Adjuvant therapy for T3N0 rectal cancer in the total mesorectal excision era- identification of the high risk patients

<p>Abstract</p> <p>Background</p> <p>Adjuvant therapy for T3N0 rectal cancer was controversial with respect to both radiation and the use of a combined regimen of chemotherapy. We evaluated both clinical features and biomarkers and sought to determine risk factors for those patients retrospectively.</p> <p>Methods</p> <p>A total of 122 patients with T3N0 rectal cancer were analyzed in this study from January 2000 to December 2005. Clinicopathologic and biomarkers were used to predict local recurrence (LR), disease-free survival (DFS), and overall survival (OS).</p> <p>Results</p> <p>The median follow-up interval was 45.4 months. Five-year LR, DFS, and OS rates were 10.4%, 68.3%, and 88.7%. Having a lower tumor location and showing low P21 and high CD44v6 expression were identified as risk factors for LR: patients with two or three of these risk factors had a higher 5-year LR rate (19.3%) than did patients with none or one of these risk factors (6.8%) (p = 0.05). A poorer DFS was related to low P21 nor high CD44v6 expression but not to tumor location: the 5-year DFS rates were 79.3% for those with neither, 65.9% for those with either one or the other, and 16.9% for those with both (p = 0.00).</p> <p>Conclusions</p> <p>The prognostic model including tumor location, P21 and CD44v6 expressions could help to distinguish these patients with high risk T3N0 patients and determine whether adjuvant therapy was beneficial.</p

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049) and CIMP positive (P=0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy

Intensified paraglacial slope failures due to accelerating downwasting of a temperate glacier in Mt. Gongga, southeastern Tibetan Plateau

Topographic development via paraglacial slope failure (PSF) represents a complex interplay between geological structure, climate, and glacial denudation. Southeastern Tibet has experienced amongst the highest rates of ice mass loss in High Mountain Asia in recent decades, but few studies have focused on the implications of this mass loss on the stability of paraglacial slopes. We used repeat satellite- and unpiloted aerial vehicle (UAV)-derived imagery between 1990 and 2020 as the basis for mapping PSFs from slopes adjacent to Hailuogou Glacier (HLG), a 5 km long monsoon temperate valley glacier in the Mt. Gongga region. We observed recent lowering of the glacier tongue surface at rates of up to 0.88 m a−1 in the period 2000 to 2016, whilst overall paraglacial bare ground area (PBGA) on glacier-adjacent slopes increased from 0.31 ± 0.27 km2 in 1990 to 1.38 ± 0.06 km2 in 2020. Decadal PBGA expansion rates were ∼ 0.01 km2 a−1, 0.02 km2 a−1, and 0.08 km2 in the periods 1990–2000, 2000–2011, and 2011–2020 respectively, indicating an increasing rate of expansion of PBGA. Three types of PSFs, including rockfalls, sediment-mantled slope slides, and headward gully erosion, were mapped, with a total area of 0.75 ± 0.03 km2 in 2020. South-facing valley slopes (true left of the glacier) exhibited more destabilization (56 % of the total PSF area) than north-facing (true right) valley slopes (44 % of the total PSF area). Deformation of sediment-mantled moraine slopes (mean 1.65–2.63 ± 0.04 cm d−1) and an increase in erosion activity in ice-marginal tributary valleys caused by a drop in local base level (gully headward erosion rates are 0.76–3.39 cm d−1) have occurred in tandem with recent glacier downwasting. We also observe deformation of glacier ice, possibly driven by destabilization of lateral moraine, as has been reported in other deglaciating mountain glacier catchments. The formation, evolution, and future trajectory of PSFs at HLG (as well as other monsoon-dominated deglaciating mountain areas) are related to glacial history, including recent rapid downwasting leading to the exposure of steep, unstable bedrock and moraine slopes, and climatic conditions that promote slope instability, such as very high seasonal precipitation and seasonal temperature fluctuations that are conducive to freeze–thaw and ice segregation processes

Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model.

Immuno-oncology (IO)-based therapies such as checkpoint inhibitors, bi-specific antibodies, and CAR-T-cell therapies have shown significant success in the treat- ment of several cancer indications. However, these therapies can result in the de- velopment of severe adverse events, including cytokine release syndrome (CRS). Currently, there is a paucity of in vivo models that can evaluate dose-response relationships for both tumor control and CRS-related safety issues. We tested an in vivo PBMC humanized mouse model to assess both treatment efficacy against specific tumors and the concurrent cytokine release profiles for individual human donors after treatment with a CD19xCD3 bispecific T-cell engager (BiTE). Using this model, we evaluated tumor burden, T-cell activation, and cytokine release in response to bispecific T-cell-engaging antibody in humanized mice generated with different PBMC donors. The results show that PBMC engrafted NOD-scid Il2rgnull mice lacking expression of mouse MHC class I and II (NSG-MHC-DKO mice) and implanted with a tumor xenograft predict both efficacy for tumor control by CD19xCD3 BiTE and stimulated cytokine release. Moreover, our find- ings indicate that this PBMC-engrafted model captures variability among donors for tumor control and cytokine release following treatment. Tumor control and cytokine release were reproducible for the same PBMC donor in separate experi- ments. The PBMC humanized mouse model described here is a sensitive and re- producible platform that identifies specific patient/cancer/therapy combinations for treatment efficacy and development of complications

Multidisciplinary Treatment for Colorectal Peritoneal Metastases: Review of the Literature

Peritoneum is one of the common sites of metastasis in advanced stage colorectal cancer patients. Colorectal cancer patients with peritoneal metastases (PM) are traditionally believed to have poor prognosis, which indicates it is of no value to adopt surgical treatment. With the advancement of surgical techniques, hyperthermic intraperitoneal chemotherapy (HIPEC), and multidisciplinary treatment in recent years, the cognition and treatment strategies of colorectal peritoneal metastases (CPM) have changed dramatically. In terms of prognosis, CPM under the palliative systemic treatment shows an inferior outcome compared with nonperitoneal metastasis. Nevertheless, some CPM patients amenable to the complete peritoneal cytoreductive surgery (CRS) combined with HIPEC may achieve long-term survival. The prognostic factors of CPM comprise peritoneal carcinomatosis index (PCI), completeness of cytoreduction score (CC score), the presence of extraperitoneal metastasis (liver, etc.), Peritoneal Surface Disease Severity Score (PSDSS), Japanese peritoneal staging, and so forth. Taken together, literature data suggest that a multimodality approach combining complete peritoneal CRS plus HIPEC, systemic chemotherapy, and targeted therapy may be the best treatment option for PM from colorectal cancer

Complete chloroplast genome sequence of Bletilla striata (Thunb.) Reichb. f., a Chinese folk medicinal plant

Bletilla striata (Thunb.) Reichb. f. is one of the commonly used traditional Chinese medicine with tuber as medicine. We report herein the complete chloroplast genome sequence of Bletilla striata (Thunb.) Reichb. f. It has a length of 159,491 bp, which contained a small single-copy (SSC) region of 18,778 bp and a large single-copy (LSC) region of 87,139 bp, separated by two copies of an inverted repeat (IR) of 26,787 bp. The chloroplast genome contains 114 unique genes, including 80 PCG, 30 tRNA, and 4 rRNA genes. In addition, 18 genes contained one or two introns, which of those including 10 PCG genes possess a single intron, and 2 PCG genes harbor two introns; and 6 tRNA genes harbor a single intron. In this study, Bletilla stariata is sister to Bletilla formosana and clustered within the group consisting of the species that belong to Orchiidaceae

Complete chloroplast genome sequence of Pinellia ternata (Thunb.) Breit, a medicinal plants to China

Pinellia ternata (Thunb.) Breit is one of the commonly used traditional Chinese medicine with tuber as medicine. We report herein the complete chloroplast genome sequence of Pinellia ternata (Thunb.) Breit. It is length of 167,280 bp, which contained a small single-copy (SSC) region of 23,618 bp and a large single-copy (LSC) region of 92,450 bp, separated by two copies of an inverted repeat (IR) of 25,606 bp. The chloroplast genome contains 113 unique genes, including 79 PCG, 4 rRNA genes, and 30 tRNA genes. In addition, 19 genes contained one or two introns, which of those including 13 PCG genes possess a single intron and 2 PCG genes harbor two introns; and 6 tRNA genes harbor a single intron. In this study, Pinellia ternata is sister to Pinellia pedatisecta and clustered within the group consisting of the species that belong to Araceae