Basic and Clinical Cancer Research
Volume:14 Issue: 4, Autumn 2022

Inositol-requiring enzyme 1 (IRE1), an endoplasmic reticulum (ER) transmembrane protein with both kinase and endoribonuclease activities, plays an essential role during ER stress and its subsequent unfolded protein response (UPR). Recent evidence shows IRE1 signaling contributes to tumorigenesis and cancer progression, pointing to the therapeutic importance of this conserved arm of the UPR. Here, we employed different computational tools to design and predict short peptides with the capability of disrupting IRE1 dimerization/oligomerization, as a strategy for inhibiting its Kinase and RNase activities. A mutation-based peptide library was constructed using mCSM-PPI2 and OSPREY 3.0. The molecular interaction analyses between the designed peptides and IRE1 protein were conducted using the HADDOCK 2.2 online server, followed with molecular dynamics analysis by the GROMACS 2020 package. We then selected short peptide candidates that exhibited high affinity and best predicted physicochemical properties in complex with IRE1. Finally, online servers, such as ToxinPred and AllerTop, were used to identify the best peptide candidates that showed no significant allergenic or cytotoxic properties. These rational designed peptides with the capability of binding to IRE1 oligomerization domain can be considered as potential drug candidates for disrupting IRE1 activity in cancer and related diseases, pending for further validation by in silico and experimental studies.

When people hear about someone who has cancer, it is not uncommon for them to experience feelings of sympathy and pity. However, while these reactions are well-intentioned, they can have negative consequences for the patient. Sympathy is a feeling or emotional response characterized by compassion, understanding, and concern for the suffering or hardship experienced by another person. It involves the ability to share in the feelings of others and to genuinely care about their well-being. This article will explore the negative consequences of sympathy and pity reactions of people toward cancer patients.

Isocitrate Dehydrogenase (IDH) plays an important role in cellular metabolism. In gliomas, the mutational status of IDH1/2 genes have paramount significance, however, study from Western India is limited. Therefore, in the current study, we sought to explore the clinical impact of IDH1/2 mutations on glioma patients from Western India.

A total of 50 pre-therapeutic, histopathologically confirmed patients with astrocytoma tumors were included and IDH1/2 mutations were detected using real-time PCR. IDH1/2 mutations were correlated with clinicopathological parameters and disease outcomes. Data were evaluated by SPSS software.

 The overall incidence of IDH1/2 mutations was noted in 24% (12/50) of glioma patients. Out of 12 patients whose tumors showed IDH mutations, 83% of patients have IDH1 mutations, whereas 17% showed IDH2 mutation.  Further, in IDH1 mutations, IDH1 R132H & IDH1 R132C mutations were noted in, 80% and 20% of patients, respectively.  When correlated with clinicopathological parameters, a significant inverse correlation was found with patients' age (χ2= 9.75, r = -0.476, p=0.001) and grade of tumors (χ2=17.51, r =-0.636, p=0.0001). In Kaplan-Meier survival analysis, apart from age (Log rank=5.443, p=0.020), IDH mutation status (Log rank=3.855, p=0.050), and both, IDH mutation and low-grade glioma tumors (Log rank=6.492, p=0.039) remained significant parameters for predicting better 24 months PFS and OS of glioma patients. However, in multivariate survival analysis using the Cox Proportional Hazard Forward Stepwise Model, only a combination of low-grade glioma with the presence of IDH mutation emerged at step one as a positive significant independent prognostic factor that predict better PFS (HR=2.92, 95% CI=1.12-7.61, p=0.028)  and OS  (HR=3.0, 95% CI=1.45-6.19, p=0.003).

Based on this data, we concluded that for glioma patients, apart from patients' age, low-grade tumors with the presence of IDH mutations remained significant independent positive prognosticators and would be helpful to clinicians for better management of glioma patients.

Breast cancer (BC) is one of the main causes of death among women in Iran. Biomarkers involved in promotion and progression of disease is very important in management and control of BC outcomes. In this research, we aim to estimate the expression levels of Ezrin and Radixin, as two important factors in morphogenesis, endocytosis, exocytosis, adherence, and migration of cells, in BC patients and their relationship with pathological factors.

One hundred and thirteen BC patients were involved in this research. Relative expression of Ezrin and Radixin genes were estimated with quantitative real-time PCR. Pathological data include the histology, tumor size, grade, lymphovascular invasion and clinical TNM (Tumor, Node, and Metastasis) staging of patients were recorded based on the pathology report and their relationship with relative expression of Ezrin and Radixin were estimated.

According to result Ezrin were over expressed in tumor samples in comparison to adjacent normal tissue. There is a significant relationship between over expression of Ezrin and Radixin and grade of tumor and necrosis. Also there is a direct relationship between relative expression of Ezrin and Radixin expression.

These data support the role of Ezrin and Radixin in the biology of breast cancer and additional studies needed that determine the Ezrin and Radixin associated with phenotype and may validate them as markers of cancer progression and as a potential target for cancer therapy.

Self-management process of diseases aims to equip patients with specific information that will improve compliance with prescribed medication and develop strategies that will help maintain quality of life.  

A set of 35-potential self-management model was developed for the breast cancer patients in 2 domains from extensive literature search. The Instrument was validated using Delphi technique, item-total correlation analysis, factor analysis, construct validity and reliability analysis. Consensus was reached on the content validation of the self-management scale with mean score > 3.5, median > 3.5, absolute value between the median and mode < 1.00.

Forty-three items emerged after content validation in 2 domains: demographic characteristics of patients, and self-management content. Construct validity for selected items of the instrument showed values above 0.5. Item-total correlation analysis resulted in 31-items of the instrument. Factor analysis revealed a multi-dimensional instrument. The internal consistency of the instrument was determined with values between 0.5 - 0.8.

Preliminary validation of the instrument showed the instrument to be valid but the internal consistency needs to be evaluated further with larger population size. The self-management scale revealed level of self-management among the breast cancer patients. This instrument should form a reliable tool for evaluating self-management in breast cancer patients in Nigeria.

Gastric cancer (GC) is the fifth most prevalent cancer and the fourth in terms of cancer-related death worldwide. The GC is the most commonly diagnosed and the most important cause of cancer-related death in Iranian. Due to the heavy burden of stomach cancer in Iran, we aimed to review all articles that have been conducted on the Incidence, Prognostic Factors, and survival of Gastric Cancer in Iran and compare them with the global situation. We surveyed google scholar, Pub Med, Scopus, Web of Science (ISI), and Science Direct databases using the keywords of Gastric Cancer, Stomach Cancer, Gastric Neoplasm, Stomach Neoplasm, and Iran and obtained English language articles. After a two-step screening of articles, 52 out of 202 remained eligible for our study (related to Incidence, Prognostic Factors, and survival of stomach Cancer in Iran). We found that although Iran is one of the high-burden countries for GC, the incidence rate, and mortality rate are very different in different provinces (up to a six-fold and thirty-fold difference in mortality rate and incidence rate have been reported respectively in reviewed articles between Northern and Southern Iran). Considering that the initial stage is one of the most important and perhaps the most important prognostic factors, through upper endoscopy screening, the disease can be diagnosed in earlier stages and the survival of patients can be improved. We recommend the Ministry of Health prioritize people according to their combination of risk factors (especially geographical region) and make a national cost-effective screening algorithm for Iran.