Cetuximab and irinotecan interact synergistically to inhibit the growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice.

PURPOSE: Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody against epidermal growth factor receptor, offers new treatment potentials for patient with ATC. Cetuximab has also been reported to have synergistic effects when combined with irinotecan, a topoisomerase inhibitor. Therefore, we hypothesized that cetuximab and irinotecan would be effective in inhibiting the growth and progression of ATC in a murine orthotopic model. EXPERIMENTAL DESIGN: The in vitro antiproliferative effects of cetuximab and irinotecan on ATC cell line ARO were examined. We also studied the in vivo effects of cetuximab and irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was also compared with that of doxorubicin. RESULTS: Cetuximab alone did not show any antiproliferative or proapoptotic effect on this cell line. However, when combined with irinotecan, cetuximab potentiated the in vitro antiproliferative and proapoptotic effect of irinotecan. Cetuximab, irinotecan, and cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal invasion, and tumor microvessel density were also significantly decreased in these treatment groups. Furthermore, the cetuximab/irinotecan combination was significantly more effective than doxorubicin in inhibiting the growth of orthotopic ATC xenografts. CONCLUSIONS: Combination therapy with cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC xenografts in nude mice. Given the lack of curative options for patients with ATC, combination therapy with cetuximab and irinotecan treatment warrants further study.     

Combined use of histopathology with touch smear cytology in biopsies of the larynx

The aim of this prospective study is to evaluate the effectiveness of combined use of histopathology with cytology in biopsies of the larynx. Biopsies taken for this purpose are studied by using two different methods and the results are evaluated. One hundred and thirty-five patients with suspected malignant laryngeal lesions were examined by direct microlaryngoscopy for primary diagnosis. Each lesion was biopsied first. Subsequently touch smear cytology was obtained from the biopsies. In all cases, cytologic slides (one or two per biopsy) were screened and compared to corresponding biopsies. Lesions were categorized as benign, laryngeal intraepithelial neoplasia and malignant. Results obtained were compared with surgical samples obtained from patients who have undergone surgery. In other cases, where surgery was not applied, results of the follow-up were evaluated. In larynx biopsies the results for histopathology were as follows: sensitivity 93.9%, specificity 100% and accuracy 96.3%. The results for cytology were as follows: sensitivity 82.5%, specificity 94.5% and accuracy 87.4%. A comparison of cytologic evaluation versus histopathologic evaluation in laryngeal biopsies reveals that histopathology is superior. According to the study results, in 88.9% (120/135) of the cases the agreement between cytological and histopathological results was found. In two other cases (1.5%) cytologic evaluation contributed to the histopathologic diagnosis.     

Trefoil factor expression in biliary epithelium of graft-versus-host disease of the liver after allogeneic hematopoietic cell transplantation

BACKGROUND: The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury.     

Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients

BACKGROUND: Sleep complaints are common in end-stage renal disease. We aimed to investigate the relationship between sleep-related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels. METHODS: Predialysis serum interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels in nine patients with sleep complaints were compared with those of nine patients without sleep complaints and nine healthy controls. Patients with sleep complaints underwent polysomnography the night after HD and the following night. RESULTS: Patients with sleep complaints had significantly higher predialysis IL-1beta levels compared with those without and healthy controls (P=0.004 and P=0.000, respectively). They also had higher predialysis IL-6 and TNF-alpha levels than those without sleep complaints; however, the difference was not significant. Patients without sleep complaints had higher mean IL-6 and TNF-alpha and similar mean IL-1beta levels compared with healthy controls (P=0.001, P=0.024, P=0.26, respectively). Obstructive sleep apnoea syndrome (OSAS) was found in six out of nine (66%) patients with sleep complaints. Sleep architecture and cytokine levels did not differ between the two nights. The mean serum IL-1beta, IL-6 and TNF-alpha levels did not differ in the pre- and post-polysomnographic samples. There was no correlation between IL-1beta, IL-6 or TNF-alpha levels and the apnoea-hypopnoea index. CONCLUSIONS: Proinflammatory cytokines, IL-1beta in particular, might be associated with sleep complaints in HD patients. OSAS is not uncommon in HD patients with sleep-related complaints and sleep architecture does not appear to be effected by the HD procedure itself.     

Impact of surgical treatment on respiratory muscle dysfunction in symptomatic hyperparathyroidism

HYPOTHESIS: We hypothesized that surgical treatment would improve respiratory muscle strength in symptomatic hyperparathyroidism (HPT). DESIGN: Prospective clinical trial. SETTING: A tertiary referral center. PATIENTS: Fifteen consecutive patients with symptomatic HPT and 10 with euthyroid multinodular goiter (control group) without a history of obstructive or restrictive lung disease. INTERVENTIONS: Forced vital capacity and forced expiratory volume in 1 second were measured before and 6 months after surgery to estimate respiratory muscle involvement. These measurements were compared with the reference values estimated individually in each patient. Mann-Whitney and Wilcoxon signed rank tests were used for statistical analysis, and P<.05 was considered statistically significant. MAIN OUTCOME MEASURES: Respiratory dysfunction in patients with symptomatic HPT, pulmonary function after parathyroidectomy, and the correlation between the preoperative serum parathyroid hormone and total serum calcium values and the impairment in pulmonary function. RESULTS: Preoperative forced vital capacity and forced expiratory volume in 1 second measurements were below the reference values in 11 (73%) and 9 (60%) patients, respectively. All the patients were normocalcemic, and forced vital capacity and forced expiratory volume in 1 second measurements significantly improved at postoperative month 6 (P = .001). No significant difference was detected in the control group. Improvement in pulmonary function correlated with preoperative serum calcium and parathyroid hormone values in patients with HPT (P<.05 and P<.001, respectively). CONCLUSIONS: Symptomatic HPT impairs inspiratory and expiratory components of respiratory function, and normalization of serum calcium levels after surgical treatment is associated with a significant improvement in lung function.     

High serum leptin levels in depressive disorders with atypical features

Leptin is thought to be related to vegetative symptoms of depression such as alterations in food intake and weight. Fifty-seven drug-free patients and 26 healthy controls were enrolled in this study. We have found that the serum leptin levels were higher in patients with atypical depressive disorder than in controls, but not in patients with non-atypical depressive disorder, however, body mass index, age, and gender were not significantly different between these groups. Probably, these findings seem to be associated with some features of the atypical depressive disorders such as weight gain, a result of hyperphagia.     

Analysis of MTHFR 1298A>C in addition to MTHFR 677C>T polymorphism as a risk factor for neural tube defects in the Turkish population

Maternal folic acid intake in the periconceptional period is strongly related to reduction in recurrence and occurrence of birth defects involving the neural tube. Among the single nucleotide polymorphisms (SNPs) influencing the folate metabolism, the methylenetetrahydrofolate reductase (MTHFR) gene has been the one most exclusively studied. Many studies have reported significant association between MTHFR 677C>T and increased risk of neural tube defects (NTDs). Our previous study did not support this observation. The present study aimed to determine the prevalence of 1298A>C polymorphism in addition to 677C>T in the same Turkish population as a risk factor for NTDs. We genotyped case (95 offspring with NTDs, 80 mothers, 72 fathers) and control (93 healthy children) populations for MTHFR 677C>T and MTHFR 1298 A>C polymorphisms. The comparison demonstrated a significant increase in the 1298AA/677TT genotype frequency among mothers of offspring with NTDs (OR 5.23 [1.06-25.9]; p=0.067). The 677CT genotype was only 1.35 times higher than controls among mothers when 677C>T polymorphism was evaluated alone, while 677CT/1298AC in the current study demonstrated a 3.8 times increase in this risk. These observations led us to conclude that although not statistically significant, MTHFR 1298AC polymorphism might be a risk factor for the occurrence of NTDs in the Turkish population.     

Celiac disease screening in 100 Turkish children with Down syndrome

The aim of this study was to screen a group of children with Down syndrome (DS) for celiac disease, and to define future strategies for screening the patients followed at our center. One hundred children over the age of two years with Down syndrome were serologically screened using antiendomysium antibody (EMA) IgA and serum IgA in order to exclude a concomitant IgA deficiency. Clinical assessment included detailed physical examination, measurement of weight and height plotted on growth charts for DS children followed by an interview of the patients and parents about gastrointestinal symptoms. Only one patient out of 100 (1%) was detected to be EMA IgA-positive. The child's family refused consent for the biopsy procedure. None of the patients had IgA deficiency. Abdominal distention was present in 13 (13%) patients, and anorexia in 9 (9%), vomiting in 7 (7%) and alopecia areata in 2 (2%) patients were also noted. Despite the small number of patients in our group, this result yielding 1% EMA-positivity is the lowest yet determined among DS patients. It has led us to discuss whether or not a change in our screening strategy is necessary.     

Familial aquagenic acrokeratoderma: case reports and review of the literature

In recent years, a number of authors have described the development of palmar or palmoplantar keratoderma after brief exposure to water. Herein, we report a father and son with this condition, which we prefer to call aquagenic acrokeratoderma. These cases are interesting because they mark the first documentation of this entity in males. Also, they provide further evidence of familial occurrence.