Expression and Functional Analysis of Immuno-Micro-RNAs mir-146a and mir-326 in Colorectal Cancer.

Micro-RNAs (miRNAs) are non-coding RNAs with importance in the development of cancer. They are involved in both tumor development and immune processes in tumors. The present study aims to characterize the behavior of two miRNAs, the proinflammatory miR-326-5p and the anti-inflammatory miR-146a-5p, in colorectal cancer (CRC), to decipher the mechanisms that regulate their expression, and to study potential applications. Tissue levels of miR-326-5p and miR-146a-5p were determined by qrt-PCR (real-time quantitative reverse transcription polymerase chain reaction) in 45 patients with colorectal cancer in tumoral and normal adjacent tissue. Subsequent bioinformatic analysis was performed to characterize the transcriptional networks that control the expression of the two miRNAs. The biomarker potential of miRNAs was assessed. The expression of miR-325-5p and miR-146a-5p was decreased in tumors compared to normal tissue. The two miRNAs are regulated through a transcriptional network, which originates in the inflammatory and proliferative pathways and regulates a set of cellular functions related to immunity, proliferation, and differentiation. The miRNAs coordinate distinct modules in the network. There is good biomarker potential of miR-326 with an AUC (Area under the curve) of 0.827, 0.911 sensitivity (Sn), and 0.689 specificity (Sp), and of the combination miR-326-miR-146a, with an AUC of 0.845, Sn of 0.75, and Sp of 0.89. The miRNAs are downregulated in the tumor tissue. They are regulated by a transcriptional network in which they coordinate distinct modules. The structure of the network highlights possible therapeutic approaches. MiR-326 and the combination of the two miRNAs may serve as biomarkers in CRC.

Exploring miRNA Profiles in Colon Cancer: A Focus on miR101-3p, miR106a-5p, and miR326.

Early diagnosis and prognosis of cancer progression through biomarker profiling are crucial in managing colon cancer patients. Our research aimed to investigate the expression of miR-101-3p, miR-106a-5p, and miR-326 in tumor and adjacent healthy tissues of colon cancer patients and determine their potential diagnostic utility. This study included 40 patients divided into four groups according to the TNM staging classification. MiRNA expression was analyzed using qRT-PCR. The results showed that miR-101-3p, miR-106a-5p, and miR-326 are overexpressed in adjacent healthy tissues but decrease in advanced cancer stages. MiR-106a-5p and miR-326 are strongly correlated with colon cancer severity. These findings suggest that miRNA profiling could be useful for early diagnosis and prognosis in colon cancer management.

miRNA patterns in male LUSC patients - the 3-way mirror: Tissue, plasma and exosomes.

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. It is classified into two main histological groups: non-small cell lung cancer (NSCLC) and small cell lung cancer. Improving the outcome of cancer patients could be possible by enhancing the early diagnosis. In the current study, we evaluated the levels of three microRNAs - miR-21-5p, miR-155-5p, and miR-181a-5p in tumor (TT) vs adjacent normal tissue (NT), as well as their expression levels in plasma and extracellular vesicles (EVs) from plasma in lung squamous cell carcinoma (LUSC) male patients vs healthy individuals as means to identify a panel of miRNAs that could serve as novel biomarkers for the diagnosis of LUSC in male patients. Matched paired tissue samples from male LUSC (n=40) patients were used for miRNA expression analysis. MiR-21-5p and miR-155-5p in tumor tissue were overexpressed, while underexpression of miR-181a-5p was observed in LUSC TT vs NT. These results were further validated in the TCGA LUSC dataset, considering 279 male samples. These alterations of miR-21-5p, miR-181a-5p, and miR-155-5p in tumor tissue are also present in plasma and plasma extracellular vesicles in LUSC male patients. In addition, ROC curves were performed to assess the sensitivity and specificity of different combinations of these miRNAs, confirming a high diagnostic accuracy for LUSC of up to 88 % in male subjects. The expression levels in tissue samples and the abundance in plasma and plasma EVs of the three miRNAs combined - miR-21-5p, miR-155-5p and miR-181a-5p - could be considered for further studies on biomarkers for the early detection of LUSC in male subjects.

Serum Interleukins 8, 17, and 33 as Potential Biomarkers of Colon Cancer.

This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome.

MicroRNAs expression profile in chemotherapy-induced cardiotoxicity in NSCLC using a co-culture model.

Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed the potential of specific miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in lung cancer. We employed two lung adenocarcinoma cell lines (Calu6 and H1792) and ventricular normal human cardiac fibroblasts (NHCF-V) in single and co-culture experiments. Functional tests were conducted using 100 µM carboplatin and 1µM vinorelbine doses. The effects of carboplatin and vinorelbine, both individually and in combination, were evaluated at cellular and molecular levels 48h post-therapy for both mono- and co-cultures. miR-205-5p, miR-21-5p, and miR-30a-5p, modulated by anticancer treatments and influencing cardiotoxicity, were analyzed. Vinorelbine and carboplatin treatment promoted apoptosis and autophagy in lung cancer cells and cardiac fibroblasts more than in controls. Western blot analyses revealed BCL2 and p53 protein upregulation. Using qRT-PCR, we investigated the expression dynamics of miR-21-5p, miR-30c-5p, and miR-205-5p in co-cultured cardiomyocytes and lung cancer cells, revealing altered miRNA patterns from vinorelbine and carboplatin treatment. Our findings underscore the intricate relationship between chemotherapy, miRNA regulation, and cardiotoxicity, highlighting the importance of cardiac health in lung cancer treatment decisions.

Vinorelbine Alters lncRNA Expression in Association with EGFR Mutational Status and Potentiates Tumor Progression Depending on NSCLC Cell Lines' Genetic Profile.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most common type. In addition, NSCLC has a high mortality rate and an overall adverse patient outcome. Although significant improvements have been made in therapeutic options, effectiveness is still limited in late stages, so the need for a better understanding of the genomics events underlying the current therapies is crucial to aid future drug development. Vinorelbine (VRB) is an anti-mitotic chemotherapy drug (third-generation vinca alkaloid) used to treat several malignancies, including NSCLC. However, despite its widespread clinical use, very little is known about VRB-associated genomic alterations in different subtypes of NSCLC. This article is an in vitro investigation of the cytotoxic effects of VRB on three different types of NSCLC cell lines, A549, Calu-6, and H1792, with a closer focus on post-treatment genetic alterations. Based on the obtained results, VRB cytotoxicity produces modifications on a cellular level, altering biological processes such as apoptosis, autophagy, cellular motility, cellular adhesion, and cell cycle, but also at a genomic level, dysregulating the expression of some coding genes, such as EGFR, and long non-coding RNAs (lncRNAs), including CCAT1, CCAT2, GAS5, MALAT1, NEAT1, NORAD, XIST, and HOTAIR, that are implicated in the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, although extensive validation is required, these results pave the way towards a better understanding of the cellular and genomic alterations underlying the cytotoxicity of VRB.

Doxorubicin as a Potential Treatment Option in Canine Mammary Tumors.

Canine mammary tumors represent one of the leading malignant pathologies in female dogs, displaying the importance of efficient therapeutic findings, besides the golden-standard surgery, able to limit the development of the disease. Studies in human cancers demonstrated that Doxorubicin presents a good effect in different biological processes like apoptosis, autophagy, the cell cycle, cell invasion, and the epithelial-to-mesenchymal transition. This study followed the effects of Doxorubicin on two canine mammary cancer cell lines P114 and CMT-U27. Doxorubicin treatment in both cell lines shows an inhibitory effect in cell proliferation and an alteration in expression of the EMT-related genes. The obtained results provide valuable information for revealing the link between Doxorubicin, phenotypic changes, and proliferation dynamics in canine mammary tumor models.

TP53 gene implications in prostate cancer evolution: potential role in tumor classification.

Background and aims: Prostate adenocarcinoma (PRAD) is a complex disease that can be driven by alterations in both coding and noncoding genes. Recent research has identified coding and non-coding genes that are considered to play important roles in prostate cancer evolution and which may be used as biomarkers for disease diagnosis, prognosis, and treatment. TP53 is a critical hub gene in prostate cancer. Advanced studies have demonstrated the crosstalk between coding and non-coding RNAs, particularly microRNAs (miRNAs). Methods: In this study, we investigated the roundabout of TP53 and their regulatory miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) based on the TCGA data set. We validated an additional patient cohort of 28 matched samples of patients with PRAD at tissue and plasma level. Results: Therefore, using the UALCAN online database, we evaluated the expression level in PRAD of these genes revealing overexpression of TP53. qRT-PCR validation step endorsed the expression level for these genes. Additionally, we evaluated the expression level of the four key miRNAs (miR-15a-5p, miR-34a-5p, and miR-141-3p) interconnected as a network at tissue and plasma levels. Conclusions: Through these results, we demonstrated the essential function of TP53 and its associated miRNAs that play a significant role in tumor control, highlighting miRNAs' potential as future therapeutic targets and biomarkers with important implications in managing prostate cancer.

Current aspects in biobanking for personalized oncology investigations and treatments.

Background/Aim: A biobank is an organization that gathers, refines, preserves and provides access to biospecimens along with relevant clinical data that can be used in applied or clinical research. Biobanking is a critical component of the scientific foundation for personalized medicine; this implies the accessibility of high-quality human biospecimens, such as blood, tissue, and other body fluids, along with the patient clinical data that goes with them. Methods: This paper summarizes the function of biobanks in oncology and the requirements for biobank development in translational and clinical research. Results: Biobanks raise numerous ethical issues that government agencies address by enacting particular laws. To develop personalized medicine, biobanks are crucial, given that the availability of an extensive collection of patient samples with thoroughly annotated clinical and pathological data is an essential necessity. Also, data related to biobanking raises complex ethical, legal, and social issues, particularly concerning the protection of donor privacy and the appropriate use of collected samples. International standards have been developed to address these issues to ensure biobanking practices' quality, safety, and integrity. Conclusions: Biobanking is vital in advancing biomedical research, supporting clinical applications, and enhancing our understanding of human health and disease. Using real-world data and biobanking can accelerate medical research, support personalized medicine initiatives, and improve patient care.

Discovering the Biological Significance and Therapeutic Potential of miR-29b-3p in Triple-Negative Breast Cancer.

The lack of estrogen or progesterone receptors and absence of HER2 amplification/overexpression in triple-negative breast cancer (TNBC) restricts therapeutic options used in clinical management. MicroRNAs (miRNAs) are small, non-coding transcripts which affect important cellular mechanisms by regulating gene expression at the post-transcriptional level. Among this class, attention was focused on miR-29b-3p with a high profile in TNBC and correlated with the overall survival rates, as TCGA data revealed. This study aims to investigate the implication of the miR-29b-3p inhibitor in TNBC cell lines by identifying a potential therapeutic transcript, improving the clinical outcomes of this disease. The experiments were performed on two TNBC cell lines (MDA-MB-231 and BT549) as in vitro models. An established dose of 50 nM was used for all functional assays performed on the miR-29b-3p inhibitor. A decreased level of miR-29b-3p determined a significant reduction in cell proliferation and colony-forming capacity. At the same time, the changes occurring at the molecular and cellular levels were highlighted. We observed that, when inhibiting the expression level of miR-29b-3p, processes such as apoptosis and autophagy were activated. Further, microarray data revealed that the miRNA expression pattern was altered after miR-29b-3p inhibition, pointing out 8 overexpressed and 11 downregulated miRNAs specific for BT549 cells and 33 upregulated and 10 downregulated miRNAs that were specific for MDA-MB-231 cells. As a common signature for both cell lines, three transcripts were observed, two downregulated, miR-29b-3p and miR-29a, and one upregulated, miR-1229-5p. According to DIANA miRPath, the main predicted targets are related to ECM (extracellular matrix) receptor interaction and TP53 signaling. An additional validation step through qRT-PCR was performed, which showed an upregulation of MCL1 and TGFB1. By inhibiting the expression level of miR-29b-3p, it was shown that complex regulatory pathways targeted this transcript in TNBC cells.

Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms.

Melanoma is the most aggressive type of skin cancer. Although different anti-melanoma treatments are available, their efficacy is still improvable, and the number of deaths continues to increase worldwide. A promising source of antitumor agents could be presented by polyphenols-natural plant-based compounds. Over the past decades, many studies have described multiple anticancer effects of polyphenols in melanoma, presenting their potential interactions with targeted molecules from different signaling pathways. However, to our knowledge, there is no comprehensive review on polyphenols-regulated mechanisms in melanoma cells available in the literature. To fulfill this gap, this article aims to summarize the current knowledge of molecular mechanisms of action regulated by polyphenols involved in melanoma initiation and progression. Here, we focus on in vitro and in vivo effects of polyphenol treatments on tumor-essential cellular pathways, such as cell proliferation, apoptosis, autophagy, inflammation, angiogenesis, and metastasis. Moreover, emerging studies regarding the well-marked role of polyphenols in the regulation of microRNAs (miRNAs), highlighting their contribution to melanoma development, are also epitomized. Finally, we hope this review will provide a firm basis for developing polyphenol-based therapeutic agents in melanoma treatment.

A Group of Tumor-Suppressive micro-RNAs Changes Expression Coordinately in Colon Cancer.

MicroRNAs (miRNAs) are molecules with a role in the post-transcriptional regulation of messenger RNA, being involved in a wide range of biological and pathological processes. In the present study, we aim to characterize the behavior of a few miRNAs with roles in the cell cycle and differentiation of colon cancer (CC) cells. The present work considers miRNAs as reflections of the complex cellular processes in which they are generated, their observed variations being used to characterize the molecular networks in which they are part and through which cell proliferation is achieved. Tumoral and adjacent normal tissue samples were obtained from 40 CC patients, and the expression of miR-29a, miR-146a, miR-215 and miR-449 were determined by qRT-PCR analysis. Subsequent bioinformatic analysis was performed to highlight the transcription factors (TFs) network that regulate the miRNAs and functionally characterizes this network. There was a significant decrease in the expression of all miRNAs in tumor tissue. All miRNAs were positively correlated with each other. The analysis of the TF network showed tightly connected functional modules related to the cell cycle and associated processes. The four miRNAs are downregulated in CC; they are strongly correlated, showing coherence within the cellular network that regulates them and highlighting possible approach strategies.

Identification of Potential microRNA Panels for Male Non-Small Cell Lung Cancer Identification Using Microarray Datasets and Bioinformatics Methods.

Background: Non-small cell lung cancer (NSCLC) is still one of the types of cancer with the highest death rates. MicroRNAs (miRNAs) play essential roles in NSCLC development. This study evaluates miRNA expression patterns and specific mechanisms in male patients with NSCLC. Methods: We report an integrated microarray analysis of miRNAs for eight matched samples of males with NSCLC compared to the study of public datasets of males with NSCLC from TCGA, followed by qRT-PCR validation. Results: For the TCGA dataset, we identified 385 overexpressed and 75 underexpressed miRNAs. Our cohort identified 54 overexpressed and 77 underexpressed miRNAs, considering a fold-change (FC) of ±1.5 and p < 0.05 as the cutoff value. The common miRNA signature consisted of eight overexpressed and nine underexpressed miRNAs. Validation was performed using qRT-PCR on the tissue samples for miR-183-3p and miR-34c-5p and on plasma samples for miR-34c-5p. We also created mRNA-miRNA regulatory networks to identify critical molecules, revealing NSCLC signaling pathways related to underexpressed and overexpressed transcripts. The genes targeted by these transcripts were correlated with overall survival. Conclusions: miRNAs and some of their target genes could play essential roles in investigating the mechanisms involved in NSCLC evolution and provide opportunities to identify potential therapeutic targets.

A role for serum cytokines and cell adhesion molecules in the non-invasive diagnosis of colorectal cancer.

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Consequently, new diagnostic and therapeutic approaches are being investigated including the serum levels of cytokines and other molecules, although the results are often inconclusive. Thus, the present study aimed to determine whether serum level of cytokines, cell adhesion molecules or matrix metalloproteinases (MMPs), alone or in combination, may contribute to the non-invasive diagnosis of CRC. The serum levels of nine cytokines [ILs; IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22 and IL-33, and interferon (IFN)-γ], two cell adhesion molecules (intercellular adhesion molecule-1 and P-selectin) and an MMP-7 were measured by ELISA in 33 patients with CRC and 35 healthy controls. Combined capacity of all molecules to detect the presence of CRC was assessed by logistic regression. Molecules and molecule combinations were tested for all stages and tumor grades. A significant increase was identified for IL-8 in patients compared with healthy controls; IL-10 was found to be significantly decreased. The biomarker potential of each significantly modified molecule was tested: IL-8 had a sensitivity of 0.865, a specificity of 0.600 and an area under the curve (AUC) of 0.777; for IL-10, sensitivity was 0.65, specificity was 0.69, with an AUC of 0.689. Logistic regression determined the best discriminative potential between patients and control groups for the combination IL-4 + IL-6 + IL-8 + IFN-γ, with 0.97 sensitivity and 0.58 specificity. For the early stages of CRC, the combination IL-6 + IL-8 + IL-22 showed good performance. It was concluded that increased IL-8 had potential as single biomarker in CRC. Cytokine combinations are superior to single cytokine analysis in showing the presence of CRC.

Dysregulation of miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p in Oral Squamous Cell Carcinoma: A Potential Biomarkers Panel?

Oral squamous cell carcinoma (OSCC) is considered the sixth most common cancer worldwide. To reduce the high mortality of the disease, sensitive and specific diagnostic and prognostic biomarkers are urgently needed. Non-coding RNA, microRNAs (miRNAs), which are short length non-coding transcripts, or long non-coding RNA (lncRNA) seem to be potential biomarkers, considering that they have an important role in regulation of cell fate being involved in a wide range of biological processes. Literature data emphasized the important role of these transcripts as a biomarker for diagnosis and prognosis in oral squamous cell carcinoma. Therefore, we have evaluated the expression levels of a panel of four miRNAs (miR-21-5p, miR-93-5p, miR-200c-3p and miR-205-5p) and H19, MALAT1 by quantitative real-time PCR (qRT-PCR) from 33 fresh frozen tissues and 33 normal adjacent tissues. Our date revealed miR-21-5p and miR-93-5p to be upregulated, while miR-200c-3p and miR-205-5p to be downregulated. Regarding the long non-coding RNAs, H19 and MALAT1, were also downregulated. We also investigated the expression of BCL2, which is another important gene correlated to non-coding RNAs investigated by as, and it was also under-expressed. Additional validation step at protein level was done for KI67, TP53 and BCL2. In our patient cohort no correlation with clinical stage and smoking status was observed. The results of the present study indicated the important role of miR-21-5p, miR-93-5p, miR-200c-3p, miR-205-5p and H19 in OSCC. Differential expression of these transcripts at sub-sites, may serve as a diagnostic marker with further elaboration on a larger sample size. Additional studies should be conducted to confirm the results, particularly the interconnection with coding and non-coding genes.

Targeting Cell Death Mechanism Specifically in Triple Negative Breast Cancer Cell Lines.

Triple negative breast cancer (TNBC) is currently associated with a lack of treatment options. Arsenic derivatives have shown antitumoral activity both in vitro and in vivo; however, their mode of action is not completely understood. In this work we evaluate the response to arsenate of the double positive MCF-7 breast cancer cell line as well as of two different TNBC cell lines, Hs578T and MDA-MB-231. Multimodal experiments were conducted to this end, using functional assays and microarrays. Arsenate was found to induce cytoskeletal alteration, autophagy and apoptosis in TNBC cells, and moderate effects in MCF-7 cells. Gene expression analysis showed that the TNBC cell lines' response to arsenate was more prominent in the G2M checkpoint, autophagy and apoptosis compared to the Human Mammary Epithelial Cells (HMEC) and MCF-7 cell lines. We confirmed the downregulation of anti-apoptotic genes (MCL1, BCL2, TGFß1 and CCND1) by qRT-PCR, and on the protein level, for TGFß2, by ELISA. Insight into the mode of action of arsenate in TNBC cell lines it is provided, and we concluded that TNBC and non-TNBC cell lines reacted differently to arsenate treatment in this particular experimental setup. We suggest the future research of arsenate as a treatment strategy against TNBC.

The World of Oral Cancer and Its Risk Factors Viewed from the Aspect of MicroRNA Expression Patterns.

Oral cancer is one of the leading causes of death worldwide, with a reported 5-year survival rate of around 50% after treatment. Epigenetic modifications are considered to have a key role in oral carcinogenesis due to histone modifications, aberrant DNA methylation, and altered expression of miRNAs. MicroRNAs (miRNAs) are small non-coding RNAs that have a key role in cancer development by regulating signaling pathways involved in carcinogenesis. MiRNA deregulation identified in oral cancer has led to the idea of using them as potential biomarkers for early diagnosis, prognosis, and the development of novel therapeutic strategies. In recent years, a key role has been observed for risk factors in preventing and treating this malignancy. The purpose of this review is to summarize the recent knowledge about the altered mechanisms of oral cancer due to risk factors and the role of miRNAs in these mechanisms.

MicroRNA Dysregulation in Prostate Cancer.

Prostate cancer biology is complex, and needs to be deciphered. The latest evidence reveals the significant role of non-coding RNAs, particularly microRNAs (miRNAs), as key regulatory factors in cancer. Therefore, the identification of altered miRNA patterns involved in prostate cancer will allow them to be used for development of novel diagnostic and prognostic biomarkers. PATIENTS AND METHODS: We performed a miRNAs transcriptomic analysis, using microarray (10 matched pairs tumor tissue versus normal adjacent tissue, selected based on inclusion criteria), followed by overlapping with TCGA data. A total of 292 miRNAs were differentially expressed, with 125 upregulated and 167 downregulated in TCGA patients' cohort with PRAD (prostate adenocarcinoma), respectively for the microarray experiments; 16 upregulated and 44 downregulated miRNAs were found in our cohort. To confirm our results obtained for tumor tissue, we performed validation with qRT-PCR at the tissue and plasma level of two selected transcripts, and finally, we focused on the identification of altered miRNAs involved in key biological processes. RESULTS: A common signature identified a panel of 12 upregulated and 1 downregulated miRNA, targeting and interconnected in a network with the TP53, AGO2, BIRC5 gene and EGFR as a core element. Among this signature, the overexpressed transcripts (miR-20b-5p, miR-96-5p, miR-183-5p) and the downregulated miR-542-5p were validated by qRT-PCR in an additional patients' cohort of 34 matched tumor and normal adjacent paired samples. Further, we performed the validation of the expression level for miR-20b-5p, miR-96-5p, miR-183-5p plasma, on the same patients' cohort versus a healthy control group, confirming the overexpression of these transcripts in the PRAD group, demonstrating the liquid biopsy as a potential investigational tool in prostate cancer. CONCLUSION: In this pilot study, we provide evidence on miRNA dysregulation and its association with key functional components of the PRAD landscape, where an important role is acted by miR-20b-5p, miR-542-5p, or the oncogenic cluster miR-183-96-182.

Natural compounds modulate the crosstalk between apoptosis- and autophagy-regulated signaling pathways: Controlling the uncontrolled expansion of tumor cells.

Due to the high number of annual cancer-related deaths, and the economic burden that this malignancy affects today's society, the study of compounds isolated from natural sources should be encouraged. Most cancers are the result of a combined effect of lifestyle, environmental factors, and genetic and hereditary components. Recent literature reveals an increase in the interest for the study of phytochemicals from traditional medicine, this being a valuable resource for modern medicine to identify novel bioactive agents with potential medicinal applications. Phytochemicals are components of traditional medicine that are showing promising application in modern medicine due to their antitumor activities. Recent studies regarding two major mechanisms underlying cancer development and regulation, apoptosis and autophagy, have shown that the signaling pathways of both these processes are significantly interconnected through various mechanisms of crosstalk. Phytochemicals are able to activate pro-autophagic and pro-apoptosis mechanisms. Understanding the molecular mechanism involved in apoptosis-autophagy relationship modulated by phytochemicals plays a key role in development of a new therapeutic strategy for cancer treatment. The purpose of this review is to outline the bioactive properties of the natural phytochemicals with validated antitumor activity, focusing particularly on their role in the regulation of apoptosis and autophagy crosstalk that triggers the uncontrolled expansion of tumor cells. Furthermore, we have also critically discussed the limitations and challenges of existing research strategies and the prospective research directions in this field.

Links between Infections, Lung Cancer, and the Immune System.

Lung cancer is the leading disease of cancer-related deaths worldwide. Since the beginning of the 20th century, various infectious agents associated with lung cancer have been identified. The mechanisms that include systemic inflammatory pathways as effect of microbial persistence in the lung can secondarily promote the development of lung carcinogenesis. Chronic inflammation associated with lung-cancer infections is known to precede tumor development, and it has a strong effect on the response(s) to therapy. In fact, both viral and bacterial infections can activate inflammatory cells and inflammatory signaling pathways. In this review, an overview of critical findings of recent studies investigating associations between each of viral and bacterial pathogens and lung carcinoma is provided, with particular emphasis on how infectious organisms can interfere with oncogenic processes and all the way through immunity. Moreover, a discussion of the direct crosstalk between lung tumor development and inflammatory processes is also presented.