Label-free electrochemical cancer cell detection leveraging hemoglobin-encapsulated silver nanoclusters and Cu-MOF nanohybrids on a graphene-assisted dual-modal probe.

Breast cancer detection at an early stage significantly increases the chances of successful treatment and survival. This study presents an electrochemical biosensor for detecting breast cancer cells, utilizing silver nanoclusters encapsulated by hemoglobin and Cu (II)-porphyrin-metal organic framework (BioMOF) in a graphene-incorporated nanohybrid probe. This Hb-AgNCs@MOF-G probe demonstrates high electrochemical activity, superior dispersity, porosity, and a large surface area for effective functionalization. Using a green ultrasonic-assisted stirring method, we fabricate ultra-small 5 nm particles that readily immobilize on a glassy carbon electrode, generating a detection signal when interacting with ferricyanide/ferrocyanide redox probes. The resulting immunosensor detects as few as 2 cells/mL using Electrochemical Impedance Spectroscopy (EIS) "signal on" and 16 cells/mL via Square Wave Voltammetry (SWV) "signal off", within a broad range of cell concentrations (102-5 × 104 cells/mL). Our designed sensor shows improved selectivity (5- to 16-fold) and robust detection in human blood with a recovery efficiency between 94.8-106% (EIS method) and 95.4-111% (SWV method). This sensor could streamline early cancer diagnosis and monitor patient treatment without requiring labelling or signal amplification. As a pioneering endeavor, we've utilized integrated porous MOFs with Hb-encapsulated silver nanoclusters in cancer detection, where these components collectively enhance the overall functionality.

Differential Expression of miR-20a and miR-145 in Colorectal Tumors as Potential Location-specific miRNAs.

BACKGROUND: MicroRNAs (miRNAs), as tissue specific regulators of gene transcription, may be served as biomarkers for Colorectal Cancer (CRC). OBJECTIVE: This study aimed to investigate the potential role of the cancer-related hsa-miRNAs as biomarkers in Colon Cancer (CC) and Rectal Cancer (RC). METHODS: A total of 148 CRC samples (74 rectum and 74 colon) and 74 adjacent normal tissues were collected to examine the differential expression of selected ten hsa-miRNAs using quantitative Reverse Transcriptase PCR (qRT-PCR). RESULTS: The significantly elevated levels of miR-21, miR-133b, miR-18a, miR-20a, and miR-135b, and decreased levels of miR-34a, miR-200c, miR-145, and let-7g were detected in colorectal tumors compared to the healthy tissues (P<0.05). Hsa-miR-20a was significantly overexpressed in rectum compared to colon (p =0.028) from a cut-off value of 3.15 with a sensitivity of 66% and a specificity of 60% and an AUC value of 0.962. Also, hsa-miR-145 was significantly overexpressed in colon compared to the rectum (p =0.02) from a cut-off value of 3.9 with a sensitivity of 55% and a specificity of 61% and an AUC value of 0.91. CONCLUSION: In conclusion, hsa-miR-20a and hsa-miR-145, as potential tissue-specific biomarkers for distinguishing RC and CC, improve realizing the molecular differences between these local tumors.

MicroRNA Expression Levels and Histopathological Features of Colorectal Cancer.

INTRODUCTION: Non-coding RNAs have opened a new window in cancer biology. MicroRNAs (miRNAs), as a family of non-coding RNAs, play an important role in the gene regulation. The aberrant expression of these small molecules has been documented to involve in colorectal cancer (CRC) pathogenesis. This study aimed to examine the expression of miRNAs in CRC and to correlate their expression levels with histological markers (Ki-67 and CD34). MATERIALS AND METHODS: Tumor tissues and matched normal adjacent tissues were collected from 36 patients with newly diagnosed CRC. Immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. A polyadenylation SYBER Green quantitative real-time PCR technique was used to quantify the expression of a panel of five CRC-related miRNAs (hsa-miR-21, 31, 20a, 133b, and 145). Histopathological (H) scores and miRNA expression levels were correlated with clinicopathological features including the degree of differentiation, staging, and lymphovascular invasion. RESULTS: Our results showed the significant difference between the two groups for the expression level of hsa-miR-21, hsa-miR-31, hsa-miR-145, and miR-20a (P < 0.001), but not for hsa-miR-133b (P = 0.57). Further analysis revealed an inverse significant correlation between hsa-miR-145 and Ki-67 (r = - 0.942, P < 0.001). While a positive correlation was observed between hsa-miR-21 and Ki-67 (r = 0.920, P < 0.001), and hsa-miR-21 and CD34 (r = 0.981, P < 0.001). Also, a positive correlation between hsa-miR-31 and Ki-67 (r = 0.913, P < 0.001), hsa-miR-31 and CD34 (r = 0.798, P < 0.05), hsa-miR-20a and Ki-67 (r = 0.871, P < 0.001), and hsa-miR-20a and CD34 (r = 0.890, P < 0.001) was found. CONCLUSION: Dysregulation of miRNAs and correlation with molecular histopathology indicate a biological role for miRNAs in various cellular processes including cell proliferation and angiogenesis in CRC development. On the other hand, the pattern of miRNA expression and its correlation with histological markers are potentially valuable to apply as diagnostic biomarkers for CRC.

Clinical significance of NDRG3 in patients with breast cancer.

AIM: The expression level of NDRG3 gene is investigated among breast cancer (BC) patients. METHODS: Real-time quantitative PCR was performed. RESULTS:  NDRG3 was downregulated in BC patients particularly in advanced stage of the disease. HER2 status was significantly correlated with the expression of NDRG3. Also, triple-negative BC patients showed low levels of NDRG3 expression in comparison to other subtypes. Lastly, the expression of NDRG3 had significant impact on survival, with NDRG3 downregulated patients having the worst event-free survival rate among others. CONCLUSION: We have presented that NDRG3 might be a tumor suppressor candidate. NDRG3 downregulation might be involved in the tumorigenesis and development of invasive BC in an advanced phase of the disease.

High expression of CEACAM19, a new member of carcinoembryonic antigen gene family, in patients with breast cancer.

Carcinoembryonic antigen (CEA) family members play important roles in malignancies and are introduced as biomarkers in different types of cancers. Among them CEACAM19 (CEAL1) gene, a new member of the CEA family, remains to be fully elucidated. The aim of this study was investigating the mRNA expression level of CEACAM19 in tumor samples of breast cancer patients compared to breast tissue of normal individuals. We evaluated the expression level of this gene in 75 breast tumors by using real-time quantitative PCR. Also, we studied the correlation between CEACAM19 expression and clinicopathological features and hormone receptors status, including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 of patients. Out of the enrolled patients, six of them (7.9%) showed low expression, ten (13.2%) showed normal expression and 59 (77.6%) showed high expression of CEACAM19. There was a significant correlation between high expression of CEACAM19 gene in tumor samples compared to normal tissues (P = 0.039). No significant correlation was seen between clinicopathological factors and disease-free survival with mRNA levels of CEACAM19 in tumor samples, while the difference between the expression of CEACAM19 in ER/PR-positive and ER/PR-negative breast cancer patients was statistically significant (P = 0.046). In conclusion, CEACAM19 showed high expression in tumor samples compared to normal mammary tissue. In addition, CEACAM19 may represent as a novel therapeutic target in certain subgroups of breast cancer patients such as ER/PR-negative. Critical roles of CEA proteins in tumor progression may nominate them as robust potential targets for therapeutic intervention in near future.

Iranian women's attitude toward prophylactic mastectomy for breast cancer.

AIM: Breast cancer is the most common cancer among women worldwide. Science has already proved that some breast cancer genes are inherited from parents. It is generally believed that the probability of cancer diagnosis in carriers of those genes is considerably higher than the normal population. It is in the same direction that modern medicine has introduced prophylactic mastectomy - one of the key preventive methods which is the focus of the present research. Nevertheless, whether women that have been diagnosed with breast cancer would take this approach depends on their local culture and their set of beliefs. In this regard, the present research was meant to evaluate the acceptability rate of prophylactic mastectomy among women in Iran after they are informed of the positive genetic test results. METHODS: Six hundred and five healthy women, who had no history of breast cancer, were selected by nonprobability sampling method. A predesigned questionnaire was filled out by the interviewer. RESULTS: Results showed that about 15% of respondents were willing to pick the prophylactic mastectomy in case they are identified as carriers of breast cancer genes. Twenty-two percent of participants with positive family history was agreed with prophylactic mastectomy while in the negative family history group it was about 14%. CONCLUSION: Preventive mastectomy has a higher rate of acceptability among women who have had a family history of breast cancer. Therefore, it may be concluded that raising public awareness about the advantages of prophylactic mastectomy could help better address breast cancer in Iran.

Iranian Breast Cancer Bio-Bank: the activity and challenging issues.

The information gained from the Human Genome Project has facilitated molecular as well as cellular studies not only to find the origins of Breast Cancer (BC), but also to create novel, and effective treatments. In order to provide an infrastructure for local and international research in this area, Iranian Center for Breast Cancer (ICBC) has established a Bio-Bank (BB) for BC. This article describes the aim, structure, and activities in general, and the challenging issues confronting the bank as a model for the establishment of Bio-Banks in developing countries in particular. The methods employed by the Bank could be explained in the following categories: Blood and Tissue sampling, Preparation and Banking of collected Samples, Clinical and Histopathology data collection, Collaboration Protocol, Challenging issues, and the programs to confront the problems. During the five-year activity of the bank, 110 families were enrolled for genetic counseling, from whom 600 biologic samples were obtained, including 387 blood samples and 213 tissue samples. Of 387 blood samples, 317 (82%) were found to belong to the BC patients and the remaining 70 (18%) belonged to their available relatives. The number of samples increased over the study period partly as a result of the programs designed to confront the problems. During the study period, there were some finished research studies using the samples of BB, and many other studies which are still ongoing. ICBC-BB is a model of biologic sample banking which provides a significant number of biological samples for local and international collaborative research projects regarding molecular and cellular aspects of BC. In establishing the ICBC-BB we have experienced problems and challenges, some general and some local. Some were expected and others not, but we have identified solutions.

Survey of the level of anti-HBs antibody titer in vaccinated Iranian general dentists.

Hepatitis B is an infectious disease to which dentists are susceptible. The main aim of this study was to determine the level of antibody titer and immunity in vaccinated Iranian general dentists. A total of 861 general dentists were invited to participate in this study; 598 persons who could recall their history of vaccination and consented to have blood samples taken were recruited. Demographic and work-related data were recorded, and anti-Hepatitis B surface antigen (anti-HBs-Ag) evaluations were measured using the enzyme-linked immunosorbent assay (ELISA). Of the 598 participants, 35 (5.9%) were nonimmune (anti-HBs <10 IU/l), 101 (16.9%) were relatively immune (anti-HBs = 10-99 IU/l), and 462 (77.3%) were completely immune (anti-HBs > or =100 IU/l). Only 218 (36.5%) of the dentists knew their HBs antibody titer. Fourteen (2.3%) persons reported receiving one dose and 65 (10.9%) had received two doses. The number of those who had received the three recommended doses totaled 519 (86.8%), 491 (82.1%) of them receiving their vaccine on schedule. Age, city, pack-years of smoking, years of smoking, and the interval between the last vaccination and the commencement of the study had a significant relationship to the antibody titer level, whereas sex, marital status, place of practice, smoking, and vaccination schedule were not related. Only 36.5% of the general dentists had checked their antibody titer. We, therefore, recommend that dentists, as a potential high-risk group, should know their level of anti-HBs antibody titer so that those who require revaccination can get treatment.