scholarly journals Small GTPase Rab3B: biological properties and possible role in carcinogenesis

2019 ◽  
Vol 5 (4) ◽  
pp. 78-85
Author(s):  
A. A. Budko ◽  
P. A. Khesina ◽  
L. M. Diakov ◽  
N. L. Lazarevich

Proteins of the superfamily of small guanosine triphosphate hydrolase (GTPase) perform various functions: from the control of cell proliferation to the regulation of vesicular transport. The superfamily of small GTPase Ras includes more than 150 proteins, devided to 5 major families (Arf, Ran, Rho, Ras and Rab), and plays an important role in carcinogenesis. Compared to the other families, the Rab family was investigated by relatively small number studies, which does not equally reflect their role in malignant transformation processes. In our review  we have focused on both the subfamily Rab3 and its poorly investigated member Rab3B. Recent findings allow to consider Rab3B not only  as a promising diagnostic or prognostic marker for several types of neoplasms, but also is a potential target for antitumor therapy. Our analysis of publicly available transcriptional databases revealed that kidney, lung and liver cancer patients with low Rab3B gene expression demonstrate a better overall five-year survival.

2012 ◽  
Vol 5 ◽  
pp. CGM.S8821 ◽  
Author(s):  
Mohammad A. Tabatabai ◽  
Wayne M. Eby ◽  
Nadim Nimeh ◽  
Karan P. Singh

This paper analyzes the survival of breast cancer patients, exploring the role of a metastasis variable in combination with clinical and gene expression variables. We use the hypertabastic model in a detailed analysis of 295 breast cancer patients from the Netherlands Cancer Institute given in. 1 In comparison to Cox regression the increase in accuracy is complemented by the ability to analyze the time course of the disease progression using the explicitly described hazard and survival curves. We also demonstrate the ability to compute deciles for survival and probability of survival to a given time. Our primary concern in this article is the introduction of a variable representing the existence of metastasis and the effects on the other clinical and gene expression variables. In addition to making a quantitative assessment of the impact of metastasis on the prospects for survival, we are able to look at its interactions with the other prognostic variables. The estrogen receptor status increase in importance, while the significance of the gene expression variables used in the combined model diminishes. When considering only the subgroup of patients who experienced metastasis, the covariates in the model are only the clinical variables for estrogen receptor status and tumor grade.


2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Li-Hsin Chen ◽  
Kun-Ling Tsai ◽  
Yi-Wei Chen ◽  
Cheng-Chia Yu ◽  
Kuo-Wei Chang ◽  
...  

MicroRNAs have emerged as important regulators of cell proliferation, development, cancer formation, stress responses, cell death, and other physiological conditions in the past decade. On the other hand, head and neck cancer is one of the top ten most common cancers worldwide. Recent advances in microRNAs have revealed their prominent role in regulating gene expression and provided new aspects of applications in diagnosis, prognosis, and therapeutic strategies in head and neck squamous carcinoma. In the present paper, we focus on microRNAs showing significant differences between normal and tumor cells or between cells with differential ability of metastasis. We also emphasize specific microRNAs that could modulate tumor cell properties, such as apoptosis, metastasis, and proliferation. These microRNAs possess the potential to be applied on clinical therapy in the future.


Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1765
Author(s):  
Faegheh Ghanbari ◽  
Sylvie Mader ◽  
Anie Philip

Breast cancer is the 2nd leading cause of cancer-related death among women. Increased risk of breast cancer has been associated with high dietary cholesterol intake. However, the underlying mechanisms are not known. The nuclear receptor, estrogen-related receptor alpha (ERRα), plays an important role in breast cancer cell metabolism, and its overexpression has been linked to poor survival. Here we identified cholesterol as an endogenous ligand of ERRα by purification from human pregnancy serum using a GST-ERRα affinity column and liquid chromatography-tandem mass spectrometry (LC-MS/MS). We show that cholesterol interacts with ERRα and induces its transcriptional activity in estrogen receptor positive (ER+) and triple negative breast cancer (TNBC) cells. In addition, we show that cholesterol enhances ERRα-PGC-1α interaction, induces ERRα expression itself, augments several metabolic target genes of ERRα, and increases cell proliferation and migration in both ER+ and TNBC cells. Furthermore, the stimulatory effect of cholesterol on metabolic gene expression, cell proliferation, and migration requires the ERRα pathway. These findings provide a mechanistic explanation for the increased breast cancer risk associated with high dietary cholesterol and possibly the pro-survival effect of statins in breast cancer patients, highlighting the clinical relevance of lowering cholesterol levels in breast cancer patients overexpressing ERRα.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shiro Iuchi ◽  
Joao A. Paulo

AbstractRNA plays a central role in macromolecule biogenesis for various pathways, such as gene expression, ribosome biogenesis, and chromatin remodeling. However, RNA must be converted from its nascent to functional forms for that role. Here, we describe a large RNA metabolic network (RNAmetasome network) for macromolecule biogenesis in human cells. In HEK293T, the network consists of proteins responsible for gene expression, splicing, ribosome biogenesis, chromatin remodeling, and cell cycle. Reciprocal immunoprecipitations show that MKI67, GNL2, MDN1, and ELMSAN1 are core proteins of the network, and knockdown of either MKI67 or GNL2 affects the state of the other protein, MDN1, and some other network members. Furthermore, GNL2 knockdown retards cell proliferation. Several proteins of the RNAmetasome network are diminished in Hela.cl1, and this diminishment is associated with low expression of MDN1 and elevated MKI67 degradation. These results together suggest that the RNAmetasome network is present in human cells and associated with proliferation, and that MKI67, GNL2, and MDN1 play an important role in organizing the RNAmetasome network.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10590-10590
Author(s):  
A. Barrier ◽  
P. Boelle ◽  
D. Brault ◽  
S. Houry ◽  
F. Lacaine ◽  
...  

10590 Background and Aims: Postoperative chemotherapy has become part of the standard treatment for stage III colon cancer patients. Since approximately half of patients are cured by surgery alone, adjuvant chemotherapy should not be used in all patients. This study aimed to assess the possibility to use microarray-based gene expression profiles to predict the prognosis of stage III colon cancer patients. Material and Methods: Forty-two patients operated on for a stage III colon cancer were included in this study. Twenty-one patients have received an adjuvant chemotherapy, while the other 21 have received no treatment. Twenty patients have developed a liver metastasis, while the other 22 have remained disease-free for at least 5 years. Tumor mRNA samples were profiled using the Affymetrix HGU133A GeneChip. Two analyses were performed: one with the 42 patients, the other with the 21 patients who did not receive any adjuvant chemotherapy. For each analysis, patients were repeatedly and randomly divided into 10,000 training (TS) and validation sets (VS) of 10 different sizes. For each TS/VS split, a 30-gene prognosis predictor (PP), identified on the TS, was used to predict the prognosis of VS patients. Performances of a 15-gene PP and a 34-gene PP, proposed by another research team, were also assessed on the same TS and VS. Results: First analysis (42 patients). The 10,000 30-gene PP yielded the following average prognosis prediction performance measures: 73.8% accuracy, 74.6% sensitivity, and 73.0% specificity. Improvements in prognosis prediction were observed with increasing TS size. A total of 4,446 genes were included in the 10,000 PP. The 15-gene PP yielded a 69.7% accuracy; the 34-gene PP yielded a 71.2% accuracy. Second analysis (21 patients). The 10,000 30-gene PP yielded the following average prognosis prediction performance measures: 77.7% accuracy, 75.8% sensitivity, and 79.9% specificity. Improvements in prognosis prediction were observed with increasing TS size. A total of 5,478 genes were included in the 10,000 PP. The 15-gene PP yielded a 78.5% accuracy; the 34-gene PP yielded a 81.9% accuracy. Conclusion: Microarray gene expression profiling is able to predict the prognosis of stage III colon cancer patients and, thus, might be used for an appropriate use of adjuvant chemotherapy. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13676-e13676
Author(s):  
Elena Poddubskaya ◽  
Maxim Sorokin ◽  
Andrew Garazha ◽  
Alex Glusker ◽  
Alexey Moisseev ◽  
...  

e13676 Background: Analysis of mutation profiles in cancer patients does not provide clinical benefits in 80-90% of cases in the US (Marquart et al., 2018). Gene expression analysis potentially complements standard detection of clinically relevant mutations. Methods: 239 adult late-stage cancer patients. RNA gene expression sequencing completed on solid tumor samples using FFPE blocks. Patient mRNA profiles were analyzed using Oncobox bioinformatics, prioritizing target drugs according to their personalized predicted efficacy. Summary reports were provided to oncologists and resulting treatment selection and outcomes were assessed. Results: As of February 2020, feedback was received from participating doctors for 224 patients; 34 patients died before therapy prescription, 52 patients received treatment other than targeted therapy (chemo, surgery, radiation, or palliative care), 75 patients received at least one targeted therapy (single or combination therapy) predicted to be effective based on Oncobox analysis (“RNAseq cohort”). 63 patients received chemo or other drug therapy predicted to be potentially ineffective from Oncobox analysis (“other cohort”). Therapeutic response was obtained on 46 patients with biopsies collected no longer than 6 months prior to analysis who had no further surgery (30 in the RNAseq cohort and 16 in the other cohort). 63% of the RNAseq cohort obtained either partial response or stable disease using Oncobox guided therapies, compared to 44% of the other cohort (19% increase of disease control). The RNAseq cohort had higher mean prior therapies (1.3) compared to the other cohort (0.8) indicating more advanced disease. The similarly designed WINTHER trial reported ~8% increase of disease control using gene expression-guided vs mutation-guided therapeutics in a cohort of advanced cancer patients averaging three prior therapies (Rodon et al., 2019). Conclusions: Collectively these data suggest that gene expression profiling provides a more clinically relevant therapeutic match, and better response rates, than mutation guided therapeutic treatments. This potentially results in improved clinical outcomes for cancer patients. Clinical trial information: NCT03724097.


Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A104-A104
Author(s):  
Jandeleit‐Dahm K ◽  
Wu Ll ◽  
Johnson Rj ◽  
Cox Aj ◽  
Kelly Dj ◽  
...  

2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.


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