Potential role of CXCR4 in trastuzumab resistance in breast cancer patients.

Despite the efficacy of trastuzumab in treating HER2-positive breast cancer patients, a significant proportion of patients relapse after treatment. The role of C-X-C chemokine receptor type 4 (CXCR4) in trastuzumab resistance was studied only in cell lines and the underlying mechanisms remain largely unclear. This study investigated the role of CXCR4 in trastuzumab resistance in breast cancer patients and explored the possible underlying mechanisms. The study was performed retrospectively on tissue samples from 62 breast cancer patients including 42 who were treated with trastuzumab and chemotherapy and 20 who received chemotherapy alone in adjuvant setting. Expression levels of CXCR4 and its regulators hypoxia-inducible factor 1-alpha (HIF-1α), tristetraprolin (TTP), human antigen R (HuR), itchy E3 ubiquitin protein ligase (ITCH), miR-302a and miR-494 were determined and their associations with tumor recurrence and disease-free survival were analyzed. In trastuzumab-treated patients, high CXCR4 expression was associated with recurrence and was an independent predictor of progression risk after therapy. CXCR4 correlated positively with its transcriptional regulator, HIF-1α, and negatively with its post-translational regulator, ITCH. HIF-1α, HuR and ITCH were significantly associated with clinical outcome. In chemotherapy-treated patients, neither CXCR4 nor any of its regulators were associated with recurrence or predicted disease progression risk after chemotherapy. In conclusion, this study suggests a potential role for CXCR4 in recurrence after trastuzumab-based therapy in human breast cancer that could be mediated, at least in part, by hypoxia and/or decreased ubiquitination. These findings highlight the potential utility of CXCR4 as a promising target for enhancing trastuzumab therapeutic outcome.

Coat's like vasculopathy in leber congenital amaurosis secondary to homozygous mutations in CRB1: a case report and discussion of the management options.

BACKGROUND: Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, and retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features such as coat's like vasculopathy in retinitis pigmentosa patients. This is the first report of the occurrence of coat's like vasculopathy in a patient diagnosed with Leber congenital amaurosis caused by a CRB1 mutation. CASE PRESENTATION: An 18-year old Syrian female patient presented with bilateral gradual loss of vision since early childhood, with recent deterioration in her left eye. She appeared to have an asymmetric bilateral coat's like vasculopathy which was more severe in the left eye. The diagnosis of Leber congenital amaurosis was suggested, and a genetic CRB1 sequencing for the patient and her two younger siblings, who also had severe vision loss, was done, upon which the diagnosis of Leber congenital amaurosis associated with exudative retinal detachment due to coat's like vasculopathy was made. Treatment with panretinal photocoagulation was attempted in the worse left eye, but with no improvement. As the disease suddenly progressed in both eyes, pars plana vitrectomy with endolaser and silicone oil tamponade was performed in the better right eye which led to anatomical stabilization of the case without improvement in the visual acuity. CONCLUSION: Leber congenital amaurosis is reported to be associated with multiple systemic and ocular findings, none of which is coat's like vasculopathy. CRB1 gene mutations are associated with remarkable retinal findings in patients with retinitis pigmentosa and other fundus dystrophies. In this unique case we are reporting the incidence of coat's like vasculopathy in a patient diagnosed with Leber congenital amaurosis caused by CRB1 gene mutation, and its management. CRB1 mutant patients should be followed up closely as sudden progression can have permanent poor outcomes and as early management is vital in such cases.

Nutrition, physical activity, and gender risks for adolescent obesity in Southwestern Saudi Arabia.

BACKGROUND/AIM: The aim of the study was to investigate gender differences in obesity and related behavior among adolescent school boys and girls in southwestern Saudi Arabia. PATIENTS AND METHODS: A cross-sectional study on a stratified sample of 1,249 adolescent boys and 620 adolescent girls, was conducted in southwestern Saudi Arabia. They were interviewed and examined for weight and height using standardized techniques. RESULTS: The prevalence of obesity and overweight in the present study amounted to 23.2% among boys and 29.4% among girls. The following significant risk factors were identified; being a female [adjusted odds ratio (aOR) =1.372, 95% confidence interval (CI) =1.099-1.753] and lack of class physical exercise (aOR =1.452, 95% CI =1.149-2.117). CONCLUSION: Obesity among adolescents is a public health problem in Southwestern Saudi Arabia. The problem is more prevalent among girls. Thus, there is a need for a national programme in the country to prevent and control obesity among adolescents.

Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice.

The repeated chemotherapy of schistosomiasis has resulted in the emergence of drug-resistant schistosome strains. The development of such resistance has drawn the attention of many authors to alternative drugs. Many medicinal plants were studied to investigate their antischistosomal potency. The present work aimed to evaluate antischistosomal activity of crude aqueous extract of ginger against Schistosoma mansoni. Sixteen mice of C57 strain were exposed to 100 ± 10 cercariae per mouse by the tail immersion method; the mice were divided into two groups: untreated group and ginger-treated one. All mice were sacrificed at the end of 10th week post-infection. Worm recovery and egg counting in the hepatic tissues and faeces were determined. Surface topography of the recovered worms was studied by scanning electron microscopy. Histopathological examination of liver and intestine was done using routine histological procedures. The worm burden and the egg density in liver and faeces of mice treated with ginger were fewer than in non-treated ones. Scanning electron microscopical examination revealed that male worms recovered from mice treated with ginger lost their normal surface architecture, since its surface showed partial loss of tubercles' spines, extensive erosion in inter-tubercle tegumental regions and numerous small blebs around tubercles. Histopathological data indicated a reduction in the number and size of granulomatous inflammatory infiltrations in the liver and intestine of treated mice compared to non-treated mice. The results of the present work suggested that ginger has antischistosomal activities and provided a basis for subsequent experimental and clinical trials.

Cardiovascular risk factors among adolescent secondary school boys in Ahad Rufeida, southwestern Saudi Arabia.

A cross-sectional stratified sample of 1249 adolescent secondary school boys was studied. More than 25% of boys did not practice any physical exercise. More than half of the parents (54.5%) were consanguineous. High prevalence of parental history of hypertension, diabetes and high blood lipids was found. Smoking amounted to 11.8%. The prevalence of obesity was 23.3%. The study showed that 6.8% had a high systolic blood pressure and 13.0% (162) had high diastolic blood pressure. There is a need for a national programme to prevent and control cardiovascular risk factors among adolescents.

Isoenzyme electrophetic characterization of Leishmania major, the causative agent of zoonotic cutaneous Leishmaniasis in North and West Saudi Arabia.

Several expeditions were carried out to four localities (Al-Madinah Almona-warah, Tabouk region, Al-Jouf and Northern Frontiers regions) in Northern and Western Saudi Arabia for sampling zoonotic cutaneous leishmaniasis (ZCL) cases from patients and rodents. Biopsy samples were collected from 51 patients complaining of skin lesions, most of which (40 or 78.4%) proved to be ZCL. Amastigotes were detected in 33 patients (64.7%), but only 30 (58.9%) gave successful growth of promastigotes in the culture media. The positive cases were Saudis 14(35%) and non-Saudis 26 (65%). Five species of rodents were caught, Meriories libycus, Psammomys obesus, Rattus rattus, jaculus and Hystrix indica. The first species was the most dominant (90%) in which Leishmania parasites were detected. The Leishmania isolates from man and rodents were identified by isoenzyme electrophoresis and proved to be Zymodeme LON-4.