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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and thirty-eight adenocarcinomas of human kidney were assessed histologically with special reference to the tumor malignancy as indicated by the 5-year survival of the patients. Four different grading systems were used; the classification based on the histologic type of tumor growth, the grading of malignancy according to Arner et al., the grading based on the nuclear structure of carcinoma cells and finally a combined grading system based on the nuclear structure and the demarcation of the tumor from the surround tissue. The histologic type of growth was observed to be an inappropriate basis for grading of renal carcinoma. The grading system of Arner et al. was an appropriate method of malignancy grading despite its somewhat low reproducibility. The grading system based on the nuclear structure of the tumor cells was an accurate measure of the intrinsic malignancy of renal carcinoma and gave an excellent correlation between tumor grade and the 5-year survival rate of the patients. The combined grading system was an equally accurate method in estimating the 5-year prognosis of ranal carcinomas and indicated that the poor demarcation of the tumor from the surroundings in an unfavorable prognostic sign.
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PMID:Grading of human renal adenocarcinoma. 63 86

In a group of 102 selected cases of renal cell carcinoma which at various periods after nephrectomy terminated fatally, age, sex, and 23 gross and/or histologic tumor characteristics were examined, subclassified, and evaluated. An attempt was made to correlate these parameters statistically to postoperative survival time. A newly developed and programmed statistical method, i.c. "dichotomic variance analysis", proved to be superior to both multiple regression and cluster analysis. Using infiltrative-destructive tumor growth, polymorphy, and chromatin density of tumor cell nuclei, extension of renal vein invasion, age and sex, as the only 6 required out of 25 distinguished tumor parameters, this statistical multivariate method comprised 7 distinctive groups of different mean geometrical postoperative survival time, obviously corresponding to 7 tumor types of increasing degree of malignancy. By step-wise dichotomic splitting of tumor groups it therefore was possible to delinate schematically some of the complex connections between the criteria or variables of prognostic significance. Conceivable sources of errors possibly influencing reproducibility and practical applicability of the presented dichotomic variance analysis in evaluating prognostic criteria in renal cell carcinoma are discussed.
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PMID:[Morphology versus prognosis in renal cell carcinoma a statistical approach]. 81 72

A response to diethylstilbestrol (DES) of DES-induced renal carcinoma in Syrian hamster was studied by comparing subcutaneous growth of this tumor in DES-treated and untreated animals with respect to the growth curve, cell cycle time, Tc, growth fraction, GF, and cell loss factor, phi. In both conditions the tumor growth followed the Gompertz curve, but the latent period was 14 days longer without DES than with DES. In the untreated animals, Tc was 80% longer due to increases of TGl and TS. However, phi was not changed significantly and GF rather increased without DES. It was concluded that DES-dependency of this tumor growth was manifested in the prolongation of Tc.
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PMID:Effect of diethylstilbestrol on the cell kinetics of subcutaneous growth of diethylstilbestrol-induced renal carcinoma. 91 54

Synergy, when it can be convincingly established, is an effective strategy for the development of novel drug combinations. We have evaluated the interaction between 2'-deoxy-5-azacytidine (DAC) and 9-dimethylaminomethyl-10-hydroxycamptothecin (topotecan) based on our hypothesis that DAC, through DNA hypomethylation, might increase the transcription of topoisomerase I (topo I) leading to increased sensitivity to topotecan. Five human tumor cell lines, A375 melanoma, DX-3 melanoma, DMS4C non-small cell lung carcinoma, UP-1 unknown primary adenocarcinoma, SN12C renal carcinoma, and the murine CT-26 tumor cell line, were studied. Drug interactions were assessed using the multiple drug effect analysis of Chou and Talalay (Chors, T-C, and Talalay, P. Adv. Enzyme Regul., 22:27-54, 1984.). A synergistic interaction was documented in four human cell lines and the murine CT-26 line. An antagonistic interaction was observed with the SN12C cell line. The toxicology and efficacy of this combination were analyzed using CT-26 in BALB/c mice. Various treatment schedules were studied, including: single doses of each agent; single sequential combination treatments where DAC was administered followed by topotecan 24 h later; and multiple sequential treatments where DAC and topotecan were administered on days 1, 2, 8, and 9. Efficacy studies showed that the single sequential combination of DAC (50 mg/kg) and topotecan (10 mg/kg) resulted in tumor growth delay as compared to single doses of DAC (50 mg/kg) or topotecan (10 mg/kg). When the multiple sequential combination schedule was used, the antitumor effect was more pronounced. In that experiment 50% of the control animals had tumors of 20 mm by day 28. For animals receiving a single sequential treatment with DAC and topotecan, the median time until the mean tumor size reached 20 mm was 38 days, and for the group with multiple sequential combination treatments the time was 51 days. Studies of the mechanism of the interaction showed that the activity of topotecan versus each cell line correlated with the topo I activity in nuclear extracts However, there was no correlation between topo I levels and synergy and no reproducible increase in topo I activity following exposure to DAC. Thus, while the exact mechanism of the interaction remains unclear, DAC can be effectively combined with topotecan to enhance antitumor activity.
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PMID:Synergistic cytotoxicity with 2'-deoxy-5-azacytidine and topotecan in vitro and in vivo. 137 5

The transplantable rat kidney carcinoma (RKC) provides an excellent experimental model for immunological and therapeutic studies of renal cell carcinoma. In this report, we define the biological characteristics of RKC and explore the interactions between RKC and natural killer (NK) cells. RKC, a transplantable tumor of spontaneous origin, grows progressively over a 12-week period and metastasizes to the lung when implanted orthotopically in the kidneys of female Lewis rats. Rats bearing RKC survived for an average of 10.5 +/- 1.5 (SD) weeks postimplantation. Lung metastases were visible between 7.5 and 8.5 weeks postimplantation, and by 9 to 10 weeks the incidence of metastases reached approximately 67%. Injection of the NK cell-specific monoclonal antibody 3.2.3 depleted Lewis rats of their NK activity for up to 14 days. Adherent lymphokine-activated killer cells generated from the spleens of 3.2.3-injected rats were significantly less lytic than those from control rats and contained a significantly lower percentage of 3.2.3+ cells when analyzed by flow cytometry. Groups of rats were implanted with RKC and received injections of 3.2.3 biweekly to maintain depletion of NK cells or of a control antibody, NK1.1, specific for mouse NK cells. At 10 weeks postimplantation, 3.2.3-injected rats had significantly (P < or = 0.005) larger tumors (104.4 +/- 20.1 g) than NK1.1-injected rats (75.4 +/- 13.9 g). Spleen cells and peripheral blood cells from uninjected, tumor-bearing rats had a slight but nonsignificant decrease in NK activity against 51Cr-labeled YAC-1 targets over the course of RKC progression. The activity of adherent lymphokine-activated killer cells from tumor-bearing rats was lower than that from normal rats, but not significantly. Cultured RKC cells were killed by both splenic NK cells and adherent lymphokine-activated killer cells. These data demonstrate that RKC is NK sensitive and that tumor growth does not abrogate NK activity. The RKC tumor provides a model system for the analysis of immunological factors in renal cell carcinoma growth and presents opportunities for testing therapeutic interventions in a system that closely mimics the human disease.
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PMID:Renal cell carcinoma and natural killer cells: studies in a novel rat model in vitro and in vivo. 142 74

This study clarified whether and when the blood-brain barrier in experimental brain metastases is impaired by using hydrosoluble sodium fluorescein (MW 376) as a blood-brain barrier function indicator. Cells from eight human tumor lines (four melanomas, two breast carcinomas, one colon carcinoma, and one renal carcinoma) were inoculated into the internal carotid artery of nude mice. Brain metastases at different stages of development were sampled and the permeability of the blood-brain barrier around the metastases determined. Histologic examination showed two patterns of tumor growth. In the first, tumor cells formed isolated, well-defined nodules in the parenchyma of the brain. In lesions smaller than 0.2 mm2, the blood-brain barrier was intact. In the second, small diffuse nests of tumor cells were distributed throughout the brain parenchyma. The blood-brain barrier was intact until the small tumor cell colonies coalesced to form large tumor masses. These results suggest that the permeability of the blood-brain barrier varies among different experimental brain metastases and that its function is related to the growth pattern and size of the lesions.
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PMID:Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. 144 46

Chromosomal abnormalities have been believed to be responsible for neoplastic transformation and tumor growth for a long time. The confirming observations are of two types: (1) primary cytogenetic alterations that are responsible for tumor initiation and (2) secondary abnormalities that are acquired late and are associated with tumor growth, heterogeneity, and metastasis. Primary chromosomal abnormalities (such as the 13q deletion in retinoblastoma, 11p deletion in Wilms' tumor, 3p anomalies in renal cell carcinoma, and 5q deletion in colorectal carcinomas) first were identified in lymphocyte cultures as constitutional defects. Later, similar types of defects were observed as tumor-specific aberrations from patients whose lymphocytes otherwise had normal chromosomes. Recently, it has become clear that classes of known cancer-related genes (dominant protooncogenes and recessive tumor-suppressor or anti-oncogenes) are located at those hot spots that are involved in neoplasia-associated chromosomal alterations. In breast carcinoma, such a specific chromosomal alteration has not been identified conclusively in lymphocyte cultures, although chromosome 1 alterations have been observed in cell lines, directly processed effusions, and primary breast tumors. Lymphocyte cultures; primary tumors; and established cell lines from breast carcinomas, colorectal carcinomas, and renal cell carcinomas were analyzed to identify (1) primary chromosomal alterations precisely and (2) secondary cytogenetic defects that are associated with these most common solid adult neoplasms. Peripheral blood analysis indicated that chromosomes 1, 17, and 18 in breast carcinomas; chromosomes 3 and 14 in renal cell carcinomas; and chromosomes 5, 12, and 17 in colorectal carcinomas were involved nonrandomly in structural anomalies in a small number of lymphocyte cells (1-4%). These chromosomal aberrations were considered primary defects because of their involvement as marker formations in tumor cells; other structural and numeric abnormalities also were found. These results indicate that lymphocyte chromosomal analysis might identify those at high risk for breast, colorectal, and renal cell carcinomas, among other malignant lesions. Such identifications could facilitate early selection for primary and secondary cancer prevention or interventional trials.
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PMID:Cytogenetics of epithelial malignant lesions. 151 22

Ilmofosine (BM 41.440, 1-hexadecylthio-2-methoxymethyl-rac-glycero-3-phosphocholine) is a synthetic alkyl lysophospholipid analog with activity against a variety of tumor models in vitro and in vivo. The i.v. form is presently undergoing early clinical investigation in phase I trials. In order to help define types of tumors that might be clinically sensitive to this agent we have studied the anti-tumor effects of ilmofosine against a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 1.0-30 microgram/ml were used in continuous incubations experiments. Of 348 specimens tested, 134 (39%) were evaluable for determination of tumor growth modulating activity. The most common tumor types recruited included non-small cell lung, breast, colorectal, ovarian, renal cell cancer and melanoma. A concentration-dependent increase in the frequency of inhibited tumor specimens was observed with 6/134 (4%) sensitive specimens at 1 microgram/ml as compared with 113/133 (85%) sensitive specimens at 30 micrograms/ml (p less than 0.0000005). We conclude that ilmofosine is active against a variety of tumors in vitro. Clinical phase II trials with ilmofosine including the tumor types with in vitro sensitivity are warranted if adequate plasma concentrations of this agent can be reached in patients.
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PMID:Preclinical activity of ilmofosine against human tumor colony forming units in vitro. 162 15

The process of metastasis is not random. Rather, it consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Although some of the steps in this process contain stochastic elements, as a whole, metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumor systems. Moreover, we have found tumor growth that is specific to a particular site within one organ. Whether the same conclusions can be reached for human cancers remained unanswered until very recently. Studies from our laboratory and from others have shown that the implantation of human cancer cells derived from surgical specimens into correct anatomical sites of nude mice can provide a suitable model of metastasis of human tumors. Clonal analysis of a human renal carcinoma, colon carcinomas, and melanomas has revealed that these tumors are indeed heterogeneous for metastatic properties, an observation made only after orthotopic implantation. Thus, growth in the environment of specific organs can be selective and the environment per se influences this process. While it is clear that vascularity and local immunity can facilitate or retard tumor growth, we have concentrated on understanding how damage to an organ and the subsequent repair process can facilitate tumor cell proliferation. Accelerated growth of human colon cancer cells was found in hepatectomized nude mice, whereas accelerated growth of human renal cancer cells was found in nephrectomized nude mice. These data suggest that systemic physiological signals can be recognized by neoplastic cells presumably by mechanisms similar to those shared by their normal cell counterparts. In summary, the critical factors that regulate metastasis are the intrinsic properties of metastatic cells and host factors involved in homeostasis. The recent increase in our understanding of metastasis should provide important leads for developing more effective approaches to the treatment of disseminated cancer.
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PMID:Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. 169 18

The direct antitumor effects of combined administration of alpha-interferon and chemotherapeutic agents against the human tumor cell line derived from renal cell carcinoma were examined in vivo as xenograft in nude mice. The administration regimen was as follows: Human lymphoblastoid interferon (HLBI) was injected intramuscularly (1 x 10(5) IU/mouse/day) every day for 14 days. Peplomycin (PEP), adriamycin (ADM), or 5-fluorouracil (5-FU) was also administered at a dose of one third of their LD50. We evaluated the effect 20 days after initial administration using the ratio of mean tumor weight. Combined administration of HLBI and PEP or ADM was determined effective and inhibited tumor growth more strongly than HLBI alone or control. Furthermore, the histopathological examination suggested that the effect of combined administration was cytostatic rather than cytolytic.
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PMID:[Combined effects of alpha-interferon and anticancer drugs against renal cell carcinoma]. 170 35


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