Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-one patients with locally extensive and metastatic renal cell carcinoma were observed over an eight year period. At onset of the disease, symptoms due to metastatic deposits were the most frequent mode of presentation, followed by manifestation of local tumor growth (hematuria, flank pain or palpable mass) and paraneoplastic syndromes. Hormonal therapy with testosterone propionate, a progestational agent or both was assessed in 21 cases. Five instances of tumor regression, two involving recalcification of lytic osseous metastases, were documented. Endocrine studies to elucidate possible mechanisms of hormonal effectiveness were carried out in seven cases. Median survival from diagnosis was ten months. Following the rapid early mortality, a very gradual decrease in survival occurred, with 25% alive at ten years. Factors influencing survival include the duration of the interval between diagnosis of the primary tumor and appearance of metastases and the association of certain paraneoplastic syndromes.
 ...
PMID:Renal cell carcinoma: analysis of 31 cases with assessment of endocrine therapy. 61 Apr 16

Alpha interferon is effective in the treatment of metastatic renal cell cancer. To obtain a maximal efficacy, alpha interferon should be used at a dose of 10 MU/m2, or 18 MU total dose, given daily or three times a week. At such doses interferon produces flu-like symptoms and severe asthenia and thus should be proposed only to patients who have a good performance status. The response rate is low, in the order of 15-20%, and the median remission duration is short (6-10 months). However a few patients experience very durable remissions, sometimes for more than 5 years. The response rate may possibly be improved to 20% to 35% by combining interferon alpha with antineoplastic agents or to other cytokines, namely interleukin 2. Finally because of its supposed mechanisms of action-direct tumor growth inhibition and enhancement of the host's immune defenses--interferon may be of benefit in the adjuvant setting.
 ...
PMID:[Role of interferon in the treatment of renal cancer in adults]. 137 37

Whereas cytokine therapy has proven efficacy in the treatment of metastatic renal cell carcinoma (RCC), many questions regarding the use of these drugs remain unanswered. In the present study we evaluated the antiproliferative effects of human recombinant alpha-interferon (IFN), gamma-interferon and tumor necrosis factor-alpha (TNF) on eight human RCC xenografts. In particular, the importance of the administration route, dosage and tumor load was investigated. Response to the cytokines differed widely amongst the different tumors. Of three tested routes of administration (i.v., i.p. and s.c. peritumoral), only the s.c. peritumoral route was effective against tumor growth. After 6 weeks of therapy consisting of 150 or 1,500 units IFN/g given s.c. peritumorally three times a week or 30,000 units TNF/g given five times a week, alpha-IFN treatment resulted in 2%-100% growth inhibition; gamma-IFN, in 7%-80%; and TNF, in 35%-75% as compared with the untreated control. Growth of five of eight tumor lines could be inhibited completely by combinations of IFN and TNF, whereby the tumor dimensions at the beginning of therapy were decisive for the results. In some cases IFNs had optimal doses; however, the antitumor effects of TNF were always dose-dependent. Our studies indicate that the doses at which the optimal direct effects of cytokines are measured are critically dependent on the tumor treated. Although direct effects are only one part of the mode of action of cytokines, our results indicate that dosage of cytokines may need individualisation.
 ...
PMID:Differential sensitivity of renal cell carcinoma xenografts towards therapy with interferon-alpha, interferon-gamma, tumor necrosis factor and their combinations. 190 59

Following preliminary studies suggesting that some patients with metastatic renal cell carcinoma had accelerated tumor growth after entry into chemotherapy studies, 73 patients with measurable metastatic disease referred to a tertiary referral center for consideration for experimental treatment protocol have been observed to attempt to establish the incidence of spontaneous regression. Initially, patients went off study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients only went into therapy protocols with the development of symptomatic progression. In this selective series, on observation, three complete (histologically documented) and two partial unexplained "spontaneous" regressions were observed and a further four patients had prolonged stable disease for more than 12 months. On progression, 52 were entered into treatment protocols (BCG n = 19, Mitozantrone n = 12, and Welferon n = 21). A further two complete and five partial responses (14%) and four prolonged stable disease were observed confirming that the previously reported responses with these agents are not totally explicable on the basis of "spontaneous" response.
 ...
PMID:A phase 2 study of surveillance in patients with metastatic renal cell carcinoma and assessment of response of such patients to therapy on progression. 326 68

The most challenging aspect of cancer treatment remains the management of invasive and metastatic tumor growth. Recent progress in the development and use of biologic response modifiers for immunomodulation has raised the possibility that the immune system can be used as an additional antitumor treatment modality in conjunction with surgery, chemotherapy, and/or radiotherapy for the treatment of established tumors and their metastases. As a model for adoptive chemoimmunotherapy (ACIT) of renal cancer we have used a murine renal cancer (Renca) of spontaneous origin that mimics the tumor progression characteristically observed for human renal cell carcinoma. In the present study, we demonstrate that broadly cytotoxic lymphocytes, generated by in vitro culture with human recombinant interleukin 2, and used in conjunction with the chemotherapeutic drug doxorubicin hydrochloride, are effective in treating invasive and metastatic renal cell cancer. Administration of ACIT i.v. or i.p., alone, or after nephrectomy of the tumor-bearing kidney, did not cure mice with stage II (locoregional invasive tumor) or stage III (lymph node metastases) disease. In contrast, nephrectomy followed by simultaneous bicompartmental i.v. and i.p. ACIT administration cured 80% of mice with either stage II or stage III Renca. These data demonstrate that simultaneous bicompartmental ACIT affords dramatically improved cure rates for advanced and metastatic Renca. This effect most likely results from efficient control of both locoregional and metastatic tumor growth.
 ...
PMID:Successful treatment of advanced murine renal cell cancer by bicompartmental adoptive chemoimmunotherapy. 349 54

Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.
 ...
PMID:Results of xenogeneic I-RNA therapy in patients with metastatic renal cell carcinoma. 616 71

Despite extensive investigations with many different treatment modalities, metastatic renal cell carcinoma (RCC) remains a disease highly resistant to systemic therapy. The outlook for patients with metastatic RCC is poor, with a 5-year survival rate of less than 10%. Late relapses after nephrectomy, prolonged stable disease in the absence of systemic therapy, and rare spontaneous regression are clinical observations that suggest host immune mechanisms could be important in regulating tumor growth. Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) have been extensively studied in advanced RCC with responses in the 10 to 20% range. Two randomized trials suggest that treatment with IFN-alpha compared with vinblastine or medroxyprogesterone results in a small improvement in survival. Prolonged responses with high-dose IL-2 is significant but is accompanied by formidable toxicity. Although the combination of IFN-alpha and IL-2 compared with monotherapy with IFN-alpha or IL-2 increases the response proportion, no improvement in survival could be demonstrated in a recent randomized trial. In addition, three randomized trials showed no survival benefit associated with IFN-alpha therapy given as adjuvant therapy following complete resection of locally advanced RCC. Small numbers of patients exhibit complete or partial responses to IFN-alpha and/or IL-2, but most patients do not respond and there are few long-term survivors. Clinical investigation of new agents and treatment programs to identify improved antitumor activity against metastases remain the highest priorities in this refractory disease.
 ...
PMID:Cytokine therapy in renal cell cancer. 1100 93

Interleukin-6 (IL-6) is a multifunctional cytokine which provides multiple signals on various tissues and cells. In addition, IL-6 is produced by some human renal carcinoma cell lines in vitro and is expressed in a majority of primary renal cell carcinoma (RCC). Serum IL-6 influence the response to immunotherapy. IL-6 appears as a target for rational drug design highly promising for development of new cancer therapies. IL-6 effects are mediated by Stat. Stat (Signal transducers and activators of transcription) signaling pathways represent novel molecular targets for therapeutic implications in metastatic renal cell carcinoma. Inhibitors of Stat signaling pathway will not only block tumor growth by inducing apoptosis, but may also increase the sensitivity of tumors to conventional treatment (immunotherapy). The processes involved in tumor associated angiogenesis should lead to compounds able to interfere with angiogenesis. Il-6 has been implicated in the osteoclastic bone resorption and hypercalcemia associated with metastatic RCC. Different agents were shown to be effective in treating lytic bone disease mediated by osteoclast activation: bisphosphonates and osteoprotegerin.
 ...
PMID:[Interleukin-6 and bone metastasis of renal cancer: molecular bases and therapeutic implications]. 1140 May 11

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that has been increasingly recognized as key to the regulation of cell growth and proliferation. mTOR either directly or indirectly regulates translation initiation, actin organization, tRNA synthesis, ribosome biogenesis, and many other key cell maintenance functions, including protein degradation and transcription functions. Inhibition of mTOR blocks traverse of the cell cycle from the G1 to S phase. Preclinical data show inhibition of tumor growth in a number of cell lines and xenograft models. Clinical trials are ongoing. In metastatic renal cell cancer, both tumor regression and prolonged stabilization have been noted. mTOR inhibition appears to be a key pathway that may be useful in antitumor therapy. Renal cell cancer may be particularly susceptible through both the translation inhibition pathway and pathways that enhance HIF-1alpha gene expression, a factor believed to stimulate growth in metastatic renal cell cancer. Additional clinical trials that use agents that inhibit mTOR are ongoing.
 ...
PMID:Mammalian target of rapamycin inhibition. 1544 35

Metastatic renal cell carcinoma, inherently resistant to conventional treatments, is considered immunogenic. Indeed, partial responses are obtained after treatment with cytokines such as IL-2 or IFN-alpha, suggesting that the immune system may control the tumor growth. In this study, we have investigated the ability of the main subset of peripheral gammadelta lymphocytes, the Vgamma9Vdelta2-TCR T lymphocytes, to induce an effective cytotoxic response against autologous primary renal cell carcinoma lines. These gammadelta T cells were expanded ex vivo using a Vgamma9Vdelta2 agonist, a synthetic phosphoantigen called Phosphostim. From 11 of 15 patients, the peripheral Vgamma9Vdelta2 T cells were amplified in vitro by stimulating PBMCs with IL-2 and Phosphostim molecule. These expanded Vgamma9Vdelta2 T cells express activation markers and exhibit an effector/memory phenotype. They display a selective lytic potential toward autologous primary renal tumor cells and not against renal NC. The lytic activity involves the perforin-granzyme pathway and is mainly TCR and NKG2D receptor dependent. Furthermore, an increased expression of MHC class I-related molecule A or B proteins, known ligands of NKG2D, are detected on primary renal tumor cells. Interestingly, from 2 of the 11 positive cultures in response to Phosphostim, expanded-Vgamma9Vdelta2 T cells present an expression of killer cell Ig-like receptors, suggesting their prior recruitment in vivo. Unexpectedly, on serial frozen sections from three tumors, we observe a gammadelta lymphocyte infiltrate that was mainly composed of Vgamma9Vdelta2 T cells. These results outline that Vgamma9Vdelta2-TCR effectors may represent a promising approach for the treatment of metastatic renal cell carcinoma.
 ...
PMID:Phosphostim-activated gamma delta T cells kill autologous metastatic renal cell carcinoma. 1566 91


1 2 3 4 5 6 Next >>