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Non-Curcuminoids from Turmeric and Their Potential in Cancer Therapy and Anticancer Drug Delivery Formulations.

Over the past decades curcuminoids have been extensively studied for their biological activities such as antiulcer, antifibrotic, antiviral, antibacterial, antiprotozoal, antimutagenic, antifertility, antidiabetic, anticoagulant, antivenom, antioxidant, antihypotensive, antihypocholesteremic, and anticancer activities. With the perception of limited toxicity and cost, these compounds forms an integral part of cancer research and is well established as a potential anticancer agent. However, only few studies have focused on the other bioactive molecules of turmeric, known as non-curcuminoids, wh

Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies.

In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K) pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical an

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets.

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, s

Transcription and Translation Inhibitors in Cancer Treatment.

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targ

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… PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro . Breast Cancer Res. 11:R77. 10.1186/bcr2419 Finn R. S., Martin M., Rugo H. S., Jones S., Im S.-A., Gelmon K., et al. (2016). …

New Therapeutic Strategies for Adult Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy. Chromosomal and genetic analyses are important for the diagnosis and prognosis of AML. Some patients experience relapse or have refractory disease, despite conventional cytotoxic chemotherapies and allogeneic transplantation, and a variety of new agents and treatment strategies have emerged. After over 20 years during which no new drugs became available for the treatment of AML, the CD33-targeting antibody-drug conjugate gemtuzumab ozogamicin was developed. This is currently used in combination with standard

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… The cyclin D-CDK4/6 complex is negatively regulated by p16INK4A, which is encoded by a respective gene [ 112 ]. … Absence of cyclin D/cdk complexes in cells lacking functional retinoblastoma protein Oncogene 1994 9 1633 1640 8183557 112. Russo A.A. Tong L. Lee J.O. Jeffrey P.D. Pavletich N.P. …

Ginsenoside Rg3 inhibits melanoma cell proliferation through down-regulation of histone deacetylase 3 (HDAC3) and increase of p53 acetylation.

Malignant melanoma is an aggressive and deadly form of skin cancer, and despite recent advances in available therapies, is still lacking in completely effective treatments. Rg3, a monomer extracted from ginseng roots, has been attempted for the treatment of many cancers. It is reported that the expressions of histone deacetylase 3 (HDAC3) and p53 acetylation correlate with tumor cell growth. However, the antitumor effect of Rg3 on melanoma and the mechanism by which it regulates HDAC3 expression and p53 acetylation remain unknown. We found high expression of HDAC3 in human melanoma tissues to

Benzyl isothiocyanate suppresses development of thyroid carcinoma by regulating both autophagy and apoptosis pathway.

Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, characterized by rapid growth and invasion and poor prognosis. Due to its rarity and aggressive nature, ATC is a difficult condition to treat, thus knowledge of the mechanisms underlying its progression represents important research challenges. Benzyl isothiocyanate (BITC) is a natural compound that has shown promising anticancer properties. The aim of this study was to evaluate the antitumor effect of BITC in ATC, highlighting signaling pathways involved in BITC mechanism of action. This work included in vitro a

DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.

Resistance to chemo- and radiotherapy is a common event among cancer patients and a reason why new cancer therapies and therapeutic strategies need to be in continuous investigation and development. DNA damage response (DDR) comprises several pathways that eliminate DNA damage to maintain genomic stability and integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made in recent years, providing several drugs and therapeutic strategies for cancer patients, including those targeting the DDR pathways. Currently, poly (ADP-ribose) polymera

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… There are two major classes of G1 cyclins that regulate cell cycle progression during the G1 phase: cyclin D, which cooperates with either CDK4 or CDK6, and cyclin E, which binds CDK2. During cell cycle progression in the early G1 phase, cyclin D–CDK4/6 complexes phosphorylate the Rb protein. … Downregulation of cyclin D has been shown to confer resistance to CHK1 inhibition. CHK1, a serine/threonine kinase that acts as an ATM–ATR effector, is activated following exogenous DNA damage, including nicks caused by chemotherapeutic drugs. …

Keyword Index for Volume 88

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Gene and Cell Therapy for Sarcomas: A Review.

Background: The heterogeneity of sarcomas and resulting distinct sub-type specific characteristics, their high recurrence rates, and tendency for distant metastasis, continue to present significant challenges to providing optimal treatments. Objective: To provide a comprehensive review of current literature and clinical trials in gene and cell therapies for sarcomas. Methods: A comprehensive literature search was conducted utilizing the following databases: PubMed, Medline, Google Scholar and clinicaltrials.gov. Search terms included "gene therapy", "cell therapy", "NK cell therapy, "CAR-T the

CS-6-induced p62 accumulation exacerbates DNA damage in colorectal cancer.

BACKGROUND: Gamabufotalin (CS-6), a bufadienolide derived from Chansu, has been reported to exhibit anti-tumor effects in various cancers, including glioblastoma, nonsmall cell lung cancer, and breast cancer. However,its role in colorectal cancer (CRC) remains unexplored. OBJECTIVE: Our study aimed to evaluate the inhibition of CS-6 to CRC cells by cell viability assay, colony formation assay, comet assay, and cell cycle analysis firstly. And its molecular mechanism was studied by immunofluorescence (IF) assay, western blot (WB) assay, siRNA transfection, protein-protein interaction (PPI) net

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma.

The launch of novel chemotherapeutic agents-in particular, proteasome inhibitors and immunomodulatory drugs-dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory f

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… Cyclin D is a cell cycle regulator that promotes G1/S transition and is encoded by the CCND1 gene. It is suggested that dysregulation of cyclin D is a unifying factor in MM pathogenesis [ 3 ]. … Moreover, cyclin D is thought to generate oxidative stress in myeloma cell and, therefore, increase cell migration and adhesion. This phenomenon is peculiar to MM cells expressing cyclin D1 [ 4 ]. …

Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer.

Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and tre … /STAT and modulate the expression of numerous signaling molecules such as the farnesoid X receptor, cyclin D1, survivin, caspases, HIF-1α, MMP-9, EMT proteins, tumor suppressor proteins, angiogenic proteins, and apoptotic proteins. The current review is an attempt to summarize the biological activities and diverse anticancer activities (both in vitro and i …

Curcumin: An age-old anti-inflammatory and anti-neoplastic agent.

Curcumin is a natural anti-inflammatory agent that has been used for treating medical conditions for many years. Several experimental and pharmacologic trials have demonstrated its efficacy in the role as an anti-inflammatory agent. Curcumin has been shown to be effective in treating chronic conditions like rheumatoid arthritis, inflammatory bowel disease, Alzheimer's and common malignancies like colon, stomach, lung, breast, and skin cancers. As treatments in medicine become more and more complex, the answer may be something simpler. This is a review article written with the objective to syst

Редкий случай плазмабластической миеломы с двойным Каппой и Lambda mRNA экспрессией, представляющий себя как одинокая тяжёлая опухоль.

Плазмабластическая миелома является агрессивным вариантом миэломы плазменных клеток, которая может имитировать плазмобластную лимфому, когда она представляет собой одиночную массу. Двойное выражение каппы и лямбды светоцепной цепи является исключительно редким и может быть упущено, если оценка основывается только на обнаружении уровня протеина. Мы сообщаем о случае с женщиной в 80 лет, которая подавала опухоль с левым опухолью и перерезала одинокий опухоль и опухоль. Гистология показала, что листы больших плазмбластических клеток являются положительными для CD38, CD138, множественной миэломы о

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Plasmablastic myeloma is an aggressive variant of plasma cell myeloma that can mimic plasmablastic lymphoma when it presents as a solitary m … showed marked hypercellularity with extensive replacement by plasmablastic plasma cells expressing cyclin D1, while Epstein-Barr virus studies and anaplastic lymphoma kinase were negative. Light-chain immunohistochemistry showed absent kappa staining and lambda staining in only a small subset of tumor cells, whereas RNA in situ hybridization demonstrated …

Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem.

Laryngeal squamous cell cancer (LSCC) accounts for almost 25-30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising

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… More recently, increased p21 expression has been significantly associated with higher cyclin D, cyclin E, and Ki67 levels, while p27 upregulation was correlated with p53 accumulation and increased proliferation, thus suggesting the establishment of a protective mechanism against the inhibitory effect …

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three protea

Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.

Thymoquinone (TQ), the active compound in Nigella sativa (black seed), has shown promising effects against cancer in many laboratory studies. In this review, we explore how TQ works on different aspects of cancer, from stopping cancer cell growth and spread, to triggering cancer cell death, reducing inflammation, and helping the immune system fight back. We also highlight how TQ may overcome one of the biggest problems in cancer treatment-chemoresistance. When used together with common treatments like chemotherapy, radiation, or immunotherapy, TQ has been shown to improve their effects and red

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… Specifically, TQ induces cell cycle arrest by blocking the activation of cyclin E and cyclin D and up-regulating cell cycle inhibitors p27 and p21, causing G1 phase arrest in breast, colon, and osteosarcoma cancer cells. …

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the su

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… Evading the cancer therapy, cancer cells usually instigate high activities of cyclin-dependent kinase (CDK), with the abnormal amplification of cyclin D, to accelerate the cancer cell proliferation [ 11 , 12 ]. …

The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.

Ubiquitination, a highly adaptable post-translational modification, plays a pivotal role in maintaining cellular protein homeostasis, encompassing cancer chemoresistance-associated proteins. Recent findings have indicated a potential correlation between perturbations in the ubiquitination process and the emergence of drug resistance in CRC cancer. Consequently, numerous studies have spurred the advancement of compounds specifically designed to target ubiquitinates, offering promising prospects for cancer therapy. In this review, we highlight the role of ubiquitination enzymes associated with c