Damnacanthal is an anthraquinone, extracted, and purified from the root of Morinda citrifolia in Thailand. This study aimed to measure acute oral toxicity and to investigate the anticancer activity of damnacanthal in colorectal tumorigenesis. We found that the growth of human colorectal cancer cells was inhibited by damnacanthal in a dose- and a time-dependent manner. The growth inhibitory effect of damnacanthal was better than that of 5-FU used as a positive control in colorectal cancer cells, along with the downregulation of cell cycle protein cyclin D1. Similarly, an oral treatment of damnacanthal effectively inhibited the growth of colorectal tumor xenografts in nude mice, which was approximately 2-3-fold higher as compared to 5-FU by tumor size as well as expression of bioluminescence. Furthermore, the study of acute oral toxicity in mice exhibited a relatively low toxicity of damnacanthal with a LD50 cut-off value of 2500 mg/kg according to OECD Guideline 423. These results reveal the potential therapeutic activity of a natural damnacanthal compound as an anti-colorectal cancer drug.

The field of cardio-oncology was born from the necessity for recognition and management of cardiovascular diseases among patients with cancer. This need for this specialty continues to grow as patients with cancer live longer as a result of lifesaving targeted and immunologic cancer therapies beyond the usual chemotherapy and/or radiation therapy. Often, potentially cardiotoxic anticancer treatment is necessary in patients with baseline cardiovascular disease. Moreover, patients may need to continue therapy in the setting of incident cancer therapy-associated cardiotoxicity. Herein, we present and discuss the concept of permissive cardiotoxicity as a novel term that represents an essential concept in the field of cardio-oncology and among practicing cardio-oncology specialists. It emphasizes a proactive rather than reactive approach to continuation of lifesaving cancer therapies in order to achieve the best oncologic outcome while mitigating associated and potentially off-target cardiotoxicities.

UNASSIGNED: The microscopic tumor extension before, during or after radiochemotherapy (RCHT) and its correlation with the tumor microenvironment (TME) are presently unknown. This information is, however, crucial in the era of image-guided, adaptive high-precision photon or particle therapy.
UNASSIGNED: In this pilot study, we analyzed formalin-fixed paraffin-embedded (FFPE) tumor resection specimen from patients with histologically confirmed squamous cell carcinoma (SCC; n = 10) or adenocarcinoma (A; n = 10) of the esophagus, having undergone neoadjuvant radiochemotherapy followed by resection (NRCHT + R) or resection (R)]. FFPE tissue sections were analyzed by immunohistochemistry regarding tumor hypoxia (HIF-1α), proliferation (Ki67), immune status (PD1), cancer cell stemness (CXCR4), and p53 mutation status. Marker expression in HIF-1α subvolumes was part of a sub-analysis. Statistical analyses were performed using one-sided Mann-Whitney tests and Bland-Altman analysis.
UNASSIGNED: In both SCC and AC patients, the overall percentages of positive tumor cells among the five TME markers, namely HIF-1α, Ki67, p53, CXCR4 and PD1 after NRCHT were lower than in the R cohort. However, only PD1 in SCC and Ki67 in AC showed significant association (Ki67: p = 0.03, PD1: p = 0.02). In the sub-analysis of hypoxic subvolumes among the AC patients, the percentage of positive tumor cells within hypoxic regions were statistically significantly lower in the NRCHT than in the R cohort across all the markers except for PD1.
UNASSIGNED: In this pilot study, we showed changes in the TME induced by NRCHT in both SCC and AC. These findings will be correlated with microscopic tumor extension measurements in a subsequent cohort of patients.

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The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease.
Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies.
In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

BACKGROUND: Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction.
OBJECTIVE: The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio).
METHODS: Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed.
RESULTS: A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (P > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95; P < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84; P = 0.022).
CONCLUSIONS: Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population.

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

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