The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients.

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

Synthesis and characterization of chitosan hybridized zinc phosphate/hydroxyapatite core shell nanostructure and its potentiality as delivery system of oxaliplatin drug.

An advanced form of zinc phosphate/hydroxyapatite nanorods with a core-shell structure (ZPh/HPANRs) was made and then hybridized with chitosan polymeric chains to make a safe biocomposite (CH@ZPh/HPANRs) that improves the delivery structure of traditional oxaliplatin (OXPN) chemotherapy during the treatment of colorectal cancer cells. The qualifications of CH@ZPh/HPANRs in comparison with ZPh/HPANRs as a carrier for OXPN were followed based on loading, release, and cytotoxicity. CH@ZPh/HPANRs composite exhibits a notably higher OXPN loading capacity (321.75 mg/g) than ZPh/HPANRs (127.2 mg/g). The OXPN encapsulation processes into CH@ZPh/HPANRs display the isotherm behavior of the Langmuir model (R2 = 0.99) and the kinetic assumptions of pseudo-first-order kinetics (R2 > 0.89). The steric studies reflect a strong increment in the quantities of the free sites after the chitosan hybridization steps (Nm = 34.6 mg/g) as compared to pure ZPh/HPANRs (Nm = 18.7 mg/g). Also, the capacity of each site was enhanced to be loaded by 10 OXPN molecules (n = 9.3) in a vertical orientation. The OXPN loading energy into CH@ZPh/HPANRs (<40 KJ/mol) reflects physical loading reactions involving van der Waals forces and hydrogen bonding. The OXPN release profiles of CH@ZPh/HPANRs exhibit slow and controlled properties for about 140 h at pH 7.4 and 80 h at pH 5.5. The release kinetics and diffusion exponent (>0.45) signify non-Fickian transport and a complex erosion/diffusion release mechanism. The free CH@ZPh/HPANRs particles display a considerable cytotoxic effect on the HCT-116 cancer cells (9.53 % cell viability), and their OXPN-loaded product shows a strong cytotoxic effect (1.83 % cell viability).

Canagliflozin ameliorates ulcerative colitis via regulation of TLR4/MAPK/NF-κB and Nrf2/PPAR-γ/SIRT1 signaling pathways.

Ulcerative colitis (UC) is one of the most common subtypes of inflammatory bowel disease (IBD) that affects the colon and is characterized by severe intestinal inflammation. Canagliflozin is a widely used antihyperglycemic agent, a sodium-glucose cotransporter-2 (SGLT2) inhibitor that enhances urinary glucose excretion. This study aims to provide insights into the potential benefits of canagliflozin as a treatment for UC by addressing possible cellular signals. Acetic acid (AA; 4% v/v) was administered intrarectally to induce colitis. Canagliflozin is given orally at a dose of 10 mg/kg/day. Canagliflozin attenuates inflammation in AA-induced colitis, evidenced by significant and dose-dependently downregulation of p38 MAPK, NF-κB-p65, IKK, IRF3, and NADPH-oxidase as well as colonic levels of IL-6 and IL-1ß and MPO enzymatic activity. Canagliflozin mitigates colonic oxidative stress by decreasing MDA content and restoring SOD enzymatic activities and GSH levels mediated by co-activating of Nrf2, PPARγ, and SIRT1 pathways. Moreover, an in-silico study confirmed that canagliflozin was specific to all target proteins in this study. Canagliflozin's binding affinity with its target proteins indicates and confirms its effectiveness in regulating these pathways. Also, network pharmacology analysis supported that canagliflozin potently attenuates UC via a multi-target and multi-pathway approach.

Taurine attenuated methotrexate-induced intestinal injury by regulating NF-κB/iNOS and Keap1/Nrf2/HO-1 signals.

Methotrexate (MTX) is a well-known and widely used cytotoxic chemotherapeutic agent. However, intestinal mucosa damage is a serious adverse effect of MTX. Taurine (TUR) is a sulfur-containing free ß-amino acid with antioxidant and therapeutic value against several diseases. The current study aimed to determine the protective effect of TUR against MTX-induced intestinal injury. Rats were allocated into four groups. The first group received vehicles only. The second group received TUR at a dose of 250 mg/kg i.p. For induction of intestinal injury, the rats in the third group were given MTX once at a dose of 20 mg/kg, i.p. The fourth group received TUR 7 days before and 7 days after MTX, as previously described. TUR significantly attenuated the cytokine release by suppressing NF-κB and iNOS expressions. Moreover, cotreatment with TUR attenuated the increased MDA level while it enhanced the antioxidant GSH and SOD levels mediated by effective downregulation of Keap1 expression, while the expression of Nrf2, HO-1, and cytoglobin were up-regulated. Additionally, TUR mitigated the apoptosis and proliferation indices by decreasing the elevated levels of intestinal PCNA and caspase-3. Finally, TUR potently increased the cytotoxic activity of MTX toward Caco-2, MCF-7, and A549 cancer cells. In conclusion, TUR was a promising agent for relieving MTX-mediated intestinal injury via various antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Transcatheter Atrial Septal Defect Closure Before Versus After Adulthood.

Objectives: To evaluate the long-term outcome of patients who underwent percutaneous transcatheter closure of secundum atrial septal defects during teenage life versus adulthood. Methods: The study included 100 patients with secundum type ASD who were treated by transcatheter closure of their defects 2-5 years before enrollment. The study population was subdivided into 2 equal groups: group 1 who underwent transcatheter closure during teenage life (13-19 years) and group 2 who underwent transcatheter closure after the age of 30 years. The two groups were compared according to resting 12 lead ECG, 24-h Holter ECG and transthoracic echocardiographic findings (Right ventricular size and functions, right atrial size, etc.). Results: The study population showed female predominance. The average follow up period was similar in both groups. Adult patients had more frequent right bundle branch block morphology in their resting 12 lead ECG than teenagers (69% versus 45% respectively, p < 0.01). The incidence of arrhythmias encountered in Holter ECG was also significantly higher in the adult group. Premature atrial contractions (PAC) were present in 10 patients (20%) in adult group while 3 patients (6%) had PACs in teenagers' group with p < 0.01. The mean PAC burden was also higher in the adult group (9% versus 1.3%, p < 0.001). Paroxysmal AF lasting more than 30 seconds was found in 6 patients (12%) in the adult group while 1 patient in teenagers developed AF, p < 0.01. Regarding transthoracic echocardiography, adult patients showed significantly larger RV diameter, indexed RA area, indexed LA volume and more LV diastolic dysfunction. RV systolic functions were better in the teenage group as measured by 2D echocardiography. Adult patients with higher age, bigger defect size and device size had more abnormal ECG and echocardiographic findings. Conclusion: Early trans-catheter closure of secundum ASD during teenage life yields better right ventricular systolic function, better right ventricular size and less incidence of atrial arrhythmia.

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking.

In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds 6b,d-g, and 7b showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound 6e displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, 6e was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound 6e endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.

Synthesis of novel calcium channel blockers with ACE2 inhibition and dual antihypertensive/anti-inflammatory effects: A possible therapeutic tool for COVID-19.

Hypertension has been recognized as one of the most frequent comorbidities and risk factors for the seriousness and adverse consequences in COVID-19 patients. 3,4-dihydropyrimidin-2(1H) ones have attracted researchers to be synthesized via Beginilli reaction and evaluate their antihypertensive activities as bioisosteres of nifedipine a well-known calcium channel blocker. In this study, we report synthesis of some bioisosteres of pyrimidines as novel CCBs with potential ACE2 inhibitory effect as antihypertensive agents with protective effect against COVID-19 infection by suppression of ACE2 binding to SARS-CoV-2 Spike RBD. All compounds were evaluated for their antihypertensive and calcium channel blocking activities using nifedipine as a reference standard. Furthermore, they were screened for their ACE2 inhibition potential in addition to their anti-inflammatory effects on LPS-stimulated THP-1 cells. Most of the tested compounds exhibited significant antihypertensive activity, where compounds 7a, 8a and 9a exhibited the highest activity compared to nifedipine. Moreover, compounds 4a,b, 5a,b, 7a,b, 8a,c and 9a showed promising ACE2:SARS-CoV-2 Spike RBD inhibitory effect. Finally, compounds 5a, 7b and 9a exerted a promising anti-inflammatory effect by inhibition of CRP and IL-6 production. Ultimately, compound 9a may be a promising antihypertensive candidate with anti-inflammatory and potential efficacy against COVID-19 via ACE2 receptor inhibition.

Mechanism of antidiabetic effects of Plicosepalus Acaciae flower in streptozotocin-induced type 2 diabetic rats, as complementary and alternative therapy.

BACKGROUND: Diabetes and its related complications remain to be a major clinical problem. We aim to investigate the antidiabetic mechanistic actions of Plicosepalus Acaciae (PA) flowers in streptozotocin (STZ)-induced diabetic rats. METHODS: After diabetes induction, rats were divided randomly into five groups, including: 1) normal control group, 2) diabetic control group, 3) diabetic group treated with 150 mg/kg of ethanolic extract of PA flowers, 4) diabetic group treated with 300 mg/kg of ethanolic extract of PA flowers, and 5) diabetic group treated with 150 mg/kg of metformin. After 15 days of treatment; fasting blood glucose, glycated hemoglobin (HBA1c%), insulin, C-peptide, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA), triglyceride (TGs), total cholesterol (Tc), low density lipoprotein cholesterol (LDL-c), very LDL (VLDL), high DLc (HDL-c), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were assessed. Histopathology of pancreas was also assessed. RESULTS: The results showed that PA flower ethanolic extract significantly reduced blood glucose, HBA1c%, MDA, TGs, Tc, VLDL, LDL-c, TNF-α, and IL-6 levels in a dose-dependent manner. All these parameters were already increased by diabetic induction in the untreated diabetic group. Treatment of diabetic rats with PA flower increased insulin, HDL-c, GSH, catalase, and SOD levels. Histological examination showed that the PA flower caused reconstruction, repair, and recovery of damaged pancreas when compared with the untreated group. CONCLUSIONS: PA flower has a potential role in the management of diabetes as complementary and alternative therapy, due to its antioxidant, anti-inflammatory, hypolipidemic, hypoglycemic and insulin secretagogue effects.

Antioxidant and anti-proliferative activities of Acalypha fruticosa: Possible elucidated mechanism.

This study aimed to investigate the potential anti-oxidant activity of methanol (Aca-M) extract and n-hexane (Aca-H), chloroform (Aca-Ch), ethyl acetate (Aca-E), n-butanol (Aca-B) and aqueous (Aca-A) fractions obtained from the aerial parts of Acalypha fruticosa (Aca) using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Data obtained revealed that A. fruticosa methanol extract and different fractions inhibited the DPPH radicals in the following descending order: Aca-E >Aca-B >Aca-M >Aca-A >Aca-Ch >Aca-H compared to ascorbic acid. Additionally, in vitro 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium (MTT) assay against MCF-7, HCT-116, HepG-2 and non-cancerous MRC-5 cell lines was performed to determine their selective anti-cancer activity. The Aca-Ch fraction exhibited remarkable cytotoxic activity against all tested cancerous cell lines with IC50 4.81- 12.2µg/mL, while both Aca-Ch and Aca-H fractions possessed potent cytotoxic activities on HCT-116 (IC50 4.81 and 10.1, respectively) with negligible harm but selective effect on non-cancerous MRC-5 cells (IC50 20.4 and 85.2, respectively).

Neural and Endocrinal Pathobiochemistry of Vitiligo: Comparative Study for a Hypothesized Mechanism.

The etiology of vitiligo is still unclear. The aim is to investigate a neural and hormonal etio-pathology of vitiligo. Sixty acrofacial vitiligo patients were divided into two subgroups as active vitiligo patients group (AVPs; n = 35) and stable vitiligo patients group (SVP; n = 25). Forty healthy subjects without any systemic or dermatological disease were used as controls. Blood samples were collected, and the samples were used for measurement of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), cortisol, estrogen, testosterone, melatonin, and prolactin levels by ELISA, while norepinephrine (NE), epinephrine (Epi), dopamine (DA), homo-vanillic acid (HVA), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) by high-pressure liquid chromatography. The current results showed a significant increase in plasma levels of Epi, NE, DA, HVA, serotonin, 5-HIAA, melatonin, and in serum level of TSH and prolactin either in SVP or AVP groups than the control group and in AVP than SVP group. The serum levels of fT3 and fT4 were significantly decreased either in SVP or AVP groups than the control group. A significant increase in estradiol levels was observed in females within AVP than females in either SVP or control groups. There was a significant increase in serum level of cortisol in AVP than either SVP or control group. There was a significant decrease in serum level of ACTH in either AVP or SVP than control and in AVP than SVP group. In conclusion, there are some neural and endocrine markers that play a pivotal role in pathogenesis and/or consequences of vitiligo. The abnormally disturbed levels of theses markers lead to melanocyte destruction and/or depigmentation.

Homocysteine as a predictive biomarker in early diagnosis of renal failure susceptibility and prognostic diagnosis for end stages renal disease.

Glomerular filtration rate and/or creatinine are not accurate methods for renal failure prediction. This study tested homocysteine (Hcy) as a predictive and prognostic marker for end stage renal disease (ESRD). In total, 176 subjects were recruited and divided into: healthy normal group (108 subjects); mild-to-moderate impaired renal function group (21 patients); severe impaired renal function group (7 patients); and chronic renal failure group (40 patients) who were on regular hemodialysis. Blood samples were collected, and serum was separated for analysis of total Hcy, creatinine, high sensitive C-reactive protein (CRP), serum albumin, and calcium. Data showed that Hcy level was significantly increased from normal-to-mild impairment then significantly decreases from mild impairment until the patient reaches severe impairment while showing significant elevation in the last stage of chronic renal disease. Creatinine level was increased in all stages of kidney impairment in comparison with control. CRP level was showing significant elevation in the last stage. A significant decrease in both albumin and calcium was occurred in all stages of renal impairment. We conclude Hcy in combination with CRP, creatinine, albumin, and calcium can be used as a prognostic marker for ESRD and an early diagnostic marker for the risk of renal failure.

Pretreatment levels of serum osteoprotegerin and p53 protein and urine telomerase as prognostic factors affecting survival in Egyptian bladder cancer patients.

A non-invasive marker is required for the diagnosis and follow-up of patients with bladder cancer. The aim of the current study was to evaluate the potential prognostic significance of serum osteoprotegerin (OPG), p53 protein and urine telomerase in patients with bladder cancer. For all patients, serum levels of OPG and p53 protein were determined using enzyme-linked immunosorbent assay (ELISA), and urine telomerase was assessed using a polymerase chain reaction ELISA technique. Patients were assigned into group 1 (cystectomy and adjuvant radiotherapy) or group 2 (transurethral resection and chemoradiotherapy). The results revealed that serum OPG and p53, and urine telomerase levels were significantly higher in bladder cancer patients compared with in healthy individuals (P<0.0001). High serum OPG was associated with significantly lower overall survival and disease-free survival rates (both P=0.001), and was correlated with advanced tumor stages (P<0.0001), high tumor grades (P<0.0001) and the occurrence of disease relapse (P=0.001). Serum p53 and urine telomerase did not demonstrate prognostic significance. These findings indicate that serum OPG level may be used as a diagnostic tool and a prognostic variable for patients with muscle invasive bladder cancer. Future trials are required to elucidate its therapeutic role in such patients.

Definitive chemoradiation for non-small-cell lung cancer: could a consensus be reached?

AIMS AND BACKGROUND: There is currently no consensus as to which chemotherapy to combine with thoracic radiotherapy (TRT) in the setting of definitive chemoradiation for non-small-cell lung cancer (NSCLC). We aimed to retrospectively evaluate the efficacy and report outcome measures of cisplatin/etoposide with conventionally fractionated TRT over a 9-year period. METHODS: Cisplatin 50 mg/m² on days 1, 8, 29, and 36 and etoposide 50 mg/m² on days 1-5 and 29-33 with conventionally fractionated conformal radiation therapy starting on day 1 was given to 201 eligible patients. Patient records were reviewed for overall survival (OS) and progression-free survival (PFS). RESULTS: The 2-year OS and PFS were 53% and 47%, respectively, while the 3-year OS and PFS were 18% and 17%, respectively. No grade 4 or treatment-related deaths were recorded, and grade 3 hematologic toxicity occurred in only 22 patients (11%) in the form of granulocytopenia and thrombocytopenia. Multivariable analysis showed clinical stage and Eastern Cooperative Oncology Group performance status to statistically significantly affect PFS and OS. CONCLUSIONS: Cisplatin and etoposide in these doses with conventionally fractionated TRT is a well-tolerated, effective treatment schedule in the definitive treatment of unresectable or inoperable NSCLC.

Catha edulis chewing effects on treatment of paranoid schizophrenic patients.

BACKGROUND: The current study's aim is to evaluate the possible interaction effects of khat chewing on treatment of paranoid schizophrenic patients. PATIENTS AND METHODS: In the study group, 42 male subjects suffered from paranoid schizophrenia and were classified according to their khat chewing habits into two subgroups: either khat-chewer subgroup (SKc; n=21; r=11, h=10) or non-khat-chewer subgroup (SNKc; n=21, r=11, h=10). Each subgroup was further subdivided according to type of treatment into r (risperidone) and h (haloperidol). Healthy male subjects (37) were subdivided into healthy khat-chewer as positive controls (HKc, n=17) and healthy non-khat-chewer as negative controls (HNKc, n=20). Plasma dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid, 5-hydroxytryptamine (serotonin), 5-hydroxyindoleacetic acid, epinephrine, and norepinephrine were estimated. RESULTS: ANOVA and post hoc analysis showed that dopamine was illustrating significant elevation in all khat chewing groups. DOPAC was illustrating significant decrease in all khat chewing groups with an interesting outcome showing significant increase in DOPAC in SNKcr group due to risperidone effect. Homovanillic acid, serotonin, hydroxyindoleacetic acid, and norepinephrine were illustrating significant elevations in all khat chewing groups. Epinephrine was illustrating significant elevation in all chewers than non-chewers groups. Unexpected significant decrease in epinephrine in the SNKcr group indicated that risperidone drug is decreasing epinephrine through indirect mechanism involving calcium. CONCLUSION: Khat chewing in schizophrenic patients is contraindicated because it aggravates the disease symptoms, attenuates all used treatment medications, and deteriorates all biochemical markers of the patients.

Mechanism of endothelial cyto-protective and thrombo-resistance effects of sildenafil, vardenafil and tadalafil in male rabbit.

INTRODUCTION: PDE5 inhibitors (PDE5inhs) have proven to be of great impact in the treatment of numerous human extra-sexual diseases and their chronic use may induce endothelial rehabilitation. This study aimed to assess the effects of PDE5inhs at chronic administration to explore the possible endothelial cyto-protective and thrombo-resistance effects. MATERIAL AND METHODS: One hundred New Zealand white male rabbits were divided into four groups. The first group (control, C) received 1 ml saline/kg, the second group (S) received 10 mg/kg sildenafil, the third group (V) received 2 mg/kg vardenafil, and the fourth group (T) received 2 mg/kg tadalafil in saline I.P. three times weekly for 4 weeks. Blood samples were collected and plasma was isolated for determination of 2,3-dinor-6-keto-prostaglandin F-1α (PGF1α), 11-dehydro-TXB2 (TXB2), fibrinogen, calcium levels, prothrombin (PT), and thrombin times (TT). RESULTS: PDE5inhs significantly increase PGF1α, calcium levels, PT and TT (p < 0.001) when compared with baseline data or with the saline group at the end of treatment. In contrast, PDE5inhs significantly decrease TXB2 and fibrinogen levels (p < 0.001) when compared either with their baseline data or with the saline group at the end of treatment. The tadalafil group showed a lower increase in PGF1α (p < 0.001), lower decrease in TXB2 (p < 0.001), and higher increase in calcium levels (p < 0.01, p < 0.05), lower increase in PT and TT levels (p < 0.001) when compared with sildenafil or vardenafil. CONCLUSIONS: The prolonged use of PDE5inhs has time-dependent mild to moderate endothelial cyto-protective, thrombo-resistance anti-inflammatory and anti-nociception effects via activation of endothelial NOS (eNOS), increase of PGI2 synthesis and decrease of fibrinogen with significant increase in PT and TT.

Impact of treatment-related toxicity on outcome of HCV-positive diffuse large B-cell lymphoma in rituximab era.

UNLABELLED: NOVELTY AND IMPACT: This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed in toxicity and the outcome. BACKGROUND: The effect of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era is unclear. The treatment and the outcome of patients with DLBCL and HCV infection are still a matter of debate. METHODS: We analyzed 137 DLBCL patients positive to HCV, treated with chemotherapy regimens include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab. Survival outcomes and hepatic toxicity were compared in DLBCL patients positive to HCV infection according to CHOP ± rituximab. RESULT: Our result showed that the group of patients treated with R-CHOP has significant high incidence of hepatic toxicity grade (3-4) (28 vs. 18%, P value 0.001) and worse progression-free survival (55 vs. 80%, P value 0.002) in comparison with the group treated with CHOP, and also there is significant difference between both groups in overall survival. This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed significant differences. CONCLUSION: We conclude that HCV-positive patients with DLBCL treated with rituximab plus CHOP have high incidence in hepatic toxicity. Specific protocols evaluating antiviral therapy should be designed for these patients.

Biological markers and response to neoadjuvant taxane-based chemotherapy in patients with locally advanced breast cancer.

Introduction. Biological markers as Her2/neu, p53, and hormonal receptors (HmRs) may be reliable parameters for prognostic assessment of patients of locally advanced breast cancer (LABC). This work aims at assessing the potential value of these biological markers for the prediction of disease outcome after neoadjuvant taxane-based chemotherapy and its implication on the surgical role. Patients and Methods. From March 2006 to September 2011, 95 patients with LABC were treated by neoadjuvant taxane-based chemotherapy given at intervals of 3 weeks. Expression of Her2/neu and p53 was examined in the initial tissue biopsy by using ELISA technique. Status of HmRs was determined using a commercial enzyme immunoassay. Three weeks after the third cycle, patients underwent surgical resection followed by 3 more cycles of taxane-based chemotherapy and radiotherapy as an adjuvant therapy. Relations of Her2/neu overexpression to p53, HmRs, and conventional prognostic factors were analyzed. Results. Median followup was 61 months. The 5-year DFS and OAS rates were significantly higher in patients with positive HmRs than in those with negative HmRs, patients with Her2- than those with Her2+ breast cancer, and patients with intact p53 breast cancer than those with inactive p53. HER-2 overexpression was statistically significant associated with loss of HmR positive immunostaining (P < 0.0001), grade III breast cancer (P < 0.0001), advanced nodal status (P = 0.0039), and younger (<50 years) age (P = 0.0108). Conclusion. Her2/neu overexpression was associated with poor DFS and OAS rates, as it was significantly associated with negative HmR and high grade.

Effects of Portulaca oleracea L. seeds in treatment of type-2 diabetes mellitus patients as adjunctive and alternative therapy.

UNLABELLED: ETHNPHARMACOLOGICAL RELEVANCE: To investigate antidiabetic activity of purslane seeds on type-2 diabetic subjects and to provide scientific basis for the clinical use of Portulaca oleracea (PO). MATERIALS AND METHODS: A thirty subject with type-2 diabetes divided into two groups, to receive 5 g of PO seeds twice daily while in the second group, their participants receive 1,500 mg of metformin/day. All participants were requested to report the effects of treatments on diabetic manifestations, their weights, body mass index (BMI), adverse effects, fasting and post-prandial blood glucose during treatment schedule. Blood samples from participants before and after treatment were taken for serum separation, which are used for measurement of serum lipids, liver enzymes, total and direct bilirubin, albumin, and insulin. RESULTS: It showed a significant decrease in serum levels of triglycerides (TGs), total cholesterol (T(C)), low density lipoprotein cholesterol (LDL(C)), liver alanine-, aspartate- and gamma glutamyl transaminase (ALT, AST, and GGT), total and direct bilirubin, fasting and post-prandial blood glucose, insulin, body weight and BMI while a significant increase in high density lipoprotein cholesterol (HDL(C)) and albumin but non-significant change of alkaline phosphatase (ALP) in PO seeds treated subjects. Metformin (M) group has the same results of PO group except in high density lipoprotein cholesterol (HDL(C)), LDL(C), and ALP levels had a different pattern. CONCLUSIONS: PO seeds could be effective and safe as adjuvant therapy for Type-2 diabetic subjects. These results demonstrated that PO seeds possessed notable hypoglycaemic, hypolipidaemic and insulin resistance reducer effects; possibly due to its contents of polyunsaturated fatty acids, flavonoids, and polysaccharides.

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study.

BACKGROUND: We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. METHODS: This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. RESULTS: Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. CONCLUSION: Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered.

Feasibility of breast conservation after neoadjuvant taxene based chemotherapy in locally advanced breast cancer: a Prospective Phase I trial.

BACKGROUND: Neoadjuvant chemotherapy is the standard care for locally advanced breast cancer. Our study aimed at evaluating the feasibility of breast conversation surgery (BCS) after neoadjuvant chemotherapy. PATIENTS AND METHODS: Forty five patients had stage IIB (except those with T2N1 disease) and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤5 cm underwent a tentative BCS while patients who had tumour size >5 cm underwent radical surgery. Negative margin is essential for BCS. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients. RESULTS: Thirty four patients had BCS. Response to chemotherapy was the only statistically significant factor which influences the BCS. Incidence of local recurrence was 5.9% for patients who had BCS at a median follow up 24 months. CONCLUSION: Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤4 cm after chemotherapy are the best candidates for BCS.