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A Deeper Dive into understanding BREAST CANCER

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The blog “A Deeper Dive into Understanding Breast Cancer” explains the disease’s development, risk factors, and treatment options. Breast cancer begins in the milk ducts or lobules and can spread if untreated, becoming life-threatening. Risk factors include genetic mutations (like BRCA1/BRCA2), hormonal influences, and lifestyle choices such as obesity and alcohol consumption.
Globally, breast cancer is the most common cancer in women, with rising rates, especially in India. Early detection through screening and genetic testing is key to improving survival rates. The article also describes various breast cancer types and stages, highlighting that treatment options include surgery, chemotherapy, and hormonal or targeted therapies. Lastly, it emphasizes prevention through regular self-exams, a healthy lifestyle, and awareness campaigns to encourage early diagnosis.

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Advent of Chimeric Antigen Receptor-T Cell (Car-T Cell)Therapy: Offering Hope for Cancer Patients

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Advent-of-CART-cell-therapy

Cancer cases in India are expected to rise 12.8% by 2025 due to mutations in genes that impact, protein expression, and alter cells. Chimeric Antigen Receptor T cells (CAR-T) are genetically modified fusion proteins that can be expressed and transfused into patients. CAR-redirected T cells offer a promising cell-based immunotherapy method that can enhance and maintain antitumor GVL response without major histocompatibility complex restriction. The structure of CARs includes an intracellular signaling domain, a transmembrane domain, and an extracellular domain. The importance of single-chain variable fragment (scFv) in CAR-T cell therapy is due to their complete antigen-binding capability, which allows for faster and more even penetration to tumors and other tissues. Five generations of CAR-T cells have been created since 1989, with the first generation having limited expansion and persistence due to lack of a costimulatory signal. The manufacturing process for CAR T cells involves stimulating, transducing, expanding, and cryopreserving T cells under Good Manufacturing Practices conditions. This blog describes the evolution and brief applications of approved CART cell therapy.

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Distinct Characteristics of Nab-Paclitaxel from Solvent-Based Paclitaxel in Anti-Tumour Activity

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Nab-Paclitaxel

This blog discusses the use of human serum albumin as a drug delivery tool to improve the characteristics of drugs like paclitaxel. Albumin is highly soluble in hydrophobic drugs like paclitaxel and can be transported across blood vessels via the gp60 albumin receptor. Nanotechnology holds significant potential in pharmaceutical applications, especially in drug delivery, as nanomaterials enable efficient administration, protection, and transport of therapeutic agents. Solvent-based Paclitaxel (PTX) is a crucial chemotherapeutic agent used to treat lung, breast cancer, and AIDS-related Kaposi’s sarcoma. Non-toxic nano-delivery systems can protect the drug, lower toxicity, increase circulation half-life, improve pharmacokinetic profiles, and reduce side effects. Nab-paclitaxel, a solvent-free formulation, has shown superior transport across endothelial cells and enhanced extravascular distribution in patients.

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Emergence of Adeno Associated Virus Vector in Gene Therapy

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Emergence of AAV in Gene Therapy

Gene therapy has been a significant development in medicine for nearly 40 years, focusing on treating genetic disorders by injecting specific genetic material into a patient to alter cell activity and address hereditary illnesses. Four fundamental gene therapy techniques include gene silencing, gene addition, gene replacement, and gene editing. Adeno-associated viruses (AAVs) are a type of gene therapy vehicle that was initially discovered as a contaminant of adenovirus preparations. The first human gene therapy study was conducted in 1970 when American physician Stanfield Rogers tried to cure argininemia with a papillomavirus-containing arginase. The primary vector for in vivo gene therapy delivery is recombinant AAVs (rAAVs). The first rAAV gene therapy treatment, Alipogene tiparvovec (Glybera), received approval in 2012 for lipoprotein lipase deficiency. In 2017, the US FDA approved Luxturna (Voretigene Neparvovec) as the first retinal gene therapy for human use, specifically for patients with LCA type 2, an inherited retinal degeneration caused by mutations in the RPE65 gene. AveXis developed Onasemnogene abeparvovec (Zolgensma®) for spinal muscular atrophy (SMA). This blog summarises the emergence and applications of AAV in gene therapy platform.

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Gadolinium based Contrast Agents (GBCAs) in Magnetic Resonance Imaging (MRI)

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Gadolinium based Contrast Agents (GBCAs) in Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) is a crucial technique for disease diagnosis and treatment, with gadolinium-based contrast agents (GBCAs) being useful and safe in some cases. GBCAs are pharmaceuticals that enhance diagnostic image information by altering tissue properties, influencing contrast mechanisms. They are used in MRI to study proton (1H) relaxation processes in water and soft tissues in biological systems. GBCAs are administered intravenously and distributed throughout the body, with most being eliminated within hours. They shorten the T1 and T2 relaxation times of water molecules, resulting in brighter signals on T1-weighted images and darker signals on T2-weighted images. When administered at relatively low doses in individuals with normal renal function, all GBCAs approved for clinical use have a broad safety margin. Understanding an agent’s relaxivity, concentration, and chelate stability is important for radiologists as these properties impact patient safety and the effectiveness of diagnosis. This blog summarizes an overview of Gadolinium based contrast agents usage in the diagnostic MRI imaging.

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Therapeutic Modalities for Spinal Muscular Atrophy (SMA)

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Spinal Muscular Atrophy (SMA) is a genetic disorder causing muscle weakness and atrophy due to the degeneration of alpha motor neurons in the spinal cord. SMA is a major cause of hereditary mortality globally, with carriers estimated to be 1/40–1/60. Assistive equipment include, adaptive strollers, wheelchairs, and support devices. Target therapies like Nusinersen, Risidiplam, and Onasemnogene abeparvovec target the underlying disease mechanism and may prevent or slow SMA progression. Risdiplam compensates for the loss of SMN2 function in SMA patients, while Onasemnogene abeparvovec is a gene therapy that delivers a functional copy of the human survival motor neuron gene to patients, showing significant improvement in developmental motor milestones. Nusinersen is an antisense oligonucleotide (ASO) used to treat 5q Spinal Muscular Atrophy (5q SMA). It alters SMN2 gene splicing to increase SMN protein synthesis, correcting the disease’s underlying cause. Nusinersen helps produce full-length (100%) SMN protein essential for motor neuron function. Palliative, supportive, and rehabilitative treatment for SMA includes orthopaedic care, dietary assistance, end-of-life care, and pulmonary management, with severity varying based on disease type. The numerous therapy approaches to treat and assist people with SMA are the main topic of this blog.

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Role of Ferroptosis – A Novel Programmed Cell Death in Temozolomide Therapy for Brain Cancer

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TEMOZOLOMIDE- Role of Ferroptosis in Brain Cancer

Glioblastoma (GBM) are the most prevalent type of primary malignant brain tumor in adults that can develop in the brain stem, cerebellum, or spinal cord. Temozolomide (TMZ) is an alkylating agent that is used to treat adults with newly diagnosed GBM and resistant anaplastic astrocytoma who have progressed on a nitrosourea and procarbazine-containing therapy regimen. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioblastoma therapy. Cell membrane damage produced by mechanisms such as intracellular iron build-up, reactive oxygen species (ROS), lipid peroxidation, glutathione peroxidase (GPX) activity failure, and x-catenin (xCT) causes ferroptosis (iron dependent programmed cell death). This blog discusses the molecular mechanisms of ferroptosis, its application, and challenges in the development and treatment of glioblastoma. GBM invasiveness and treatment resistance may increase if ferroptosis is avoided due to changes in glucose, lipid, glutamine, and iron metabolism. Targeting ferroptosis, which involves fatal phospholipid peroxidation due to dysregulated redox homeostasis and cellular metabolism, could be a promising treatment for GBM, as it is essential for tumor cell viability.

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Artificial Intelligence (AI) making strides in Electrocardiography (ECG)

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AI-in-ECG

Cardiovascular disease continues to be a major concern, and the electrocardiogram (ECG) is a proven non-invasive technique for detecting cardiac issues. Traditional diagnosis, on the other hand, is based on an individual patient’s medical history and clinical examinations, which are ineffective owing to diverse data. By analyzing the electrical activity of the heart, AI is being used to identify prognostic arrhythmias such as atrial fibrillation. Deep convolutional neural networks (CNNs) are the basic building blocks of machine learning algorithms used in cardiovascular medicine to analyze ECG data. The adoption and use of AI-based diagnostic tools in clinical settings, however, may be limited by issues with interpretability and openness, such as evaluating models’ performance across datasets, processing power consumption, privacy and security concerns, imbalanced and limited datasets, and lack of clear guidelines for CNNs. Nevertheless, these technologies offer standardization, continuous, real-time monitoring, and more accurate interpretation—all of which have the potential to improve patient outcomes. This blog provides an overview of AI technologies applied and the challenges associated with the ECG in the diagnosis of cardiovascular diseases.

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PERTUZUMAB Advancing in HER2-Positive Breast Cancer

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PERTUZUMAB ADVANCING IN HER2 POSITIVE BREAST CANCER

Breast cancer is a diverse disease with varying clinical presentations, morphologic features, and molecular characteristics. It is influenced by various genetic pathways and is a major trend in breast cancer care. Neoadjuvant chemotherapy is a major trend, requiring integrated multidisciplinary care from pathologists, radiologists, surgeons, and oncologists. Anti-HER2 therapy has improved clinical results for HER2-positive breast cancer patients.

Pertuzumab, a humanized monoclonal antibody, targets the extracellular dimerization domain of HER2, inhibiting downstream signaling and cell survival pathways. It is used in conjunction with trastuzumab and docetaxel to treat HER2-positive metastatic breast cancer. In addition to directly encouraging the death of cancer cells, monoclonal antibodies also trigger immunological activation, which is deadly to tumour cells.

Pertuzumab possesses the capability to elicit immune effector responses, including cell-mediated cytotoxicity that is dependent on antibodies. The antibody targets the PI3K/AKT and RAS/MEK/ERK pathways, protecting normal cells from suicide. It can activate immunological effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity. Trastuzumab and pertuzumab function in complementary ways, highlighting the importance of understanding the biology of this devastating disease. This blog focuses on the mechanism of pertuzumab in patients with early-stage HER2-positive breast cancer receiving neoadjuvant treatment.

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Gene Therapy Perspective of Autosomal Recessive & Dominant Disorders

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Gene Therapy Perspective of Autosomal Recessive & Dominant Disorders

In this blog, our focus would be on autosomal dominant disorders and autosomal recessive disorders that can be cured with a gene therapy approach. Gene therapy has faced numerous obstacles and it took an extensive period of time for reaching up to the clinic from the research lab. However, continuous and rapid advancement in the molecular biology and genomics field set the stage to develop gene therapies for a range of inherited disorders. Because of the certain limitation of the application of drug and surgical treatment, some of the cardiovascular disease also needed gene therapy approaches. Though huge progress has been observed in the treatment of autosomal recessive disorders by delivering the normal exogenous genes that can restore the proper biological function of the affected or mutated gene. However, a similar outcome cannot be expected in the case of autosomal dominant disorder as precise differentiation is required between diseases/mutated alleles from that of healthy/unaffected alleles.

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