Vascular endothelial growth factor expression correlates with serum CA125 and represents a useful tool in prediction of refractoriness to platinum-based chemotherapy and ascites formation in epithelial ovarian cancer

There is an increasing need for the identification of novel biological markers and potential therapeutic targets in epithelial ovarian cancer (EOC). Given the critical role of growth factors in the biology of EOC, we aimed in the present study to evaluate the intratumoral expressions of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) proteins and their clinical relevance in a cohort of 100 patients with EOC. All patients received platinum-based chemotherapy after surgery. A comparative immunohistochemical study of normal ovarian and EOC tissues showed that both growth factors were expressed at higher levels in tumor samples. In our statistical analysis, while no association existed between the FGF expression status and the clinicopathological characteristics of patients, intratumoral VEGF was identified as a potential biomarker for the prediction of ascites formation. In addition, the expression status of VEGF appeared to independently predict overall survival and response to chemotherapy. Furthermore, a direct association was demonstrated between the pre-treatment VEGF expression and serum CA125 after three cycles of chemotherapy. In sum, we report for the first time to our knowledge the correlation between intratumoral VEGF and serum CA125 in EOC. Our data also shows the prognostic value of VEGF expression in EOC. These results suggest the potential value of intratumoral VEGF in patient stratification. Dual inhibition of VEGF and CA125 might bring about a better outcome for patients with EOC.     

Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles

Background

Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system.

Methods

The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed.

Results

The particle size of NPs ranged from 170 to 190 nm and increased about 20–30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased further after HSA conjugation. The HSA conjugation in prepared NPs was proved by Fourier transform infrared (FT-IR) spectroscopy, faster degradation of HSA in Differential scanning calorimetry (DSC) characterization, and other evidences such as the increasing in size and the decreasing in zeta potential. The PTX released in a biphasic mode for all colloidal suspensions. A sustained release profile for approximately 33 days was detected after a burst effect of the loaded drug. The in vitro cytotoxicity evaluation also indicated that the HSA NPs are more cytotoxic than plain NPs.

Conclusions

HSA decoration of PLGA NPs may be a suitable method for longer blood circulation of NPs.     

Various durations of a standard regimen (amoxycillin, metronidazole, colloidal bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial

INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.     

The novel combination of fat clearance and immunohistochemistry improves prediction of the outcome of patients with colorectal carcinomas: a preliminary study

To evaluate the significance of micrometastases in relation to survival rate, specimens from 48 colorectal carcinoma patients were analysed after fat clearance. The number and size of the lymph nodes harbouring metastases and the significance of micrometastases for patients' survival were assessed. We found that although the majority of metastatic lymph nodes (71.8%) were 5 mm or less in diameter, their size had no effect on survival. Immunohistochemical staining of lymph nodes revealed that 15 of 25 patients with Dukes' stage B diagnosed by routine staining had micrometastases, 86% of these lymph nodes being less than 5 mm in diameter. The survival rate of this subgroup was found to be considerably poorer than that of Dukes' stage B patients with no micrometastases. None of the three patients with Dukes' stage A carcinoma had micrometastases. Since most of the metastases and micrometastases occur in lymph nodes of 5 mm and less and can be easily missed by routine examination, we suggest that fat clearance and routine immunohistochemical analysis of Dukes' stage B improve the prediction of outcome of colorectal cancer patients. Accepted: 10 February 1998     

Altered lipid profile, leptin, insulin, and anthropometry in offspring of South Asian immigrants in the United States

South Asians who immigrate to the United States have a propensity toward insulin resistance, central obesity, and elevated total cholesterol:high-density lipoprotein (HDL) ratio. To evaluate whether these alterations are apparent at a younger age, we studied 32 offspring of South Asian immigrants and compared them with 29 of European descent between 18 to 30 years of age. American-born South Asian males had significantly higher total cholesterol, low-density lipoprotein (TC:LDL) ratios, triglycerides, and fasting insulin levels (13.9 +/- 7.1 and 10.0 +/- 5.5 microU/mL, P <.01) than their European counterparts. The South Asian females only had increased plasma insulin levels (15.3 +/- 8.8 and 10.0 +/- 5.1 microU/mL, P =.05). The entire South Asian group had higher truncal skinfold thickness (40.1 +/- 18.1 and 30.3 +/- 12.6 mm, P = <.05) and lower insulin-like growth factor binding protein (IGFBP)-1 levels (46.8 +/- 33.4 and 56.0 +/- 33.4 microg/L, P =.05). Plasma leptin levels were also significantly higher in both males (4.3 +/- 2.5 v 2.8 +/- 1.3 ng/mL, P =.0001) and females (20.5 +/- 10.3 v 10.3 +/- 6.3 ng/mL, P =.002) South Asian subjects. A significant correlation between plasma leptin and insulin, triglycerides, TC, and body mass index (BMI) was seen in the South Asian males. South Asians born in the United States show evidence for an altered metabolic profile in young adulthood. The relative contributions of inheritance and nutritional practices early in life to this alteration remain unclear.     

Determining viability of fresh or cryopreserved homograft valves at implantation

Summary Studies of homograft valves in the past two decades have suggested that viable valves, i.e., those maintaining chemical and structural integrity of their leaflet intercellular matrix, have a better long-term function than nonviable valves. The most effective qualitative methods of assessing leaflet viability involve destruction of the valve leaflets; thus, these methods have been limited to random use in selected valves. A study was conducted in swine in an attempt to establish a control tissue which could be tested in place of the homograft leaflets, thereby determining viability levels of every valve clinically implanted and correlating the results with long-term clinical function. Thirty samples each of the aortic and pulmonary artery wall and tricuspid leaflet were compared with aortic and pulmonary leaflets. Utilizing the technique of C¹⁴-proline uptake, viability was assessed at procurement, following sterilization, and following cryopreservation and short-term storage. The tricuspid leaflet was found to retain the same level of viability as the aortic and pulmonary leaflets before and after the cryopreservation period. It was concluded that the tricuspid leaflet could be utilized as the control tissue.     

Hb Dhonburi (Neapolis) [beta126(H4)Val-->Gly] identified in a family from northern Iran

Thalassemias are the most common hereditary diseases in Iran, resulting from synthesis defects in one or more hemoglobin (Hb) subunits. The majority of patients suffer from beta-thalassemia (thal), but cases with microcytic hypochromic anemia and normal electrophoretic patterns are suspected to have alpha- or silent beta-thal. A family from the northern part of Iran, an area highly prevalent for thalassemias, was referred to us for prenatal diagnosis. The hematological data of the father indicated a pattern of beta-thal minor. Reverse hybridization analysis for the most common beta-globin mutations identified IVS-II-1 (G-->A) in the heterozygous state. The maternal laboratory data indicated a case more compatible with alpha-thal. Iron deficient anemia was ruled out, and common alpha-thal point mutations and deletions were investigated. As no mutation was detected, chain synthesis was performed and showed an alpha/beta chain ratio of 2.1, that was in the range of beta-thal minor. DNA sequencing of the entire beta-globin gene identified a heterozygous GTG-->GGG (Val-->Gly) mutation at codon 126, also known as Hb Dhonburi (Neapolis). Prenatal diagnosis of the fetal DNA showed the absence of the IVS-II-1 and codon 126 anomalies. This result demonstrates the importance of screening of individuals with mild microcytic hypochromic anemia for both alpha- and silent beta-thal mutations.