She brought some joy into a friend’s life.

The Hot Girl leader has been a bright spot for her fans.

She was diagnosed with stage 4 neuroblastoma in 2014.

Williams lost his mother and four aunts to breast cancer.

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.

BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC. Notably, CDCP1 cooperates with the loss of the tumor suppressor gene PTEN to promote the emergence of metastatic prostate cancer. Mechanistically, we find that androgens suppress CDCP1 expression and that androgen deprivation in combination with loss of PTEN promotes the upregulation of CDCP1 and the subsequent activation of the SRC/MAPK pathway. Moreover, we demonstrate that anti-CDCP1 immunoliposomes (anti–CDCP1 ILs) loaded with chemotherapy suppress prostate cancer growth when administered in combination with enzalutamide. Thus, our study identifies CDCP1 as a powerful driver of prostate cancer progression and uncovers different potential therapeutic strategies for the treatment of metastatic prostate tumors.

Mayo Clinic and IBM Watson Health today unveiled results from early use of the Watson for Clinical Trial Matching, an IBM cognitive computing system. Use of this system in the Mayo Clinic oncology practice has been associated with more patients enrolled in Mayo’s breast cancer clinical trials.

Watson matched tumor board treatment recommendations in up to 96% of cases;reduced clinical trial screening time by 78%, studies find. Prostate cancer is latest add to Watson for Oncology; the tech will be available to support 80 percent of the incidence of cancer by year-end. Nine new adopters of Watson oncology offerings around the globe expands Watson's reach to 55 organizations worldwide.

A Peter MacCallum Cancer Centre study has demonstrated the potential for artificial intelligence to help reduce the time for clinicians to match lung cancer patients to relevant clinical trials.

  These were the words of Captain Peter Berger of Hallandale Beach Fire Rescue as he spoke to a full house of fire service industry leaders — along with his partner Captain Greg Moulin of DFW Airport Fire Services — on the topic of

This is a paper produced as part of the PROP2 (Practitioner Research: Outcomes and Partnership) programme, a partnership between the Centre for Research on Families and Relationships (CRFR) at the University of Edinburgh and IRISS that was about health and social care in Scotland. This paper was written by Elaine Monteith from ENABLE Scotland who participated in the PROP2 programme. What this research paper explores: All women are asked to go to the doctor every few years to get a check for cancer but women who have a learning disability don’t go for these checks as often as other women. The paper explore what barriers there are for women attending for checks and also looks at what could be done to encourage women them to attend.

A team of Princeton researchers led by Bridgett vonHoldt found that microbes are linked to cancer in a threatened species: the Santa Catalina foxes, found only on one island off the California coast.

Using sophisticated algorithms to explore regions of the genome whose roles in cancer have been largely uncharted, an international team of researchers including from Princeton has opened the door to a new understanding of the disease’s genetic origins.

A team of Princeton chemists has identified a way to tag a protein's nearest molecular neighbors, enabling the precise mapping of their micro-environment. This could open new avenues to cancer treatment and other drug therapies.

The heartwarming reunion, which clearly made little Mila Sneddon's day, took the young girl completely by surprise.

The heartwarming reunion, which clearly made little Mila Sneddon's day, took the young girl completely by surprise.

Dodgers minor league Connor Joe, 27, said Wednesday he's been diagnosed with testicular cancer, saying he underwent surgery Tuesday and he is recovering.

The heartwarming reunion, which clearly made little Mila Sneddon's day, took the young girl completely by surprise.

The heartwarming reunion, which clearly made little Mila Sneddon's day, took the young girl completely by surprise.

Anwar, who had leukemia, struggled to find a donor match, underscoring the frustratingly high odds that people of South Asian descent face in such an endeavor.

A diagnosis of breast cancer is always accompanied by angst and uncertainty. It's even more fraught when it comes in the midst of the coronavirus crisis.

The news that estrogen may boost resistance to COVID-19 offered a silver lining to my husband's prostate cancer and a cure for my isolation envy.

The star-studded event honoring Renée Zellweger featured a performance by the Jonas Brothers. Guests included Tom Ford, Katie Couric, Lisa Rinna and Paris Hilton.

On Tuesday, Simon & Schuster announced it will publish Alex Trebek's memoir, "The Answer Is…: Reflections on My Life," on July 21.

If you're a cancer patient, you should not avoid treatment because of the pandemic. Surgery and follow-up care cannot wait.

CANCER be tricky to detect because you may not experience any symptoms in the initial stages and when you do, they can be confused with more benign conditions. An easily overlooked sign of cancer is a colour patch on your tongue.

A GoFundMe page aims to match the nearly $600,000 that Tia Stokes' non-profit dance group Kalamity has raised for people facing real-life calamities.

Among the unaccounted for items were seven boxes of masks, 50 tubs of sanitizing wipes, 10 containers of soap and 20 bottles of hand sanitizer.

It's time for a short break to deal with some cancer issues. But I'll be back.

The Indiana congressional delegation introduced a House resolution expressing support for the goals and ideas of ''Stomach Cancer Awareness Month."

Pat O'Neil, an Indiana Baseball Hall of Fame inductee, was declared cancer-free Tuesday.

Men with advanced prostate cancer can now take highly targeted hormone therapies at home.

Known as “My Special Aflac Duck,” the robot is merging play with tools that help doctors do their jobs.

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

Mathias Uhlén
Dec 1, 2005; 4:1920-1932
Research

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

(DGIST (Daegu Gyeongbuk Institute of Science and Technology)) A drug-loaded microrobotic needle effectively targets and remains attached to cancerous tissue in lab experiments without needing continuous application of a magnetic field, allowing more precise drug delivery. The details were published by researchers at DGIST's Microrobot Research Center in Korea and colleagues in the journal Advanced Healthcare Materials.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

(Impact Journals LLC) Volume 11, Issue 18 of @Oncotarget Clinical implications of chromatin accessibility assessed by ATAC-seq profiling in human cancers especially in a large patient cohort is largely unknown.

(Center for Genomic Regulation) An analysis of 13,000 tumours highlights two previously overlooked genes as potential new therapeutic targets for cancer treatment. Researchers also identify potential new therapeutic targets for male infertility. Both findings are the result of the most comprehensive evolutionary analysis of RNA modification proteins to date, published today in the journal Genome Biology.

(European Society for Medical Oncology) A study of 4,532 men in the Veneto region of Italy has found that those who were being treated for prostate cancer with androgen-deprivation therapies (ADT) were less likely to develop the coronavirus COVID-19 and, if they were infected, the disease was less severe. The study is published in Annals of Oncology.

(Wiley) A recent Psycho-Oncology analysis of published studies found that few cancer survivors received financial information support from healthcare facilities during their initial treatment, even though cancer-related financial toxicity has multiple impacts on survivors' health and quality of life.

(Wiley) Heart failure and cancer are conditions with a number of shared characteristics. A new study published in the Journal of Internal Medicine found that in patients with heart failure, several known tumor markers can also be indicators of heart failure severity and progression.

(Luxembourg Institute of Health) Scientists at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH) revealed a novel mechanism through which the immune system controls autoimmunity and cancer. In the special focus of the researchers were regulatory T cells -- a type of white blood cells that act as a brake on the immune system.

(Walter and Eliza Hall Institute) The anti-cancer medicine venetoclax could improve the current therapy for estrogen receptor-positive (ER+) breast cancer - the most common form of breast cancer in Australia - according to preclinical studies led by Walter and Eliza Hall Institute researchers. The promising preclinical results for this 'triple therapy' have underpinned a phase 1 clinical trial in Melbourne, Australia, that is combining venetoclax with hormone therapy and CDK4/6 inhibitors in patients with ER+ breast cancer.

(JAMA Network) Death certificate data were used to compare the rate of opioid-related deaths in the US among cancer survivors with that of the general population from 2006 through 2016. Whether opioid-associated deaths in cancer survivors, who are often prescribed opioids for cancer-related pain, are rising at the same rate as in the general population is unknown.