Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overall survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has not improved appreciably over the past few decades. Novel therapeutic approaches, such as immunotherapy, are under clinical investigation since the standard treatments are toxic and have not successfully controlled this disease with sufficiently high success rates. Cancer immunotherapy describes various techniques to expand and activate the immune system to control tumor growth in vivo, and clinical evaluation has so far demonstrated low toxicity. Immunotherapy appears to have the most applicability in settings of minimal residual disease and to reduce distant metastases after other therapeutic interventions, and its potential clinical value is now receiving intensive evaluation. Emerging forms of SCCHN immunotherapy involve both the use of monoclonal antibodies (mAb) that target growth factor receptors where immune activation appears to contribute to tumor cell lysis, as well as various forms of active vaccination strategies which activate and direct the patient's cellular immunity against the tumor. This article reviews immunotherapeutic strategies currently in clinical trials or under development for patients with SCCHN.
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PMID:Immunotherapy for head and neck cancer. 1944 65

Imaging of cancer by radioimmunoscintigraphy (RIS) following administration of radiolabeled monoclonal antibodies (mAbs) or fragments has been under development for two decades. Efficacy is a function of many variables: antigen expression on tumor cells relative to normal tissues and body fluids, affinity, specificity, pharmacokinetics and immunogenicity of the mAb and properties of the radionuclide and imaging techniques. CEA-Scan (a 99mTclabeled Fab' fragment of a mouse mAb directed against CEA) has several advantageous properties, and has been approved for use in colorectal cancer SPECT imaging in North America and Europe, and is also under investigation in Japan. It has been shown to complement CT in detecting recurrent or metastatic disease, even in the liver where 111In mAbs frequently fail. In breast cancer, it provides clearer identification of malignant disease in patients with indiscriminate mammography. Recently, it has also been used intra-operatively in radio-immunoguided surgery in both colorectal and breast cancer patients. These new applications are currently under active investigation and clinical trials are planned. Clinically useful information is obtained in a relatively high percentage of patients, which can alter treatment decisions. In most cases the benefits are in reducing unnecessary surgery or biopsies in inoperable patients, but major benefits (especially in colorectal cancer) would be obtained if new therapies effective against the RIS-detected minimal residual disease were forthcoming.
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PMID:Technology evaluation: CEA-Scan, Immunomedics Inc. 1962 71

In this study we present the models of preventive and therapeutic vaccination of sarcoma-bearing rats with dendritic cells that present tumour antigens from killed tumour cells. We present the characteristics of dendritic cell-based vaccine and its capacity to induce anti-tumour immune response both in vitro and in vivo. We show that preventive vaccination efficiently prevents tumour growth. On the other hand, vaccination of rats with established tumours did not lead to eradication of the tumours. Despite the induction of a vigorous immune response after administration of dendritic cell-based vaccine and transient decrease in tumour progression, tumours eventually resumed their growth and animals vaccinated with dendritic cells succumbed to cancer. In both settings, preventive and therapeutic, dendritic cell-based vaccination induced a vigorous tumour-specific T-cell response. These results argue for the timing of cancer immunotherapy to the stages of low tumour load. Immunotherapy initiated at the stage of minimal residual disease, after reduction of tumour load by other modalities, will have much better chance to offer a clinical benefit to cancer patients than the immunotherapy at the stage of metastatic disease.
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PMID:Dendritic cell-based immunotherapy induces transient clinical response in advanced rat fibrosarcoma - comparison with preventive anti-tumour vaccination. 1969 18

Local recurrences at the site of tumor resection or after chemotherapy, as well as distant micrometastases represent major problems in oncology. Therapeutic strategies based on insertion of immunostimulatory genes into the genome of tumor cells followed by vaccination with the resulting genetically modified and irradiated cellular vaccines represent a new potential prospect for the treatment of cancer patients. These strategies are based on the presumption that many, if not all tumors, possess cell surface antigens capable of being recognized by defence effectors of the immune system, as well as on the presumption that local treatment of primary tumors can, due to its immunizing potential, result also in the inhibition of distant metastases. Genetically modified cellular vaccines were found to be efficient against cancer both in experimental models and in tumor-bearing patients. It was also shown in various systems that the efficacy of conventional therapeutic modalities can be supported by adjuvant administration of genetically modified vaccines, as well as by depletion of immunosuppressive immunocyte subsets. The purpose of this review was to summarize and evaluate the results obtained with the administration of genetically modified cellular vaccines as well as with depletion of immunosuppressive immunocytes performed as treatment of minimal residual disease after surgery / chemotherapy in the experimental model of murine tumors mimicking human HPV16-associated neoplasms. The prospects and limitations of these adjuvant immunotherapeutic modalities are discussed.
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PMID:Genetically modified cellular vaccines against human papillomavirus type 16 (HPV16)-associated tumors: adjuvant treatment of minimal residual disease after surgery/chemotherapy. 1978 61

Preclinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase 1 vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of the HLA-A*0201 allotype, with at least one metastatic lesion, were included. Irradiated vaccine cells were applied in increasing doses of 2.5, 10, and 40 x 10(6) cells over 22 weeks. Primary study parameters included safety and toxicity. Sequential blood samples were analyzed by interferon-gamma enzyme-linked immunospot assays to detect tumor antigen-associated (TAA) effector cells. The vaccine was well tolerated and the designated vaccination course was completed in 9 of 15 patients. Neither vaccine-induced autoimmunity nor systemic side effects were observed. Delayed-type hypersensitivity skin reactions were detected in 11 of 12 evaluated patients and were particularly strong in patients with prolonged survival. In parallel, vaccine-induced immune responses against vaccine or overexpressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria; however, median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. We conclude that vaccine use was safe and feasible in mRCC. Clinical benefits were limited in these patients with advanced disease; however, immune monitoring revealed vaccine-induced responses against multiple TAAs in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.
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PMID:Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma. 1978 91

The present study was undertaken to determine the pattern and incidence of predictable lymphatic spread and skip metastasis in oral cancer and analyze the prognostic implications of different therapeutic modalities in the neck metastases. The study includes 81 patients with squamous cell carcinoma of oral cavity with T1-2N0M0 and T1-3N1-3M0 who were admitted to the Department of ENT and Head and Neck Surgery, SMS Medical College and Hospital, Jaipur, from June 2006 to May 2008. After complete diagnostic evaluation (imaging, FNAC), all these patients were operated (wide primary excision with SOHND/Extended SOHND/MRD-I) and followed up periodically till date. Occult metastasis was found in 26% of the patients. Level I, II, III was most commonly involved. We did not find any metastasis or recurrence at level IV in N0 cases. Involvement of level IV node in N0 and N+ neck were 0 and 9%, respectively. We did not find any "skip metastasis" at level IV in oral cancers. We concluded that SOHND for N0 and MRND type I for N+ neck for oral cancers is an appropriate treatment.
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PMID:A 3-year study of supraomohyoid neck dissection and modified radical neck dissection type I in oral cancer: with special reference to involvement of level IV node metastasis. 1992 16

BACKGROUND: The mechanisms responsible for resistant or recurrent disease in childhood non-Hodgkin lymphoma (NHL) are not yet fully understood. A unique mechanism suggesting the role of the mitochondria as the key energy source responsible for residual cells has been assessed in the clinical setting on specimens from patients on therapy were found to have increased copies of mitochondrial DNA (mtDNA) associated with positive minimal residual disease and/or persistent disease (MRD/PD) status. The potential role of mtDNA in MRD/PD emphasizes queries into the contributions of relevant enzymatic pathways responsible for MRD/PD. This study hypothesized that in an in-vitro model, recovering or residual cells from chemotoxicity will exhibit an increase in both citrate synthase and isocitrate dehydrogenase expression and decrease in succinate dehydrogenase expression. PROCEDURE: Ramos cells (Burkitt lymphoma cell line) were exposed to varying concentrations of doxorubicin and vincristine for 1 hr; and allowing for recovery in culture over a 7-day period. cDNA was extracted on days 1 and 7 of the cell culture period to assess the relative expression of the aforementioned genes. RESULTS: Increase citrate synthase, increase isocitrate dehydrogenase and decrease succinate dehydrogenase expressions were found in recovering Ramos cells. CONCLUSION: Recovering lymphoma cells appear to compensate by regulating enzymatic levels of appropriate genes in the Krebs Cycle suggesting an important role of the mitochondria in the presence of residual cells.
Cancer Growth Metastasis 2008 Nov 24
PMID:Possible Mitochondria-Associated Enzymatic Role in Non-Hodgkin Lymphoma Residual Disease. 1993 79

Osteosarcoma (OS) is the most common bone tumor in humans. Newer, more clinically relevant models of OS are required to investigate novel therapeutics. The ability to study spontaneous micrometastases in the absence of a primary tumor is important since this is the manner in which most patients are treated clinically. Therefore, we have developed a novel model of murine OS using the DLM8 cell line, which is syngeneic to C3H mice. We have engineered these cells to express firefly luciferase so the development of metastases can be followed serially and non-invasively. These cells form osteolytic/osteoproductive lesions and metastasize spontaneously after orthotopic implantation in the proximal tibia, and the development of soft-tissue metastasis can be followed serially by luciferase expression following amputation. We have demonstrated a significant prolongation of disease-free and overall survival in the surgical adjuvant setting following treatment with doxorubicin or carboplatin, drugs which form the mainstay of treatment for human OS. In conclusion, we have developed a novel surgical adjuvant model of metastatic OS in immunocompetent mice that closely recapitulates the clinical situation, allowing the evaluation of novel therapeutics in the context of minimal residual disease.
Clin Exp Metastasis 2010 Mar
PMID:An orthotopic, postsurgical model of luciferase transfected murine osteosarcoma with spontaneous metastasis. 2021 24

Bcr-abl kinase inhibitors have provided proof of principal that targeted therapy holds great promise for the treatment of cancer. However, despite the success of these agents in treating chronic myelogenous leukemia (CML), the majority of patients continue to present with minimal residual disease contained within the bone marrow microenvironment. These clinical observations suggest that the bone marrow microenvironment may provide survival signals that contribute to the failure to eliminate minimal residual disease. The bone marrow microenvironment is comprised of multiple sub-domains which vary in cellular composition and gradients of soluble factors and matrix composition. Experimental evidence indicate that exposure of tumor cells to either bone marrow derived soluble factors or the extracellular matrix can confer a multi-drug resistance phenotype. Together, these data indicate that targeting such pathways may be a viable approach for increasing the efficacy of chemotherapy. Moreover, we propose that personalized medicine must go beyond understanding predictive models inherent to tumors but rather build predictive models that consider diversity in response due to interactions with the tumor microenvironment. Although review will focus on CML, understanding the contribution of the bone marrow microenvironment could contribute to rationale combination therapy in other types of leukemia, multiple myeloma and solid tumors which metastasize to the bone.
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PMID:The bone marrow microenvironment as a sanctuary for minimal residual disease in CML. 2038 30

The cancer stem cell (CSC) hypothesis provides an attractive model of tumour development and progression, holding that solid tumours are hierarchically organized and sustained by a minority of the tumour cell population with stem cell properties, such as self-renewal, tumorigenicity and multilineage differentiation capacity. Therapeutic resistance, underlying tumour recurrence and the lack of curative treatments in metastatic disease, raise the question if conventional anticancer therapies target the right cells. Indeed, these treatments might miss CSCs, which represent a more chemoresistant and radioresistant subpopulation within cancer. Recently, a direct link between the epithelial-mesenchymal transition process and the gain of stem cell competence were demonstrated in cultured breast cells. In particular, it was shown that the induction of EMT program not only allow cancer cells to disseminate from the primary tumor, but also promotes their self-renewal capability. Furthermore, the expression of stemness and EMT markers in CTCs were associated with resistance to conventional anti-cancer therapies and treatment failure, highlighting the urgency of improving tools for detecting and eliminating minimal residual disease.
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PMID:Cancer stem cells and epithelial-mesenchymal transition: revisiting minimal residual disease. 2038 75


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