Long noncoding RNAs in triple-negative breast cancer: A new frontier in the regulation of tumorigenesis.

In recent years, triple-negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%-24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease-free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms.

Alarming Burden of Triple-Negative Breast Cancer in India.

Breast cancer is the most prevalent cancer among women worldwide. Among the different breast cancer subtypes, triple-negative breast cancer (TNBC), which is more prevalent among younger age women, is the most aggressive form. Numerous clinicopathologic studies performed throughout the world strongly support the utterly poor prognoses and high recurrence rate of TNBC. The present report details a thorough data survey from Google and PubMed on the burden of TNBC worldwide and other associated factors, with special emphasis on its ever increasing incidence among Indian women. Our analysis revealed that the proportion of TNBC ranges from 6.7% to 27.9% in different countries, with the highest reported percentage in India among all, followed by Indonesia, Algeria, and Pakistan. Most of the other countries (Netherlands, Italy, London, Germany) had a TNBC incidence less than the mean level (ie, 15%). The high incidence of TNBC in the Indian population is associated with vivid risk factors, which primarily include lifestyle, deprivation status, obesity, family history, high mitotic indexes, and BRCA1 mutations. The treatment of TNBC is greatly hampered due to the lack of targeted therapies. Hence, it requires earnest attention towards extensive research for the prevention and development of treatment modalities with high efficacy.

Therapeutic implications of toll-like receptors in peripheral neuropathic pain.

Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain. Indeed considering the prevalence of neuropathic pain and suffering of the affected patients, insights into the diverse mechanism(s) of activation of TLR signaling cascades may open novel avenues for the management of this chronic condition. Moreover, existing therapies like antidepressants, anticonvulsants, opiates and other analgesic are not sufficiently effective in reducing the pain. In this review, we present substantial evidences highlighting the diverse roles of TLRs and their signaling pathways involved in the progression of neuropathic pain. Furthermore, an elaborate discussion on various existing treatment regimens and future targets involving TLRs has also been included.

Role of toll-like receptors in multiple myeloma and recent advances.

Multiple myeloma (MM) is a hematologic malignancy characterized as an abnormal proliferation and invasion of plasma cells into the bone marrow. Toll-like receptors (ТLRs) connect the innate and adaptive immune responses and represent a significant and potentially linking element between inflammation and cancer. When TLRs bind to their ligands, they trigger two major signaling pathways such that both share overlapping downstream signals: one is a myeloid differentiation primary response 88 (MyD88)-dependent production and activation of nuclear factor-κB, whereas the other is a MyD88-independent production of type-I interferon. Whereas the MyD88 pathway results in proinflammatory cytokine production, the other pathway stimulates cell proliferation. Dysregulations of these pathways may eventually lead to abnormal cell proliferation and MM. Despite recent biomedical advances, MM continues to be an incurable disease. There are an increasing number of TLR-based therapeutic approaches currently being tested in a number of preclinical and clinical studies. We here attempt to outline in detail the currently available information on TLRs in various types of cancer.