Background: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen. Patients and methods: ...Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease. Results: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation. Conclusions: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.
Goals of the work
Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonates treatment. Bisphosphonates reduce skeletal adverse events and give a clinical benefit to cancer patients. ...Therefore, it is necessary to identify appropriate procedures to reduce ONJ injures by using a successful monitoring program. In a retrospective study we analyzed the impact of a prevention program based on clinical oral cavity examination, dentists, and patients’ education. The aim of the study was to evaluate if this approach might improve ONJ outcome in patients receiving pamidronate or zoledronate.
Materials and methods
We analyzed retrospectively two different groups of patients treated at our Institution: patients treated from October 2003 to June 2005 (group A) and patients treated from June 2005 to April 2007 (group B). In June 2005 the prevention program started for all our patients.
Main results
One hundred and eighty-six cancer patients with bone involvement, treated with bisphosphonates, were considered. Sixteen of them developed ONJ: eight before and eight after June 2005. We observed a consistent difference in the evolution of the two groups. In the first group, four patients underwent a major surgery (one partial maxillectomy, complicated by septic shock and oronasal communication; two partial mandibulectomies; and one segmental mandibular resection), with an important impairment of their quality of life; while the eight new ONJ cases, diagnosed after June 2005, were successfully treated without aggressive dental interventions, and achieved a good control of symptoms.
Conclusions
Bisphosphonates-related ONJ is a frequent adverse event (8.6%). The monitoring program proved very efficient to improve the clinical outcome of ONJ, avoiding an aggressive treatment and using a conservative approach and medical therapy.
Long term treatment with tamoxifen has produced few side effects, which are generally mild. Of the serious ones, all of them except eye toxicity seem to be related to the molecule's intrinsic mildly ...estrogen-like action, such as, for example, endometrial carcinoma. This property is also responsible for some favorable clinical effects including a lower risk of osteoporosis and cardiovascular disease. Whether tamoxifen causes neoplastic growth in patients who develop resistance to this drug is still controversial. Further prospective clinical studies are therefore needed to investigate such problems and also to evaluate less frequent side effects. Moreover, decisions on the overall duration of hormone therapy should be based on possible side effects as well as on therapeutic response.
Serum neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), and carcinoembryonic antigen (CEA) were measured in 60 patients with small-cell lung carcinoma (SCLC) and in 94 patients with ...advanced non-small-cell lung carcinoma (NSCLC) at diagnosis, during induction chemotherapy, and at restaging. At diagnosis, the positivity rates of NSE, TPA, and CEA were 88, 52, and 43% in SCLC, and 20, 62, and 53% in NSCLC, respectively. Serum NSE and TPA levels were significantly higher in extensive than in limited SCLC. TPA and CEA levels were significantly correlated with the extent of NSCLC. NSE and TPA were significantly concordant with the clinical response to initial combination chemotherapy, the former in SCLC, the latter in both SCLC and NSCLC. By discriminant analysis, the presentation levels of the markers were not predictive of response to induction chemotherapy, whereas changes in NSE and TPA levels after the first cycle of chemotherapy were.
To evaluate collateral effects of a TAM prolonged treatment, we analyzed, in a retrospective study, 243 pts, whose mean age was 59.2 years (27-85), all BC treated with radical surgery and adjuvant ...TAM for more than 2 years, 61/243 in premenopausal (25.1%) and 182/243 in postmenopausal age (74.9%). Twenty-nine out of 243 pts (11.9%) had a precedent hysterectomy for other benign gynaecological diseases. Fortythree pts (17.7%) received TAM 20 mg/die and 200 (82.3%) 30
mg/die; median treatment duration was 50.5 months (24-120 m) (front 2 to 3 years: 58 pts, from 3 to 4 years: 39 pts, from 4 to 5 years: 97 pts,
>
5 years: 49 pts, in which TAM was readministrated as first line too). The median follow-up was 70.3 m (2-15 years). For intolerance, 22 (9.1%) pts reduced TAM from 30 to 20
mg/die while 12 (4.9%) pts stopped for the same problem. We reported these side effects: thrombophlebitis in 13 pts (5.3%), epigastralgia of mild entity in 18 pts (7.4%), leucopaenia grade I WHO in 5 pts (2.1%), thrombocytopenia grade II in 2 pts (0.8%), mild hyperglycemia in 15 pts (6.2%), mild nausea in 8 pts (3.3%), leukorrea in 5 pts (2.1%), flashing in 12 pts (4.9%), spotting from endometrial hyperplasia in 22/214 pts (10.3%). Only 3 pts had a contralateral BC (1.2%). We reported 4 gynaecological cancers (1.9%): 2 endometrial adenocarcinomas after 22 and 60 months of TAM treatment, 1 ovarian granulosa-cells tumor after 30 months and 1 ovarian tumor-not style typized-after 60 months. Two pts (0.8%) had gallbladder cancer (1 pt after 52 months; 1 pt after 67), 1 pt (0.4%) had a stomach cancer after 6 months interruption of therapy with TAM for 96 months, I pt (0.4%) had a pancreas cancer after 51 months. In conclusion, our results reflect the literature about the risk of a secondary endometrial cancers in long term treated pts (Lancet 1989, i, 117); the correlation between TAM and endometrial cancer is sure; there is no evidence of correlation with other tumors. We suggest periodic gynaecological control in patients treated with TAM for more than two years.
Computer programs were developed for the selection of a minimum set of biochemical tests that allow the identification of the species of Enterobacteriaceae with major clinical significance. The ...system proposed consists of nine conventional biochemical tests, the results of which are interpreted with the help of a numeric code. This selects the most probable species for each result and, when necessary, additional tests can be performed to confirm the identification proposed. The system (SYS9E) was used in the identification of 66 strains of nosocomial origin. The results were compared with those of commercial systems.
Glucose control, glucose variability (GV), and risk for hypoglycemia are intimately related, and it is now evident that GV is important in both the physiology and pathophysiology of diabetes. ...However, its quantitative assessment is complex because blood glucose (BG) fluctuations are characterized by both amplitude and timing. Additional numerical complications arise from the asymmetry of the BG scale. In this Perspective, we focus on the acute manifestations of GV, particularly on hypoglycemia, and review measures assessing the amplitude of GV from routine self-monitored BG data, as well as its timing from continuous glucose monitoring (CGM) data. With availability of CGM, the latter is not only possible but also a requirement-we can now assess rapid glucose fluctuations in real time and relate their speed and magnitude to clinically relevant outcomes. Our primary message is that diabetes control is all about optimization and balance between two key markers-frequency of hypoglycemia and HbA1c reflecting average BG and primarily driven by the extent of hyperglycemia. GV is a primary barrier to this optimization, including to automated technologies such as the "artificial pancreas." Thus, it is time to standardize GV measurement and thereby streamline the assessment of its two most important components-amplitude and timing.
We experimentally investigate the statistics of zero-height isolines in gravity wave turbulence as physical candidates for conformal invariant curves. We present direct evidence that they can be ...described by the family of conformal invariant curves called stochastic Schramm-Löwner evolution (or SLE_{κ}), with diffusivity κ=2.88(8). A higher nonlinearity in the height fields is shown destroy this symmetry, though scale invariance is retained.
Summary Objective To determine the strain-induced signaling pathways involved in regulating the transactivation of the transcription regulator Cbp/p300 Interacting Transactivator with ED-rich tail 2 ...(CITED2) and downstream targets in chondrocytes. Methods Primary human chondrocytes or C28/I2 chondrocytic cells were subjected to various strain regimes. C57BL/6 mice were subjected to treadmill running. Loss-of-function was carried out using siRNA or inhibitors specific for targeted molecules. mRNA levels were assayed by RT-qPCR, and proteins by western blotting, immunofluorescence, and/or immunohistochemical staining. CITED2 promoter activity was assayed in chondrocytes using wild-type or mutant constructs. Results Cyclic strain at 5%, 1 Hz induced CITED2 expression and suppressed expression of matrix metalloproteinase (MMP)-1 and -13 at the messenger RNA (mRNA) and protein levels in human chondrocytes. Abolishing primary cilia through knockdown of intraflagellar transport protein (IFT88) attenuated CITED2 gene expression and decreased protein levels. Similar effects were observed with inhibitors of extracellular adenosine triphosphate (ATP) or P2 purinergic receptors, or antagonists of Ca2+ signaling. Knockdown of IFT88 in articular chondrocytes in vivo diminished treadmill induced-CITED2 expression and upregulated MMPs. Knockdown of hypoxia-inducible factor (HIF)1α, specificity protein 1 (Sp1), or deletion of the shear stress response element (SSRE) in the CITED2 promoter limited cyclic strain-induced transactivation of CITED2. However, the strain induced-transactivation of CITED2 was abolished only on knockdown of HIF1α, Sp1, and SSRE or by loss-of-function of IFT88 or extracellular-signal-regulated kinases (ERK)1/2. Conclusions CITED2 transactivation is a critical event in signaling generated by strain and transduced by primary cilia, extracellular ATP, P2 purinergic receptors, and Ca2+ signaling. Strain-induced CITED2 transactivation requires HIF1α, Sp1, and an intact SSRE and leads to the downregulation of MMPs such as MMP-1 and MMP-13.
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