Association of frailty with mortality in cancer survivors: results from NHANES 1999-2018.

Cancer survivors are vulnerable to frailty. While few studies have focused on the association of frailty with mortality risk among cancer survivors, the current study aimed to reveal this association. In this cohort study, 4723 cancer survivors were enrolled from the National Health and Nutrition Examination Surveys (NHANES, 1999-2018). Frailty status was quantified using the 53-item frailty index. Death outcomes were linked to National Death Index mortality data (as of December 31, 2019). Cox proportional hazard models were used to estimate HRs (95% CIs). The median (IQR) frailty score was 0.190 (0.132, 0.277). During the median follow-up of 6.7 years, 1775 all-cause deaths (including 581 cancer deaths and 385 cardiac deaths) were documented. Compared to the lowest tertile of frailty scores, the adjusted HRs (95% CIs) for the highest tertile were 2.698 (2.224, 3.272) for all-cause mortality (P trend < 0.001), 2.145 (1.547, 2.973) for cancer mortality (P trend < 0.001), and 3.735 (2.231, 6.251) for cardiac mortality (P trend < 0.001). Moreover, a positive dose‒response association between the frailty score and mortality risk was determined. Each per-unit increase in the frailty score (natural logarithm transformed) was found to increase all-cause mortality by 159% (P < 0.001), cancer mortality by 103% (P < 0.001), and cardiac mortality by 256% (P < 0.001). A consistent result was shown when stratifying by age, sex, race, body mass index, and type of cancer. This study suggested that the frailty index was positively associated with all-cause mortality and cause-specific mortality (including cancer and cardiac deaths) among cancer survivors.

Controllable Synthesis of ZnO Nanoparticles with Improved Photocatalytic Performance for the Degradation of Rhodamine B under Ultraviolet Light Irradiation.

In this work, two-dimensional (2D) Zn-HMT (Zn(NO3)2(HMT)2(H2O)2]n) nanosheets were synthesized using a facile one-step chemical precipitation in the presence of Zn(NO3)2, hexamine (HMT), and anhydrous ethanol at room temperature. Subsequently, hexagonal Tx-ZnO (Tx-ZnO refers to the zinc oxide (ZnO) nanoparticles) were synthesized by a high-temperature solid-phase method at different temperatures (x = 500, 550, 600, 650, 700, 750, and 800 °C) nanoparticles with different morphologies were synthesized by a high-temperature calcination approach using 2D Zn-HMT nanosheets as precursor. The crystal structure, morphology, specific surface areas, surface and interface properties, optical properties, and charge migration behaviors of the as-synthesized Tx-ZnO nanoparticles were characterized by powder X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), automatic specific surface and aperture analyzer, X-ray photoelectron spectroscopy (XPS), UV-visible spectrophotometer, photoluminescence (PL) spectra, and electrochemical impedance spectroscopy (EIS). The photocatalytic performances and stabilities of the as-synthesized typical Tx-ZnO nanoparticles with various morphologies were evaluated and compared with the commercial ZnO (CM-ZnO) nanoparticle. The T700-ZnO nanoparticle with spherical and irregular morphology exhibited the highest photocatalytic activity (99.12%) for the degradation of Rhodamine B (RhB), compared to T500-ZnO (92.32%), T600-ZnO (90.65%), T800-ZnO (44.04%), and the CM-ZnO (88.38%) nanoparticle, which can be attributed to the cooperative effects of higher crystallinity, bigger crystal size, the strongest separation efficiency, the lowest recombination rate, the fastest charge carrier transfer path, and the highest charge-transfer efficiency. The superior photocatalytic activity illustrated by the T700-ZnO nanoparticle makes it have potential application prospects for the treatment of organic wastewater.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy.

OBJECTIVE: The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). METHODS: The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. RESULTS: We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. CONCLUSIONS: Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

Research advances in nanomedicine applied to the systemic treatment of colorectal cancer.

The systematic treatment of colorectal cancer (CRC) still has room for improvement. The efficacy of chemotherapy, that of anti-vascular therapy, and that of immunotherapy have been unsatisfactory. In recent years, nanomaterials have been used as carriers to improve the bioavailability of anticancer drugs. For the treatment of colorectal cancer, nanodrugs increase the possibility of more precise targeted delivery. However, the actual benefits may cover more aspects. Nanocarriers can produce synergistic effects with anticancer drugs, including the scavenging of reactive oxygen species and co-delivery of a variety of drugs. Currently, immunotherapy has very limited clinical applications in CRC. Modified nanocarriers can activate the immune microenvironment, which can be used for staging antigen recognition or the immune response. Cancer vaccines based on nanomaterials and modified immune checkpoint inhibitors have shown therapeutic potential in animal models. Considering the direct or indirect relationship between the intestinal microflora and CRC, a variety of nanodrugs that regulate microbial function have been explored as an anticancer strategy, and the special structure of microorganisms can also be used as a basis for improving the delivery of traditional nanoparticles (NPs). This review summarizes recent research performed on nanocarriers in in vivo and in vitro models and the synergistic anticancer effects of nanocarriers, focusing on the interaction between NPs and the body, resulting in enhanced efficacy and immune activation. Furthermore, this review describes the current trend of NPs used in the treatment of CRC.

An esterase-activatable prodrug formulated liposome strategy: potentiating the anticancer therapeutic efficacy and drug safety.

Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (∼1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients.

Programmed cell death-1 inhibitor combination treatment for recurrent proficient mismatch repair/ miscrosatellite-stable type endometrial cancer: A case report.

BACKGROUND: Endometrial cancer (EC) is one of the most common cancers of the female reproductive tract, and the incidence is increasing rapidly. Immunotherapy using programmed cell death-1 (PD-1) inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies. However, clinical management of EC with checkpoint inhibitors requires improvement. Herein, we discuss a case of refractory proficient mismatch repair (pMMR)/miscrosatellite-stable (MSS) EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies. CASE SUMMARY: A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy. Four years later, she developed chest pain, and lung biopsy indicated thyroid transcription factor-1 (-), Napsin A (-), estrogen receptor (+), progesterone receptor (+), anaplastic lymphoma kinase (D5F3) (-), and receptor tyrosine kinase (D4D6) (-) metastatic EC. Genetic testing results showed low tumor mutation burden, pMMR, PD ligand 1 (-), MSS, and HLA-class 1 heterogeneous disease. The patient was started on toripalimab combined with nab-paclitaxel for seven cycles (every 3 wk), but this regimen was terminated because of an intolerable chemotherapy adverse event. The disease progressed in 2020, and the patient's treatment was switched from nab-paclitaxel to anlotinib, while immunotherapy using toripalimab was continued. The patient achieved a major partial response with well-tolerated toxicities, and treatment is ongoing. CONCLUSION: Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity. In this case, the patient had pMMR/MSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment. These results warrant further clinical exploration.

Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy.

PURPOSE: Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model. RESULTS: The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer. CONCLUSION: These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.

The efficiency and regimen choice of adjuvant chemotherapy in biliary tract cancer: A STROBE-compliant retrospective cohort study.

Biliary tract cancer (BTC) patients have poor prognosis even following radical resection. To improve the current status, more evidence is required clarifying the role of adjuvant chemotherapy. This study aim is to evaluate the efficacy of adjuvant chemotherapy and discuss the regimen choices.We retrospectively analyzed the clinical data of 80 patients who underwent curative-intent R0 resection from 2008 to 2016. Among them, 40 patients had received adjuvant chemotherapy, and the others in the observation group were 1:1 matched by clinical characteristics including gender, age, tumor stage, and ECOG performance status score. Kaplan-Meier analysis was performed to compare DFS and OS. Potential confounding factors were adjusted by Multivariate analysis.In the entire patient cohort, the mean disease-free survival (DFS) time of BTC patients with adjuvant chemotherapy and observation was 18.63 ±â€Š3.63 months versus 10.36 ±â€Š1.67 months, respectively (P = .029). There was no significant difference observed in overall survival (OS) time (33.72 ±â€Š5.02 vs 21.05 ±â€Š4.12 months, P = .114). On multivariate analysis, adjuvant chemotherapy and N factor were found to be significant factors for DFS, and sex, age, T factor were found to be significant factors for OS. Besides, subgroup analysis indicated that combination chemotherapy prolonged DFS time of BTC patients than single-agent to some extent, and oral agents showed efficacy to improve OS.This retrospective study demonstrates that adjuvant chemotherapy contributes to DFS, but is unsatisfactory for improving OS. Combination chemotherapy contained oral agents provides a possibility of therapeutic strategy for improving surgical outcomes of BTC patients.