bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of Tropomysin-Related Kinase B in Metastatic Human Pancreatic Cancer Cells
Authors: Sclabas Guido M. , Fujioka Shuichi , Schmidt Christian , Li Zhongkui , Frederick Wayne A.I. , Yang Wentao , Yokoi Kenji , Evans Douglas B. , Abbruzzese James L. , Hess Kenneth R. , Zhang Wei , Fidler Isaiah J. , Chiao Paul J. 
Published: June 2022

Abstract
Purpose: Pancreatic adenocarcinoma is currently the fourth leading cause of cancer death in the United States, and most pancreatic cancers develop locally advanced disease or metastasis at the time of diagnosis. The mechanisms by which it invades and metastasizes are not known.
Experimental Design: To identify the genes involved in pancreatic cancer metastasis, we analyzed the gene expression profiles between highly metastatic Colo357L3.6pl and parental Colo357FG pancreatic cancer cell lines using cDNA microarrays and confirmed differential gene expression by reverse transcription-PCR, Western blotting, and immunologic analysis of 54 samples from pancreatic cancer patients. The correlation with clinical outcome was also examined. The possible signaling pathways involved with tropomyosin-related kinase B (TrkB) were analyzed.
Results: Our findings showed that TrkB was overexpressed in the highly metastatic Colo357L3.6pl cells, which correlated with perineural invasion (P = 0.026), positive retroperitoneal margin (P = 0.0005), and shorter latency to development of liver metastasis (Cox proportional hazard ratio, 0.3; 95% confidence interval, 0.1-0.8; P = 0.01) in patient samples. Extracellular signal-regulated kinases 1 and 2 were activated and Elk-1 and AP-1 DNA binding activity was induced in Colo357L3.6pl cells. Furthermore, interleukin 8 and vascular endothelial growth factor were more strongly expressed in Colo357L3.6pl than Colo357FG cells, and these findings were confirmed in Colo357L3.6pl and Colo357FG orthotopic tumors.
Conclusion: These results suggest that overexpression of TrkB and activation of mitogen-activated protein kinase and AP-1, which may in turn induce the expression of vascular endothelial growth factor and interleukin 8, may mediate the cardinal clinical features of locally aggressive growth and metastasis of pancreatic cancer. Our results also imply that TrkB receptor may be a novel therapeutic target for pancreatic cancer.
The Thioredoxin-1 Inhibitor 1-Methylpropyl 2-Imidazolyl Disulfide (PX-12) Decreases Vascular Permeability in Tumor Xenografts Monitored by Dynamic Contrast Enhanced Magnetic Resonance Imaging
Authors: Jordan Bénédicte F. , Runquist Matthew , Raghunand Natarajan , Gillies Robert J. , Tate Wendy R. , Powis Garth , Baker Amanda F. 
Published: June 2022

Abstract
Purpose: The purpose of this study was to use dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure changes in tumor xenograft permeability produced by the antitumor thioredoxin-1 (Trx-1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) and to assess the relationship to Trx-1 and vascular endothelial growth factor (VEGF) levels.
Experimental Design: DCE-MRI was used to monitor the dynamics of gadolinium-diethylenetriaminepentaacetic acid coupled bovine serum albumin as a macromolecular contrast reagent to measure hemodynamic changes in HT-29 human colon xenografts in immunodeficient mice treated with PX-12. Blood vessel permeability was estimated from the slope of the enhancement curves, and tumor vascular volume fraction from the ordinate. Tumor Trx-1 and VEGF was also measured.
Results: PX-12 caused a rapid 63% decrease in the average tumor blood vessel permeability within 2 hours of administration. The decrease lasted 24 hours and had returned to pretreatment values by 48 hours. The changes in vascular permeability were not accompanied by alterations in average tumor vascular volume fraction. There was a decrease in tumor and tumor-derived VEGF in plasma at 24 hours after treatment with PX-12, but not at earlier time points. However, tumor redox active Trx-1 showed a rapid decline within 2 hours following PX-12 administration that was maintained for 24 hours.
Conclusion: The rapid decrease in tumor vascular permeability caused by PX-12 administration coincided with a decrease in tumor redox active Trx-1 and preceded a decrease in VEGF. DCE-MRI responses to PX-12 in patients of Trx-1 inhibition at early time points and decreased VEGF at later times, may be useful to follow tumor response and even therapeutic benefit.
Age- and Disease-Related Methylation of Multiple Genes in Nonneoplastic Duodenum and in Duodenal Juice
Authors: Matsubayashi Hiroyuki , Sato Norihiro , Brune Kieran , Blackford Amanda Lapides , Hruban Ralph H. , Canto Marcia , Yeo Charles J. , Goggins Michael 
Published: June 2022

Abstract
Purpose: Methylation of CpG islands contributes to gene silencing during cancer development, and although some methylation alterations are promising diagnostic markers of cancer, some CpG islands are also methylated in normal tissues. We have previously observed that some normally unmethylated CpG islands that undergo methylation in pancreatic cancers are normally methylated in the adjacent duodenum. Because duodenal methylation patterns are an important consideration when sampling pancreatic tissues for pancreatic cancer methylation alterations, we determined the DNA methylation patterns of 24 genes in the normal duodenum of patients with pancreatic disease and related these patterns to demographic factors.
Experimental Design: The nonneoplastic duodenal mucosa of 158 patients with pancreatic carcinoma and 41 patients with chronic pancreatitis was analyzed using methylation-specific PCR and combined bisulfite restriction analysis. Secretin-stimulated pancreatic/duodenal juice from 15 individuals undergoing endoscopic investigation for upper gastrointestinal disease was also analyzed.
Results: Low-level methylation was detectable by methylation-specific PCR in the nonneoplastic duodenum of many patients with pancreatic cancer and chronic pancreatitis as well as in the pancreaticoduodenal secretions of patients without pancreaticobiliary disease. For many genes, the prevalence of methylation increased with age and was more prevalent in patients with pancreatic cancer than in age-matched patients with chronic pancreatitis.
Our results indicate that strategies to detect pancreatic cancer using aberrantly methylated genes should rely on analysis of pure pancreatic juice rather than on pancreatic juice collected within the duodenal lumen. Patients who develop pancreatic cancer may have a greater propensity to methylate CpG islands than age-matched controls.
Vaccination of Dendritic Cells Loaded with Interleukin-12-Secreting Cancer Cells Augments In vivo Antitumor Immunity: Characteristics of Syngeneic and Allogeneic Antigen-Presenting Cell Cancer Hybrid Cells
Authors: Suzuki Takuji , Fukuhara Tatsuro , Tanaka Masashi , Nakamura Akira , Akiyama Kenichi , Sakakibara Tomohiro , Koinuma Daizo , Kikuchi Toshiaki , Tazawa Ryushi , Maemondo Makoto , Hagiwara Koichi , Saijo Yasuo , Nukiwa Toshihiro 
Published: June 2022

Abstract
Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-γ production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.
Down-Regulation of S100C Is Associated with Bladder Cancer Progression and Poor Survival
Authors: Memon Ashfaque Ahmed , Sorensen Boe Sandahl , Meldgaard Peter , Fokdal Lars , Thykjaer Thomas , Nexo Ebba 
Published: June 2022

Abstract
Purpose: The goal of this study was to identify proteins down-regulated during bladder cancer progression.
Experimental design: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months).
Results: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P &lt; 0.0001] compared with superficial tumors (Ta). A negative correlation between S100C and histopathologic grade (P = 0.0003) was also observed. Furthermore, the papillary type showed higher expression of S100C than did the solid type of the tumor (P &lt; 0.0001). Importantly, we found that loss of S100C was associated with survival in bladder cancer patients (P = 0.0006).
Conclusions: Our results show that low expression of S100C is associated with poor survival in patients with bladder cancer. Furthermore, loss of S100C in T1 as compared with Ta stage tumors emphasize that S100C expression is suppressed early during bladder cancer development.
Gene Copy Number Change Events at Chromosome 20 and Their Association with Recurrence in Gastric Cancer Patients
Authors: Yang Sang Hwa , Seo Min Young , Jeong Ha Jin , Jeung Hei-Cheul , Shin Jihye , Kim Sang Chul , Noh Sung Hoon , Chung Hyun Cheol , Rha Sun Young 
Published: June 2022

Abstract
Purpose: This study examined the gene copy number change events at chromosome 20 in gastric cancer, and their possible relationship with recurrence using cDNA microarray-based comparative genomic hybridization.
Experimental Design: Thirty pairs of gastric tumor and normal gastric tissues were used in the cDNA microarray-based comparative genomic hybridization. The cDNA microarrays containing 17,000 sequence-verified human gene probes were used in a direct comparison design, where genomic DNAs from the normal and tumor tissues were labeled with fluorescent dyes Cy3 and Cy5, respectively, and cohybridized. Genes with log2 (Cy5/Cy3) ≥ 0.58 in at least one case were selected as the amplified genes. In order to search for the association between gene copy number changes and the recurrence status, patients were grouped according to their recurrence status. Gene selection between the two groups was done, and each patient was given a score based on the sum of the selected genes' ratios. Logistic regression analysis was carried out in order to determine if the score of a group of patients was correlated with a recurrence.
Results: A group of genes including NCOA6, CYP24A1, PTPN1, and ZNF217 was amplified in gastric cancer. Another group of 39 genes, whose sum of copy number change levels was significantly associated with a poor prognosis for recurrence, was selected (P &lt; 0.05).
Conclusion: Ninety-six amplified genes at chromosome 20 of gastric cancer are reported. A scoring system based on gene copy changes at chromosome 20 can provide an independent patient grouping system that can distinguish patient recurrence status and survival.
Classic and Molecular Cytogenetic Analyses Reveal Chromosomal Gains and Losses Correlated with Survival in Head and Neck Cancer Patients
Authors: Bérgamo Nádia Aparecida , da Silva Veiga Luciana Caricati , dos Reis Patricia Pintor , Nishimoto Inês Nobuko , Magrin José , Kowalski Luiz Paulo , Squire Jeremy A. , Rogatto Sílvia Regina 
Published: June 2022

Abstract
Purpose: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables.
Experimental Design: Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis.
Results: Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer.
Conclusions: The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.
Subcellular Localization of p27kip1 Expression Predicts Poor Prognosis in Human Ovarian Cancer
Authors: Rosen Daniel G. , Yang Gong , Cai Kathy Qi , Bast Robert C. , Gershenson David M. , Silva Elvio G. , Liu Jinsong 
Published: June 2022

Abstract
Purpose: The cyclin-dependent kinase inhibitor p27kip1 regulates cellular progression from G1 to S phase. Several studies have shown that loss of p27kip1 protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival.
Experimental Design: Subcellular localization of p27kip1 was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27kip1 protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma.
Results: The presence of p27kip1 in the cytoplasm regardless of the nuclear stain correlated strongly with late-stage disease (P &lt; 0.03), extent of cytoreduction (P = 0.03), and shorter disease-specific survival (P &lt; 0.0001).
Conclusion: Cytoplasmic localization of p27kip1 predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.
Gene Expression in Kidney Cancer Is Associated with Cytogenetic Abnormalities, Metastasis Formation, and Patient Survival
Authors: Sültmann Holger , Heydebreck Anja von , Huber Wolfgang , Kuner Ruprecht , Buneβ Andreas , Vogt Markus , Gunawan Bastian , Vingron Martin , Füzesí Laszlo , Poustka Annemarie 
Published: June 2022

Abstract
Current diagnosis of renal cancer consists of histopathologic examination of tissue sections and classification into tumor stages and grades of malignancy. Until recently, molecular differences between tumor types were largely unknown. To examine such differences, we did gene expression measurements of 112 renal cell carcinoma and normal kidney samples on renal cell carcinoma–specific cDNA microarrays containing 4,207 genes and expressed sequence tags. The gene expression patterns showed deregulation of complete biological pathways in the tumors. Many of the molecular changes corresponded well to the histopathologic tumor types, and a set of 80 genes was sufficient to classify tumors with a very low error rate. Distinct gene expression signatures were associated with chromosomal abnormalities of tumor cells, metastasis formation, and patient survival. The data highlight the benefit of microarrays to detect novel tumor classes and to identify genes that are associated with patient variables and tumor properties.
Phase I/II Study of the Rituximab-EPOCT Regimen in Combination with Granulocyte Colony-Stimulating Factor in Patients with Relapsed or Refractory Follicular Lymphoma Including Evaluation of Its Cardiotoxicity Using B-Type Natriuretic Peptide and Troponin T Levels
Authors: Niitsu Nozomi , Khori Mika , Hayama Miyuki , Kajiwara Koichi , Higashihara Masaaki , Tamaru Jun-ichi 
Published: June 2022

Abstract
Purpose: Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin is often given during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by doxorubicin-induced cardiomyopathy.
Experimental Design: The R-EPOCT (rituximab with etoposide, vincristine, pirarubicine, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic pirarubicine is used instead of doxorubicin, with granulocyte colony-stimulating factor (G-CSF) was administered to 20 patients with relapsed or refractory follicular lymphoma. The safety (especially cardiotoxicity) and efficacy of this regimen were studied. As markers of cardiotoxicity, serum troponin T and plasma B-type natriuretic peptide (BNP) levels were measured.
Results: Adverse reactions occurred in 14 of the 20 patients and mainly consisted of grade 3/4 hematologic toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated before the treatment in two patients and the BNP level did not significantly increase after R-EPOCT treatment. The troponin T level was undetectable before and after the treatment in all patients. The response rate was 100%, with complete remission in 16 patients (80%). G-CSF administration increased both Fc γ receptor type I expression on neutrophils and antibody-dependent cellular cytotoxicity activity. There were no significant differences in the levels of Fc γ receptor type I expression nor antibody-dependent cellular cytotoxicity activity after three or five cycles of the treatment.
Conclusion: We conclude that the combination of R-EPOCT and G-CSF is well tolerated. This regimen was not cardiotoxic. We are planning a randomized trial to compare the efficacy between R-EPOCT and a combination of R-EPOCT with G-CSF.
Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer
Authors: Demaria Sandra , Kawashima Noriko , Yang Anne Marie , Devitt Mary Louise , Babb James S. , Allison James P. , Formenti Silvia C. 
Published: June 2022

AbstractPurpose: Ionizing radiation therapy (RT) is an important component in the management of breast cancer. Although the primary tumor can be successfully treated by surgery and RT, metastatic breast cancer remains a therapeutic challenge. Here we tested the hypothesis that the combination of RT to the primary tumor with CTLA-4 blockade can elicit antitumor immunity inhibiting the metastases.Experimental Design: The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were injected s.c. with 4T1 cells, and treatment was started 13 days later when the primary tumors measured 5 mm in average diameter. Mice were randomly assigned to four treatment groups receiving: (1) control IgG (IgG), (2) RT + IgG, (3) 9H10 monoclonal antibody against CTLA-4, (4) RT + 9H10. RT was delivered to the primary tumor by one or two fractions of 12 Gy. 9H10 and IgG were given i.p. thrice after RT.Results: Consistent with the fact that 4T1 is poorly immunogenic, 9H10 alone did not have any effect on primary tumor growth or survival. RT was able to delay the growth of the primary irradiated tumor, but in the absence of 9H10 survival was similar to that of control mice. In contrast, mice treated with RT + 9H10 had a statistically significant survival advantage. The increased survival correlated with inhibition of lung metastases formation and required CD8+ but not CD4+ T cells.Conclusions: The combination of local RT with CTLA-4 blockade is a promising new immunotherapeutic strategy against poorly immunogenic metastatic cancers.
Therapy of Small Subcutaneous B-Lymphoma Xenografts with Antibodies Conjugated to Radionuclides Emitting Low-Energy Electrons
Authors: Michel Rosana B. , Rosario Adriane V. , Andrews Philip M. , Goldenberg David M. , Mattes M. Jules 
Published: June 2022

Abstract
Purpose: Radionuclides emitting low-energy electrons (Auger and conversion electrons of &lt;50 keV) are potentially useful for cancer therapy when conjugated to an antibody, because they can irradiate the cell to which they bind while producing relatively little irradiation of surrounding cells and tissues. We showed previously the ability of such antibody conjugates to treat micrometastatic, disseminated human B-lymphoma in a severe combined immunodeficient mouse model using an anti-CD74 antibody. In this study, we have evaluated the ability of such conjugates to treat s.c. tumors.
Experimental Design: Severe combined immunodeficient mice were injected s.c. with Raji, Daudi, or RL B-lymphoma human tumor cells. Antibodies to CD74, CD20, or HLA-DR were radiolabeled with 111In or 125I and injected i.v. at various times starting at day 5, and tumor growth was monitored. Controls included the testing of unlabeled antibodies, labeled nonreactive antibodies, and a combination of the two.
Results: Therapy of s.c. B-lymphoma was more difficult than therapy of tumor cells that had been injected i.v. Although large, macroscopic tumors were not effectively treated, therapy was effective on s.c. Daudi tumors on day 36 after injection of this slowly growing tumor, with an 111In anti-CD74 antibody given in two doses. An anti-CD20 antibody labeled with either 111In or 125I was able to effectively treat s.c. RL tumors when given as late as day 16 after tumor inoculation. The largest tumors that were effectively treated were macroscopic thin discs (&lt;2 mm in diameter) growing on the mesentery.
Conclusion: These results extend previous evidence that antibody conjugates with emitters of low-energy electrons can be effective therapeutic agents for micrometastatic cancer.