Muhammad Shahbaz

Bio: Muhammad Shahbaz is an academic researcher from Shandong University. The author has contributed to research in topics: Cancer & Colorectal cancer. The author has an hindex of 9, co-authored 19 publications receiving 259 citations. Previous affiliations of Muhammad Shahbaz include Chinese Ministry of Education.

Comparison of the BISAP scores for predicting the severity of acute pancreatitis in Chinese patients according to the latest Atlanta classification

Abstract: Background The bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactor scoring system. As there were no studies designed to validate this system according to the latest Atlanta classification in China and more data are needed before clinical application, we compared BISAP, the Acute Physiology and Chronic Health Evaluation (APACHE) II and Ranson scoring systems in predicting the severity, pancreatic necrosis and mortality of acute pancreatitis (AP) using the latest 2012 Atlanta classification in a tertiary care center in China. Methods The medical records of all patients with AP admitted to our hospitals between January 2010 and June 2013 were reviewed retrospectively. Severe AP was defined as the persistence of organ failure for more than 48 h. The capacity of the BISAP, APACHE II and Ranson's score system to predict severity, pancreatic necrosis and mortality was evaluated using linear-by-linear association. The predictive accuracy of the BISAP, APACHE II and Ranson's score was measured as the area under the receiver operating characteristic curve (AUC). Results Of 155 patients enrolled in the study, 16.7% were classified as having severe AP, and six (3.2%) died. There were statistically significant trends for increasing severity (P < 0.001), PNec (P < 0.001) and mortality (P < 0.001) with increasing BISAP. The AUC for severity predicted by BISAP was 0.793 (95% confidence interval [CI] 0.700–0.886), APACHE II 0.836 (95% CI 0.744–0.928) and by Ranson score was 0.903 (95% CI 0.814–0.992). The AUC for PNec predicted by BISAP was 0.834 (95% CI 0.739–0.929), APACHE II 0.801 (95% CI 0.691–0.910) and by Ranson score was 0.840 (95% CI 0.741–0.939). The AUC for mortality predicted by BISAP was 0.791 (95% CI 0.593–0.989), APACHE II 0.812 (95% CI 0.717–0.906) and by Ranson score was 0.904 (95% CI 0.829–0.979). Conclusions BISAP score may be a valuable source for risk stratification and prognostic prediction in Chinese patients with AP. A prospective and multicenter validation study is required to confirm our results and further our recognition of BISAP scores in AP.

Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma

Abstract: Purpose: Adjuvant chemotherapy is one of the significant treatments for colon cancer in clinic. However, it does not achieve the desired therapeutic efficacy, largely due to chemotherapeutic resistance. Integrinβ6 (ITGB6) is expressed in malignant colonic epithelia, but not in normal epithelia, and is associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, it is necessary to design therapeutic approaches for efficient and targeted drug delivery into ITGB6-positive cancer cells to improve chemotherapeutic efficacy in colon cancer. Experimental Design: PEGylated liposomes were employed to design ITGB6-targeted immunoliposomes, which have ITGB6 monoclonal antibodies (mAbs) conjugated. We evaluated the ITGB6-targeted immunoliposomes internalization into colon cancer cells and examined 5-fluorouracil (5-FU)–induced cellular apoptosis produced by ITGB6-targeted immunoliposomes+5-FU. In addition, the biodistribution and antitumor efficiency of ITGB6-targeted immunoliposomes were observed in vivo . Results: ITGB6-targeted immunoliposomes enhanced cellular internalization in ITGB6-positive colon cancer cells compared with liposomes. Furthermore, the ITGB6-targeted immunoliposome internalization was dependent on the ITGB6 expression level on cellular surface. ITGB6-targeted immunoliposomes decreased the 5-FU IC 50 more than 90% in HT-29 and SW480β6 cells relative to liposomes. Moreover, when loaded with 5-FU, ITGB6-targeted immunoliposomes produced an approximately 1.5-fold higher 5-FU–induced cellular apoptosis rate than liposomes. In vivo , the therapeutic activity of ITGB6-targeted immunoliposomes+5-FU was significantly superior, resulting in 25% to 35% reduction of tumor weight compared with 5-FU or liposomes+5-FU. Conclusions: ITGB6-targeted immunoliposomes provide a highly efficient approach for targeted drug delivery in colon cancer and thus offer the potential of a novel and promising anticancer strategy for clinical therapy. Clin Cancer Res; 21(5); 1183–95. ©2014 AACR .

The Role of Grb2 in Cancer and Peptides as Grb2 Antagonists.

Abstract: Background Growth factor receptor-bound protein 2 (Grb2) is a 25 kDa adaptor protein, which was originally discovered to accomplish basic cellular events such as cell growth, cell proliferation, and metabolism. However, recent studies evidenced that Grb2 was largely involved in multiple tumor malignancies. The mature Grb2 is a 217 amino acid sequence, which consists of one Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. Using these binding motives, the ubiquitously expressed Grb2 acts as an intermediate between cell-surface activated receptors and downstream targets. Objectives Consequently, the Grb2 becomes the key element of this oncogenesis and launched a number of defected signaling cascades. Therefore, vast concern of the Grb2 in multiple cancer patterns makes it an attractive therapeutic target. In this review, we have compiled the maximum tumor conformations caused by the involvement of the Grb2, the central role of Grb2 in numerous oncogenic pathways and particular approaches that can be useful to downregulate the Grb2 overexpression. We will discuss in details the activity of different types of novel peptides, their high affinity for the Grb2 protein and blockade of Grb2 mediated signaling pathways by targeting the SH2/SH3 binding sites. Methods & results There is a three-fold aspect to this review: Grb2 protein introduction, Grb2 protein involvement in cancer, and the role of peptides as Grb2 antagonists. First, Grb2 and compiled maximum tumor conformations induced by Grb2 involvement were introduced. Secondly, several oncogenic pathways of Grb2 involvement and particular approaches potentially useful to downregulate Grb2 overexpression were outlined. The activity of different types of novel peptides for the Grb2 protein was also detailed. Last but not least, the blockade of Grb2-mediated signaling pathways by targeting SH2/SH3 binding sites were summarized. Conclusion We have epitomized the utmost cancer malignancies caused by abnormal signaling of the Grb2 adaptor molecule. Indeed, Grb2's enormous involvement in the progression and development of different cancers broaden our tactics to build anticancer drug candidates. Depending on the high affinity and increased specificity we have described the major potent peptides which may efficiently target and block the SH2 or SH3 arms of the Grb2. It may be of benefit for developing novel anticancer peptides. However, further work is needed to pinpoint more binding motives of Grb2 to generate efficacious anticancer agents for diverse human cancers in the near future.

ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms

Abstract: a Gastroenterology Department, Hampshire Hospitals NHS Trust, Hampshire , UK; b Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam , The Netherlands; c Department of Digestive and Liver Disease, Ospedale Sant’Andrea, Rome , d NET Centre, Umbria Regional Cancer Network, Università degli Studi di Perugia, Perugia , and e Department of Endocrine and Metabolic Sciences (DIMI), University of Genoa, Genoa , Italy; f Pancreatic Diseases Branch, Kyushu University Hospital, Fukuoka , Japan; g Department of Gastroenterology, Beaujon Hospital, Clichy , France; h Department of Radiology, Section for Molecular Imaging, University Hospital, Uppsala , Sweden; i Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, N.Y. , USA; j Department of Endocrinology, Peking Union Medical College Hospital, Beijing , China; k Netherlands Cancer Centre, Lijnden , The Netherlands; l Department of Visceral and Transplant Surgery, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin , Germany

5-Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes

Abstract: Colorectal cancer (CRC) is a public health problem. It is the third most common cancer in the world, with nearly 1.8 million new cases diagnosed in 2018. The only curative treatment is surgery, especially for early tumor stages. When there is locoregional or distant invasion, chemotherapy can be introduced, in particular 5-fluorouracil (5-FU). However, the disease can become tolerant to these pharmaceutical treatments: resistance emerges, leading to early tumor recurrence. Different mechanisms can explain this 5-FU resistance. Some are disease-specific, whereas others, such as drug efflux, are evolutionarily conserved. These mechanisms are numerous and complex and can occur simultaneously in cells exposed to 5-FU. In this review, we construct a global outline of different mechanisms from disruption of 5-FU-metabolic enzymes and classic cellular processes (apoptosis, autophagy, glucose metabolism, oxidative stress, respiration, and cell cycle perturbation) to drug transporters and epithelial-mesenchymal transition induction. Particular interest is directed to tumor microenvironment function as well as epigenetic alterations and miRNA dysregulation, which are the more promising processes that will be the subject of much research in the future.

The early prediction of mortality in acute pancreatitis : a large population-based study. Commentary

Abstract: Background: Identification of patients at risk for mortality early in the course of acute pancreatitis (AP) is an important step in improving outcome. Methods: Using Classification and Regression Tree (CART) analysis, a clinical scoring system was developed for prediction of in-hospital mortality in AP. The scoring system was derived on data collected from 17 992 cases of AP from 212 hospitals in 2000-2001. The new scoring system was validated on data collected from 18 256 AP cases from 177 hospitals in 2004-2005. The accuracy of the scoring system for prediction of mortality was measured by the area under the receiver operating characteristic curve (AUC). The performance of the new scoring system was further validated by comparing its predictive accuracy with that of Acute Physiology and Chronic Health Examination (APACHE) II. Results: CART analysis identified five variables for prediction of in-hospital mortality. One point is assigned for the presence of each of the following during the first 24 h: blood urea nitrogen (BUN) >25 mg/dl; impaired mental status; systemic inflammatory response syndrome (SIRS); age >60 years; or the presence of a pleural effusion (BISAP). Mortality ranged from >20% in the highest risk group to <1% in the lowest risk group. In the validation cohort, the BISAP AUC was 0.82 (95% Cl 0.79 to 0.84) versus APACHE II AUC of 0.83 (95% Cl 0.80 to 0.85). Conclusions: A new mortality-based prognostic scoring system for use in AP has been derived and validated. The BISAP is a simple and accurate method for the early identification of patients at increased risk for in-hospital mortality.