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At least 19 recordsLinked to original sources
PubMed1992

Coordinate expression of Wilms' tumor genes correlates with Wilms' tumor phenotypes.

The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity. A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology. Tumors were scored for the percentage of mesenchymal and epithelial derived tissue components. Homotypic tumors comprised blastema, tubular epithelium, and a fibroblast-like mesenchyme. In addition to these tissue components, the group of tumors designated as heterotypic also contained ectopic cell phenotypes such as muscle and squamous epithelium. The analyses suggest that heterotypic differentiation patterns occur when WT1 and WIT1 expression is low relative to normal fetal kidney. In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors. The ratio of WT1:WIT1 expression remained relatively constant in homotypic tumors but deviated significantly in heterotypic tumors. These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology.

Blotting, Northern↗
PubMed1992

[B-cells in thymic epithelial tumors: phenotype, distribution and relation to the intramedullary B-cell population of the normal thymus].

Immunohistochemical analysis of 26 thymomas and thymic carcinomas revealed the occurrence of two different intratumoral B-cell populations. High numbers of B-lymphocytes with formation of lymphoid follicles were found in the extra-epithelial perivascular spaces of cortical thymomas and well differentiated thymic carcinomas associated with myasthenia gravis. On the other hand, B-cells within the epithelial meshwork frequently occurred in organoid medullary islands of predominantly cortical and cortical thymomas. In their distribution and phenotype, these cells correspond to the intramedullary B-cell population of the normal thymus, reflecting a specific intratumoral B-cell homing dependent on medullary epithelial differentiation.

Antigens, CD↗
PubMed1992

[Tumor proliferation, MDR phenotype and tumor associated t-lymphocytes in non-Hodgkin's lymphomas].

In this study we examined the P170-expression (mdr-phenotype) in 42 non-Hodgkin's Lymphomas with variant entities immunohistochemically with the mab JSB1. The mdr-phenotype was related to the tumor proliferation as measured by Ki67-expression and AgNOR numbers. Furthermore the mdr-phenotype was related to the tumor associated T-lymphocytes. The mdr-phenotype showed no relation to histological type and the proliferation of the tumor. There was a positive correlation between the mdr-phenotype and CD2-reactive lymphocytes. There was also a significant positive correlation between CD4-reactive lymphocytes and the mean number of AgNOR's. Possibly P170-expression and proliferation of the tumor cells have a lymphotactic effect on T-lymphocytes. The latter could promote tumor progression by means of paracrine mechanisms.

CD4 Antigens↗
PubMed1992

Tumorigenicity and metastatic ability of MmB16 mouse melanoma cell line and its two Aleuria aurantia agglutinin resistant variants.

The availability of neoplastic cell lines with well defined growth characteristics has greatly facilitated study of the tumor phenotype, tumor progression and metastatic process. MmB16 cell line has been established in vitro from the B16 mouse melanoma serially passaged in C57BL/6 mice. From MmB16 cells two lectin-resistant (LecR) variants were selected with the use of Aleuria aurantia agglutinin (AAA). The correlation between the lectin resistance and their in vivo growth parameters, especially tumorigenicity and metastatic ability, were evaluated. The local tumor growth and the average survival time of mice after subcutaneous (s.c.) inoculation of AAAR variant cells did not differ significantly from those of the parent MmB16 cells. However, the AAAR variants revealed significantly higher experimental lung colonizing ability after intravenous (i.v.) administration and slightly increased spontaneous metastatic ability after s.c. inoculation, as compared to parent MmB16 cells.

Animals↗
PubMed1992

Tumor antigen phenotype, biologic staging, and prognosis in head and neck squamous carcinoma.

Prior studies of alterations in tumor expression of normal blood group antigens and A9/alpha 6 beta 4 integrin, an extracellular matrix receptor, have suggested that these immunohistologic markers reflect the biologic aggressiveness of head and neck squamous carcinomas. To confirm these preliminary observations, prospective long-term follow-up of 82 previously untreated head and neck squamous carcinoma patients was performed. All patients were treated with conventional therapy. Median follow-up was 57 months. Tumor immunohistology for ABH blood group and A9/alpha 6 beta 4 integrin expression was performed and correlated with measures of host cellular immunity, disease-free survival, and overall survival. Loss of blood group expression and high A9/alpha 6 beta 4 integrin expression were each directly related to an increased frequency of early tumor recurrence. The combination of both variables was significantly associated with both disease-free (P = .029) and overall survival (P = .05). Increased expression of A9/alpha 6 beta 4 was associated with impaired T-lymphocyte function (P = .005), and loss of blood group expression was associated with decreased peripheral blood levels of CD8+ T-lymphocytes (P = .013). The findings suggest that these phenotypic characteristics of antigen expression in head and neck squamous carcinomas are important markers of biologically aggressive cancers and impaired host immune response. The clinical use of these biologic staging parameters in the initial assessment of patients should allow selection of more aggressive primary treatment strategies for individual patients.

ABO Blood-Group System↗
PubMed1975

[Viruses and brain tumors (author's transl)].

This brief review paper deals mainly with oncogenic DNA viruses originally isolated from human patients, i.e., human adenoviruses and human papova JC viruses. Human adenovirus type 12 was first isolated in 1953 in cell cultures derived from the adenoids of infected children. Since then, 32 antigenic types of human adenovirus have been identified. At least eight serotypes (12, 18, 31, 3, 7, 14, 16, and 21) are now known to be capable of producing tumors in newborn rodents. A direct causal relationship between a human adenovirus and malignant transformations in target cells (sensory neuronal precursors) has been definitely established by the development of a medullo-epitheliomatous neoplasm in the brain and spinal cord of an outbred strain of CD rats at as high an incidence as 90%. Intraocular inoculation of adenovirus in newborn rats within one week also has produced typical retinoblastomatous neoplasms. The remarkably uniform histopathologic appearance of all these malignancies in nervous tissue can be attributed to a primitive neuro-epitheliomatous neoplasm derived from sensory microneuron precursors that densely populate both the ventricular zone and the premature sensory retina at the point of virus inoculation. All of these brain and retinal tumors appear to share a common tumor phenotype, as all tumor cells contain cilia with the same morphology (a 9+0 pattern of doublets associated with a pair of centrioles). The production of adenovirus tumor-specific neoantigen (T), an earmark of the viral genome, can be regularly demonstrated by the immunofluorescein microscopic procedure. All transformed cells within both the ventricular zone and the retinal ganglion cell anlage thus appear to continue the production of (T) antigens. These findings lead us to assume that the target cell determinants in adenovirus tumorigenesis may reside in differentiating microneuron precursors ordained for the sensory neuronal complex.

Abdominal Neoplasms↗
PubMed1992

Genetic alterations by human papillomaviruses in oncogenesis.

The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.

Chromosomes, Human, Pair 12↗
PubMedDate not supplied

Comparison of cellular phenotypes in tumor cyst and ascitic fluid from ovarian serous carcinoma.

Density gradient centrifugation was applied to isolate cell subsets from tumor cyst and ascitic fluid in eight patients with ovarian serous carcinoma. A comparison of cellular composition and immunologic reactivity of cells from the cysts and from ascitic fluid in each patient was performed. Some differences in density profiles were found, but in each case the consistency of morphologic cell forms in the primary tumor and ascites was documented. Immunophenotypic analyses of isolated cellular fractions using polyclonal and monoclonal antibodies against ovarian carcinoma-associated antigens showed significant immunologic intratumoral heterogeneity. However, there was a similarity of antigen expression in cells from the primary tumors and ascitic fluids. Our study indicated that morphologic and antigenic characterization of a given tumor could be determined in a single representative sample of ascitic fluid.

Ascitic Fluid↗
PubMed2026

Prognostic Role of Global DNA Methylation in Renal Cancer Reveals Decitabine Treatment Benefit.

BACKGROUND: Renal cancer presents a significant global health challenge due to its rising incidence and mortality rates. Often undetected in early stages, it complicates diagnosis and treatment. Current therapies face resistance and limited effectiveness, especially in advanced stages. The diverse subtypes of renal cancer highlight the need for new biomarkers and risk assessment tools for targeted treatments. OBJECTIVE: This study aims to assess the prognostic significance of global DNA methylation (GM) levels in renal cancer, identify new biomarkers, and evaluate the therapeutic potential of the DNA methyltransferase inhibitor decitabine. METHODS: Data on RNA sequencing, gene mutations, DNA methylation, and clinical outcomes were collected from TCGA and GEO databases. We calculated global DNA methylation scores (GMS) and categorized patients into high, intermediate, and low GMS groups. Survival analysis and genomic analyses were conducted to explore the relationships between GMS, clinical outcomes, and tumor characteristics. RESULTS: Higher GMS was identified as an independent prognostic factor associated with worse outcomes in renal cancer. Patients with elevated GMS showed increased mutations, copy number variations, and a more aggressive tumor phenotype. Treatment with decitabine was observed to reduce tumor hypermethylation and downregulate cell cycle pathway activity, indicating potential therapeutic benefits. CONCLUSION: Global DNA methylation plays a significant role in renal cancer prognosis. GMS may serve as valuable biomarkers for prognosis and personalized treatment strategies. Decitabine shows potential efficacy for high GMS patients, particularly through its impact on cell cycle regulation, underscoring the importance of personalized approaches in cancer treatment.

Humans↗
PubMed1979

Mouse mammary tumor virus genome expression in chemical carcinogen-induced mammary tumors in low- and high-tumor-incidence mouse strains.

Involvement of mouse mammary tumor virus (MMTV) in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis was investigated in low- (BALB/c) and high- (BALB/cfC3H) mammary-tumor-incidence mouse strains. Both strains contain endogenous MMTV integrated into the cellular genome. Additionally, BALB/cfC3H mice are infected with exogenous MMTV-S which is responsible for a higher incidence of mammary tumors in breeding females. Administration of DMBA to virgin mice of both strains resulted in a moderate frequency of mammary tumors within 40 wk after treatment. No differences were found in DMBA-induced tumor incidences at 18 wk (6% and 7%) or at 38 wk (29% and 36%) after treatment of BALB/c and BALB/cfC3H mice, respectively. Expression of MMTV in these tumors was examined by assaying for the presence of MMTV RNA by hybridization using MMTV-specific cDNA and by immunohistochemical staining utilizing antibodies against MMTV 52,000-dalton glycoprotein, gp52, and 28,000-dalton internal protein, p28. Of 16 BALB/c tumors assayed, 11 did not contain detectable levels of MMTV RNA and the remaining 5 tumors contained only low levels (0.0005-0.0010%) of viral RNA. Importantly, MMTV RNA was not detected in 5 of 27 BALB/cfC3H tumors. The other BALB/cfC3H tumors contained quantities of MMTV RNA ranging from 0.0006 to 0.4170%. Most BALB/cfC3H tumors with detectable levels of MMTV RNA also synthesized viral proteins gp52 and p28. Thus, expression of the complete MMTV genome is not requisite for maintenance of the tumor phenotype in DMBA-induced mammary tumors in either BALB/c or BALB/cfC3H virgin mice under 1 year of age.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2026

Loss of PBRM1 accelerates pancreatic cancer progression by inducing acquisition of mesenchymal phenotype and inflammatory cancer-associated fibroblasts reprogramming.

BACKGROUND: PBRM1 is an important subunit of the SWI/SNF complex, which broadly regulates gene transcription by chromatin remodeling. Genomic alterations of PBRM1 have been found in patients with pancreatic ductal adenocarcinoma (PDAC), but its molecular functions remain unclear. METHODS: Clinical relevance of PBRM1 was analyzed by using human PDAC samples and public genomic datasets. Mice with concomitant pancreas-specific Pbrm1 deletion in Kras-driven genetic PDAC models were generated. Single-cell transcriptomics were performed to determine tumor phenotype and microenvironment reprogramming. RESULTS: Reduction of PBRM1 expression was observed in human PDAC tissues and correlated with poor prognosis and metastasis. Pbrm1 loss promoted ductal metaplasia and delayed epithelial recovery in mice with caerulein-induced pancreatic injury. In PDAC model with either mutant Kras alone or in combination with Trp53 mutation, lack of Pbrm1 markedly accelerated tumor development and progression. Bulk transcriptomics and scRNA-seq identified reprogramming of both tumor compartment with mesenchymal phenotype acquisition and stroma compartment with inflammatory cancer-associated fibroblasts (iCAFs) transformation. Mechanistically, Pbrm1 deletion induced Zeb1 upregulation through epigenetic chromatin remodeling, thereby enhancing epithelial-mesenchymal and basal-like subtype transition. CONCLUSIONS: These findings indicated a tumor-suppressing role of PBRM1 in PDAC. PBRM1-deficient PDAC constitutes a specific subgroup of patients with aggressive phenotype and prognostic significance.

Animals↗
PubMed1992

Immunogenetics of cell surface antigens of human cancer.

Hybridoma technology, immunohistochemistry and molecular genetic techniques have paved the way for a general serological mapping of molecules expressed on the surface of normal and neoplastic cells. The emerging findings challenge cell lineage-based models of differentiation and point to new, modular concepts to explain complex tumor phenotypes. In parallel studies, the repertoire of T-cell recognized tumor antigens--still mysterious but probably quite distinct from the antibody-defined repertoire--has also become accessible to molecular analysis.

Antigens, Neoplasm↗
PubMed2025

Cancer-associated fibroblast-derived SOD3 enhances lymphangiogenesis to drive metastasis in lung adenocarcinoma.

Despite advancements in diagnostic and therapeutic strategies, lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality due to its aggressive metastatic potential. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme that regulates oxidative stress and is regarded as a tumor suppressor. However, studies have demonstrated that SOD3 can either promote or inhibit cell proliferation and survival in various cancers, and its molecular mechanisms within the tumor microenvironment are poorly understood. In this study, we report a breakthrough in uncovering the role of SOD3 derived from cancer-associated fibroblasts (CAFs) in LUAD. Using LUAD xenograft models co-implanted with SOD3-overexpressing CAFs (CAFSOD3), we observe an aggressive tumor phenotype characterized by increased lymphangiogenesis and lymphatic vessel invasion (LVI) of the tumor. Additionally, LUAD patients with elevated SOD3 levels exhibit a higher incidence of LVI and metastasis. Notably, RNA sequencing of CAFSOD3 reveals that SOD3-mediated VEGF-dependent tumor progression and lymphangiogenesis are up-regulated. Furthermore, single-cell transcriptomic analysis of LUAD clinical samples confirms a strong correlation between SOD3 expression in fibroblasts and characteristics of tumor exacerbation, such as lymphangiogenesis and metastasis. These findings underscore new insights into the role of CAF-derived SOD3 in LUAD progression and highlight its potential as a biomarker and therapeutic target.

Lymphangiogenesis↗
PubMed2023

GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.

BACKGROUND: Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data. METHODS: We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best. RESULTS: Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis. CONCLUSIONS: GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.

Humans↗
PubMed1992

Overexpression of p53: a rare event in a large series of white patients with hepatocellular carcinoma.

Mutant p53 has been found in a wide variety of human malignancies including carcinomas of the lung, breast and colon. Because of the controversial mutational rate of the p53 gene in hepatocellular carcinoma, a large series of liver tumors from white patients with different risk factors was examined immunohistochemically for expression of the p53 mutant to assess its prevalence and the relationships between p53 overexpression and clinicopathological data. Nine of 58 specimens were found to have detectable evidence of p53 gene mutation by virtue of the immunohistochemical detection of mutant p53 protein. The p53 mutation was more frequent in patients with serological hepatitis B and C markers than in patients without these markers (p = 0.046). The prevalence of p53-positive tumors was also significantly higher in the group of tumors with invaded portal branches than in the group without (p = 0.02). Our results showed that p53-positive hepatocellular carcinoma is a rare finding in patients exposed to a low dietary aflatoxin intake and that p53 mutation seems to occur at a late stage of the tumoral process and could contribute to an aggressive tumoral phenotype.

Adult↗
PubMed1976

Suppression of the neoplastic state with the acquisition of specialized functions in cells, tissues, and organs of crown gall teratomas of tobacco.

The neoplastic state in cells of tissues and organs that develop from cloned lines of crown gall teratomas of tobacco may be completely but reversibly suppressed. Stems and leaves found on teratoma shoots may appear morphologically normal and such organs contain all of the specialized cell types and are histologically and functionally indistinguishable from those found in normal tobacco shoots of comparable age. When however, specialized cells of several different kinds that are present in stems and leaves of the teratomas are excised from the plant and grown on a basic culture medium they again assume their neoplastic properties. The results of this study indicate that the morphogenetic factors and mechanisms that govern so precisely growth, cellular differentiation, and organogenesis during the normal course of development can completely suppress the tumorous state, leading to the formation of cells, tissues, and organs that appear normal in every respect but are, in fact, inherently neoplastic. Whether the normal or tumor phenotype is expressed appears to depend on the activation or repression of select biosynthetic systems, one of which, the auxin sytems, has been identified here.

Cell Differentiation↗
PubMed2026

SHMT2: a Metabolic and Immune Biomarker of Aggressive Lung Adenocarcinoma.

Serine/glycine-one-carbon (SGOC) metabolism is frequently altered in lung adenocarcinoma (LUAD), but its relationship to tumor behavior and predicted immunotherapy responsiveness remains incompletely defined. Metabolomic profiling of 23 paired LUAD and adjacent normal lung tissues was performed using internal extractive electrospray ionization mass spectrometry. Transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort (TCGA-LUAD) were analyzed to assess SHMT2 expression, prognosis, differentially expressed genes, and immune-related features. Predicted response to immune checkpoint blockade was evaluated using Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA), and drug sensitivity was inferred using oncoPredict. Single-cell RNA-seq data were used to examine the cellular distribution of SHMT2. Experimental validation included quantitative reverse-transcription PCR (RT-qPCR), western blotting, Human Protein Atlas (HPA) immunohistochemistry, and short hairpin RNA (shRNA)-mediated SHMT2 knockdown followed by proliferation, wound-healing and colony formation assays. Metabolomic analysis identified glycine, serine, and threonine metabolism as a prominently altered pathway in LUAD. SHMT2 was upregulated in LUAD and associated with worse overall survival and adverse clinicopathological features. SHMT2-high tumors displayed enrichment of cell-cycle and SGOC-related transcriptional programs, lower immune and stromal scores, and reduced predicted responsiveness to immunotherapy. Single-cell analysis showed relative enrichment of SHMT2 expression in B cell populations. In vitro, SHMT2 was overexpressed in LUAD cells, and its knockdown suppressed proliferation, migration, and clonogenic growth. Collectively, SHMT2 is associated with SGOC metabolic reprogramming, aggressive tumor phenotypes, and an immune-disadvantaged state in LUAD, supporting its potential relevance as a biomarker; therapeutic targeting requires additional pharmacologic and in vivo validation.

Humans↗