SETDB1: A perspective into immune cell function and cancer immunotherapy

Oncogene SET Domain Bifurcated 1 (SETDB1)/ESET, an H3K9 methyltransferase, was originally discovered over two decades ago; however, its function in the immune response was not first reported until 2011. SETDB1 immune functions include B cell maturation, T cell activity regulation, and immune escape in cancer cells. In B lymphocytes, SETDB1 mediates the transition from pro-B to pre-B cells and represses endogenous retroviruses (ERV) to encourage B cell lineage differentiation and maturation. SETDB1 alters T cell function by methylating IL-2 and IL-17 promoters and mediating T cell lineage commitment and development. In addition, SETDB1 plays a critical role in ERV silencing within a variety of immune cells, which can indirectly weaken the immune response. Although SETDB1 is critical for normal immune cell function, overexpression in cancer cells negatively impacts immune cell fights against cancer through decreased tumour immunogenicity. Within cancer cells, SETDB1 overexpression represses production and infiltration of antitumour immune cells, mediates immune escape through TE and ERV silencing, represses the type I interferon pathway, and interferes in immune checkpoint blockade (ICB) outcomes by regulation of PD-L1 expression and IFN signalling. In this review, we further discuss the immunological mechanisms of SETDB1 in normal and cancerous cells and its implications in cancer immunotherapy.     

Hand-assisted laparoscopic radical nephrectomy in pregnancy

Purpose

To demonstrate the beneficial results of hand-assisted laparoscopic tumor nephrectomy in pregnancy and to emphasize the proper timing of such surgery for its crucial importance attempting to avoid fatal cancer-related outcomes as a result of late interventions of aggressive tumors.

Methods

A report of a 32-year-old woman with a 61 × 41 mm chromophobe renal cell carcinoma (RCC) successfully treated with laparoscopic transperitoneal hand-assisted nephrectomy during the 20th week of gestation is presented.

Results

The fetus was stable during the intervention; the postoperative period was uneventful; she had a normal vaginal delivery at term and gave birth to a healthy female child. The patient remained tumor-free at her 34-month follow-up.

Conclusion

Although the pure laparoscopic interventions have become recognized in the treatment of RCC over the last decade, these methods have their limitations and dangers as well. The hand-assistance method makes the procedure faster and safer which is especially important during second or third trimester. Renal biopsy may play a specifically important role in predicting the malignant potential of a renal tumor, whereas postponement of this surgery until after delivery, may lead to the mother’s death. To our knowledge, this is the first report on hand-assisted laparoscopic nephrectomy in pregnancy.     

Effects of acupressure on the childbirth satisfaction and experience of birth: A randomized controlled trial

BackgroundComplementary and alternative medicines have been used to increase comfort and relaxation in mothers during labor. Comforting and preparing the mother in labor can create a positive birth experience. The aim of this study was to evaluate the effect of acupressure on childbirth satisfaction and the experience of giving birth in women with full-term pregnancy, before the onset of labor.MethodsIn 2016, a randomized clinical trial study was conducted in Shahid Akbar Abadi Hospital, Tehran, Iran, enrolling 120 pregnant women at 39–40 gestational weeks with no signs of the onset of labor. They were divided randomly into acupressure, sham acupressure, and control groups. Acupressure points including SP6, BL 60, and BL 32 were pressured bilaterally. Interventions were performed by the researcher, the mother and her relative (husband). Childbirth satisfaction was measured 24 h after delivery. The collected data were analyzed by SPSS software and comparing tests were Chi-squared, Kruskal-Wallis, ANOVA tests (P ≤ 0.05).ResultsThe total childbirth satisfaction did not differ significantly among the three groups (P = 0.460), but the acupressure group had a higher level of satisfaction than the other two groups. Moreover, statistical tests regarding the expectations of the childbirth experience showed a significant difference among the groups (P = 0.033). The actual birth was closest to the expectations of subjects in the acupressure group.ConclusionThis study demonstrated that acupressure may be used as a method in order to attempt to provide a good birth experience and satisfaction of childbirth.     

Long-term deaths from melanoma according to tumor thickness at diagnosis

There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872–879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness <0.80 mm, 10.6% for tumors 0.8 to <1.0 mm and generally more than 30% for melanomas measuring 3 mm and more. For melanomas <1.0 mm, most deaths occurred between 5 and 20 years after diagnosis, whereas for thicker melanomas the reverse was true with most deaths occurring within the first 5 years. Five-year case fatality decreased over successive calendar time periods for melanomas <1.0 mm, but not for melanomas ≥1.0 mm. These findings demonstrate that the time course for fatal melanomas varies markedly according to tumor thickness at diagnosis. Improved understanding of the patient factors and characteristics of melanomas, in addition to tumor thickness, which increase the likelihood of progression, is needed to guide clinical diagnosis, communication with patients and ongoing surveillance pathways of patients with potentially fatal lesions.     

Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

OBJECTIVE: The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT(3))antagonists in revolutionizing the management of platinum-based chemotherapy-induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT(3) antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting cleary endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. METHODS: Data for patients (n=159) receiving platinum-based chemotherapy regimens were retrospectively collected . Patients getting 5-HT(3) antagonists without steriods or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered , number of cycles, and Eastern Cooperative Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of > or = grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic eficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. RESULTS: A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron ( n=157), granisetron ( n=81), and ondansetron ( n=131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p=0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p=0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting ( p= 0.15 and p=0.63, respectively). However, complete nausea control was signinficantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p<0.05). CONCLUSION: No significant difference exists in the antiemetic efficacy of the three 5-HT(3) antagonists studied in controlling CINV when administered in combination with dexamethasone. Choicce of antiemetic regimen should therefore be based on drug cost.     

Hyperpolarized helium-3 MR imaging of pulmonary function

Recent advances in HP MR imaging contrast agents have led to novel tests of pulmonary function. Many of these tests show promise in the clinical arena.     

The intriguing encounters of Pavlov and Cushing

Ivan Petrovich Pavlov and Harvey William Cushing were two of the most prominent neuroscientists of the early 20th century. Their contributions helped advance the understanding of the brain and its disorders, and propelled neuroscience into a new era of research and treatment. Although separated geographically and culturally, Pavlov and Cushing exchanged letters and followed one another's careers from afar. They met only a few times, during international scientific gatherings in the US and abroad. These encounters were captured in journal entries, letters, and photographs, and provide a glimpse into the lives of these two great men and the history of neuroscience at the turn of the last century.