The Results of Chemotherapy with Two Variants of Intravenous CMF in Patients with Early Stage Breast Carcinoma; Does Dose Density Matter?

No direct comparisons can be made in early stages of breast cancer, between the intravenous combinations of: cyclophosphamide, methotrexate, and fluorouracil; named modified versions of CMF with the classical oral version of CMF. Since these modifications have different dose intensities and densities, the outcomes for their subsequent treatments may be varied, and not produce the same results. Despite that, classical CMF has been commonly replaced with intravenous modifications. This study aimed to assess the results of treatment with two common intravenous modification of CMF chemotherapy; to represent the most effective and successful substitute of classical CMF. Five hundred patients in two groups were eligible to take part in the experiment. For two hundred and twenty‐nine patients in the group CMF 1&8, chemotherapy was administered intravenously on days 1 and 8 every 28 days for six cycles consisting of: cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m². In the group CMF 1 which consisted of 271 patients, chemotherapy was administered with all the same drugs and doses, however, it was only administered on day 1 and repeated at 21‐day intervals for six cycles. Overall survival (OS), disease‐free survival (DFS), the prognostic factors and other probable interventional factors were then compared between the two groups. The 5‐year OS rate of 87.5% and 10‐year OS rate of 82% in the group CMF 1&8 were statistically significantly better than 5‐year OS of 84% and 10‐year OS of 61.5% in the group CMF 1 (p = 0.01). The 5‐year and 10‐year DFS rates were 76% and 60% respectively, in the group CMF 1&8 compared with 77% and 54% respectively in the group CMF 1 (p = 0.8). Two groups were comparable regarding their distribution of different prognostic factors and other probable interventional factors. Considering 30% higher dose density of drugs in the protocol of CMF 1&8, the improving outcome can be related to the efficacy of dose‐dense chemotherapy. Therefore, this intravenous modification is the better substitute of classical CMF.     

Immunosuppression following dietary aflatoxin B1 exposure: a review of the existing evidence

Aflatoxin B1 is a toxic and secondary metabolite secreted by some natural molds, such as Aspergillus, and has been associated with severe toxic effects in humans and animals. They contaminate food and feed supplies, and are commonly found in grains and nuts. These toxins are synthesized under suitable physical, chemical and biological conditions. High-temperature stress, moisture stress and insect injury of the product are the most important factors in mold invasion and subsequent toxin production. These toxins have different carcinogenic and cytotoxic properties. The immunological effects of exposure to AFB1 are assessed in the present review.     

Evaluation of CAIX and CAXII Expression in Breast Cancer at Varied O<Subscript>2</Subscript> Levels: CAIX is the Superior Surrogate Imaging Biomarker of Tumor Hypoxia

Purpose

Hypoxia is commonly observed in regions of primary tumors and metastases, and is associated with resistance to treatment, more aggressive tumor phenotypes and poor prognosis. Reliable and validated imaging biomarkers of hypoxia are needed for pre-clinical studies and clinical use. Expression of cell-surface carbonic anhydrases IX and XII (CAIX and CAXII) in tumor cells has been associated with tumor hypoxia. CAIX and CAXII specific antibodies conjugated to fluorescent dye were evaluated for the non-invasive detection of hypoxia in vivo.

Procedures

Human breast cancer cell lines (MCF10A, DCIS, MCF7, ZR-75.1 and MDA-mb231) were characterized for CAIX and CAXII expression by real-time RT-PCR and immunocytochemistry (ICC) under normoxic and hypoxic conditions. Immunohistochemical (IHC) staining of CAIX, CAXII and the commercially available exogenous hypoxia marker, pimonidazole, was performed using sections of ZR-75.1 and MDA-mb-231 orthotopic breast cancer xenograft tumors from nude mice. In vivo fluorescence imaging of ZR-75.1 tumors in animals housed at varied levels of oxygen was used to quantify the relative uptake of the CAIX and CAXII agents and a commercially available sulfonamide-based agent. Corresponding tumor sections were IHC stained for CAIX, CAXII and pimonidazole.

Results

CAIX mRNA expression was significantly higher (p?<?0.05) in hypoxia for all cell lines, which was in agreement with protein expression by ICC. CAXII expression was mixed, with a modest hypoxia-related increase in two cell lines (p?<?0.05) and no change in others. Quantified IHC staining of ZR-75.1 and MDA-mb-231 tumor sections showed that CAIX and CAXII expression was elevated in regions with pimonidazole staining, but CAXII levels were lower than CAIX. Tumor uptake of the CAIX targeted agent, and IHC staining of CAIX and pimonidazole in corresponding tumor sections were correlated, and co-registered, and shown to be significantly elevated by level of oxygenation (p?<?0.001): hypoxia?>?normoxia?>?hyperoxia. However, the CAXII and sulfonamide agents were not significantly correlated with hypoxia.

Conclusion

These studies suggest that the fluorescently labeled CAIX-specific agent is a more robust indicator of hypoxia in vivo compared to the CAXII-specific agent or the agent specific to the CA active site.

     

Benefits of Zataria multiflora Boiss in Experimental Model of Mouse Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic condition of theintestine with unknown etiology involving multiple immune, geneticand environmental factors. We were interested to examine theeffect of total extract from Zataria multiflora Boiss, a folkmedicinal plant on prevention and treatment of experimentalIBD. Z. multiflora was administered (400, 600, 900 p.p.m.) throughdrinking water to IBD mice induced by intrarectal administrationof acetic acid. Prednisolone was used as the standard drug forcomparison. Biochemical, macroscopic and microscopic examinationsof colon were performed. Biochemical evaluation of inflamedcolon was done using assay of myeloperoxidase (MPO) activityand thiobarbituric acid reactive substances (TBARS) concentrationas indicators of free radical activity and cell lipid peroxidation.The activity of MPO and lipid peroxidation products (TBARS)increased in acetic acid-treated groups while recovered by pretreatmentof animals with Z. multiflora (400–900 p.p.m.) and prednisolone.Z. multiflora (600 and 900 p.p.m.) and prednisolone-treatedgroups showed significantly lower score values of macroscopicand microscopic characters when compared with the acetic acid-treatedgroup. The beneficial effect of Z. multiflora (900 p.p.m.) wascomparable with that of prednisolone. The antioxidant, antimicrobialand anti-inflammatory potentials of Z. multiflora might be themechanisms by which this herbal extract protects animals againstexperimentally induced IBD. Proper clinical investigation shouldbe carried out to confirm the activity in human.     

p57KIP2 immunohistochemical expression: a useful diagnostic tool in discrimination between complete hydatidiform mole and its mimics

Purpose  

The purpose of this study was to evaluate the results of immunohistochemical expression of p57KIP2 in the complete hydatidiform mole (CHM) and other types of hydropic pregnancy.     

The first study of patient safety culture in Iranian primary health centers

Although the error in health care has received attention recently, patient safety culture in health centers has been relatively neglected. To measure the patient safety culture in primary health centers. A cross-sectional study, utilizing the modified version of the Hospital Survey on Patient Safety Culture (HSOPSC) developed by the Agency for Healthcare Research and Quality (AHRQ) and a demographic questionnaire. Healthcare staffs from health centers were participated in the survey. The patient safety culture score including subscores on 11 dimensions and 39 items; patient safety grade and number of events reported. The overall positive response rate of patient safety culture was 57 ±16.8 (CI 9555%-59%). The dimensions that received higher positive response rate were "Teamwork across units of health center", "Teamwork within units", "Head of center support for patient safety". The lowest percentage of positive responses was "Non punitive response to error". There were no relationship between working years and patients safely culture score. Similarly, no relationship was found between professional, gender and total patients safely culture score. Statistical analysis showed discrepancies between Iranian health centers and the US hospitals in three dimensions. For improving patient safety culture in health centers, it is necessary to have enough staff and establish an environment to be open and fair with staff which helps report errors spontaneously and without any fear. The findings of this study could be used to measure changes in patient safety culture over the time.     

Curcuminoids rescue long-term potentiation impaired by amyloid peptide in rat hippocampal slices

Curcuminoids are vital constituent of turmeric, with therapeutic potential in the treatment of Alzheimer's disease. Electrically, stimulus train-elicited plastic changes in hippocampal CA1 excitability were used as an experimental paradigm to study the effects of curcuminoid mixture and individual components on functional failure induced by Aβ peptide in vitro. Electrical stimulation was applied on Schaffer collaterals, and population spikes (PS) were recorded from stratum pyramidale. To induce long-term potentiation (LTP) of PS, primed burst stimulation (PBs) was used. Aβ peptide inhibited PS LTP induction. Sinking PS LTP due to Aβ peptide was rescued when curcuminoid mixture was applied before PBs only at lower dose (0.1 μM) resulting in PS potentiation to 127.42% ± 1.83% at 5 min and 123.98% ± 1.06% at 60-min post-PBs. Similarly, when bisdemethoxycurcumin was applied, PS LTP was induced and lasted only at a single dose (0.1 μM). Demethoxycurcumin was effective at a middle dose (1 μM), so that the PS amplitude was changed to 140.15% ± 2.68% and 129.82% ± 0.44% at 5 and 60 min, respectively. PS LTP was effectively induced in the presence of curcumin at middle and high doses (1 and 30 μM) with resultant PS LTP to 155.68% ± 1.23% and 127.72% ± 1.23%, respectively, at 60-min post-PBs. These results showed that curcuminoids can restore susceptibility for plastic changes in CA1 excitability that is injured by exposure to Aβ peptide and rescue sinking PS LTP in Aβ-peptide-exposed hippocampal CA1 neurons.