Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Metastatic”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2003

Number of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma.

OBJECTIVES: To perform a retrospective study to determine whether survival and immunotherapy response are related to the site of metastases (lung versus bone) and to the number of organ sites involved (one versus multiple). The most common sites of metastatic renal cell carcinoma (mRCC) are the lung and bone. METHODS: The records of 434 patients with mRCC were reviewed. Patients with pathologic evidence of nodal involvement were excluded, leaving 120 patients with mRCC to lung only, 33 patients to bone only, and 144 patients with multiple organ involvement. The response rates to immunotherapy and overall survival were compared. The variables evaluated in statistical analyses included Eastern Cooperative Oncology Group score, grade, 1997 tumor stage, and multiple organ involvement. RESULTS: The median survival for patients with lung only and bone only mRCC was 27 months; patients with multiple organ involvement had a median survival of 11 months. In patients who underwent nephrectomy followed by immunotherapy, the median survival time was 31, 31, and 13 months in the lung, bone, and multiple sites groups, respectively. The response rate to immunotherapy after nephrectomy was 44%, 20%, and 14% in the lung, bone, and multiple organ groups, respectively. Multivariate analysis confirmed that metastatic disease to more than one organ site was associated with poor prognosis (2.05 risk ratio, P <0.001). CONCLUSIONS: Patients with mRCC to only one organ site fared significantly better than patients who had evidence of disease in multiple organs. Survival in patients with disease limited to the lung was similar to that of patients whose disease was limited to bone.

Bone Neoplasms↗
PubMed1985

Colony-stimulating activity from the new metastatic TS/A cell line and its high- and low-metastatic clonal derivatives.

We investigated the presence of colony-stimulating factor (CSF) in supernatants obtained from TS/A, a new metastatic murine cell line, and from its high-and low-metastatic clonal derivatives (E and F clones, respectively). TS/A cells produced a CSF in vitro that induced proliferation and differentiation of murine monocytic and granulocytic progenitors in agar cultures. In TS/A-bearing mice remarkable splenomegaly, blood granulocytosis and thymus depletion were observed along with a stimulatory activity in serum and a strong proliferative activity both in spleen and in bone marrow populations. Conditioned media from E clones showed an in vitro colony-stimulating activity greater than those of F clones. Mice injected subcutaneously with cells of all clones studied showed granulocytosis, splenomegaly and thymus depletion, although to varying degrees. However, no direct correlation between granulocytosis-splenomegaly and the number of spontaneous lung metastases was observed.

Animals↗
PubMed2005

Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease.

HER-2 overexpression, a predictive marker of tumour aggressiveness and responsiveness to therapy, occurs in 20-30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 measurement is carried out in primary tumour. This study aims to evaluate HER-2 overexpression in primary and metastases and its effect on treatment decisions. Biopsies from primary breast cancer and corresponding metastases from 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically in all primary and metastatic sites. Positive overexpression in primary and/or metastases was confirmed by fluorescence in situ hybridisation (FISH). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (eight of 58 patients). Concordance was found in 50 (86%) of patients (95% CI: 77-95). In one patient (2%), HER-2 was negative in metastasis but positive in primary. In seven (12%) patients, HER-2 was positive in metastases and negative in primary (95% CI: 3.7-20), and three of them responded to trastuzumab. Gene amplification by FISH was found in all cases with HER-2 positive (+2 and +3) by immunohistochemistry. Our data suggest that a possible discordance of HER-2 overexpression between primary and metastases should be considered when making treatment decisions in patients with primary HER-2-negative tumours.

Adult↗
PubMed1997

Phase II study of high-dose cyclophosphamide, etoposide, and carboplatin (CEC) followed by autologous hematopoietic stem cell rescue in women with metastatic or high-risk non-metastatic breast cancer: multivariate analysis of factors affecting survival and engraftment.

Seventy women with high-risk stage II (n = 10), IIIA (n = 12), IIIB (n = 11), or IV (n = 37) breast cancer received cyclophosphamide 6000 mg/m2, etoposide 2400 mg/m2, and carboplatin 1200 mg/m2 followed by infusion of autologous hematopoietic stem cells (AHSC). Women with high-risk stage II disease had eight or more involved axillary lymph nodes (n = 9) or axillary and breast relapse following lumpectomy, chemotherapy, and radiation therapy (n = 1). Women with measurable stage III or stage IV disease were required to demonstrate complete or partial response to conventional-dose chemotherapy prior to transplant. The overall (complete plus partial) response rate for the 31 patients not in complete remission at the time of transplant was 55%. With a median follow-up of 545 days, the 2-year actuarial progression-free survival rates for patients with stage II, IIIA, IIIB and IV are 86, 75, 42 and 13%, respectively. Factors independently predictive of longer progression-free survival by multivariate analysis included lower stage disease, status of disease at transplant (in CR vs not in CR), and positive estrogen receptor status. Factors predictive of more rapid neutrophil engraftment by multivariate analysis included post-transplant administration of hematopoietic growth factors, greater number of infused CFU-GM, mobilization with G-CSF or cyclophosphamide/G-CSF (vs mobilization with GM-CSF or no mobilization), and lower stage disease. Only one patient (1.4%) died prior to day 100 from any cause. High-dose cyclophosphamide, etoposide, and carboplatin followed by infusion of AHSC constitutes an active and well-tolerated regimen in the treatment of women with high-risk non-metastatic or metastatic breast cancer.

Adult↗
PubMed2003

Tumour cell and stromal features in metastatic and non-metastatic non-small cell lung carcinomas.

AIMS: Tumour cell behaviour depends on the interactions between nuclear genetic changes in the malignant cells and a stroma favourable for growth, invasion and metastasis. To evaluate such interactions, we studied the relationship between tumour cell and stromal features for proliferative factors, p53, microvessel density and metalloproteinases, controlled for the extent of the primary lesion (T1 to T4), in early (non-metastatic) and late (metastatic) non-small cell lung carcinomas (NSCLC). METHODS AND RESULTS: Variables were examined for differences and correlations in the frequency of p53, AgNOR, CD34 and MMP-9 expression in primary lesions and metastases of NSCLC using a general linear model. The patients included 58 males and 22 females (mean age 62 +/- 9 years) with 19 T1 (23.8%), 40 T2 (50.0%), 14 T3 (17.5%) and seven T4 (8.8%). In late disease, AgNOR and p53 were statistically related to the extent of the primary lesion, whereas in early disease AgNOR tended to be increased in tumours without metastasis, while p53 expression tended to decrease progressively in tumours with metastasis. Microvessel density in late disease was of no statistical significance, whereas in early disease strong CD34 expression was seen in tumours with metastasis, being at its maximum in T3 primary lesions. The best marker for the extent of the lesion and its progression was MMP-9, with greater expression by tumours with metastasis than those without. CONCLUSIONS: Different tumour cell and stromal interactions control metastasis and therefore the biological risk of NSCLC. A panel of molecular markers, such as p53, MMP-9 and CD34 could help to identify subgroups of patients that could benefit from adjuvant therapy.

Adult↗
PubMed1985

Expression of the metastatic phenotype in cells transfected with human metastatic tumor DNA.

NIH 3T3 mouse fibroblasts form nonmetastasizing fibrosarcomas upon transformation by the Ha-ras oncogene isolated from the EJ human bladder carcinoma cell line and subcutaneous inoculation into immunocompetent NFS/NCr mice. DNA from a human metastatic tumor was transfected into these Ha-ras transformants, and one of the resulting colonies yielded a lung metastasis after subcutaneous inoculation. DNA was isolated from this metastasis and subjected to a second round of transfer into Ha-ras-transformed NIH 3T3 cells. Inoculation of these transfected cultures into mice led once again to formation of metastases, this time at a higher frequency. Examination of four of the resulting metastases revealed discrete human DNA fragments that were common to all four. These findings demonstrate that the metastatic phenotype can be transferred via DNA from cell to cell and is associated with the presence of a discrete DNA segment. This segment is not identical to the myc oncogene or to any of the frequently detected ras tumor oncogenes.

Animals↗
PubMed1986

Metastatic uveal melanoma: an ocular melanoma associated antigen in the serum of patients with metastatic disease.

Two monoclonal antibodies, MAb8-1H and ME491, which bind to different determinants of the same highly glycosylated melanoma-associated antigen, were used to determine melanoma-associated antigen levels in serum samples from patients treated for primary choroidal or ciliary body melanoma and who subsequently developed systemic metastasis. An immunoassay was developed in which ME491 was absorbed to polystyrene beads in order to bind the melanoma-associated antigen present in serum. 125I-MAb8-1H was used to detect the bound antigen. This double-determinant immunoassay is both sensitive and reproducible. Supernatant fluids of tissue cultured melanoma cell lines served as positive standards for the calculation of melanoma-associated antigen units. The mean serum levels of melanoma-associated antigen were 7.7 units for patients with benign ocular conditions, 9.51 units for patients with choroidal melanoma without documented metastatic disease, and 48.3 units for patients with choroidal melanoma and documented systemic metastasis. The clinical implications of using this test as a screening method for the detection of metastatic disease is discussed.

Antibodies, Monoclonal↗
PubMed1999

Hydroxyurea treatment enhances metastatic cell adhesiveness: a possible chemotherapy-induced increase in metastatic potential?

Treatment of tumor cells with certain chemotherapeutic agents, including hydroxyurea, increases their metastatic potential. In the present study the adhesiveness of SW620 colonic metastasis cells treated with hydroxyurea was compared with untreated cells by measuring their ability to remain attached to tissue flask walls during gentle saline washes. Treatment of SW620 cells was found to significantly increase their adhesiveness, suggesting a mechanism by which hydroxyurea may enhance the metastatic potential of tumor cells.

Antineoplastic Agents↗
PubMed1999

Metastatic cutaneous plasmacytoma: a case report associated with IgA lambda multiple myeloma and a review of the literature of metastatic cutaneous plasmacytomas associated with multiple myeloma and primary cutaneous plasmacytomas.

We present the case of a 67-year-old Japanese woman with immunoglobulin A lambda (IgA lambda) multiple myeloma (MM). She had firm nodular cutaneous lesions on the trunk and scalp without adjacent bone involvement. The patient was diagnosed as having IgA lambda MM of stage IIIA with 52% plasmacytosis in the bone marrow six months before the appearance of the cutaneous lesions. The abnormal plasma cells showed moderate to marked dysplasia in both the bone marrow and skin lesions. The abnormal plasma cells in the bone marrow exhibited abnormal karyotypes: 41, XX, der (1) t (1p; 1q), -4, -10, -14, -16, -17, 17p+, that differed from the "unfavorable" karyotype reported previously. We reviewed the cases of metastatic cutaneous plasmacytoma in MM and cases of primary cutaneous plasmacytoma that have been reported in English or Japanese and identified the Ig class. Among the 83 cases of metastatic cutaneous plasmacytomas in MM, IgG, IgA, IgD, and Bence-Jones protein were found in 52%, 23%, 16%, and 6%, respectively. A disproportionately high frequency of IgD lambda MM was found to have spread to the skin, compared with the frequency of IgD MM itself, which was present in only around 2% of the MM cases. Among the 18 primary cutaneous plasmacytomas, IgG, IgA, and Bence-Jones protein were found in 56%, 11%, and 17%, respectively, but no IgD was found.

Aged↗
PubMed1986

Renal handling of calcium and sodium in metastatic and non-metastatic malignancy.

Investigation of the renal handling of calcium and sodium in rehydrated patients with hypercalcaemia associated with malignancy showed enhanced reabsorption of calcium in most cases. This was a feature of both metastatic and non-metastatic malignancy, and in this respect the patients were indistinguishable from patients with primary hyperparathyroidism. As the increased calcium reabsorption was inversely correlated with the rate of excretion of sodium modest salt loading can be used to inhibit this process. This is an important practical aspect of the treatment of patients with this type of hypercalcaemia.

Absorption↗
PubMed2005

Identification of differentially expressed genes in metastatic and non-metastatic nasopharyngeal carcinoma cells by suppression subtractive hybridization.

BACKGROUND & OBJECTIVE: Nasopharyngeal carcinoma (NPC) is an epithelial neoplasm with high occurrence rates in southern China. The disease often metastasizes to regional lymphnodes at a very early stage. Local recurrences and metastasis occur frequently in patients with NPC and are a leading cause of death, despite improvements on treatment modalities. The molecular mechanism underlying the metastasis of nasopharyngeal carcinoma remains poorly understood, however, and requires additional elucidation. The aim of this study was to explore possible NPC gene candidates that may play key roles in NPC metastasis. METHODS: Subtractive suppression hybridization (SSH) was performed to isolate differentially expressed clones between the metastatic 5-8F and non-metastatic 6-10B nasopharyngeal carcinoma cell lines. Differentially expressed clones were screened and confirmed by reverse Northern blotting. The sequences of cDNA fragments were subsequently analyzed and compared to known sequences in Genbank. RESULTS & DISCUSSION: The SSH library contained thousands of positive clones. Random analysis of 300 clones by PCR demonstrated that 269 clones contained inserted fragments. Reverse Northern blot confirmed that 20 out of 192 clones examined were significantly up-regulated in the 5-8F cell line. Among these 20 clones, 16 were previously identified genes (flotilin-2, ezrin, pim-3, fli-1, mel, neugrin, znf216, ASB1, raly, UBE2A, keratin6A, TMED7, EIF3S9, FTL, two ribosomal proteins RPL21 and RPL16), two were predicted genes (c9orf74 and MDS006), and two sequences shared no homology with known genes listed in GenBank and may represent novel genes. The proposed functions of the genes identified in this study include cell signal transduction, cell survival, transcription regulation, cell mobility, protein synthesis, and DNA damage repair. Flotillin-2, fli-1, pim-3 and ezrin have previously been reported to be associated with tumor metastasis and progression. The remaining up-regulated genes identified in this study have not been reported to be markers of metastasis and may represent new candidates of NPC metastasis-related genes. The results of this study may provide novel points of therapeutic intervention for NPC.

DNA, Complementary↗
PubMed2006

Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors.

Electroporation is a novel therapeutic modality that uses pulsed electrical currents to enhance the uptake of drugs, vaccines and genes into cells, and has been used for over 20 years. Electroporation therapy using cytotoxic drugs is called electrochemotherapy. Electrochemotherapy has been studied in vitro, in vivo and in clinical trials. It is potentially useful for treating patients with metastatic tumors, such as melanoma, and even select primary tumors, such as head and neck squamous cell carcinomas and basal cell carcinoma. Various chemotherapeutic agents have been tested with electroporation therapy, but bleomycin and cisplatin are the two most widely used. The biological basis of electroporation therapy is outlined in this review and basic science studies and the limited clinical studies that have involved electrochemotherapy are reviewed. Particular focus is placed on trials involving melanoma, head and neck cancers and other primary and metastatic skin cancers.

Antibiotics, Antineoplastic↗
PubMed1996

Renal cell carcinoma metastases. Review of unusual clinical metastases, metastatic modes and patterns and comparison between clinical and autopsy metastatic series.

We reviewed all cases of unusual clinical metastases of renal cell carcinoma found in the English literature. The percentages of usual and unusual clinical metastases are compared with data of some large autopsy series. The involvement of various organs is considered and some metastatic modes and patterns are reported. The analysis shows that clinical metastases are obviously underdiagnosed. Correct staging based on careful clinical investigations is paramount for optimal management of metastatic renal cancer.

Autopsy↗
PubMed2000

TGF-beta1 and IGF-1 expression are differently regulated by serum in metastatic and non-metastatic human breast cancer cells.

Transforming growth factor-beta (TGF-beta) exerts an inhibitory effect on epithelial cell proliferation while insulin-like growth factor-1 (IGF-1) is a positive regulator of proliferation and together they may participate in driving neoplastic progression. The regulation of TGF-beta1 and IGF-1 gene expression was analyzed in an in vitro model of an estrogen receptor positive (ER+), non-metastatic (MCF-7) and an (ER-), metastatic (MDA-MB-435) breast cancer cell line, respectively. Our results indicate a loss of the regulation of TGF-beta1 and the gain of the expression and upregulation of IGF-1 pathways during malignant progression. These data demonstrate that two factors, convergent on cell growth, can have divergent roles in the regulation of the expression of TGF-beta1.

Blood↗
PubMedDate not supplied

Modulation of apoptosis, tumorigenesity and metastatic potential with antisense H-ras oligodeoxynucleotides in a high metastatic tumor model of hepatoma: LCI-D20.

BACKGROUND/AIMS: To investigate the effect of antisense H-ras DNA on tumorigenesity, apoptosis and metastasis of a high metastatic tumor model of human hepatocellular carcinoma in nude mice LCI-D20. METHODOLOGY: LCI-D20 cells in primary culture were treated with 10 microns/L antisense oligodeoxynucleotide (ODN) drugs in vitro. 1.5 x 10(6) LCI-D20 cells with or without pretreatment were inoculated into each elevated subcutaneous (s.c.) flap in 14 nude mice, 6 animals for antisense H-ras oligodeoxynucleotide treated cells, 4 for H-ras non-specific antisense oligodeoxynucleotide treated cells, and the rest 4 for cells without pretreatment. RESULTS: In in vitro cell culture study, 5-day continuous suppression of H-ras expression by antisense H-ras oligodeoxynucleotide resulted in significant inhibition of the proliferation of LCI-D20 cells (t = 31.529, P < 0.01). In situ end-labeling detection showed that apoptotic cell death was significantly increased in cells with 5-day treatment of antisense H-ras oligodeoxynucleotide (34.0 +/- 4.5%) in comparing with cells without treatment (2.5 +/- 1.2%, t = 13.434, P < 0.01) or treated with non-specific antisense oligodeoxynucleotide (4.8 +/- 1.4%, t = 12.453, P < 0.01) at the corresponding time. In the in vivo experiment, at week 6, no palpable tumor could be found in 50% (3/6) of animals receiving cells with pretreatment of antisense H-ras oligodeoxynucleotide, while 100% (4/4, 4/4) of animals in the 2 control groups developed palpable tumors. Tumor growth in antisense H-ras treated animals was significantly retarded in comparison with that of the untreated (t = 3.509, P < 0.01) or non-specific antisense oligodeoxynucleotide treated animals (t = 3.452, P < 0.01). 75% to 100% of animals in the 2 control groups developed lung metastases, while in antisense H-ras treated animals lung metastasis foci could not be found by random serial section and microscopy (u = 2.536, P < 0.01; u = 3.162, P < 0.01, respectively). CONCLUSIONS: Specific inhibition of H-ras expression by antisense H-ras oligodeoxynucleotides could not only induce apoptotic cell death, inhibit the growth rate of LCI-D20 cells in vitro and in vivo, but also alter in vivo tumorigenesity and metastatic potential of LCI-D20 cells.

Animals↗
PubMed2000

[Facial paralysis of metastatic origin. Review of metastatic lesions of the temporal bone].

Metastatic lesions in temporal bone were rare in the past but are increasing, it seems, nowadays. We present the case of a women patient which first and only metastatic symptom was her peripheral facial paralysis. In our review of world literature of this topic only 148 published cases were found. Tumors more frequently spreading to temporal bone, in decreasing order of development, are those of the breast, lungs, kidney, stomach and prostate. Clinically these metastases become manifest by hypoacusy, buzzing ears, body unbalance, vertigo and facial palsy. The prognosis of these disorders are related to the serverity of the systemic disease.

Adenocarcinoma↗
PubMed2001

[Relationship between the anti-metastatic effect of UFT and in vitro chemosensitivity to 5-FU in metastatic tumors from orthotopic implanted colon cancer in nude rats].

We have investigated the correlation between the in vitro chemosensitivity to 5-FU, measured using the collagen gel droplet embedded culture drug sensitivity test (CD-DST), and the anti-tumor effect of UFT, a prodrug of 5-FU, in metastatic tumors from orthotopic implanted colon cancer in nude rats. Human colon cancer cells (KM12SM) were injected into the cecal wall of the nude rats. Five weeks later, the implanted cecal tumors were removed. Oral UFT (a daily dose of 30 mg/kg) was administered postoperatively for four weeks. After the UFT administration period, the lung and lymph nodes were analyzed macroscopically and microscopically. In vitro chemosensitivity to 5-FU in the lung and lymph node metastases was tested using CD-DST, and the enzymatic activities of thymidine synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in the lung and lymph node metastases were measured. A daily administration of UFT produced an inhibitory effect on lung metastasis compared with the control group. However, there was no difference in the frequency of lymph node metastasis. The inhibition rate produced by 5-FU in CD-DST was significantly higher for lung metastases than for lymph node metastases. There was no difference in the TS and DPD activities between the metastatic tumoral tissues. These results suggest that the organ specificity of the anti-tumor effects of UFT on colon metastases may be determined by CD-DST of 5-FU for individual tumors. The TS and DPD activity in the tumoral tissues may not affect the organ specificity of the anti-tumor effect of UFT on colon metastases.

Animals↗