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

The fate of clonal lineages in tumor formation and metastasis has been studied by genotypic marking of cells from three separate tumor lines of different malignant potential. Marking was accomplished by random incorporation of the neomycin resistance gene and visualized by Southern blot analysis of integration sites. Primary tumors formed by polyclonal cell suspensions of all three cell lines injected s.c. usually remained polyclonal even at late stages of tumor growth and metastatic spread. Lung metastases were often clonal, but it was not unusual to find ones of polyclonal origin. Lymph node metastases were almost always polyclonal and remained so, as they grew large. Sometimes clones present in the original inoculum were absent in the primary. Other times clones visible in the metastases were undetectable in the corresponding primary tumor. Occasionally a single clone became dominant in the primary, and others were eliminated, but this was not a necessary prelude to the onset of invasive or metastatic behavior. It is concluded that there is considerable variation in the results obtained with various cell lines in different circumstances. Even clones which are underrepresented in the original inoculum or the primary tumor can acquire metastatic capability. Hence, progression of malignancy is not uniformly dependent on prior or concurrent extinction of other non- or less metastatic clones in the neoplasm, and the underlying mechanisms of invasion and metastasis can be separated from those which sometimes confer growth supremacy on a clone of tumor cells. The frequent continuing genetic heterogeneity of cells in a neoplasm has substantial implications for clinical treatment protocols.
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PMID:Fate of clonal lineages during neoplasia and metastasis studied with an incorporated genetic marker. 155 Nov 2

We report the growth characteristics of seven human laryngeal carcinomas transplanted into athymic mice. Six of the tumors were harvested from surgical pathology specimens and one was from a laryngeal carcinoma cell line. Tumor tissue measuring 2-3 cubic millimeters was implanted subcutaneously into the flank of the mice. Time intervals between implantation and active growth were recorded and tumor volume was calculated weekly. Mice were sacrificed at various time intervals. For three tumors, second and third passages of the tumor were performed. Successful tumor growth was achieved in 6/7 (85.7%) tumors. Primary implantation of tumor was performed in a total of 26 mice, 17 of which grew successfully. The average time interval between tumor implantation and measurable tumor growth for the five zenografts derived directly from patients was 36 days (range 25-40 days). The mean doubling time was 16 days (range 7-30 days). The overall take rate per animal for serial passage of tumor was 36 out of 43 (83.7%). The lag phase and the mean tumor doubling time decreased with each successive passage. At autopsy most tumors were confined to the subcutaneous structures by a well-formed capsule. Lymph node metastases and disseminated metastases were not seen. We conclude that the athymic mouse model is suitable to establish primary tumor growth of human laryngeal cancer.
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PMID:Growth characteristics of human laryngeal carcinoma in athymic mice. 204 Oct 60

From 1960 to 1982, a total number of 216 patients with Stage I melanoma underwent local excision as the single treatment. Life-table analysis was performed on 211 evaluable patients to investigate the prognostic value of several factors on survival as well as disease-free survival. The influence of sex, age, localization of the tumor, and margin of the excision on prognosis was not statistically significant. The Clark level and Breslow thickness were important factors to predict the prognosis. Local recurrence occurred in only one patient; in most cases tumor growth close to the original site of excision indicates early manifestation of hematogenic spread. Lymph node metastases developed in 31 patients; ten of them remained free of disease after node dissection. Six patients died from hematogenic metastases without nodal involvement. Tumors with thickness less than 1.5 mm have excellent prognosis regardless of the location of the melanoma or the margin of the excision. With increasing thickness of the tumor, prognosis is proportionally worse. By performing wide excisions the final outcome can not be improved.
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PMID:Prognoses and surgical treatment of patients with stage I melanomas of the skin: a retrospective analysis of 211 patients. 371 94

The presence of lymphoid aggregates within the muscularis propria or pericolic fibroadipose tissue apposing invasive colorectal carcinoma, termed the Crohn's-like lymphoid reaction, has been related to improved patient length of survival according to univariate statistical analysis. We tested the Crohn's-like lymphoid reaction as an indicator of prognosis in a multivariate statistical analysis of 344 resected right-sided colonic cancers. Improved 5-year survival in univariate analysis was associated with low tumor grade, regular tubule configuration, expanding tumor growth pattern, prominent peritumoral lymphocytic infiltration, absence of tumoral invasion of extramural veins, all levels of intramural and extramural invasion short of widespread local tumor permeation, conspicuous Crohn's-like lymphoid reaction, and absence of both nodal metastasis and nodal-independent tumor nodules in pericolic fat. By the Cox proportional hazard model using the stepwise method, depth of tumor invasion, lymph node metastasis, Crohn's-like lymphoid reaction, and metastatic tumor nodules in pericolic fat retained independent prognostic significance. Combining the four variables to formulate pathological prognostic categories yielded a highly favorable prognostic group-92% 5-year survival and 95% confidence limits (88% to 96%)--encompassing 53% of the study population. It included all Dukes' stage A carcinomas, 66% of Dukes' stage B adenocarcinomas, and 11% of Dukes' stage C cancers. Lymph node metastases coupled with intramural and extramural extent of tumor invasion are the cornerstones of colorectal cancer staging. Addition of other variables improves prognostication for the cecum and ascending colon. From this study the Crohn's-like lymphoid reaction and metastatic tumor nodules in pericolic fat emerge as significant independent indicators of prognosis for right-sided colon cancer. Complex correlations of both indicators with nonselected variables were observed.
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PMID:Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: results of multivariate analysis. 782 14

The relation between tumor tissue blood flow (tBF) reduction and antitumor effects was investigated. Changes in tBF of normal tissues (liver, kidney cortex, bone marrow and brain cortex) and tumors (Yoshida sarcoma subline, LY80 and Sato lung carcinoma, SLC) due to i.v. administration of AC7700 (1, 3, 10 mg/kg), one of the combretastatin A-4 derivatives, were measured with the hydrogen clearance method. The change in blood flow in tumor microfoci was also observed directly using a rat transparent chamber. Chemotherapy against the solid tumors (LY80, SLC) was performed by administering AC7700 7 times at intervals of 3 days and the effect on the tumor growth, the histological effect, the effect on lymph node metastasis and the survival rate were investigated. Tumor tBF showed a dose-dependent response to AC7700. Although tumor tBF decreased markedly at a dose of 1 mg/kg, it tended to recover partly within several hours. At 10 mg/kg, however, tumor tBF completely stopped within approximately 30 min and never recovered in many regions. The irreversible stoppage of tumor tBF was observed in large s.c. tumors and in microfoci as well. On the other hand, in normal tissues, tBF changes due to AC7700 were not uniform. In the liver, although tBF decreased by approximately 50% at 10 mg/kg AC7700, it recovered within 8 h. In the brain, although the mean maximum reduction was 35%, the blood flow recovered to the original level within 24 h. The blood flow in the kidney cortex did not change at all. In the bone marrow, tBF decreased by approximately 80%. Generally, the blood flow reduction in normal tissues tended to be reversible. The effect on tumor growth and the histological effect were also dependent on the dose of AC7700. The tumor growth was markedly inhibited by 10 mg/ kg AC7700 and extensive necrosis was induced. Lymph node metastases were significantly inhibited and survival was prolonged significantly. In the control group, all 8 SLC tumor-bearing rats died of cancer, the presence of which was verified by gross and microscopic evaluation, within 45 days after tumor implantation. On the other hand, in the treated group, 2 of 8 rats recovered completely and survived. No obvious side effects such as body weight loss, anemia or diarrhea were observed at the dose used in this experiment. From these results, we conclude that strong antitumor effects are obtained by stopping tumor tBF irreversibly and by shutting off the nutritional supply into tumor tissue. AC7700 has been demonstrated to be a promising anticancer compound which has such an action.
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PMID:Antitumor effects due to irreversible stoppage of tumor tissue blood flow: evaluation of a novel combretastatin A-4 derivative, AC7700. 1055 34

Lymph node metastasis is one of the prognostic factors in gastric cancer. We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression on cancer cells is associated with lymph node metastasis using a gastric cancer cell. In this study, we transfected ICAM-1 gene into a gastric cancer cell line, 2MLN, and analyzed the effect on lymph node metastasis in vitro and in vivo. A significantly greater amount of peripheral blood mononuclear cells (PBMC) adhered to ICAM-1 transfected 2MLN cells, 2MLN / ICAM cells, than to 2MLN / Vector cells. The lysis of 2MLN / ICAM cells by PBMC was significantly increased compared with that of 2MLN / Vector cells. The tumor growth rate of 2MLN / ICAM cells was significantly decreased in vivo. Lymph node metastases caused by 2MLN / ICAM cells were recognized as being fewer in number and smaller, while many lymph node metastases were caused by 2MLN cells. Histologic findings showed that leukocytes were heavily infiltrated in both the 2MLN / ICAM tumors and metastatic lesions, while only a few leukocytes were observed in the lesions associated with 2MLN cells. The above findings indicate that ICAM-1 gene transduction could prove to be an effective gene therapy for lymph node metastasis of gastric cancer.
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PMID:ICAM-1 (intercellular adhesion molecule-1) gene transfection inhibits lymph node metastasis by human gastric cancer cells. 1101 Nov 21

The suppressors of cytokine signaling (SOCS) are inhibitors of cytokine signaling that function via the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Recently, methylation of SOCS-1 and SOCS-3 has been implicated in the tumorigenesis of liver and lung cancer. This study was performed to elucidate the role of SOCS-1 and SOCS-3 in squamous cell carcinoma of the head and neck (HNSCC) and its precursor lesions. HNSCC of 94 patients and corresponding normal mucosa, lymph node metastases as well as 16 high- and 21 low-grade squamous cell dysplasias were studied by using methylation-specific PCR (MSP) for the SOCS-1 and SOCS-3 promoter after microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real-time PCR, and the SOCS-3 protein was analysed immunohistochemically. SOCS-3 hypermethylation was found in 85/94 HNSCC (90%) and in 10/16 high-grade and 9/21 low-grade dysplasias (63 and 43%, respectively). SOCS-1 promoter hypermethylation was detected in 10/94 HNSCC samples (11%) and in 2/16 high-grade and 1/21 low-grade dysplasias (13 and 5%, respectively). Lymph node metastases exhibited an identical methylation status as the primary tumors. Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumors and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased upon treatment with the demethylation compound 5-aza-2-deoxycytidine (5-AZA-DC). Overexpression of wild-type SOCS-3 in carcinoma cells with methylated SOCS-3 resulted in the induction of apoptosis and growth suppression as well as downregulation of STAT3, bcl-2 as well as bcl-xL. Our data suggest that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of HNSCC. During its involvement in tumor growth, restoration of SOCS-3 may hold treatment potential for HNSCC.
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PMID:SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. 1600 69

Squamous cell carcinomas (SCC) of the nasal cavity and the paranasal sinuses are a very rare and poorly understood tumor entity. To date, no consistent management strategy exists. The purpose of our study was to demonstrate our therapeutic strategy and to correlate clinicopathological features with clinical follow-up data.45 patients with primarily resected SCC of the nasal cavity (n=35) and the paranasal sinuses (n=10) between 1994 and 2010 were reviewed retrospectively (mean follow-up period 2.6 years; range 0.3 to 14.9 years).Tumors of the nasal cavity were diagnosed at an early stage (97% T1 and T2) whereas tumors of the parasinuses were found at an advanced stage (90% T3 and T4). Lymph node metastases were only found 2 patients. 13 patients (29%) had a local tumor progress, 2 patients showed lymph node metastases and 4 patients had distant metastases in follow up. The prognosis of tumors of the nasal cavitiy or the paranasal sinuses was bad (31% 5-year overall survival) especially by patients with a relapse.Reconstructive surgery was performed after 12 months, when early local relapse could be excluded. There was no positive correlation between clinicopathological features and survival data.The prognosis of tumors of the nasal cavity and paranasal sinuses depends mainly on the control of local tumor growth. Modern strategies of surgical treatment in combination with radiotherapy need to be implemented in an effort to achieve continuous tumor-free survival.
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PMID:[Management and prognosis of patients with squamous cell carcinomas of the nasal cavity and the paranasal sinuses]. 2293 Feb 78