Prostate cancer metastases to the rectum: A case report

Prostate cancer rarely metastasis to the rectum. Findings in the patient reported here emphasize the importance of the relationship between urinary and gastrointestinal symptoms in detecting prostatic neoplasms in older male patients

Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians

Abstract Background Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied. Methods Using Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan® SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs. Results Three chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene. Conclusion Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific. </jats:sec

CrossLink: a novel method for cross-condition classification of cancer subtypes

BACKGROUND: We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition-specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another. METHODS: To address the problem of current normalization approaches, we propose a novel algorithm called CrossLink (CL). CL recognizes that there is no universal, condition-independent normalization mapping of signatures. In contrast, it exploits the fact that the signature is unique to its associated class under any condition and thus employs an unsupervised clustering algorithm to discover this unique signature. RESULTS: We assessed the performance of CL for cross-condition predictions of PAM50 subtypes of breast cancer by using a simulated dataset modeled after TCGA BRCA tumor samples with a cross-validation scheme, and datasets with known and unknown PAM50 classification. CL achieved prediction accuracy >73 %, highest among other methods we evaluated. We also applied the algorithm to a set of breast cancer tumors derived from Arabic population to assign a PAM50 classification to each tumor based on their gene expression profiles. CONCLUSIONS: A novel algorithm CrossLink for cross-condition prediction of cancer classes was proposed. In all test datasets, CL showed robust and consistent improvement in prediction performance over other state-of-the-art normalization and classification algorithms

Abdominal Leiomyoma in an Adult Transgender with Adrenogenital Syndrome: A Rare Case Report

Leiomyomas of the abdomen are rare intra-abdominal tumors, particularly in male patients with adrenal hyperplasia. We report the case of a 50-year-old considers himself a with a man, who was born as a female, and has several surgeries related to transitioning from intersex to male gender. These procedures include bilateral oophorectomy with silicone testicular implantation, bilateral mastectomy with closure of the labial cleft, reconstruction of the urethral canal, and placement of testicular implants. He has a wife and two adopted children. The patient presented to the emergency department suffering from lower abdominal pain and vomiting. On examination, the abdomen appeared distended and soft. In addition to positive bowel sounds, there is a palpable large, firm, slightly tender mass occupying the lower abdomen and extending above the umbilicus, a small penis, and bilateral suspected testes in the proximal inguinal region. Abdominal radiographs, abdominal ultrasounds, and computer tomography (CT) of the abdomen and pelvis with intravenous contrast revealed a large pelvic-abdominal mass, bilaterally enlarged adrenal glands, and bilaterally implanted tests seen in the inguinal region. An ultrasound-guided tissue biopsy and an exploratory laparotomy were performed, and the tumor was completely resected. A rounded, firm mass arises from the pelvis, with histopathology revealing its origin from the remnants of the uterus and vaginal adhesions adherent to the mesentery. A tissue biopsy confirmed the leiomyom

Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p<0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p<0.0001; Nectin-2, p<0.0001; NT5E, p<0.0001; Siglec-7, p<0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p<0.0001; MICA, p<0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients.This research was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar, grant number MRC-01-20-507 and the Article Processing Charges was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar

Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80 <91.7 pg/ml and CEA <1614 pg/ml were found to be significantly associated with better progression free survival (PFS). Indeed, multivariate analysis identified the cutoff-value of CEA <1614 pg/ml as an independent predictor of response in our patients. We identified here novel immune inhibitory/stimulatory soluble mediators as potential surrogate/predictive biomarkers for TPD-L1 status, treatment response and PFS in NSCLC patients treated with anti-PD-1/PD-L1 therapy.This research was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar, grant number MRC-01-20-507 and the Article Processing Charges was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. AcknowledgmentsScopu

Circulating exosomal immuno-oncological checkpoints and cytokines are potential biomarkers to monitor tumor response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients

Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes of NSCLC patients with better overall survival. However, 15-40% of the patients still fail to respond to ICIs therapy. Identification of biomarkers associated with responses are mandated in order to increase the efficacy of such therapy. In this study we evaluated 27 serum-derived exosomal immuno-oncological proteins and 44 cytokines/chemokines before and after ICIs therapy in 17 NSCLC patients to identify surrogate biomarkers for treatment/monitoring patient stratification for maximum therapeutic benefit. We first confirmed the identity of the isolated exosomes to have their specific markers (CD63, CD81, HSP70 and CD91). We have demonstrated that baseline concentration of exosomal-PD-L1 (p&lt;0.0001), exosomal-PD-L2 (p=0.0413) and exosomal-PD-1 (p=0.0131) from NSCLC patients were significantly higher than their soluble-free forms. Furthermore, the exosomal-PD-L1 was present in all the patients (100%), while only 71% of patients expressed tissue PD-L1. This indicates that exosomal-PD-L1 is a more reliable diagnostic biomarker. Interestingly, exosomal-PD-L2 expression was significantly higher (p=0.0193) in tissue PD-L1-negative patients compared to tissue PD-L1-positive patients. We have also shown that immuno-oncological proteins isolated from pre-ICIs treated patients were significantly higher in exosomes compared to their soluble-free counterparts (CD152, p=0.0008; CD80, p=0.0182; IDO, p=0.0443; Arginase, p&lt;0.0001; Nectin-2, p&lt;0.0001; NT5E, p&lt;0.0001; Siglec-7, p&lt;0.0001; Siglec-9, p=0.0335; CD28, p=0.0092; GITR, p&lt;0.0001; MICA, p&lt;0.0001). Finally, the changes in the expression levels of exosomal immuno-oncological proteins/cytokines and their correlation with tumor response to ICIs treatment were assessed. There was a significant downregulation of exosomal PD-L1 (p=0.0156), E-Cadherin (p=0.0312), ULBP1 (p=0.0156), ULBP3 (p=0.0391), MICA (p=0.0391), MICB (p=0.0469), Siglec7 (p=0.0078) and significant upregulation of exosomal PD-1 (p=0.0156) and IFN- γ (p=0.0156) in responding patients. Non-responding patients showed a significant increase in exosomal-PD-L1 (p=0.0078). Furthermore, responding-patients without liver-metastasis showed significant-upregulation of PD-1 (p=0.0070), and downregulation of ULBP1 (p=0.0137) and Siglec-7 (p=0.0037). Non-responding patients had significant-downregulation of ULBP3 (p=0.0317) in patient without brain-metastasis and significant-upregulation/downregulation of PD-L1 and ULBP3 (p=0.0262/0.0286) in patients with pulmonary-metastasis. We demonstrated for the first time that exosomal immuno-oncological proteins/cytokines are potential biomarkers to monitor response to ICIs therapy and can predict the clinical outcomes in NSCLC patients

Retroperitoneal lymphangiomyomatosis diagnosed by fine needle aspiration: A case report

Lymphangiomyomatosis is a rare condition affecting women of childbearing age. It is characterized by an abnormal proliferation of smooth muscle cells around lymphatics, giving rise to blockage of the large lymphatics, including the thoracic duct, and resulting in chylothorax and/or chyloascitis. The lung is the most common site of involvement. Retroperitoneum and lymph nodes can be also involved. Case A 40-year-old woman presented with lower urinary tract symptoms after a history of trauma and was found to have a retroperitoneal mass. Fine needle aspiration cytologic examination of the milky fluid aspirated from the mass revealed a few cohesive, 3-dimensional clusters of medium-sized cells with scanty cytoplasm, and ovoid and hyperchromatic nuclei. The background contained numerous mature lymphocytes. Laparoscopy revealed a multicystic mass filled with milky fluid. Histologic examination confirmed the cytologic diagnosis of lymphangiomyomatosis. Conclusion: Fine needle aspiration of lymphangiomyomatosis can be performed if cohesive clusters and a lymphoid background are present in chylous-type fluid and provided that adequate clinical information is availabl