pinecone/core-2020-05-10-deduplication huggingface dataset:
Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient‐derived primary HNSCC specimens were analyzed for CSC‐proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non‐CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC‐proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 317–326, 201
Detection of Helicobacter pylori in head and neck cancer patients: Results from a prospective comparative study combining serology, PCR, and rapid urease test

BACKGROUND: The goal of this study was to evaluate prospectively the presence and impact of the gastric carcinogen Helicobacter pylori in the upper aerodigestive tract. Previous studies suggested it could represent a risk factor for head and neck squamous cell carcinoma.\ud
METHODS: Serology, rapid urease test, and quantitative polymerase chain reaction (qPCR) for H. pylori were performed in head and neck cancer patients (N=56) and cancer-free controls (N=90). Comparison between groups was done using logistic regression analysis.\ud
RESULTS: Rates of positive serology and rapid urease test did not differ between the two groups in logistic regression analysis (P=0.677 and P=0.633, respectively). Birth in a developing country and age above 50 years old were predictors of positive serology (P<0.001 and P=0.040, respectively). Using qPCR, no biopsy showed presence of H.pylori.\ud
CONCLUSION: This study challenges the concept that H. pylori may be a risk factor for head and neck squamous cell carcinoma. This article is protected by copyright. All rights reserved
Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds.

<p>Background: Microenvironmental cues play a major role in head and neck cancer. Biodegradable scaffolds used for bone regeneration might also act as stimulative cues for head and neck cancer. The purpose of this study was to establish an experimental model for precise and noninvasive evaluation of tumorigenic potential of microenvironmental cues in head and neck cancer.</p>
<p>Methods: Bioluminescence was chosen to image tumor formation. Early neoplastic oral keratinocyte (DOK) cells were luciferase-transduced (DOKLuc), then tested in nonobese diabetic severe combined immunodeficient IL2r&gamma;null mice either orthotopically (tongue) or subcutaneously for their potential as &ldquo;screening sensors&rdquo; for diverse microenvironmental cues.</p>
<p>Results: Tumors formed after inoculation of DOKLuc were monitored easier by bioluminescence, and bioluminescence was more sensitive in detecting differences between various microenvironmental cues when compared to manual measurements. Development of tumors from DOKLuc grown on scaffolds was also successfully monitored noninvasively by bioluminescence.</p>
<p>Conclusion: The model presented here is a noninvasive and sensitive model for monitoring the impact of various microenvironmental cues on head and neck cancer in vivo.</p
Geographic variation in human papillomavirus-related oropharyngeal cancer: Data from 4 multinational randomized trials

Background. There are variations in the proportions of head and neck cancers caused by the human papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays. Methods. We tested formalin-fixed paraffin-embedded diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs). Results. Twenty-one percent of patients (170 of 801) showed both HPV-DNA and p16-positivity, detected almost exclusively in oropharyngeal cancer (55%; 15 of 302); and only 1% of the patients (5 of 499) with nonoropharyngeal cancer were HPV positive. HPV-positive oropharyngeal cancer differed between Western and Eastern Europe (37%, 155 of 422 vs 6%, 8 of 144; p < .0001) and between Western Europe and Asia (37% vs 2%; 4 of 217; p < .0001). Other independent determinants of HPV positivity were tumor site and smoking. Conclusion. This is the first study to establish geographic variability as an independent risk factor in HPV-positive oropharyngeal cancer prevalence, with higher prevalence in Western Europe. (C) 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc
Impact of chemotherapy on the outcome of osteosarcoma of the head and neck in adults

Contains fulltext :
                  169705.pdf (publisher's version ) (Open Access)BACKGROUND: There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. METHODS: All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. RESULTS: We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). CONCLUSION: In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local recurrence. Therefore, we suggest (neo-)adjuvant chemotherapy in patients amenable to chemotherapy. (c) 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 140-146, 2017
Human papillomavirus and other biomarkers in neck masses of unknown origin and in head and neck cancer

Background. Human papillomavirus (HPV) is, in addition to smoking and alcohol, a risk factor for developing oropharyngeal squamous cell carcinoma (OPSCC), and more specifically tonsillar- and base of tongue squamous cell carcinoma (TSCC & BOTSCC respectively). Interestingly, HPV-positive (HPV+) TSCC/BOTSCC has a remarkably better clinical outcome than HPV-negative (HPV-) TSCC/BOTSCC and head and neck cancer in general. However, the role of HPV and other biomarkers in cancer of unknown primary in the head and neck region (HNCUP), i.e. where only a lymph node metastasis and no primary tumour is found, is not well understood. Moreover, the genetic landscape of HPV-positive HNCUP and the prognostic implications of certain mutations in TSCC/BOTSCC has not been studied extensively. Furthermore, using fine-needle aspiration cytology (FNAC) from neck masses for HPV-detection and potentially for predicting an HPV-positive TSCC/BOTSCC as the final diagnosis would be highly clinically useful, but has not been studied prospectively in a cohort consisting of both malignant and benign neck masses.



Aims. To investigate HPV DNA and mRNA and other prognostic biomarkers (p16, p53, CD8+ tumour infiltrating lymphocytes (TILs), HLA Class I expression) in HNCUP in relation to clinical outcome. Moreover, to study mutations in HPV+ HNCUP and TSCC/BOTSCC in relation to prognosis and to analyse whether HPV-detection in FNAC from neck masses is reliable and if a finding of HPV could predict an HPV+ TSCC/BOTSCC as the final diagnosis.



Results. In Paper I, we show that HPV is a favourable prognostic factor in HNCUP, and in Paper II, we validate this finding in a separate cohort (3-year overall survival 86% vs. 54% for HPV+ and HPV- HNCUP respectively, in the combined cohorts). In Paper II, we also demonstrate that HPV mRNA is expressed in the vast majority of HPV DNA+ HNCUP. Moreover, in Paper I we find that high p53-expression correlates to a poor prognosis, and in Paper II that a low number of CD8+ TILs are potentially related to a poor outcome, while HLA Class I expression does not appear to be a prognostic factor in HNCUP. In Paper III, we show that TP53, CDKN2A and PIK3CA are the most commonly mutated genes in HPV+ HNCUP, and that having a mutation in FGFR3 correlated to a poor prognosis in HPV+ TSCC/BOTSCC. In Paper IV, we demonstrate that HPV DNA detection in FNAC from neck masses of unknown origin is reliable and could be used prospectively to predict an HPV+ TSCC/BOTSCC as the final diagnosis. HPV DNA was not found in malignant conditions other than HPV+ TSCC/BOTSCC or in any benign conditions, including branchial cleft cysts.



Conclusions. HPV appears to have a similar causative and prognostic role in HNCUP as in TSCC/BOTSCC. Investigation of HPV-status should therefore be part of the diagnostic work-up of an HNCUP. Examination of HPV DNA-status using FNAC is useful in the clinical investigation of patients with neck masses of unknown origins, including patients eventually diagnosed with HNCUP or TSCC/BOTSCC
Androgen deprivation therapy for androgen receptor-positive advanced salivary duct carcinoma: A nationwide case series of 35 patients in The Netherlands

Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT). Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care. Results: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P=.02). Conclusion: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit
Morphologic and Biochemical Changes in Dogs After Portacaval Shunt Plus Bile Fistula or Ileal Bypass: Failure of Bile Fistula or Ileal Bypass to Prevent Hepatocyte Atrophy

External biliary fistula (BF) or ileal bypass (IB) was performed in dogs at the time of or 2 weeks after portacaval shunt (PCS). The pathologic changes in the dog livers 2 to 4 weeks later were compared to those caused by PCS alone. Histopathologic differences between PCS alone vs. PCS plus BF or IB could not be found. Thus, the experiments did not confirm recent observations by others in rats that BF prevents or reverses the hepatic injury of PCS. As estimated by plasma mevalonic acid determinations, the increase in hepatic cholesterol synthesis that is characteristic after BF or IB was suppressed in animals with PCS. BF and IB reduced but did not eliminate the postprandial elevation in serum bile acid that occurs after PCS. The findings have possible relevance in planning the treatment of patients with familial hypercholesterolemia with the combined use of PCS and IB. Copyright © 1983 American Association for the Study of Liver Disease
Idiopathic Hemochromotosis and Alpha‐1‐Antitrypsin Deficiency: Coexistence in a Family with Progressive Liver Disease in the Proband

A patient with coexistent hemochromatosis and alpha‐1‐antitrypsin deficiency which led to cirrhosis and death despite adequate therapy for hemochromatosis is reported. Evaluation of the family revealed first degree relatives with iron overload and others with alpha‐1‐antitrypsin deficiency but none with both conditions. The role of family studies in the early recognition and possible prevention of overt clinical disease in individuals with either of these two genetic diseases is discussed. Copyright © 1983 American Association for the Study of Liver Disease
Liver Procurement for Orthotopic Transplantation: An Analysis of the Pittsburgh Experience

The incidence of prospective organ donors in the United States and the techniques which are to used to guarantee their optimal use after identification are analyzed. Attitudes of the public and health professionals toward organ donation are discussed. The organization of the Pittsburgh Organ Procurement Agency and its relationship to other such agencies is described. Finally, the presently used techniques of liver salvaging and preservation are outlined. Copyright © 1984 American Association for the Study of Liver Disease
Prognostic value of thyroid hormone levels in patients evaluated for liver transplantation

The thyroid hormones T4, T3, rT3 and TSH were assayed in 134 adult patients evaluated and accepted as potential liver transplant candidates at the Universty of Pittsburgh from March, 1981 to December, 1983. The subsequent course of these patients was evaluated with respect to the levels of these hormones obtained at the time of acceptance for transplantation. T4 levels were increased significantly while their T3 levels were reduced (both p < 0.01) in those who survived and were discharged home as compared to either those who died waiting to be transplanted or died following the procedure. As a result, the ratio of T3/T4 was reduced markedly (p < 0.01) in those who were transplanted and survived as compared to those not transplanted or dying following transplantation. Importantly, the rT3 levels clearly separated (p < 0.01) those who would die prior to transplantation from those who would survive to be transplanted. Finally, the ratio rT3/T3 even more clearly separates those who will die prior to transplantation (p < 0.01) from the other two groups. These data suggest that thyroid hormone levels, particularly rT3 levels, might be useful in setting priorities for which patients referred for a transplantation evaluation should be accepted into the program and in determining who among accepted patients should be operated upon in preference to others also accepted and waiting to be transplanted. Copyright © 1985 American Association for the Study of Liver Disease
Value of Ascitic Lipids in the Differentiation between Cirrhotic and Malignant Ascites

Ascitic fluid concentrations of cholesterol, triglycerides and phospholipids, were compared with ascitic fluid total protein in 40 patients with chronic liver disease, 51patients with various neoplasms and 1 patient with cardiac failure. Seven patients withboth chronic liver disease and malignancy were considered separately. The first 54 patients (23 cirrhotic and 31 with malignancy) were used to determine median values and ranges and to define the most suitable cutoff concentrations between both groups. Median values for cholesterol (75 mg per dl), phospholipids (0.79 mmole per liter), triglycerides (75 mg per dl) and protein (3.8 gm per dl)were higher in malignant ascites compared to ascitic fluid concentrations of cholesterol (20 mg per dl), phospholipids (0.33 mmole per liter), triglycerides (51 mg per dl) and protein (1.9 gm per dl) in patients withcirrhosis. The best discrimination values were 48 mg per dl for cholesterol, 0.6 mmole per liter for phospholipids, 65 mg per dl for triglycerides and 2.5 gm per dl for protein. Application of these cutoff points to 38 subsequent patients (17 cirrhotic, 1 with cardiac failure and 20 with malignancy) revealed an efficiency of 86.8% for cholesterol, 86.8% for phospholipids, 68.4% for triglycerides and 79.0% for protein. From the data of all 92 patients, an efficiency of 92.3% forcholesterol, 79.4% for phospholipids, 72.8% for triglycerides and 79.4% for protein was calculated.
We conclude that ascitic fluid cholesterol determination offers an excellent, cost-effective discrimination of ascites due to cirrhosis vs. ascites caused by malignancies.
Adult liver transplantation: An analysis of the early causes of death in 40 consecutive cases

One hundred twenty‐nine adult patients who received an orthotopic liver transplantation and survived at least 24 hr after surgery were evaluated. During the period of follow‐up, 48 of the 129 patients (37%) died. Only 40 of these 48 patients died at our institution and were included in this study. Seventeen of the 40 deaths (42.5%) occurred during the first month after orthotopic liver transplantation and 30 of the 40 deaths (75%) occurred during the first 60 days post‐orthotopic liver transplantation. Death was related to infection in 21 cases (52.5%), to multiorgan failure in 8 (20%) and to uncontrollable rejection in 3 (7.6%). The remaining eight deaths (20%) were attributed to a variety of other causes. Eleven of the 21 deaths related to infection (52%) occurred during the first month after orthotopic liver transplantation. Bacterial sepsis was the leading cause of death and accounted for 17 of the 21 deaths (81%) in which infection was present at the time of death. The most frequently isolated bacteria were Pseudomonas and other enteric Gram‐negative bacilli. Three patients had complete occlusion of the hepatic artery of the grafted liver. Six patients developed massive infarction of the liver despite patent vascular anastomoses. Histological signs of rejection were seen in 9 of the 31 patients autopsied (29%), but in only 3 of these (9.6%) was rejection the principal cause of death. The biliary anastomoses were patent in all 31 cases examined at autopsy. Copyright © 1986 American Association for the Study of Liver Disease
Prognostic value of preoperatively obtained clinical and laboratory data in predicting survival following orthotopic liver transplantation

Twenty‐seven clinical and laboratory data and the subsequent clinical course of 93 consecutive adult patients who underwent orthotopic liver transplantation for various chronic advanced liver diseases were analyzed retrospectively to assess the risk factors of early major bacterial infection and death after the procedure. Forty‐one patients (44%) had early major bacterial infection during hospitalization for orthotopic liver transplantation. The mortality rate was 70.7% in patients with early major bacterial infection and was 7.7% in patients without early major bacterial infection (p < 0.001). Total serum bilirubin, total white blood cell count and polymorphonuclear cell count, IgG (all p < 0.05) and plasma creatinine level (p < 0.001) were higher in patients that developed early major bacterial infection than in those who did not. By step‐wise discriminant analysis, the strongest risk factor for early major bacterial infection was the serum creatinine level, which achieved an accuracy of 69% for a creatinine level greater than 1.58 mg per dl. Seven variables (ascites, hepatic encephalopathy, elevated white blood and polymorphonuclear cell count, decreased helper to suppressor T cell ratio and elevated plasma creatinine and bilirubin levels) were associated with a significant increased risk for death. A step‐wise discriminant analysis of these seven factors resulted in the demonstration of serum creatinine as the greatest risk factor for mortality. A preoperative serum creatinine either less than or greater than 1.72 mg per dl accurately predicts survival or death, respectively, in 79% of cases. These data suggest that the baseline preoperative serum creatinine level provides the best indication of the short‐term prognosis after liver transplantation than does any other preoperatively obtained index of the patient's status. Copyright © 1986 American Association for the Study of Liver Disease
The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D‐galactosamine

Galactosamine induces a dose‐dependent hepatic injury in rats and many other animals. The toxicity of D‐galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D‐galactosamine‐induced hepatic necrosis in rats. D‐Galactosamine (2.6 gm per kg of body weight) was administered intraperitoneally to 438 male Lewis strain rats. The animals were divided into six groups according to the type of treatment: Group 1 (n = 131) saline; Group 2 (n = 40) cytosol (75 mg total protein); Group 3 (n = 75) hepatic stimulatory substance (20 mg total protein); Group 4 (n = 42) 300,000 subfraction (4 mg total protein); Group 5 (n = 68) 300,000 subfraction (2 mg total protein), and Group 6 (n = 82) 50,000 subfraction (0.6 mg total protein). All rats received 4 ml of the test solution intraperitoneally at 48 hr after D‐galactosamine administration. The percentage of rats surviving in each group was determined daily for 20 days. Although hepatic stimulatory substance and 50,000 subfraction tended to improve survival in intoxicated rats, only those rats treated with the 300,000 subfraction attained statistical significance with respect to the saline control. Copyright © 1986 American Association for the Study of Liver Disease