Notes

Efficiency associated with postoperative radiotherapy joined with taxol+carboplatin radiation treatment programs inside the management of high-risk early-stage endometrial cancer.
001). However, dry mouth ratings on both the EORTC QLQ-OH17 (p=0.036) and NRS (p=0.045) improved more in the SO group than in the NS group. Plaque on the teeth improved in both the SO (p=0.008) and NS (p=0.018) groups, but plaque on the tongue and erythema only improved with NS.

This study did not detect an overall significant difference between SO and NS. Both mouth rinses improved oral health parameters, indicating that systematic assessment and oral care may reduce oral discomfort.

NCT02067572.
NCT02067572.Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.In the course of chronic kidney disease (CKD), alterations in the bone-vascular axis augment the risk of bone loss, fractures, vascular and soft tissue calcification, left ventricular hypertrophy, renal and myocardial fibrosis, which markedly increase morbidity and mortality rates. A major challenge to improve skeletal and cardiovascular outcomes in CKD patients requires a better understanding of the increasing complex interactions among the main modulators of the bone-vascular axis. Serum parathyroid hormone (PTH), phosphorus (P), calcium (Ca), fibroblast growth factor 23 (FGF23), calcidiol, calcitriol and Klotho are involved in this axis interact with RANK/RANKL/OPG system and the Wnt/β-catenin pathway. The RANK/RANKL/OPG system controls bone remodeling by inducing osteoblast synthesis of RANKL and downregulating OPG production and it is also implicated in vascular calcification. The complexity of this system has recently increased due the discovery of LGR4, a novel RANKL receptor involved in bone formation, but possibly also in vascular calcification. The Wnt/β-catenin pathway plays a key role in bone formation when this pathway is activated, bone is formed, but when it is inhibited, bone formation is stopped. In the progression of CKD, a downregulation of the Wnt/β-catenin pathway has been described which occurs mainly through the not coincident elevations of sclerostin, Dickkopf1 (Dkk1) and the secreted Frizzled Related Proteins (sFRPs). This review analyzes the interactions of PTH, P, Ca, FGF23, calcidiol, calcitriol and Klotho with the RANKL/RANKL/OPG system and the Wnt/β-catenin, pathway and their implications in bone and cardiovascular disorders in CKD.
The aim of this study was to test whether CES1, UMPS, DPYS and TPYS polymorphisms influence the outcomes of gastroenteric cancer patients.

We consecutively enrolled 338 patients who were diagnosed with colorectal and gastric cancer from January 2016 to December 2018 at the Harbin Medical University Cancer Hospital, China.

We found that the patients with CES1 rs7187684 CC genotype had a higher proportion of stage III-IV and relapse rate significantly compared with CT/TT genotype, and the patients with rs7187684 CC genotype had a higher level of CA199 than CT/TT genotype after adjusted for tumor stage, and medication, age, sex, smoking, and drinking. Moreover, the patients with rs7187684 CC genotype had shorter event-free survival (EFS) than CT/TT genotype, and a significant shorter EFS was also found in the patients with rs2244613 TT genotype than GG or GT genotype. Subset analysis results showed that the male, less-drinking or gastric cancer patients with rs7187684 CC genotype had shorter EFS than the patients with CT/TT genotype. Compared with the patients with CES1 rs2244613 TT genotype, the stage I-II patients with GG/GT genotype had longer progression-free survival (PFS), and the male patients with GG/GT genotype had longer EFS. Multivariate Cox regression analysis showed that stage III-IV and tumor metastasis could reduce the patients' PFS and EFS.

The identified CES1 polymorphisms might provide guide for the identification of gastroenteric cancer patients who were likely to benefit from capecitabine-based chemotherapy.
The identified CES1 polymorphisms might provide guide for the identification of gastroenteric cancer patients who were likely to benefit from capecitabine-based chemotherapy.
Preclinical studies support the JAK2-STAT3 signaling pathway as a key driver in CD44+ CD24- "stem-cell-like" breast cancer cells. Plumbagone Ruxolitinib is an orally bioavailable JAK1/2 inhibitor. We aimed to identify the recommended phase 2 dose (RP2D) of ruxolitinib in combination with paclitaxel in patients with HER2-negative metastatic breast cancer (MBC).

Eligible patients had HER2-negative MBC and had received ≤ 3 chemotherapy regimens for advanced disease. Patients received oral ruxolitinib (10-25mg bid) in a 3 + 3 dose escalation design in combination with weekly paclitaxel 80mg/m
in a 3-week cycle. The primary objective was to determine the maximum tolerated dose (MTD) and the RP2D.

Nineteen patients received protocol therapy (mean age 52years). Eight (42%) had triple-negative breast cancer and 11 (58%) had hormone receptor-positive disease; 12 (63%) had visceral disease. Ten (53%) patients had not received prior treatment for advanced disease. Patients received a median number of 5 cycles of combination therapy (range 1-12) and five patients continued single-agent ruxolitinib. The MTD of ruxolitinib was 25mg bid when combined with paclitaxel, and the RP2D for the combination was 15mg bid. Thirteen (68%) patients required dose reductions or holds. Most frequent toxicities reported of any grade were neutropenia (50%) and anemia (33%). There were no grade 4/5 toxicities attributed to study drug. Four (21%) patients had PR, 12 (63%) had SD and three (16%) had PD as their best response.

The combination of ruxolitinib and weekly paclitaxel was well tolerated with evidence of clinical activity. Further analysis of this combination is ongoing (NCT02041429).

NCT02041429. Date of registration January 22, 2014.
NCT02041429. Date of registration January 22, 2014.
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