The effects of kiwifruit dressing on hypertrophic scars in a rabbit ear model.

AIMS: Hypertrophic scars show abnormal responses during healing. These scars, associated with dysregulated growth and excessive collagen formation, can have both functional and cosmetic consequences for patients. The present study evaluated the effects of kiwifruit on hypertrophic scars in a rabbit ear model. METHODS: This study included 13 New Zealand albino rabbits with full thickness wounds down to the cartilage (four wounds per ear; total: 104 scars). Sixteen days after initial wound formation, one ear of each rabbit was treated with daily kiwifruit dressing, while the other ear (control group) was dressed after normal saline irrigation for 10 days. Harvested skin samples were examined for histopathological, morphometric and immunohistochemical results. RESULTS: In comparison with the control group, early kiwifruit dressing significantly reduced the scar elevation index, fibroblast count and dermal collagen organisation. The ratio of collagen type III to total collagen immunoreactivity, inflammation and dermal capillary count increased significantly in the treated group, compared to the untreated controls. CONCLUSION: Based on the findings, early kiwifruit dressing improved the histological features of cutaneous wounds in rabbits. Therefore, this approach may be effective in clinical practice.

Association of immunohistochemical markers of tumor subtype with response to neoadjuvant chemotherapy and survival in patients with muscle-invasive bladder cancer.

PURPOSE: A readily accessible biomarker to identify which patients with bladder cancer are more likely to respond to neoadjuvant chemotherapy (NAC) could help clinicians avoid unnecessary chemotherapy and prevent its subsequent complications in some patients. The primary objective of this study was to investigate the association of immunohistochemical markers of tumor subtype with response to NAC and survival of patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: MIBC patients treated with NAC were retrospectively included. The tissue microarrays were assembled from transurethral resection of bladder tumor (TURBT) specimens and immunohistochemistry (IHC) was performed. The association of independent variables, including IHC markers, and clinical covariates with clinical complete response to NAC and with overall survival was assessed by using logistic regression and Cox proportional hazard regression analysis, respectively. Kaplan-Meier curves were plotted for different IHC-based tumor subtypes. RESULTS: Data from 140 MIBC patients treated with NAC were retrospectively reviewed. A total of 63 patients with available TURBT specimens were eligible to be included in the analysis. Our results showed that the IHC signature of KRT5/6(+)/KRT20(-), as a combined marker of basal subtype, was the only covariate significantly associated with complete response to NAC (p=0.037). Moreover, we found no statistically significant differences in overall survival between different IHC-based subtypes (p=0.721). CONCLUSIONS: The IHC expression of KRT5/6 and KRT20, as a readily accessible combined marker, may help us to identify the patients most likely to benefit from chemotherapy. The clinical utility of this marker needs to be established in larger prospective studies.

Data-Driven Discovery of Molecular Targets for Antibody-Drug Conjugates in Cancer Treatment.

Antibody-drug conjugate therapy has attracted considerable attention in recent years. Since the selection of appropriate targets is a critical aspect of antibody-drug conjugate research and development, a big data research for discovery of candidate targets per tumor type is outstanding and of high interest. Thus, the purpose of this study was to identify and prioritize candidate antibody-drug conjugate targets with translational potential across common types of cancer by mining the Human Protein Atlas, as a unique big data resource. To perform a multifaceted screening process, XML and TSV files including immunohistochemistry expression data for 45 normal tissues and 20 tumor types were downloaded from the Human Protein Atlas website. For genes without high protein expression across critical normal tissues, a quasi H-score (range, 0-300) was computed per tumor type. All genes with a quasi H - score ≥ 150 were extracted. Of these, genes with cell surface localization were selected and included in a multilevel validation process. Among 19670 genes that encode proteins, 5520 membrane protein-coding genes were included in this study. During a multistep data mining procedure, 332 potential targets were identified based on the level of the protein expression across critical normal tissues and 20 tumor types. After validation, 23 cell surface proteins were identified and prioritized as candidate antibody-drug conjugate targets of which two have interestingly been approved by the FDA for use in solid tumors, one has been approved for lymphoma, and four have currently been entered in clinical trials. In conclusion, we identified and prioritized several candidate targets with translational potential, which may yield new clinically effective and safe antibody-drug conjugates. This large-scale antibody-based proteomic study allows us to go beyond the RNA-seq studies, facilitates bench-to-clinic research of targeted anticancer therapeutics, and offers valuable insights into the development of new antibody-drug conjugates.

Ameliorative effect of a nano chromium metal-organic framework on experimental diabetic chronic kidney disease.

Metal-Organic Frameworks (MOFs) are a new class of crystalline porous structures which can be used as a novel structure in diverse fields of medical science. Several studies have shown that chromium supplementation can be effective in amelioration of biochemical parameters of diabetes and its renal complications. Therefore, a chromium-containing MOF (DIFc) was synthetized by nanochelating technology in the present study and then its effect on biochemical indices in diabetic rats was evaluated. Diabetes was induced by high-fat diet consumption and streptozotocin (35 mg/kg) injection and then the treatment started 8 weeks after disease induction and continued for 8 weeks. The results showed that DIFc treatment decreased HOMA-IR index, blood urea nitrogen, uric acid and malondialdehyde in plasma samples. This nano MOF also reduced albumin, malondialdehyde and 8-isoprostane in urine specimen, while it increased creatinine clearance. In conclusion, DIFc MOF demonstrated promising results in the present study, indicating that it can be developed and evaluated in future investigations with the aim of designing a novel agent for management of diabetes and its renal complications.

DIBc nano metal-organic framework improves biochemical and pathological parameters of experimental chronic kidney disease.

BACKGROUND: The growing morbidity and mortality rate of chronic kidney disease (CKD) has forced researchers to find more efficient strategies for controlling this disease. Studies have proven the important role of alteration in iron, zinc and selenium metabolism in CKD pathological process. Nanotechnology, through synthetizing nano metal-organic framework (NMOF) structures, can be employed as a valuable strategy for using these trace elements as the key for modification and improvement of CKD-related pathological events. After proving the anti-diabetic property of DIBc NMOF (which contains selenium and zinc) in the previous study, the impact of this NMOF on some important biochemical and pathological parameters of CKD was evaluated in the current study. METHODS: Knowing that diabetic nephropathy (DN) is the leading cause of CKD, male wistar rats were selected and given a high fat diet for 2 weeks and then were injected with streptozotocin (35 mg/kg) to induce DN. Six weeks after streptozotocin injection, DIBc or metformin treatment started and continued for 8 weeks. RESULTS: Eight weeks of DIBc treatment decreased plasma fasting blood glucose, blood urea nitrogen, uric acid, malondialdehyde (MDA) and HOMA-IR index compared to DN control and metformin groups. This NMOF significantly reduced urinary albumin excretion rate, MDA and 8-isoprostane, while it increased creatinine clearance in comparison to the above-mentioned groups. Renal histo-pathological images indicated that DIBc ameliorated glomerular basement membrane thickening and wrinkling, mesangial matrix expansion and hypercellularity and presence of intra-cytoplasmic hyaline droplets in proximal cortical tubules of kidney samples. CONCLUSION: The results showed the therapeutic effect of DIBc on important biochemical and histo-pathological parameters of CKD, so this NMOF could be regarded as a promising novel anti-CKD agent.

Microbiological Profile of Corneal Ulcers at a Tertiary Referral Center.

The aim of this study was to describe patient demographics, microbiological profile, and antibiotic susceptibility of corneal ulcer at a tertiary referral center to improve and optimize diagnosis and treatment of this potentially blinding entity and to reduce antibiotic misuse. Detailed external and slit-lamp bio-microscopic examination of 123 consecutive patients with suspected corneal ulcer was performed at an ophthalmology clinic. Corneal scraping was carried out under slit-lamp bio-microscopy. The obtained material was inoculated on culture media and smeared on a slide for Gram's staining for morphological identification of bacteria and fungus. For samples that developed colony in culture media, antibiotic susceptibility testing was performed. In a significant percentage of patients (72%) neither bacterial agents nor fungi were the cause of corneal ulcer. Of the 34 culture-proven corneal ulcers, in 79% of the cases, bacteria were detected while in 21% of cases, fungi were found. Of the 27 bacterial corneal ulcers, the majority were (67%) caused by Gram-positive bacteria, of which 50% were Streptococcus pneumoniae, and in the Gram-negative bacterial corneal ulcers, most of the cases (44%) were caused by Pseudomonas aeruginosa. In the antibiotic susceptibility report, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli were resistant to Cotrimoxazole (TS), Streptococcus pneumoniae to Erythromycin (E), Staphylococcus aureus to Peniciline (PG), Pseudomonas aeruginosa to Ceftriaxone (CRO) and Nitrofurantoin (NI), and finally, Escherichia coli to Gentamicin (GM). In conclusion, in a significant number of the patients neither bacterial agents nor fungi were offending microorganisms and bacteria were the most common agent of microbiological corneal ulcer, found in 79% of culture-proven corneal ulcers, followed by fungus, found in 21% of culture-proven corneal ulcers.

Lack of CHEK2 gene mutations in differentiated thyroid carcinoma patients using high resolution melting analysis.

Recently, mutations in the genes involved in cell cycle control, including CHEK2, are being considered as etiological factors in different kinds of cancers. The CHEK2 protein plays an important role in protecting damaged DNA from entering mitosis. In this study the potential effects of two common mutations IVS2+1G?A and Ile157Thr of CHEK2 gene in differentiated thyroid carcinoma (DTC) were evaluated. A total of 100 patients admitted to the Research Institute for Nuclear Medicine were diagnosed with DTC based on pathology reports of surgery samples. An additional 100 people were selected as a control group with no cancer history. PCR-HRM (high resolution melting) analysis was performed to deal with each of mutations in all case and control samples separately. During the analysis of IVS2+1G?A and Ile157Thr mutations of CHEK2 gene in the case and control groups, all the samples were identified as wild homozygote type. The finding suggests that IVS2+1G?A and Ile157Thr mutations of CHEK2 gene do not constitute a risk factor for DTC in the Iranian population. However, further studies with a larger population are required to confirm the outcome.

Increased risk of differentiated thyroid carcinoma with combined effects of homologous recombination repair gene polymorphisms in an Iranian population.

Homologous recombination (HR) repair has a crucial role to play in the prevention of chromosomal instability, and it is clear that defects in some HR repair genes are associated with many cancers. To evaluate the potential effect of some HR repair gene polymorphisms with differentiated thyroid carcinoma (DTC), we assessed Rad51 (135G>C), Rad52 (2259C>T), XRCC2 (R188H) and XRCC3 (T241M) polymorphisms in Iranian DTC patients and cancer-free controls. In addition, haplotype analysis and gene combination assessment were carried out. Genotyping of Rad51 (135G>C), Rad52 (2259C>T) and XRCC3 (T241M) polymorphisms was determined by PCR-RFLP and PCR-HRM analysis was carried out to evaluate XRCC2 (R188H) . Separately, Rad51, Rad52 and XRCC2 polymorphisms were not shown to be more significant in patients when compared to controls in crude, sex-adjusted and age-adjusted form. However, results indicated a significant difference in XRCC3 genotypes for patients when compared to controls (p value: 0.035). The GCTG haplotype demonstrated a significant difference (p value: 0.047). When compared to the wild type, the combined variant form of Rad52/XRCC2/XRCC3 revealed an elevated risk of DTC (p value: 0.007). It is recommended that Rad52 2259C>T, XRCC2 R188H and XRCC3 T241M polymorphisms should be simultaneously considered as contributing to a polygenic risk of differentiated thyroid carcinoma.

An assessment of parathyroid hormone, calcitonin, 1,25 (OH)2 vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors.

The aim of this study is to investigate the serum levels of parathyroid hormone (PTH), calcitonin, 1,25 (OH)(2) vitamin D3, estradiol and testosterone in male patients with active renal calcium stone disease compared with controls and investigate their relationship with serum/urinary biochemistry. Male active renal calcium stone formers (ASF) were enrolled from December 2008 to April 2009. Controls were selected from age and sex matched individuals. Two 24-h urine samples and a blood sample were withdrawn from each participant while they were on free diet. Serum 1,25 (OH)(2) vitamin D3 levels in the ASF and control groups were 127 ± 40 and 93 ± 35 pmol/l (p < 0.001). Serum levels of PTH, calcitonin, estradiol and testosterone were not statistically different between the ASF and control groups (all p > 0.05). Serum 1,25 (OH)(2) vitamin D3 was associated with higher urinary excretion of calcium and phosphorus in ASF patients. Serum levels of calcitonin were related to less urinary excretion of calcium in the control group. Serum testosterone was related to higher urinary excretion of uric acid in ASF patients and to higher urinary excretion of oxalate in the control group. 1,25 (OH)(2) Vitamin D3 is an important hormone in the pathogenesis of recurrent renal calcium stone disease and could increase renal stone risk by increasing the urinary excretion of calcium and phosphorus. There is a possibility of testosterone involvement in the pathogenesis of renal stones through higher urinary uric acid and oxalate excretion.

Partial ureterectomy for a huge primary leiomyoma of the ureter.

A case of a huge primary leiomyoma of the ureter in which only partial ureterectomy was performed is presented. The benign nature of the mass was primarily confirmed with frozen section at the time of surgery and then with immunohistochemistry (IHC). To the best of our knowledge, this case is a unique form of leiomyoma of the ureter due to its large size. There have been only ten cases of primary leiomyoma of the ureter reported since 1955 and all of them were very small in size. Our case is considered to be the eleventh.

Correlation of telomere length shortening with promoter methylation profile of p16/Rb and p53/p21 pathways in breast cancer.

Unregulated cell growth, a major hallmark of cancer, is coupled with telomere shortening. Measurement of telomere length could provide important information on cell replication and proliferation state in cancer tissues. Telomere shortening and its potential correlation with downregulation of cell-cycle regulatory elements were studied by the examination of relative telomere length and methylation status of the TP53, P21 and P16 promoters in tissues from breast cancer patients. Telomere length was measured in 104 samples (52 tumors and paired adjacent normal breast tissues) by quantitative PCR. Methylation profile of selected genes was analyzed in all samples using a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Our results demonstrated a significant shortening of tumor telomere regions compared with paired adjacent normal tissues (P<0.001). Similarly, telomere lengths were significantly shorter in advanced stage cases and in those with higher histological grades (P<0.05). Telomere shortening in cancer tissues was correlated with a different level of hypermethylation in the TP53, P21 and P16 promoters (r=-0.33, P=0.001; r=-0.70, P<0.0001 and r=-0.71, P<0.0001, respectively). The results suggested that inactivation of p16/Rb and/or p53/p21 pathways by hypermethylation may be linked to critical telomere shortening, leading to genome instability and ultimately to malignant transformation. Thus, telomere shortening and promoter hypermethylation of related genes both might serve as breast cancer biomarkers.

High-throughput hacking of the methylation patterns in breast cancer by in vitro transcription and thymidine-specific cleavage mass array on MALDI-TOF silico-chip.

Over the last decade, the rapidly expanding interest in the involvement of DNA methylation in developmental mechanisms, human diseases, and malignancies has highlighted the need for an accurate, quantitative, and high-throughput assay. Existing methods are limited and are often too laborious for high-throughput analysis or inadequate for quantitative analysis of methylation. Recently, a MassCLEAVE assay has been developed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to analyze base-specific methylation patterns after bisulfite conversion. To find an efficient and more cost-effective high-throughput method for analyzing the methylation profile in breast cancer, we developed a method that allows for the simultaneous detection of multiple target CpG residues by using thymidine-specific cleavage mass array on matrix-assisted laser desorption/ionization time-of-flight silicon chips. We used this novel quantitative approach for the analysis of DNA methylation patterns of four tumor suppressor genes in 96 breast tissue samples from 48 patients with breast cancer. Each individual contributed a breast cancer specimen and corresponding adjacent normal tissue. We evaluated the accuracy of the approach and implemented critical improvements in experimental design.