Single-Institute Review of HER-2/Neu-Positive Invasive Lobular Breast Carcinoma in an Arab Population.

BACKGROUND Invasive lobular carcinoma is special subtype of breast cancer that has clinical behavior and morphology distinct from other breast cancer subtypes. It accounts for 5-15% of breast cancer. Overall, HER-2 gene amplification occurs at a significantly lower rate in ILC, but also has been linked to adverse outcomes. Most cases of ILCs with HER-2 overexpression and or amplification generally have the pleomorphic variant. We report the first series of cases from Saudi Arabia for this rare cancer in an Arab population. CASE REPORT Nine patients retrospectively were evaluated with HER-2/neu-positive ILC of the breast that were diagnosed and managed from 2003 to 2020. Four patients were diagnosed as early breast cancer, 3 had metastatic disease and 2 were locally advanced at their initial presentation. The mean age was 58 years; 30% were classic ILC and another 60% were of mixed non-classic variants (histologic pattern represented by nuclear pleomorphism). Management of patients with HER-2-positive ILC was performed according to standard multimodality breast cancer guidelines, consisting of surgery, chemotherapy with anti-HER-2/neu blockade, radiation, and endocrine therapy, based on stage and hormone status. CONCLUSIONS In conclusion, HER-2-positive invasive lobular carcinoma of the breast is uncommon in the Arab population, which has not been previously reported in the literature. Further studies are warranted to explore the biology, molecular characteristics, and clinical course in this group of patients.

Microbial dysbiosis in irritable bowel syndrome: A single-center metagenomic study in Saudi Arabia.

BACKGROUND: The focus of this study was to explore potential differences in colonic mucosal microbiota in irritable bowel syndrome (IBS) patients compared to a control group utilizing a metagenomic study. METHODS: Mucosal microbiota samples were collected from each IBS patient utilizing jet-flushing colonic mucosa in unified segments of the colon with distilled water, followed by aspiration, during colonoscopy. All the purified dsDNA was extracted and quantified before metagenomic sequencing using an Illumina platform. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota, which were obtained during screening colonoscopies. RESULTS: The microbiota data on 50 IBS patients (31 females), with a mean age 43.94 ± 14.50 (range19-65), were analyzed in comparison to 50 controls. Satisfactory DNA samples were subjected to metagenomics study, followed by comprehensive comparative phylogenetic analysis. Metagenomics analysis was carried out, and 3.58G reads were sequenced. Community richness (Chao) and microbial structure in IBS patients were shown to be significantly different from those in the control group. Enrichment of Oxalobacter formigenes, Sutterella wadsworthensis, and Bacteroides pectinophilus was significantly observed in controls, whereas enrichment of Collinsella aerofaciens, Gemella morbillorum, and Veillonella parvula Actinobacteria was observed significantly in the IBS cohort. CONCLUSION: The current study has demonstrated significant differences in the microbiota of IBS patients compared to controls.

Microbial dysbiosis in inflammatory bowel diseases: results of a metagenomic study in Saudi Arabia.

BACKGROUND: The intestinal microbiota plays an essential role in the pathogenesis of ulcerative colitis (UC)and Crohn disease (CD). METHODS: Metagenomic studies were used to study microbiota in the diagnosed cases of UC and CD at King Fahad Medical City, Riyadh, Saudi Arabia. Each segment of the colon was flushed with distilled water during colonoscopy, and the material was aspirated, immediately frozen for the study. The patients attending for screening colonoscopies were taken as age-matched healthy controls. The UC patients were followed clinically for any signs of exacerbation relapse, and CD patients were followed for any complications. RESULTS: The metagenomic data on 46 (24 females) patients with CD were analyzed along with a group of age and gender-matched controls. Their age ranged from 14 to 65 years, mean age 25.19±10.67 years. There were 50 UC patient (28 females) mean age of 34.42±12.58, and their age ranged from 13-58 years. This study identified enrichment of 19 genera in the control group (Abiotrophia, Anaerofustis, Butyrivibrio, Campylobacter, Catenibacterium, Coprococcus, Dorea, Eubacterium, Facklamia, Klebsiella, Lactococcus, Oscillibacter, Paenibacillus, Parabacteroides, Parasutterella, Porphyromonas, Prevotella, Ruminococcus, Treponema). There was a significant enrichment of 14 genera in our CD cohort (Beggiatoa, Burkholderia, Cyanothece, Enterococcus, Escherichia, Fusobacterium, Jonquetella, Mitsuokella, Parvimonas, Peptostreptococcus, Shigella, Succinatimonas, ThermoanaerobacterVerrucomicrobiales, Vibrio). There was a significant enrichment of 7 genera in UC cohort (Beggiatoa, Burkholderia, Parascardovia, Parvimonas, Pseudoflavonifractor, Thermoanaerobacter, Verrucomicrobiales). CONCLUSIONS: A significant dysbiosis was found in UC and CD patients compared to controls.

Colonic Mucosal Microbiota in Colorectal Cancer: A Single-Center Metagenomic Study in Saudi Arabia.

BACKGROUND AND AIM: Because genetic and geographic variations in intestinal microbiota are known to exist, the focus of this study was to establish an estimation of microbiota in colorectal cancer (CRC) patients in Saudi Arabia by means of metagenomic studies. METHODS: From July 2010 to November 2012, colorectal cancer patients attending our hospital were enrolled for the metagenomic studies. All underwent clinical, endoscopic, and histological assessment. Mucosal microbiota samples were collected from each patient by jet-flushing colonic mucosa with distilled water at unified segments of the colon, followed by aspiration, during colonoscopy. Total purified dsDNA was extracted and quantified prior to metagenomic sequencing using an Illumina platform. Satisfactory DNA samples (n = 29) were subjected to metagenomics studies, followed by comprehensive comparative phylogenetic analysis. An equal number of healthy age-matched controls were also examined for colonic mucosal microbiota. RESULTS: Metagenomics data on 29 patients (14 females) in the age range 38-77 years were analyzed. The majority 11 (37%) of our patients were overweight (BMI = 25-30). Rectal bleeding was the presenting symptom in 18/29 (62%), while symptomatic anemia was the presenting symptom in 11/29 (37%). The location of colon cancer was rectal in 14 (48%), while cecal growth was observed in 8 (27%). Hepatic flexure growth was found in 1 (3%), descending colonic growth was found in 2 (6%), and 4 (13%) patients had transverse colon growth. The metagenomics analysis was carried out, and a total of 3.58G reads were sequenced, and about 321.91G data were used in the analysis. This study identified 11 genera specific to colorectal cancer patients when compared to genera in the control group. Bacteroides fragilis and Fusobacterium were found to be significantly prevalent in the carcinoma group when compared to the control group. CONCLUSION: The current study has given an insight into the microbiota of colorectal cancer patients in Saudi Arabia and has identified various genera significantly present in these patients when compared to those of the control group.

Camelid genomes reveal evolution and adaptation to desert environments.

Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

Analysis of free ACh and 5-HT in milk from four different species and their bioactivity on 5-HT(3) and nACh receptors.

Milk is one of the most beneficial aliments and is highly recommended in normal conditions; however, in certain disorders, like irritable bowel syndrome, cow milk and dairy products worsen the gastric symptoms and their use is not recommended. Among the most recognized milk-induced gatrointestinal symptoms are abdominal pain, nausea and vomiting, which are processes controlled by cholinergic and serotonergic transmission. Whether the presence of bioavailable ACh and 5-HT in milk may contribute to normal peristalsis, or to the developing of these symptoms, is not known. In this work we attempt to determine whether the content of free ACh and 5-HT is of physiological significance in milk from four different species: cow (bovine), goat, camel and human. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to identify and quantify free ACh and 5-HT in milk, and activation of the serotonergic and cholinergic ionotropic receptors was investigated using electrophysiological experiments. Our principal hypothesis was that milk from these four species had sufficient free ACh and 5-HT to activate their correspondent receptors expressed in a heterologous system. Our results showed a more complex picture, in which free ACh and 5-HT and their ability to activate cholinergic and serotonergic receptors are not correlated. This work is a first step to elucidate whether 5-HT and ACh, at the concentrations present in the milk, can be associated to a direct function in the GI.

The endogenous GABA bioactivity of camel, bovine, goat and human milks.

GABA orally administered has several beneficial effects on health, including the regulation of hyperglycaemic states in humans. Those effects are similar to the effects reported for camel milk (CMk); however, it is not known whether compounds with GABAergic activity are present in milk from camels or other species. We determined CMk free-GABA concentration by LS/MS and its bioactivity on human GABA receptors. We found that camel and goat milks have significantly more bioavailable GABA than cow and human milks and are able to activate GABAρ receptors. The relationship between GABA and taurine concentrations suggests that whole camel milk may be more efficient to activate GABAρ1 receptors than goat milk. Because GABAρ receptors are normally found in enteroendocrine cells in the lumen of the digestive tract, these results suggest that GABA in camel and goat milk may participate in GABA-modulated functions of enteroendocrine cells in the GI lumen.