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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor progression of cancers is manifested by phenotypic property changes including development of hormone/growth factor independence and metastatic ability. The progression results from acquired genomic alterations leading to clonal heterogeneity and outgrowth of more aggressive and therapy-resistant sublines. Previously, a cultured rat "Nb2 lymphoma" cell line was established, whose viability depends critically on the hormone, prolactin, acting as the principal growth factor. By prolactin starvation, prolactin-independent sublines were generated which possessed the parent karyotype plus extra acquired chromosomal changes (clonal evolution). In this study, the parent line (Nb2-U17) and a cloned subline (SFJCD1) were compared for metastatic ability using single s.c. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 tumors showed no evidence of metastases at autopsy, even when tumors at implantation site reached a size of 9 cm (length + width). In contrast, rats (19) bearing SFJCD1 tumors showed multiple metastases (liver, kidney) when transplants exceeded 5 cm. This difference in metastatic ability may be related to the acquisition of an inversion in chromosome 1, i.e. inv(1)(q31q41). The 1q41 locus is adjacent to the reported H-ras-1 proto-oncogene locus (1q41-q42). In another subline, tetraploidization (flow cytometric analysis, karyotyping) occurred spontaneously following prolonged culturing (20 mo). Together, the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellular and molecular mechanisms underlying tumor progression to the metastatic phenotype.
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PMID:The rat Nb2 lymphoma: a novel model for tumor progression. 787 71

We report on eight meningiomas that have been operated on via the transsphenoidal route since May 1988. Six patients harbored cavernous sinus meningiomas with intrasellar extension. The intrasellar tumor extension and the parasellar tumor portion medial to the carotid artery were removed. Decompression of the pituitary gland with normalization of prolactin levels was achieved in all patients. It is a well-tolerated approach to confirm the diagnosis and still allows the option of major transcranial surgery in the event of tumor progression. Additionally, we report complete tumor removal in two rare cases with intrasellar and suprasellar merely subdiaphragmatic meningiomas.
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PMID:The role of transsphenoidal microsurgery in the management of sellar and parasellar meningioma. 845 14

Resistance to bromocriptine, defined as the absence of normalization of prolactin (PRL) levels despite a 15-30 mg daily dose of bromocriptine during at least 6 months, has been observed in 5-17% of the prolactinomas according to the literature. The recent availability of a new potent dopamine agonist, quinagolide, prompted us to analyze its long-term therapeutic effects in 28 patients with prolactinomas resistant to bromocriptine. Before bromocriptine, their PRL levels were 520 +/- 185 micrograms/l (mean +/- SEM) and decreased to 291 +/- 154 micrograms/l after a 6-21 month period of bromocriptine treatment. All the women (N = 20) remained amenorrheic and hypogonadism was not improved in men (N = 8). Subsequently, after 1 year of 150-300 micrograms/day quinagolide, 12/28 patients of the present series recovered normal gonadal function and their initial mean baseline PRL value (404 +/- 180 micrograms/l) was 16 +/- 2 micrograms/l after 1 year of treatment. A significant tumor shrinkage was observed in 5/8 macroadenomas (62%). During the 3-year follow-up period under quinagolide, a similar good control was achieved in these patients, with the exception of one man presenting with a secondary rise of PRL under quinagolide. In contrast, 15 other patients (one patient interrupted quinagolide at 6 months because of poor tolerance) were not normalized under 150-450 micrograms/day quinagolide. Their initial PRL levels (606 +/- 298 micrograms/l) were reduced to 343 +/- 187 micrograms/l (versus 463 +/- 265 micrograms/l under bromocriptine after the same duration of treatment). Despite such a partial inhibitory effect of quinagolide, 7/12 women resumed menstrual cycles and three pregnancies occurred. In no case was any tumor shrinkage noticed during the 3-4-year follow-up. Three patients even presented, after 2 years of quinagolide treatment, with a secondary rise of PRL values associated with a further tumor growth in two patients. During the 3-year follow-up period, nine pregnancies occurred in seven women. In five women, after quinagolide withdrawal, the plasma PRL baseline values ranged from 52 to 158 micrograms/l and from 65 to 192 micrograms/l, respectively, at the first trimester and at the end of uneventful pregnancies. In contrast, in two women a rapid increase of PRL (240-400 micrograms/l) correlated with tumor growth during the first trimester. Such a tumor progression was blocked by quinagolide treatment but not by bromocriptine. These data, although observed in a limited series, justify the careful follow-up of pregnancies in this subclass of patients at risk. Finally, in the whole population, long-term control of hyperprolactinemia by quinagolide was obtained in 11/28 patients (39%) previously resistant to bromocriptine, and 15/20 women (75%) resumed normal gonadal function with a quinagolide daily dose of 300 micrograms in most of them.
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PMID:Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy. 892 22

A 49-yr-old woman presented with an extensive prolactinoma (serum PRL > 10,000 mU/L, normal range < 450 mU/L). Over a 5-yr period following transsphenoidal surgery and pituitary irradiation, she became increasingly resistant to high doses of bromocriptine and underwent transfrontal surgery followed by stereotactic radiotherapy. In spite of these treatments, serum prolactin estimations rose progressively to > 100,000 mU/L. Magnetic resonance imaging scanning demonstrated a massive cystic tumor invading the temporal lobes, extending into the cervical and thoracic spine, with metastases to cervical lymph nodes. High-dose cabergoline administration resulted in a 30% decrease in serum PRL. Octreotide was administered as a continuous sc infusion with a profound analgesic effect on facial pain but with no effect on tumor progression. She was treated with a course of chemotherapy consisting of carboplatin and etoposide without any noticeable effect. The patient died 6 months following chemotherapy. Immunocytochemical analysis demonstrated positive nuclear staining for WAF-1, Rb protein, c-myc, and p53 both in the original and metastatic tumors. The metastases but not the primary tumor stained for c-jun. Metastatic prolactinoma remains a therapeutic challenge. It is associated with a variable proto-oncogene expression, which may be coincidental or causal. Cabergoline had no advantage over bromocriptine. Octreotide relieved facial pain but did not alter tumor progression. An effective therapy for metastatic prolactinoma remains to be identified.
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PMID:Metastatic prolactinoma: effect of octreotide, cabergoline, carboplatin and etoposide; immunocytochemical analysis of proto-oncogene expression. 928 27

The clinical and neuro-endocrine data of seven young male patients with suprasellar germinomas seen between 1984 and 1992 are reported. The most common initial symptom was 'idiopathic' central diabetes insipidus (DI), which occurred in all seven patients. The time interval between the appearance of this first clinical sign and the definitive diagnosis of a suprasellar germinoma ranged from 3 to 66 months. Raised prolactin levels and growth hormone deficiency were indicators of a process located in the hypothalamic-pituitary region. An increased beta-HCG level in the serum or the CSF confirmed the diagnostic suspicion of a germinoma and was helpful as a tumor marker in follow-up. Neuro-radiologic studies (CT or MRI) were also disappointing in the early stage when patients presented only with DI. Later on, as patients developed additional symptoms or signs related to the tumor, imaging studies were positive. Given the variable rate of tumor progression, the nonspecific early signs of hypothalamic-pituitary dysfunction (DI) as well as the often negative early imaging studies, the diagnosis of suprasellar germinoma is difficult but should always be considered in the presence of so-called 'idiopathic' central DI. Repeated brain MRIs are mandatory in young patients with idiopathic DI in order not to miss an underlying suprasellar germinoma.
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PMID:Suprasellar germinomas in childhood and adolescence: diagnostic pitfalls. 982 22

Colony stimulating factor (CSF-1) and its receptor (CSF-1R, product of c-fms proto-oncogene) were initially implicated as essential for normal monocyte development as well as for trophoblastic implantation. However, recent findings have suggested that CSF-1 and CSF-1R might have additional roles in mammary gland development during pregnancy and lactation. Studies with osteopetrotic (op-/op-) mice, which bear a specific mutation that inactivates the CSF-1 gene, demonstrated that op-/op- mothers are incapable of normal milk production due to the incomplete development of their mammary glands during pregnancy. Also, significant increases in the levels of CSF-1 and CSF-1R proteins are observed in the epithelial cells of mammary gland during pregnancy and lactation. In vitro studies investigating the effect of the three major lactogenic hormones (prolactin, insulin, and glucocorticoids) on the expression of CSF-1 and CSF-1R have demonstrated that expression of CSF-1 can be regulated by prolactin and insulin whereas CSF-1R expression is regulated by glucocorticoids. This apparent role for CSF-1/CSF-1R in normal mammary gland development is very intriguing because this receptor/ligand pair has also been found to be important in the biology of breast cancer, where they regulate tumor cell invasion by a urokinase-dependent mechanism. This review aims to summarize recent findings on the role of CSF-1 and its receptor in normal and neoplastic mammary development which may elucidate potential relationships of growth factor-induced biological changes in the breast during pregnancy and tumor progression.
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PMID:The role of CSF-1 in normal and neoplastic breast physiology. 989 62

Cultured rat pre-T Nb2 lymphoma cell lines have provided a useful model for tumor progression of T-cell cancers. Comparative analysis of the non-metastatic, prolactin (PRL)-dependent parental Nb2-U17 line and its PRL-independent and/or metastatic sublines, can be used in a search for progression-related genomic alterations. In the present study, the PRL-dependent, cloned Nb2-11C and PRL-independent Nb2-Sp sublines were used to examine development of metastatic ability and PRL independence relative to chromosomal alterations. Metastatic ability was determined using Noble rats carrying subcutaneous tumor transplants; PRL dependence/autonomy was checked in culture. Nb2-11C tumor transplants quickly gave rise to morbidity, associated with metastases in kidney and liver. Transplants of the slower growing Nb2-Sp cells showed variable tumorigenicity as metastases developed in only 40% of the rats (in lungs, kidney, stomach). G-banded chromosome analysis showed the Nb2-11C culture had the karyotype of the parental Nb2-U17 line plus an extra chromosome 19, thus, indicating an association between the development of metastatic ability in Nb2-11C cells and trisomy 19. The Nb2-Sp subline was not clonal. Its stemline showed two alterations in the parental karyotype: acquisition of an add(7)(q10) and loss of the extra chromosome add(15)(p12). Additional abnormalities, add(6)(q11) and trisomy 19, occurred in 15% and 5% of the Nb2-Sp population, respectively. Passaging of the Nb2-Sp subline in vivo resulted in generation and/or outgrowth of new sublines, a major one of which showed an apparent transient growth requirement for lactogens. Possible mechanisms underlying the PRL independence and in vivo properties of the Nb2-Sp cells are discussed.
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PMID:Malignant progression of rat Nb2 lymphoma cells: chromosomal alterations and metastatic properties. 1021 59

In the present study, we investigated the time-dependent interactive effects of daily injections of prolactin (PRL) and corticosterone (CORT) on the activation of lymphocyte function and inhibition of tumor growth in vivo in mice. BALB/c mice were injected subcutaneously with EMT-6 fibrosarcoma cells (a murine connective tissue tumor cell derived from mammary gland), and then different groups of animals were treated with PRL (1 microg/g body weight [BW] ip) at Oh, 4h, 8h, 12h, 16h, or 20h after CRT (1 microg/g BW ip) daily for 10 days. Different control groups were vehicle treated or treated with either hormone alone. Mice were kept in constant light 1 week before and during injections and in a 14:10 light-dark cycle thereafter. Tumor progression was monitored for up to 21 days after the cessation of treatment, and thereafter spleen lymphocytes were harvested and tested for mitogen-triggered proliferation. Prolactin administration at 8h or 16-20h after corticosteroid treatment reduced tumor volume by 77% and 49%, respectively, relative to vehicle-treated controls. Other time relations of hormone treatment were ineffectual. Further studies indicated that the immunosuppressant cyclosporin A (CSA) substantially stimulated tumor growth; this effect was completely abrogated by a simultaneous 8h related hormone treatment. How ever, the 8h hormone treatment was ineffective in inhibiting tumor growth in T-cell-deficient nude mice. Spleen lymphocytes from tumor-bearing (TB) mice showed an elevated basal proliferative capacity stimulated by concanavalin A (ConA; a stimulus for T-cell proliferation) and lipopolysaccharide (LPS; a stimulus for B-cell proliferation) compared to non-TB mice. Spleen lymphocytes from TB mice treated with CORT and PRL at 8h intervals exhibited an increased spontaneous (as well as LPS- and ConA- triggered) proliferation (by 104%, 48%, and 70%, respectively) compared with vehicle control TB mice. Fluorescence-activated cell sorting (FACS) analysis of splenocytes from hormone-treated animals indicated a 34-100% increase in the CD4+ (e.g., T helper cell) population. Treatment of animals with either hormone alone did not inhibit tumor growth or stimulate immune function relative to vehicle controls. The daily rhythms of plasma PRL, CORT, and thyroxine were all substantially altered by the presence of tumor in these mice. These results indicate that appropriately timed daily treatment of PRL and CORT can attenuate tumor growth, in part, via activation of antitumor immune mechanisms. Collectively, these data suggest that circadian neuroendocrine activities must be temporally organized appropriately to inhibit tumor growth.
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PMID:Timed daily administration of prolactin and corticosteroid hormone reduces murine tumor growth and enhances immune reactivity. 1037 1

Keratinocyte growth factor (KGF), alone and in synergism with progesterone (P) and prolactin (PRL), is mitogenic for normal mammary epithelium (ME) in vitro. In addition, P can upregulate ME sensitivity to KGF by slowing KGF receptor (KGFR) mRNA turnover in vitro. These hormonal interactions with KGF in vitro raise the possibility that alterations in these interactions can play a role in hormone-dependent mammary tumor growth and progression. The effect of hormones on KGF mitogenesis and the regulation of KGFR expression was examined in pregnancy-dependent (PDT) and ovarian-independent (OIT) mouse mammary tumors. In serum-free, collagen gel cell culture, dose/response (2-20 ng/ml) and time course studies showed that KGF stimulated the proliferation of PDT (not OIT) cells but synergism with P or PRL was not observed. The level of KGFR mRNA in PDT cells was not significantly different from normal ME but in OIT it was reduced more than 90%. P did not affect KGFR mRNA turnover in cultured PDT cells. However, KGFR mRNA was more stable in PDT cells compared to normal ME; after 6 days culture in basal medium, KGFR mRNA levels declined 40% vs. 85% previously shown for normal ME. Determination of KGF mRNA levels in tissues showed that it was lower in PDT compared to normal mammary gland and not detectable in OIT. These data show that in PDT both KGF-stimulated mitogenesis and the regulation of KGFR expression are independent of hormones. OIT has progressed to independence from any KGF influence. Thus, a subset of hormonally regulated pathways related to epithelial/stromal cell interactions can be lost in hormone-dependent mammary tumors during tumor progression.
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PMID:Attenuation and loss of hormonal modulation of KGF (FGF-7)/KGF receptor expression and mitogenesis during mammary tumor progression. 1086 47

Angiogenesis, the formation of new blood vessels out of pre-existing capillaries, is essential for tumor progression. Many factors have been identified that are able to inhibit angiogenesis. Here, we report the construction of a tricistronic retroviral vector encoding two inhibitors of angiogenesis expressed in mammals: the N-terminal fragment of rat prolactin (16KrPRL) and a secreted form of human platelet factor 4 (sPF4). When transduced by this retroviral vector, a rat glioblastoma cell line loses its ability of promoting endothelial cell locomotion, the initial step of angiogenesis, and the formation of an endothelial cell tube network. In spite of this encouraging in vitro result, however, the anti-angiogenic vector cannot block glioblastoma progression in animal models. These results suggest that therapeutic strategies aiming to block tumor progression through the inhibition of tumor-associated angiogenesis, should not only provide large numbers of angiogenesis inhibitors, but also target the angiogenic factors produced by tumor cells. Moreover, the data described herein may confirm recent findings from other groups which indicate that in order to successfully counteract tumor progression, drugs inhibiting new blood vessel formation should be employed in combination with traditional anti-tumor strategies, such as chemotherapy or radiotherapy.
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PMID:A tricistronic retroviral vector expressing natural antiangiogenic factors inhibits angiogenesis in vitro, but is not able to block tumor progression in vivo. 1189 69


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