Thrombospondin 1 expression and angiogenesis in breast carcinoma and their relation with platelet activity

This study investigates angiogenesis and the expression of thrombospondin 1 in invasive ductal carcinoma of the breast and their possible relation to platelet counts and platelet activity. The study included 20 cases of invasive ductal carcinoma. Platelet activity was evaluated by determining thromboxane B2 and cyclic guanosine monophosphate (cGMP) levels by enzyme immunoassay (EIA).Thrombospondin (TSP) 1 and CD34 expression was studied immunohistochemically. Mean platelet count of the patient group was significantly greater than the mean platelet count of the control group (P < 0.05). The platelet counts were positively correlated with tumour size (r=0.609; P < 0.01). Platelet counts were higher in the patients who had grade 3 microvessel density (P < 0.05). The mean basal platelet cGMP level in the patient group was significantly lower than it was in the control group (P < 0.05). Focal TSP immunoreactivity was detectable in 5 (20%) cases in the tumour cells, and in 9 (45%) cases in the stroma. We did not find any correlation between TSP-1 staining and angiogenesis, platelet counts, platelet activity, and the histological prognostic parameters. Our study confirms the essential role of platelets in tumour growth and angiogenesis. Decreased levels of cGMP in the patient group may cause platelet hyperreactivity. Although thrombospondin 1 may be upregulated in malignant breast tissue, this is not sufficient for tumour growth and dissemination according to our results.     

Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk

Virginia G. Kaklamani, MD, DSc; Kari B. Wisinski, MD; Maureen Sadim, BS; Cassandra Gulden, MS; Albert Do, BS; Kenneth Offit, MD, MPH; John A. Baron, MD; Habibul Ahsan, MD, MPH; Christos Mantzoros, MD, MPH; Boris Pasche, MD, PhD

JAMA. 2008;300(13):1523-1531.

Context  Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date.

Objective  To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk.

Design, Setting, and Patients  Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity.

Main Outcome Measures  ADIPOQ and ADIPOR1 SNP frequency among cases and controls.

Results  In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis of both studies shows an association of rs266729 with decreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99).

Conclusion  The SNP rs266729, which tags the 5' flanking region of the ADIPOQ gene, is associated with decreased colorectal cancer risk.

     

Obstructive sleep apnea syndrome and erectile dysfunction: does long term continuous positive airway pressure therapy improve erections?

ObjectivesThe aim of this age-matched, controlled, prospective clinical study was to investigate frequency and degree of erectile dysfunction (ED) in patients with obstructive sleep apnea syndrome (OSAS) and to evaluate the results of only continuous positive airway pressure (CPAP) therapy on ED in patients with OSAS.ResultsWhen compared to the control group, a decrease in IIEF-5 scores was found in patients with OSAS. However, this decrease was not statistically significant. After 3 months of CPAP usage in patients with mild to moderate and severe degree OSAS, improvement in IIEF-5 scores was statistically significant. Mean value of IIEF-5 score was 16.63±5.91 before CPAP and were improved up to 20.92±6.79 (P=0.001).ConclusionIt is not certainly possible to say that OSAS is clearly associated with ED. However, after 3 months of regular CPAP usage, ED complaints in patients with OSAS might improve positively. Trials with larger series may give more conclusive data.     

A new approach to postoperative peritoneal adhesions: Prevention of peritoneal trauma by aloe vera gel

Objective

Covering peritoneal surfaces with aloe vera gel may prevent peritoneal trauma and hence postoperative peritoneal adhesions.

Study design

Forty Wistar albino out-bred female rats (mean weight, 180 ± 25 g; mean age, 6 months) were divided into four groups. In Group 1, 0.1 mL aloe vera gel was injected into the peritoneal cavities. In Group 2, peritoneal adhesions were induced. In Group 3, adhesions were induced and the modeled area was covered by 0.1 mL aloe vera gel. In Group 4, the area was covered with aloe vera gel prior to adhesion induction. The rats were sacrificed on postoperative day 10 and the adhesions were scored both microscopically and macroscopically.

Results

The mean macroscopic adhesion score in the four groups was 0, 5.8 ± 0.42, 5.2 ± 0.79, and 1.1 ± 1.2 respectively, with the difference between Group 4 and Groups 2 (p < 0.001) and 3 (p < 0.05) statistically significant. The mean histopathological fibrosis values were significantly higher in Group 3 than in Group 4 (2.6 ± 0.51 vs 1.2 ± 0.91, p = 0.002).

Conclusion

Aloe vera gel can effectively decrease adhesion formation if applied before, but not after, after peritoneal trauma. This effect is likely due not to its chemical properties but to its viscosity, providing a covering to prevent peritoneal trauma.     

Molecular diagnosis and molecular profiling to detect treatment-resistant ovarian cancer

Introduction: Epithelial ovarian cancer remains the gynecologic tumor with the highest rate of recurrence after initial optimal cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately, with the development of recurrent ovarian cancer often comes the discovery of chemo-resistant disease. The absence of improvement in long term survival, notwithstanding the use of newer agents as is seen in other cancers, emphasizes the need for improved understanding of the processes that lead to chemo-resistant disease.

Areas Covered: This review will cover the following topics: 1. Molecular and cellular mechanisms in platinum and paclitaxel resistance 2. Other molecular mediators of chemo-resistance 3. Expression of stem cell markers in ovarian cancer and relationship to chemo-resistance 4. MicroRNA and long non-coding RNA expression in chemo-resistant ovarian cancer 5. Determination of chromosomal aberrations as markers of chemo-resistance 6. Molecular profiling in chemo-resistant disease.

A standard MEDLINE search was performed using the key words; ovarian cancer, chemo-resistant disease, molecular profiling, cancer stem cells and chemotherapy.

Expert Commentary: Over the next few years the challenge remains to precisely determine the mechanisms responsible for the onset and maintenance of chemo-resistance and to effectively target these mechanisms.     

Effects of aminoguanidine and melatonin on intestinal ischemia/reperfusion injury in rats: An assessor-blinded, controlled experimental study

Background: The reactive oxygen and nitrogen species generated during reperfusion of tissue are characteristic of intestinal ischemia and reperfusion (IIR) injury.Objective: This study was designed to assess whether the administration of aminoguanidine (AG), a selective nitric oxide synthase inhibitor, and/or melatonin has protective potential in IIR injury.Methods: Male Wistar albino rats (age, 3–4 weeks; weight, 100–150 g) were divided in a nonrandom fashion into 5 groups of equal size: group 1, IIR injury + AG 100 mg/kg; group 2, IIR injury + melatonin 10 mg/kg; group 3, IIR injury + AG 100 mg/kg + melatonin 10 mg/kg; group 4, sham operation; and group 5, IIR injury alone. Sixty minutes of intestinal ischemia and 4 hours of reperfusion were carried out in all but the sham-operation group. Ileal specimens were obtained from all rats to determine the extent of histologic changes, measure tissue concentrations of malondialdehyde (MDA) and protein carbonyl (PC), and assess the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Specimens were also assessed and scored by a pathologist blinded to the experiment and the data.Results: Forty rats were divided into 5 groups of 8 each; all 40 survived until study end. In the IIR injury-alone group, mean (SD) MDA concentration and PC content were significantly higher than that of the sham-operation group, and SOD and GPx activity were significantly lower: MDA concentration, 0.86 (0.03) versus 0.54 (0.01) mmol/g protein, respectively; PC content, 0.60 (0.02) versus 0.34 (0.01) mmol/g protein; SOD activity, 104.33 (43.14) versus 2954.72 (109.55) U/g protein; and GPx activity, 10.44 (0.63) versus 24.34 (1.77) U/g protein (all, P < 0.001). Administration of AG, melatonin, and the AG/melatonin combination was associated with significantly higher SOD (1802.31 [102.35], 1776.50 [58.41], and 1924.28 [98.10] U/g protein, respectively) and GPx (17.36 [1.23], 15.96 [1.08], and 18.06 [1.72] U/g protein) activity and significantly lower MDA concentration (0.62 [0.02], 0.64 [0.02], and 0.56 [0.01] mmol/g protein) and PC content (0.53 [0.03], 0.51 [0.01], and 0.49 [0.02] mmol/g protein) compared with the IIR injury-alone group (P < 0.001). Mean intestinal mucosal injury scores were significantly lower in the 3 treatment groups (2.12 [0.35], 1.75 [0.46], and 1.12 [0.35]) compared with the IIR injury-alone group (3.87 [0.35]; all, P < 0.001).Conclusion: In this study, AG, melatonin, or both administered in combination were associated with improvements in oxidative markers in this rat model of IIR injury.     

Long-term follow-up of pachychoroid pigment epitheliopathy and lesion characteristics

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate conversion of pachychoroid pigment epitheliopathy (PPE) lesions and the development of other pachychoroid spectrum...