Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Progression”

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 1,351 records · Page 75Linked to original sources

Progression of superficial venous thrombosis to deep vein thrombosis.

PURPOSE: We have evaluated the progression of isolated superficial venous thrombosis to deep vein thrombosis in patients with no initial deep venous involvement. METHODS: Patients with thrombosis isolated to the superficial veins with no evidence of deep venous involvement by duplex ultrasound examination were evaluated by follow-up duplex ultrasonography to determine the incidence of disease progression into the deep veins of the lower extremities. Initial and follow-up duplex scans evaluated the femoropopliteal and deep calf veins in their entirety; follow-up studies were done at an average of 6.3 days, ranging from 2 to 10 days. RESULTS: From January 1992 to January 1996, 263 patients were identified with isolated superficial venous thrombosis. Thirty (11%) patients had documented progression to deep venous involvement. The most common site of deep vein involvement was progression of disease from the greater saphenous vein in the thigh into the common femoral vein (21 patients, 70%), with 18 of these extensions noted to be nonocclusive and 12 having a free-floating component. Three patients had extended above-knee saphenous vein thrombi through thigh perforators to occlude the femoral vein in the thigh, three patients had extended below-knee saphenous disease into the popliteal vein, and three patients had extended below-knee thrombi into the tibioperoneal veins with calf perforators. At the time of the follow-up examination all 30 patients were being treated without anticoagulation. CONCLUSIONS: Proximal saphenous vein thrombosis should be treated with anticoagulation or at least followed by serial duplex ultrasound evaluation so that definitive therapy may be initiated, if progression is noted. More distal superficial venous thrombosis should be carefully followed clinically and repeat duplex ultrasound scans performed, if progression is noted or patient symptoms worsen.

Adult↗

Enhanced embryonic nonmuscle myosin heavy chain isoform and matrix metalloproteinase expression in aortic abdominal aneurysm with rapid progression.

Abdominal aortic aneurysms (AAAs) are characterized by structural deterioration of aortic wall leading to progressive dilatation. The histopathological changes in AAAs are particularly evident within the elastic media, which is normally comprised mainly of vascular smooth muscle cells (SMCs). There are vascular myosin heavy chain (MHC) isoforms; SM2 is specifically expressed in differentiated SMCs and SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of the fetal aorta with an immature phenotype. Although AAA altered expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), pathophysiological role of SMC phenotypic modulation in the AAA progression remains uncertain. To determine whether phenotypic modulation in vascular SMCs contributes to arterial medial degeneration, we examined MHC expression in SMCs of AAA. Aortic specimens were obtained from patients with slowly progressed AAA (n = 12) and rapidly progressed AAA (n = 5), and compared with normal aortic tissue (n = 3). Immunohistochemical staining was performed for detection of SMemb, SM2, MMP (types 2 and 9) and TIMP (types 1 and 2). Faint SMemb and abundant SM2 were observed in normal aorta, while the balance shifted to SMemb predominance in AAAs. Compared with slowly progressed AAA tissue, rapidly expanded AAA tissue demonstrated marked increases in SMemb expression with suppressed SM2. Predominant SMemb expression indicates presence of phenotypic modulated SMCs and enhanced MMP; while abundant TIMP was seen in mature SMCs expressing SM2. SMemb expression is markedly increased in AAA with MMP enhancement, and a significant imbalance between SMemb and SM2 results in rapid progression of AAA.

Aged↗

Vascular alterations during the development and progression of experimental heart failure.

BACKGROUND: Congestive heart failure (HF) is a multifactorial and progressive condition associated with multiple systemic and vascular alterations. The onset and progression of these alterations and the cause of the condition remain undefined. The main purpose of the present study was to help understand the temporal evolution of vascular alterations and their contribution to the pathogenesis of HF. Vascular reactivity to angiotensin II (Ang II) and norepinephrine (NE), as well as circulating and local angiotensin-converting enzyme (ACE) activity, were assessed in the Syrian cardiomyopathic hamster (SCH) model. METHODS AND RESULTS: We have shown previously that in 2-month-old SCH animals that had not yet developed the clinical manifestations of HF, the contractile response of aortic rings to Ang II was markedly enhanced compared with normal animals. In addition, SCHs showed increased ACE activity in aortic tissue. To assess the relevance of these findings to the development and progression of HF, the temporal evolution of the contractile response of aortic rings to Ang II and NE was evaluated in hamsters at 2, 6, and 11 months of age. Age-matched normal hamsters were used as controls. Within the SCH group, the maximal contraction induced to 10 mumol/L of NE in 2- and 11-month-old animals was similar, but significantly greater than in the age-matched controls (for 2-month-old animals; 1.43 +/- 0.21 g in SCHs v 1.04 +/- 0.15 g in controls; P < .05 and for 11-month-old animals; 1.41 +/- 0.14 g in SCHs v 1.06 +/- 0.07 g in controls; P < .05). The drug concentrations necessary to obtain 50% of the maximal response from the NE concentration-response curves were similar for SCHs and controls at all ages tested. In contrast, the contractility induced by 0.1 mumol/L of Ang II increased progressively in cardiomyopathic animals from 2 to 11 months of age (from 1.3 +/- 0.1 to 1.8 +/- 0.2 g; n = 9; P < .05). In age-matched normal hamsters, the contractile response to Ang II (0.9 +/- 0.1 g) did not vary with age. These findings were observed concomitantly with an increased ACE activity in plasma (18.65 +/- 1.77 nmol/mg x min in controls v 26.5 +/- 1.79 nmol/mg x min in SCHs; P < .05; n = 7) and in heart tissue (0.244 +/- 0.016 nmol/mg x min in controls v 0.563 +/- 0.027 nmol/mg x min in SCHs; P < .05; n = 20) of 11-month-old SCHs. CONCLUSIONS: These results suggest that, in young animals, increased vascular response to elevated levels of NE and hyperreactivity to Ang II could be critical factors in the development and progression of HF. Indeed, Ang II-induced contractility, as well as plasma and heart ACE activity, are good predictors of the progression and severity of HF.

Angiotensin II↗

A retrospective analysis of the results of p(65) + Be neutrontherapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: Survival and progression-free survival.

PURPOSE: To retrospectively evaluate survival, progression-free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. PATIENTS AND METHODS: Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neoadjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neoadjuvant hormonotherapy; seven patients only had an initial PSA < or = 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). RESULTS: The median follow-up was 2.8 years (0-7.8). Five-year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% CI: 54-74%) for the entire series. PFS in patients with an initial PSA > or = 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age. Biological responses with PSA < 1.5 ng/mL, < 1 ng/mL and < 0.5 ng/mL at any time after treatment were documented in 70%, 61% and 47% of the patients, respectively. CONCLUSION: Five-year OAS was 79%, PFS was 64%, and biological response was 70% for prostate cancer patients treated with mixed photon/neutron beams as applied at Louvain-la-Neuve, which are good results as compared with the literature. The usual prognostic factors were confirmed.

Adenocarcinoma↗

Ha-ras oncogene mutation associated to progression of papillomavirus induced lesions of uterine cervix.

BACKGROUND: Epidemiological and virological surveys suggest that the HPV presence is not enough condition to generate anogenital cancer, others factors (genetic, environmental, hormonal, etc) may have an important role. Mutations of ras genes were observed in several human neoplasias, including cervical cancer. OBJECTIVE: The aim of the study was to assess the frequency of Ha-ras oncogene mutations in cervical intraepithelial neoplasia (CIN) grade III and invasive squamous cell carcinomas and to examine this genetic factor in relation to HPV infection and the clinical evolution of cervical lesions. STUDY DESIGN: They were selected for (a) evaluation of the frequency of Ha-ras mutations: 39 cases of invasive carcinomas (InCa), 47 CIN III and 12 normal tissues taken from areas adjacent to the tumor (NT). (b) Retrospective follow-up: 18 cases of lesion progression; 9 cases of persistence and 12 of regression to mature or immature metaplasia after specific treatment. All biopsies obtained from each patient during the follow-up done between 5 and 10 years were included. HPV typing and scanning of possible mutations in Ha-ras were made by single-strand conformation polymorphism analysis/polymerase chain reaction. RESULTS: HPV-DNA was detected in 95% of InCa and 84% of CIN III; HPV 16/18 was found in 65% of patients, mainly associated with persistent infection and lesion progression. The undetermined HPV types (18%) could indicate the circulation in our country of types other than those screened (6, 11, 16, 18, 31 and 33). Twenty percent of CIN III and 41% of InCa had patterns compatible with Ha-ras mutations. Mutated Ha-ras was detected in 61 and 44% of progression and persistence cases, respectively, including early stages of progression. CONCLUSIONS: Ha-ras mutations were detected in CIN II-III lesions; in mutated cases, the progression took place in under 2 years, then this detection may be an early predictive marker of rapid progression.

Carcinoma, Squamous Cell↗

Secondary progressive multiple sclerosis: current knowledge and future challenges.

The secondary progressive phase of multiple sclerosis (MS), which is characterised by a steady accrual of fixed disability after an initial relapsing remitting course, is not clearly understood. Although there is no consensus on the mechanisms underlying such a transition to the progressive phase, epidemiological and neuroimaging studies indicate that it is probably driven by the high prevalence of neurodegenerative compared with inflammatory pathological changes. This notion is lent support by the limited efficacy of available immunomodulating and immunosuppressive treatment strategies, which seems to be further decreased in the late stages of secondary progressive MS. No established clinical or paraclinical predictors of the transition from relapsing remitting to secondary progressive MS have been described. However, the use of quantitative MRI-derived measures is warranted to monitor natural history studies and therapeutic trials of secondary progressive MS with increased reliability. In view of the small effects of immunomodulating and immunosuppressive treatments in preventing the transition to secondary progression, the development of treatments promoting neuroaxonal repair remains an important goal in this disease.

Adjuvants, Immunologic↗

A retrospective study on presbyopia onset and progression in a Hispanic population.

BACKGROUND: This study evaluates differences in age and presbyopia progression between an ethnic Hispanic and a non-Hispanic patient population. METHODS: Patient records from the Optometric Center of Los Angeles were examined retrospectively from 1998 through 2001. The first part of the study compared ages at onset and progression of presbyopia as a function of ethnicity. The second part of the study compared the amplitude of accommodation for the cohort of patients to Hofstetter's expected norms. RESULTS: A total of 332 patient records were evaluated: 61% (n = 203) Hispanic and 39% (n = 129) non-Hispanic. For an add power of +0.75 D, presbyopia developed in the reviewed Hispanic population at 39.31 years of age in comparison to development in non-Hispanics at 40.22 years. Hispanics also had a similar progression of reading add power (0.105 D/year) as compared to non-Hispanics (0.097 D/year) (t= 0.798, p = 0.43). The progression of amplitude of accommodation for the Hispanic (amplitude = 11.2 - 0.132 x age) and non-Hispanic populations (amplitude = 9.72 - 0.18 x age) (t= 0.0997, p = 0.92) were comparable, but both groups show a slower decline of amplitude when compared to Hofstetter's norms (p< 0.001). CONCLUSIONS: No statistically significant difference in the age at onset and progression of presbyopia was found between Hispanic and non-Hispanic patients; however, both groups of patients have a later onset and slower progression of presbyopia when compared to Hofstetter's norms.

Adult↗

Is cytomegalovirus infection a co-factor in HIV-1 disease progression?

The influence of cytomegalovirus (CMV) infection as a co-factor in HIV-1 disease progression has mainly been studied in haemophiliacs and remains controversial. Based on the files of 1683 HIV-1-infected patients in the Seropositive Cohort (SEROCO) and Haemophiliacs Cohort (HEMOCO) cohorts, we studied the role of CMV infection in progression to CD4+ cell counts of less than 200 microl, AIDS onset and death, in various HIV exposure groups. Adjusted relative risk (aRR) of progression to AIDS and to death was respectively 1.30 (P = 0.05) and 1.58 (P = 0.007). In the sexual exposure group the influence of CMV infection on the risk of progression to AIDS was of borderline significance (aRR = 1.50; P = 0.07) and was more marked on the risk of death (aRR = 2.00; P = 0.03). No such influence of CMV infection was observed in the transfusion and intravenous drug use exposure groups. When we studied the influence of CMV infection according to the stage of HIV disease, the main effect was on progression from AIDS to death, probably because CMV disease is a late event. Sexual CMV transmission and frequent re-exposure to CMV may explain why CMV infection emerged as an important co-factor for HIV progression only in the sexual exposure group.

Acquired Immunodeficiency Syndrome↗

Proposed synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis.

Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic modality to retard the progression of coronary atherosclerosis. An additional approach for prevention of the progression of atherosclerosis is calcium channel blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is less unequivocal than the clear evidence for lipid-lowering therapy. Many investigations support the view that a number of key processes in atherosclerosis may be influenced by CCBs. From the "negative" and "positive" studies with CCBs performed in animals and humans we must conclude that apparently some, but not all, types or stages of the atherosclerotic process are inhibited by CCBs. To assess whether lipid-lowering therapy and CCB treatment may have an additive or synergistic beneficial effect on human atherosclerosis, which is conceivable because their anti-atherosclerotic properties differ, data from the angiographic lipid-lowering trial REGRESS (pravastatin vs. placebo) were reviewed. In REGRESS, patients in the pravastatin group had significantly less progression if cotreated with CCBs as compared with those with no CCB cotreatment, whereas in the placebo (no pravastatin) group no effect of CCB treatment was observed. With respect to angiographic new lesion formation, in the pravastatin group there were 50% less patients with new angiographic lesions if cotreated with CCBs as compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, again, no significant effect of CCB treatment was observed. No beneficial effects of CCB treatment on clinical events were observed during the 2-year study follow-up. In view of the correlation between angiographic progression and subsequent clinical events as demonstrated in several large trials, it is not unrealistic to also anticipate in this population, a beneficial effect on clinical events with longer follow-up. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest that addition of CCBs to HMG-CoA reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis. These results appear to warrant prospective randomized trials to determine in a more definitive manner the merits of this combination in the prevention of progression of coronary atherosclerosis. Currently a number of studies in these fields are being designed or are already underway.

Anticholesteremic Agents↗

High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol.

BACKGROUND: Among the 566 patients with follicular lymphomas (FL) included in the GELF 86 prospective trials from October 1986 to September 1995, 372 with progressive/relapsing disease were analyzed retrospectively to identify prognostic factors at first relapse. PATIENTS AND METHODS: For progressive FL, patients received mono- (22%) or polychemotherapy (78%) followed by high-dose therapy (HDT) with ASCT for 83 patients (22%). The median time to progression from initial treatment was 23 months (range 3-102 months) and 24% of documented patients (52 of 217) had histological transformation (HT). Salvage therapy produced an overall response in 64% of patients and the five-year survival from progression was 42%. RESULTS: For patients who underwent HDT with ASCT compared to standard treatment, five-year freedom from second failure was at 42% vs. 16% (P = 0.0001) and five-year survival was 58% vs. 38% (P = 0.0005), respectively. The benefit of HDT and ASCT remained if we consider only patients less than 65 years (five-year survival at 60% vs. 40%; P = 0.001). Multivariate analysis of parameters significant according to univariate analysis found that no ASCT at first progression, age at relapse > 50 years, progression on-therapy were adversely significant on survival. CONCLUSIONS: HDTwith ASCT compared to standard treatment prolonged remission and survival after first progression of FL patients.

Age Factors↗

Cell death, tissue hypoxia and the progression of heart failure.

An important feature of heart failure is the progressive deterioration of left ventricular function that occurs in the absence of clinically apparent intercurrent adverse events. The mechanism or mechanisms responsible for this hemodynamic deterioration are not known. We and others have advanced the hypothesis that this hemodynamic deterioration results from progressive intrinsic contractile dysfunction of viable cardiomyocytes and/or from ongoing loss of cardiomyocytes. This review will focus on the concept of ongoing cardiac myocyte loss as a contributing factor to the progression of left ventricular dysfunction that characterizes the heart failure state. Specifically, the discussion will center on apoptosis or "programmed cell death" as a potential mediator of cardiomyocyte loss. In recent years, several studies have shown that constituent myocytes of failed explanted human hearts and hearts of animals with experimentally induced heart failure undergo apoptosis. Studies have also shown that cardiomyocyte apoptosis occurs following acute myocardial infarction, in the hypertrophied heart as well as in the aging heart; conditions frequently associated with the development of failure. While available data support the existence of myocyte apoptosis in the failing heart, lacking are studies which address the importance of myocyte apoptosis in the progression of LV dysfunction. As part of this discussion, we will address this issue and construct a case in support of a concept that the failing myocardium is subject to regional hypoxia, an abnormality that can potentially trigger cardiomyocyte apoptosis. If loss of cardiac myocytes through apoptosis can be shown to be an important contributor to the progression of heart failure, and if exact physiologic and molecular factors that trigger apoptosis in the heart can be identified, the stage will be set for the development of novel therapeutic modalities aimed at preventing, or at the very least retarding, the process of progressive ventricular dysfunction and the ultimate transition toward end-stage, intractable heart failure.

Animals↗

Noninvasive prediction of coronary artery disease progression by comparison of serial exercise electrocardiography and dipyridamole stress echocardiography.

BACKGROUND: The possibility of noninvasive prediction of angiographically assessed coronary artery disease (CAD) progression by comparison of serial studies of exercise electrocardiography (EET) and dipyridamole stress echocardiography (DET) is not known. AIM: To assess the relative value of EET and DET in predicting angiographically assessed progression of CAD. METHODS: From the Institute of Clinical Physiology, National Research Council, Pisa Italy stress echo data bank (1983-1998), we selected 46 patients with two repeated EET, DET and coronary angiography (CA) in two different hospital admissions (46+/-30 months). A priori, angiographic progressors were defined as any stenosis progression to occlusion and/or any stenosis >30% with >20% stenosis progression measured by visual and quantitative CA. EET progressors were defined as a previous negative test becoming positive or as a positive test with decrease in ischemic threshold response in the second test. DET progressors were defined as previous negative test becoming positive or as a positive test with a more severe ischemic response in the second test. RESULTS: Angiographic progressors were 31/46 patients (67%) and angiographic nonprogressors were 15/46 (33%). When angiography was taken as the gold standard, there were no differences in sensitivity for EET and DET (87 vs. 87%). Specificity was significantly higher for DET (93 vs. 40% p =< 0.001). By kappa statistics DET had a good concordance (kappa = 0.768) and EET a poor concordance (kappa = 0.299) with angiographic progression. CONCLUSION: DET is more accurate than EET at predicting angiographically assessed CAD progression.

Coronary Angiography↗

Role of eicosanoids in prostate cancer progression.

Metabolism of arachidonic acid through cyclooxygenase, lipoxygenase, or P450 epoxygenase pathways leads to the formation of various bioactive eicosanoids. In this review, we discuss alterations in expression pattern of eicosanoid-generating enzymes found during prostate tumor progression and expound upon their involvement in tumor cell proliferation, apoptosis, motility, and tumor angiogenesis. The expression of cyclooxygenase-2, 12-lipoxygenase, and 15-lipoxygenase-1 are up-regulated during prostate cancer progression. It has been demonstrated that inhibitors of cyclooxygenase-2, 5-lipoxygenase and 12-lipoxygenase cause tumor cell apoptosis, reduce tumor cell motility and invasiveness, or decrease tumor angiogenesis and growth. The eicosanoid product of 12-lipoxygenase, 12(S)-hydroeicosatetraenoic acid, is found to activate Erkl/2 kinases in LNCaP cells and PKCalpha in rat prostate AT2.1 tumor cells. Overexpression of 12-lipoxygenase and 15-lipoxygenase-1 in prostate cancer cells stimulate prostate tumor angiogenesis and growth, suggesting a facilitative role for 12-lipoxygenase and 15-lipoxygenase-1 in prostate tumor progression. The expression of 15-lipoxygenase-2 is found frequently to be lost during the initiation and progression of prostate tumors. 15(S)-hydroxyeicosatetraenoic acid, the product of 15-lipoxygenase-2, inhibits proliferation and causes apoptosis in human prostate cancer cells, suggesting an inhibitory role for 15-lipoxygenase-2 in prostate tumor progression. The regulation of prostate cancer progression by eicosanoids, in either positive or negative ways, provides an exciting possibility for management of this disease.

Apoptosis↗

CD44 standard form expression as a predictor of progression in high risk superficial bladder tumors.

OBJECTIVE: The purpose of this study was to assess the significance of the standard CD44 adhesion molecule expression in predicting progression of high risk superficial bladder carcinoma in the short term. METHODS: Sixty-six patients (51 males and 15 females, aged 27 to 89 years (mean 64.75 years) with primary superficial transitional cell bladder cancer initially treated with transurethral resection (TURBT) were enrolled in the study. Only pTa/pT1 grade 2 multiple tumors as well as all grade 3 tumors were included in this study. All tumor samples obtained after the resection were immunohistochemically evaluated for the expression of the CD44 standard molecule. Fifty eight patients remained during the follow up period which ranged from 3 to 36 months (mean 11.8 months). Tumor progression in the short term was considered as the critical end point of interest in this study. The prognostic significance of tumor stage, grade, presence of carcinoma-in-situ (CIS) and expression of CD44 in determining the risk for progression, was studied with both univariate (log rank test) and multivariate (Cox proportional hazards) methods of analysis. RESULTS: Kaplan-Meier survival curves indicated that a shorter median progression-free survival is expected for those patients with G3 bladder tumors (p = 0.0055), concomitant CIS (p = 0.0051), and loss of expression of CD44 (p = 0.0015), whereas a similar association with stage was not detected (p = 0.5793). The cox regression multivariate analysis did not yield a significant result for any of the studied parameters therefore no one of the factors taken into account can serve as an independent predictor of progression in superficial bladder cancer in the short term. CONCLUSION: The immunohistochemically detectable loss of the expression of CD44 standard form from superficial bladder tumor samples may be, complementary to the established prognostic factors, a useful predictor of tumor progression in the short term.

Adult↗

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy.

PURPOSE: This retrospective evaluation of data from two randomized, multicenter trials examined whether tumor responses to further endocrine therapy were seen in postmenopausal women with advanced breast cancer who had progressed on both initial endocrine therapy, usually tamoxifen, and on the estrogen receptor (ER) antagonist fulvestrant ('Faslodex'). PATIENTS AND METHODS: A combined total of 423 patients received fulvestrant 250 mg as a monthly intramuscular injection. After progression on fulvestrant, some patients received another endocrine therapy. Responses to subsequent endocrine therapy were assessed using a questionnaire sent to the trial investigators. Best responses were classified as a complete or partial response (CR or PR), stable disease (SD) lasting > or = 24 weeks, or disease progression. RESULTS: Follow-up data were available for 54 patients who derived clinical benefit (CB, defined as CR, PR or SD) from fulvestrant and who received subsequent endocrine therapy, resulting in a PR in 4 patients, SD in 21 patients, and disease progression in 29 patients. Data were available for 51 patients who derived no CB from fulvestrant and who received further endocrine therapy, resulting in a PR in 1 patient, SD in 17 patients, and disease progression in 33 patients. Aromatase inhibitors were used as subsequent endocrine therapy in > 80% of patients. CONCLUSIONS: After progression on fulvestrant, patients may retain sensitivity to other endocrine agents. Fulvestrant provides an additional option to existing endocrine therapies for the treatment of advanced or metastatic breast cancer in postmenopausal women, and may provide the opportunity to extend the sequence of endocrine regimens before cytotoxic chemotherapy is required.

Adult↗

Intraocular pressure and progression in exfoliative eyes with ocular hypertension or glaucoma.

PURPOSE: This retrospective study was conducted in exfoliative eyes in order to study the influence of IOP and other possible factors on the conversion from ocular hypertension (OHT) to glaucoma and progression of glaucoma. METHODS: 139 patients with exfoliation OHT or glaucoma with exfoliation syndrome were included (mean follow-up 5.2 +/- 3.6 years). The effects of age, gender, weighted mean IOP, maximum IOP, stage of glaucoma at the first visit, refraction, glaucoma medication, and interventions on the hazard of progression were studied by multivariate survival analysis. RESULTS: Conversion from OHT to glaucoma or progression of glaucoma was detected in 63 eyes (45.3%). A significant association with progression was found for age (relative risk 1.042; p-value 0.043), weighted mean IOP (1.076; <0.001), and stage of glaucoma (1.436; <0.001). History of trabeculectomy (0.360; 0.002) related to a decreased risk. CONCLUSION: The risk of conversion from OHT to glaucoma and progression of glaucoma increased in exfoliative eyes with severity of stage of glaucoma, weighted mean IOP, and the age of the patient. A history of trabeculectomy was related to decreased risk of progression.

Aged↗

Cancer cell progression and chemoimmunotherapy--dual effects in the induction of resistance to therapy.

To determine whether resistance to chemoimmunotherapy is acquired during therapy, we investigated the effects of chemotherapeutic agents and anti-tumour polysaccharide, lentinan, on the progression of Rous sarcoma virus-induced S908.D2 fibrosarcomas. The chemoimmunotherapy was effective against the parental S908.D2-bearing mice. Nearly all the mice that were treated with cyclophosphamide (CY) and lentinan achieved complete tumour regression. Only a few of the mice that achieved complete regression of the primary tumours showed a recurrence of the tumour in regional lymph nodes. S908.D2-vp.1 was established from metastatic tumours that developed in the regional lymph nodes of parental S908.D2-bearing mice during therapy. S908.D2-vp.2-or vp.3 cells were sequentially derived in a similar way from S908.D2-vp.1-or-vp.2-bearing mice respectively, in which complete tumour regression at each primary site was achieved during therapy. These lines acquired resistance to CY and lentinan and also to 5-fluorouracil (5-FU)/5'-deoxy-5-fluorouracil and lentinan. No significant difference in either the sensitivity to 5-FU or 4-deoxycyclophosphamide in vitro or in the susceptibility to immune effector cells was observed between the parental and progressed lines (S908.D2-vp1 -vp3). There was an increase in the level of prostaglandin E2 (PGE2) in the progressed lines during repeated therapy (parental, 1171 pg ml(-1); vp.1, 2199 pg ml(-1); vp.2, 5500pg ml(-1); vp3, 16187 pg ml(-1)). There was no significant increase in the production of transforming growth factor beta (TGF-beta). The amount of interleukin-2 (IL-2) produced by spleen cells isolated from the S908.D2-vp.2-bearing mice was decreased compared with the amount produced by the parental S908.D2- bearing mice. Furthermore, combination therapy with lentinan and IL-2 achieved complete tumour regression in all the mice transplanted with S908.D2 progressed tumour lines, although IL-2 alone did not show any anti-tumour effects in either the S908.D2 parental or progressed lines. The findings suggest that the reduced production of IL-2 induced an increase in the production of the PGE2 by progressed tumour lines is involved in the acquisition of resistance.

Animals↗

A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation.

Viral and host factors influence the rate of HIV-1 disease progression. For HIV-1 to fuse, a CD4+ cell must express a co-receptor that the virus can use. The chemokine receptors CCR5 and CXCR4 are used by R5 and X4 viruses, respectively. Most new infections involve transmission of R5 viruses, but variants can arise later that also use CXCR4 (R5-X4 or X4 viruses). This is associated with an increased rate of CD4+ T-cell loss and poor prognosis. The ability of host cells to support HIV-1 entry also influences progression. The absence of CCR5 in approximately 1% of the Caucasian population, due to homozygosity for a 32-nucleotide deletion in the coding region (delta32-CCR5 allele), very strongly protects against HIV-1 transmission. Heterozygosity for the delta32-CCR5 allele delays progression typically by 2 years. A recent study showed that a conservative substitution (V64I) in the coding region of CCR2 also has a significant impact on disease progression, but not on HIV-1 transmission. This was unexpected, since CCR2 is rarely used as a co-receptor in vitro and the V64I change is in a transmembrane region. Because a subsequent study did not confirm this effect on progression to disease, we analyzed CCR2-V64I using subjects in the Chicago MACS. We show that CCR2-V64I is indeed protective against disease progression and go on to show that the CCR2-V64I allele is in complete linkage disequilibrium with a point mutation in the CCR5 regulatory region.

Alleles↗