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AVN944 Elicits Apoptotic Responses and Impedes Tumorigenic Potential in Ewing's Sarcoma Cells.

Inosine monophosphate dehydrogenase 2 (IMPDH2) is implicated in survival and proliferation of cancer cells because of its role in guanine nucleotide biosynthesis. This study evaluates the efficacy of AVN944, an IMPDH2 inhibitor, as a treatment for Ewing's sarcoma, a challenging malignancy in pediatric and young adult patients. Gene expression data, as well as clinical outcomes for sarcoma patients, from The Cancer Genome Atlas (TCGA) were analyzed to determine the association between IMPDH2 expression and survival. Human Ewing's sarcoma cell lines and xenograft models were used to evaluate the

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Cyclin D transcription is activated by growth factors and combines with cyclin-dependent protein kinase 4 (CDK4) [ 28 ]. … The activation of Cdk4, when in complex with cyclin D, activates the E2F transcription system that aids in the induction of events resulting in DNA synthesis at the interface of the G 1 and S phase [ 29 ]. …

Palbociclib: A New Option for Front-Line Treatment of Metastatic, Hormone Receptor-Positive, HER2-Negative Breast Cancer.

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… Initially, patients were enrolled into two cohorts: Cohort 1 was enrolled on the basis of ER+/HER2– status alone, whereas cohort 2 also required that cyclin D be amplified and/or there be a loss of p16. … 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 Research. 2009;11:R77. doi: 10.1186/bcr2419. 9. …

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

Clinical management and therapeutic development for the rare disease rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare disease that arises from skeletal muscle mainly affects children and adolescents. Patients with RMS have diverse symptoms and prognosis based on tumor sizes, tumor anatomical locations, histological subtypes of the tumors and genetic testing of paired-box-forkhead box O1 (PAX-FOXO1) fusion gene. The 4 subtypes of RMS include embryonal RMS (eRMS), alveolar RMS (aRMS), spindle cell/sclerosing RMS (scRMS) and pleomorphic RMS (pRMS). Treatment for RMS patients remains challenging due to its heterogeneous nature. Thus, a combinatory approach is likely to warrant bet

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… CDK4 conjugates with cyclin D to drive the transition from G1 to S phase during DNA replication. The CDK4-cyclin D complex and phosphorylates the retinoblastoma (RB) protein which then releases the E2F transcription factor to initiate gene expression for DNA synthesis. … INK4 family members are able to bind only to CDK4/6-cyclin D complexes and block the progression of the cell cycle 67 . Deregulation of the CDK4/6-cyclin D-INK-RB pathway has been found in a variety of cancers. …

Bavachin suppresses proliferation of laryngopharyngeal cancer by regulating the STAT3 and MAPK signaling pathways.

Purpose: The present study aimed to explore the underlying antitumor effects of bavachin on laryngopharyngeal cancer in-vitro and in-vivo. Methods: Tu212 and FaDu cells were cultured in the incubator. Cells were treated with 0.1% DMSO (control group) and different concentrations of bavachin (experimental groups) for exploring the results of proliferation and apoptosis. We revealed the underlying mechanism of bavachin on laryngopharyngeal cancer through western blotting, qRT-PCR assay and immunofluorescence staining. Results: Bavachin could suppress the proliferation and migration of laryngopha

A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway.

Multiple myeloma (MM), the second most common haematological malignancy, is currently incurable because patients often develop multiple drug … via caspase-mediated apoptotic pathways, and induction of G0/G1 phase arrest via downregulation of cyclin D1, CDK4, and CDK6. Further investigation of the molecular mechanism shows that DCZ0358 suppresses the JAK2/STAT3 signaling pathway. In conclusion, DCZ0358 can successfully counter BTZ resistance in MM cells. This study provides evidence that warrants …

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

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… P16 interrupts the formation of cyclin D/CDK complexes. Its frequent inactivation, coupled with cyclin D1 amplifications, present in up to 28% of HNSCC, facilitates S phase entry and replication. …

New landscapes and horizons in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The

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… Cells enter the G 1 phase after stimulation with mitogenic signals, with the intracellular increase of D-type cyclins (D1, D2 and D3), resulting in cyclin D/CDK4 and cyclin D/CDK6 complexes [ 154 , 155 ]. …

MicroRNA-195 reverses the resistance to temozolomide through targeting cyclin E1 in glioma cells.

Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients' clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair,

The anti-tumor potential of sinomenine: a narrative review.

BACKGROUND AND OBJECTIVE: Currently, chemotherapy is the main treatment for most tumors. However, drug resistance and many adverse reactions associated with chemotherapy greatly limit its use. Therefore, an increasing number of researchers have shifted the research focus the anti-tumor activity of traditional Chinese medicine. The objective of this article is to review the anti-tumor mechanism of sinomenine and its derivatives to provide a reference for further study and clinical transformation. METHODS: In this study, we searched for relevant articles on the anti-tumor mechanism of Sinomeniu

Медицинский каннабис и признаки рака: критический обзор.

Онкология остаётся сложным и гетерогенным заболеванием, вызывающим значительную morbidity и mortality по всему миру, несмотря на продвижение в диагностике и лечении. Характерные черты онкологии раскрывают биологические механизмы, поддерживающие развитие опухолей и злокачественное эволюцию, а также помогают выявить потенциальные мишени для терапии. Медикаментозный кресс-масло в основном используется в онкологии для поддерживающей терапии, но растущее предклиническое доказательство указывает на взаимодействие с сигнальными путями, связанными с онкологией. Этот обзорный материал обобщает текущие

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

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… D, ↑p21, ↓AKT, ↑AMPK | [ 153 ] Oleanolic acid (leaves, fruits, and rhizomes) | Breast cancer | 40 μM | MCF‐10a, 7 MDA‐MB‐231, 4T1‐luc | ↓cell proliferation, ↑apoptosis | ↓EDN1, CACNG4, CCN2, THBS1, AXIN2 and BMP4, ↑ATF4, SERPINE1, SESN2, PPARGC1A, EGR1, JAG1 | [ 154 ] Bladder cancer | 20–50 μM | T24 … Additionally, it inhibits cell growth, migration, and invasion, upregulating AMPK and downregulating cyclin D and AKT [ 86 ]. …

Ирисин предотвращает повреждение трабекулярных костей и проникновение опухоли в мышиную модель множественной миэломы.

Болезни костей, связанные с множественной миеломой (ММ), характеризуются остеолитическими повреждениями и патологическими переломами, которы … стью понижать регулирование выражения Нотч. 3, что важно для связи между клетками в нише опухоли, и Cyclin D1, поддерживающий ингибиторное воздействие ирисина на распространение клеток MM. В целом, наши выводы говорят о том, что ирисин может стать новой перспективной стратегией борьбы с MMBD и опухолью one Стреляй.

Notch3 signaling between myeloma cells and osteocytes in the tumor niche promotes tumor growth and bone destruction.

In multiple myeloma (MM), communication via Notch signaling in the tumor niche stimulates tumor progression and bone destruction. We previously showed that osteocytes activate Notch, increase Notch3 expression, and stimulate proliferation in MM cells. We show here that Notch3 inhibition in MM cells reduced MM proliferation, decreased Rankl expression, and abrogated the ability of MM cells to promote osteoclastogenesis. Further, Notch3 inhibition in MM cells partially prevented the Notch activation and increased proliferation induced by osteocytes, demonstrating that Notch3 mediates MM-osteocyt

Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies.

Polyphenols are one of the largest plant-derived natural product and they play an important role in plants' defense as well as in human health and disease. A number of them are pleiotropic molecules and have been shown to regulate signaling pathways, immune response and cell growth and proliferation which all play a role in cancer development. Hematological malignancies on the other hand, are cancers of the blood. While current therapies are efficacious, they are usually expensive and with unwanted side effects. Thus, the search for newer less toxic agents. Polyphenols have been reported to po

A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity

Clinically proven natural products against breast cancer, with mechanistic insights.

BackgroundBreast cancer still stands to be the foremost contributor to cancer-related incidence and mortality in women globally accounting for about 14% of all female cancer-related deaths worldwide. This research seeks to illustrate the mechanisms and clinical findings of natural products against breast cancer treatment.MethodologyRequired data for this review article was retrieved employing several readily obtainable search databases, including Web of Science® (Thomson Reuters, USA), PubMed® (U.S. National Library of Medicine, USA), and SciVerse Scopus® (Elsevier Properties S.A., USA), takin

A Natural Organic Compound "Decursin" Has Both Antitumor and Renal Protective Effects: Treatment for Osteosarcoma.

Osteosarcoma is a rare malignant tumor that commonly occurs in children. Anticancer drugs, for example, cisplatin, aid in postsurgery recovery but induce side effects such as renal damage, affecting the life prognosis of patients. Decursin which is one of the bioactive components has been reported for its anti-inflammatory, antioxidant, and antitumor effects, but the effect on osteosarcoma is unexplained. In this study, the research theme was to examine the sensitizing effect of decursin and its influence on cisplatin-induced nephrotoxicity. The cell viability and half maximal inhibitory conce

The role of Rhizoma Paridis saponins on anti-cancer: The potential mechanism and molecular targets.

Cancer is a disease characterized by uncontrolled cell proliferation, leading to excessive growth and invasion that can spread to other parts of the body. Traditional Chinese medicine has made new advancements in the treatment of cancer, providing new perspectives and directions for cancer treatment. Rhizoma Paridis is a widely used Chinese herbal medicine with documented anti-cancer effects dating back to ancient times. Modern research has shown that Rhizoma Paridis saponins (RPS) have various pharmacological activities. RPS can inhibit cancer in multiple ways, such as suppressing tumor growt