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[Clinical and pathological study of dysplasia, early invasive carcinoma and invasive carcinoma (the invasion 5mm deep) in oral cavity].

This study was carried out to clarify the clinico-pathological conditions of dysplasia, early carcinoma and invasive carcinoma (the invasion 5mm deep) in oral cavity. 57 cases (61 lesions), Which were resected by surgery alone, and diagnosed histologically as dysplasia, early invasive carcinoma and invasive carcinoma (the invasion 5mm deep), were used. All lesions were serially sectioned, and the relationship between clinical and histological appearances were examined. Further, a disease map was made in order to examine the distribution of carcinoma. Age of patients with an early carcinoma showed a wide distribution. Sex were 33 males and 24 females. Twenty-two cases of dysplasia showed white, red, red and white patch, and papillary outgrowth. Twenty-three cases of early invasive carcinoma showed same appearance as those of dysplasia. Sixteen cases of 5mm depth invasive carcinoma showed white, red, white and red patch, and granular and ulcerous appearance. In red lesions, so-called atypical vessels were seen. Atypical vessels were recognized as punctation. The punctation in area of dysplasia and carcinoma in situ were regular in shape. On the other hand, the punctation in 5mm deep invasive carcinoma became irregular in size and orientation. There was no correlation between the size and level of invasion. Fixed survival was 95.5% in early invasive carcinoma, 92.9% in 5mm deep invasive carcinoma. There were two types of distribution patterns of early invasive and 3mm deep invasive carcinoma; multi-centric and mono-centric pattern. All of 5mm deep invasive carcinoma showed mono-centric pattern, but the outline of carcinomatous area was more complicated in shape.

Carcinoma, Squamous Cell

A retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. 4. The relation of cross-sectional profile, level of invasion, ulceration and vascular invasion to tumour type and prognosis.

A selected series of 669 primary cutaneous malignant melanomas, stage I, was studied. The series includes 86 lentigo maligna melanomas, 259 superficial spreading malignant melanomas, 194 nodular malignant melanomas and 130 unclassifiable malignant melanomas. The cross-sectional profile, level of invasion, ulceration and vascular invasion were graded. The relation of these features to each other and to tumour type was studied by X2 tests. The prognostic value was also studied. The most common finding was a slightly elevated surface, level III of invasion, no ulceration and no vascular invasion. Most of these tumours were superficial spreading malignant melanomas. A good prognosis was associated with a flat cross-sectional profile, level II of invasion, no ulceration and no vascular invasion. A poor prognosis was associated with marked protrusion of the surface, level IV--V of invasion, ulceration and vascular invasion. Lentigo maligna melanomas tended to be more benign while nodular malignant melanomas tended to be more malignant than the average. A superficial spreading malignant melanoma could vary in either direction. The prognostic value of level of invasion and ulceration was found to be greater than that of tumour type. The prognostic importance of invasion no further than level III is stressed. Level of invasion ought to be reported to the clinician as well as the tumour type.

Blood Vessels

Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial.

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.

Aged

Nonmuscle-Invasive Recurrence and Management During Surveillance in Patients with Muscle-Invasive Bladder Cancer Who Achieve Clinical Complete Response to Neoadjuvant Chemotherapy.

PURPOSE: Many patients are medically unfit for or refuse radical cystectomy. Few postchemotherapy bladder-sparing active surveillance programs have reported on nonmuscle-invasive recurrences and treatment outcomes. In this study, we present data on nonmuscle-invasive recurrences and their management in this population. MATERIALS AND METHODS: This is a retrospective review of a prospectively maintained database. All patients received cisplatin-based neoadjuvant chemotherapy and were determined to have a clinical complete response (cCR) based on negative endoscopic resection, urine cytology, and cross-sectional imaging. Patient data were entered into a strict active surveillance protocol. Primary outcomes of interest were number of nonmuscle-invasive recurrences, grade and stage, and treatment. Secondary outcomes of interest were nonmuscle-invasive treatment response rate and muscle-invasive and metastatic recurrence rate. RESULTS: A total of 61 cCR patients were identified. In total, 28 patients experienced a median of 1 nonmuscle-invasive recurrence over a median follow-up of 28.3 months. There were a total of 46 nonmuscle-invasive recurrences, including 9 (20%) low-grade recurrences and 37 (80%) high-grade recurrences. Of the 37 high-grade recurrences, the majority (60%) were treated with Bacillus Calmette-Guérin induction. Nonmuscle-invasive recurrence was not associated with later muscle-invasive recurrence or metastasis. Genomic analysis of paired tumor samples demonstrated clonal relatedness in one patient sample while another sample demonstrated a likely precancerous urothelial field effect. CONCLUSIONS: There is a high rate of nonmuscle-invasive recurrences in patients who achieve cCR to neoadjuvant chemotherapy. However, most of these patients may be safely managed with bladder-preserving treatments. These findings emphasize the importance of vigilant surveillance protocols and appropriate patient selection.

bladder cancer

Invasive v. non-invasive blood pressure measurements--the influence of the pressure contour.

A reasonable correlation exists between invasive and non-invasive methods of measuring systemic blood pressure. However, there are frequent individual differences between these methods and these variations have often caused the validity of the non-invasive measurement to be questioned. The hypothesis that certain invasive systolic blood pressures may represent a pressure impulse rather than a flow-generating pressure was used to classify the invasive pulse pressure contour into various types, and the invasive pressure measurement was then correlated with the non-invasive. There was a significantly greater difference between these two methods of measuring systolic blood pressure in patients exhibiting prominent inotropic pressure pulse phenomena compared with patients without such phenomena. Since non-invasive monitors measure blood pressure by volume displacement or flow detection and invasive ones measure pressure impulses rather than flow, it was concluded that the pressure measured by the non-invasive monitor more accurately reflects the propulsive pressure-causing flow when inotropic pressure pulse phenomena are present.

Adult

Invasive human fibrosarcoma DNA mediated induction of a 92 kDa gelatinase/type IV collagenase leads to an invasive phenotype.

Proteolytic enzymes, such as gelatinase/type IV collagenase, play a pivotal role in cancer invasion and metastasis. Invasive human fibrosarcoma cells (HT1080) secrete two species of gelatinase/type IV collagenase, 68-72 kDa and 92 kDa enzymes. The purpose of this study is to elucidate which species of gelatinase/type IV collagenase plays a more important role in invasion. We have found that HT1080 x human fibroblast hybrids have reduced ability to invade a reconstituted basement membrane (Matrigel) in vitro compared to HT1080 cells, and abundantly secrete only the 68-72 kDa gelatinase/type IV collagenase. These data suggest that the 92 kDa gelatinase/type IV collagenase may be more important in HT1080 cell invasion. We next transfected HT1080 genomic DNA into non-invasive mouse C3H/10T1/2 fibroblast cells, which secrete only 68-72 kDa gelatinase/type IV collagenase. Four invasive transfectants were established. These invasive transfectants secreted the 92 kDa gelatinase/type IV collagenase in addition to the 68-72 kDa gelatinase/type IV collagenase, whereas non-invasive control DNA transfectants did not secrete the 92 kDa gelatinase/type IV collagenase. These results suggest that the induction of the 92 kDa gelatinase/type IV collagenase is important in the invasive phenotype.

Animals

[Study on in vitro invasive potential of renal cell carcinoma cell lines and effect of growth factors (EGF and TGF-beta 1) on their in invasions].

Renal cell carcinomas (RCCs) frequently metastasize to distant organs in their clinical course. However, the mechanism of the metastasis had not been fully elucidated. In vitro invasion assay has been reported to be a rapid method for the evaluation of the invasive potential of various malignant cells. In vitro invasive potential of RCC has not been investigated by this method. Thus, in the present study, we first attempted to characterize the in vitro invasive potential of four human RCC cell lines which had been established in our institute. Secondly, we investigated the influence of two growth factors (EGF, TGF-beta 1) on the invasive potential of these cell lines when the two factors were applied as chemoattractants. SMKT-R-3 and R-4 cell lines showed more cell penetration through Matrigel than SMKT-R-1 and R-2 cell lines, suggesting that the former cell lines have higher invasive potential. While invasive potential varied in each cell line, it was enhanced by EGF in all cell lines. However, TGF-beta 1 suppressed the invasive potential of all four cell lines. These results suggest that two factors have different actions on the invasion of RCCs.

Carcinoma, Renal Cell

NR3C1 Modulates Wnt Signalling to Influence the Invasiveness and Immune Features of Nonfunctioning Invasive Pituitary Adenomas.

Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.

Humans

ras gene alterations in invasive and non-invasive rat bladder carcinomas induced by N-methyl-N-nitrosourea.

We have established a reliable method to induce invasive and non-invasive carcinomas in the heterotopically transplanted urinary bladder of rats by repeated injection of N-methyl-N-nitrosourea (MNU), and examined the alterations of the ras oncogenes and ras oncogene product (p21) in the induced tumours. The incidence of muscle-invasive carcinomas was proportional to the total dose of MNU. When 5, 6 or 12 doses of MNU were used, muscle invasive carcinomas developed in 22, 58 or 45% of animals, respectively, after a mean observation period, respectively, of 54 +/- 9, 45 +/- 13 and 38 +/- 3 weeks. Whereas activated H-ras gene was detected in only one non-invasive carcinoma by DNA transfection assay, seven of 18 non-invasive and invasive carcinomas showed activated ras p21 when examined by immunoblot analysis. Amplification or rearrangement of myc or epidermal growth factor (EGF) receptor gene was not observed. The results indicate that alterations of ras gene may be involved in the development of rat bladder carcinomas but not of invasiveness.

Animals

Expression of urokinase and its receptor in invasive and non-invasive prostate cancer cell lines.

We previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 10(6) cells per 48 h) than DU-145 cells (63 ng/ml per 10(6) cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.

Blotting, Northern

A biometrical study on esophageal invasion of carcinoma of the upper stomach. Part II: Radiographic evaluation of esophageal invasion on the basis of its occurring point and size.

Esophageal invasion of upper stomach cancer was analized on the resected specimen based on its occurring point and size. The distance of esophageal invasion was calculated by subtracting the distance between the occurring point and esophagogastric junction (EJG) from the radius of the cancer on the preoperative X-ray films. Fifty-six (76.7%) out of 73 resected cancers of the upper stomach invaded the esophagus. The average distance of invasion was 19.8 +/- 12.7 mm; the longest distance was 64.0 mm. The shorter was the distance of the occurring point from the EGJ, the longer was the esophageal invasion. The calculated distance of esophageal invasion of the cancer was correlated significantly with its histological distance (p less than 0.01). The distance of esophageal invasion can be seen with acceptable accuracy on the X-ray films preoperatively, even when the proximal edge of esophageal invasion is not clear on the films.

Adenocarcinoma

Tubulolobular invasive breast cancer: a variant of lobular invasive cancer.

Attention is directed to an apparently unique form of invasive breast cancer designated as tubulolobular invasive cancer. These neoplasms exhibit small tubules as well as cords of neoplastic cells in a lobular configuration reminiscent of lobular invasive carcinoma. The clinical and pathologic characteristics encountered in 24 examples were statistically compared with those of infiltrating ductal carcinomas without special specific features, pure tubular, and pure lobular invasive cancer. The results of these analyses as well as the morphologic characteristics of these lesions prompt the conclusion that this lesion represents a tubular variant of lobular invasive carcinoma. Short term treatment failure rates in patients with tubulolobular invasive carcinoma are intermediate between those of pure tubular cancer and lobular invasive carcinoma.

Breast Neoplasms

[Significance of blood vessel invasion in gastric carcinoma--prediction of liver metastases from the blood vessel invasion in the primary tumors].

This study was conducted to elucidate the factors related with liver metastases, to clarify the significance of blood vessel invasion and then to predict liver metastases from these findings. Patients examined were 102 cases which underwent gastrectomy and were followed-up for more than 5 years or until death at our department. Two new staining methods were applied in this study; Victoria blue + hematoxylin eosin double staining for elastic fiber and Factor VIII related antigen for vascular endothelium. Significant differences in qualitative frequency of blood vessel invasion, the number of lymph node metastases, and the depth of invasion were found in those patients with liver metastases, as compared with 5 year survivors. Quantitative analysis of blood vessel invasion revealed significant importance of blood vessel invasions in the submucosa, in the forms of complete thrombus, wall invasion and partial thrombus, in the diameters of 0.01-0.1 mm and 0.1-1.0 mm. Applying discrimination coefficients of linear discrimination analysis, prediction of liver metastases was possible with 81.8% sensitivity, 85.3% specificity, and 83.6% accuracy. Liver metastases can be predicted from the qualitative and quantitative analyses of blood vessel invasion in the primary tumors by elastic fiber staining.

Gastric Mucosa

Invasive epithelial cells show more fast plasma membrane movements than related or parental non-invasive cells.

Fast plasma membrane movements (FPMM) are involved in ruffling, blebbing, fast shape change, and fast translocation. A simple method for the quantification of FPMM was used to study the relation between FPMM and invasive capacity in five pairs of invasive and noninvasive variants from four different epithelial cell types. The human mammary cell line MCF-7/6, the ras-transformed dog kidney cell line ras-MDCK, the ras-transformed mouse mammary gland cell lines NM9-ras-12 and NM-f-ras-TD, and spontaneously transformed late passage mouse lens explant MLE cells, all of which were invasive in vitro, showed more FPMM in our measurements and displayed more ruffling activity on time-lapse video films than the related or parental MCF-7/AZ, MDCK-3, NM9, and NM-f cell lines and early passage MLE cells, none of which were invasive. Interestingly, induction of invasive capacity in MCF-7/AZ cells by retinoic acid was accompanied by an increase in FPMM, but speed of translocation was not increased. Together these observations support the hypothesis that a certain level of FPMM is a prerequisite for invasive capacity.

Animals

Incidence of invasive group A streptococcal infections and comparison of emm types from invasive infections, pharyngitis, and throat carriage in American Indian communities in the Southwest United States.

BACKGROUND: American Indian/Alaska Native (AI/AN) communities in the US have high rates of group A streptococcal (GAS) infections. We determined the incidence of invasive infections in AI communities in the Southwest and compared emm types from invasive infections, pharyngitis, and throat carriage. METHODS: Activities conducted in the White Mountain Apache Tribal lands (WMA) and Navajo Nation (NN) included active, laboratory-based surveillance for invasive GAS infections (WMA: 2019─2024; NN: 2023─2024; all ages); surveillance for GAS pharyngitis (2023-2024; children 0─17 years); and culture for GAS from oropharyngeal carriage samples (2019 and 2022─2023; children 0─14 years). Emm types were determined by whole-genome sequencing. Annual incidence rates were calculated using Poisson regression. RESULTS: In WMA, age-standardized rates of invasive infections ranged from 80-270/100,000 persons between 2019-2024. Predominant emm types varied (n=74 isolates): 91 (59%) and 49 (32%) in 2019-2020, and 43 (40%) and 53 (30%) in 2023. In NN, rates were 40-60/100,000 persons in 2023-2024; common emm types (n=51) were 53 (28%), 101 (18%), and 12 (16%). In WMA and NN, emm types 1, 12, and 53 predominated in pharyngitis (n=190), and 1, 12, and 91 in throat carriage (n=119). CONCLUSIONS: Rates of invasive GAS infections in these communities were 3-35 times higher than the national US average (12.2/100,000 in 2024). Emm types varied over time with limited overlap in strains from throat carriage or pharyngitis isolates and those from invasive infections. Findings support continuing GAS surveillance and engaging AI/AN communities throughout vaccine development and evaluation.

Indigenous health

Tumor invasion-inhibiting factor 2: primary structure and inhibitory effect on invasion in vitro and pulmonary metastasis of tumor cells.

The primary structure of tumor invasion-inhibiting factor 2 (IIF-2) purified from bovine liver (A. Isoai et al., Jpn. J. Cancer Res., 81:909-914, 1990) was determined. A computer homology search of the National Biomedical Research Foundation data bank revealed that IIF-2 is identical to the carboxyl-terminal region, residue number [69-89], of high mobility group 17 which is a DNA-binding non-histone protein. IIF-2 synthesized by an automated peptide synthesizer showed similar invasion-inhibitory activity as compared with the purified factor, when tested with the monolayer invasion assay system using highly invasive rat ascites tumor cells. When examined with the other in vitro assay systems using a modified Boyden chamber, the synthetic IIF-2 suppressed the chemotactic migration of highly metastatic B16 melanoma (B16FE7) cells to fibronectin or laminin and invasion through Matrigel. The IIF-2 inhibited neither the cell proliferation nor the binding of cells to fibronectin or Matrigel and also showed no significant inhibition of Mr 90,000 type IV collagenase (gelatinase) obtained from human schwannoma (YST-3) cells. The formation of lung colonies in mice given injections of B16FE7 and Lewis lung carcinoma cells was significantly reduced by the coinjection of the IIF-2. These results suggest that IIF-2 suppresses tumor invasion by impairing cell motility and inhibits the migration of metastasizing cells through extracellular matrix (extravasation steps) following their arrest in the capillary bed of the lung in vivo.

Amino Acid Sequence

T- and B-lymphocyte subpopulations in pre-invasive and invasive carcinoma of the cervix.

Lymphocyte subpopulations in patients with pre-invasive and invasive cervical carcinoma, other gynaecological malignancies and controls were studied. T lymphocytes were recognized by their ability to form spontaneous rosettes with sheep red blood cells (E rosettes). Two surface marker characteristics were used to detect B lymphocytes: the receptors for activated complement responsible for erythrocyte-antibody-complement (EAC) rosette formation, and surface membrane immunoglobulin (SMIg), which is readily stainable by immunofluorescence. There was a significant depression in T cells in association with invasive but not pre-invasive cervical carcinoma. The results for B cells varied according to the method used for their detection. EAC rosette-forming (EAC-RFC) were significantly raised in patients with invasive cancers but not in patients with pre-invasive cancer. SMIg-bearing cells were not significantly altered by the presence of malignant disease. The changes in E-RFC and EAC-RFC numbers were more marked in patients with extensive cancers. Possible functional implications of these findings are discussed.

Adolescent

Putative invasion-specific proteins in mouse T-cell hybridomas that differ in invasive and metastatic potential.

Fusion of invasive, activated T-lymphocytes with non-invasive BW5147 T-lymphoma cells mainly yields highly invasive (HI), highly metastatic T-cell hybridomas. In addition, several non-invasive (NI), non-metastatic hybrids have been obtained, probably due to loss of involved gene(s) by chromosome segregation. Here we have compared a panel of HI and NI hybrids in a search for proteins specifically expressed by either cell type. MAbs were raised against HI hybrids, but out of more than 1,000 none bound exclusively to HI cells. Furthermore, polyclonal rat, rabbit and chicken antisera did not immunoprecipitate specific proteins from total lysates, and the expression of 18 (T-cell) surface markers did not correlate with invasiveness. These results indicated that the number of differences between HI and NI hybridomas was surprisingly small. This notion was confirmed by 2-dimensional gel electrophoresis. Among 1,000 detectable spots, we found only 2 clear-cut differences between HI and NI T-cell hybridomas, whereas multiple differences were found between individual hybrids. One protein (p130) was expressed at much higher levels by HI than by NI hybrids in this panel, whereas the other (p15) was only seen in NI hybrids. These proteins are primary candidates for a role in invasion.

Animals