The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study / 中华肿瘤杂志

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

DEPTOR improves cisplatin chemosensitivity in esophageal squamous cell carcinoma cells by inducing Caspase-1-mediated pyroptosis / 药学学报

Chemotherapy resistance is the main cause of poor prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). Pyroptosis is one of the anti-tumor mechanisms by chemotherapy drugs. Studies have shown that DEP-domain containing mTOR-interacting protein (DEPTOR) is correlated with sorafenib and gefitnib resistance, which is discovered as a naturally negative regulator of mammalian/mechanistic target of rapamicin (mTOR). In this study, DEPTOR knockdown (shDEPTOR) lentivirus was used to establish the stable DEPTOR knockdown ESCC cell lines. The results showed that knockdown of DEPTOR reduced chemosensitivity to cisplatin in ESCC cells in vitro. The lower expression of DEPTOR caused less extensive morphological characteristics of pyroptosis than that was observed in sh-con cells with the treatment of cisplain. Further studies showed that knockdown of DEPTOR induced downregulation of Caspase-1 expression and reduction of Caspase-1 activation, thereby inhibiting the activation of the classical pathway of pyroptosis. This paper demonstrates that DEPTOR can improve cisplatin chemosensitivity in ESCC cells via inducing Caspase-1-mediated pyroptosis.

Epidemiological characteristics and pathogenic analysis of bacillary dysentery in Zhengzhou city from 2004 to 2016 / 天津医药

Objective To understand the epidemic and etiological characteristics of bacillary dysentery and provide scientific evidence for the prevention strategies. Methods The surveillance data and serotyping of bacillary dysentery in Zhengzhou city from 2004 to 2016 were analyzed by descriptive epidemiological method.Results A total of 29 284 cases of bacillary dysentery were reported in Zhengzhou from 2004-2016.The average annual incidence was 31.28 per 100 000 and decreased annually(χ2=103.60,P<0.001).The peak season was from May to October.The incidence was higher in city than that of county,and male was higher than female.The majority of the bacillary dysentery cases was children under 3 years old, and scattered children were the main population at risk.A total of 385 Shigella strains were isolated and identified from 2004 to 2016, and 72.35% (280 strains) of strains were Shigella flexneri. F2a subtype was dominated, but the detective rate of Shigella sonnei was increased gradually. Conclusion Bacillary dysentery is still one of important infectious diseases in Zhengzhou,comprehensive measures should be taken to decrease the incidence including health education in targeted area and people in epidemic season.

Cis-CA1P inhibits tumor cell proliferation and prevents blood vessel formation / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of cis-combretastatin-A1 phosphate (cis-CA1P) on tumor cell proliferation, and its effects on the blood vessel formations.</p><p><b>METHODS</b>MTT and IC50 values were used to assess the inhibitory effects of cis-CA1P on tumor cell proliferation. Chicken embryo chorioallantoic membrane and thoracic aorta annulations isolated from rats were used to investigate the effects of cis-CAIP on the blood vessel formation.</p><p><b>RESULTS</b>Cis-CA1P concentration-dependently inhibited the proliferations of several cancer cell lines, including human gastric carcinoma cell line MGC-803, human leukemic monocyte lymphoma cell line U937, human melanoma cell line A375, human colon cancer cell line HCT116, human breast carcinoma cell line MDA-MB-231, and human leukemia cell line K562. Cis-CAIP significantly decreased the formation of blood vessels in chicken embryo chorioallantoic membrane and in thoracic aorta annulations.</p><p><b>CONCLUSION</b>Cis-CA1P inhibits cancer cell proliferation and prevents blood vessel formation.</p>

An outbreak of gastroenteritis caused by contaminated well water in a village, Henan province / 中华流行病学杂志

Objective To identify the cause and mode of transmission of a gastroenteritis outbreak in a village, Henan province. Methods Gastroenteritis patients were identified through family visits, interviewing the village doctors and reviewing diagnosis and prescription records at the village health clinic. Cases were defined as onset of one of the four symptoms from the village resident during July 20 to August 12,2010. The symptoms would include diarrhea ( ≥ 3 times/day), abdominal pain, nausea or vomiting. A retrospective cohort study was conducted to assess the association between drinking raw well water or eating noodles rinsed by raw well water and gastroenteritis. Stools or vomits of the ease-patients and the well water samples were tested for bacterial pathogens. Results Data for 60 case-patients were collected. All cases occurred in the northern part of the village. Persons who used water from a public well in the northern part of the village had an attack rate of 55%, which was 3.5 times of those who did not use the well water (16%) (RR=3.5,95%CI: 1.2-10). Results from the retrospective cohort study showed that drinking un-boiled water from the well was a risk factor (RR=1.7,95%CI: 1.3-2.3). Laboratory testing showed that total coliform and E. coli both greatly exceeded the limit considered safe for drinking, indicating there was fecal contamination in the well water. No bacterial pathogens were detected in the patients' stools or vomits. Conclusion The outbreak was mainly caused by drinking contaminated water from the public well in the northern part of the village.

Calcium-dependent chloride channels in plasma membrane of oocytes from toad, Bufo bufo gargarizans / 生理学报

In this paper, membrane current properties of the fully-grown oocytes from toad, Bufo bufo gargarizans, were studied by using two-microelectrode voltage clamp technique. Axion of adult female toad was destroyed, and then ovarian lobes containing oocytes in stage I to VI were removed and incubated in Ca(2+)-free ND96 solution with collagenase (1.5 mg/ml) for 1 h. Subsequently, the oocytes were washed in Ca(2+)-free ND96 solution for 10 min to completely remove the follicular layer. For the experiments only the oocytes in stage V and VI were selected and used during 1 to 5 d. The membrane was depolarized from a holding potential of -80 mV to +60 mV in 10 mV step. It was found that a sustained outward current was elicited by depolarization. Potassium channel blockers (tetraethylammonium chloride, TEA, 10 mmol/L and 4-aminopyridine, 4-AP, 10 mmol/L) reduced the outward current to (23.4+/-0.72)% of the maximum. However, further addition of chloride channel blocker (5-nitro-2, 3-phenypropylamino benzoate, NPPB, 30 micromol/L) could almost completely block the outward current to (2.1+/-0.08)% of the maximum. In the presence of TEA and 4-AP, removal of extracellular Ca(2+) or adding verapamil (40 micromol/L), could also reduce the outward current to (2.2+/-0.04) % and (3.1+/-0.15) % of the maximum, respectively. It is concluded that calcium-dependent chloride channels exist in plasma membrane of Bufo bufo gargarizans oocytes, besides potassium channels.