Targeting the Microenvironment in Esophageal Cancer

Esophageal cancer (EC) is the eighth most common type of cancer and the sixth leading cause of cancer-related deaths worldwide. At present, the clinical treatment for EC is based mainly on radical surgery, chemotherapy, and radiotherapy. However, due to the limited efficacy of conventional treatments and the serious adverse reactions, the outcome is still unsatisfactory (the 5-year survival rate for patients is less than 25%). Thus, it is extremely important and urgent to identify new therapeutic targets. The concept of tumor microenvironment (TME) has attracted increased attention since it was proposed. Recent studies have shown that TME is an important therapeutic target for EC. Microenvironment-targeting therapies such as immunotherapy and antiangiogenic therapy have played an indispensable role in prolonging survival and improving the prognosis of patients with EC. In addition, many new drugs and therapies that have been developed to target microenvironment may become treatment options in the future. We summarize the microenvironment of EC and the latest advances in microenvironment-targeting therapies in this review.

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A randomized clinical study of surgery versus radiotherapy in the treatment of resectable esophageal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4013 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4013-4013 ◽

Cited By ~ 7

Author(s):

J. Yu ◽

R. Ren ◽

X. Sun ◽

Y. Yin ◽

Z. Fu

Keyword(s):

Esophageal Cancer ◽

Survival Rate ◽

Radical Surgery ◽

Hematogenous Metastasis ◽

Treatment Results ◽

Thoracic Esophageal Cancer ◽

Clinical Recurrence ◽

Radiotherapy Group ◽

Randomized Clinical Study ◽

Surgery Group

4013 Background: To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy (LCAHFR) for patients with resectable thoracic segment esophageal cancer. Methods: From June 1998 to September 2002, 269 patients with resectable thoracic esophageal cancer were randomized into two groups. 135 were with surgery and 134 with late-course accelerated hyperfractionated (LCAF) radiotherapy. Chemotherapy only for clinical recurrence and salvage therapy. Results: The 1-, 3- and 5- year overall survival rate were 88.6%, 56.2% and 34.7% in the surgery group and 93.3%, 61.5% and 36.9% in the radiotherapy group. There was no statistical difference between the two groups (P =0.58). Median survival was 28.5 months and 30.5 months respectively. The 1-, 3-and 5-year progression-free survival rate was 73.3%, 39.7% and 20.6% in the surgery group and 75.9%, 43.7% and 23.1% in the radiotherapy group (P =0.65) . There was no difference between the two groups in survival rates including different location and length (P > 0.05). The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group (16.6% and 13.3% respectively ) was lower than in the surgery group ( 25.3% and 20.3 % respectively ), there was no significance between them. The incidence of local failure in the radiotherapy and surgery group was 57.3% and 27.8% respectively (P = 0.001) The incidence of death by local reasons was higher than in the surgery group (P = 0.02 ). The incidence of death by distant metastasis was lower than in the surgery group (P = 0.02 ). Conclusion: The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable. No significant financial relationships to disclose.

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Observation on the clinical effect and survival period of patients with esophageal cancer treated with UMIPIC combined with low dose radiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16517 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16517-e16517

Author(s):

Jian Liu ◽

Peng Jing ◽

Feng Gao ◽

Wei Shang ◽

Peicheng Zhang ◽

...

Keyword(s):

Esophageal Cancer ◽

Survival Rate ◽

Adverse Reactions ◽

Low Dose ◽

Clinical Effect ◽

Survival Rates ◽

Low Dose Radiotherapy ◽

Group A ◽

The Common ◽

Group B

e16517 Background: To observe the clinical effect and survival period of UMIPIC (ultra-minimum incision personalized intratuoral chemoimmunotherapy) combined with radiotherapy in the treatment of esophageal cancer. Methods: 712 patients with esophageal cancer who received UMIPIC treatment in our hospital from January 2011 to December 2015 were selected for the study subjects, 540 cases were treated by UMIPIC combination with radiotherapy in group A and 172 cases were treated by UMIPIC without radiotherapy in group B. All patients were diagnosed with esophageal cancer, and signed the consent for treatment. The patients were treated according to the UMIPIC treatment guidelines. This study was to observe the adverse reactions, clinical efficacy, survival and survival rate of esophageal cancer patients treated with UMIPIC combined with low-dose radiotherapy. Results: The common adverse reactions in group A were fever (18.06%), pain (8.89%), hemoglobin reduction (5.59%), leucopenia (5.40%), nausea (1.48%) and thrombocytopenia (1.12%);The common adverse reactions in group B were fever (26.16%), hemoglobin reduction (17.16%), pain (16.86%), leucopenia (3.55%), thrombocytopenia (2.35%), nausea (1.74%), liver function damage (2.42%), renal function damage (1.21%) and vomiting (1.16%). The other adverse reactions were all lower than 1.00%; The fever, pain and hemoglobin decrease in group A were significantly lower than those in group B (P < 0.05). There were 522 patients whose clinical efficacy could be evaluated in 712 patients. The benefit rate of group A was 95.28%, higher than that of group B 91.84%.The mean and median survival time of group A was 28.412 and 15.670 months, significantly higher than that of group B at 22.103 and 7.070 months. The 1-year survival rate of group A was significantly higher than that of group B (P < 0.05). The 1-year, 2-year and 5-year survival rates of group A were 60.05%, 35.61% and 28.26% while the 1-year, 2-year and 5-year survival rates of group B were 36.94%, 26.44% and 25.00%. Conclusions: The main adverse reactions of UMIPIC in the treatment of esophageal cancer are fever and pain, and other adverse reactions are relatively low. Combined radiotherapy can improve the clinical benefit rate, prolong the survival time and the clinical treatment effect is good, it is encouraged to treat esophageal cancer using local therapy of UMPIC with radiotherapy at low dose.

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A Case of Chylothorax after Radical Surgery for Esophageal Cancer Cured by Lipiodol Lymphangiography

The Japanese Journal of Gastroenterological Surgery ◽

10.5833/jjgs.38.7 ◽

2005 ◽

Vol 38 (1) ◽

pp. 7-12 ◽

Cited By ~ 7

Author(s):

Mamoru Uemura ◽

Yuichiro Doki ◽

Osamu Ishikawa ◽

Jun Ueda ◽

Kouichi Yoshikawa ◽

...

Keyword(s):

Esophageal Cancer ◽

Radical Surgery

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The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review

Cancer Control ◽

10.1177/1073274821997430 ◽

2021 ◽

Vol 28 ◽

pp. 107327482199743

Author(s):

Ke Chen ◽

Xiao Wang ◽

Liu Yang ◽

Zheling Chen

Keyword(s):

Overall Survival ◽

Esophageal Cancer ◽

Survival Rate ◽

Meta Analysis ◽

Response Rates ◽

Control Group ◽

Term Survival ◽

Long Term Survival ◽

And Control

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.

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PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy

Biology ◽

10.3390/biology10040266 ◽

2021 ◽

Vol 10 (4) ◽

pp. 266

Author(s):

Juan Alfonso Redondo ◽

Romain Bibes ◽

Alizée Vercauteren Drubbel ◽

Benjamin Dassy ◽

Xavier Bisteau ◽

...

Keyword(s):

Esophageal Cancer ◽

Circadian Rhythm ◽

Survival Rate ◽

Circadian Clock ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Human Cancer ◽

Response To Therapy ◽

Circadian Oscillation ◽

Resistance To Therapy

Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy.

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Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

Cancers ◽

10.3390/cancers13040909 ◽

2021 ◽

Vol 13 (4) ◽

pp. 909

Author(s):

Krzysztof Kotowski ◽

Jakub Rosik ◽

Filip Machaj ◽

Stanisław Supplitt ◽

Daniel Wiczew ◽

...

Keyword(s):

Current Knowledge ◽

Treatment Options ◽

Protein Structures ◽

New Drugs ◽

Proliferating Cells ◽

Cancer Tissues ◽

The Impact ◽

Rate Limiting ◽

Synthesis And Degradation

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

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The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer

Breast Care ◽

10.1159/000439462 ◽

2015 ◽

Vol 10 (5) ◽

pp. 312-315 ◽

Cited By ~ 8

Author(s):

Lorenzo Rossi ◽

Olivia Pagani

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Ovarian Function ◽

Treatment Options ◽

Endocrine Resistance ◽

Premenopausal Women ◽

New Drugs ◽

Fine Tuning ◽

Individual Risk ◽

Ovarian Function Suppression

The optimal endocrine therapy for premenopausal women with early and advanced breast cancer still remains an important and controversial issue. For over 30 years, tamoxifen has been the gold standard in the adjuvant setting. New therapeutic options, such as the addition of ovarian function suppression to oral endocrine therapy (either tamoxifen or aromatase inhibitors), can improve outcomes over tamoxifen alone in well-selected patients. Treatment duration has also been revisited, and extended therapy is becoming a new standard of care, especially in high-risk patients. Endocrine therapy for advanced disease still represents a challenge and a research priority. New drugs and combinations able to overcome endocrine resistance are at the horizon, and their role in premenopausal women should be better elucidated. Side effects and quality of life (including family planning considerations) play an important role in treatment selection and in the patients' treatment adherence and should always be discussed before start of treatment. The paper will specifically focus on how to integrate all new treatment options in the current armamentarium of endocrine therapy of premenopausal women, with the aim of best fine-tuning treatment selections according to the individual risk/benefit evaluation.

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Overexpression of UBE2C in Esophageal Squamous Cell Carcinoma Tissues and Molecular Analysis

10.21203/rs.3.rs-405953/v1 ◽

2021 ◽

Author(s):

Rong Li ◽

xingfeng pang ◽

Zhiguang Huang ◽

Lihua Yang ◽

Zhigang Peng ◽

...

Keyword(s):

Esophageal Cancer ◽

Survival Analysis ◽

Survival Rate ◽

Comprehensive Evaluation ◽

Synergistic Effects ◽

Comprehensive Treatment ◽

Rna Seq ◽

Mrna Expression Data ◽

Risk Of Recurrence ◽

Lower Survival Rate

Abstract Background: The treatment of esophageal cancer is mainly based on a combination of traditional surgery and radiotherapy/chemotherapy. Some new progress has been made in multidisciplinary comprehensive treatment and imaging diagnosis in recent years, but the 5-year survival rate for esophageal cancer is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of UBE2C in ESCC.Methods: In this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in house RNA- seq, in hosue IHC, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined SMD and sROC. K-M method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the DEGs of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C.Results: UBE2C protein and mRNA were highly expressed in ESCC tissues. The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51–2.45, P < 0.001), and the the AUC of the sROC was 0.93 (95% CI: 0.90–0.95). The results of survival analysis suggested an association between high expression of UBE2C and a poor prognosis and a higher risk of recurrence. Pathways anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/hsa-mir-139-5p/UBE2C).Conclusion: UBE2C mRNA and protein level were highly expressed in ESCC and a higher UBE2C expression generally predicts a lower survival rate and a higher risk of recurrence.

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EVALUATION OF DRUG THERAPY PROBLEMS IN ASTHMA PATIENTS RECEIVING CARE IN TWO HOSPITALS IN SOUTH-EASTERN NIGERIA

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i2.22472 ◽

2018 ◽

Vol 10 (2) ◽

pp. 50

Author(s):

Kosisochi Chinwendu Amorha ◽

Anthony Chukwuma Onu ◽

Chigozie Gloria Anene-okeke ◽

Chinwe Victoria Ukwe

Keyword(s):

Drug Therapy ◽

Adverse Reactions ◽

Tertiary Hospital ◽

Medical Centre ◽

New Drugs ◽

Inappropriate Drug ◽

Cross Sectional ◽

South Eastern ◽

Asthma Patients ◽

Drug Therapy Problems

Objective: To evaluate drug therapy problems in asthma patients visiting a secondary and tertiary hospital in South-Eastern Nigeria.Methods: This study was a retrospective, cross-sectional analyses of the medical records of adult asthmatic patients receiving care in two hospitals in Enugu State, within a 15-year period. The Pharmaceutical Network Care Europe (PCNE) tool version 6.2 was used to assess drug therapy problems. The IBM Statistical Product for Services Solution (SPSS) version 20.0 was used for analysis. For all results, P ≤ 0.05 was considered statistically significant.Results: Majority of the patients were below 60 y old (81.2%); female (68.8%) and were on more than two drugs (95.3%). Majority of the identified drug therapy problems (DTPs) were adverse reactions (65.7%). The inappropriate drug combination was the major cause of DTPs (65.6%). Only about 23.4% of the intervention outcomes were known. University of Nigeria Teaching Hospital (UNTH) had more interventions (35.9%) than Medical Centre (8.0%) (χ2 = 6.323; df = 1; **P = 0.012); and more of the outcomes of their interventions known (38.5%) compared to Medical Centre (0.0%) (χ2 = 12.559; df = 1; **P ˂ 0.001).Conclusion: Adverse reactions and inappropriate drug selection were the major identified DTPs and major cause of DTPs, respectively. Most DTPs had no interventions. The documented interventions included stopping of the drugs, change of drugs or dosage, change of instructions for use and starting of new drugs. Most interventions had unknown outcomes. UNTH had more interventions with known outcomes than the University of Nigeria Medical Centre.

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