Search results for "malignant [complication]"
showing 10 items of 197 documents
Abstract 3512: MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts
2014
Abstract The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect …
Cytokines in cancer therapy
1989
The treatment options for patients with cancer are presently limited to surgical and radiotherapeutic strategies for localized disease and the systemic use of cytotoxic drugs for disseminated disease. So far, chemotherapy remains the mainstay for the treatment of metastatic cancer. Treatment results, however, have been stagnant particularly for the more frequent cancers such as lung cancer, breast cancer and colorectal cancer. Current research is seeking new concepts of cancer treatment, based upon a more profound understanding of tumor cell biology. The oncogenetic defect in neoplastic cells is a genetic alteration in a primordial cancer cell, which subsequently leads to clonal expansion a…
Coordinate mutation and transformation of mouse fibroblasts: induction by nitroquinoline oxide and modulation by caffeine
1981
Mutation and malignant transformation were followed in the same cells. Mouse fibroblasts (C3H 10T 1/2) were mutated and transformed by 4-nitroquinoline-1-oxide with similar, approximately linear dose-responses. The presence of caffeine immediately after exposure to 4-nitroquinoline-1-oxide potently inhibited mutation and transformation at high but not at low doses of 4-nitroquinoline-1-oxide. Whilst the coordinate induction of mutation and transformation could be explained by both a common target (DNA) or a common reactive species hitting several targets, the identical modulation by a DNA repair inhibitor of both end points suggests fundamental similarities in the nature of the lesions lead…
Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover
2020
This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg
Ha-rasVa112 but not p53Ser247 leads to a significant neoplastic transformation rate of the putative rat liver stem cells (oval cell)
1996
In order to test the controversially discussed hypothesis that oval cells are part of a liver stem cell compartment and can give rise to cholangiocellular as well as hepatocellular carcinomas in the course of liver carcinogenesis, we transfected an oval cell line established in our laboratory with an oncogenically activated genomic Ha-ras clone (pUC EJ 6.6), carrying a valine at position 12 instead of the wild-type glycine, or a rat p53 cDNA mutated by site-directed mutagenesis at codon 247, which corresponds to codon 249 in the human p53. This codon is of particular interest since it represents a mutation hotspot observed in hepatocellular carcinoma especially in regions with high aflatoxi…
Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.
1997
We have shown that the oval cell line OCICDE 22 can be transformed by the highly carcinogenic fiord-region diol epoxides of benzo[c]phenanthrene. Mutational activation of the ras proto-oncogene family has been proposed to be a critical event in the formation of tumors induced by polycyclic aromatic hydrocarbons. Therefore, we investigated whether in the earlier transformed OCICDE 22 cells any point mutations were detected in the ras proto-oncogene. The results indicate that the malignant transformation of OCICDE 22 cells by the 4 stereoisomeric benzo[c]phenan-threne diol epoxides in vitro is independent of activation of the Ha-ras proto-oncogene. In addition, Northern and Western blot analy…
Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development
2008
Abstract Purpose: Antibody-based cancer therapies have emerged as the most promising therapeutics in oncology. The purpose of this study was to discover novel targets for therapeutic antibodies in solid cancer. Experimental Design: We combined data mining and wet-bench experiments to identify strictly gastrocyte lineage–specific cell surface molecules and to validate them as therapeutic antibody targets. Results: We identified isoform 2 of the tight junction molecule claudin-18 (CLDN18.2) as a highly selective cell lineage marker. Its expression in normal tissues is strictly confined to differentiated epithelial cells of the gastric mucosa, but it is absent from the gastric stem cell zone. …
Altered CD94/NKG2A and perforin expression reduce the cytotoxic activity in malignant pleural effusions.
2010
CD94/NKG2A is an inhibitory receptor expressed by NK cells and cytotoxic lymphocytes and, upon activation by HLA-E, downregulates the cytolytic activities of these cells thus representing a tumour immune escape mechanism. This study was aimed at assessing whether cytotoxic lymphocytes (CD8+) and NK cells from malignant pleural effusions have a deregulated expression of CD94/NKG2A. The expression of membrane CD94/NKG2A and perforin was evaluated by flow-cytometry in CD8+ and NK cells from pleural effusions and autologous peripheral blood of cancer (n=19) and congestive heart failure (CHF) (n=11) patients. Intracellular CD94/NKG2A expression was evaluated by flow-cytometry in pleural effusion…
MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts
2013
The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect and a hyp…
Zolbetuximab combined with EOX as first-line therapy in advanced CLDN18.2+ gastric (G) and gastroesophageal junction (GEJ) adenocarcinoma : Updated r…
2019
16 Background: Physiologically, the tight junction protein CLDN18.2 is present only in the gastric mucosa. Upon malignant transformation, CLDN18.2 epitopes are exposed on the cell surface and accessible to targeted therapy. Zolbetuximab (formerly IMAB362) is a chimeric mAb that mediates specific killing of CLDN18.2+ cancer cells through immune effector mechanisms; single-agent activity has been reported in G/GEJ cancer. Methods: Patients (pts) with advanced HER2-negative (HER–) G/GEJ cancer with CLDN18.2 expression of ≥ 2+ staining intensity with the anti-CLDN18 43-14A mAb in ≥ 40% tumor cells were eligible (NCT01630083). Patients were randomized 1:1 to receive first-line EOX ± zolbetuxima…