The synthesis and functionalization of metal organic frameworks and their applications for the selective separation of proteins/peptides.

Recently, proteins separation has drawn great interest for the full investigation of a proteome because the proteins separation is the precondition when conducting clinical research or proteomics research. Metal organic frameworks (MOFs) are fabricated via covalent connection between organic ligands and metal ions/clusters units. MOFs have attracted much attention due to the ultra-high specific surface area, tunable structure, more metal site or unsaturated site, and chemical stability. Over the past decade, different functionalization types of MOFs have been reported in combination with amino acids, nucleic acids, proteins, polymers, and nanoparticles for various applications. In this review, the synthesis and functionalization of MOFs have been thoroughly discussed, and we introduced the existing problems and development trends in these fields. Furthermore, MOFs as advanced adsorbents for selective separation of proteins/peptides are summarized. Additionally, we present a comprehensive prospects and challenges in the preparation of robust functional MOFs-based adsorbents and make a final outlook on their future development prospects in selective separation of proteins/peptides.

The impact of prophylactic oophorectomy on the survival for postmenopausal patients with pT4a colorectal cancer.

PURPOSE: This study aimed to evaluate the prognostic effect of prophylactic oophorectomy (PO) in postmenopausal patients with pT4 colorectal cancers (CRC) in terms of overall survival (OS), disease-free survival (DFS), and peritoneal metastasis. METHODS: The data of postmenopausal female patients with pT4 CRC undergoing surgical resection between 2000 and 2019 were analyzed. Kaplan-Meier analysis was used to evaluate survival outcomes between patients treated with and without PO. Risk factors for DFS and peritoneal metastasis were evaluated using Cox regression analysis. p-values <0.05 were considered statistically significant. RESULTS: Totally, 176 (34.3%) patients received PO. There was no significant difference in estimated blood loss, rates of postoperative complications, and hospitalization between the PO and non-PO groups. The 5-year OS and DFS rates were similar in the two groups (47.9% vs. 54.1%, p = 0.278; 53.5% vs. 50.5%, p = 0.161, respectively). In the subgroup analysis of patients with peritoneal metastasis, the median survival was significantly longer for the PO group compared with the non-PO group (14 vs. 11 months, p < 0.001). CONCLUSION: Undertaking PO in pT4 CRC female patients did not confer a survival benefit. Indication of PO even for advanced CRC patients should require caution. It has potential survival benefit only when the patients developed metachronous peritoneal metastases.

Recent advances in development of functional magnetic adsorbents for selective separation of proteins/peptides.

Nowadays, proteins separation has attracted great attention in proteomics research. Because the proteins separation is helpful for making an early diagnosis of many diseases. Magnetic nanoparticles are an interesting and useful functional material, and have attracted extensive research interest during the past decades. Because of the excellent properties such as easy surface functionalization, tunable biocompatibility, high saturation magnetization etc, magnetic microspheres have been widely used in isolation of proteins/peptides. Notably, with the rapid development of surface decoration strategies, more and more functional magnetic adsorbents have been designed and fabricated to meet the growing demands of biological separation. In this review, we have collected recent information about magnetic adsorbents applications in selective separation of proteins/peptides. Furthermore, we present a comprehensive prospects and challenges in the field of protein separation relying on magnetic nanoparticles.

Minimally invasive para-aortic lymph node dissection in left-sided colonic and rectal cancer: experience based on a high-volume centre.

AIM: There is no established consensus on the optimal surgical approach to para-aortic lymph node (PALN) dissection in patients with colorectal cancer. This study aimed to demonstrate the technical and oncological safety of minimally invasive PALN dissection for left-sided colonic and rectal cancer patients with clinically suspected infrarenal PALN metastasis. METHOD: One hundered and one patients who underwent primary tumour resection and minimally invasive (laparoscopic n = 92, robotic n = 9) PALN dissection for left-sided colonic and rectal cancer were included. Logistic regression analysis was used to identify risk factors for PALN metastasis. Survival outcomes were evaluated using the Kaplan-Meier (log-rank) method. RESULTS: Para-aortic lymph node metastasis was pathologically confirmed in 23 patients (22.8%). Postoperative complications occurred in 22 patients (21.8%). Pathological N2 stage (OR = 9.337, p = 0.003) and inferior mesenteric artery LN metastasis (OR = 7.499, p = 0.009) were independently associated with PALN metastasis. The median follow-up time was 32 months (range 3-92 months). In all patients, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 76.1% and 69.5%, respectively. The 5-year OS and PFS rates in patients with PALN metastasis were 49.8% and 47.5%, respectively. Patients with PALN metastasis had lower 5-year OS (p = 0.023) and PFS rates (p = 0.035) than those without PALN metastasis. CONCLUSION: Minimally invasive PALN dissection had acceptable postoperative complications and may be oncologically beneficial in selected patients with clinically suspicious PALN metastasis.

A refined prediction of early recurrence combining tumor deposits in patients with resected rectal mucinous adenocarcinoma.

PURPOSE: Early recurrence (ER) of rectal mucinous adenocarcinoma (MAC) has yet to be defined. We therefore explored risk factors for ER and constructed a predictive nomogram. METHOD: A total of 145 rectal MAC patients undergoing radical surgery were included. The minimum P value method was used to determine the optimal cut-off point to discriminate between ER and late recurrence (LR). Risk factors for ER were determined by a logistic regression analysis, and a predictive nomogram was constructed. RESULTS: A total of 62 (42.8%) patients developed tumor recurrence. The optimal time to define ER was 12 months. A pre-treatment tumor distance from the anal verge ≤ 7 cm, pathological N stage, lymphovascular invasion, tumor deposits, and time to recurrence ≤ 12 months were significantly associated with a poor post-recurrence survival in patients with recurrence. A pre-treatment serum carcinoembryonic antigen (CEA) level > 10 ng/ml, pre-treatment tumor distance from the anal verge ≤ 7 cm, pathological N + stage, perineural invasion, and tumor deposits were identified as independent risk factors associated with ER. A nomogram predicting ER was constructed (C-index 0.870). CONCLUSION: The pre-treatment serum CEA level, pre-treatment tumor distance from the anal verge, pathological N + stage, perineural invasion, and tumor deposits were significantly predictive of ER for rectal MAC patients.

Preoperative combination score of neutrophils, monocytes, and lymphocytes as a predictor for locally advanced rectal cancer.

OBJECTIVE: The aim of this study was to investigate the prognostic value of baseline peripheral blood neutrophils, monocytes, and lymphocytes on locally advanced rectal cancer (LARC) patients. METHODS: Clinicopathologic data of 317 LARC patients during July 2010 and October 2016 were retrospectively gathered. X-tile software was used to acquire the optimal cutoff values of neutrophils, monocytes, and lymphocytes. Peripheral blood immune score (PBIS) system was proposed and built based on neutrophils, monocytes, and lymphocytes. The Cox model was used to analyze the associations between clinicopathological characteristics and potential outcomes. C-index was used to assess model performance. A nomogram was constructed to predict prognosis, and a calibration plot was used to verify the accuracy of the nomogram prediction model. RESULTS: Cutoff values of neutrophils, lymphocytes, and monocytes were 4.46 (× 109/L), 1.66 (× 109/L), and 0.39 (× 109/L), respectively. PBIS was related to sex (P < 0.001), tumor length (P = 0.003), and tumor thickness (P = 0.014). Multivariate Cox regression analysis revealed that PBIS (HR = 0.707, 95% CI: 0.549-0.912, P = 0.008) was an independent predictor of DFS. High PBIS (HR = 0.697, 95% CI: 0.492-0.988, P = 0.043) and high lymphocyte count (HR = 0.511, 95%CI: 0.273-0.958, P = 0.036) were favorable factors of OS. Both C-index (0.74, 95% CI: 0.549-0.912) and the calibration plot showed good prediction ability of the nomogram for DFS. CONCLUSION: PBIS, composed of baseline peripheral blood neutrophils, monocytes, and lymphocytes, is an independent predictor of the prognosis of LARC. Combination of PBIS and ypTNM stage may be a promising marker to guide adjuvant therapy after the operation.

Para-aortic lymph node dissection in left-sided colorectal cancer: Risk factors, prognostic impact, and therapeutic value.

AIM: This study aimed to clarify risk factors, prognostic impact, and the therapeutic value of para-aortic lymph node (PALN) dissection in left-sided colorectal cancer. METHOD: One hundred and fifty-four patients who underwent primary tumor resection and PALN dissection for left-sided colorectal cancer were included. Logistic regression analysis was used to identify risk factors for PALN metastasis. Cox regression analysis was performed to identify risk factors for overall survival (OS). RESULTS: PALN metastasis was pathologically confirmed in 47 patients (30.5%). Postoperative complications occurred in 42 patients (27.3%). Pathological N stage (OR = 4.661, p = 0.034) and inferior mesenteric artery LNs metastasis (OR = 6.048, p = 0.003) remained to be independently associated with PALN metastasis, the 5-year OS rate and median survival in patients with PALN metastasis was 37.7% and 24 months. Elevated preoperative serum CA19-9 level (HR = 1.006, p = 0.007), number of positive LNs > 7 (HR = 7.263, p = 0.001), and mucinous adenocarcinoma or signet ring cell carcinoma (HR = 6.511, p = 0.001) were independently associated with OS in patients with PALN metastasis. CONCLUSION: PALN dissection in addition to primary tumor resection have acceptable postoperative complications and may be oncologically beneficial in selected left-sided colorectal cancer patients with clinically suspicious PALN metastasis.

Identification of proteins associated with treatment response of neoadjuvant chemoradiotherapy in rectal mucinous adenocarcinoma by co-expression network analysis based on proteomic analysis.

For rectal mucinous adenocarcinoma (MAC), identifying biomarkers of neoadjuvant chemoradiotherapy (NCRT) response has become imperative. This study applied label-free mass spectrometry and weighted gene co-expression network analysis to identify hub proteins in association with the NCRT response in 20 rectal MAC patients. We identified 131 differentially abundant proteins and 7 candidate proteins associated with the NCRT response. The immunostaining expressions of six proteins (ENOA, ILEU, MDHM, RM11, PTGDS, and RL3) were significantly associated with the NCRT response. Logistic regression analysis revealed that ENOA (OR = 6.275, P = 0.006) was independent risk hub protein for the NCRT response. Tow hub proteins (ENOA and PTGDS) were identified as significant risk factors by Cox regression analysis. A prognostic risk score system was constructed: risk score = (0.910 × EXPENOA) + (-1.519 × EXPPTGDS), and found to be an independent predictor of DFS in rectal MAC patients (HR = 10.308, P < 0.001). Our study suggested that ENOA may be a novel biomarker for the NCRT response and prognosis in rectal MAC patients. A two-hub-protein-based risk score system might be used for predicting tumor recurrence in rectal MAC patients. SIGNIFICANCE: NCRT resistance is a major problem in the treatment of rectal MAC patients. Identifying robust predictive biomarkers for NCRT resistance is beneficial to the stratified treatment of rectal MAC patients. In this study, label-free mass spectrometry and weighted gene co-expression network analysis identified ENOA as a potential novel biomarker for the NCRT response and prognosis. ENOA may be involved in the process of the NCRT resistance and tumor recurrence through the carbon metabolism pathway.

Educational needs, perception, and perspectives of oncologists regarding compassionate use programs in Asia.

OBJECTIVE: This study was conducted to capture the educational needs, perceptions, and perspectives of oncologists towards Compassionate Use Programs (CUPs) in Asia, with the aim of gathering insights related to unmet needs for physician and patient assistance. METHODS: The participants responded to a voluntary, self-administered, closed-ended questionnaire through an online platform between 29 April 2020 and 17 June 2020. RESULTS: A total of 111 oncologists provided informed consent to participate in the study. Of these, 102 respondents fully completed the questionnaire and were included in the analyses. Maximum respondents (35.3%) had 10-20 years of experience after specialization with 19.6, 23.5, and 21.6% respondents having <5, 5-10, and ≥20 years of experience, respectively. Practice type plays a statistically significant role in the awareness of the existing compassionate program (p = .0066). While many respondents seem clear on the application process for CUP set in place by pharmaceutical companies, a higher number of respondents are unclear about the country regulations and processes for applying to CUPs set in place by regulatory authorities. Most respondents (75.5%) reported that there are no resources or training provided to them regarding CUPs. There was a significant association between the clarity of the application process for CUP set in place by the sponsors and the number of applications submitted (p = .0321). CONCLUSIONS: Our study brings light on various issues faced by physicians in accessing CUPs especially related to the lack of education and training on utilizing CUPs. There are significant unmet needs related to improving the clarity for the application process, providing resources and related training, particularly for oncologists who do not have previous experience with CUPs.