Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research.

Exosomes are small extracellular vesicles (30-150 nm) that are formed by endocytosis containing complex RNA as well as protein structures and are vital in intercellular communication and can be used in gene therapy and drug delivery. According to the cell sources of origin and the environmental conditions they are exposed to, these nanovesicles are very heterogeneous and dynamic in terms of content (cargo), size and membrane composition. Exosomes are released under physiological and pathological conditions and influence the pathogenesis of cancers through various mechanisms, including angiogenesis, metastasis, immune dysregulation, drug resistance, and tumor growth/development. Gastrointestinal cancer is one of the deadliest types of cancer in humans and can involve organs e.g., the esophagus and stomach, or others such as the liver, pancreas, small intestine, and colon. Early diagnosis is very important in this field because the overall survival of patients is low due to diagnosis in late stages and recurrence. Also, various therapeutic strategies have failed and there is an unmet need for the new therapeutic agents. Exosomes can become promising candidates in gastrointestinal cancers as biomarkers and therapeutic agents due to their lower immunity and passing the main physiological barriers. In this work, we provide a general overview of exosomes, their biogenesis and biological functions. In addition, we discuss the potential of exosomes to serve as biomarkers, agents in cancer treatment, drug delivery systems, and effective vaccines in immunotherapy, with an emphasis on gastrointestinal cancers.

Investigation of the therapeutic role of native plant compounds against colorectal cancer based on system biology and virtual screening.

This study investigated the anticancer effects of compounds extracted from native plants on colon cancer following drug-target-network analysis and molecular docking. Based on the ChEBI database, compounds were identified in medicinal plants and weeds in the Chaharmahal and Bakhtiari provinces of Iran. A drug-target network was constructed based on candidate colon cancer protein targets and selective compounds. Network pharmacology analysis was conducted against the identified compounds and subjected to molecular docking studies. Based on molecular dynamics simulations, the most efficient compounds were evaluated for their anticancer effects. Our study suggests that TREM1, MAPK1, MAPK8, CTSB, MIF, and DPP4 proteins may be targeted by compounds in medicinal plants for their anti-cancer effects. Multiorthoquinone, Liquiritin, Isoliquiritin, Hispaglabridin A, Gibberellin A98, Cyclomulberrin, Cyclomorusin A, and Cudraflavone B are effective anticancer compounds found in targeted medicinal plants and play an important role in the regulation of important pathways in colon cancer. Compounds that inhibit MIF, CTSB, and MAPK8-16 appear to be more effective. Additional in vitro and in vivo experiments will be helpful in validating and optimizing the findings of this study.

The incidence and features of Delphian lymph node involvement in patients with papillary thyroid carcinoma.

INTRODUCTION: In papillary thyroid cancer patients, the extent of dissection is still a matter of debate. Evaluating Delphian lymph nodes (DLNs) during the surgery has been speculated as a valuable tool to determine the extent of dissection. Herein, we aimed to evaluate the incidence and features of DLNs involvement in patients with papillary thyroid carcinoma. METHOD: We conducted this cross-sectional study among surgical cases of papillary thyroid cancer. Patients were divided based on their DLNs involvement status. Their age, gender, location of the mass, lymphatic involvement, tumor size, tumor characteristics, pathology report, and operation note features were compared between the two groups. Definitive pathology slides of the patients were evaluated regarding DLN features. RESULTS: Of the 61 patients (mean age: 38.2 ± 12.0), 45 (73.8%) were females. In 13 (21.3%) patients, DLNs involvement was reported. A statistically significant relationship was noted between DLNs involvement and other lymph nodes' involvement on the same side of the mass (P < 0.001), the opposite side (P = 0.041), and also central lymph nodes (P < 0.001). Vascular invasion was also significantly higher among patients with DLNs involvement (P = 0.012). CONCLUSION: Since DLNs involvement is significantly associated with extensive nodal involvement, intraoperative evaluation of DLNs is recommended to establish the extent to which dissection should be performed.

Herbal Medicines as Potential Inhibitors of SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) is the result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding molecular pathogenesis is an essential factor for the allocation of effective preventive measures and the development of targeted therapeutics against COVID-19. The genome of SARS-CoV-2 encodes structural and nonstructural proteins, which can be targets for compounds with potential therapeutic ability. On the other hand, the virus life cycle has stages susceptible to targeting by drug compounds. Many natural antiviral compounds have been studied and evaluated at the cellular and molecular levels with antiviral potential. Meanwhile, many studies over the past few months have shown that plant polysaccharides have a good ability to target proteins and stages of the virus life cycle. In this regard, in this review study, the virus specifications and infectious process and structural and functional components of SARSCoV- 2 will be reviewed, and then the latest studies on the effect of plant compounds with more focus on polysaccharides on viral targets and their inhibitory potential on the infectious process of COVID-19 will be discussed.

The Epigenetic Modification of SLC5A8 in Papillary Thyroid Carcinoma and its Effects on Clinic-Pathological Features.

Background: Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes, especially thyroid cancer. Identification of novel and effective markers are important in diagnosis and prevention of thyroid cancer. In the present study, the expression and methylation of Solute carrier family 5 member 8 (SLC5A8) in Papillary Thyroid Carcinoma (PTC) in comparison to multinodular goiter (MNG) have been studied. Methods: Overall, 41 patients with PTC and 36 patients affected by MNG were recruited from four hospitals in Tehran and Qazvin, Iran in 2018. Thyroid tissues were obtained during thyroidectomy. RNA and DNA were extracted from thyroid tissues. Quantitative RT-PCR assay was performed for determining the mRNA level of SLC5A8 while Methylation-Sensitive High-Resolution Methylation was applied for assessing the methylation status. Results: Methylation status of three regions composed of 52 CpG islands in the promoter of SLC5A8 gene was studied by HRM assay. SLC5A8 level in PTC tissues was significantly downregulated in average 0.4 fold in comparison with MNG tissues (P=0.05). The aberrant methylation of SLC5A8 (b) region was remarkably different in PTC and MNG cases. The promoter methylation of SLC5A8 (c) was significantly related to BRAF mutations and vascular invasion in PTC patients. Conclusion: The aberrant promoter hyper methylation of SLC5A8 was related to aggressive PTC. Therefore, there is some evidence to support the hypothesis that SLC5A8 could be a paly important role in the development of PTC.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = -2.853, 95% CI 2.50-3.19) and MDA (d = -1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46-0.34) and GPx (d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

Comparison of therapeutic effects of chemo-radiotherapy with neoadjuvant chemotherapy before radical surgery in patients with bulky cervical carcinoma (stage IB3 & IIA2).

BACKGROUND: Cervical cancer is one of the most common malignancies among women. Appropriate and timely treatment of these patients can reduce the complications and increase their survival. The objective of this study was to compare neoadjuvant chemotherapy plus radical hysterectomy (NACTRH) and chemo-radiotherapy (CRT) in patients with bulky cervical cancer (stage IB3 & IIA2). MATERIAL AND METHODS: The medical records of patients with bulky cervical cancer (stage IB3 & IIA2) that received NACTRH or CRT between 2007 and 2017 were evaluated for therapeutic effects. Demographic characteristics, complications of chemo-radiotherapy and neoadjuvant chemotherapy, were collected in a researcher-made questionnaire. Our primary outcome was comparison of overall survival (OS), and disease-free survival (DFS) between two groups receiving NACTRH and CRT modalities. RESULTS: One-hundred and twenty three patients were enrolled in the study. The median age and the proportion of patients with stage IIA2 were higher in the CRT group compared to the NACTRH group (p < 0.05). The medians (95% CI) OS were 3.64 (3.95-6.45) and 3.9 (3.53-4.27) years in the NACTRH and CRT groups, respectively (P = 0.003). There were 16 (34.8%) and 22 (43.1%) recurrences in the NACTRH and CRT group, respectively (P = 0.4). The median (95% CI) DFS was 4.5 (3.88-5.12) years in the NACTRH group and 3.6 (2.85-4.35) years in the CRT group (P = 0.004). The 3-year OS rate in NACTRH and CRT groups were 97 and 90% respectively. The 3-year DFS rate in NACTRH and CRT groups were 88 and 66% respectively. CONCLUSIONS: NACTRH is associated with a higher OS and DFS compared to CRT.

Sentinel lymph node biopsy for papillary thyroid cancer: the effect of dose, tracer and application of massage.

OBJECTIVES: In patients with papillary thyroid cancer (PTC), sentinel lymph node (SLN) radio-guided biopsy is not routinely used for detection of involved neck lymph nodes (NLN); 99mTc- antimony sulfide colloid (99mTc- ASC) has been used for this purpose. In this study, besides 99mTc-ASC another radiotracer, 99mTc-phytate (99mTc-P) with different doses and injection methods were evaluated. METHODS: Twenty-two patients, scheduled to undergo thyroidectomy for PTC, were injected for radio-guided SLN biopsy in the morning of operation in 3 groups: intra tumoral injection of about 1 mCi 99mTc-P (group A; n=5); peritumoral injection of less than 3 mCi 99mTc-ASC (group B; n=6); and peritumoral injection of 3 to 5 mCi 99mTc-ASC with application of massage (group C; n=9). A patient refused to complete the study. A patient with follicular thyroid cancer was also excluded. No NLN was detected in the pre-operative ultra-sonographic examinations of all patients. Central neck dissection was done for all the participants. The presence of radio guided detected NLN and results of pathology were assessed. RESULTS: In group A and B, no SLN was detected. NLNs were resected in 4 patients in group A and B; 2 of them involved by the tumor. In group C, 6 out of 9 patients (66.7%) had between 1 to 6 SLNs; the procedure failed to detect NLN in a patient in group C with surgically resected reactive NLN (failure rate 1 out of 7). CONCLUSION: The results underscored the significance of SLN radio guided biopsy in patients with PTC; the radiotracer, dose and method of injection may affect the detection rate.

Inhibition of miR-155 in MCF-7 breast cancer cell line by gold nanoparticles functionalized with antagomir and AS1411 aptamer.

MicroRNAs are key factors for many biological functions. These regulatory molecules affect various gene networks and involve the subsequent signaling pathways. Therefore, disrupting the expression of these molecules is associated with multiple anomalies in the cells and body. One of the most important related abnormalities is the incidence of cancer. Thus, targeting microRNAs (miRNAs) is an effective approach for cancer gene therapy. Various factors are used for this purpose, including the antagomir nucleotide structure. There are some obstacles in the delivery of nucleotide therapeutics to the target cells, however, the use of nanoparticles could partly overcome these defeciencies. On the other hand, targeted delivery of antagomirs using aptamers, reduces nonspecific effects on nontarget cells. Considering the above, in this study, we designed and fabricated a nanocarrier composed of gold nanoparticles (GNPs), antagomir-155, and nucleolin specific aptamer for breast cancer study and therapy. Here, GNPs were synthesized using citrate reduction and were modified by polyA sequences, AS1411 aptamer, and antagomir-155. Attachment of molecules were confirmed using gel electrophoresis, atomic force microscopy imaging and electrochemical test. The specific entry of modified nanoparticles was investigated by fluorescence microscopy. The efficacy of modified nanoparticles was evaluated using a quantitative polymerase chain reaction (q-PCR) for miR-155 and its target gene. Efficient and specific delivery of AuNP-Apt-anti-miR-155 to target cells was confirmed in comparison with the control cell. The q-PCR analysis showed not only a significant decrease in mir-155 levels but also an elevated TP53INP1 mRNA, direct target of miR-155. The proposed structure inhibits proliferation and stimulates apoptosis by increasing the expression of TP53INP1. Our results suggest that AuNP-Apt-anti-miR-155 could be a promising nano constructor for breast cancer treatment.

Pancreatic neuroendocrine tumors (pNETs): the predictive value of MDCT characteristics in the differentiation of histopathological grades.

PURPOSE: To investigate the correlation between multiple detector computed tomography (MDCT) features of pancreatic neuroendocrine tumors (pNETs) and histopathologic grade and find valuable imaging criteria for grade prediction. MATERIAL AND METHODS: MDCT of 61 patients with 65 masses, which pNETs were approved histopathologically, underwent revision retrospectively. Each MDCT was evaluated for various radiologic characteristics. Absolute and relative (R: tumor/pancreas, D: tumor-pancreas) tumor enhancements were calculated in multiple post contrast phases. RESULTS: 61 patients [mean age = 50.70 ± 14.28 y/o and 30(49.2%) were male] were evaluated and classified into 2 groups histopathologically: G1: 32 (49.2%) and G2,3: 33 (50.8%). Significant relationships were observed between histopathologic tumor grade regarding age (p = 0.006), the longest tumor size (p = 0.006), presence of heterogeneity (p < 0.0001), hypodense foci in delayed phase (p = 0.004), lobulation (p = 0.002), vascular encasement (p < 0.0001), adjacent organ invasion (p = 0.01), presence (p < 0.0001) and number (0.02) of liver metastases, presence of lymphadenopathy with short axis of more than 10 mm (LAP) (p = 0.008), pathologic lymph node size (p = 0.004), relative (R and D) (p = 0.05 and 0.02, respectively), and percentage of arterial hyper-enhancing area (p = <0.0001). Tumor grades, however, had no significant relationship with gender, tumor location, tumor outline, calcification, cystic change, or pancreatic (PD) or biliary duct (BD) dilation (p = 0.21, 0.60, 0.05, 0.05 1, 0.10, and 0.51, respectively). Then, we suggested a novel imaging criteria consisting of six parameters (tumor size > 33 mm, relative (R) tumor enhancement in arterial phase ≤ 1.33, relative (D) tumor enhancement in arterial phase ≤ 16.5, percentage of arterial hyper-enhancing area ≤ 75%, vascular encasement, and lobulation), which specificity and accuracy of combination of all findings (6/6) for predicting G2,3 were 100% and 70.1%, respectively. The highest accuracy (84.21%) was seen in combinations of at least 4 of 6 findings, with 80.00% sensitivity, 87.5% specificity, 83.33% PPV, and 84.85% NPV. CONCLUSION: We suggested reliable imaging criteria with high specificity and accuracy for predicting the histopathologic grade of pNETs.

NOL4 is Downregulated and Hyper-Methylated in Papillary Thyroid Carcinoma Suggesting Its Role as a Tumor Suppressor Gene.

BACKGROUND: Thyroid cancer is the fourth most common cancer in the world. Papillary thyroid carcinoma (PTC) accounts for 80% of all types of thyroid neoplasm. Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes. OBJECTIVES: In the present study, the expression and methylation of suggested gene namely nucleolar protein 4 (NOL4) in PTC in comparison to multi nodular goiter (MNG) have been studied. METHODS: Forty-one patients with PTC and 38 patients affected by MNG were recruited. Thyroid tissues were obtained during thyroidectomy. RNA and DNA were extracted from thyroid tissues. Quantitative RT-PCR assay was performed for determining the mRNA level of NOL4 while methylation-sensitive high resolution methylation was applied for assessing the methylation status with designing six pairs primers for six regions on gene promoter which were named from NOL4 (a) to NOL4 (f). RESULTS: Methylation assessment of 81 CpG islands in the promoter region of NOL4 gene revealed that NOL4 (f), the nearest region to the start codon, was significantly hypermethylated in PTC cases compared to MNG cases. NOL4 level in PTC cases in comparison with MNG cases were downregulated. The methylation status and mRNA level of NOL4 (f) were associated with age of diagnosis (Age of the patient at the time of diagnosis), lymph node metastasis, and advanced stages of disease. CONCLUSIONS: These data suggested an aberrant promoter hyper-methylation of NOL4 in PTC cases may be linked with its downregulation. Therefore, NOL4 gene can be proposed as a potential tumor suppressor gene in PTC tissues.

Antibody-drug therapeutic conjugates: Potential of antibody-siRNAs in cancer therapy.

Codelivery is a promising strategy of targeted delivery of cytotoxic drugs for eradicating tumor cells. This rapidly growing method of drug delivery uses a conjugate containing drug linked to a smart carrier. Both two parts usually have therapeutic properties on the tumor cells. Monoclonal antibodies and their derivatives, such as Fab, scFv, and bsAb due to targeting high potent have now been attractive candidates as drug targeting carrier systems. The success of some therapeutic agents like small interfering RNA (siRNA), a small noncoding RNAs, with having problems such as enzymatic degradation and rapid renal filtration need to an appropriate carrier. Therefore, the aim of this study is to review the recent enhancements in development of antibody drug conjugates (ADCs), especially antibody-siRNA conjugates (SRCs), its characterizations and mechanisms in innovative cancer therapy approaches.

Evaluation of the diagnostic potential of trans abdominal ultrasonography in detecting intra-abdominal adhesions: A double-blinded cohort study.

BACKGROUND: Intra-abdominal adhesion is one of the most important complications of abdominopelvic surgery. It increases morbidity and mortality for patients. Although laparoscopy is the gold standard of adhesion diagnosis, it can cause visceral damage during the operation. Therefore, surgeons prefer to use non-invasive methods for planning the operation. We designed this study to evaluate transabdominal ultrasonography ( TAU) accuracy for diagnosing Intra-abdominal Adhesions. MATERIAL & METHODS: This double-blinded cohort study was conducted on 47 patients with previous laparotomy who undergo another surgery. Spontaneous visceral slide (SVS) and induced visceral slide (IVS) were measured during TAU. RESULTS: The mean age and BMI of 47 patients were 43.21±10.3 and 27.545±5.76. The majority of the patients were female (76%). Mean SVS and IVS in patients with intra-abdominal adhesion were 8.73±1.60 and 44.84±11.60. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of TAU in intra-abdominal diagnosis were 83.33%, 51.72%, 51.72%, 83.33%, 63.83%. CONCLUSIONS: Although TAU is an appropriate method for detecting the intra-abdominal adhesion, it isn't good enough for diagnosing free adhesion area. We recommended further researches with greater sample size and other non-invasive techniques.

Effect of Acyl Homoserine Lactone on Recombinant Production of Human Insulin-like Growth Factor-1 in Batch Culture of Escherichia coli.

BACKGROUND: IGF-I as a human growth factor produced in Escherichia coli is a single, non-glycosylated, polypeptide chain containing 70 amino acids and having a molecular mass of 7.6 kDa. Up to now, E. coli expression system has been widely used as the host to produce rhIGF-1 with high yields. Acyl Homoserine Lactones (AHLs) are intercellular signaling molecules used in quorum sensing by Gram-negative bacteria. Quorum sensing is a cell density-dependent gene regulation process that allows bacterial cells to express specific genes only when signaling molecules reach the sufficient concentration. OBJECTIVE: For the first time, this study focuses on the N-hexanoyl-L- Homoserine Lactone (HHL) activity on increasing the cell growth and rh-IGF-1concentration in batch culture of E. coli. METHOD: The maximum production of rhIGF-I was previously optimized in 32y culture medium at 32°C with 0.05 mM IPTG as inducer and 10 g/l glucose concentration. Under this condition, different amounts of HHL (0.001 µg/ml, 1 µg/ml, and 100µg/ml) were evaluated as an inducer for IGF-1 production. RESULTS: Generally, with increasing of HHL concentration, an increase in dry cell weight (2.45 mg/ml to 4.63 mg/ml) and IGF-I expression level (0.4 mg/ml to 0.77 mg/ml) was observed. CONCLUSION: HHL or other types of AHLs can be considered as protein production inducer in bacterial expression systems through the quorum sensing pathways.

Anti-Cancer Drug Delivery Using Carbohydrate-Based Polymers.

Polymeric drug delivery systems in the form of nanocarriers are the most interesting vehicles in anticancer therapy. Among different types of biocompatible polymers, carbohydrate-based polymers or polysaccharides are the most common natural polymers with complex structures consisting of long chains of monosaccharide or disaccharide units bound by glycosidic linkages. Their appealing properties such as availability, biocompatibility, biodegradability, low toxicity, high chemical reactivity, facile chemical modification and low cost led to their extensive applications in biomedical and pharmaceutical fields including development of nano-vehicles for delivery of anti-cancer therapeutic agents. Generally, reducing systemic toxicity, increasing short half-lives and tumor localization of agents are the top priorities for a successful cancer therapy. Polysaccharide-based or - coated nanosystems with respect to their advantageous features as well as accumulation in tumor tissue due to enhanced permeation and retention (EPR) effect can provide promising carrier systems for the delivery of noblest impressive agents. Most challenging factor in cancer therapy was the toxicity of anti-cancer therapeutic agents for normal cells and therefore, targeted delivery of these drugs to the site of action can be considered as an interesting therapeutic strategy. In this regard, several polysaccharides exhibited selective affinity for specific cell types, and so they can act as a targeting agent in drug delivery systems. Accordingly, different aspects of polysaccharide applications in cancer treatment or diagnosis were reviewed in this paper. In this regard, after a brief introduction of polysaccharide structure and its importance, the pharmaceutical usage of carbohydrate-based polymers was considered according to the identity of accompanying active pharmaceutical agents. It was also presented that the carbohydrate based polymers have been extensively considered as promising materials in the design of efficient nanocarriers for anti-cancer biopharmaceuticals including peptide and proteins or nucleic acid-based therapeutics. Then, the importance of various polysaccharide co-polymers in the drug delivery approaches was illustrated.

Nanobodies As Novel Agents for Targeting Angiogenesis in Solid Cancers.

Solid cancers are dependent on angiogenesis for sustenance. The FDA approval of Bevacizumab in 2004 inspired many scientists to develop more inhibitors of angiogenesis. Although several monoclonal antibodies (mAbs) are being administered to successfully combat various pathologies, the complexity and large size of mAbs seem to narrow the therapeutic applications. To improve the performance of cancer therapeutics, including those blocking tumor angiogenesis, attractive strategies such as miniaturization of the antibodies have been introduced. Nanobodies (Nbs), small single-domain antigen-binding antibody fragments, are becoming promising therapeutic and diagnostic proteins in oncology due to their favorable unique structural and functional properties. This review focuses on the potential and state of the art of Nbs to inhibit the angiogenic process for therapy and the use of labeled Nbs for non-invasive in vivo imaging of the tumors.

Targeted cancer therapy through antibody fragments-decorated nanomedicines.

Active targeting in cancer nanomedicine, for improved delivery of agents and diagnose, has been reviewed as a successful way for facilitating active uptake of theranostic agents by the tumor cells. The application of a targeting moiety in the targeted carrier complexes can play an important role in differentiating between tumor and healthy tissues. The pharmaceutical carriers, as main part of complexes, can be polymeric nanoparticles, micelles, liposomes, nanogels and carbon nanotubes. The antibodies are among the natural ligands with highest affinity and specificity to target pharmaceutical nanoparticle conjugates. However, the limitations, such as size and long circulating half-lives, hinder reproducible manufacture in clinical studies. Therefore, novel approaches have moved towards minimizing and engineering conventional antibodies as fragments like scFv, Fab, nanobody, bispecific antibody, bifunctional antibody, diabody and minibody preserving their functional potential. Different formats of antibody fragments have been reviewed in this literature update, in terms of structure and function, as smart ligands in cancer diagnosis and therapy of tumor cells.

Biodegradable nano-polymers as delivery vehicles for therapeutic small non-coding ribonucleic acids.

Nowadays, small non-coding Ribo Nucleic Acids (sncRNAs) such as siRNA, miRNA and shRNA are extremely serving to gene regulation. They are involved in many biological processes and in an increasing number of studies regarding a variety of application of sncRNAs toward human health and relieving diseases ranging from metabolic disorders to those involving various organ systems as well as different types of cancer. One of the most severe limitations for applying RNA interference technology is the absence of safe and effective carriers for in vivo delivery, including localizing the molecules to a specific site of interest and sustaining the presentation of the payloads for a controlled period of time. In this review, we focus on the sncRNA functions and recent advances on the delivery of these molecules by biodegradable, biocompatible and nontoxic biopolymers including chitosan, cyclodextrins, poly-l-lysine, dextran, poly (lactic co-glycolic acid), polyglutamic acid, hyaluronic acid and gelatin.

Incidence of Post-Operative Sepsis and Role of Charlson Co-Morbidity Score for Predicting Postoperative Sepsis.

Sepsis and septic shock are among mortality causes following major surgeries. The Charlson co-morbidity index consists of 19 weighted categories related to chronic health which measures the burden of co-morbidity. The goal of this study was to determine the incidence of postoperative sepsis in patients underwent gynecological and gastrointestinal cancer surgeries and predictive role of Charlson index for this situation. Two hundred and twenty-two patients who underwent gynecological and gastrointestinal cancer surgeries were evaluated. Sixty-four (28.6%) patients developed SIRS postoperatively. Forty-four (19.7%) patients developed sepsis postoperatively. Mean age, duration of hospitalization and surgery, the Charlson score were significantly higher in patients who developed sepsis than other cases. Blood transfusion and Charlson score were independent predictors of sepsis occurrence. Charlson co-morbidity index is a predictive factor for developing postoperative sepsis.