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101.
Obermair A Mileshkin L Bolz K Kondalsamy-Chennakesavan S Cheuk R Vasey P Wyld D Goh J Nicklin JL Perrin LC Sykes P Janda M 《Gynecologic oncology》2011,120(2):179-184
Objective
Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach.Methods
This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators.Results
Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1-3 disease (44.8%) recurred (average follow-up 28.1 months, range 8-60 months).Conclusion
This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC. 相似文献102.
Tolerance in mixed chimerism – a role for regulatory cells? 总被引:1,自引:0,他引:1
The establishment of mixed hematopoietic chimerism induces life-long donor-specific organ graft tolerance while obviating the need for chronic immunosuppression. Recent advances have dramatically reduced the conditioning toxicity required to achieve mixed chimerism. We argue that the achievement of high levels of donor chimerism ensures life-long deletion of donor-reactive T cells, precluding and obviating the need for regulatory mechanisms in the maintenance of tolerance. However, in situations where high levels of donor chimerism cannot be established or sustained, control of immune responsiveness can be achieved through additional mechanisms, including regulatory T cells. 相似文献
103.
Nanotherapy silencing the interleukin‐8 gene produces regression of prostate cancer by inhibition of angiogenesis 下载免费PDF全文
Ravikumar Aalinkeel Bindukumar Nair Chih‐Kuang Chen Supriya D. Mahajan Jessica L. Reynolds Hanguang Zhang Haotian Sun Donald E. Sykes Kailash C. Chadha Steven G. Turowski Katelyn D. Bothwell Mukund Seshadri Chong Cheng Stanley A. Schwartz 《Immunology》2016,148(4):387-406
Interleukin‐8 (IL‐8) is a pro‐angiogenic cytokine associated with aggressive prostate cancer (CaP). We detected high levels of IL‐8 in sera from patients with CaP compared with healthy controls and patients with benign prostatic hypertrophy. This study examines the role of IL‐8 in the pathogenesis of metastatic prostate cancer. We developed a biocompatible, cationic polylactide (CPLA) nanocarrier to complex with and efficiently deliver IL‐8 small interfering RNA (siRNA) to CaP cells in vitro and in vivo. CPLA IL‐8 siRNA nanocomplexes (nanoplexes) protect siRNA from rapid degradation, are non‐toxic, have a prolonged lifetime in circulation, and their net positive charge facilitates penetration of cell membranes and subsequent intracellular trafficking. Administration of CPLA IL‐8 siRNA nanoplexes to immunodeficient mice bearing human CaP tumours produced significant antitumour activities with no adverse effects. Systemic (intravenous) or local intra‐tumour administration of IL‐8 siRNA nanoplexes resulted in significant inhibition of CaP growth. Magnetic resonance imaging and ultrasonography of experimental animals demonstrated reduction of tumour perfusion in vivo following nanoplex treatment. Staining of tumour sections for CD31 confirmed significant damage to tumour neovasculature after nanoplex therapy. These studies demonstrate the efficacy of IL‐8 siRNA nanotherapy for advanced, treatment‐resistant human CaP. 相似文献
104.
Burwinkel B; Maichele AJ; Aagenaes O; Bakker HD; Lerner A; Shin YS; Strachan JA; Kilimann MW 《Human molecular genetics》1997,6(7):1109-1115
Glycogen storage disease due to phosphorylase kinase deficiency occurs in
several variants that differ in mode of inheritance and tissue-
specificity. This heterogeneity is suspected to be largely due to mutations
affecting different subunits and isoforms of phosphorylase kinase. The gene
of the ubiquitously expressed beta subunit, PHKB, was a candidate for
involvement in autosomally transmitted phosphorylase kinase deficiency of
liver and muscle. To identify such mutations, the complete PHKB coding
sequence was amplified by RT-PCR of RNA isolated from blood samples of
patients and analyzed by direct sequencing of PCR products. The
characterization of mutations was complemented by PCR of genomic DNA. In
one female and four male patients, we identified five independent nonsense
mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one
single-base insertion in codon N421, one splice-site mutation affecting
exon 31, and a large deletion involving the loss of exon 8. Although these
severe translation-disrupting mutations occur in constitutively expressed
sequences of the only known beta subunit gene of phosphorylase kinase,
PHKB, they are associated with a surprisingly mild clinical phenotype,
affecting virtually only the liver, and relatively high residual enzyme
activity of approximately 10%.
相似文献
105.
Determination of optimal cryoprotectants and procedures for their addition and removal from human spermatozoa 总被引:9,自引:7,他引:9
The objective was to test the hypothesis that the optimal cryoprotective
agent for cryopreservation of human spermatozoa would be a solute for which
cells have the highest plasma membrane permeability, resulting in the least
amount of volume excursion during its addition and removal. To test this
hypothesis, theoretical simulations were performed using membrane
permeability coefficients to predict optimal procedures for the addition
and removal of a cryoprotectant. Simulations were performed using data from
four different cryoprotectants: (i) glycerol, (ii) dimethyl sulphoxide,
(iii) propylene glycol and (iv) ethylene glycol. Thermodynamic formulations
were applied to determine approaches for the addition and removal of 1 M
and 2 M final concentrations of cryoprotectant, allowing the spermatozoa to
maintain a cell volume within their osmotic tolerance limits. Based on
these data, ethylene glycol was predicted to be optimal for minimizing
volume excursions among the solutes evaluated. These predictions were then
experimentally tested using glycerol as the control cryoprotectant and
ethylene glycol as the experimental cryoprotectant. The results indicate
that there was a higher (P < 0.05) recovery of motile spermatozoa after
cryopreservation when using 1 M ethylene glycol than with 1 M glycerol,
supporting the hypothesis that use of the cryoprotectant for which the cell
has the highest permeability will result in higher cell survival.
相似文献
106.
Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception 总被引:3,自引:4,他引:3
McMahon CA; Ungerer JA; Beaurepaire J; Tennant C; Saunders D 《Human reproduction (Oxford, England)》1997,12(1):176-182
The aim of this study was to compare 70 couples who had conceived by in-
vitro fertilization (IVF) with 63 matched controls for the prevalence of
anxiety and quality of attachment to the baby during pregnancy. Results for
mothers showed no group differences using a global measure of anxiety, the
Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific
measures revealed significantly higher levels of anxiety in IVF mothers
about the survival and normality of their unborn babies, about damage to
their babies during childbirth and about separating from their babies after
birth. When IVF mothers were differentiated according to the number of
treatment cycles, more differences in anxiety level were revealed, with
most increases occurring in mothers who had experienced two or more
treatment cycles. IVF fathers did not differ from controls on the global
anxiety measure. No data on pregnancy-specific anxiety were available for
fathers. Neither IVF mothers nor IVF fathers differed from controls on
measures of attachment to the baby during pregnancy. Results are discussed
in the context of the need for researchers to employ differentiated and
issue-specific measures to identify concerns that may be unique to IVF
couples. Clinical implications regarding the need for psychological support
during pregnancy are also discussed.
相似文献
107.
Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx? 总被引:4,自引:7,他引:4
Sowter MC; Akande VA; Williams JA; Hull MG 《Human reproduction (Oxford, England)》1997,12(10):2147-2150
A pilot study was designed to examine whether the outcome of embryo
transfer in women with a hydrosalpinx might be improved by surgical
drainage of the hydrosalpinx at the time of oocyte collection for in- vitro
fertilization treatment. A comparative, controlled but retrospective
analysis of the results was performed of all women with infective tubal
damage aged <40 years old, who had ovulatory cycles, a normal uterus and
a partner with normal spermatozoa. A standardized treatment regimen was
used. A maximum of three embryos were transferred. Hydrosalpinx was defined
by prior hysterosalpingography and/or laparoscopy with transcervical dye
injection. A total of 237 embryo transfer cycles in women with
hydrosalpinges (tubal distension not visible in 151, visible but not
drained in 30 and drained in 56) were compared with 705 embryo transfer
cycles in women with tubal disease but no hydrosalpinx. Results were
analysed in the first three cycles but also separately in the first cycle
to check for bias. Success rates were higher in the first cycle, but did
not significantly influence overall differences. Implantation rates were
significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2%
for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup
without evident tubal distension and 7.5% (not significant) in the drained
hydrosalpinx group. This study shows that tubal damage with distal
occlusion is associated with a marked reduction in embryo implantation,
even in the absence of obvious fluid distension. Surgical drainage of
distended hydrosalpinges appears to offer no benefit.
相似文献
108.
Immunological factors in endometriosis-associated reproductive failure: studies in fertile and infertile women with and without endometriosis 总被引:7,自引:4,他引:7
Martinez-Roman S; Balasch J; Creus M; Fabregues F; Carmona F; Vilella R; Vanrell JA 《Human reproduction (Oxford, England)》1997,12(8):1794-1799
Immunopathophysiological mechanisms in endometriosis-associated
reproductive failure were studied in appropriate populations: infertile and
fertile women with and without endometriosis. The incidence of sera
positive for any of the autoantibodies tested among infertile women with
endometriosis (n = 25) was similar to that observed in the three control
groups [unexplained infertility patients (n = 25) and fertile women with (n
= 10) and without (n = 25) endometriosis]. The mean volume of peritoneal
fluid was significantly elevated in women with endometriosis (both fertile
and infertile) as compared with patients without endometriosis (fertile or
infertile). The concentration of peritoneal fluid leukocytes and the
percentage of cells positive for macrophage markers were significantly
increased and the percentage of T lymphocytes significantly decreased in
infertile women with endometriosis but not in patients with unexplained
infertility and fertile women with endometriosis, as compared with fertile
controls without endometriosis. Macrophages from infertile patients with
endometriosis had higher sperm phagocytosis than did those from infertile
women without endometriosis or fertile subjects with or without
endometriosis. Incidences of serum and peritoneal fluid samples embryotoxic
to the in-vitro development of 2-cell mouse embryos were significantly
higher in infertile patients with endometriosis than in unexplained
infertility patients and fertile women with or without endometriosis. It is
concluded that immunological mechanisms of endometriosis-associated
infertility exist but that these peritoneal immunological factors in
infertile women with endometriosis are related to their subfertility rather
than to the presence of ectopic endometrial implants. This is supported by
the lack of immunological abnormalities observed among fertile women with
endometriosis. These immunological abnormalities are lacking in patients
with unexplained infertility.
相似文献
109.
110.
Sands MF Ohtake PJ Mahajan SD Takyar SS Aalinkeel R Fang YV Blume JW Mullan BA Sykes DE Lachina S Knight PR Schwartz SA 《Clinical immunology (Orlando, Fla.)》2009,130(2):186-198
Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma. 相似文献