transforming-growth-factor-beta and Adenocarcinoma--Mucinous

Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1-C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs).. Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs.. Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-β dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways.. The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; CD8-Positive T-Lymphocytes; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Female; Genes, MHC Class I; Humans; Inflammation; Interferon-gamma; Lymphocytes; Macrophages; Male; Microsatellite Instability; Monocytes; Neovascularization, Pathologic; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins p21(ras); Receptors, Antigen, T-Cell; Signal Transduction; Th1 Cells; Th17 Cells; Th2 Cells; Transforming Growth Factor beta; Tumor Microenvironment; Wnt Signaling Pathway; Wound Healing

Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non-mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non-mucinous CRC.. Data from The Cancer Genome Atlas-colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken.. Mucinous CRC was more likely to be microsatellite instability-high (MSI-H) and hypermutated. When corrected for microsatellite status the single-nucleotide variation and insertion-deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK-RAS, transforming growth factor-β, and TP53 pathways.. Mucinous CRC has some distinct genomic aberrations when compared with non-mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI-H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Cohort Studies; Colonic Neoplasms; Datasets as Topic; DNA Copy Number Variations; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Genomics; Humans; INDEL Mutation; Microsatellite Instability; Mucins; Mutation; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Smad4 Protein; Transforming Growth Factor beta; Tumor Suppressor Protein p53

Although the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR.. Of the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-β, and PI3K).. Mutation of genes within the WNT, P53, RTK-RAS, TGF-β, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-β pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-β pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p <  0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-β pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-β pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation.. Mutation in genes within TGF-β pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Capecitabine; Chemotherapy, Adjuvant; Colon; Colorectal Neoplasms; Deoxycytidine; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Microsatellite Instability; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaloacetates; Palliative Care; Prognosis; Rectum; Signal Transduction; Survival Analysis; Transforming Growth Factor beta

A recent study reported that long non-coding RNA activated by TGF-β (lncRNA-ATB) induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-β (TGF-β)/miR-200s/ZEB axis in hepatocellular carcinoma. Herein, we focused on the clinical significance of lncRNA-ATB in gastric cancer (GC) patients.. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in GC tissues (n = 183). Patients were divided into high and low lncRNA-ATB expression groups using a cutoff of lncRNA-ATB/GAPDH ≥0.60 or <0.60 to determine the clinicopathological significance of lncRNA-ATB in GC. Moreover, we evaluated the expression of TGF-β, lncRNA-ATB, miR-200s, and ZEB1 in GC cell lines by qRT-PCR. GC cell lines were treated by recombinant TGF-β1 or TGF-β receptor inhibitor to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype.. The high lncRNA-ATB group experienced a lower overall survival rate compared with the low lncRNA-ATB group, and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (hazard ratio 3.50; 95 % CI 1.73-7.44; p = 0.0004). miR-200c levels were lower and ZEB1 levels were higher in the high lncRNA-ATB group than in the low lncRNA-ATB group. Treatment with TGF-β in GC cell lines resulted in morphological EMT changes, upregulation of lncRNA-ATB and ZEB1, and downregulation of miR-200c and CDH1. SB431542 reduced lncRNA-ATB expression.. LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in GC. LncRNA-ATB is a novel biomarker of lncRNA, indicative of a poor prognosis in GC patients.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Apoptosis; Biomarkers, Tumor; Carcinoma, Signet Ring Cell; Cell Proliferation; Female; Follow-Up Studies; Homeodomain Proteins; Humans; Immunoenzyme Techniques; Liver Neoplasms; Lymphatic Metastasis; Male; MicroRNAs; Neoplasm Invasiveness; Neoplasm Staging; Peritoneal Neoplasms; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Long Noncoding; RNA, Messenger; Stomach Neoplasms; Survival Rate; Transcription Factors; Transforming Growth Factor beta; Tumor Cells, Cultured; Zinc Finger E-box-Binding Homeobox 1

Epithelial ovarian cancer (EOC) is an immunogenic tumour and exploits many suppressive ways to escape immune eradication. EOC is known to spread primarily by tumour cell implantations in peritoneal cavity. Therefore, ascites may be an ideal fluid compartment to unravel the immune status of the peritoneal cavity. We analysed the expression of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, TNF-α, TNF-β, TGF-β and CCL22 in ovarian cancer ascites, representing immune activating and suppressing cytokines. We observed high expression of pro-inflammatory cytokines IL-6, IL-8 and immune suppressive cytokines IL-10, CCL22 and TGF-β in most samples whereas Th1 (IL-12p70, IFN-γ) and Th2 (IL-4, IL-5) cytokines were only detectable in 13% of the samples. TGF-β was only detected in latent form, questioning its immune suppressive role. CCL22 was in similar levels present in early stage compared to advanced stage tumours. At advanced stage, we observed a negative correlation with CCL22 levels and Th1/2 cytokine expression. We found a positive correlation between IL-6 concentration in ascites and residual disease after debulking. Additionally, IL-6 levels were remarkably higher at recurrence compared to primary advanced disease, which opens an opportunity for inhibition of IL-6 expression in the prevention of recurrence. Despite the heterogeneity of EOC and the complexity of cytokine functions, our results show that cytokine analysis in ascites may aid in understanding tumour-host interaction in EOC.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Ascites; Carcinoma, Ovarian Epithelial; Chemokine CCL22; Cystadenocarcinoma, Serous; Cytokines; Female; Gene Expression Regulation, Neoplastic; Humans; Interferon-gamma; Interleukins; Middle Aged; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Sarcoma; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

To detect the expression of transforming growth factor-beta 1(TGF-beta 1) in epithelial neoplasms and its clinicopathologic features and prognosis.. TGF-beta 1 expression was detected in 77 cases of epithelial ovarian neoplasms by SABC immunohistochemistry (including 21 benign tissues, 7 borderline tissues, and 49 epithelial ovarian cancer tissues), and they were compared with 14 normal ovarian tissues.. 1. The positive rate of TGF-beta 1 expression was 71.42% in the normal ovary, 76.19% in benign tissues, 4/7 in borderline tissues and 38.78% in epithelial ovarian cancer tissues. 2. TGF-beta 1 expression was associated with the grade, the FIGO stage, and the histologic type of the patients with epithelial ovarian cancer (P < 0.05).. The expression of TGF-beta 1 may play an important role in the progression of epithelial ovarian cancer and may be related to the prognosis of epithelial ovarian cancers.

Topics: Adenocarcinoma, Mucinous; Adolescent; Adult; Aged; Cystadenocarcinoma, Serous; Female; Humans; Immunohistochemistry; Middle Aged; Ovarian Neoplasms; Transforming Growth Factor beta; Transforming Growth Factor beta1

Using the differential display method, latent transforming growth factor-beta 1 (TGF-beta 1) binding protein 1 (LTBP-1) mRNA was identified as one of the enriched mRNAs in ovarian carcinoma tissues after isolation of genes responsible for the development of ovarian cancer. Semi-quantitative reverse transcription (RT)-PCR analysis showed that expression of LTBP-1 and TGF-beta 1 mRNAs was much higher in both serous and mucinous adenocarcinomas than in their benign counterparts, including serous and mucinous cystadenomas and cystadenomas of low malignant potential (LMPs). Immunohistochemical analysis demonstrated that only proliferating benign adenoma cells were immunoreactive for both LTBP-1 and TGF-beta 1 proteins. In contrast, most serous and mucinous adenocarcinoma cells and their surrounding stroma were intensely immunoreactive for LTBP-1 and TGF-beta 1. LTBP-1 and TGF-beta 1 proteins, and their complex forms were identified in ovarian carcinoma cell lines and in their culture media by western blot analysis, suggesting these products were produced in ovarian carcinoma cells. RT-PCR analysis demonstrated that LTBP-1L, one of the LTBP-1 transcripts that has a strong activity in targeting the latent form of TGF-beta 1 to extracellular matrix (ECM), was predominantly expressed in ovarian carcinomas. Taken together, the results suggest that upregulation of LTBP-1 in ovarian carcinoma cells may have an important role in distributing TGF-beta1 in the stromal tissues surrounding carcinoma cells.

Topics: Adenocarcinoma, Mucinous; Blotting, Western; Carrier Proteins; Cystadenocarcinoma, Serous; Cystadenoma, Mucinous; Female; Gene Expression; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Latent TGF-beta Binding Proteins; Ovarian Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor beta

A subset of hereditary and sporadic colorectal carcinomas is defined by microsatellite instability (MSI), but the spectra of gene mutations have not been characterized extensively. Thirty-nine hereditary nonpolyposis colorectal cancer syndrome carcinomas (HNPCCa) and 57 sporadic right-sided colonic carcinomas (SRSCCa) were evaluated. Of HNPCCa, 95% (37/39) were MSI-positive as contrasted with 31% (18/57) of SRSCCa (P < 0.000001), but instability tended to be more widespread in SRSCCa (P = 0.08). Absence of nuclear hMSH2 mismatch repair gene product by immunohistochemistry was associated with germline hMSH2 mutation (P = 0.0007). The prevalence of K-ras proto-oncogene mutations was similar in HNPCCa and SRSCCa (30% (11/37) and 30% (16/54)), but no HNPCCa from patients with germline hMSH2 mutation had codon 13 mutation (P = 0.02), and two other HNPCCa had multiple K-ras mutations attributable to subclones. 18q allelic deletion and p53 gene product overexpression were inversely related to MSI (P = 0.0004 and P = 0.0001, respectively). Frameshift mutation of the transforming growth factor beta type II receptor gene was frequent in all MSI-positive cancers (85%, 46/54), but mutation of the E2F-4 transcription factor gene was more common in HNPCCa of patients with germline hMSH2 mutation than in those with germline bMLH1 mutation (100% (8/8) versus 40% (2/5), P = 0.04), and mutation of the Bax proapoptotic gene was more frequent in HNPCCa than in MSI-positive SRSCCa (55% (17/31) versus 13% (2/15), P = 0.01). The most common combination of mutations occurred in only 23% (8/35) of evaluable MSI-positive cancers. Our findings suggest that the accumulation of specific genetic alterations in MSI-positive colorectal cancers is markedly heterogeneous, because the occurrence of some mutations (eg, ras, E2F-4, and Bax genes), but not others (eg, transforming growth factor beta type II receptor gene), depends on the underlying basis of the mismatch repair deficiency. This genetic heterogeneity may contribute to the heterogeneous clinical and pathological features of MSI-positive cancers.

Topics: Adaptor Proteins, Signal Transducing; Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; bcl-2-Associated X Protein; Carrier Proteins; Cell Cycle Proteins; Chromosomes, Human, Pair 18; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA Mutational Analysis; DNA-Binding Proteins; DNA, Neoplasm; E2F Transcription Factors; E2F4 Transcription Factor; Female; Genes, APC; Humans; Male; Microsatellite Repeats; Middle Aged; MutL Protein Homolog 1; MutS Homolog 2 Protein; Neoplasm Proteins; Nuclear Proteins; Point Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins p21(ras); Retinoblastoma-Binding Protein 1; Transcription Factor DP1; Transcription Factors; Transforming Growth Factor beta; Tumor Suppressor Protein p53

Pancreatic neoplasms harbor different prognoses according to their histological type: a benign course for serous cystadenoma, a low malignant potential for intraductal papillary mucinous neoplasms (IPMN), and high aggressiveness for ductal adenocarcinoma (ADC). Transforming growth factor beta 1 (TGF beta 1) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta 1-latency-associated peptide (beta 1-LAP), its latent binding protein (LTBP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5). LTBP is thought to play a strategic role in the processing and active secretion of latent TGF beta 1 and its stockage in the extracellular matrix. Localization of beta 1-LAP and LTBP was assessed by immunohistochemistry using specific antibodies and expression of TGF beta 1 mRNA by reverse-transcriptase polymerase chain reaction analysis. beta 1-LAP was only slightly expressed in normal specimens, while LTBP was not detected. beta 1-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one carcinoma in situ. LTBP was detected only in stromal cells and in the surrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta 1-LAP was strongly expressed in the epithelial cells, while it was poorly detected in invasive IPMN; stromal cells were poorly or not all stained by beta 1-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benign IPMN and two of two cases with cystadenoma, while stroma was not immunostained. TGF beta 1 mRNA was strongly expressed in most of the tumors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta 1 in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta 1 efficiently, in contrast to ductal ADC as shown by the ability of the neoplastic cells to express both beta 1-LAP and LTBP. Invasive stroma reaction was associated with enhanced beta 1-LAP and LTBP expression in stromal cells and could be mediated by TGF beta 1 via LTBP

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Carcinoma, Ductal, Breast; Carcinoma, Papillary; Carrier Proteins; Cystadenoma, Serous; DNA Primers; Female; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Latent TGF-beta Binding Proteins; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Peptide Fragments; Protein Biosynthesis; Protein Precursors; Proteins; RNA, Messenger; RNA, Neoplasm; Transforming Growth Factor beta; Transforming Growth Factor beta1

The DiFi human colorectal cancer cell line was recently established from a familial adenomatous polyposis patient with extracolonic features characteristic of the Gardner syndrome. These cells have now been propagated for 150 passages in standard culture media and vessels without feeder layers or collagen coatings. They retain features of colonic epithelial cells such as surface microvilli, secretory vesicles, and desmosomes. Cytosol of DiFi cells contains a high level (502 U/mg protein) of the mucin CA 19-9. In addition, DiFi cells produce carcinoembryonic antigen, and induce tumors in athymic mice. Cytoskeleton analysis of DiFi cells by fluorescence microscopy showed a pronounced disorganization of actin cable structure. The isozyme genetic signature of DiFi cells is unique (0.01 probability of finding the same genetic signature in a different cell line), differs from that of HeLa cells, and has expressional features seen in other colorectal cell lines. The DiFi cell karyotype is tetraploid, contains many marker chromosomes, and shows numerous episomal particles. Two copies of chromosome 18 were absent, and only a single normal chromosome 17 was found. This parallels detection of allelic losses from DiFi cell DNA at loci on chromosomes 17p and 18 using molecular (cDNA) probes. DiFi cells clearly express transcripts for the c-myc proto-oncogene, the c-myb proto-oncogene, and the p53 tumor suppressor gene. Transforming growth factor beta inhibits DiFi cell growth in soft agar and suppresses c-myc expression in these cells. The value of this cell line in the study of genetic alterations in colorectal cancer is discussed.

Topics: Actins; Adenocarcinoma, Mucinous; Animals; Antigens, Tumor-Associated, Carbohydrate; Cell Cycle; Cell Line; Cytoplasmic Granules; Desmosomes; Female; Gene Expression Regulation, Neoplastic; Genotype; Humans; Karyotyping; Mice; Mice, Nude; Microscopy, Fluorescence; Middle Aged; Proto-Oncogene Mas; Proto-Oncogene Proteins c-myc; Rectal Neoplasms; Transforming Growth Factor beta

Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival. We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months. In 167 patients the expression of TGF-beta 1 was inversely correlated with node status (P = 0.065) but not ER status, tumour size or menopausal status. Patients with high levels of TGF-beta 1 had a longer disease free interval with a significantly longer probability of survival at 80 months although the overall relapse free survival was not increased. EGFR mRNA expression was measured in 106 patients and was inversely correlated with ER status (P = 0.018). EGFR levels did not predict for early relapse or survival. TGF alpha mRNA levels were measured in 104 patients, no correlation was seen tumour size, node status, Er status, or clinical outcome.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; ErbB Receptors; Female; Follow-Up Studies; Humans; Immunoblotting; Middle Aged; Prognosis; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor alpha; Transforming Growth Factor beta; Transforming Growth Factors

Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor for many cell types, including tumor cells. We recently have reported the establishment and characterization of two human gastric scirrhous carcinoma cell lines, HSC-39 and HSC-43. Here we examined the effect of TGF-beta 1 on the growth of these lines as compared to five other human gastric adenocarcinoma cell lines. Proliferation of HSC-39 and HSC-43 cells was strongly inhibited by TGF-beta 1, whereas the other gastric adenocarcinoma cell lines were unresponsive to TGF-beta 1. Both HSC-39 and HSC-43 cells gradually lost viability following exposure to TGF-beta 1. This response was dose dependent up to 4 ng/ml. When TGF-beta 1 was removed, the cells failed to exhibit regrowth, indicating an irreversible growth-inhibitory effect of this agent, leading to cell death. DNA fragments were observed consisting of multimers of approximately 180 base pairs 24 h after TGF-beta 1 treatment. The chromatin condensation of each cell line was confirmed by Hoechst 33258 fluorochrome staining. Ultrastructurally, condensed and fragmented nuclei were observed in TGF-beta 1-treated cells. These features are generally associated with apoptotic processes. Both cell death and DNA fragmentation were partially inhibited by cycloheximide, suggesting the requirement for new protein synthesis. Our results suggest that TGF-beta 1 induces cell death in human gastric scirrhous carcinoma cells in vitro which is mediated by activation of a signal transduction pathway for apoptosis.

Topics: Adenocarcinoma, Mucinous; Cell Death; Cell Division; DNA, Neoplasm; Humans; Stomach Neoplasms; Transforming Growth Factor beta; Tumor Cells, Cultured