ABSTRACT
OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.
Subject(s)
Brachial Plexus Neuropathies , Radiation Injuries , Radiosurgery , Humans , Radiosurgery/adverse effects , Radiotherapy Dosage , Organs at Risk , Brachial Plexus Neuropathies/etiology , Radiotherapy Planning, Computer-AssistedABSTRACT
Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard-risk patients were planned to receive 30 Gy (range 21-36) with median fractions of 3 (range 1-3) and high-risk patients 35 Gy (range 24-50) with median fractions of 5 (range 4-5) according to the spinal cord and esophagus dose constraints. The median follow-up time was 17.07 months (range 3.1-118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1-year and 2-year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1-4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk-adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.
Subject(s)
Carcinoma , Fractures, Compression , Radiosurgery , Spinal Fractures , Spinal Neoplasms , Humans , Radiosurgery/adverse effects , Fractures, Compression/complications , Spinal Neoplasms/radiotherapy , Spinal Neoplasms/secondary , Spinal Fractures/complications , Pain/complicationsABSTRACT
To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS.
Subject(s)
Brachytherapy , Neoplasms , Brachytherapy/adverse effects , Humans , Iodine Radioisotopes , Neoplasms/etiology , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
PURPOSE: This study evaluated the analgesic effect of stereotactic body radiotherapy (SBRT) in combination with celiac plexus block (CPB), relative to SBRT alone, in locally advanced pancreatic cancer (LAPC) patients. PATIENTS AND METHODS: We reviewed medical records of all patients with LAPC, who received SBRT between 1 January 2017 to 31 August 2019 at our center. The average numeric rating scale (NRS) of ≥3 was used in all patients at admission. We recorded average and worst NRS in a 24-hour period, and daily narcotic doses before SBRT, followed by weekly for 1 month and monthly for 3 months. RESULTS: A total of 23 patients in the SBRT group and 12 under SBRT+CPB who met the inclusion criteria were enrolled. All patients in the SBRT+CPB group received CPB within 10 days after SBRT. Pain intensity and narcotic consumption were comparable in both groups at initial assessment. However, a significant decrease (P < 0.05) in average NRS was recorded in the SBRT+CPB group relative to SBRT at 2, 3 and 4 weeks after SBRT. A comparison of daily narcotic consumption with baseline values showed a significant decrease in the SBRT+CPB group at 3 and 4 weeks after SBRT (P < 0.05), while no significant differences were observed in the SBRT group. CONCLUSION: CPB after SBRT appears to be an effective therapeutic option in patients with LAPC and warrants further evaluation with increased number of patients in prospective clinical trials.
ABSTRACT
To determine the therapeutic efficacy and safety of risk-adapted stereotactic body radiation therapy (SBRT) schedules for patients with early-stage central and ultra-central inoperable non-small cell lung cancer. From 2006 to 2015, 80 inoperable T1-2N0M0 NSCLC patients were treated with two median dose levels: 60 Gy in six fractions (range, 48-60 Gy in 4-8 fractions) prescribed to the 74% isodose line (range, 58%-79%) for central lesions (ie within 2 cm of, but not abutting, the proximal bronchial tree; n = 43), and 56 Gy in seven fractions (range, 48-60 Gy in 5-10 fractions) prescribed to the 74% isodose line (range, 60%-80%) for ultra-central lesions (ie abutting the proximal bronchial tree; n = 37) on consecutive days. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), tumor local control rate (LC), and toxicity. Median OS and PFS were 64.47 and 32.10 months (respectively) for ultra-central patients, and not reached for central patients. Median time to local failure, regional failure, and any distant failures for central versus ultra-central lesions were: 27.37 versus 26.07 months, 20.90 versus 12.53 months, and 20.85 versus 15.53 months, respectively, all P < .05. Multivariate analyses showed that tumor categorization (ultra-central) and planning target volume ≥52.76 mL were poor prognostic factors of OS, PFS, and LC, respectively (all P < .05). There was one grade 5 toxicity; all other toxicities were grade 1-2. Our results showed that ultra-central tumors have a poor OS, PFS, and LC compared with central patients because of the use of risk-adapted SBRT schedules that allow for equal and favorable toxicity profiles.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Radiosurgery/methods , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Dose Fractionation, Radiation , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Progression-Free Survival , Radiosurgery/adverse effects , Retrospective Studies , Time Factors , Treatment FailureABSTRACT
Six new macrolides named myrothecines D-G (1-4), 16-hydroxymytoxin B (5), and 14'-dehydrovertisporin (6), including four 10,13-cyclotrichothecane derivatives, in addition to 12 known compounds (7-18), were isolated from three endophytic Myrothecium roridum, IFB-E008, IFB-E009, and IFB-E012. The isolated compounds were characterized by MS, NMR, CD, and single-crystal X-ray crystallography. The isolated macrolides exhibited an antiproliferation effect against chronic myeloid leukemia K562 and colorectal carcinoma SW1116 cell lines. Compounds 1-6 were cytotoxic, with IC50 values ranging between 56 nM and 16 µM. Since slight structural changes led to obvious activity differences, the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were then used to explore the 3D QSAR (three-dimensional quantitative structure-activity relationship) of these macrolides. The result showed that the steric, electrostatic, hydrophobic, and H-bond acceptor factors were involved in their cytotoxicity and provided an in-depth understanding of the structure-activity relationships of these metabolites.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Hypocreales/chemistry , Macrolides/pharmacology , Mitosporic Fungi/chemistry , Protein Synthesis Inhibitors/pharmacology , Trichothecenes/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Crystallography, X-Ray , Macrolides/chemistry , Macrolides/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Protein Synthesis Inhibitors/chemistry , Protein Synthesis Inhibitors/isolation & purification , Quantitative Structure-Activity Relationship , Trichothecenes/chemistry , Trichothecenes/isolation & purificationABSTRACT
BACKGROUND: Contactin1 (CNTN1) has been shown to play an important role in the invasion and metastasis of several tumors; however, the role of CNTN1 in breast cancer has not been fully studied. The purpose of this study is to investigate the role of CNTN1 in regulating tumor growth, migration and invasion in breast cancer. RESULTS: To investigate its function, CNTN1 was expressed in Hs578T cells. CNTN1 expression was confirmed by western blot, immunohistochemistry and real-time RT-PCR. The effect of CNTN1 overexpression on proliferation, migration and invasion of Hs578T breast cancer cells was assessed in vitro and in vivo. Our results showed that CNTN1 overexpression promoted Hs578T cell proliferation, cell cycle progression, colony formation, invasion and migration. Notably, overexpression of CNTN1 in Hs578T cells enhanced the growth of mouse xenograft tumors. CONCLUSIONS: CNTN1 promotes growth, metastasis and invasion of Hs578T breast cancer cell line. Thus, therapies targeting CNTN1 may prove efficacious for breast cancer. However, further investigation is required to understand the mechanism by which CNTN1 influences proliferation, metastasis and invasion in breast cancer.
Subject(s)
Breast Neoplasms/pathology , Cell Movement , Contactin 1/metabolism , Animals , Cell Line, Tumor , Cell Proliferation , Female , Humans , Male , Mice, Nude , Neoplasm Invasiveness , Xenograft Model Antitumor AssaysABSTRACT
Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P < 0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P < 0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P = 0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.
Subject(s)
Biomarkers, Tumor/metabolism , RNA/metabolism , Stomach Neoplasms/metabolism , Adult , Aged , Biomarkers, Tumor/blood , Cell Line, Tumor , Down-Regulation , Female , Humans , Male , Middle Aged , RNA/blood , RNA, Circular , Stomach Neoplasms/blood , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND AND AIM: The aim of this study is to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using CyberKnife in the treatment of patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. PATIENTS AND METHODS: Between October 1, 2006 and May 1, 2015, patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery were enrolled and treated with SBRT at our hospital. The primary end point was local control rate after SBRT. Secondary end points were overall survival, time to symptom alleviation, and toxicity, assessed using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Twenty-four patients with 24 lesions (17 abdominal lymph nodes and seven stumps) were treated with SBRT, of which five patients presented with abdominal lymph nodes and synchronous metastases in the liver and lung. The 6-, 12-, and 24-month actuarial local control rates were 95.2%, 83.8%, and 62.1%, respectively. For the entire cohort, the median overall survival from diagnosis and SBRT was 28.9 and 12.2 months, respectively. Symptom alleviation was observed in eleven of 14 patients (78.6%) within a median of 8 days (range, 1-14 days) after SBRT. Nine patients (37.5%) experienced Common Terminology Criteria for Adverse Events version 4.0 grade 1-2 acute toxicities; one patient experienced grade 3 acute toxicity due to thrombocytopenia. CONCLUSION: SBRT is a safe and effective treatment for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Further studies are needed before SBRT can be recommended routinely.
ABSTRACT
AIM: This study was to evaluate the diagnostic value of OSR2, VAV3, and PPFIA3 hypermethylation in gastric cancer (GC) patients. PATIENTS AND METHODS: By using methylation-specific polymerase chain reaction (MSP), we detected the methylation status in tissue and serum samples from 48 gastric cancer (GC) patients and 25 normal individuals. RESULTS: We found that OSR2, VAV3, and PPFIA3 were methylated in 70.8% (34/48), 54.2% (26/48), and 60.4% (29/48) of GC tissue, respectively. On the contrary, those genes were barely methylated in their paired paracancerous histological normal tissues (PCHNTs) (all P values < 0.01). We next analyzed the methylated OSR2, VAV3, and PPFIA3 in serum DNA. Compared with 25 normal individuals, those three genes were significantly hypermethylated in GC patients serum samples (all P values < 0.01). Regarding their diagnostic value in serum samples, the combined sensitivity of at least one positive among the three markers in serum was 83.3%, with a specificity of 88%. CONCLUSION: Our test suggested that methylation of OSR2, VAV3, and PPFIA3 genes in serum sample may offer a good alternative in a simple, promising, and noninvasive detection of GC.
Subject(s)
DNA Methylation , Membrane Proteins/genetics , Proto-Oncogene Proteins c-vav/genetics , Stomach Neoplasms/genetics , Transcription Factors/genetics , Adult , Aged , Epigenesis, Genetic , Female , Humans , Male , Middle Aged , Promoter Regions, Genetic , Stomach Neoplasms/blood , Stomach Neoplasms/pathologyABSTRACT
AIMS: This study evaluated the safety and efficacy of stereotactic radiation therapy (SRT) for the treatment of patients with oligometastases or oligorecurrence within mediastinal lymph nodes (MLNs) originating from different tumors. METHODS: Between October 2006 and May 2015, patients with MLN oligometastases or oligorecurrence were enrolled and treated with SRT at our hospital. The primary endpoint was MLN local control (LC). Secondary endpoints were time to symptom alleviation, overall survival (OS) after SRT, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). RESULTS: Eighty-five patients with 98 MLN oligometastases or oligorecurrences were treated with SRT. For the entire cohort, the 1-year and 5-year actuarial LC rates were 97% and 77%, respectively. Of 53 symptomatic patients, symptom alleviation was observed in 47 (89%) after a median of 5 days (range, 3-30 days). The median OS was 27.2 months for all patients. For patients with non-small cell lung cancer, univariate and multivariate analyses revealed that a shorter interval between diagnosis of primary tumors and SRT and larger MLN SRT volume were associated with worse OS. CTCAE v4.0 ≥ Grade 3 toxicities occurred in six patients (7%), with Grade 5 in three patients (all with RT history to MLN station 7). CONCLUSIONS: SRT is a safe and efficacious treatment modality for patients with oligometastases or oligorecurrence to MLNs originating from different tumors, except for patients who received radiotherapy to MLN station 7. Further investigation is warranted to identify the patients who benefit most from this treatment modality.
Subject(s)
Lymph Nodes/pathology , Mediastinal Neoplasms/radiotherapy , Mediastinal Neoplasms/secondary , Neoplasm Recurrence, Local/radiotherapy , Radiosurgery/adverse effects , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/pathology , Lymphatic Metastasis/radiotherapy , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Adjuvant radiation therapy is commonly administered to breast cancer patients who received breast-conserving surgery. However, lengthy treatment times of standard radiotherapy pose certain challenges. Here, we performed a prospective controlled study comparing standard radiation to hypofractionated radiotherapy in terms of efficacy and outcome. MATERIAL AND METHODS: Eighty breast cancer patients (tumor stage pT1-2N0-1M0) who had undergone breast-conservation surgery were randomly divided into 2 groups (40 patients/group). The experimental group received 43.2 Gy to the whole breast in 18 fractions for 24 days with a concomitant boost (50.4 Gy) to the tumor bed. The control group received 45 Gy to the whole breast in 25 fractions for 44 days with a boost to the tumor bed of 59 Gy. Survival, locoregional recurrence, adverse effects, and aesthetic results were all considered for analysis. RESULTS: The following criteria were included as part of study follow-up: local control, survival, adverse skin reactions, cosmetic outcome, and hematological toxicity. At a median follow-up of 27 months (follow-up rate 100%), there were no statistical differences in any of the categories between the 2 groups. The 2-year survival rate of both groups was 100% without any locoregional recurrence. Although there was some skin toxicity, these instances were not severe and they cleared on their own within 6 weeks. The most common problems encountered by patients were breast fibrosis and altered pigmentation. CONCLUSIONS: A shortened whole-breast hypofractionated irradiation schedule with a concomitant boost is as effective as standard radiation and may be a reasonable alternative following breast conservation surgery.
Subject(s)
Breast Neoplasms/radiotherapy , Dose Fractionation, Radiation , Mastectomy, Segmental , Breast Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Middle Aged , Prospective Studies , Survival Rate , Treatment OutcomeABSTRACT
AIMS: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT, both stereotactic body RT [SBRT] and fractionated stereotactic RT [FSRT]) in the treatment of patients with recurrent or second primary mediastinal lymph node metastases (R/SP-MLNMs) originating from non-small cell lung cancer (NSCLC). METHODS: Between 10/2006 and 7/2013, patients with R/SP-MLNMs originating from NSCLC were enrolled and treated with SRT at our hospital; their data was stored in prospectively-collected database. The enrolled patients were divided into Group A (without prior RT) and Group B (with prior RT). The primary end-point was overall survival (OS). The secondary end-points were the MLNM local control (LC), the time to symptom alleviation, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). RESULTS: Thirty-three patients were treated (16 in Group A with 19 R/SP-MLNMs and 17 in Group B with 17 R/SP-MLNMs). For the entire cohort, the median OS was 25.5 months with a median follow-up of 20.9 months (range, 3.2-82). The 1-year and 3-year actuarial LC rates were 100% and 86%, respectively. Symptom alleviation was observed in 52% of patients, after a median of 6 days (range, 3-18). CTCAE v4.0 ≥ Grade 3 toxicities occurred in 5 patients (15%; all in Group B); among them, Grade 5 in 2 patients. CONCLUSIONS: We recommend exercising extreme caution in using SRT for R/SP-MLNMs in patients who received prior RT (particularly to LN station 7). For patients without previous RT, SRT appears to be safe and efficacious treatment modality; prospective studies are warranted.
Subject(s)
Lymphatic Metastasis/radiotherapy , Mediastinal Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Neoplasms, Second Primary/radiotherapy , Radiosurgery/methods , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/pathology , Lymph Nodes/pathology , Male , Mediastinal Neoplasms/mortality , Mediastinal Neoplasms/secondary , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasms, Second Primary/mortality , Prospective Studies , Radiosurgery/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
AIM: We examined the methylation status of SNCA and FBN1 genes in patients' paired tissue and stool samples for detection of colorectal cancer (CRC). PATIENTS AND METHODS: 89 DNA tissue samples (normal/cancer) and corresponding stool samples were analyzed in our study. In addition, 30 stool samples were collected as healthy controls. RESULTS: The methylation level of those samples was measured by methylation-specific polymerase chain reaction (MSP). The result shows that compared with the paired controls, both SNCA and FBN1 were significantly hypermethylated in CRC patients in tissue samples (P < 0.001). In the stool samples, hypermethylated SNCA and FBN1 were detected to be significantly higher than that in normal stool samples (P < 0.001). The combined sensitivity of at least one positive among the two markers in stool samples was 84.3%, with a specificity of 93.3%. In addition, our experiment suggested that the positive rates of SNCA and FBN1 in Dukes A stage were significantly higher than that of FOBT (P = 0.039; P = 0.006, resp.). CONCLUSION: We concluded that methylation testing of SNCA and FBN1 genes in stool sample may offer a good alternative in a simple, promising, and noninvasive detection of colorectal cancer.
Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation , Early Detection of Cancer/methods , Feces/chemistry , Microfilament Proteins/genetics , alpha-Synuclein/genetics , Adult , Aged , Case-Control Studies , Colorectal Neoplasms/pathology , Female , Fibrillin-1 , Fibrillins , Humans , Male , Middle AgedABSTRACT
Isolation and purification of chemical constituents from solid culture of endophyte Chaetomium globosum in Imperata cylindrical was performed through silica gel column chromatography, gel filtration over Sephadex LH-20 and preparative HPLC. Nine compounds were obtained and their structures were determined as chaetoglobosin F(1), chaetoglobosin Fex(2), chaetoglobosin E(3) cytoglobosin A(4), penochalasin C(S), isochaetoglobosin D (6), N-benzoylphenylalaninyl-N-benzoyphenylalaninate(7), uracil(8) and 5-methyluracil(9), respectively, based on HR-MS and NMR data and comparison with literatures. Compound 7 was isolated from Chaeeomium sp. for the first time. In vitro cytotoxicity of compounds was evaluated using MTT mothed and 1,3,4 and 5 showed inhibition activity to the human cervical carcinoma cell HeLa with IC50 values of 99.43, 23.77, 97.92, 86.25 micromol x L(-1), while positive cotolocisnin Ad apno1ch alse IC50 24.33 micromol x L(-1).
Subject(s)
Biological Factors/chemistry , Chaetomium/chemistry , Endophytes/chemistry , Poaceae/microbiology , Biological Factors/pharmacology , Cell Line , Cell Survival/drug effects , Humans , Molecular Structure , Spectrometry, Mass, Electrospray IonizationABSTRACT
The present study was designed to isolate and purify chemical constituents from solid culture of endophyte Aspergillus terreus LQ, using silica gel column chromatography, gel filtration with Sephadex LH-20, and HPLC. Fumigaclavine I (1), a new alkaloid, was obtained, along with seven known compounds, including fumigaclavine C (2), rhizoctonic acid (3), monomethylsulochrin (4), chaetominine (5), spirotryprostatin A (6), asperfumoid (7), and lumichrome (8). The structure of compound 1 was elucidated by various spectroscopic analyses (UV, MS, 1D and 2D NMR). The in vitro cytotoxicity of compound 1 was determined by MTT assay in human hepatocarcinoma cell line SMMC-7721, showing weaker cytotoxicity, compared with cisplatin, a clinically used cancer chemotherapeutic agent.
Subject(s)
Aspergillus/chemistry , Endophytes/chemistry , Ergot Alkaloids/chemistry , Ergot Alkaloids/isolation & purification , Oryza/microbiology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Aspergillus/isolation & purification , Cell Line, Tumor , Cell Survival/drug effects , Endophytes/isolation & purification , Humans , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Three compounds were isolated from solid culture of endophyte Myrothecium roridum IFB-E091 in Artemisia annua. Their structures were determined as (S)-(-)-N-[2-(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (1), N-(4-hydroxyphenethyl)acetamide (2) and asperfumoid (3), in which compound 1 was a new indole derivative. In cytotoxicity assay, the compound 1 had no obvious inhibition activity in human hepatoma cell line SMMC-7721 and human cervical carcinoma cell line HeLa.
Subject(s)
Artemisia annua/microbiology , Endophytes/chemistry , Hypocreales/chemistry , Indoles/chemistry , Cell Line, Tumor/drug effects , Humans , Indoles/isolation & purificationABSTRACT
The white croaker (Argyrosomus argentatus) derived Curvularia sp. IFB-Z10 produces curvulamine as a skeletally unprecedented alkaloid incorporating two undescribed extender units. Curvulamine is more selectively antibacterial than tinidazole and biosynthetically unique in the new extenders formed through a decarboxylative condensation between an oligoketide motif and alanine.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Ascomycota/chemistry , Perciformes/microbiology , Actinomyces/drug effects , Alkaloids/chemistry , Animals , Anti-Bacterial Agents/chemistry , Bacteroides/drug effects , Indole Alkaloids , Marine Biology , Microbial Sensitivity Tests , Mitosporic Fungi , Molecular Structure , Peptostreptococcus/drug effects , Streptococcus/drug effects , Tinidazole/pharmacology , Veillonella/drug effectsABSTRACT
Ergot alkaloids are toxins which are produced biotechnologically on an industrial scale. The chemical investigation of endophytic Aspergillus fumigatus resulted in the isolation of five new ergot alkaloids named fumigaclavines D-H (2-6), along with three known analogues, fumigaclavine C (1), festuclavine (7), and fumigaclavine A (8). Their structures were unequivocally elucidated by extensive spectroscopic analyses in association with X-ray single-crystal diffraction. Fumigaclavines D-H are interesting clavine-type ergot alkaloids featuring a reverse prenyl moiety at C-2, with 1-4, 6, and 8 bearing additional substituents, e.g., an OH or OAc group at C-9. Compounds 2, 4, and 6-8 showed a broad spectrum of antimicrobial activity against a panel of anaerobic microorganisms, of which compounds 4 and 6 were the most active against Veillonella parvula with an MIC=16 µg/mL compared to that (0.12 µg/mL) of tinidazole, co-assayed as a positive reference.
Subject(s)
Anti-Infective Agents/pharmacology , Aspergillus fumigatus/chemistry , Ergot Alkaloids/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Chromatography, High Pressure Liquid , Ergot Alkaloids/chemistry , Ergot Alkaloids/isolation & purification , Fermentation , Microbial Sensitivity Tests , Nuclear Magnetic Resonance, Biomolecular , X-Ray DiffractionABSTRACT
AIM: To study the chemical constituents of the solid culture of the endophyte Phomopsis sp. IFB-E060 in Vatica mangachapoi. METHOD: Isolation and purification were performed through silica gel column chromatography, gel filtration over Sephadex LH-20, ODS column chromatography, and HPLC. Structures of the isolated compounds were elucidated by a combination of spectroscopic analyses (UV, CD, IR, MS, 1D, and 2D NMR). The cytotoxicity of the isolates was evaluated in vitro by the MTT method against the human hepatocarcinoma cell line SMMC-7721. RESULTS: Five compounds were isolated from the solid culture of the endophyte Phomopsis sp. IFB-E060 and their structures were identified as 18-methoxy cytochalasin J (1), cytochalasin H (2), (22E, 24S)-cerevisterol (3), ergosterol (4), and nicotinic acid (5). Compound 1 had an inhibition rate of 24.4% at 10 µg·mL(-1) and 2 had an IC50 value of 15.0 µg·mL(-1), while a positive control 5-fluorouracil had an inhibition rate of 28.7% at 10 µg·mL(-1). CONCLUSION: 18-Methoxy cytochalasin J (1), produced by endophytic Phomopsis sp. IFB-E060, is a new cytochalasin with weak cytotoxicity to the human hepatocarcinoma cell line SMMC-7721.