1.The role of glutamine metabolism in castration-resistant prostate cancer.
Bing ZHAO ; Jing WANG ; Li CHEN ; Hong WANG ; Chao-Zhao LIANG ; Jiaoti HUANG ; Ling-Fan XU
Asian Journal of Andrology 2023;25(2):192-197
Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
Male
;
Humans
;
Glutamine/therapeutic use*
;
Prostatic Neoplasms, Castration-Resistant/drug therapy*
2.More microinvasive foci in larger tumours of breast ductal carcinoma in situ.
Xiao-Yang CHEN ; Aye Aye THIKE ; Johnathan Xiande LIM ; Boon Huat BAY ; Puay Hoon TAN
Singapore medical journal 2023;64(8):493-496
INTRODUCTION:
Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.
METHODS:
The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.
RESULTS:
Higher numbers of Mi foci were found in larger tumours (P = 0.031).
CONCLUSION
Greater extent of DCIS is associated with multifocal Mi.
Humans
;
Female
;
Carcinoma, Intraductal, Noninfiltrating
;
Prognosis
;
Disease-Free Survival
;
Progression-Free Survival
;
Breast Neoplasms
;
Carcinoma, Ductal, Breast/pathology*
;
Neoplasm Invasiveness
3.Influence of family smoking on children’s exposure to second-hand smoke in rural Taizhou City
Ting-ting WANG ; Wei HAO ; Jing-yi HE ; Pin-pin ZHENG ; Zi-xian PAN ; Xia XIAO ; Abdullah Abu S ; Xiao-xiao CHEN
Shanghai Journal of Preventive Medicine 2021;33(9):824-828
Objective:To analyze the household smoking behavior of smokers in rural Taizhou City of Zhejiang Province, and to provide the basis for the intervention measures to reduce children's second-hand smoke (SHS) exposure. Methods:The investigation started in May 2018. A total of 418 smoking families in Luqiao and Linhai were included. Field face-to-face questionnaire survey was conducted and cotinine level in children's urine was measured. Kernel density estimation was used for curve fitting. The results were analyzed by Wilcoxon rank sum test and chi square test. Results:The age distribution of smokers in the family was bimodal. The younger smoker group was mainly the parents. The older group was mainly the other relatives such as grandfather. The age started smoking in the parent group was younger than that in relative group, but the average number of cigarettes smoked per day in relative group was higher than that in parent group (
4.Associations of Sarcopenia, Handgrip Strength and Calf Circumference with Cognitive Impairment among Chinese Older Adults.
Bing WU ; Yue Bin LYU ; Zhao Jin CAO ; Yuan WEI ; Wan Ying SHI ; Xiang GAO ; Jin Hui ZHOU ; Virginia Byers KRAUS ; Feng ZHAO ; Xin CHEN ; Feng LU ; Ming Yuan ZHANG ; Ying Chun LIU ; Qi Yue TAN ; Shi Xun SONG ; Ying Li QU ; Xu Lin ZHENG ; Chong SHEN ; Chen MAO ; Xiao Ming SHI
Biomedical and Environmental Sciences 2021;34(11):859-870
Objective:
To evaluate the associations of sarcopenia, handgrip strength and calf circumference with cognitive impairment among Chinese older adults.
Methods:
Totally 2,525 older adults were recruited from the Healthy Aging and Biomarkers Cohort Study. Cognitive impairment was assessed by the Chinese Mini-Mental State Examination. Handgrip strength was calculated from the means of the right and left hand values. Calf circumference was measured at the site of maximum circumference of the non-dominant leg. The formula developed by Ishii was used to define sarcopenia. Multiple logistic regression was performed to evaluate the associations of sarcopenia, handgrip strength, and calf circumference with cognitive impairment.
Results:
The prevalence of cognitive impairment was 34.36%. The adjusted odds ratio (
Conclusion
Sarcopenia, identified by low handgrip strength and low calf circumference, was positively associated with cognitive impairment.
Aged
;
Aged, 80 and over
;
China/epidemiology*
;
Cognitive Dysfunction/etiology*
;
Female
;
Hand Strength
;
Humans
;
Leg/anatomy & histology*
;
Logistic Models
;
Male
;
Sarcopenia/pathology*
5.Study of occult uterine perforation in brachytherapy of cervical cancer
Xiujuan ZHAO ; Haiyan WU ; Mingsong ZHONG ; Mingfang GUO ; Yue HUANG ; Duke CHEN ; Qi ZHOU
Chinese Journal of Radiation Oncology 2021;30(7):682-687
Objective:To evaluate the difference of dosimetry between three-dimensional and two-dimensional plans based on CT images of occult perforation in brachytherapy of cervical cancer, aiming to provide clinical reference.Methods:A total of 817 patients with cervical cancer received simple intrauterine (intrauterine tandem plus vaginal colpostats) three-dimensional brachytherapy in Chongqing University Cancer Hospital from January 2019 to December 2020 were retrospectively reviewed. Among them, 16 patients had occul uterine perforation. Based on Oncentra Brachy Therapy plan system, the single prescription dose was 6Gy. Three-dimensional (3D group) and two-dimensional (2D group) plans were designed on the perforated CT images The target volume, conformal index (CI), conformal index coformity index (COIN) and organs-at-risk (OAR) D 2cm 3 parameters were used to assess the plans between two groups. Results:The incidence of pccult uterine perforation was 1.96%(16/817) during brachytherapy for cervical cancer. The volume of prescription dose curve in the 3D group was (40.74±14.98) cm 3, significantly smaller compared with (91.46±19.71) cm 3 in the 2D group ( P<0.05), whereas the volume of the high-risk clinical target area wrapped by prescription dose curve did not significantly differ between two groups ( P>0.05). The CI and COIN in the 3D group were 0.79±0.10 and 0.72±0.96, significantly higher compared with 0.38±0.09 and 0.37±0.18 in the 2D group (both P<0.05). The D 2cm 3 of bladder, rectum, sigmoid colon, small intestine in the 3D group were (306.06±77.57) cGy, (252.27±72.60) cGy, (127.25±62.84) cGy and (228.79±94.90) cGy, significantly lower than (548.03±164.21) cGy, (411.16±118.74) cGy, (227.45±94.48) cGy and (450.95±157.96) cGy in the 2D group (all P<0.05). Conclusions:Application of image guidance in brachytherapy of cervical cancer is helpful to detect occult uterine perforation. When occult uterine perforation occurs, the use of three-dimensional plan can basically meet the clinical needs, which is significantly better than the two-dimensional plan.
6.Dynamics of the coronavirus disease 2019 (COVID-19) epidemic in Wuhan City, Hubei Province and China: a second derivative analysis of the cumulative daily diagnosed cases during the first 85 days
Bin YU ; Xinguang CHEN ; Shannan RICH ; Qiqing MO ; Hong YAN
Global Health Journal 2021;5(1):4-11
Background: Controlling the coronavirus disease 2019 (COVID-19) epidemic requires information beyond new and cumulative cases.This study aims to conduct an in-depth analysis by geographic strata: Wuhan City (hereafter referred to as Wuhan) only,Hubei Province (hereafter referred to as Hubei) excluding Wuhan,and China excluding Hubei.Methods: Daily cumulative confirmed COVID-19 cases between December 8,2019 (the date of symptom onset based on patients' recall during the investigation),and March 1,2020,from official sources and published studies were analyzed.The second derivative model was used for information extraction.Data analysis was conducted separately for the three strata.Results: A total of 80 026 diagnosed COVID-19 cases were reported during the first 85 days of the epidemic,with 49 315 cases from Wuhan,17 788 from Hubei excluding Wuhan,and 12 923 from China excluding Hubei.Analytical results indicate that the COVID-19 epidemic consists of an Acceleration,a Deceleration,and a Stabilization Phase in all three geographic strata,plus a Silent Attack Phase for Wuhan only.Given the reported incubation period of 14 days,effects of the massive anti-epidemic actions were revealed by both the Acceleration and Deceleration Phases.The Acceleration Phase signaled the effect of the intervention to detect the infected;the Deceleration Phase signaled the declines in new infections after the infected were detected,treated and quarantined.Conclusion: Findings of the study provide new evidence to better monitor the epidemic,evaluate its response to intervention,and predict the trend long.In addition to re-evaluating the control of the COVID-19 epidemic in China,this study provided a model for monitoring outbreaks of COVID-19 in different countries across the world.
7.Caring for the mother-child dyad as a family physician.
Li Ping Marianne TSANG ; David Chee Chin NG ; Yoke Hwee CHAN ; Helen Yu CHEN
Singapore medical journal 2019;60(10):497-501
Infant social, emotional and neurological development is shaped by the mother-child dyad. Dysfunction in this bond, as well as maternal mental health problems, can negatively impact child development. The family physician is well-placed to spot dysfunction in the mother-child dyad and screen for postnatal depression during well-child visits. If any issues are identified, the family physician can provide support and help the mother-child dyad to access community resources and specialist psychiatric services.
8.Management of scabies.
Farhad Fakhrudin VASANWALA ; Chong Yau ONG ; Chen Wee Derrick AW ; Choon How HOW
Singapore medical journal 2019;60(6):281-285
Scabies is a common infestation worldwide, affecting persons of any age and socioeconomic status. In Singapore, it is more common in institutions rather than in homes. The two variants are classic scabies and crusted scabies, with the latter having a significantly higher mite burden. Early identification, isolation of index patients and prophylactic treatment of contacts are essential in dealing with the outbreak. Locally, most primary care practitioners make the diagnosis based on visual inspection and clinical examination. A skin scrape is done to confirm the diagnosis, especially in atypical presentations. Scabietic mites, eggs or faeces can be seen on microscopy. The usual treatment for adult scabies in Singapore is the use of topical malathion or permethrin. A combination of topical permethrin and oral ivermectin is used for crusted scabies.
9.Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia
Choon Jin OOI ; Ida HILMI ; Rupa BANERJEE ; Sai Wei CHUAH ; Siew Chien NG ; Shu Chen WEI ; Govind K MAKHARIA ; Pises PISESPONGSA ; Min Hu CHEN ; Zhi Hua RAN ; Byong Duk YE ; Dong Il PARK ; Khoon Lin LING ; David ONG ; Vineet AHUJA ; Khean Lee GOH ; Jose SOLLANO ; Wee Chian LIM ; Wai Keung LEUNG ; Raja Affendi Raja ALI ; Deng Chyang WU ; Evan ONG ; Nazri MUSTAFFA ; Julajak LIMSRIVILAI ; Tadakazu HISAMATSU ; Suk Kyun YANG ; Qin OUYANG ; Richard GEARY ; Janaka H DE SILVA ; Rungsun RERKNIMITR ; Marcellus SIMADIBRATA ; Murdani ABDULLAH ; Rupert WL LEONG ;
Intestinal Research 2019;17(3):285-310
The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
Adalimumab
;
Asia
;
Asian Continental Ancestry Group
;
Biological Factors
;
Biosimilar Pharmaceuticals
;
Colitis
;
Colitis, Ulcerative
;
Consensus
;
Cooperative Behavior
;
Crohn Disease
;
Gastroenterology
;
Hepatitis B
;
Humans
;
Immunologic Factors
;
Inflammatory Bowel Diseases
;
Infliximab
;
Pharmacogenetics
;
Philippines
;
Practice Guidelines as Topic
;
Tuberculosis
;
Ulcer
10.Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy.
Zhao ZHANG ; Jun JIANG ; Xiaodong WU ; Mengyao ZHANG ; Dan LUO ; Renyu ZHANG ; Shiyou LI ; Youwen HE ; Huijie BIAN ; Zhinan CHEN
Frontiers of Medicine 2019;13(1):57-68
Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.
Animals
;
Carcinoma, Non-Small-Cell Lung
;
immunology
;
therapy
;
Cell Line, Tumor
;
ErbB Receptors
;
immunology
;
metabolism
;
Female
;
Humans
;
Immunotherapy, Adoptive
;
methods
;
Lung Neoplasms
;
immunology
;
therapy
;
Mice
;
Mice, Inbred NOD
;
Receptors, Chimeric Antigen
;
immunology
;
T-Lymphocytes
;
immunology
;
Xenograft Model Antitumor Assays

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