Notes

Earlier Management associated with Tolvaptan Could Boost Survival within Sufferers with Cirrhotic Ascites.
In irradiation-induced, p53-dependent pathways of apoptosis, the pro-apoptotic Noxa represents one of several, yet to be identified, pathways simultaneously triggered by p53 to produce mitochondrial ceramide accumulation and apoptosis. In contrast, Bcl-2 functions as a broader inhibitor of both ceramide accumulation and apoptosis. Altogether, these results indicate that members of the Bcl-2 family differentially regulate ceramide accumulation and reveal the existence of crosstalk between Bcl-2 family members and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.Regulatory T cells (Tregs) and transforming growth factor β (TGF-β) are believed to play key roles in both postoperative pro-inflammatory and anti-inflammatory responses of malignancies. Recombinant human thrombomodulin (rTM) is implied to inhibit the interaction between TGF-β and Tregs. The aim of this study is to evaluate the antitumor effects of rTM against gastrointestinal tumors under systemic inflammation. Mice were subjected to cecal ligation and puncture and percutaneous allogeneic tumor implantation. rTM were introduced by percutaneous injection into the abdominal cavity. The effects of rTM were evaluated by weight of implanted tumor, proportion of Tregs in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and temporal evaluation of serum cytokines. The effect of rTM was also evaluated on the in vitro differentiation of naïve T cells into induced Tregs induced by TGF-β and interleukin (IL) -2. rTM significantly inhibited the proliferation of the implanted tumor cells in an inflammation-dependent manner. rTM also reduced the fractions of regulatory T cells and induced regulatory T cells among both PBL and TIL. Temporal evaluation of serum cytokine levels in the model mice showed that rTM significantly suppressed the increases in the serum levels of IL-2 and TGF-β. An in vitro differentiation assay revealed that rTM inhibited the differentiation of naïve T cells into Tregs triggered by IL-2- and TGF-β. rTM has suppressive effects on inflammation-induced gastrointestinal tumor growth by suggestively affecting differentiation of Tregs.More than 50% of colorectal cancer (CRC) deaths are attributed to metastasis, and the liver is the most common distant metastatic site of CRC. The molecular mechanisms underlying CRC liver metastasis are very complicated and remain largely unknown. Accumulated evidence has shown that non-coding RNAs (NcRNAs) play critical roles in tumor development and progression. Here we reviewed the roles and underlying mechanisms of NcRNAs in CRC liver metastasis.Depression and anxiety co-occur with chronic pain, and all three are thought to be caused by dysregulation of shared brain systems related to emotional processing associated with body sensations. Understanding the connection between emotional states, pain, and bodily sensations may help understand chronic pain conditions. We developed a mobile platform for measuring pain, emotions, and associated bodily feelings in chronic pain patients in their daily life conditions. Sixty-five chronic back pain patients reported the intensity of their pain, 11 emotional states, and the corresponding body locations. These variables were used to predict pain 2 weeks later. Applying machine learning, we developed two predictive models of future pain, emphasizing interpretability. One model excluded pain-related features as predictors of future pain, and the other included pain-related predictors. The best predictors of future pain were interactive effects of (a) body maps of fatigue with negative affect and (b) positive affect with past pain. Our findings emphasize the contribution of emotions, especially emotional experience felt in the body, to understanding chronic pain above and beyond the mere tracking of pain levels. The results may contribute to the generation of a novel artificial intelligence framework to help in the development of better diagnostic and therapeutic approaches to chronic pain.
Immunogenic chemotherapy promotes antitumor immune response in the tumor microenvironment (TME). In gastric cancer, the effect of a preexisting T-cell-inflamed TME on the efficacy of adjuvant chemotherapy (ACT) is unclear. The purpose of the present study was to evaluate the benefits of ACT in T-cell-inflamed gastric cancer.

Three cohorts (n = 267, 300, and 198) of gastric cancer patients who underwent gastrectomy with or without ACT were included in this study. Based on a well-defined T-cell-inflamed gene signature, which includes 13 genes, these patients were classified into non-T-cell-inflamed, intermediate T-cell-inflamed, and T-cell-inflamed subgroups. The CIBERSORT software was used to estimate the immune cells infiltrating the TME, and the Kaplan-Meier curve was plotted for survival analysis.

The T-cell-inflamed patients had high levels of CD8 + T, gamma delta T, and activated CD4 + memory T cells, whereas low level of resting NK cells was observed in all the three cohorts (all P < 0.05). In patients with stage II-IV disease without distant metastasis, those who were T-cell-inflamed were more likely to benefit from ACT (all P < 0.05), regardless of the chemotherapy regimen. Furthermore, patients with both T-cell-inflamed and high microsatellite instability status also were likely to benefit from ACT (P = 0.019).

The present study shows that T-cell inflammation is predictive of a survival benefit from ACT. Our findings will be helpful in making decisions regarding the use of chemotherapy in combination with immunotherapy to improve the clinical outcomes in patients with gastric cancer.
The present study shows that T-cell inflammation is predictive of a survival benefit from ACT. Our findings will be helpful in making decisions regarding the use of chemotherapy in combination with immunotherapy to improve the clinical outcomes in patients with gastric cancer.
The American Society of Clinical Oncology guidelines recommend early referral to reproductive endocrinology and infertility (REI) specialists for young women diagnosed with breast cancer. Current practice patterns demonstrate an increased utilization of neoadjuvant chemotherapy (NAC). We evaluated premenopausal women with breast cancer after consultation with a Fertility Nurse Specialist (FNS) and determine factors associated with referral to REI specialists.

This retrospective review included all premenopausal women diagnosed at our institution with stage 0-III unilateral breast cancers between 2009 and 2015 who completed an FNS consultation. Clinicopathologic features and factors associated with referral to REI after FNS consultation were analyzed.

A total of 334 women were identified. Median age was 35years (interquartile range 32-38). The majority of women were single (n = 198, 59.3%) and nulliparous (n = 239, 71.6%). REI referrals were common (n = 237, 71.0%). The Breast Surgery service was the mosre frequently declined referral to REI, suggesting that the need to start NAC may influence decisions regarding fertility preservation. With increasing utilization of NAC, our study supports the need for further counseling and education regarding fertility preservation for women undergoing NAC.
Advanced low rectal cancer has a non-negligible risk of lateral pelvic lymph node (LPLN) metastasis (LPLNM) and lateral local recurrence (LR) after neoadjuvant (chemo)radiotherapy and total mesorectal excision. LPLN dissection (LPLND) reduces LR but increases postoperative complications and sexual/urinary dysfunction.

The aim of this study was to develop a new radiomics-based prediction model for LPLNM in patients with rectal cancer.

A total of 247 patients with rectal cancer and enlarged LPLNs treated by (chemo)radiotherapy and LPLND were enrolled in this retrospective, multicenter study. LPLN radiomic features were extracted from pretreatment portal venous-phase computed tomography images. A radiomics score of LPLN was constructed based on the least absolute shrinkage and selection operator regression in a primary cohort of 175 patients. Model performance was assessed in terms of discrimination, calibration, and decision curve analysis, and was externally validated in 72 patients.

The radiomics score showed significantly better discrimination compared with pretreatment short-axis diameter measurements in both the primary (area under the curve [AUC] 0.91 vs. 0.83, p = 0.0015) and validation (AUC 0.90 vs. 0.80, p = 0.0298) cohorts. Decision curve analysis also indicated the superiority of the radiomics score. In a subanalysis of patients with a short-axis diameter ≥ 7mm, the radiomics nomogram, incorporating the radiomics score and LPLN shrinkage to ≤ 4mm, had better discrimination compared with a model incorporating only LPLN shrinkage in both cohorts.

Radiomics-based prediction modeling provides individualized risk estimation of LPLNM in rectal cancer patients treated with (chemo)radiotherapy, and outperforms measurements of pretreatment LPLN diameter.
Radiomics-based prediction modeling provides individualized risk estimation of LPLNM in rectal cancer patients treated with (chemo)radiotherapy, and outperforms measurements of pretreatment LPLN diameter.
Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario.

This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS.

From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS).

SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.
SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.The current study intends to investigate a novel drug delivery system (DDS) based on niosomes structure (NISM) and bovine serum albumin (BSA) which was formulated to BSA coated NISM (NISM-B). Also, selenium nanoparticles (SeNPs) have been prepared by BSA mediated biosynthesis. Finally, the NISM-B was hybridized with SeNPs and was formulated as NISM-B@SeNPs for drug delivery applications. Physicochemical properties of all samples were characterized by UV-Vis spectroscopy, FT-IR, DLS, FESEM, and EDX techniques. The cytotoxicity of all samples against A549 cell line was assessed by cell viability analysis and flow cytometry for apoptotic cells as well as RT-PCR for the expression of MDR-1, Bax, and Bcl-2 genes. Besides, in vivo biocompatibility was performed by LD50 assay to evaluate the acute toxicity. The proposed formulation has a regular spherical shape and approximately narrow size distribution with proper zeta-potential values; the proposed DDS revealed a good biocompatibility. The compound showed a significant cytotoxic effect against A549 cell line.
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