Systematic review of available guidelines on fertility preservation of young patients with breast cancer

Background: Since the survival rate of breast cancer patients has improved, harmful effects of new treatment modalities on fertility of the young breast cancer patients has become a focus of attention. This study aimed to systematically review and critically appraise all available guidelines for fertility preservation in young breast cancer patients. Materials and Methods: Major citation databases were searched for treatment guidelines. Experts from relevant disciplines appraised the available guidelines. The AGREE II Instrument that includes 23 criteria in seven domains (scope and purpose of the guidelines, stakeholder involvement, rigor of development, clarity, applicability, editorial independence, and overall quality) was used to apprise and score the guidelines. Results: The search strategy retrieved 2,606 citations; 72 were considered for full-text screening and seven guidelines were included in the study. There was variability in the scores assigned to different domains among the guidelines. ASCO (2013), with an overall score of 68.0, had the highest score, and St Gallen, with an overall score of 24.7, had the lowest scores among the guidelines. Conclusions: With the promising survival rate among breast cancer patients, more attention should be given to include specific fertility preservation recommendations for young breast cancer patients

Noise-induced outer hair cells' dysfunction and cochlear damage in rabbits

Background: Outer hair cells' (OHCs') dysfunctions as the extent of temporary and permanent threshold shifts (TTS and PTS) and cochlear damage were assessed in rabbits exposed to continuous noise. Methods: Twelve New Zealand white rabbits were studied in noise (N) (n=6; exposed to continuous noise; 95 dB SPL, 500-8000 Hz for 8 h per day during 5 consecutive days) and control (C) (n=6; not exposed to noise). OHCs' functions were assessed by distortion product otoacoustic emission (DPOAE) level (Ldp) measurements in different periods and comparing TTS and PTS. Animals were anaesthetized by CO2; cochleae were extracted, fixed in 10 formaldehyde for 48 hours, decalcified by 10 nitric acid for 24 hours, and dehydrated, embedded, sectioned 5 \am thickness and stained by Hematoxylin and Eosin for light microscopy. Results: The most and least Ldp or TTS or PTS were related to 5888.50 Hz and 588.00 Hz respectively in noise subjected rabbits (P0.05). Severely vacuolated OHCs, pyknotic IHCs, swollen SC, and slightly thickened BM were found. Conclusion: Continuous noise extensively led to OHCs' dysfunctions as decreased Ldp (both TTS and PTS) and highly damage to cochlea. © Iranian Red Crescent Medical Journal

Studying angiogenesis in autochthonous xenograft models of glioblastoma multiforme by MVD-CD34 technique in Iranian patients

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Despite advances in cancer diagnosis and treatment, survival rate of patients suffering from glioblastoma multiform (GBM) has not been significantly improved. Therefore, novel therapeutic adjuncts to routine therapies have been suggested over time. Inhibition of angiogenesis by antiangiogenic drugs is one of the new approaches to inhibit the growth of malignant cells. Microvessel density (MVD) assay is a technique performed by counting immunohistochemically-stained blood vessels. Nowadays, athymic nude mice are widely used for the establishment of xenograft tumor models in cancer research. The aim of this study was to evaluate the MVD of autochthonous xenograft models of GBM isolated from Iranian patients for use in pharmaceutical research on antiangiogenic drugs."n"nMethods: Fresh tumor samples of GBM were obtained from three patients in Cancer Institute of Tehran University of Medical Sciences in Fall of 2010 and Winter of 2011. After preliminary processing, minced tumor samples were implanted heterotopically on flanks of athymic nude mice. Two months later, the animals were sacrificed and the xenograft tumor samples were sent to the pathology laboratory. After establishing the proof of the xenograft tumor type, MVD-CD34, an endothelial cell marker, was assessed by counting hot spot areas in 22 samples."n"nResults: The mean number of microvessels in these xenograft tumor models was 30±2.1."n"nConclusion: These autochthonous xenograft models of GBM can be used in preclinical settings for research on antiangiogenic drugs regarding a pharmacogenomics-based treatment regimen for the Iranian population. Moreover, such models can be used in future studies for determining the sensitivity or resistance to antiangiogenic drugs in individualized cancer therapy

Down-regulation of immune checkpoints by doxorubicin and carboplatin-containing neoadjuvant regimens in a murine breast cancer model

Objective(s): Immune checkpoint expression on tumor-infiltrating lymphocytes (TILs) has a correlation with the outcome of neoadjuvant chemotherapy (NAC) in breast cancer. However, the reciprocal effect of these regimens on the quality and quantity of immune checkpoints has hitherto not been addressed. We aimed to evaluate the impact of three NAC regimens on TILs and immune checkpoints in a murine triple-negative breast cancer model. Materials and Methods: Syngeneic model of locally-advanced breast cancer was established in immunocompetent mice using a 4T1 cell line. Tumor-bearing animals were treated with human-equivalent dosages of doxorubicin, paclitaxel, paclitaxel and carboplatin combination, and placebo. Infiltration of CD3+, CD8+, and FoxP3+ cells into the tumor was assessed by immunohistochemistry. Expression of immune checkpoints, including PD-1, CTLA-4, and TIM-3, was evaluated by real-time PCR. Results: Doxorubicin led to a significant (P<0.01) increase in the percentage of the stromal infiltrating CD3+ and CD8+ lymphocytes. Doxorubicin also suppressed significantly (P<0.05) the relative expression of PD-1 compared with the placebo. PD-1 expression was significantly (P<0.05) lower in the group treated with paclitaxel and carboplatin combination as compared with the placebo. The relative expression of TIM-3 was significantly (P<0.05) suppressed in doxorubicin-treated mice in comparison with other interventions. Conclusion: Our findings hypothesize that NAC with doxorubicin may potentiate antitumor immunity not merely by recruitment of TILs, but via down-regulation of PD-1 and TIM-3 checkpoints. Carboplatin-containing NAC may suppress PD-1 as well. © 2021 Mashhad University of Medical Sciences. All rights reserved

Temporary and Permanent Level Shifts in Distortion Product Otoacoustic Emissions following Noise Exposure in an Animal Model

Background: Noise-induced hearing loss (NIHL) is one of the most common occupational illnesses. Most of the studies on NIHL were conducted at high noise levels that people are rarely exposed to but in industries. The function of the outer hair cells (OHCs) is impaired after exposure to industrial noise. Distortion product otoacoustic emissions (DPOAEs) are useful in examination of noise-induced level shifts. Objectives: To assess the function of OHCs by DPOAE temporary and permanent level shifts (TLSdp and PLSdp) in rabbits exposed to white noise at realistic levels typically found in industrial settings over a broad range of frequencies. Methods: 12 albino rabbits were divided into two groups: the experimental group rabbits which were exposed to 95 dB SPL white noise at 500–8000 Hz for 8 hrs/day for 5 consecutive days, and the control group rabbits with no exposure to noise. The function of OHCs was examined by DPOAE level (Ldp) in different occasions. The study groups were compared for DPOAE temporary and permanent level shifts (TLSdp and PLSdp) to assess the effect of noise on OHCs function. Results: Noise-induced DPOAE levels (Ldp) were decreased up to 20.65 dB (on day 8) and 18.93 dB (on day 11) at 5888.50 Hz (p=0.081). TLSdp and PLSdp were significantly decreased up to 17.99 dB and 16.27 dB, respectively in the experimental group. The most and least Ldp were significantly different (p<0.05); they occurred at 5888.50 and 588.00 Hz, respectively. There were significant differences between temporary and permanent threshold shift at various frequencies (p<0.05). These differences were mainly related to 5888.50 Hz compared to other frequencies in each ear (p<0.05). Conclusion: DPOAEs are an attractive tool for obtaining information about small temporary or permanent threshold shifts, even when the pure tone audiogram is normal

In vivo identification of novel TGIF2LX target genes in colorectal adenocarcinoma using the cDNA-AFLP method

Background and study aims: Homeobox-containing genes are composed of a group of regulatory genes encoding transcription factors involved in the control of developmental processes. The homeodomain proteins could activate or repress the expression of downstream target genes. This study was conducted to in vivo identify the potential target gene(s) of TGIF2LX in colorectal adenocarcinoma. Methods: A human colorectal adenocarcinoma cell line, SW48, was transfected with the recombinant pEGFPN1-TGIF2LX. The cells were injected subcutaneously into the flank of the three groups of 6-week-old female athymic C56BL/6 nude mice (n = 6 per group). The transcript profiles in the developed tumours were investigated using the cDNA amplified fragment length polymorphism (cDNA-AFLP) technique. Results: The real-time RT-PCR and DNA sequencing data for the identified genes indicated that the N-terminal domain-interacting receptor 1 (Nir1) gene was suppressed whereas Nir2 and fragile histidine triad (FHIT) genes were upregulated followed by the overexpression of TGIF2LX gene. Conclusion: Downregulation of Nir1 and upregulation of Nir2 and FHIT genes due to the overexpression of TGIF2LX suggests that the gene plays an important role as a suppressor in colorectal adenocarcinoma. © 2018 Pan-Arab Association of Gastroenterolog