Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are prognostic in primary and metastatic breast cancer. Peripheral blood (PB) immune cells contribute to an unfavorable ...microenvironment for CTC survival. This study aimed to correlate CTCs with the PB T-cell immunophenotypes and functions of patients with inflammatory breast cancer (IBC).
This study included 65 IBC patients treated at the MD Anderson Cancer Center. PB was obtained from patients prior to starting a new line of chemotherapy for CTCs enumeration by CellSearch(®), and T cell phenotype and function by flow cytometry; the results were correlated with CTCs and clinical outcome.
At least 1 CTC (≥1) or ≥5 CTCs was detected in 61.5% or 32.3% of patients, respectively. CTC count did not correlate with total lymphocytes; however, patients with ≥1 CTC or ≥5 CTCs had lower percentages (%) of CD3+ and CD4+ T cells compared with patients with no CTCs or <5 CTCs, respectively. Patients with ≥1 CTC had a lower percentage of T-cell receptor (TCR)-activated CD8+ T cells synthesizing TNF-α and IFN-γ and a higher percentage of T-regulatory lymphocytes compared to patients without CTCs. In multivariate analysis, tumor grade and % CD3+ T-cells were associated with ≥1 CTC, whereas ≥5 CTC was associated with tumor grade, stage, % CD3+ and % CD4+ T cells, and % TCR-activated CD8 T-cells synthesizing IL-17.
IBC patients with CTCs in PB had abnormalities in adaptive immunity that could potentially impact tumor cell dissemination and initiation of the metastatic cascade.
Abstract
Background: The 5-year survival rates for inflammatory breast cancer (IBC) are significantly lower than non-IBC, highlighting the importance of cancer prevention in IBC. We investigated the ...risk factors for IBC subtypes based on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2neu) status to determine distinct etiological pathways. The Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at University of Texas MD Anderson Cancer Center (UTMDACC) treats the largest number of IBC patients in a single center. The center maintains a prospective, comprehensive epidemiology registry, through which we were able to conduct the largest single center case-control study on IBC. Methods: We identified 246 patients diagnosed with IBC using strict consensus criteria and 397 cancer free patients seen at the UTMDACC Dan L. Duncan Cancer prevention clinic. We used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between breast cancer reproductive and lifestyle risk factors and IBC tumor subtypes. The tumor subtypes of IBC patients were classified as ER-positive (ER+/PR+/Her2neu-), Her2neu-positive (Her2neu+) and triple negative (ER-/PR-/Her2neu-). Results: In age-adjusted univariate analysis, body mass index (BMI), history of smoking, number of children, age at first pregnancy, breastfeeding, menopausal status, and first degree family history of breast cancer were statistically significant associated with risk of IBC (p<0.05). In multivariable analysis of IBC tumor subtypes, compared to cancer free controls, patients with triple negative (OR = 3.73, 95% CI = 1.52 – 9.13) and Her2neu-positive (OR = 19.27, CI = 4.14 – 89.62) tumors were significantly more likely to have ≥ 2 vs 0-1 children. Patients with triple negative (OR = 0.19, 95% CI = 0.09 – 0.45) and ER-positive (OR = 0.42, CI = 0.19 – 0.88) tumors were significantly less likely to have a history of breastfeeding. Patients with ER-positive (OR = 5.02, CI = 2.29 – 10.99) tumors were also significantly more likely to have a history of smoking. Patients with triple negative (OR = 6.07, CI = 2.62 – 17.07), ER-positive (OR = 7.22, CI = 2.94 – 17.78) and Her2neu-positive (OR = 12.81, CI = 4.59 – 35.78) were more likely to be overweight or obese (BMI ≥ 25kg/m2). Conclusion: The associations identified suggest that overweight or obese status is an important modifiable risk factor for all IBC subtypes. Triple negative IBC share similar risk factors as non-IBC triple negative tumors with increasing number of children and lack of breastfeeding associated with increased risk. Interestingly lack of breastfeeding was also associated with ER-positive IBC tumors, and Her2neu-positive IBC tumors were associated with increasing number of children; two associations that have not been previously reported. Impact: These results highlight the importance of evaluating epidemiologic risk factors of IBC, which could lead to the identification of subtype specific prevention strategies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-04.
Abstract
Background: The rate of pathologic complete response (pCR) to neoadjuvant systemic treatment (NST) of patients with a body mass index (BMI) of ≥25 has been reported to be significantly lower ...than that of patients with a BMI <25. However, only patients with a BMI of ≥30 have been found to have worse overall survival (OS) than patients with a BMI <25. Several studies have shown that an increasing body weight after surgery is a poor prognostic factor for OS. Whether a higher BMI after NST and before surgery truly predicts response to chemotherapy or outcomes remains unclear. We hypothesized that higher BMI will be associated with lower rates of pCR and long-term clinical outcomes. The purpose of this study was to determine whether a change in BMI from baseline to after NST and definitive surgery affects pCR and OS in patients with inflammatory breast cancer (IBC) or locally advanced non-IBC.
Material and Methods: We retrospectively reviewed the medical records of 263 patients with primary IBC and 865 patients with stage III non-IBC who underwent standard NST consisting of anthracyclines and/or taxanes with or without concurrent trastuzumab followed by definitive surgery at our institution between November 1, 2006, and December 31, 2012.
Results: The median follow-up time for survivors was 19.8 months (0.1-69.9 months). One hundred forty-five (55.1%) IBC and 566 (65.7%) non-IBC were hormone receptor-positive and 91 (34.6%) IBC and 198 (22.9%) non-IBC were human epidermal growth factor receptors (HER2)-positive. One hundred forty-four (54.8%) IBC and 446 (51.9%) non-IBC were postmenopausal. Of the 1128 patients included in the study, 223 (19.8%) achieved pCR, including 42 (16.0%) IBC and 181 (20.9%) non-IBC. The median change in BMI during NST of the patients who achieved pCR (0.1) was significantly higher than that of the patients who did not achieve pCR (-0.1; p = 0.04). The pCR rate of the patients whose BMIs had positive change post NST (23.2%) was higher than that of the patients whose BMIs were lower after NST (18.2%), but this difference was not significant (p = 0.054). Multivariate analysis did not reveal positive change in BMI post NST to be a significant predictor of pCR.
Univariate analysis with the log-rank test revealed that higher BMI change from pre NST as a categorical variable (BMI change >0 vs. ≤0) predicted increased OS in all patients (p = 0.005) and in IBC patients (p<0.001). After adjust for other clinical variables, none of the BMI-related measures (i.e., baseline BMI, BMI at surgery, and BMI change during NST) predicted OS. Although univariate analysis revealed that BMI change as a continuous variable predicted OS in IBC patients (p = 0.031), after adjust for other clinical variables BMI change no longer predicted OS. None of the BMI measures as continuous or categorical variables predicted recurrence-free survival.
Conclusion: In patients with stage III breast cancer, a higher BMI after NST than at baseline does not predict lower pCR rate or decreased survival after adjust for other clinical variables.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD2-4.
Abstract
Background: Very little is known about the survival of patients with inflammatory breast cancer (IBC) and distant metastasis. Furthermore, the American Joint Committee on Cancer ...classification of breast cancer does not recognize metastatic IBC as a distinct entity within stage IV. We hypothesized that the survival of patients with IBC and distant metastasis is worse than the survival of patients with stage-matched non-IBC.
Patients and Methods: We retrospectively reviewed 5314 consecutive patients with stage III or IV breast cancer (IBC or non-IBC) who were treated at our institution between 1986 and 2012. A total of 1079 patients presented with IBC (stage III: 861; stage IV: 218) and 4235 non-IBC (stage III: 2781; stage IV: 1454). We compared the time to distant metastasis from initial diagnosis, distant metastasis–free survival (DMFS), and overall survival (OS) in stage-matched patients with IBC or non-IBC.
Results: The median follow-up periods were 3.3 years for patients with stage III disease (range, 0-32.2 years) and 1.8 years for patients with stage IV disease (range, 0-19.9 years). The total number of recorded events (metastasis/death) was 1657 for stage III, while the numbers of deaths for stage III and IV were 1337 and 973, respectively. In patients with stage III, the time to distant metastasis was shorter in IBC than in non-IBC (median 1.3 vs. 1.7 years, P < .001). DMFS and OS were shorter in patients with stage III IBC than in those with stage III non-IBC (2.5 vs. 6.9 years, P < .001; and 4.7 vs. 8.9 years, P < .001; respectively). However, there was no significant difference in OS after development of distant metastasis between stage III IBC and non-IBC (median for both 1.3 years, P = .83). In multivariate analysis, the diagnosis of IBC remained significantly associated with mortality after adjusting for potential confounders. De novo stage IV IBC presented more frequently with multiple sites of metastasis than de novo stage IV non-IBC (P = .02). In patients with de novo stage IV disease, OS was shorter in IBC than in non-IBC (2.3 vs. 3.4 years, P = .004). In the multicovariate Cox model, while ethnicity, tumor grade, hormone receptor status and HER2 status, site of metastasis, number of sites of metastasis, and definitive breast surgery by 1 year were all significant factors in OS for stage IV breast cancer, the diagnosis of IBC conferred a hazard ratio of 1.33 (95% confidence interval: 1.05 - 1.69) in multivariate analysis.
Conclusion: Our findings suggest that IBC patients with metastasis at diagnosis have worse outcomes than stage-matched non-IBC patients. IBC patients presenting with de novo stage IV disease should be considered as a separate subcategory of stage IV in the tumor-node-metastasis classification because their clinical course and prognosis are different from those of patients with stage IV non-IBC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-12-02.
(1) Background: Potentially inappropriate medications (PIMs) in older adults are associated with drug-related problems, adverse health consequences, repeated hospital admissions and a higher risk of ...mortality. In Saudi Arabia and some Arab countries, studies of PIMs among large cohorts of older adults are limited. This study aimed to determine the prevalence of PIMs, trends and associated factors among outpatient older adults in Saudi Arabia. (2) Methods: A cross-sectional study was carried out. Over three years (2017-2019), data on 23,417 people (≥65 years) were retrieved from outpatient clinics in a tertiary hospital in Riyadh, Saudi Arabia. PIMs were assessed using the 2019 Beers Criteria. Covariates included sex, age, nationality, number of dispensed medications, and number of diagnoses. A generalized estimating equation model was used to assess trends and factors associated with PIMs. (3) Results: The prevalence of PIMs was high and varied between 57.2% and 63.6% over the study years. Compared with 2017, the prevalence of PIMs increased significantly, with adjusted odds ratios (OR) (95% confidence interval (95% CI)) of 1.23 (1.18-1.29) and 1.15 (1.10-1.21) for 2018 and 2019, respectively. Factors associated with being prescribed PIMs included ≥5 dispensed medications (OR_adjusted = 23.91, 95% CI = 21.47-26.64) and ≥5 diagnoses (OR_adjusted = 3.20, 95% CI = 2.88-3.56). Compared with females, males had a lower risk of being prescribed PIMs (OR_adjusted = 0.90, 95% CI = 0.85-0.94); (4) Conclusions: PIMs were common with an increasing trend among older adults in Saudi Arabia. A higher number of dispensed medications, increased number of diagnoses and female sex were associated with being prescribed PIMs. Recommendations on how to optimize prescriptions and implement de-prescribing strategies are urgently needed.
Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in ...reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible antischistosomal effect of eugenol on
.
The murine model of
was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined.
Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups.
Although eugenol could not totally eradicate adults of
, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol's role as a promising antifibrotic and a complementary antischistosomal agent.
Background: Retinopathy of prematurity (ROP) is increasing in incidence in developing nations, including Egypt. Secondary prevention requires timely detection through the development of regional ...screening guidelines, which should be preceded by large-scale studies to characterize the population at risk. Methods: A prospective, multicentric exploratory study that included five large tertiary institutions in an urban Egyptian setting. All infants born with gestational age (GA) < 37 weeks and/or birth weight (BW) < 2000 grams were screened. More mature and heavier infants with unstable clinical course were also included. The primary outcome measure was the rate of ROP and high-risk disease occurrence in relation to underlying risk factors. Results: Of the 768 eyes (384 screened infants), 347 eyes (45.2%) had stage 1 or higher disease, and 43 eyes (5.6%) had high-risk disease. Eyes with stage 1 or higher ROP and treatment-requiring ROP had a mean (+ or - SD) GA of 33.4 (+ or - 2.6) weeks and 32.8 (+ or - 3.2) weeks, and BW of 1842.3 (+ or - 570.1) grams and 1747.6 + or - (676.2) grams, respectively. Treatment- requiring eyes belonged to infants that had significantly lower GA and significantly higher prevalence of co-morbidities than non-treatment-requiring eyes. Conclusion: The incidence of ROP and high-risk disease in an urban Egyptian setting are similar to those in comparable settings elsewhere and locally. This exploratory study supports tailoring local screening criteria for ROP, and may aid the future development of national guidelines. Keywords: retinopathy of prematurity, ROP, screening, plus disease, preterm
Shp‐1, Shp‐2 and corkscrew comprise a small family of cytoplasmic tyrosine phosphatases that possess two tandem SH2 domains. To investigate the biological functions of Shp‐2, a targeted mutation has ...been introduced into the murine Shp‐2 gene, which results in an internal deletion of residues 46–110 in the N‐terminal SH2 domain. Shp‐2 is required for embryonic development, as mice homozygous for the mutant allele die in utero at mid‐gestation. The Shp‐2 mutant embryos fail to gastrulate properly as evidenced by defects in the node, notochord and posterior elongation. Biochemical analysis of mutant cells indicates that Shp‐2 can function as either a positive or negative regulator of MAP kinase activation, depending on the specific receptor pathway stimulated. In particular, Shp‐2 is required for full and sustained activation of the MAP kinase pathway following stimulation with fibroblast growth factor (FGF), raising the possibility that the phenotype of Shp‐2 mutant embryos results from a defect in FGF‐receptor signalling. Thus, Shp‐2 modulates tyrosine kinase signalling in vivo and is crucial for gastrulation during mammalian development.
Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in ...sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37 +/- 4 to 49 +/- 5 U, P < 0.05) and hypotension-prone (from 42 +/- 6 to 66 +/- 12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotension-prone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading of cardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope.
Scrotal cooling increases rectal temperature in man Vash, Peter D; Engels, 3rd, Thomas M; Kandeel, Fouad R ...
Experimental biology and medicine (Maywood, N.J.),
02/2002, Letnik:
227, Številka:
2
Journal Article
Recenzirano
The aim of this study was to evaluate the effect of scrotal cooling on rectal temperature in man. Pilot studies suggested that immersing the scrotum in a 30 degrees C water bath increased rectal ...temperature, but immersing the scrotum in a 0 degree C water bath did not. Six healthy young men immersed their scrotums in a 35 degrees C water bath for 11 min followed by 21 min at 30 degrees C. Rectal temperature rose by 0.38 +/- 0.04 degrees C (P < 0.01) in response to the 30 degrees C water bath. Repetition of the study by immersing the hands instead of the scrotum in the water bath had no effect on rectal temperature. The scrotum appears to play a role in human temperature regulation.
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