ABSTRACT
Increased incidence of breast cancer has stimulated development of new diagnostic and therapeutic methods. The programmed cell death 1 (PD1) pathway and its inhibitors are promising avenues for investigation. PD1 includes PD ligands 1 (PDL1) and 2 (PDL2). We investigated the expression of PD1 and PDL1 in invasive breast carcinomas using immunohistochemical staining. We used 171 invasive breast carcinoma specimens from which tissue microarray blocks were created. Immunohistochemical staining of PD1 using NAT105, and PDL1 using CAL10 was performed on tissue microarray sections. NAT105 and CAL10 are useful clones for detecting expression of PD1 and PDL1. PD1 and PDL1 immunostaining was significantly stronger in carcinomas with basal-like phenotype compared to other molecular breast cancer types. PD1 and PDL1 expression also was associated with a high histologic grade and a high Ki-67 index. PD1 expression also was associated with lymphovascular invasion and axillary metastasis. PD1 and PDL1 expression is associated with aggressive tumor behavior and a basal-like phenotype in breast cancer. We suggest that inhibition of the PD1/PDL1 pathway, particularly in triple negative breast carcinomas with basal-like phenotype, might be useful for targeted immunotherapy.
Subject(s)
Apoptosis , LigandsABSTRACT
PURPOSE: Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity. METHODS: We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm. RESULTS: A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use. CONCLUSION: Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.
Subject(s)
Febrile Neutropenia , Neoplasms , Algorithms , Antineoplastic Combined Chemotherapy Protocols , Febrile Neutropenia/chemically induced , Febrile Neutropenia/epidemiology , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Neoplasms/drug therapy , Prospective StudiesABSTRACT
Background and Objectives: In this study, we investigated the frequency and type of second primary malignant tumors (SPMTs) accompanying gastrointestinal stromal tumors (GISTs), patient and tumor characteristics, and follow-up and survival data. Materials and Methods: We included 20 patients with SPMTs from a total of 103 patients with GISTs in a single center in Turkey. At the time of GIST diagnosis, patient age, sex, presentation symptoms, localization, pathological features of the tumor, stage, recurrence risk scoring for localized disease, treatments received, time of SPMT association, follow-up times, and survival analysis were recorded for each patient. Localization, histopathology, and stage of SPMT accompanying GISTs were also recorded accordingly. Results: SPMT was detected in 19.4% of patients with GISTs. Of the patients, 50% were men and 50% were women. The mean age at the time of diagnosis of GIST was 63.8 ± 10.81 years (range: 39-77 years). Of the GISTs, 60% were localized in the stomach, 25% in the small intestine, and 70% were at low risk. Of the SPMTs, 60% were in the gastrointestinal system. SPMTs were diagnosed as synchronous with GISTs in 50% of the patients. The mean follow-up period of the patients from the diagnosis of GIST was 45.6 (0.43-129.6) months. When the data were finalized, 5% died due to GIST, 35% died due to SPMT, and 15% died due to non-disease-related causes. Conclusions: SPMT was detected in 19.4% of patients with GISTs. GISTs were frequently located in the stomach, and most of them were at low risk. The most common SPMTs were gastrointestinal system tumors, and their coexistence was found to be synchronous. Most patients died due to SPMT during follow-up.
Subject(s)
Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Neoplasms, Second Primary , Female , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/epidemiology , Humans , Intestine, Small , Male , Neoplasms, Second Primary/epidemiology , Turkey/epidemiologyABSTRACT
Background/aim: This study aimed to investigate the effect of clinical and pathological indicators at the time of the diagnosis on overall survival in patients recently diagnosed with non-small cell lung cancer. Materials and methods: The study population consisted of patients who were diagnosed at the Faculty of Medicine at Isparta Süleyman Demirel University Hospital between January 1, 2010 and December 31, 2017 and presented to the medical oncology outpatient clinic. Results: A total of 518 patients were evaluated, including 260 patients with squamous cell carcinoma, 207 patients with adenocarcinoma, 50 patients with non-small cell lung cancer-not otherwise specified, and 1 patient with large cell carcinoma. The average life expectancy was found to be 11.50 ± 1.40 months in patients with squamous cell carcinoma, 12.60 ± 1.59 months in patients with adenocarcinoma, and 8.70 ± 1.87 months in the other patients. The estimated 5-year relative survival rate for non-small cell lung cancer was 8% (7% for men and 18% for women). In the multivariate analysis, sex being male (HR, 2.41; P < 0.001), a performance status >2 (HR, 1.70; P < 0.001), the stage of cancer (HR, 1.37; P = 0.045), the presence of bone or liver metastasis (HR, 1.44, P = 0.009, HR, 1.57; P = 0.016, respectively), and the patient not having received radiotherapy (HR, 3.25; P < 0.001) or chemotherapy (HR, 1.85; P = 0.001) were defined as statistically significant predictive factors that reduced the overall survival. Conclusions: In this study, sex, stage, performance status, the presence of liver or bone metastases, and treatment had an effect on overall survival.
Subject(s)
Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Neoplasms, Second Primary/mortality , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/therapy , Female , Humans , Lung Neoplasms/therapy , Male , Middle Aged , Severity of Illness Index , Sex Factors , Survival Analysis , Turkey/epidemiologyABSTRACT
BACKGROUND/AIMS: Gastroenteropancreatic neuroendocrine tumors are rarely seen and have heterogeneous clinical outcomes. Mostly half of the patients had metastatic disease at presentation. Palliative resection of primary site in metastatic disease is still controversial. The aim of this study was to find out the influence of resection of primary tumor site on progression-free survival and overall survival in metastatic non-functioning gastroenteropancreatic neuroendocrine tumors. The secondary end point is to determine the prognostic factors influencing the survivals. MATERIALS AND METHODS: This study was conducted at a single medical oncology center, Antalya Education and Research Hospital. Patients who had non-functioning metastatic gastroenteropancreatic neuroendocrine tumors with primary site resected or unresected were compared retrospectively. Resection of metastases was excluded. RESULTS: Fifty-three patients were included in the study and 29 patients had primary tumor resection. The primary site resected group had favorable outcomes with the overall survival (median unreached) compared to the median overall survival of 30 months in the unresected group (p=0.001). Median progression-free survival was also better in the primary site resected group than the unresected group (60 months vs. 14 months, respectively) (p=0.013). In multivariate analysis, unresected primary site and high-grade tumors were found to be independent prognostic factors on low survivals (Hazard ratio (HR): 4.6; 95% CI: 1.21-17.47 and HR: 10.1; 95% CI: 1.15-88.84, respectively). Age (p=0.131), gender (p=0.051), chromogranin A level (p=0.104), Ki-67 index (p=0.550), tumor size (p=0.623), and primary tumor area (p=0.154) did not influence the overall survival. CONCLUSION: Gastroenteropancreatic neuroendocrine tumors with primary site resected had improved survivals when compared to the unresected group.
Subject(s)
Intestinal Neoplasms/mortality , Neuroendocrine Tumors/mortality , Palliative Care/statistics & numerical data , Pancreatic Neoplasms/mortality , Stomach Neoplasms/mortality , Aged , Female , Humans , Intestinal Neoplasms/surgery , Male , Middle Aged , Neuroendocrine Tumors/surgery , Palliative Care/methods , Pancreatic Neoplasms/surgery , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/surgery , Survival RateABSTRACT
We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively ( P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.
Subject(s)
Heparin, Low-Molecular-Weight/administration & dosage , Neoplasms/drug therapy , Venous Thromboembolism/prevention & control , Aged , Female , Follow-Up Studies , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle Aged , Neoplasms/blood , Risk Factors , Venous Thromboembolism/blood , Venous Thromboembolism/etiologyABSTRACT
BACKGROUND: We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS). RESULTS: The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months. CONCLUSION: This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Interferon-alpha/administration & dosage , Kidney Neoplasms/drug therapy , Protein Kinase Inhibitors/administration & dosage , Adult , Aged , Aged, 80 and over , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Interferon-alpha/therapeutic use , Longitudinal Studies , Male , Middle Aged , Neoplasm Metastasis , Protein Kinase Inhibitors/therapeutic use , Survival Analysis , Treatment Outcome , TurkeyABSTRACT
BACKGROUND: Recently, there are several studies about cancer stem cells (CSC), indicating that they are the cells that initiate the tumor, provide progression, metastasis and responsible for the aggressive tumor behavior. MATERIALS AND METHODS: The purpose of this study is to investigate the expressions of CD24, CD44, their different combinations, ALDH1 and CD133 in invasive ductal carcinoma. Their relationships with clinicopathologic parameters, such as tumor grade, lymphovascular invasion, tumor size, axillary lymph node involvement, stage, hormone receptors, HER2 expression, basal like tumors, triple negative status and prognosis were also investigated. Tissue microarray method was used to investigate immunohistochemical CD24, CD44, ALDH1 and CD133 expressions in 105 invasive ductal carcinoma cases. RESULTS: CD133 expression was significantly associated with tumor size (p=0.023) and stage (p=0.009). CD133 expression was decreased in tumors with larger tumor size, higher stage and lymphovascular invasion. CD133 expression was positively correlated with CD44 (r=0.212, p=0.032) and CD44(+)/CD24(+) (r=0.202, p=0.040) expressions. CD44, CD24 and ALDH1 expressions showed no significant relationship and correlation with clinicopathologic features. There was a significant relationship (p=0.048) between CD44(+)/CD24(-/low) phenotype and basal like tumors. EGFR expression was positively correlated with CD44(+)/CD24(-/low) phenotype (r=0.211, p=0.036). CONCLUSIONS: Basal like tumors are enriched for CSCs with CD44(+)/CD24(-/low) phenotype. CD133 can detect a different population of CSC in breast carcinoma.
Subject(s)
Antigens, CD/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , CD24 Antigen/metabolism , Carcinoma, Ductal, Breast/metabolism , Glycoproteins/metabolism , Hyaluronan Receptors/metabolism , Isoenzymes/metabolism , Peptides/metabolism , Retinal Dehydrogenase/metabolism , AC133 Antigen , Adult , Aged , Aged, 80 and over , Aldehyde Dehydrogenase 1 Family , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry/methods , Middle Aged , PrognosisSubject(s)
Fibroma/diagnosis , Fibroma/pathology , Fibrosarcoma/diagnosis , Fibrosarcoma/pathology , Testicular Neoplasms/diagnosis , Testicular Neoplasms/pathology , Biomarkers, Tumor/analysis , Fibroma/surgery , Fibrosarcoma/surgery , Histocytochemistry , Humans , Immunohistochemistry , Male , Microscopy , Middle Aged , Testicular Neoplasms/surgeryABSTRACT
BACKGROUND: A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western populations. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer. METHODS: A total of 554 stage II colon cancer patients were retrospectively enrolled in the study. Three hundred fifty-three patients had received adjuvant chemotherapy (5-FU-LV, FOLFOX or FLOX) and 201 had received no adjuvant chemotherapy. T4 tumor stage, lymphovascular invasion, perineural invasion, bowel obstruction and/or perforation, <12 harvested lymph nodes, and poor differentiation were defined as high-risk factors. RESULTS: The median age of the patients was 62 years (range 26-88). The median disease-free survival (DFS) was 58.1 months (95% CI, 47.6 months to 68.5 months) in the non-treatment group and has not been reached in the treatment group (P <0.01). In univariate analysis, patient age >60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors. Adjuvant chemotherapy reduced the risk of recurrence with statistical significance (P <0.01). In multivariate analysis, patient age >60 years and T4 tumor stage were independent risk factors affecting DFS. In addition, adjuvant chemotherapy was an independent favorable prognostic factor for DFS (P <0.01). CONCLUSIONS: Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other populations. Further prospective studies in colon cancer are needed to understand the differences in biology and risk factors between races.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Neoadjuvant Therapy/methods , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colectomy , Colonic Neoplasms/complications , Colonic Neoplasms/surgery , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Intestinal Obstruction/etiology , Intestinal Perforation/etiology , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Odds Ratio , Organoplatinum Compounds/administration & dosage , Retrospective Studies , Risk Factors , Treatment Outcome , TurkeyABSTRACT
BACKGROUND: Bisphosphonates (BPs) like zoledronic acid (ZOL) are widely used for the treatment of different diseases such as osteoporosis, metastatic bone diseases and hypercalcaemia. However, the effects of BPs on apoptosis of the liver and kidney after treatment are unclear. Furthermore, basic fibroblast growth factor (bFGF) is an angiogenic molecule, which plays an important role in angiogenesis and tissue repair. The present study investigated the expression of caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and bFGF. OBJECTIVE: The present study investigated the expression of caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and bFGF. ANIMALS AND METHODS: An animal model with 32 male Sprague Dawley rats was used. The effects of ZOL and bFGF on liver and kidney with the expressions of different apoptosis markers were studied histopathologically and immunohistochemically. Data were analyzed using Cronbach's alpha, Kruskal-Wallis and Bonnferroni-Dunn tests. RESULTS: The main microscopic findings were mononuclear cell infiltrations around the bile ducts, binuclear and markedly enlarged hepatocytes (cytomegaly) and mitotic figures in the liver of rats treated with ZOL only. Immunohistochemically, both APAF-1 and caspase-3, -5 and -7 expressions were found elevated significantly (P < 0.05) in the liver and kidney of these rats. CONCLUSIONS: Our findings showed that ZOL treatment increased while bFGF treatment decreased apoptosis significantly in the liver and kidney of Sprague Dawley rats. CLINICAL IMPORTANCE: The addition of bFGF to ZOL treatment of various diseases might reduce the ZOL effects.
Subject(s)
Bone Density Conservation Agents/metabolism , Caspases/metabolism , Diphosphonates/metabolism , Fibroblast Growth Factors/metabolism , Imidazoles/metabolism , Kidney/pathology , Liver/pathology , Animals , Apoptosis , Apoptotic Protease-Activating Factor 1 , Bone Density Conservation Agents/adverse effects , Caspase 3 , Caspase 7 , Diphosphonates/adverse effects , Disease Models, Animal , Imidazoles/adverse effects , Immunohistochemistry/veterinary , Random Allocation , Rats , Rats, Sprague-Dawley , Zoledronic AcidABSTRACT
BACKGROUND: Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. MATERIALS AND METHODS: Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. RESULTS: Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. CONCLUSIONS: According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients.
Subject(s)
Carcinoma, Hepatocellular/epidemiology , Hepatitis B/epidemiology , Liver Neoplasms/epidemiology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Epidemiologic Studies , Female , Follow-Up Studies , Hepacivirus/pathogenicity , Hepatitis B/pathology , Hepatitis B/virology , Humans , Incidence , Liver Neoplasms/pathology , Liver Neoplasms/virology , Male , Middle Aged , Neoplasm Staging , Prognosis , Risk Factors , Turkey/epidemiology , alpha-Fetoproteins/metabolismABSTRACT
PURPOSE: In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis. METHODS: Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34). RESULTS: Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02]. DISCUSSION: Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/secondary , Breast Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Brain Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Lapatinib , Middle Aged , Quinazolines/administration & dosage , Receptor, ErbB-2/metabolism , Retrospective Studies , Survival Analysis , Trastuzumab , Treatment OutcomeABSTRACT
We investigated the effects of bisphosphonate (BP) on oxidative stress levels in blood of patients with cancer. In total, 19 patients with cancer and 21 healthy subjects were included in the study. BP was intravenously administrated to the participants for 6 weeks. The patients had higher lipid peroxidation (LP) levels in the plasma and erythrocyte samples but lower glutathione peroxidase (GSH-Px) and plasma vitamin E values. In patients treated with BP, calcium and LP levels decreased, but GSH-Px and vitamin E values improved. In conclusion, we observed that treatment with BP alleviated oxidative stress induced by cancer.
Subject(s)
Diphosphonates/administration & dosage , Neoplasms/blood , Oxidative Stress/drug effects , Aged , Case-Control Studies , Female , Glutathione Peroxidase/blood , Humans , Lipid Peroxidation/drug effects , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/enzymology , Vitamin E/bloodABSTRACT
The administration of chemotherapeutic agents for colorectal carcinoma is associated with an increase in oxidative stress and a concomitant decrease in antioxidant and element levels in the blood. This study investigated the effects of 5-fluorouracil (5-FU) chemotherapy on the levels of lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), antioxidant vitamins, and elements in colorectal cancer patients. Twelve patients with newly diagnosed colorectal carcinoma and 12 healthy subjects were included in this study. Blood samples were collected from both the healthy controls and patients. 5-FU was intravenously administered to the patients for 6 weeks, and blood samples were collected again from the treatment group. In the patient group, lipid peroxidation levels were increased in both the plasma and erythrocyte samples, whereas GSH-Px activity and concentrations of GSH, vitamin E, and ß-carotene in erythrocytes were decreased. The oxidant, antioxidant, and plasma calcium values were lower in 5-FU-treated patients than in the controls. Plasma vitamin A, chloride, sodium, and potassium concentrations did not change with 5-FU treatment. In conclusion, oxidative stress in patients with newly diagnosed colorectal cancer is attributable to the disease and not to 5-FU treatment. Blood vitamin E, ß-carotene, GSH, and GSH-Px levels could be useful as early biomarkers of the prognosis of colorectal cancer patients.
Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Calcium/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Oxidative Stress/drug effects , Colorectal Neoplasms/metabolism , Female , Humans , Male , Middle AgedABSTRACT
Recent studies have reported oxidative damage due to bisphosphonate (BP) in various cancer tissues and neurons, although basic fibroblast growth factor (bFGF) induced antioxidant effects in the cells. The bFGF may modulate the BP-induced oxidative stress in oral epithelium of rats. This study was undertaken to explore possible beneficial antioxidant effects of bFGF on oxidative stress induced by BP in oral epithelium of rats. Twenty-eight rats were equally divided into four groups. The first group was used as control. The second, third and fourth groups intraperitoneally received BP (zoledronic acid), bFGF and BP + bFGF. At the end of 10 weeks, the rats were sacrificed, and oral epithelium samples were taken for analyses. In BP group, the lipid peroxidation levels were increased in the oral epithelium, while the activities of glutathione peroxidase (GSH-Px) and the concentrations of total antioxidant status (TAS) were decreased. In rats treated with bFGF, lipid peroxidation levels decreased, and the activities of GSH-Px and concentrations of TAS improved in the oral epithelium. However, zinc and copper levels were decreased in the oral epithelium by BP and bFGF treatments. Concentrations of vitamin E and reduced glutathione in the samples did not change in the groups. In conclusion, treatment with bFGF modulated the antioxidant redox system and reduced the oral epithelium oxidative stress induced by BP. However, zinc and copper levels were decreased by BP and bFGF treatments.
Subject(s)
Copper/metabolism , Diphosphonates/adverse effects , Fibroblast Growth Factor 2/physiology , Mouth Mucosa/drug effects , Oxidative Stress/drug effects , Zinc/metabolism , Animals , Biomarkers/metabolism , Male , Rats , Rats, WistarABSTRACT
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.
Subject(s)
ABO Blood-Group System/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mesothelioma/blood , Mesothelioma/drug therapy , Rh-Hr Blood-Group System/blood , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cisplatin/administration & dosage , Confidence Intervals , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Glutamates/administration & dosage , Guanine/administration & dosage , Guanine/analogs & derivatives , Humans , Male , Mesothelioma/pathology , Middle Aged , Pemetrexed , Retrospective Studies , Turkey , GemcitabineABSTRACT
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.
Subject(s)
ABO Blood-Group System/blood , Gastrointestinal Stromal Tumors/blood , Rh-Hr Blood-Group System/blood , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Medical Oncology , Middle Aged , Prognosis , TurkeyABSTRACT
BACKGROUND: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. METHODS: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. RESULTS: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). CONCLUSIONS: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.
Subject(s)
Brain Neoplasms/secondary , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Receptor, ErbB-2/metabolism , Adult , Age Factors , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Female , Humans , Lapatinib , Middle Aged , Multivariate Analysis , Quinazolines/therapeutic use , Retrospective Studies , Survival Rate , Tamoxifen/therapeutic use , Trastuzumab , TurkeyABSTRACT
Paclitaxel is highly active against a variety of solid tumors including breast lung, ovarian and head and neck cancer. Although peripheral neurotoxicity is well-known side effect, central nervous system (CNS) toxicity-related standard dose of paclitaxel is extremely uncommon, because paclitaxel dose not cross the blood-brain barrier and is not detectable in the cerebrospinal fluid. We present a patient with advanced stage breast carcinoma who developed acute and spontaneous resolving encephalopathy after weekly dose of paclitaxel. The patient did not have brain metastasis, or prior whole-brain irradiation, or any type of neurosurgery. Radiological imaging studies showed no abnormalities. CNS toxicity of paclitaxel should be kept in mind in patients without a previous history of brain metastasis or brain irradiation and even with low weekly doses.