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Drug resistance is a big problem in cancer treatment and one of the most prominent mechanisms underlain is overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2. Inhibition of ABC transporters is an important approach to overcome drug resistance. The inositol-requiring enzyme 1α (IRE1α), an arm of unfolded protein response (UPR), splices XBP1 mRNA to generate an active transcription factor XBP1s. UPR is implicated in drug resistance. However, the underlying mechanism is unclear. We found that the anticancer drugs such as 5-fluorouracil (5-FU) activated the IRE1α-XBP1 pathway to induce the expression of ABCB1, ABCC1 and ABCG2 in colon cancer cells. Inhibition of IRE1α RNase activity with small molecule 4μ8c suppressed the drug-induced expression of these ABC transporters and sensitized 5-FU-resistant colon cancer cells to drug treatment. In vivo xenograft assay indicates that administration of 4μ8C substantially enhanced the efficacy of 5-FU chemotherapy on 5-FU-resistant colon cancer cells. These results suggest that IRE1α-targeting might be a strategy to cope with drug resistance of colon cancer., Competing Interests: Declaration of competing interest The authors declare that there are no potential conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report a prevalence rate of 23.6% human papillomavirus (HPV) infection with oncogenic subtypes and 2.4% cervical intraepithelial neoplasia (CIN) III and cervical cancer (CC) in rural middle-aged women in 2 counties with the highest CC mortality in Shanxi Province, China. We examined the association of risk factors to HPV infection and to CIN III and CC in 8,798 unscreened women aged 35-50 years. Multivariate odds ratios (OR) and 95% confidence intervals (CI) for each endpoint were obtained for risk factors after adjustment for covariates. The OR of oncogenic HPV were: 1.41 (95% CI = 1.25-1.60) and 1.42 (95% CI = 1.24-1.61) for the participant and her husband having multiple sexual partners, respectively; 1.67 (95% CI = 1.37-2.04), 1.15 (95% CI = 1.04-1.26), and 0.82 (95% CI = 0.72-0.94) for ever (vs. never) diagnosed with tuberculosis, cervical inflammation and vaginal trichomoniasis, respectively; while bathing in a public (v. private) facility had an OR of 1.23 (95% CI =1.11-1.35). Seasonal fluctuations in HPV infection, but not CC, appeared in Xiangyuan County, with OR of 1.23 (95% CI = 1.14-1.33) and 1.51 (95% CI = 1.35-1.67) in Spring and Winter compared to Summer, respectively. The OR of CIN III and CC in the HPV positives were: 2.03 (95% CI = 1.63-2.53) for ages > or =45 years (vs. <40); and 4.01 (95% CI = 1.46-11.0) for > or =3 (vs. no) home births. Public health interventions and control strategies for improving the reproductive health of women in these rural populations need to be developed to reduce risk of HPV and subsequent CC., (Copyright 2005 Wiley-Liss, Inc.)

Objective: To determine the association between viral load of high risk type human papillomavirus (HR-HPV) and stage of cervical intraepithelial neoplasia (CIN) lesion., Methods: Cervical exfoliated cells were collected from 1997 women aged 35-45 in a cross-sectional screening study. HPV DNA was detected by hybrid capture 2 (HC2) system, and viral load was measured by the ratios of relative light units compared to standard positive control (RLU/PC). Log10RLU/PC were categorized into four groups: negative (< 0), low viral load (0 - 1.12), medium viral load (1.13 - 2.23), and high viral load (2.24 - 3.37). Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2-3, and squamous cervical cancer (SCC). Association between HR-HPV and CINs were evaluated by unconditional multinomial logistic regression., Results: 100% (12/12) SCC, 97.3% (72/74) of CIN 2-3, 58.3% (74/127) of CIN 1, and 11.5% (205/1784) of normal women were positive for HPV DNA. The median log10RLUs for the positive women with SCC, CIN 2-3, CIN 1 and in normal women were 2.60, 2.32, 2.18 and 1.18 respectively. The odds ratio (OR) between low viral load of HPV DNA and CIN 1 was 3.8 (1.9 - 7.3) while between high viral load and CIN 2-3 was OR=865.9 (200.1 - 3738.0) which showed that higher viral load could increase the risk of cervical lesions (P <0.001)., Conclusion: Both cervical cancer and CINs were highly influenced by HR-HPV viral load.

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for >CIN II than the direct test, but similar to liquid based cytology.

Background & Objective: At present, the incidence of cervical cancer is still high in less developed areas of China; one of the reasons is that cytology in screening for cervical cancer is not feasible in these areas. The aim of this study was to analyze the sensitivity and specificity of acetic acid smear test as a cervical cancer screening test, and evaluate the value of this method for cervical cancer screening., Methods: Acetic acid smear test was performed on 1997 previously unscreened women aged 35-45 years in Xiangyuan County, Shanxi Province. All women had cervical cytology, testing for high-risk types of human papillomavirus DNA, colposcopy, an endocervical curettage and at least five cervical biopsies. Biopsies were done at the lesions, or one biopsy at 2, 4, 8, 10 o'clock at the squamocolumnar junction in each normal quadrant., Results: According to histological diagnosis, 43 women had CIN II, 31 had CIN III, and 12 had invasive carcinoma. In two women only the endocervix was positive. Smear test yielded normal results in 1445 women (72.4%), low-grade squamous intraepithelial lesions (LSILs, CIN I) in 525 (26.3%), high-grade squamous intraepithelial lesions (HSILs, CIN II- III) in 21 (1.1%), and cancer in 6 (0.3%). With abnormal visual inspection defined as LSILs or worse, the sensitivity of acetic acid smear test for HSILs or worse was 70.9% (61 of 86), the specificity was 74.3% (1420 of 1911). The sensitivity was 64.9% for smaller lesions (37 of 57), and 88.9% for larger lesions (24 of 27) (P=0.03). The sensitivity of colposcopy for high-grade SILs or worse was 81.4% (70 of 86), the specificity was 76.5% (1462 of 1911)., Conclusion: This study showed the high specificity and sensitivity of acetic acid smear test as a primary screening test for cervical cancer. Acetic acid smear test and colposcopy have similar specificity profiles for CIN II or more severe lesions. Acetic acid smear test as a primary screening test will be possible and effective with the benefits of low-cost and simple test in low-resource settings.

Objectives: To investigate the prevalence of oncogenic type of human papillomavirus (HPV) infection and identify the high risk population for conducting immuno/chemoprevention of cervical cancer., Methods: All married women aged 30 to 50 with no history of hysterectomy, pelvic radiation and non-pregnant from certain villages of Xiangyuan and Yangcheng County were invited. This study was conducted through two phases. In phase one, subjects sampled the vaginal secretions using the collectors after signing the informed consent. And physicians sampled exfoliated cells from cervix in the phase two. All the specimens were tested with the Hybrid Capture 2 test. The data was managed and analyzed by VFP and SPSS software., Results: There were 9,683 women participated in this study. Local women welcomed this study and population compliance rate was 75.4%. In tested population, we found 2,666 subjects of HPV DNA positive and HPV prevalence was 27.5%. The rates of different age group were 24.5% (30-34 yrs), 27.4% (35-39 yrs), 28.2% (40-44 yrs), 27.4% (45-50 yrs) respectively and had no significant differences (P = 0.604). The rates were slightly increased with the higher education level and had no differences (P = 0.106). The rate in mountain areas was higher than that in half-mountain areas (P = 0.001)., Conclusions: The prevalence of HPV infection is indeed high in this region. Local women and health professionals welcome the activities of cervical cancer screening and prevention. It is an emergent task to improve their sanitary condition and prevent them from cervical cancer in these women. A women health cohort is established successfully among high HPV exposed women in rural China. The extensive biologic specimen repository has been successfully established to simultaneously study the etiology, early detection, and immuno/chemoprevention of cervical cancer.

Objective: To confirm the accuracy of the ThinPrep Pap Test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) on the basis of histologic diagnosis by biopsy and the detection of human papillomavirus (HPV) DNA in mass screening., Study Design: A total of 1,997 women residing in Xiangyuan County, Shanxi Province, P.R.C., an area with a high incidence of cervical carcinoma, were enrolled in this study. We collected exfoliative cervical samples from all subjects into a liquid buffer (Preserv-Cyt [Cytyc]) and utilized for both cytologic screening using the ThinPrep Pap Test and HPV DNA testing. Subsequent colposcopic biopsies were taken on all subjects. All the tests were performed in an independent and blinded fashion. We compared the ThinPrep Pap test with colposcopic biopsy and HPV test., Results: High grade squamous intraepithelial lesions (HSIL) (CIN 2/3) were identified in 74 (3.7%) of 1,993 women adequately assessed, and there were 12 cases of squamous cell carcinoma (SCC). The false negative rate of ThinPrep cytology was 3.2% for biopsy-confirmed CIN 3 and 9.3% for CIN 2. Twenty-seven (87%) of the 31 women with biopsy-confirmed CIN 3 and 12 (100%) of 12 with biopsy-confirmed SCC had a diagnosis of either HSIL or greater abnormalities on ThinPrep cytology. In addition, the HPV DNA detection rates offered a good correlation between cytology and biopsy., Conclusion: The ThinPrep Pap performed extremely well in this primary screening trial. We found a good correlation between ThinPrep cytology and colposcopic biopsy on detection of HSIL and SCC; cervical specimens collected in ThinPrep liquid buffer serve as a direct test for HPV as well.

Objective: To analyze the effect of gold standard, blind comparison and different cut-points choosing on screening techniques assessment, and to promote the application of evidence-based medicine theory in screening study., Methods: A screening study for cervical cancer in rural China in 1999, where 1997 women had been tested for pathology as gold standard and simulating situations without gold standard, blind comparison and under different cut-points. Indices such as detectable rate, sensitivity and specificity were calculated for each technique. Receiver operating characteristics (ROC) curves were drawn and areas under ROC curves between screening techniques were tested., Results: Without gold standard, diagnostic techniques could not be evaluated correctly, and without the blind comparison, the sensitivity and specificity of the tests would be subjectively increased. Furthermore, use of different cut-points led to different sensitivities and specificities of test., Conclusions: Gold standard, blind comparison and perfect cut-points can improve the quality of screening test and drawing ROC curves is an effective way to confirm cut-points and evaluate diagnostic techniques. It is necessary to enforce the application of evidence-based medicine theory in scientific research.

Objective: To determine the sensitivity and specificity of liquid-based cytology in a high-risk, unscreened population., Study Design: A cross-sectional comparative trial of multiple screening techniques. This report focuses on the performance of liquid-based cytology using biopsy as the standard., Results: In total, 1,997 women were screened. All subjects had a minimum of five cervical biopsies. Of the subjects, 4.3% had CIN 2 on biopsy. The ThinPrep Pap with ASCUS as positive had a sensitivity for CIN 2 of 94% and specificity of 78%; the sensitivity for CIN 3 was 98% and for cancer, 100%. The unsatisfactory rate due to bloody specimens was 7.9% (158/1,997). After reprocessing, the unsatisfactory rate was 0.15% (3/1,997)., Conclusion: Reprocessing effectively recovers ThinPrep samples otherwise unsatisfactory due to blood and mucus. The ThinPrep Pap test is a highly sensitive screening test when used in a high-risk, unscreened population.

Several screening methods for cervical cancer and its precancerous lesion are reviewed. Cervical cancer screening using visual inspection, colposcopy, oncogenic human papillomavirus DNA testing, liquid-based monolayers and automated Pap smear screening instruments are all potentially valuable when used alone or in combination. Newly developed techniques provide an opportunity to extend practical cervical cancer screening to large population in limited resource areas, and help do more cost-effectiveness of screening tests in high risk population.

An epidemiologic study of penile cancer involving 141 cases and 150 community controls was undertaken in a high-risk area in China. Personal interviews, as well as physical examinations among the prospectively ascertained subjects, enabled evaluation of a variety of potential risk factors. Strongly related to risk were conditions restricting the motility of the foreskin, including phimosis or paraphimosis, particularly when so severe that circumcision was used for treatment. Poor hygiene practices also appeared to increase risk, particularly as evidenced by detection of smegma on physical examination, although it was difficult to decipher whether this association was etiologic or merely a consequence of disease. A sexual relationship outside of marriage was associated with a RR of 1.7, and appeared to be a more important discriminator than number of lifetime sexual partners. Risk was increased among subjects reporting previous genital conditions, particularly sexually transmitted diseases, and physical examinations revealed the appearance of genital warts among 13 cases vs. I control. Interviews with wives of study subjects failed to provide evidence of a "female factor" in the etiology of penile cancer. This study supports the need for further evaluation of the role of hygiene and sexually transmitted agents in the etiology of penile cancer.

A set of maps which display the patterns of cancer mortality in China has been prepared and published by the China Map Press. The 200 page atlas was edited by the National Cancer Control Office of the Ministry of Health and the Nanjing Institute of Geography of the Chinese Academy of Sciences on the basis of a nation-wide cancer mortality survey. The Cancer Institute of the Chinese Academy of Medical Sciences with related Colleges, Universities and Institutes provided the data and took part in the preparation of the atlas, which is published both in Chinese and English. 58 maps and several dozen charts depict, in seven colours, the mortality distribution in this 2392 countries and county-level administrative units of 9 types of cancer common in China--stomach, oesophagus, liver, cervix, lung, colon and rectum, breast, nasopharynx, and leukaemia as well as 5 less common cancers--brain tumours, malignant lymphoma, cancer of the bladder, of the penis, and choriocarcinoma. The Atlas of Cancer Mortality will be an important new aid for cancer control and research in the People's Republic of China.