Cancer biology research

26/07/2025

In this blog post, we will explore the cellular and molecular mechanisms underlying epithelialization, detail the key phases of the process, examine factors that regulate or impair it—particularly in chronic wound environments—and discuss therapeutic strategies that aim to enhance epithelial repair

Discover how epithelialization drives wound healing, its key stages, factors, and therapies to improve skin regeneration and repair.

26/07/2025

Neuroendocrine Regulation of Adrenal Glucocorticoids (GC) and Their Physiological Roles👇

✅The synthesis and secretion of glucocorticoids (GC) are primarily controlled by the hypothalamus-pituitary-adrenal (HPA) axis, a central neuroendocrine pathway crucial for the body's response to stress and circadian rhythms. This system regulates not only stress responses but also helps maintain physiological balance in various body systems.

🔴Activation of the HPA Axis: When stress or circadian rhythms trigger certain neurochemical signals, the paraventricular nucleus (PVN) of the hypothalamus becomes activated. This leads to the release of two key hormones:

📌Corticotropin-releasing hormone (CRH)

📌Arginine vasopressin (AVP)

These hormones stimulate the pituitary gland to produce and release adrenocorticotropic hormone (ACTH).

🔴ACTH Stimulation of Adrenal Glands: Once released, ACTH circulates through the bloodstream and acts on the adrenocortical cells in the adrenal glands. ACTH stimulates these cells to synthesize and secrete glucocorticoids (GC), primarily cortisol in humans. These hormones play key roles in managing the body’s response to stress and regulating metabolism, immune function, and inflammation.

🔴Negative Feedback Regulation: Once circulating GC levels rise, they exert negative feedback on both the hypothalamus and pituitary, reducing the release of CRH, AVP, and ACTH. This feedback loop serves to prevent excessive GC production and maintain homeostasis within the HPA axis.

🔴Physiological Roles of Glucocorticoids: GC serves a broad range of essential physiological functions, including:

📌Regulating metabolism: GCs help in the metabolism of carbohydrates, proteins, and fats, promoting the breakdown of stored energy to fuel the body during stress.

📌Immune response modulation: GCs reduce inflammation and suppress the immune response to prevent overreaction during stress.

📌Stress adaptation: GC enables the body to adapt to both acute and chronic stressors, enhancing survival by mobilizing energy stores and maintaining blood pressure.

📌Circadian rhythm regulation: GC levels fluctuate throughout the day, typically peaking in the morning and tapering off in the evening, helping regulate sleep-wake cycles.

🔴This complex, tightly regulated system ensures that GC production and release are responsive to stress and environmental cues while preventing detrimental effects of excessive GC levels, such as immune suppression or metabolic disturbances.
💡Chung S, Son GH, Kim K. Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications. Biochim Biophys Acta. 2011 May;1812(5):581-91. doi: 10.1016/j.bbadis.2011.02.003. Epub 2011 Feb 12. PMID: 21320597.

25/07/2025

CRISPR-Cas9: Revolutionizing Genetics and Microbiology👇

CRISPR-Cas9 is a potent genome-editing system originating from a naturally occurring bacterial immune defense against viruses.
CRISPR stands for short, repeated DNA sequences that enable bacteria to “remember” viral invaders.
Cas9 is an enzyme that behaves like molecular scissors, guided by a synthetic RNA to cleave DNA at precise sites.
Together, they enable scientists to locate, dissect, and edit specific genes with unprecedented accuracy.

Why is CRISPR-Cas9 Revolutionary?

a) High Specificity: Almost any gene can be targeted using custom guide RNAs.

b) Efficiency & Affordability: Faster, easier, and more cost-effective than earlier tools like TALEN or ZFN.

Broad Applications:

a) Treating genetic diseases (e.g., sickle cell anemia, muscular dystrophy)

b) Engineering disease-resistant crops

c) Editing microbial genomes for industrial or therapeutic purposes

Applications in Microbiology:

a) Gene Knockout Experiments: Disrupting genes in E. coli or S. cerevisiae to study function

b) Engineered Probiotics: Designing bacteria for enhanced gut health and targeted drug delivery

c) Antibiotic Engineering: Optimizing production in Streptomyces

d) Pathogen Resistance: Creating microbes resilient to viruses or environmental stress

CRISPR-Cas9 isn’t just changing genetics—it’s helping microbiologists rethink what’s possible.

25/07/2025

Nature Reviews Cancer: The nervous and immune systems have co-evolved to respond to threats, including cancer. This Review outlines the reciprocal interactions among neurons, immune cells and tumour cells that regulate peripheral antitumour immune responses and discusses how these mechanisms could be leveraged to enhance immunotherapy.

Link to the Review in the comments.

25/07/2025

In this post, we’ll explore how proto-oncogenes work, how mutations lead to cancer, and their role in tumor formation. We’ll also cover their connection to tumor suppressor genes and how understanding them is shaping cancer therapies and future treatments.

Learn how proto-oncogenes drive cancer, their role in tumor formation, and the latest therapies targeting these genes for better treatment outcomes.

25/07/2025

Common Experimental Methods in Molecular Biology👇

✅Molecular biology focuses on the structure and function of molecules essential to life, particularly DNA, RNA, and proteins. It provides the foundation for understanding gene regulation, cellular signaling, and disease mechanisms. A wide array of experimental methods is used to analyze these biomolecules and their interactions.

✅One of the core techniques is nucleic acid extraction, which isolates high-purity DNA or RNA from cells or tissues for downstream applications. Once extracted, Polymerase Chain Reaction (PCR) is used to amplify specific DNA sequences, while quantitative PCR (qPCR) enables real-time quantification of gene expression.

✅Gel electrophoresis is employed to separate DNA, RNA, or proteins based on size, providing a simple but powerful method for assessing molecular integrity and fragment length. Agarose gels are used for nucleic acids, whereas SDS-PAGE is applied to proteins.

✅Reverse transcription (RT) techniques convert RNA into complementary DNA (cDNA), which can then be analyzed by PCR or sequencing to study gene expression. Northern blotting and Southern blotting remain classic tools for detecting specific RNA and DNA sequences, respectively.

✅Western blotting is commonly used to detect specific proteins using antibodies, revealing information about protein expression levels and modifications. In addition, cloning and transformation techniques allow genes to be inserted into plasmids and expressed in host cells, facilitating functional studies or protein production.

✅Advanced tools like CRISPR-Cas9 genome editing, RNA interference (RNAi), and next-generation sequencing (NGS) are now integral to molecular biology, enabling precise gene manipulation and large-scale genomic analysis.

25/07/2025

In this article, we will explore the biological functions of HGF, its role in liver regeneration and cancer, its therapeutic potential in regenerative medicine, and the latest advancements in HGF-based therapies.

Discover the role of Hepatocyte Growth Factor (HGF) in cell growth, cancer, and therapy. Learn its functions, risks, and future medical applications.

25/07/2025

Mechanisms of Drug Resistance in Anti-Angiogenic Therapy👇
✅Anti-angiogenic therapy, designed to target and inhibit the formation of new blood vessels in tumors, faces significant challenges due to the development of drug resistance. This resistance can be either intrinsic (where patients are non-responsive from the beginning) or acquired (where initially responsive patients eventually stop benefiting from the treatment). Several mechanisms contribute to both types of resistance:

✅1. Compensatory Upregulation of Alternative Pro-Angiogenic Factors
After prolonged exposure to anti-angiogenic therapy, tumors often adapt by increasing the production of alternative pro-angiogenic factors. These factors can bypass the blockade of the primary angiogenic pathways. Key factors involved include:

bFGF (basic Fibroblast Growth Factor)

PDGF (Platelet-Derived Growth Factor)

PlGF (Placental Growth Factor)

These molecules promote angiogenesis by stimulating the formation of new blood vessels, allowing tumors to continue growing and spreading even in the presence of anti-angiogenic drugs.

✅2. Recruitment of Bone Marrow-Derived Endothelial Progenitor Cells (EPCs)
In response to anti-angiogenic therapy, tumors can recruit bone marrow-derived endothelial progenitor cells (EPCs) to support neovascularization. These progenitor cells are capable of differentiating into endothelial cells, contributing to the formation of new blood vessels and enhancing tumor vascularization despite the inhibition of traditional angiogenic pathways.

Mechanism: EPCs migrate to the tumor site, bypassing the need for endothelial cell proliferation from pre-existing vessels.

✅3. Increased Pericyte Coverage
The presence of pericytes, which are contractile cells that wrap around endothelial cells, is essential for maintaining the stability and integrity of blood vessels. In response to anti-angiogenic therapy, tumors may increase pericyte coverage around blood vessels, thereby enhancing the stability of newly formed vasculature. This helps protect blood vessels from the effects of therapy and prevents vessel regression.

Effect: Stable vessels are less likely to collapse under the influence of anti-angiogenic drugs, promoting continued blood supply to the tumor.

✅4. Autophagy and Tumor Survival in Hypoxic Environments
Autophagy, a cellular process by which cells degrade and recycle their own components, is a critical survival mechanism for tumor cells, especially in hypoxic conditions (low oxygen levels). Under anti-angiogenic therapy, the tumor microenvironment becomes more hypoxic due to reduced blood flow. In response, tumor cells may increase autophagy to adapt and survive in the oxygen-deprived environment, thus contributing to therapy resistance.

Effect: Autophagy allows tumor cells to survive under adverse conditions where normal cells would perish, making them less susceptible to anti-angiogenic treatments.

✅5. Increased Tumor Invasiveness and Metastasis
As tumors progress, they may increase their invasiveness, allowing tumor cells to invade distant tissues and metastasize through the blood and lymphatic circulation. This process is often facilitated by the acquisition of drug resistance, enabling tumor cells to escape localized inhibition and spread to other areas.

Effect: Anti-angiogenic therapy may not stop the metastatic spread, as tumor cells can bypass vascular dependency by traveling through alternate routes like the lymphatic system or blood vessels.

✅6. Genetic Mutations
Genetic mutations in key signaling pathways involved in angiogenesis and tumor growth can render the tumor resistant to anti-angiogenic therapies. For example, mutations in VEGFR (vascular endothelial growth factor receptor) or downstream signaling molecules may prevent the drug from effectively blocking angiogenesis.

Effect: Tumors with genetic alterations in angiogenic pathways can continue to produce and utilize alternative angiogenesis mechanisms even in the presence of targeted therapies.

✅7. Vessel Mimicry, Vessel Co-Option, and Intussusception
Vessel Mimicry: Tumor cells themselves can form vessel-like structures around existing blood vessels to provide nutrient and oxygen supply. This process bypasses the need for normal angiogenesis and enables the tumor to maintain its blood supply.

Vessel Co-option: Tumor cells may hijack existing normal blood vessels, using them for their own growth and survival, even in the presence of anti-angiogenic drugs.

Intussusception: This process involves the splitting of existing blood vessels into two, often through endothelial cell reorganization. It allows for the formation of new vessels without the need for typical endothelial sprouting.

Effect: These alternative mechanisms of vascularization help tumors overcome anti-angiogenic treatments by creating new blood vessels that are not reliant on the blocked angiogenic pathways.

💡Liu, ZL., Chen, HH., Zheng, LL. et al. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Sig Transduct Target Ther 8, 198 (2023).

25/07/2025

This article explores the major cell signaling pathways involved in cancer, their roles in tumor progression, and the current therapeutic approaches targeting these pathways.

Discover the role of cell signaling pathways in cancer, their impact on tumor growth, and advancements in targeted therapies.

25/07/2025

The Role of Angiogenesis in Cancer Progression👇

✅Angiogenesis, the formation of new blood vessels, plays a critical role in tumor progression. As a tumor grows, it requires an increasing amount of oxygen and nutrients to sustain its rapid expansion. When the tumor mass becomes too large, it exceeds the oxygen supply from existing blood vessels, creating a hypoxic microenvironment. This hypoxia triggers a cascade of events that leads to excessive angiogenesis. Here's an overview of how angiogenesis contributes to cancer progression:

✅1. Hypoxia-Induced Angiogenesis Activation
As the tumor rapidly expands, the oxygen supply becomes insufficient to meet the growing metabolic demands of the tumor cells. This hypoxic environment triggers the expression of angiogenic factors (e.g., VEGF, PDGF, FGF, and angiopoietins) that are released by the tumor cells and surrounding stromal cells. These factors promote the activation of endothelial cells (ECs) and the formation of new blood vessels, a process essential for supplying the growing tumor with the necessary oxygen and nutrients.

✅2. Formation of New Blood Vessels
The angiogenic pro-factors released in response to hypoxia stimulate sprouting angiogenesis where existing blood vessels begin to form new vascular sprouts. The growth factors trigger the migration and proliferation of endothelial cells, leading to the formation of new capillaries. These vessels are initially immature, leaky, and disorganized, but they gradually mature over time to provide a more structured blood supply. These new vessels not only support the survival of the tumor by enhancing nutrient delivery but also facilitate the removal of metabolic waste products.

✅3. Tumor Cell Growth and Proliferation
With the establishment of new blood vessels, the tumor is able to support further growth and proliferation. The enhanced blood supply allows the tumor to continue expanding, as the oxygen and nutrients needed for rapid cell division and metabolism become more accessible. Additionally, angiogenesis helps in creating a favorable microenvironment by supporting the formation of extracellular matrices (ECM), which further contributes to tumor progression.

✅4. Aggressive Tumor Phenotype and Metastasis
As the tumor evolves, it often develops a more aggressive phenotype characterized by increased cell proliferation, genetic mutations, and invasive properties. These changes not only fuel local tumor growth but also facilitate tumor cell invasion into surrounding tissues. The new blood vessels formed during angiogenesis provide an entry route for tumor cells to intravasate (enter the bloodstream), allowing them to travel to distant sites and form secondary tumors, a process known as metastasis. This circulatory spread is crucial for the establishment of metastatic colonies in distant tissues and organs.

✅5. Continued Angiogenesis in Metastasis
In metastatic tumors, angiogenesis continues to play a critical role. The formation of new blood vessels not only supports the growth of metastatic lesions but also provides a way for cancer cells to escape the primary tumor and establish secondary sites of disease. The angiogenic process becomes self-sustaining as the metastatic tumor cells secrete more angiogenic factors to maintain the vascularization of the growing tumor.

💡Liu, ZL., Chen, HH., Zheng, LL. et al. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Sig Transduct Target Ther 8, 198 (2023).

25/07/2025

In this article, we’ll explore the science behind cord blood, its medical applications, and the choices available for its storage or donation.

Discover cord blood, its uses in stem cell therapy, and the benefits of banking or donating it for future medical treatments.

25/07/2025

RNA Splicing: An Overview👇

✅RNA splicing is a critical process in eukaryotic gene expression where non-coding regions of a precursor mRNA (pre-mRNA), known as introns, are removed and coding regions, called exons, are joined together to form a mature mRNA. This mature mRNA is then used as a template for protein synthesis in the cytoplasm during translation.

✅RNA splicing occurs in the nucleus and is facilitated by a complex molecular machine known as the spliceosome. Here's a detailed breakdown of how RNA splicing happens.

✅Steps in RNA Splicing:
📌1. Transcription of Pre-mRNA
Pre-mRNA is synthesized from the DNA template by RNA polymerase II during the process of transcription. This transcript includes both exons (coding sequences) and introns (non-coding sequences).

📌2. Assembly of the Spliceosome
The spliceosome is a large and dynamic complex of small nuclear ribonucleoproteins (snRNPs) and a variety of splicing factors. The spliceosome consists of five main snRNPs:

U1 snRNP: Recognizes the 5' splice site of the intron.

U2 snRNP: Recognizes the branch point of the intron and is crucial for the catalysis of splicing.

U4, U5, and U6 snRNPs: Participate in catalyzing the actual splicing reaction.

These snRNPs work together to remove the introns and join the exons.

📌3. Recognition of Splice Sites
5' splice site: The beginning of the intron, typically marked by the sequence "GU".

3' splice site: The end of the intron, typically marked by the sequence "AG".

Branch point: A specific nucleotide within the intron (usually an A), which is critical for the splicing reaction.

The process begins when U1 snRNP binds to the 5' splice site and U2 snRNP binds to the branch point. This sets the stage for the splicing reaction.

📌4. Catalytic Splicing Reaction
Splicing is a two-step transesterification process:

🔴Step 1: Cleavage at the 5' splice site:

The U2 snRNP facilitates the attack by the 2' hydroxyl group of the branch point A on the 5' splice site.

This causes a break at the 5' end of the intron, forming a lariat structure (a loop formed by the intron). This step is known as the lariat formation.

🔴Step 2: Cleavage at the 3' splice site:

The U5 snRNP facilitates the attack by the 3' hydroxyl group of the exon at the 3' splice site on the intron.

This step results in the exon-exon ligation, effectively joining the two exons and releasing the intron in the form of the lariat structure.

The lariat structure is then degraded, and the newly spliced mRNA is free of introns.

📌5. Release of Mature mRNA
After the splicing reaction, the mature mRNA (which is now composed only of exons) is released from the spliceosome.

The mature mRNA is then processed further (such as capping at the 5' end and polyadenylation at the 3' end) before being exported from the nucleus to the cytoplasm for translation.

✅Alternative Splicing: A Mechanism for Generating Protein Diversity
Alternative splicing is a process by which different combinations of exons are joined together, producing multiple mRNA isoforms from a single gene. This mechanism allows a single gene to encode multiple protein variants, contributing to the diversity of the proteome. Types of alternative splicing include:

Exon skipping: Some exons are skipped entirely.

Mutually exclusive exons: One exon is included while the other is excluded.

Alternative 5' or 3' splice sites: The splicing can occur at alternative splice sites within the same intron.

Intron retention: An intron may be retained in the final mRNA transcript.

This ability to produce multiple protein products from a single gene is crucial for cellular complexity and functions in processes such as development, differentiation, and cell signaling.

✅Factors Influencing RNA Splicing:
Splicing Regulatory Proteins: A range of trans-acting factors, such as SR proteins and hnRNPs (heterogeneous nuclear ribonucleoproteins), bind to cis-acting sequences on the pre-mRNA and modulate splicing decisions. These factors help determine which exons are included or excluded in the final mRNA product.

RNA Sequence and Structure: The intrinsic sequence of the pre-mRNA, especially in the splice sites and branch point, plays a critical role in guiding the splicing machinery. The secondary structure of the RNA, including the formation of secondary structures like stem-loops, can also influence splicing.

Splicing in the Context of Chromatin: The chromatin environment around a gene can influence splicing by affecting the accessibility of the pre-mRNA to the spliceosome.

Cellular Signals and Stress: External signals such as stress, hormonal changes, or development stages can affect splicing decisions through the action of signal transduction pathways that modify splicing factors.

✅Significance of RNA Splicing
Regulation of Gene Expression: Splicing controls which protein isoforms are produced in a given cell at a particular time. This regulation is crucial for cell differentiation, development, and adaptive responses to environmental signals.

Diversity of the Proteome: Through alternative splicing, one gene can produce many different protein products with distinct functions, enabling organisms to adapt to changing conditions without requiring additional genes.

Implicated in Diseases: Errors in splicing, due to mutations in splice sites or splicing factors, can lead to a variety of diseases, including cancers, neurodegenerative disorders, and genetic diseases like spinal muscular atrophy (SMA) and cystic fibrosis.