Myeloid-Derived Suppressor Cell Survival and Function Are Regulated by the Transcription Factor Nrf2.

Tumor-induced myeloid-derived suppressor cells (MDSC) contribute to immune suppression in tumor-bearing individuals and are a major obstacle to effective immunotherapy. Reactive oxygen species (ROS) are one of the mechanisms used by MDSC to suppress T cell activation. Although ROS are toxic to most cells, MDSC survive despite their elevated content and release of ROS. NF erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a battery of genes that attenuate oxidative stress. Therefore, we hypothesized that MDSC resistance to ROS may be regulated by Nrf2. To test this hypothesis, we used Nrf2(+/+)and Nrf2(-/-)BALB/c and C57BL/6 mice bearing 4T1 mammary carcinoma and MC38 colon carcinoma, respectively. Nrf2 enhanced MDSC suppressive activity by increasing MDSC production of H2O2, and it increased the quantity of tumor-infiltrating MDSC by reducing their oxidative stress and rate of apoptosis. Nrf2 did not affect circulating levels of MDSC in tumor-bearing mice because the decreased apoptotic rate of tumor-infiltrating MDSC was balanced by a decreased rate of differentiation from bone marrow progenitor cells. These results demonstrate that Nrf2 regulates the generation, survival, and suppressive potency of MDSC, and that a feedback homeostatic mechanism maintains a steady-state level of circulating MDSC in tumor-bearing individuals.

Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.

Complete Pathologic Response to Gemcitabine and Oxaliplatin Chemotherapy After Prior Therapies in a Patient With Hepatocellular Carcinoma and Peritoneal Metastases Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary discussion, she underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) that removed all visible macroscopic tumor. Her pathology demonstrated a complete pathologic response. She received two additional months of postoperative chemotherapy, and then proceeded with close monitoring off therapy. To our knowledge, this is the first reported case of a complete pathologic response to GEMOX chemotherapy in the context of CRS/HIPEC for peritoneal metastases in HCC, after progression on standard immunotherapy and tyrosine kinase inhibitor treatments. In this report, we review the current systemic treatment landscape in HCC. We highlight potential consideration of cytotoxic chemotherapy, which is less frequently utilized in current practice, in selected patients with HCC, and discuss the role of CRS/HIPEC in the management of peritoneal metastases. Further investigation regarding predictors of response to systemic treatments is strongly needed. Multidisciplinary management may ultimately prolong survival in patients with advanced HCC.

Peripheral Artery Disease: Overview of Diagnosis and Medical Therapy.

Peripheral artery disease (PAD) affects approximately 230 million people worldwide and is associated with an increased risk of major adverse cardiovascular and limb events. Even though this condition is considered a cardiovascular equivalent, it remains an underrecognized and undertreated entity. Antiplatelet and statin therapy, along with smoking cessation, are the foundations of therapy to reduce adverse events but are challenging to fully implement in this patient population. Race and socioeconomic status also have profound impacts on PAD outcomes.

Peripheral Artery Disease: Treatment of Claudication and Surgical Management.

Peripheral artery disease (PAD) affects approximately 230 million people worldwide and is associated with an increased risk of major adverse cardiovascular and limb events. Even though this condition is considered a cardiovascular equivalent, it remains an under-recognized and under-treated entity. Anti-platelet and statin therapy, along with smoking cessation, are the foundations of therapy to reduce adverse events but are challenging to fully implement in this patient population. Race and socioeconomic status also have profound impacts on PAD outcomes. Exercise therapy is the gold standard treatment of claudication while revascularization procedures are often reserved for patients with limb-threatening ischemia.

Cancer Screening Differences Among Muslims and Non-Muslims: Insights from the Chicago Multiethnic Prevention and Surveillance Study.

BACKGROUND: While cancer screening disparities along socioeconomic and racial/ethnic lines are well studied, differences based on religious affiliation are under-researched. Though diverse in terms of race/ethnicity, Muslim Americans appear to share values and beliefs that similarly inform their health and healthcare seeking behaviors. Cancer screening disparities among Muslim Americans are also understudied. METHODS: To examine differences in cancer screening behaviors based on Muslim affiliation, we analyzed data from a longitudinal cohort study examining lifestyle, healthcare access, environmental, and genetic factors on the health of Chicagoans. RESULTS: Of 7552 participants, 132 (1.7%) were Muslim. Between Muslim and non-Muslims, there were no significant differences in prostate, cervical, and breast cancer screening rates, but Muslims were less likely to undergo colorectal cancer screening. When differences in obesity and insurance status were accounted for in a multivariate regression model, religious affiliation was no longer significantly associated with screening rates. DISCUSSION: Religious values can influence cancer screening behaviors; hence, tracking cancer screening along religious lines may illuminate previously unknown disparities. Our analysis of a predominately African American cohort of Chicagoans, however, did not reveal religious affiliation to predict cancer screening disparities.

Frequency of Statin Prescription Among Individuals with Coronary Artery Calcifications Detected Through Lung Cancer Screening.

Individuals eligible for lung cancer screening (LCS) are at risk for atherosclerotic cardiovascular disease (ASCVD) due to smoking history. Coronary artery calcifications (CAC), a common incidental finding on low-dose CT (LDCT) for LCS, is a predictor of cardiovascular events. Despite findings of high ASCVD risk and CAC, a substantial proportion of LCS patients are not prescribed primary preventive statin therapy for ASCVD. We assessed the frequency of statin prescription in LCS patients with moderate levels of CAC. Among 259 individuals with moderate CAC, 95% had ASCVD risk ≥ 7.5%. Despite this, 27% of patients were statin-free prior to LDCT and 21.2% remained statin-free after LDCT showing moderate CAC. Illustratively, while a substantial proportion of LCS patients are statin-eligible, many lack a statin prescription, even after findings of CAC burden. CAC reporting should be standardized, and interdisciplinary communication should be optimized to ensure that LCS patients are placed on appropriate preventive therapy.