Advances in cancer biology - metastasis最新文献

Because of emerging opportunities for cancer immunotherapy, the capacity to suppress the immune system in order to cure and eradicate cancer is currently a topic of intense study. When the bone marrow microenvironment is exposed to immune suppression, leukemia cells result in the immune system's inability to eliminate malignant cells. To get a better understanding of the immunological possibilities associated with leukemia, clinical trials have explored immunotherapy techniques such as T cell activators, checkpoint inhibitors, antibody medicinal molecules, and cell treatments. One of the most important immune pathways is the programmed cell death 1 (PD1) protein. PD1 is expressed on the surface of T-cells and controls immune reactions. CD274, B7–H1, or PD-L1 are expressed by cells of the myeloid lineage, including macrophages, dendritic cells, effector CD8⁺ T cells, tumor cells, and tumor-associated suppressor cells. Expression of PD-L1 molecule in cancer has been associated to worse prognosis and resistance to anti-cancer therapies in several malignancies. In this review, we update on the expression of PD-1 molecule in malignant hematological tumor cells and describe these molecules which inhibit the immune response to cancer cells. We provide an overview of the current scientific advancements, the significance of immunotherapy strategies and highlighting the potential for further development in targeting this specific molecule. Additionally, ascertaining if PD-1/PD-L1 can be a reliable prognostic for blood cancer diagnosis.

Colorectal cancer is one of the most prevalent cancers worldwide. An increasing number of cases around the globe are raising concerns for life quality and survival. Various factors including genetic drivers have been extensively studied regarding the disease risk, progression, and metastasis. However, the signaling mechanisms haven't been studied extensively yet. Various therapeutic methods have been established in combating the disease, and mesenchymal stem cells have come up as a crucial cell-based therapeutic strategy. Mesenchymal stem cells have been regarded as potential targets in various cancer types due to their immune-modulatory functions. They can be isolated from many body tissues including bone marrow, peripheral blood, umbilical cord, and adipose tissue. Exosomes derived from mesenchymal stem cells have been reported to affect the expression of certain proteins associated with colorectal cancer. The current review highlights the potential of mesenchymal stem cells and their derived exosomes in treating cancer by causing cytotoxicity and apoptosis. Further, T-cell mediated modulation of exosomes helps reduce the cellular proliferation in cancer cells.

Colorectal cancer (CRC) remains a significant global health challenge, with an alarming upward trend in Asia. Early detection is crucial for improving outcomes, but there is no consensus on the optimal screening approach. Despite advances in diagnosis and therapy, CRC mortality rates remain substantial. Apoptosis and autophagy, key processes in cancer cell death, exhibit complex molecular crosstalk, particularly involving BH-3-only proteins, which present potential therapeutic targets. Recent studies suggest that manipulating these pathways could enhance cancer treatment by exploiting their regulatory networks. The B-cell lymphoma 2 (BCL-2) family proteins, central to apoptosis regulation, are implicated in CRC initiation, progression, and therapy resistance. BH3-only proteins like BIM and PUMA are linked to caspase-independent cell death, suggesting alternative pathways for CRC treatment and highlighting the potential for targeted therapies. This review provides an overview of CRC management, including the current landscape and challenges of screening programs and delves into the interplay between apoptosis and autophagy in CRC cell death. It emphasizes the critical role of BCL-2 family proteins in CRC pathogenesis and calls for future research to focus on developing non-invasive, cost-effective diagnostic biomarkers, establishing prognostic biomarker panels, and defining predictive biomarkers for existing treatments. These advancements are essential for improving screening strategies, therapeutic interventions, and ultimately, patient outcomes and quality of life.

Background

The liver and lungs are the most common sites of colorectal cancer (CRC) metastases. Their involvement can take five different clinical scenarios: lung metastases only, liver metastases only, lung metastases before liver metastases, liver metastases before lung metastases and simultaneous lung and liver metastases. Using clinical and morphological data we studied the clonal trajectory of these scenarios.

Materials and methods

A total of 465 (CRC) patients with 7952 liver and 6406 lung metastases were evaluated. Metastases clinical route was deciphered from metastases number, timing, and linear/parallel ratio (LPR)- a computerized parameter used for deducing clonal trajectories. LPR of +1 suggest pure linear dissemination and −1 pure parallel.

Results

Lung-only metastases: high percentage of metachronous disease with a long lead time and a low LPR suggest parallel dissemination. Liver-only metastases: Rare metachronous disease with a short lead time, and a high LPR suggest linear spread. Lung-before-liver metastases: rare solitary metastasis, a median gap of 21 months between the organs, high lung and low liver LPRs suggest linear progression to the lungs and parallel dissemination to the liver. Liver-before-lung metastases: low liver and high lung LPRs and a median gap of 16.5 months between the organs suggest parallel dissemination to the liver and linear spread from the liver to the lungs. Simultaneous liver and lung metastases: rare solitary metastasis and similar and high LPRs suggest simultaneous linear progression to both organs.

Conclusions

CRC metastases have different dissemination trajectories in different clinical scenarios. This information can potentially impact on clinical management.

Background

In our study, we examined the 5-year survival of OSCC patients with HPV positive or negative status along with p16 protein expression.

Method

A total of 72 biopsy tissue specimens from histologically confirmed oral squamous cell carcinoma (OSCC) patients were collected. HPV detection and genotyping were performed using HPV E6/E7 and HPV- type-specific multiplex primer for nested-PCR. Immunohistochemistry evaluation of pl6 was conducted. SPSS statistical software (ver 20) was used for data analysis.

Results

High risk-HPV (hr-HPV) DNA positivity was found in 27.7% (n = 20) of OSCC patients. Stage III OSCC patients were 7.80 times more likely to survive 5 years than stage IV patients (OR-7.80 CI-95%; P-0.03). Among the hr-HPV positive OSCC patients, we found that the median survival time for the 1st year (95%), 3 years (78.5%), and 5 years (38.5%) was significantly higher than that of the hr-HPV negative [1st year (78.6%), 3 years (45.2%) and 5 years (38.5%)] OSCC patients (P-0.03 The survival of male patients with hr-HPV positive OSCC is 9.75 times greater than the survival of patients with HPV negative OSCC (OR-9.75; CI-95%; P-0.05). The p16 expression level (low to overexpression) group and negative P16 expression group of OSCC patients have not demonstrated a significant association with 5-year survival.

Conclusion

We conclude that in OSCC cases of North-East India, the presence of hr-HPV in OSCC cases could be a good predictor of 5-year survival rate. Expression of p16 does not appear to have any significant association with 5-year survival.

A significant obstacle to treating cancer is multidrug resistance (MDR), which is the capacity of cancerous cells to develop resistance to both traditional and cutting-edge chemotherapeutic treatments. Following the initial discovery that cellular pumps reliant on ATP were the root of chemotherapy resistance, more research has revealed the involvement of additional mechanisms, including increased drug metabolism, reduced drug entry, and compromised apoptotic pathways. Numerous projects have focused on MDR, and innumerable research has been conducted to better understand MDR and develop methods to mitigate its consequences. Multidrug resistance (MDR) is a key challenge in treating cancer. 90% of cancer-related fatalities are brought on by tumor metastasis and recurrence, which is possible with MDR. Drug resistance in cancerous cells is influenced by diverse internal and extrinsic variables, including genetic and epigenetic changes, drug efflux systems, DNA repair mechanisms, apoptosis, and autophagy. In this review paper, we list the potential hazards associated with cancer therapy in general, primarily multidrug resistance developing a theory for colorectal cancer in particular. We discussed the unique instance of multidrug resistance in colorectal cancer in malignancies generally and 5-fluorouracil, curcumin, and lipids as viable therapy options for the condition. The use of nanotechnology (mainly nanoparticles) has facilitated better in vitro as well as in vivo efficacy during preclinical phases, summarized below, allowing for a more thorough investigation of colorectal cancers and pancreatic carcinomas with their translation to following clinical trials.

Small cell lung cancer (SCLC) is characterized by early metastatic dissemination and rapid emergence of chemoresistance resulting in a very dismal prognosis. SCLC tumors are characterized by nearly universal biallelic inactivation of TP53 and RB1 genes and are classified into four molecular subtypes based on the expression of lineage-specific transcription factors. The integration of information encoded by the coding and non-coding genome has significantly improved our understanding of the contribution of various non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in the pathogenesis of SCLC. This has led to the concept of competing endogenous RNAs (ceRNAs) where the presence of the same miRNA response elements in one or more coding and ncRNAs may result in them competing for the same miRNA. Several studies have looked at the role of lncRNAs and circRNAs as ceRNAs by constructing ceRNA regulatory networks (ceRNETs). In this review, we discuss the role of ceRNETs in regulating various cancer hallmarks, including cell proliferation, invasion, migration, EMT, apoptosis, and chemoresistance of SCLC cells. We also discuss the potential of lncRNAs and circRNAs as biomarkers for diagnosis, prognosis, and predicting chemoresistance of SCLC.

Following the declaration of COVID-19 as a pandemic in February 2020, one of the most important public health impacts was the decrease in demand for screening mammography, with a consequent impact on the early diagnosis of breast cancer. Therefore, the aim of this study was to compare the initial clinical staging of women with breast cancer in the pre-pandemic and pandemic periods at a reference cancer hospital in southern Brazil. We performed a retrospective cross-sectional study with a database of surgical procedures on the female breast, comparing the years 2019 and 2020. A total of 1733 surgical procedures for diagnostic and curative purposes were evaluated. Among these patients, 491 (49.2 %) were diagnosed with breast cancer in 2019 and 335 (45.5 %) in 2020. We excluded 907 patients due to benign diagnoses, carcinoma in situ, recurrence, presence of metastases, missing data, and other findings. When comparing 2019 and 2020, we found no significant difference in clinical staging or tumor phenotype. The median time in days between mammography and first treatment was also similar in both years. However, we observed a higher frequency of lobular histologies and neoadjuvant therapy as first treatment choice in the pandemic year. In conclusion, there was no significant difference in clinical staging between women diagnosed with breast cancer before and during the pandemic.

Background

Triple-negative breast cancer (TNBC) is a genetically and morphologically heterogeneous group with aggressive biological behaviour and specific response to therapy. It accounts for 15–20% of all breast cancers and has two subtypes: basal like and non-basal like. MicroRNAs, which regulate gene expression, play a role in TNBC, potentially acting as oncogenes or tumor suppressors.

Objective

Identification of differentially expressed miRNA of potential clinical relevance in TNBC patients.

Methods

In this study, miRNA profiling by microarray was performed in tumor tissues of 86 patients with TNBC and 12 healthy individual. Further, the clinical relevance of differentially expressed miRNA was evaluated.

Results

In TNBC, 2410 differentially expressed miRNAs were identified and of them 98% were down-regulated, while only 2% were up-regulated. Up regulation of 55 miRNA was observed which target 16 genes. Top 5 genes identified were CDNK1A, p53, TGFB1, APC and HRAS. Of 7 ranking methods, 5 ranking method identified TGFB1 as most significant hub gene. Up regulated miRNA expression then compared between patients who undergone remission and patients who developed disease relapse and only miR-4532 was found upregulated in patients with disease relapse. Further, up regulation of miR-4532 showed a trend of reduced disease-free and overall survival. The down-regulated miRNAs target 238 genes involved in TNBC pathogenesis and progression. The top five hub genes were CDH1, PTEN, MYC, STAT3, and VEGFA. Of 7 ranking methods, 5 ranking method identified STAT3 as most significant hub gene. This study identified 32 novel miRNAs playing a tumor suppressive role and found down-regulated in TNBC. Among these two novel miRNAs, miR-1273g-3p and miR-4459 were found expressed in all TNBC patients. Patients with down-regulation of these miRNAs showed significantly reduced disease-free and overall survival. The ROC curve analysis indicated that miR-4532 and miR-4459 were successful in distinguishing TNBC patients from healthy controls.

Conclusion

Our data identified that up regulation of miR-4532 and down regulation of miR-4459 might have the potential to be used as both diagnostic and prognostic biomarker in TNBC.