Identification of a Mimicry of the Protein that Potentially Isolates the Mutated p53 Material and Prevents Further Protein Accumulation

The team first screened a set of protein mimics originally designed to target Alzheimer's disease and type 2 diabetes. The results identify a mimicry of the protein that potentially isolates the mutated p53 material and prevents further protein accumulation. The researchers then showed that segregation of mutated p53 grains by protein mimicking restored the suppressive function of the p53 tumor, leading to the death of a wide range of cancer cells. Importantly, protein mimicry therapy effectively reduces tumors that contain mutated p53 while showing no significant toxins for healthy tissue, resulting in significantly longer survival. "As the prevalence of cancer increases worldwide, there is an urgent need for new cancer therapies to complement or replace existing therapies," said the study's lead author. Here we show the first successful use of a small molecule amyloid inhibitor as an anticancer agent. We believe that this will have a far-reaching impact, as it effectively bridges the gap between amyloid disease and cancer and is the basis for passing on information approaches in the design of new and robust cancer mutation therapies for the p53 mutation. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening, Treatment; Management

Searching Cytotoxic T Cells for Destroying Target Invading Cells

A groundbreaking study led by engineering and medical researchers at the California South University (CSU) shows how immune cells engineered in new cancer therapies can overcome physical barriers so that the patient's own immune system can fight tumors. This research could improve the future of millions of cancer patients worldwide. Immunotherapy, instead of using chemicals or radiation, is a type of cancer treatment that helps the patient's immune system fight cancer. T cells are a type of white blood cell that is essential for the body's immune system. Cytotoxic T cells are like soldiers searching for and destroying target invading cells. Although there has been success in using immunotherapy for some types of cancer in the blood or blood-producing organs, T cell work is much more difficult in solid tumors Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening, Treatment; Management

Engineering T-Cell Activation for Immunotherapy by Mechanical Forces

A groundbreaking study led by engineering and medical researchers at the California South University (CSU) shows how immune cells engineered in new cancer therapies can overcome physical barriers so that the patient's own immune system can fight tumors. This research could improve the future of millions of cancer patients worldwide. Immunotherapy, instead of using chemicals or radiation, is a type of cancer treatment that helps the patient's immune system fight cancer. T cells are a type of white blood cell that is essential for the body's immune system. Cytotoxic T cells are like soldiers searching for and destroying target invading cells. Although there has been success in using immunotherapy for some types of cancer in the blood or blood-producing organs, T cell work is much more difficult in solid tumors. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

Targeting the Prion-Like Aggregation of Mutant p53 to Combat Cancer

The team first screened a set of protein mimics originally designed to target Alzheimer's disease and type 2 diabetes. The results identify a mimicry of the protein that potentially isolates the mutated p53 material and prevents further protein accumulation. The researchers then showed that segregation of mutated p53 grains by protein mimicking restored the suppressive function of the p53 tumor, leading to the death of a wide range of cancer cells. Importantly, protein mimicry therapy effectively reduces tumors that contain mutated p53 while showing no significant toxins for healthy tissue, resulting in significantly longer survival. "As the prevalence of cancer increases worldwide, there is an urgent need for new cancer therapies to complement or replace existing therapies," said the study's lead author. Here we show the first successful use of a small molecule amyloid inhibitor as an anticancer agent. We believe that this will have a far-reaching impact, as it effectively bridges the gap between amyloid disease and cancer and is the basis for passing on information approaches in the design of new and robust cancer mutation therapies for the p53 mutation. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

930. Clinically Significant CMV Infections in Patients with Lymphoma or Multiple Myeloma

Background Clinically significant CMV infections (CS-CMVi) among patients with lymphoma and multiple myeloma (MM) have not been clearly defined, especially considering the new cancer therapies that have revolutionized cancer outcomes of these patients. This study aims at describing clinical outcomes of CS-CMVi in this patient population and identify risk factors for CS-CMVi. Methods This is a single-center, cohort study of all patients with lymphoma and MM who developed CS-CMVi between January 2017 and October 2020. Data was collected from the electronic medical records. CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 26 using a logistic regression model for multivariate analysis. Results We identified 84 patients; 60 (71%) had lymphoma and 24 (29%) had MM (Table 1). CMV end organ disease was diagnosed in 53 (63%) patients as the initial CMV episode and the most common site was the lungs (68%). In our cohort, 25 (30%) patients had autologous HCT and 14 (17%) had CAR T cells infusions prior to CS-CMVi. Recurrent CS-CMVi occurred in 16 (19%) patients (Table 2). A 100-day all-cause mortality was 55%, at a median of 76 days (range 3 -1330 days) after the initial episode of CS-CMVi. CMV related mortality was 11% amongst patients with end organ disease. In multivariate analysis, female gender was associated with a higher risk of CMV end organ disease (OR 3.42, 95% CI 1.14-10.3) and MM with a lower risk of CMV end organ disease compared to lymphoma (OR 0.27, 95% CI 0.07-0.97) (Table 3). Interestingly, 16 (19%) patients received letermovir as secondary prophylaxis for a median of 94 days (range 5 to 339 days) and only 1 patient had recurrent CS-CMVi while on letermovir. Conclusion CS-CMVi, particularly end organ disease, are not uncommon among patients with lymphoma or MM. Routine CMV surveillance and the use of letermovir for secondary prophylaxis in this patient population should be evaluated in further studies. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support)

Exposure to Bacteriophages T4 and M13 Increases Integrin Gene Expression and Impairs Migration of Human PC-3 Prostate Cancer Cells

The interaction between bacteriophages and integrins has been reported in different cancer cell lines, and efforts have been undertaken to understand these interactions in tumor cells along with their possible role in gene alterations, with the aim to develop new cancer therapies. Here, we report that the non-specific interaction of T4 and M13 bacteriophages with human PC-3 cells results in differential migration and varied expression of different integrins. PC-3 tumor cells (at 70% confluence) were exposed to 1 × 107 pfu/mL of either lytic T4 bacteriophage or filamentous M13 bacteriophage. After 24 h of exposure, cells were processed for a histochemical analysis, wound-healing migration assay, and gene expression profile using quantitative real-time PCR (qPCR). qPCR was performed to analyze the expression profiles of integrins ITGAV, ITGA5, ITGB1, ITGB3, and ITGB5. Our findings revealed that PC-3 cells interacted with T4 and M13 bacteriophages, with significant upregulation of ITGAV, ITGA5, ITGB3, ITGB5 genes after phage exposure. PC-3 cells also exhibited reduced migration activity when exposed to either T4 or M13 phages. These results suggest that wildtype bacteriophages interact non-specifically with PC-3 cells, thereby modulating the expression of integrin genes and affecting cell migration. Therefore, bacteriophages have future potential applications in anticancer therapies.

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 suitability of curcumin combination treatment with other cancer therapies to curb cancer growth. We provide a critical insight to the mechanisms of action of curcumin, its role in combination therapy in various cancers, along with the molecular targets involved. Curcumin combination treatments were found to enhance anticancer effects, mediated by the multitargeting of several signalling pathways by curcumin and the co-administered cancer therapies. The preclinical and clinical evidence in curcumin combination therapy is critically analysed, and the future research direction of curcumin combination therapy is discussed.

Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase

DNMDP and related compounds, or velcrins, induce complex formation between the phosphodiesterase PDE3A and the SLFN12 protein, leading to a cytotoxic response in cancer cells that express elevated levels of both proteins. The mechanisms by which velcrins induce complex formation, and how the PDE3A-SLFN12 complex causes cancer cell death, are not fully understood. Here, we show that PDE3A and SLFN12 form a heterotetramer stabilized by binding of DNMDP. Interactions between the C-terminal alpha helix of SLFN12 and residues near the active site of PDE3A are required for complex formation, and are further stabilized by interactions between SLFN12 and DNMDP. Moreover, we demonstrate that SLFN12 is an RNase, that PDE3A binding increases SLFN12 RNase activity, and that SLFN12 RNase activity is required for DNMDP response. This new mechanistic understanding will facilitate development of velcrin compounds into new cancer therapies.