Chemotherapeutic Treatment Research Articles

Naturally Occurring Rhamnopyranosides as Anticancer Agents: Molecular Docking and ADMET Study

After heart disease, cancer continues to be the second most prevalent cause of death in the USA. Several chemotherapeutic treatments (drugs) are available for cancer that use powerful chemicals to kill the body's rapidly proliferating cells. However, recent research disclosed that many clinically viable anticancer drugs have been developed with the help of chemicals originating from plants. A number of phytochemicals isolated from plants possess rhamnopyranoses and some of them are acyl rhamnopyranoses. Encouragingly, such compounds were reported for their cell proliferation and migration inhibition activities against invasive human triple-negative breast cancer cells. In this study, four naturally occurring rhamnopyranose esters were checked against three cancer-related proteins (PDB IDs: 3TJM, 4OAR, and 5FGK) via molecular docking. Rhamnose compounds 3-6 showed better binding energy compared to the related standard drugs in use in the hospitals. Compound 6 was found highly potential against all the proteins (-8.5 to -11.3 kcal/mol). ADMET studies have also been discussed in this respect. This study indicated that natural rhamnopyranose esters could be used to stop the spreading of cancer cells like other reported sugar fatty acid esters (SFAEs).

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance.

Head and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients. Clinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. We separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments. The 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.

A moving target for drug discovery: Structure activity relationship and many genome (de)stabilizing functions of the RAD52 protein

BRCA-ness phenotype, a signature of many breast and ovarian cancers, manifests as deficiency in homologous recombination, and as defects in protection and repair of damaged DNA replication forks. A dependence of such cancers on DNA repair factors less important for survival of BRCA-proficient cells, offers opportunities for development of novel chemotherapeutic interventions. The first drugs targeting BRCA-deficient cancers, poly-ADP-ribose polymerase (PARP) inhibitors have been approved for the treatment of advanced, chemotherapy resistant cancers in patients with BRCA1/2 germline mutations. Nine additional proteins that can be targeted to selectively kill BRCA-deficient cancer cells have been identified. Among them, a DNA repair protein RAD52 is an especially attractive target due to general tolerance of the RAD52 loss of function, and protective role of an inactivating mutation. Yet, the effective pharmacological inhibitors of RAD52 have not been forthcoming. In this review, we discuss advances in the state of our knowledge of the RAD52 structure, activities and cellular functions, with a specific focus on the features that make RAD52 an attractive, but difficult drug target.

A Signaling Factor Linked to Toxoplasma gondii Guanylate Cyclase Complex Controls Invasion and Egress during Acute and Chronic Infection.

ABSTRACTToxoplasma gondii is an intracellular apicomplexan parasite that relies on cyclic GMP (cGMP)-dependent signaling to trigger timely egress from host cells in response to extrinsic and intrinsic signals. A guanylate cyclase (GC) complex, conserved across the Apicomplexa, plays a pivotal role in integrating these signals, such as the key lipid mediator phosphatidic acid and changes in pH and ionic composition. This complex is composed of an atypical GC fused to a flippase-like P4-ATPase domain and assembled with the cell division control protein CDC50.1 and a unique GC organizer (UGO). While the dissemination of the fast-replicating tachyzoites responsible for acute infection is well understood, it is less clear if the cyst-forming bradyzoites can disseminate and contribute to cyst burden. Here, we characterized a novel component of the GC complex recently termed signaling linking factor (SLF). Tachyzoites conditionally depleted in SLF are impaired in microneme exocytosis, conoid extrusion, and motility and hence unable to invade and egress. A stage-specific promoter swap strategy allowed the generation of SLF- and GC-deficient bradyzoites that are viable as tachyzoites but show a reduction in cyst burden during the onset of chronic infection. Upon oral infection, SLF-deficient cysts failed to establish infection in mice, suggesting SLF’s importance for the natural route of T. gondii infection.

Hyaluronic acid functionalized liposomes embedded in biodegradable beads for duo drugs delivery to oxaliplatin-resistant colon cancer

BackgroundOxaliplatin (OHP) resistance is a major hurdle in the chemotherapeutic treatment of colorectal cancer (CRC). The present study aimed to formulate Eudragit S-100 (ES-100) coated alginate beads bearing drugs loaded targeted liposomes for simultaneous delivery of OHP and curcumin (CUR) to exert a synergistic therapeutic effect on OHP- resistant HT-29 cell line. Research designThe liposomes were prepared by the thin-film hydration method and optimized for various formulation parameters using a Box-Behnken design (BBD) with the aid of Design-Expert® software. Hyaluronic acid (HA) was conjugated on the liposomal surface using carbodiimide chemistry to target CD44 receptors, which are overexpressed on the CRC cells. HA coupled drugs bearing liposomes (OC-L-HA) were then characterized for various attributes, viz. shape, surface-morphology, size, zeta potential, PDI, entrapment efficiency, and drug loading, as well as in-vitro cell-based studies. OC-L-HA were entrapped in the alginate beads and examined for their in vitro potential and in vivo performances. ResultsMTT assay demonstrated that OC-L-HA exhibited 2.76 and 2.58 fold higher cytotoxicity than targeted CUR liposomes and targeted OHP liposomes, respectively. The in vivo X-ray images affirmed the good targeting ability of the targeted beads to the colon. ConclusionThe outcomes of the studies revealed that these surface-modified liposomes entrapped in Eudragit S-100 coated beads could be an effective strategy for the treatment of CRC.

Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings.

Ovarian cancer is one of the most dangerous gynecologic cancers worldwide, showing a high fatality rate and recurrence due to diagnosis at an advanced stage of the disease and the occurrence of chemoresistance, which weakens the therapeutic effects of the chemotherapeutic treatments. In fact, although paclitaxel and platinum-based drugs (carboplatin or cisplatin) are widely used alone or in combination to treat ovarian cancer, the occurrence of chemoresistance significantly reduces the effects of these drugs. Metformin is a hypoglycemic agent that is commonly used for the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease. However, this drug also shows anti-tumor activity, reducing cancer risk and chemoresistance. This review analyzes the current literature regarding the role of metformin in ovarian cancer and investigates what is currently known about its effects in reducing paclitaxel and platinum resistance to restore sensitivity to these drugs.

Morbidity and Mortality of Neutropenic Patients in Visceral Surgery: A Narrative Review

Leukocytes are essential for the function of the immune system and cell–cell interaction in the human body, but hematological diseases as well as chemotherapeutic treatments due to cancer lead to occasionally or even permanent leukocyte deficiency. Normally, more than 50% of leukocytes are neutrophilic granulocytes, and leukopenia is, therefore, mostly characterized by a decrease in neutrophilic granulocytes. The consequence of neutropenia is increased susceptibility to infection, but also healing disorders are suggestable due to the disturbed cell–cell interaction. While there is no surgical treatment for leucocyte disorders, patients suffering from neutropenia are sometimes in need of surgery for other reasons. Less is known about the morbidity and mortality of this patients, which is why this narrative review critically summarizes the results of recent research in this particular field. The results of this review suggest that neutropenic patients in need of emergency surgery have a higher mortality risk compared to non-neutropenic patients. In contrast, in elective surgery, there was not a clear tendency for a higher mortality risk of neutropenic patients. The role of neutrophilic granulocytes in inflammation and immunity in surgical patients is emphasized by the results, but most of the evaluated studies showed methodological flaws due to small sample sizes or risk of bias. Further research has to evaluate the risk for postoperative complications, particularly of infectious complications such as surgical site infections, in neutropenic patients undergoing elective surgery, and should address the role of neutrophilic function in postoperative morbidity and mortality.

Antimalarial Efficacy of Aqueous Extract of Strychnos ligustrina and Its Combination with Dihydroartemisinin and Piperaquine Phosphate (DHP) against Plasmodium berghei Infection.

The development of drug resistance is one of the most severe concerns of malaria control because it increases the risk of malaria morbidity and death. A new candidate drug with antiplasmodial activity is urgently needed. This study evaluated the efficacy of different dosages of aqueous extract of Strychnos ligustrina combined with dihydroartemisinin and piperaquine phosphate (DHP) against murine Plasmodium berghei infection. The BALB/c mice aged 6-8 weeks were divided into 6 groups, each consisting of 10 mice. The growth inhibition of compounds against P. berghei was monitored by calculating the percentage of parasitemia. The results showed that the mice receiving aqueous extract and combination treatment showed growth inhibition of P. berghei in 74% and 94%, respectively. S. ligustrina extract, which consisted of brucine and strychnine, effectively inhibited the multiplication of P. berghei. The treated mice showed improved hematology profiles, body weight, and temperature, as compared to control mice. Co-treatment with S. ligustrina extract and DHP revealed significant antimalarial and antipyretic effects. Our results provide prospects for further discovery of antimalarial drugs that may show more successful chemotherapeutic treatment.

Prognosis of Human Cytomegalovirus in Cancer Patients Undergoing Chemotherapeutic Treatment in Egypt and an Emergent Prevalence of Glycoprotein B-5

The human cytomegalovirus (HCMV) is a global opportunistic β-herpes virus causing severe diseases in immune-compromised patients, such as malignant tumor patients, especially those undergoing chemotherapeutic treatment. This study aimed to determine the prevalence of HCMV-DNA in chemotherapeutic treatment naive cancer patients, and after chemotherapy, to compare between conventional nested PCR and ELISA techniques for the detection of HCMV, and to detect glycoprotein B genotypes. Plasma and serum samples before and after three chemotherapy cycles were collected from 49 chemotherapy-naive cancer patients. DNA was extracted from plasma samples using QIAamp® DNA Mini kit. HCMV-DNA was detected using a nested PCR technique. Multiplex nested PCR was used for HCMV-glycoprotein B (gB) genotyping. HCMV-IgG and -IgM were detected using ELISA technique. Thirty one (63.3 %) of the 49 plasma samples of the chemotherapy-naïve cancer patients were positive for HCMV-DNA; 21 of which remained positive after chemotherapy. However, 18 samples were negative of which 16 became positive after chemotherapy. gB-5 was the most common glycoprotein genotype detected (80.6 %), followed by gB-1, gB-3, gB-4, and gB-2. HCMV IgG was detected in the 49 serum samples of chemotherapy-naïve patients, and after exposure to chemotherapy. HCMV-DNA is commonly identified in cancer patients. Its detection after chemotherapy exposure may suggest HCMV reactivation. The most common genotype detected in cancer patients in Egypt is gB-5 in contrast to earlier research. IgG was detected in all patients. This indicates that HCMV is endemic in Egypt, necessitating the development of public awareness campaigns about HCMV infection and preventive strategies.

Predictive value of tumor-infiltrating lymphocytes detected by flow cytometry in colorectal cancer

The high heterogeneity of tumor cells and the surrounding immune microenvironment affects the response to treatment in colorectal cancer (CRC) patients. Therefore, there is a need to identify new immune biomarkers to predict the treatment efficacy of CRC. This study aimed to explore the predictive value of tumor-infiltrating lymphocytes (TIL) for survival in CRC patients. Flow cytometry and gated analysis were performed to measure the TILs in tissue samples obtained from 536 CRC patients. The COX regression analysis showed that the CD8 + CD279+ cells had the highest impact of all evaluated TILs on postoperative disease-free survival (DFS) (P < 0.05). The optimal CD8 + CD279+ cutoff point for the prediction of survival was 12.2%. The Kaplan-Meier analysis showed significantly higher DFS in the high CD8 + CD279+ group compared with the low CD8 + CD279+ group (P < 0.05). CD8 + CD279+ cells were associated with DFS in CRC patients with the KARS mutation, MSI/MMR, perineural invasion, and those treated with neoadjuvant chemotherapy and other chemotherapeutic treatments (P < 0.05). After the multivariate adjustment, the expression of CD8 + CD279+ remained an independent risk factor for DFS. Overall, the CD8 + CD279+ cells were identified as an independent prognostic factor in CRC patients and could be used as a potential marker for postoperative DFS.

Seven Fatty Acid Metabolism-Related Genes as Potential Biomarkers for Predicting the Prognosis and Immunotherapy Responses in Patients with Esophageal Cancer.

Background: Esophageal cancer (ESCA) is a major cause of cancer-related mortality worldwide. Altered fatty acid metabolism is a hallmark of cancer. However, studies on the roles of fatty acid metabolism-related genes (FRGs) in ESCA remain limited. Method: We identified differentially expressed FRGs (DE-FRGs). Then, the DE-FRGs prognostic model was constructed and validated using a comprehensive analysis. Moreover, the correlation between the risk model and clinical characteristics was investigated. A nomogram for predicting survival was established and evaluated. Subsequently, the difference in tumor microenvironment (TME) was compared between two risk groups. The sensitivity of key DE-FRGs to chemotherapeutic interventions and their correlation with immune cells were investigated. Finally, DEGs between two risk groups were measured and the prognostic value of key DE-FRGs in ESCA was confirmed in other databases. Results: A prognostic model was constructed based on seven selected DEG-FRGs. TNM staging and CD8+ T cells were significantly correlated with high-risk groups. Low-risk groups exhibited more infiltrated M0 macrophages, an activation of type II interferon (IFN-γ) responses, and were found to be more suitable for immunotherapy. Seven key DE-FRGs with prognostic value were found to be considerably influenced by different chemotherapy drugs. Conclusion: A prognostic model based on seven DE-FRGs may efficiently predict patient prognosis and immunotherapy response, helping to develop individualized treatment strategies in ESCA.

Understanding the mechano and chemo response of retinoblastoma tumor cells

IntroductionCellular homeostasis with its environment is bidirectional and dynamic in nature. Extracellular matrix plays an important role in retinoblastoma tumor cell's response to chemotherapeutic drugs. The present study was designed to investigate the effect of mechanotransduction along with the chemotherapeutic effect on RB cells grown on three-dimensional matrices. MethodsMatrigels of varying stiffness (low and high) were prepared and characterized. Drug sensitivity of RB cells on various matrigel stiffness was measured using cytotoxicity (MTT) assay and IC50 value was found for carboplatin and etoposide. Further, the effect on the proliferation and migration of RB cells in various stiffness matrigels was investigated. FindingsThe results showed that drug sensitivity decreased with an increase in matrix stiffness when compared to RB cells grown in suspension. In higher stiffness, the drug sensitivity decreases with an increase in cell proliferation. Data from a gene expression study revealed that Vinculin was variably regulated between metastatic and non-metastatic tumor cells, and upregulated RhoA was altered in different stiffness gradient matrigel during drug treatment. InterpretationThese results enhance the understanding of the fundamental molecules responding to drug sensitivity in a stiffness-altering environment. Additionally, it provides a new avenue for understanding how RB cells respond to chemotherapeutic intervention.

Early Stage Finding of an Immune-Enhanced Genetic Subtype of Nonsmall Cell Lung Cancer Related with T-Cell Depletion.

Background Molecular categorization of lung cancer in medical care is becoming increasingly important on a regular basis. One of the molecular classifications of NSCLC (early-stage NSCLC) supports that tumors of different biological varieties differ in terms of their genomes and clinical characteristics. Methods Based on published immune cell signatures and early-stage NSCLC gene expression data including cancer genome maps, we used consensus cluster analysis to identify immune molecular subtypes associated with early-stage NSCLC expression subtypes. These subtypes were correlated with early-stage NSCLC expression subtypes. Next, applying a wide range of statistical techniques, we evaluated the link between molecular subtypes and clinical features, immunological microenvironment, and immunotherapy reactivity. Molecular subtypes were defined as a classification of cancerous cells. Results Multiple RNAseq cross-platform datasets of immune genes were used to identify two molecular subtypes (C1 and C2) of NSCLC, with C1 showing a more favorable prognosis than C2. The results were validated on the CSE datasets. In terms of clinical characteristics, C2 subtype samples with a worse prognosis showed a more advanced tumor stage and higher mortality. C2 showed immuno-infiltrative characteristics but had depletion of T-cells. Biological functions such as EMT were enriched on C2. A low TIDE score in C1 indicated that C1 samples could benefit from taking immunotherapy. C2 were more susceptible to standard chemotherapeutic treatments such paclitaxel, cisplatin, sorafenib, crizotinib, and erlotinib. Conclusion According to our findings, early-stage NSCLC patients may benefit from receiving treatment with immune checkpoint blockade therapy.

Sensitization of Patient-Derived Colorectal Cancer Organoids to Photon and Proton Radiation by Targeting DNA Damage Response Mechanisms.

Simple SummaryRadiotherapy plays an important role in the treatment of colorectal cancer (CRC). Approximately one-third of patients with rectal cancer show a pathological complete response upon total neoadjuvant treatment. Patient-derived CRC organoids were investigated regarding their radiotherapeutic treatment response—both in terms of conventional photon irradiation, the combination thereof with chemotherapy, as well as proton irradiation. By inhibition of an important sensor molecule for DNA damage, which has been shown to be activated upon irradiation, radioresistant organoids could be resensitized.Pathological complete response (pCR) has been correlated with overall survival in several cancer entities including colorectal cancer. Novel total neoadjuvant treatment (TNT) in rectal cancer has achieved pathological complete response in one-third of the patients. To define better treatment options for nonresponding patients, we used patient-derived organoids (PDOs) as avatars of the patient’s tumor to apply both photon- and proton-based irradiation as well as single and combined chemo(radio)therapeutic treatments. While response to photon and proton therapy was similar, PDOs revealed heterogeneous responses to irradiation and different chemotherapeutic drugs. Radiotherapeutic response of the PDOs was significantly correlated with their ability to repair irradiation-induced DNA damage. The classical combination of 5-FU and irradiation could not sensitize radioresistant tumor cells. Ataxia-telangiectasia mutated (ATM) kinase was activated upon radiation, and by inhibition of this central sensor of DNA damage, radioresistant PDOs were resensitized. The study underlined the capability of PDOs to define nonresponders to irradiation and could delineate therapeutic approaches for radioresistant patients.

Inhibition of Mitochondrial Redox Signaling with MitoQ Prevents Metastasis of Human Pancreatic Cancer in Mice.

Simple SummaryIf improvements of diagnostic techniques and methodologies allow to increasingly detect cancers at the premetastatic stage, metastases still account for about 90% of cancer patient deaths in the clinics. Indeed, there is currently no specific treatment capable of blocking or even delaying the metastatic process. In this context, we previously showed that mitochondria are metabolic sensors initiating the metastatic process. Here, focusing on pancreatic cancer, with which about one-third of patients are diagnosed before the onset of metastases, we report that MitoQ, a mitochondria-targeted antioxidant, interrupts prometastatic redox signaling from mitochondria to the cell body. At doses compatible with the treatment of humans, we found that MitoQ represses pancreatic cancer cell migration, invasion and clonogenicity. It reduced the metastatic homing of human pancreatic cancer cells in mice by about 50%. If applied to patients, metastasis prevention with MitoQ could increase the chances of curing cancer with conventional treatments.At diagnosis, about 35% of pancreatic cancers are at the locally invasive yet premetastatic stage. Surgical resection is not a treatment option, leaving patients with a largely incurable disease that often evolves to the polymetastatic stage despite chemotherapeutic interventions. In this preclinical study, we hypothesized that pancreatic cancer metastasis can be prevented by inhibiting mitochondrial redox signaling with MitoQ, a mitochondria-targeted antioxidant. Using four different cancer cell lines, we report that, at clinically relevant concentrations (100–500 nM), MitoQ selectively repressed mesenchymal pancreatic cancer cell respiration, which involved the inhibition of the expression of PGC-1α, NRF1 and a reduced expression of electron-transfer-chain complexes I to III. MitoQ consequently decreased the mitochondrial membrane potential and mitochondrial superoxide production by these cells. Phenotypically, MitoQ further inhibited pancreatic cancer cell migration, invasion, clonogenicity and the expression of stem cell markers. It reduced by ~50% the metastatic homing of human MIA PaCa-2 cells in the lungs of mice. We further show that combination treatments with chemotherapy are conceivable. Collectively, this study indicates that the inhibition of mitochondrial redox signaling is a possible therapeutic option to inhibit the metastatic progression of pancreatic cancer.

Effects of Myristicin in Association with Chemotherapies on the Reversal of the Multidrug Resistance (MDR) Mechanism in Cancer.

A range of drugs used in cancer treatment comes from natural sources. However, chemotherapy has been facing a major challenge related to multidrug resistance (MDR), a mechanism that results in a decrease in the intracellular concentration of chemotherapeutic agents, resulting in reduced treatment efficacy. The protein most frequently related to this effect is P-glycoprotein (P-gp), which is responsible for promoting drug efflux into the extracellular environment. Myristicin is a natural compound isolated from nutmeg and has antiproliferative activity, which has been reported in the literature. The present study aimed to evaluate the effect of the association between myristicin and chemotherapeutic agents on the NCI/ADR-RES ovarian tumor lineage that presents a phenotype of multidrug resistance by overexpression of P-gp. It was observed that myristicin showed no cytotoxic activity for this cell line, since its IC50 was >1 mM. When myristicin was associated with the chemotherapeutic agents cisplatin and docetaxel, it potentiated their cytotoxic effects, a result evidenced by the decrease in their IC50 of 32.88% and 75.46%, respectively. Studies conducted in silico indicated that myristicin is able to bind and block the main protein responsible for MDR, P-glycoprotein. In addition, the molecule fits five of the pharmacokinetic parameters established by Lipinski, indicating good membrane permeability and bioavailability. Our hypothesis is that, by blocking the extrusion of chemotherapeutic agents, it allows these agents to freely enter cells and perform their functions, stopping the cell cycle. Considering the great impasse in the chemotherapeutic treatment of cancer that is the MDR acquired by tumor cells, investigating effective targets to circumvent this resistance remains a major challenge that needs to be addressed. Therefore, this study encourages further investigation of myristicin as a potential reverser of MDR.

Dialysis, Transplantation, and Work: Honoring Original Intent.

<h3>Significance and background</h3> Falls are multifactorial in medical oncology units and are potentiated by an older adult’s response to anxiolytics, opiates and chemotherapy protocols. In addition, the oncology patient is at an increased risk for injury from a fall due to coagulopathy, thrombocytopenia and advanced age. At our National Cancer Institute-designated inpatient cancer treatment centre located in the southeastern USA, 40% of the total discharges are over the age of 65. As part of a comprehensive fall prevention programme, bimonthly individual fall reports have been presented with the Chief Nursing Officer (CNO), nursing directors, nurse managers, physical therapists and front-line providers in attendance. As a result of these case discussions, in some cases, safety recommendations have not been followed by patients and families and identified as an implication in individual falls. Impulsive behaviour was acknowledged only after a fall occurred. A medical oncology unit was targeted for this initiative due to a prolonged length of stay. This patient population receives chemotherapeutic interventions, management of oncological treatment consequences and cancer progression care. <h3>Purpose</h3> The aim of this project was to explore if initiation of a Fall Prevention Agreement between the nursing team and older adults being admitted to medical oncology units would reduce the incidence of falls and the incidence of falls with injury. <h3>Interventional methods</h3> In order to promote patient and family participation in the fall reduction and safety plan, the Fall Risk and Prevention Agreement was introduced upon admission. Using the Morse Fall Scoring system, patient‘s risk for fall was communicated on the Fall Risk and Prevention Agreement. Besides admission, patients were reassessed based on change of status, transfer or after a fall occurs. <h3>Evaluation/findings</h3> Fall and fall injuries rates were compared two-quarters prior to implementation of the fall agreement and eight-quarters post implementation. Falls and fall injuries on the medical oncology unit had an overall reduction of 37% and 58.6%, respectively. <h3>Discussion/implications</h3> A robust fall prevention standard does not ensure care team participation in all elements to reduce fall occurrence. Historically, the Fall Risk and Prevention Agreement had not been initiated on admission. Incorporating patients and families in discussions related to fall risk and prevention is consistent with collaborative communication. The Joint Commission and the Centers for Medicare and Medicaid Services in 2002 encouraged patients and family participation in the acute care experience to promote safety. The medical oncology patient in many cases on admission is identified as ‘moderate’ risk for fall. It is during the course of treatment and an extended length of stay that deconditioning and treatment side effects result in a fall. This patient population often overestimates their abilities and functional status. Engagement with patients and families during the admission process will hopefully communicate the need for a collaborative effort for fall prevention during the hospitalisation. Although this project is limited in data, integrating patients and families into care planning may have a significant impact in reducing falls in the ‘moderate’ risk patient. Additional studies including a multivariate analysis are needed to determine whether supporting evidence links fall reduction to the presence and use of a patient and family agreement.

GAS5 alleviates cisplatin drug resistance in oral squamous cell carcinoma by sponging miR-196a.

The long non-coding RNA Growth-arrest-specific transcript 5 (GAS5) has been extensively linked with the ability of cancer cells to resist chemotherapeutic interventions. This prospective study aimed to investigate the role of GAS5 in oral squamous cell carcinoma (OSCC), which has been poorly characterized to date. GAS5 and miR-196a expression levels were detected by quantitative real-time PCR analysis. Cisplatin (DDP) sensitivity and apoptosis levels were determined using Cell Counting Kit 8 and flow cytometry, respectively. Luciferase reporter and RNA immunoprecipitation assays were performed to confirm target miRNAs of GAS5. We found that GAS5 was expressed at low levels in DDP-resistant OSCC cell lines and tissues, and that GAS5 levels were intricately linked to the survival rates of OSCC patients. GAS5 overexpression led to the recovery of DDP sensitivity in CAL27/DDP cells. Additionally, in both DDP-resistant and -sensitive lines, GAS5 showed a cytoplasmic distribution and downregulated miR-196a in OSCC tissues. Exogenous transfection of miR-196a alleviated the effects of GAS5 on DDP sensitivity, confirming this as the mechanism of chemoresistance. These findings may provide new targets for the treatment of chemotherapy-resistant OSCC.

META-ANALYSIS DISPLAYED TRANSCRIPTOMIC SIGNATURE OF DIFFUSE LARGE B-CELL LYMPHOMA WITH SIGNIFICANT DIFFERENCES BETWEEN SUBTYPES

Lymphomas are cancers that affect the hematological system originated in the lymphatic system with an abnormal proliferation of lymphoid cells. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. This lymphoma is well characterized by the presence of B-lineage lymphoid cells with immature features with diffuse proliferation in the affected tissue. This disease usually follows an aggressive clinical course, placing patients in immediate need of chemotherapeutic treatment. DLBCL can be further classified into two molecular subtypes, center-germinative B-cell (GCB) and activated B-cell (ABC) type lymphomas. This classification indicates the different stages of maturation of the neoplastic cells, and the different pathological mechanisms associated with them. The present work aimed to compare transcriptome signature of the center-germinative B-cell (GCB) and activated B-cell (ABC). Microarray studies were selected based on predefined criteria and downloaded from the GEO database. Data acquisition, processing, meta-data construction, as well as the differentially expressed genes were performed using R studio packages. Also, significantly enriched gene sets were identified using Gene Set Enrichment Analysis (GSEA). Gene expression and survival analysis from TCGA database were performed using the UALCAN and GEPIA webservers. From a total of 7,854 differentially expressed genes, 465 significantly down-regulated genes and 403 up-regulated genes in GCB subtype when compared to ABC subtype. Among these DEGs, in the GCB versus ABC comparison, the genes with the highest expression level were SPIN3 (FC: 1.12E+20), ZNF791 (FC: 9.43E+19) and TSPAN3 (FC: 9.18E+19), while the significant DEGs with the lowest expression level were KMT2C (FC: -3.09E+20), RIOX2 (FC: -1.49E+20) and ABHD11 (FC: -6.96E+19). Interestingly, only two genes had their expression levels significantly correlated to the DLBCL patient survival, the ABHD11 gene (p-value = 0.018) and MORF4L2 (p-value = 0.029). ABHD11 gene at low-medium level and MORF4L2 gene at high expression level significantly decrease the survival of patients. the meta-data generated from this study suggests that patients with diffuse large B-cell lymphoma pattern molecularly relevant gene expression in aspects related to cell proliferation, cell metabolism, and insensitivity to inhibitory signals to tumor progression as presented by the type of activated B cells. The findings converge the significant modulation of germinal center cells to gene expression regulation processes. Further experiments are still required, the transcriptional and translational activity, as well as cellular activity, appear to be decreased in the GCB type. Our findings, such as the one regarding the ABHD11 gene, which at low levels in GCB type, confers decreased survival rate in lymphoma patients. Therefore, this work brings important information for the understanding of the pathological process of the disease and its subtypes, and such biomarkers may serve as potential candidates for the development of molecular diagnostic methods and new therapeutic strategies for DLBCL subgroups.

Antibody-Functionalized Nanoformulations for Targeted Therapy of Colorectal Cancer: A Systematic Review

The failure of chemotherapeutic treatment in colorectal cancer (CRC), the second most mortal cancer worldwide, is associated with several drug limitations, such as non-selective distribution, short half-life, and development of multiple resistances. One of the most promising strategies in CRC therapy is the development of delivery systems based on nanomaterials that can transport antitumor agents to the tumor site more efficiently, increasing accumulation within the tumor and thus the antitumor effect. In addition to taking advantage of the increased permeability and retention effect (EPR) of solid tumors, these nanoformulations can be conjugated with monoclonal antibodies that recognize molecular markers that are specifically over-expressed on CRC cells. Active targeting of nanoformulations reduces the adverse effects associated with the cytotoxic activity of drugs in healthy tissues, which will be of interest for improving the quality of life of cancer patients in the future. This review focuses on in vitro and in vivo studies of drug delivery nanoformulations functionalized with monoclonal antibodies for targeted therapy of CRC.