity, and age were also evaluated. RESULTS: Overall, the ABO blood group and Rh factor distributions of the 162 patients with GIST were similar to those of the general population. There were no significant differences between both ABO blood types and Rh factor in terms of tumor size, mitotic activity, and age. CONCLUSION: This is the first study reported on this issue. In our study, we didn't find any relationship between GIST and ABO blood group and Rh factor. However further studies with larger number of patients are needed to establish the role of blood groups in this population.
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Sistema del Grupo Sanguíneo ABO/sangre , Tumores del Estroma Gastrointestinal/sangre , Sistema del Grupo Sanguíneo Rh-Hr/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Oncología Médica , Persona de Mediana Edad , Pronóstico , TurquíaRESUMEN
INTRODUCTION: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. PATIENTS AND METHODS: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5' UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. RESULTS: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. CONCLUSION: Pharmacogenetics might contribute to tailored therapy.
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Antimetabolitos Antineoplásicos/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Gastrointestinales/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Alelos , Capecitabina , ADN/análisis , ADN/sangre , Proteínas de Unión al ADN/genética , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Dihidrouracilo Deshidrogenasa (NADP)/genética , Erupciones por Medicamentos/etiología , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Frecuencia de los Genes , Humanos , Masculino , Metotrexato/efectos adversos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Repeticiones de Minisatélite , Mucositis/inducido químicamente , Timidilato Sintasa/genética , Turquía , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Adulto JovenRESUMEN
Neuroendocrine tumors (NET) are rare, but their incidence is gradually increasing. In this study, demographical and tumor characteristics, treatment modalities, responses, and survival rates were evaluated in the patients with NET. Seventy-one patients with NET from 3 tertiary care centers evaluated retrospectively. Overall survival (OS), progression-free survival (PFS), and disease-free survival rates were estimated by Kaplan-Meier Method. Male/female ratio was 0.86 (33/38). Median age was 52 years. Rates for family cancer history and goiter/thyroiditis were 22.4 and 17.8%, respectively. The most common primary site was lung (22.5%), in parallel with the literature, and 31% had the large cell neuroendocrine carcinoma histology. The second most common site was stomach. Carcinoid syndrome rate was found to be 30.6%. Half of the patients were in early stage at diagnosis. Surgical resection rate was 64.7, and 45% of the patient received chemotherapy (CT), 22% received radiotherapy. Seventy-six percent of resected patients had local disease. Thirty-two patients received CT for palliation or concurrent with radiotherapy or in adjuvant setting. Platin/etoposide combination was the most commonly used chemotherapy regimen. Chemotherapy response rate was 35.7%. Five patients had received somatostatin analogue. Radiotherapy was used in adjuvant setting in one-third of the patients. Median OS was 66 months, and median PFS was 30 months. Female gender and fifth decade seem to have higher risk. History for family cancer and goiter/thyroiditis was high in the patients with NET, though there is no data about an association between NET and thyroid disorders in the literature.
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Tumores Neuroendocrinos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Síndrome Carcinoide Maligno/epidemiología , Síndrome Carcinoide Maligno/etiología , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The metronomic use of chemotherapeutic drugs is presumed to have anti-angiogenic effect. In the current study, we aimed to test the effects of lower doses of cytotoxic agents on VEGF secretion from tumor cell lines. METHODS: We tested the cytotoxic effects of widely used chemotherapeutic drugs including 5-florouracil, irinotecan, oxaliplatin, paclitaxel and docetaxel in tumor cell lines, MCF-7 (human breast cancer cell line) HT-29 (human colon cancer cell line) and a primary gastric cancer cell line and calculated the IC50 values. We've also assayed the effects of the lower doses of chemotherapeutic drugs on the levels of VEGF secreted by tumor cells in vitro. RESULTS: The human primary gastric cancer cells were more resistant to 5-FU and oxaliplatin than the HT29 and MCF-7 cell lines (p < 0.001). No significant differences were noticed in terms of the IC50 values of the irinotecan, docetaxel and paclitaxel among the studied tumor cell lines (p > 0.05). The test drugs yielded significant decreases in VEGF levels at the doses of -2 log of IC50 values in MCF-7 and primary gastric cancer cell lines. While 5-florouracil did not inhibit the VEGF secretion of HT-29 cell line, irinotecan, oxaliplatin, docetaxel and paclitaxel significantly decreased the levels of secreted VEGF. CONCLUSIONS: Our results suggest that lower doses of chemotherapeutic drugs decrease VEGF secretion from tumor cells without causing substantial cell killing. The data suggest the occurrence of a kind of selective drug-tumor cell type relationship.
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Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Camptotecina/análogos & derivados , Camptotecina/farmacología , Supervivencia Celular/efectos de los fármacos , Docetaxel , Relación Dosis-Respuesta a Droga , Fluorouracilo/farmacología , Células HT29 , Humanos , Concentración 50 Inhibidora , Irinotecán , Células MCF-7 , Compuestos Organoplatinos/farmacología , Oxaliplatino , Paclitaxel/farmacología , Taxoides/farmacología , Células Tumorales CultivadasRESUMEN
BACKGROUND: Previous studies have observed an association between ABO blood group and risk for certain gastrointestinal malignancies, including pancreatic and gastric cancer. However, it is unclear whether there is such an association with colorectal cancer (CRC). In this study, possible relationships between ABO blood groups and Rh factor and KRAS status in patients with CRC were investigated. MATERIALS AND METHODS: In 1,620 patients with CRC, blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with wild type K-ras status was also evaluated. RESULTS: Overall distributions of ABO blood groups as well as Rh factor were comparable between patients (45% A, 7.2% AB, 16.4% B, 31.4% O, and 87.2% Rh+) and controls (42.2% A, 7.6% AB, 16.3% B, 33.9% O, and 87.7% Rh+) (p=0.099). However, there were statistically significant difference between patients and controls with respect to O vs. non O blood group (p=0.033) and marginally significant difference for A vs. non-A blood group (p=0.052). Among patients, the median age was 62 (range 17-97), 58.1% were male. There were no statistically significant differences respect to sex and K-ras status. CONCLUSION: In present study, the ABO/Rh blood groups were statistically significantly associated with the risk of CRC. There were no relationship between K-ras status and ABO blood group and Rh factor. However further studies with larger numbers of patients are needed to establish the role of blood groups and to define the mechanisms by which ABO blood type affect CRC.
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Sistema del Grupo Sanguíneo ABO , Sistema del Grupo Sanguíneo Rh-Hr , Sistema del Grupo Sanguíneo ABO/sangre , Adenocarcinoma/sangre , Neoplasias Colorrectales , Humanos , Sistema del Grupo Sanguíneo Rh-Hr/sangre , RiesgoRESUMEN
Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Bevacizumab , Femenino , HumanosAsunto(s)
Neoplasias Abdominales/etiología , Hemangiosarcoma/etiología , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Neoplasias Abdominales/patología , Neoplasias Abdominales/cirugía , Pared Abdominal , Resultado Fatal , Femenino , Hemangiosarcoma/patología , Hemangiosarcoma/cirugía , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
BACKGROUND AND OBJECTIVES: Previous reports suggest that including cisplatin plus etoposide in the adjuvant treatment may improve the outcomes in patients with early breast cancer. PATIENTS AND METHODS: Forty-one patients with early breast cancer and 4 or more positive lymph nodes were treated with 3 cycles of EoP (oral etoposide plus cisplatin) in addition to 3 cycles of AC (doxorubicin plus cyclophosphamide) and 3 cycles of T (docetaxel) (Group 1). Toxicity and survival results were compared to those with similar disease characteristics who were treated with 4 cycles of AC plus 4 cycles of T (Group 2) during the same period. RESULTS: There were no long-term side effects related to EoP. While median disease-free and overall survivals were not reached in Group 1, they were 107 ± 13 (p = 0.387) months and 123 ± 5 months (p = 0.618) in Group 2. Likewise 10-year disease-free survivals (DFS) were 59.3% and 44.7% respectively. CONCLUSIONS: The trend towards improvement in survival with adjuvant AC + T + EoP when compared to AC + T needs to be studied in randomized trial.