scholarly journals A Potential Anti-Tumor Herb Bred in a Tropical Fruit: Insight into the Chemical Components and Pharmacological Effects of Momordicae Semen

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3949
Author(s):  
Xiao-Rong Xu ◽  
Chuan-Hong Luo ◽  
Bo Cao ◽  
Run-Chun Xu ◽  
Fang Wang ◽  
...  

Gac fruit (Momordica cochinchinensis Spreng) is a popular tropical fruit in southeast Asia. What is amazing is that its seeds (Momordicae Semen) and arils are traditional herbs with anti-tumor activity, and have protected human health for more than 1000 years. In recent years, its anti-tumor activity has received extensive attention and research. This manuscript summarized the chemical composition of saponins, fatty acids, volatile constituents, proteins, peptides, and other components from Momordicae Semen (MSE). The effect and mechanism of MSE and its extract on breast cancer, gastric cancer, lung cancer, esophagus cancer, melanomas, and human cervical epithelial carcinoma were discussed. In addition, its antioxidant, anti-inflammatory, and other pharmacological effects were also analyzed. We hope that this review will provide new ideas for the treatment of cancer and other diseases, and become a reference for the further research into complementary and alternative medicine.

2021 ◽  
Vol 27 ◽  
Author(s):  
Qi Zhang ◽  
Yinxin Wu ◽  
Jinlan Chen ◽  
Yuxuan Cai ◽  
Bei Wang ◽  
...  

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13522-e13522
Author(s):  
Baohua Wang ◽  
Ruoying Yu ◽  
Qiuxiang Ou ◽  
Hua Bao ◽  
Xue Wu ◽  
...  

e13522 Background: Kinase domain duplication (KDD) has recently been recognized as oncogenic and targetable mutations in some cancers. EGFR KDD was identified as an oncogenic driver in lung cancer showing partial response to EGFR TKI. BRAF KDD was reported in diverse tumor types with clinical response to RAF-targeted therapy. We retrospectively investigated the prevalence of KDDs in multiple cancer types of a large Chinese population. Methods: 50742 unique cancer cases were analyzed by comprehensive genomic profiling (CGP). DNA was extracted from formalin-fixed paraffin-embedded specimens (FFPEs), fresh tissue, blood or plasma samples and sequenced with gene panels targeting 400+ cancer-relevant genes. Among them, 53 cases were detected with KDD of various kinases. Results: In this Chinese cohort, KDD was identified in 0.1% of the total population across multiple cancer types including lung cancer (39), breast cancer (5), gastric cancer (3), colorectal cancer (2), mucoepidermoid carcinoma (1), unknown (3). The median age at diagnosis was 54 which was younger than the 60 yrs median age of total population. The distribution of KDDs was in EGFR(34) MET(5), JAK1(2), BRAF(2), FGFR2(2), FGFR1(1), JAK2(1), LYN(1), MAP3K1(1), RAF1(1), RET(1), AKT3(1), and CDK8(1). Thirty-one lung cancer cases were detected with EGFR-KDD, including kinase duplications of exon18-25 (22), exon17-25 (6), exon18-26 (2), exon14-26(1). Three patients with EGFR-KDD exon18-25 showed partial anti-tumor response to target therapy. MET-KDD was exclusively found in lung cancer involving the duplication of MET exon15-21 (2), exon14-17 (1), exon15-16 (1) and exon12-21 (1) while FGFR1/2-KDD was observed only in gastric cancer. Two female patients with breast cancer were detected with JAK1-KDD at age of 45 and 37, respectively. The canonical BRAF-KDD of exon 10-18 was identified in one female patient diagnosed of lung adenocarcinoma at age of 49. Frequently altered genes in patients with KDD were TP53(72%), EGFR (23%), FAT1(13%), BRCA1(10%). MCL1 amplification, a known oncogenic alteration, was identified in fifteen patients (11 EGFR-KDD,2 MET-KDD, 1 BRAF-KDD, 1 JAK2-KDD), representing the most common copy number variation observed. Conclusions: Kinase KDDs were rare but potentially oncogenic mutations in diverse cancer types with clinical outcome of EGFR-KDD to target therapy in lung cancer. Cancer-type specific KDDs were identified including MET-KDD in lung cancer, FGFR1/2-KDD in gastric cancer and JAK1-KDD in breast cancer.


Endocrinology ◽  
2021 ◽  
Author(s):  
Nicole M Hwang ◽  
Laura P Stabile

Abstract Estrogen receptors (ERs) are known to play an important role in the proper development of estrogen-sensitive organs, as well as in the development and progression of various types of cancer. ERα, the first ER to be discovered, has been the focus of most cancer research, especially in the context of breast cancer. However, ERβ expression also plays a significant role in cancer pathophysiology, notably its seemingly protective nature and loss of expression with oncogenesis and progression. While ERβ exhibits anti-tumor activity in breast, ovarian, and prostate cancer, its expression is associated with disease progression and worse prognosis in lung cancer. The function of ERβ is complicated by the presence of multiple isoforms and single nucleotide polymorphisms, in addition to tissue-specific functions. This mini-review explores current literature on ERβ and its mechanism of action and clinical implications in breast, ovarian, prostate, and lung cancer.


2019 ◽  
Vol 73 (6) ◽  
pp. 353-357 ◽  
Author(s):  
Katsuyuki Hotta ◽  
Hiroyuki Yanai ◽  
Kadoaki Ohashi ◽  
Kiichiro Ninomiya ◽  
Hiromi Nakashima ◽  
...  

AimsHER2-positivity pattern in the specimens of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) has been hardly reported in non-small-cell lung cancer (NSCLC).MethodsWe evaluated the characteristics of HER2-positivity pattern in formalin-fixed paraffin-embedded samples using IHC and FISH in 15 patients enrolled in a larger prospective cohort study to survey a HER2-positive NSCLC.ResultsAs for the immunostaining pattern, most specimens (79%) demonstrated incomplete or mixed-typed membranous immunoreactivity with heterogeneity, resembling that observed in gastric cancer rather than breast cancer. Concordance between IHC-positivity and FISH-positivity was 87.5% according to the criteria for breast cancer scoring system. On application of the gastric cancer scoring system to the examined tumours, the IHC score increased in the seven (43.8%) specimens, and the concordance between IHC positivity and FISH positivity rose to 93.8%.ConclusionsIn our pilot series, the pattern of IHC reactivity closely resembled that observed in gastric cancer rather than breast cancer.Trial registration number000017003.


2021 ◽  
Author(s):  
Min Fu ◽  
Feng Du ◽  
Zhe Wei ◽  
Cheng Xu ◽  
Xinjun Wang ◽  
...  

Abstract Background: Heat shock protein 90α (Hsp90α) is associated with the occurrence and development of cancer. Previous studies have shown that plasma Hsp90α protein has high sensitivity and specificity in the diagnosis of liver cancer and lung cancer. Although the study of the Hsp90α protein in cancer screening is more common, the application of the Hsp90α protein in diagnosis and monitoring of cancer is rare. Methods: In this study, 370 cancer patients were enrolled from Nanyang Second People's Hospital (Henan, China). The pre- and post-treatment protein expression of Hsp90α were inspected and the data were analyzed.Results: In our research, Hsp90α expression was lower in the T1 phase of lung cancer, esophageal cancer, and gastric cancer patients with prior treatment and higher in breast cancer patients. Apart from colorectal cancer, Hsp90α expression of different cancer types in the T4 phase was highest compared to T1 to T3 phase, and the expression Hsp90α protein increased with cancer progression. These results substantiated that Hsp90α protein expression was consistent with cancer progression overall, although the expression difference between tumor stages was not obvious. Hsp90α was detected in 54 lung cancer patients pre- and post-treatment, and the coincidence rate between the progression of disease and expression change in the Hsp90α protein was 79.63%. For further verification, some patients of them underwent long-term monitoring, and the coincidence rate was 75%.Conclusions: Hsp90α was a potential biomarker for therapeutic monitoring of cancer prognosis, including lung cancer, esophageal cancer, gastric cancer and breast cancer.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A37-A38
Author(s):  
Rick Sorensen ◽  
Marianna Zavodovskaya ◽  
Ping Cheng Yi ◽  
Michael Lee ◽  
Audrey Goddard ◽  
...  

BackgroundInhibiting ecto-5’-nucleotidase (CD73) to reduce immunosuppressive adenosine in the tumor microenvironments is an anti-tumor strategy currently explored in clinical trials. Measuring soluble CD73 (sCD73) activity in plasma to evaluate pharmacodynamics of CD73 inhibitors is appealing. Quantifying phosphate in plasma after adding exogenous adenosine monophosphate (AMP) can be used to determine sCD73 activity.1 Maintaining high plasma concentration to prevent dilution of endogenous sCD73 when quantifying its activity is desirable. High protein concentrations in plasma, however, can affect accurate phosphate quantitation. By precipitating plasma proteins prior to phosphate quantitation, we developed and qualified a method to determine sCD73 activity in 95% plasma.MethodsPlatelet poor heparinized plasma (PPP), AMP, tissue nonspecific alkaline phosphatase inhibitor (TNAPi), recombinant CD73, malachite green, adenosine 5’- (α, β-methylene) diphosphate (APCP), and recombinant alkaline phosphatase (ALP) were procured commercially. sCD73 concentrations were measured by ELISA and total protein concentration was quantified by BCA. sCD73 activity was measured by combining PPP, TNAPi, and AMP at 37°C. Reactions were terminated with trichloroacetic acid (TCA) at various timepoints to generate a kinetic readout. After protein precipitation, phosphate concentrations were measured by malachite green and enzymatic rates calculated as change in free phosphate concentration per minute.ResultsIncubating TCA-terminated reaction mixtures at 4°C for ≥ 3 hours reduced protein in supernatants to below lower limits of quantitation and eliminated interference in phosphate detection. Plasma sCD73 activity was dependent on AMP concentrations (Km = 612 μM), proportional to sCD73 in the sample and could be fully inhibited by APCP. 500 μM TNAPi, an inhibitor of non-CD73 AMPase activity, fully blocked 670 IU/L of recombinant human ALP activity. sCD73 activity in PPP from colorectal carcinoma (CRC) patients was higher (p= 0.0028) than in healthy volunteers (HV). sCD73 activity in some individuals with gastric cancer (GC), non-small cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC) were also numerically higher than in healthy volunteers (figure 1a). sCD73 activity was correlated to sCD73 concentrations in these samples (figure 1b). The method was qualified for use in clinical studies (table 1).Abstract 32 Figure 1asCD73 activity in HV and cancer patient plasma. sCD73 activity in patient plasma from healthy volunteers and solid tumor indications. Abbreviations: HV, healthy volunteer; CRC, colorectal cancer; NSCLC, non-small cell lung cancer; GC, gastric cancer; HNSCC, head and neck squamous cell carcinoma; TNBC, triple-negative breast cancer.Abstract 32 Figure 1bsCD73 activity correlates to sCD73 concentration. Correlation of plasma sCD73 activity and free sCD73 concentrations in patient plasma from healthy volunteers and solid tumor indications. Spearman correlation: r = 0.75, p < 0.0001, n = 135. Abbreviations: HV, healthy volunteer; CRC, colorectal cancer; NSCLC, non-small cell lung cancer; GC, gastric cancer; HNSCC, head and neck squamous cell carcinoma; TNBC, triple-negative breast cancer.Abstract 32 Table 1Plasma sCD73 activity assay qualification limitsPlasma sCD73 activity assay characterization and fit-for-purpose qualification. Abbreviations: LOD, limit of detection; LLOQ, lower limit of quantitation; ULOQ, upper limit of quantitation; APCP, adenosine 5’- (α, β-methylene) diphosphate.ConclusionsA method to quantify sCD73 activity in 95% plasma to evaluate pharmacodynamics of CD73 inhibitors in clinical samples was developed and qualified. Plasma sCD73 activity was dependent on AMP concentration and inhibited by APCP. Plasma sCD73 activity was significantly elevated in CRC patients and selected patients with GC, NSCLC, and TNBC and was proportional to sCD73 concentration.ReferenceMorello S, Capone M, Sorrentino C, Giannarelli D, Madonna G, Mallardo D, Grimaldi AM, Pinto A, Ascierto PA. Soluble CD73 as biomarker in patients with metastatic melanoma patients treated with nivolumab. J Transl Med 2017 Dec 4;15(1):244. doi: 10.1186/s12967-017-1348-8. PMID: 29202855; PMCID: PMC5716054.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Zahra Ahmadi ◽  
Tahereh Farkhondeh ◽  
Saeed Samarghandian

Abstract Application of novel methods in cancer therapy is important in terms of management and treatment of the life-threatening disorder. It appears that autophagy is a potential target in cancer therapy, as a variety of drugs targeting autophagy have shown great potential in reducing the viability and proliferation of cancer cells. Autophagy is primarily a catabolic process which provides energy during starvation. Besides, this process contributes to the degradation of aged or potentially toxic components and organelles. On the other hand, the source of a variety of naturally occurring anti-tumor drugs are flavonoids which have high anti-tumor activity. Luteolin is a polyphenolic flavone with the great pharmacological effects such as anti-diabetic, hepatoprotective, antioxidant, anti-inflammation, and anti-tumor. At the present review, we demonstrate how luteolin affects on autophagy process to induce anti-tumor activity.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Kai Huang ◽  
Xiaoxin Sun ◽  
Haotian Wu ◽  
Jun Zhao ◽  
Yuli Jian ◽  
...  

Autophagy is a treatment target for many disorders, including cancer, and its specific role is becoming increasingly well known. In tumors, researchers pay attention to microribonucleic acids (miRNAs) with regulatory effects to develop more effective therapeutic drugs for autophagy and find new therapeutic targets. Various studies have shown that autophagy-related miRNAs play an irreplaceable role in different tumors, such as miR-495, miR-30, and miR-101. These miRNAs are associated with autophagy resistance in gastric cancer, non-small cell lung cancer, and cervical cancer. In recent years, autophagy-related miRNAs have also been reported to play a role in autophagy in urinary system tumors. This article reviews the regulatory effects of autophagy-related miRNAs in kidney, bladder, and prostate cancer and provides new ideas for targeted therapy of the three major tumors of the urinary system.


Author(s):  
W. L. Steffens ◽  
Nancy B. Roberts ◽  
J. M. Bowen

The canine heartworm is a common and serious nematode parasite of domestic dogs in many parts of the world. Although nematode neuroanatomy is fairly well documented, the emphasis has been on sensory anatomy and primarily in free-living soil species and ascarids. Lee and Miller reported on the muscular anatomy in the heartworm, but provided little insight into the peripheral nervous system or myoneural relationships. The classical fine-structural description of nematode muscle innervation is Rosenbluth's earlier work in Ascaris. Since the pharmacological effects of some nematacides currently being developed are neuromuscular in nature, a better understanding of heartworm myoneural anatomy, particularly in reference to the synaptic region is warranted.


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