bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemopreventive Effect of a Novel Nutrient Mixture on Lung Tumorigenesis Induced by Urethane in Male A/J Mice
Authors: Roomi M Waheed , Roomi Nusrath W , Kalinovsky Tatiana , Rath Matthias , Niedzwiecki Aleksandra 
Published: February 2018

Aims and background Lung cancer, a leading cause of cancer death, is associated with exposure to inhalation carcinogens, most commonly those found in tobacco smoke. We investigated the in vivo effect of dietary supplementation with a nutrient mixture containing lysine, proline, arginine, ascorbic acid, green tea extract, N-acetyl cysteine, selenium, copper and manganese on the development of urethane-induced lung tumors in male A/J mice. Methods After one week of isolation, seven-week-old male A/J mice (n = 25) weighing 17–19 g were randomly divided into three groups: group A (n = 5), group B (n = 10), and group C (n = 10). Mice in groups B and C were each given a single intraperitoneal injection of urethane (1 mg/g body weight) in saline, whereas group A mice received an injection of saline alone. Groups A and B were fed a regular diet, whereas group C was fed the same diet supplemented with 0.5% nutrient mixture. After 20 weeks, mice were sacrificed, lungs were excised and weighed, and tumors were counted and processed for histology. Results Urethane-challenged mice developed tumors. However, the mean number of tumors and the mean lung weights in the mice on the supplemented diet were significantly reduced, by 49% (P <0.0001) and 18% (P = 0.0025), respectively, compared to mice on the control diet. We observed neither significant differences in body weight gains nor in diet consumption among the mice. Pulmonary lesions were morphologically similar for both the groups (adenomas), but lesions were smaller in the test group. Conclusions The results suggest that nutrient mixture has inhibitory potential on the development of mouse lung tumors induced by urethane
Tailgut Cyst, an Unusual Cause of Pseudomyxoma Peritonei
Authors: Zappa Luis , Godwin Thomas A , Sugarbaker Paul H 
Published: February 2018

Background Retrorectal hamartoma, also known as tailgut cyst, is a rare tumor that arises from remnants of the embryonic postanal gut. The tumor occurs in the retrorectal space and may undergo malignant degeneration. Methods The clinical information on a single patient with pseudomyxoma peritonei associated with a tailgut cyst was reviewed and a literature review of the subject performed. Results In this patient there was malignant degeneration of a tailgut cyst localized to the pelvis. Twenty months later a local recurrence in the pelvis and pseudomyxoma peritonei widely distributed in the abdomen were successfully treated by cytoreductive surgery and perioperative chemotherapy. Conclusion Tailgut cyst may, if resected with tumor spillage, result in pseudomyxoma peritonei. Our treatment – which has maintained a disease-free status for one year – was cytoreductive surgery plus perioperative chemotherapy.
Fulminant Liver Failure in a Patient Affected by Polycystic Liver Disease and Liver Metastases from Breast Carcinoma
Authors: Fadda Giovanni Maria , Santeufemia Davide Adriano , Cossu-Rocca Paolo , Bardino Gianfranco , Costantino Salvatore , Sanna Giovanni , Sarobba Maria Giuseppa , Farris Antonio 
Published: February 2018

Background Polycystic liver disease (PLD) is a rare, congenital, benign condition characterized by the presence of multiple bile-duct-derived epithelial cysts in the liver parenchyma. The disease is usually asymptomatic, but cyst growth can result in complications such as ascites, esophageal varices, jaundice and hepatic failure. The exact mechanism leading to cyst growth is unclear, but estrogenic stimulation and paracrine action of vascular endothelial growth factor (VEGF) are thought to play a role in the growth of cyst epithelium. Case report We report a case of acute liver failure in a young woman with PLD and liver metastases from breast carcinoma. Results No data are available in the literature about metastatic liver involvement in PLD patients affected by breast cancer. The prognosis of patients with liver metastases is generally poor but fulminant liver failure is a very rare occurrence. Estrogen stimulation seems to be a risk factor for breast cancer and severe PLD. In the reported case, the presence of either the cysts or the metastatic lesions may have resulted in more extensive liver damage. Conclusions The adoption of drugs selected in relation to their hepatic toxicity together with careful monitoring of liver function is warranted in the management of breast cancer patients affected by PLD, in order to reduce the risk of liver failure.
Strong Seasonality in the Diagnosis of Skin Melanoma in Italy: The Italian Network of Cancer Registries (AIRTUM) Study
Authors: Crocetti Emanuele , Guzzinati Stefano , Paci Eugenio , Falcini Fabio , Zanetti Roberto , Vercelli Marina , Rashid Ivan , De Lisi Vincenzo , Russo Antonio , Vitarelli Susanna , Ferretti Stefano , Mangone Lucia , Cesaraccio Rosaria , Tumino Rosario , Busco Susanna , Buzzoni Carlotta 
Published: February 2018

Aim To evaluate seasonality in the diagnosis of cutaneous melanoma in Italy. Methods A total of 16,284 invasive (and 1,235 in situ) cutaneous melanomas incident from 1978 to 2002 in 14 cancer registries belonging to the Italian Network of Cancer Registries (AIRTUM) was analyzed. We used the Walter and Elwood test to evaluate seasonality. The monthly distribution of diagnosis was evaluated for sex, skin site, melanoma morphology and period of diagnosis. Results The overall monthly diagnosis of invasive melanoma showed a statistically significant excess around the month of June. The same pattern was present for males and females, across age-groups and periods of time. All skin sites showed a cycling trend, melanoma of the head and neck peaked around April, all the others peaked around June. As regards morphologic types, a cyclic trend was evident for superficial-spreading melanomas (peak around July), for not-specified melanomas (June) and for other histotypes (June). Diagnosis of in situ melanoma peaked in September. Conclusions The present study showed that also in Italy melanoma diagnosis has a seasonal trend, with the peak in early summer. It seemed that summer UV exposure, acting both as a late promoter of malignant melanoma development and also increasing the visibility of pigmented skin lesion, may be relevant to explain such a peak.
Sentinel Lymph Node Biopsy in Patients with Pure and High-Risk Ductal Carcinoma in Situ of the Breast
Authors: D'eredità Giovanni , Giardina Carmela , Napoli Anna , Ingravallo Giuseppe , Leopoldo Troilo Vito , Fischetti Fernando , Berardi Tommaso 
Published: February 2018

Aims and Background The role of sentinel lymph node biopsy in patients initially diagnosed with ductal carcinoma in situ resides in determining the predictors of invasive disease. The aim of the present study was to examine the incidence of sentinel lymph node metastases in a selected group of patients, with characteristics of high-risk ductal carcinoma in situ, in order to determine the clinical usefulness of sentinel lymph node biopsy. Methods A total of 90 patients with a biopsy diagnosis of ductal carcinoma in situ were treated. Fifty-two patients with high-risk ductal carcinoma in situ had sentinel lymph node biopsy. The following characteristics of the primary tumor were considered as indicative of a risk of invasive disease: presence of palpable mass, mammographic mass, multicentric disease that required mastectomy, and histologically high nuclear grade or non-high nuclear grade with necrosis. Subdermal injections of 99mTc-labeled human albumin and subareolar injection ofblue dye were used for sentinel lymph node identification. All sentinel nodes were sectioned serially and stained with hematoxylin and eosin. Immunohistochemical analysis was performed using a cytokeratin monoclonal antibody. Results A positive sentinel lymph node was found in only one patient (1.9%). The patient had a double lesion, and core-needle biopsy showed an atypical ductal hyperplasia and a intermediate degree of ductal carcinoma in situ. At pathologic review of the specimen, no invasive aspect was detected. Conclusions The results of our study indicate that sentinel lymph node metastasis in pure ductal carcinoma in situ is extremely uncommon. We therefore suggest that sentinel lymph node biopsy might be indicated for patients with ductal carcinoma in situ detected as a palpable mass or as large extensive microcalcifications, as well as for patients who are undergoing mastectomy, especially with immediate reconstruction.
DNA/RNA Markers for Colorectal Cancer Risk in Preserved Stool Specimens: A Pilot Study
Authors: Kato Ikuko , Badsha Kawsar Z , Land Susan , Nechvatal Jordan M , Matherly Larry H , Tarca Adi L , Majumdar Adhip P , Basson Marc D , Ram Jeffrey L 
Published: February 2018

Aims and Background Exfoliated cells in human stool offer excellent opportunities to non-invasively detect molecular markers associated with colorectal tumorigenesis, and to evaluate the effects of exposures to exogenous and endogenous carcinogenic or chemopreventive substances. This pilot study investigated the feasibility of determining DNA methylation and RNA expression simultaneously in stool specimens treated with a single type of nucleic acid preservatives. Methods Stool specimens from 56 volunteers that were preserved up to a week with RNAlater were used in this study. Bisulfite sequencing was used to determine methylation at 27 CpG loci on the estrogen receptor 1 ( ESR1) promoter. Taqman assay was used for quantitative reverse transcription polymerase chain reactions to measure cyclooxygenase 2 ( COX2) and epidermal growth factor receptor ( EGFR) mRNA expression. Subjects’ basic demographic and other selected risk factors for colorectal cancer were captured through questionnaires and correlated with the levels of these markers. Results Less than 10% of the samples failed in individual assays. Overall, 24.0% of the CpG loci on the ESR1 promoter were methylated. COX2 expression and alcohol use were positively correlated; an inverse association was present between EGFR expression and cigarette smoking; and subjects using anti-diabetic medication had higher ESR1 methylation. In addition, higher EGFR expression levels were marginally associated with history of polyps and family history of colorectal cancer. Conclusions The present study demonstrates that simultaneous analyses for DNA and RNA markers are feasible in stool samples treated with a single type of nucleotide preservatives. Among several associations observed, the association between EGFR expression and polyps deserves further investigation as a potential target for colorectal cancer screening. Larger studies are warranted to confirm some of our observations.
Distribution of 4-Hydroxynonenal-Protein Conjugates as a Marker of Lipid Peroxidation and Parameter of Malignancy in Astrocytic and Ependymal Tumors of the Brain
Authors: Juric-Sekhar Gordana , Zarkovic Kamelija , Waeg Georg , Cipak Ana , Zarkovic Neven 
Published: February 2018

Aims and Background Lipid peroxidation (LPO) is an autocatalytic process caused by oxidative stress. It results in the production of 4-hydroxynonenal (HNE), which plays a crucial role in hypoxic brain injury, neuronal degeneration and apoptosis. The aim of this study was to evaluate the expression of HNE in 120 astrocytic and 40 ependymal tumors in relation to tumor type, grade of malignancy, angiogenesis, and presence of necrosis and apoptosis. Methods Immunohistochemical staining was performed using a monoclonal antibody for the detection of HNE-modified proteins. Results HNE-protein adducts were found in all tumors. The incidence of HNE-im-munopositive tumor cells increased with increasing grades of malignancy. Significantly higher HNE expression was found in tumor cells of glioblastomas multiforme than in cells of pilocytic astrocytomas ( P <0.005), and in anaplastic ependymomas than in benign ependymomas ( P <0.01). HNE-immunopositive tumor cells were distributed more diffusely than in perivascular locations ( P <0.05). Pronounced HNE-protein adducts were detected in mitotic, necrotic, and apoptotic cells. HNE was expressed in the endothelium of almost all tumor vessels, but its expression in the walls of the vessels was significantly higher in diffuse and anaplastic astrocytomas than in pilocytic astrocytomas and glioblastomas multiforme ( P <0.05). The number of microvessels containing HNE in their endothelium and walls was significantly associated with the grade of malignancy in both astrocytic ( P <0.001) and ependymal tumors ( P <0.05), although microvessels in pilocytic astrocytomas were significantly more numerous ( P <0.05) than in diffuse astrocytomas. Conclusions LPO seems to be a common pathological process in astrocytic and ependymal glial tumors, proportional to the level of malignancy and neovascularization. Therefore, HNE might be involved in the damage of brain cells and the induction of malignancy.
Fibronectin Promotes Tyrosine Phosphorylation of Paxillin and Cell Invasiveness in the Gastric Cancer Cell Line AGS
Authors: Li Dan , Ding Jian , Wang Xiaozhong , Wang Chengdang , Wu Ting 
Published: February 2018

Aims and Background Paxillin is a central protein within the focal adhesion and serves as a critical transducer of signals from fibronectin. Although abnormal expression of fibronectin and paxillin is often observed during the development of human malignancies, the relationship between paxillin and cell invasion in gastric cancer is still unclear. The current study was designed to investigate the potential role and mechanisms of fibronectin in tyrosine phosphorylation of paxillin and in the invasiveness of gastric cancer cells. Methods Expression of paxillin in human gastric cancer samples was examined by immunohistochemical staining. A gastric cancer cell line, AGS, was stimulated by fibronectin with gradient concentrations, and expression of paxillin and phosphorylation of paxillin tyrosine 118 (tyr118) was detected by immunoprecipitation and Western blotting. The invasiveness of AGS cells was measured by the modified Boyden chamber assay. Small interfering RNA (siRNA) targeting paxillin was used to establish the role of paxillin (tyr118) in the process of cell invasion enhanced by fibronectin. siRNA targeting focal adhesion kinase (FAK) was used to verify the effect of FAK tyrosine 397 (tyr397) on phosphorylation of paxillin(tyr118). Results Positivity for paxillin staining in human gastric cancer was associated with tumor stage. AGS cell showed dose dependence on fibronectin for invasiveness and phosphorylation of paxillin (tyr118). Invasiveness and phosphorylation of paxillin(tyr118) in AGS cells reached their peak when the concentration of fibronectin reached 100 nmol/L. siRNA targeting paxillin decreased the phosphorylation of paxillin(tyr118) and the invasiveness of AGS cells significantly as compared with controls. Blockage of FAK(tyr397) can inhibit phosphorylation of paxillin(tyr118) stimulated by fibronectin. Conclusions Fibronectin promotes paxillin(tyr118) phosphorylation and invasiveness of AGS cells. Paxillin silencing by RNA interference inhibits the cell invasiveness stimulated by fibronectin. Paxillin is a key factor in the fibronectin-stimulated invasiveness of AGS cells.
Inhibition of HER2/estrogen Receptor Cross-Talk, Probable Relation to Prolonged Remission of Stage IV Breast Cancer: A Case Report
Authors: Tisman Glenn 
Published: February 2018

Metastatic breast cancer to the liver is considered incurable. Though many patients with liver metastases may enjoy response to chemo-, immuno- and hormonal therapy, those so inflicted rarely remain disease-free from the time of diagnosis for longer than 6-11 months. New laboratory and clinical research identified that cross-talk between activation of the epidermal growth factor family of tyrosine kinase transduction pathways (EGF/HER2) and estrogen receptor (ER) activation plays a role in resistance to hormonal therapy. A 59-year-old woman with a 4.5-cm invasive ductal, ER-positive/PR-negative, grade III adenocarcinoma of the breast was treated with mastectomy. Staging revealed biopsy-proven liver metastases. Surgery was immediately followed with vinorelbine, trastuzumab, tamoxifen and exemestane. The patient underwent a bone scan and PET/CT documented complete remission. She has remained in complete remission for 7 years. It is proposed that a possible mechanism for prolonged remission of stage IV breast cancer in this patient may be related to suppression of EGF/HER2 by trastuzumab, thus inhibiting cross-talk-associated tamoxifen/estrogen withdrawal resistance.
Relevance of Two Genes in the Multidrug Resistance of Hepatocellular Carcinoma: In Vivo and Clinical Studies
Authors: Sun Zhengang , Zhao Zizhuo , Li Gaopeng , Dong Shengli , Huang Zhiyong , Ye Lu , Liang Huifang , Qu Junyuan , Ai Xi , Zhang Wanguang , Chen Xiaoping 
Published: February 2018

Aims and background A former study evaluated the roles of four multidrug resistance-related proteins, namely multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance-related protein (MRP1), and lung resistance-related protein (LRP), in the MDR mechanism of the multidrug resistant hepatoma HepG2/ADM cell line and proposed that up-regulated MDR1 and BCRP are responsible for the MDR of hepatocellular carcinoma. This work aims to confirm that assumption in vivo and in clinical specimens. Methods First, the chemotherapeutic resistance of subcutaneous HepG2/ADM tumor and hepatocellular carcinoma samples post-transarterial chemoembolization (TACE) was determined by MTT, contrary to subcutaneous HepG2 tumor and hepatocellular carcinoma samples without TACE, respectively. Then, the mRNA and protein differential expression of the four genes between the MDR tissues and drug-sensitive tissues were quantitatively investigated by real-time RT-PCR and enhanced chemiluminescence western blot analysis, respectively. Results 1) mRNA expression of BCRP and MDR1 was respectively amplified 38.3 and 20.1 fold in tumors of HepG2/ADM mice compared to those of HepG2 mice, whereas they were respectively augmented for 14.6 and 9.3 times in TACE samples, contrary to the tumor tissues without TACE. 2) The protein presence of MDR1 and BCRP in MDR tumors was also significantly higher than those in the control group in vivo and in clinical specimens. 3) The mRNA expressions of MDR1 and BCRP were correlated to their protein levels. Conclusions The study showed that MDR1 and BCRP may be the most important factors for drug resistance in hepatocellular carcinoma. Moreover, the positive correlation between their mRNA and protein expression indicates the easy prediction of HCC MDR and possible inhibitive target of drug resistance at multi-levels.
Prognostic Factors in Cancer of Unknown Primary Site
Authors: Fernandez-Cotarelo Maria Jose , Guerra-Vales Juan Manuel , Colina Francisco , de la Cruz Javier 
Published: February 2018

Aims and background Patients with cancer of an unknown primary site (CUP) usually have a poor outcome. The identification of prognostic factors that affect survival can help clinicians find a better approach to such cases in terms of diagnostic and therapeutic management. Methods We conducted a retrospective study including the cases of CUP recorded at the University Hospital 12 de Octubre Tumor Registry between 1999 and 2003. Results CUP was diagnosed in 265 patients during the analyzed period. One hundred and seventy-one were men (64.5%) and the mean age of the patients was 66.9 years (range 32–98 years). The median survival was 2.5 months, and the survival rate was 35.1% 6 months from diagnosis (95% CI: 28.9–41.3) and 24.5% 1 year from diagnosis (95% CI: 18.7–30.3). Univariate analysis revealed as significant predictive variables of a better outcome age under 70 years; involvement of a single organ; normal serum levels of alkaline phosphatase and albumin; normal erythrocyte sedimentation rate; normal levels of the serum tumor markers CEA, CA 19.9 and CA 15.3; squamous carcinoma histology; clinical presentation as lymph node enlargement; and the administration of treatment. Multivariate analysis showed that albumin and alkaline phosphatase levels, squamous carcinoma histology, age and treatment were the most important prognostic factors. Other variables analyzed (liver, bone or lung involvement, lactate dehydrogenase levels, gender) did not affect survival. Conclusions CUP has a poor prognosis. Some prognostic factors that affect survival in these patients, however, may be identified.
Carboplatin and Etoposide Followed by Once-Daily Thoracic Radiotherapy in Limited Disease Small-Cell Lung Cancer: Unsatisfactory Results
Authors: Yilmaz Ufuk , Anar Ceyda , Korkmaz Esra , Yapicioglu Sena , Karadogan Ilker , Ozkök Serdar 
Published: February 2018

Aims and background There has been a trend to replace cisplatin with carboplatin in the treatment of small-cell lung carcinoma. The goal of the present study was to determine the efficacy of carboplatin and etoposide followed by thoracic radiotherapy in patients with previously untreated limited disease small-cell lung carcinoma. Methods From February 2001 to March 2007, 47 patients with limited disease small-cell lung cancer were enrolled in the study. Etoposide, 100 mg/m2, was administrated intravenously on days 1-3 in combination with carboplatin, AUC 6, on day 1 every 21 days for 6 cycles. In cases considered to have non-progressive disease following induction chemotherapy, thoracic radiotherapy was given with in a once daily fraction of 2.0 Gy, 5/wk, up to 50-60 Gy. Results Forty-one patients were evaluated. Median age was 62 (range, 40-78), 88% of patients were male. ECOG PS was 0-1 in 38 patients. Seven of the 41 patients (17.5%) had pleural effusion (one malignant) and 7 patients (17.5%) had involved supraclavicular lymph nodes. Ninety percent of patients had elevated serum lactate dehydrogenase levels. Median follow-up was 13.5 mo. A total of 209 cycles of chemotherapy was administered (median, 6; range, 1-6). Thoracic irradiation was given to 33 patients. The overall response rate to combined modality on an intention-to-treat basis was 73%. Median survival time was 13.7 months (95% CI, 10.3-17.1), and median progression-free survival was 9.5 months (95% CI, 8.6-10.4). Two- and four-year overall survival was 23% and 7%, respectively. Grade 3-4 neutropenia and leukopenia were the most common adverse events and occurred in 46.0% and 24.0% of the patients, respectively. Six (14%) patients experienced febrile neutropenia. Three patients (7%) died of sepsis and neutropenic fever. Non-hematological toxicities were mild. Conclusions Carboplatin and etoposide chemotherapy followed by thoracic radiotherapy in LD-SCLC appears to be unsatisfactory.