Treatment Outcomes and Effects of Ethanol Sclerotherapy on Systemic Coagulation Profile of Patients with Venous Malformation.

BACKGROUND: Venous malformations (VMs) and sclerotherapy may disrupt the normal systemic coagulation profile in individuals. This study investigated a correlation between the clinical efficacy of sclerotherapy in the treatment of VMs and the changes in coagulation indexes to provide data that will inform the future application of this therapy. METHODS: From September 2019 to September 2020, 61 patients were enrolled in this study to receive sclerotherapy with absolute alcohol. The clinical outcomes and the coagulation profile were assessed. RESULTS: Sclerotherapy induced increasing fibrin (original) degradation products (FDP) and D-dimer (D-D) levels. The changes in FDP and D-D level pretreatment and posttreatment were positively correlated with treatment outcomes. Moreover, a repeated treatment with absolute alcohol may restore normal levels of FDP and D-D. CONCLUSIONS: Upregulation of FDP and D-D levels after sclerotherapy results in good therapeutic outcomes. Therefore, monitoring changes in FDP and D-D levels in patients with VMs undergoing sclerotherapy may reflect the effects of sclerotherapy.

Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

Application of Three Different Types of Pedicled Latissimus Dorsi Flaps in Repairing Nearby Deep Soft Tissue Defects: Cosmetic Result and Shoulder Functionality Evaluation in One Center.

Objective: The latissimus dorsi (LD) flap has generally been considered a workhorse flap in clinics. However, the impairment of shoulder function and the dramatic appearance in the donor site are the major problems associated with traditional latissimus dorsi myocutaneous flap (LDMF). Here, we analyzed the reliability of three types of LD flaps in repairing deep soft tissue defects in the upper limbs, shoulder, back, and chest wall. Methods: From December 2016 to December 2020, 21 patients from our center underwent reconstruction of deep soft tissue defects using different types of LD flaps. The distribution of the thoracodorsal artery and the location of its branches were confirmed by imaging examination. Based on the defects, traditional LDMF, thoracodorsal artery perforator flap with capillary perforators (TAPcp), or low-skin-paddle pedicled LDMF was selected and specifically designed for each patient. The appearance satisfaction and shoulder functional of daily life recovery were evaluated. Results: A total of 12 traditional LDMF, 4 TAPcp, and 5 low-skin-paddle pedicled LDMFs were used. All flaps survived well. The donor site was sutured directly with satisfactory appearance (n = 7) or repaired using skin grafts (n = 14). Compared to traditional LDMF, TAPcp and low-skin-paddle pedicled LDMF have faster shoulder function of daily life recovery. Conclusion: Based on the characteristics of defects, personalized design of different types of LD flaps is a reliable option to repair different defects.

Identification of FAM107A as a potential biomarker and therapeutic target for prostate carcinoma.

FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer.

OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

[Effects of Lignum Sappen on growth and metastases of Lewis lung carcinoma at different phases in C57BL/6 mice].

OBJECTIVE: To observe the effects of Lignum Sappan (LS) on the growth and metastases of transplanted Lewis lung carcinoma (LLC) in mice and investigate its partial mechanism of action. METHODS: C57BL/6 mice were established in LLC model and divided into six groups in random: Group A was untreated; Group B was treated by chemotherapy (CM) only; Groups C-F were treated respectively with low-dose LS, high-dose LS, CM + low-dose LS and CM + high-dose LS, via intragastric administration for 21 successive days. Mice were sacrificed in batches at different time points (d 7, d 14 and d 21) to observe the tumor inhibition rate and the metastases suppressing rate was measured dynamically. Meantime, the CD44 expression in tumor cells was measured by flow cytometry and serum P-selectin concentration was measured by ELISA assay. RESULTS: Tumor weight in all treated groups, except Group C, was lower than that in Group A at the three time points (P < 0.05, P < 0.01), and that was lower in Group F than in Group B at the corresponding time points (P < 0.05, P < 0.01). Comparisons of CD44+ in tumor cells showed that as compared with Group A, on d 7, it was lower in Groups B and D (P < 0.01); on d 14, it was lower in Group E (P < 0.01) and Group F (P < 0.05); and on d 21, it was lower in Groups E and F (P < 0.01). As for the concentration of P-selectin, the intergroup comparisons showed that it was lower in Groups B-F on d 7 and in Group F on d 21 than that in Group A (P < 0.05 or P < 0.01), but showed insignificant difference in comparing the Group A with all the treated Groups on d 14 (P > 0.05). CONCLUSION: LS and CM +LS could inhibit the growth and metastases of LLC, and shows inhibition on CD44 expression in tumor cells and P-selectin level in serum, which may be one of the mechanisms of LS in suppressing tumor metastasis.

[Comparative study on the methods of Chinese medicine and Western medicine therapeutic evaluation for advanced non-small cell lung cancer].

OBJECTIVE: To compare the differences and characteristics in Chinese medicine (CM) and Western medicine therapeutic evaluation methods in the application of advanced non-small cell lung cancer. METHODS: A total of 200 cases of advanced non-small cell lung cancer from 3 subcenters were enrolled the study and assigned to two groups, 104 in the CM group treated with CM injection combined with treatment based on syndrome differentiation, 96 in the chemotherapy group treated with the international chemothearapy scheme, both the course of treatment was 6 weeks. Their short-term therapeutic effects were observed by the "clinic efficacy appraisal standard of therapy for advanced lung cancer with CM" simultaneously and by the follow-up Western medical solid tumor's effect evaluation criterion, including clinical symptoms, tumor body, Karnorfsky score, body weight and immune function evaluation. RESULTS: According to WHO solid tumor's effect evaluation criterion, the efficacy of the chemotherapy group was much better than that of the CM group (P < 0.01). While, according to the "clinic efficacy appraisal standard of therapy for advanced lung cancer with CM", the efficacy of the CM group was better than that of the chemotherapy group without statistical difference (P = 0.05), however, there was a very strong trend of appearing difference. There was difference inult o the results of the two evaluation methods. CONCLUSION: Compared with WHO solid tumor's effect evaluation criterion, "the clinic efficacy appraisal standard of therapy for advanced lung cancer with CM" can reflect more features and advantages of CM for cancer treatment, having value for further study.

Heparanase from triple­negative breast cancer and platelets acts as an enhancer of metastasis.

Triple­negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia­inducible factor­1a (HIF-1a)/vascular endothelial growth factor­a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti­Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer. METHODS: A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS). RESULTS: Compared to the SA group, the TA group didn't show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study. CONCLUSION: Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.

Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation.

A number of murine models are used to mimic the pathology of breast cancer. Tissue inoculation and cell inoculation using orthotopic implantation (OS) and subcutaneous implantation (SQ) are commonly used to generate murine models to investigate cancer. However, limited information is available in regard to the variations of these methods. The present study compared growth, metastasis, survival and histopathology of tumors produced using OS and SQ to characterize features of the tumors produced by the two distinct methods. Additionally, the present study aimed at providing increased options for investigators when designing experiments. 4T1-luc2 cell suspension or 4T1-luc2 tissue suspension was inoculated using either OS or SQ into BALB/c mice. Tumor growth and metastasis were detected using an in vivo imaging system and calipers. Excised tumors and lung were assessed by tissue staining with hematoxylin and eosin, and the vessel marker cluster of differentiation 31. The results of the present study revealed that the cell suspension generated breast tumors of increased size, which was visualized and determined, following inoculation, using calipers at an earlier time point compared with tumors produced by tissue suspension. The increasing bioluminescent trend of OS tumors was more marked compared with that of SQ tumors. The volume of OS tumor was increased with decreased variation, compared with that of SQ tumors. In addition, the OS tumor exhibited increased microvessel density. Bioluminescent signals and histological results in regard to metastasis were consistent: OS implantation produced increased lung metastasis compared with that of SQ implantation, although they exhibited similar survival times. The results of the present study indicated that the inocula from distinct sources (tissue or cell) affected tumor growth. Furthermore, breast tumor progression and histopathological characteristics were distinct between OS and SQ, whereas OS exhibited increased malignant behavior. Understanding the characteristics of murine breast cancer models established by diverse methods may aid investigators to select appropriate animal models, according to the requirements of the study.

Chinese Medicine Yishen Jiangu Granules () on Aromatase Inhibitor-Associated Musculoskeletal Symptoms.

OBJECTIVE: To assess the effectiveness of Yishen Jiangu Granules (, YSJGG) on aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). METHODS: A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks (12.4 g orally twice daily). The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form (BPI-SF) over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the Functional Assessment of Cancer Therapy-Breast (FACT-B), bone mineral density (BMD) and blood indices such as calcium (Ca), phosphate (P), and alkaline phosphatase (ALP). RESULTS: Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome (BPI-SF worst pain scores) achieved a 2.17-point reduction compared with baseline (5.75±1.87 vs 3.58±2.15, P<0.01). There were reductions in pain severity (decreased 1.65, P<0.01) and pain-related interference (decreased 2.55, P<0.01). The changes in WOMAC and M-SACRAH scores were similar to BPI-SF (P<0.05). In the FACT-B, only physical well-being and functional well-being were improved compared with baseline (P<0.05). No clinical differences were found in BMD, Ca, P and ALP. CONCLUSION: YSJGG is an effective and well-tolerated agent to reduce AIMSS.

Risk of peripheral edema in cancer patients treated with MEK inhibitors: a systematic review and meta-analysis of clinical trials.

BACKGROUND: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors. MATERIALS AND METHODS: The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau2, Chi2, and I2 analyses. RESULTS: A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98-4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66-5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved. CONCLUSION: This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.

Effect of acupuncture in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: study protocol for a randomized controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects in patients with cancer. The introduction and development of antiemetic drugs have significantly improved the ability of clinicians to control CINV, but it is not easy to translate to practical application, owing to financial issues, provider-related barriers, and patient factors. Nondrug therapies are needed to alleviate the symptoms of CINV. Acupuncture is an appropriate adjunctive treatment for CINV, but additional evidence is needed. METHODS/DESIGN: This study is a multicenter, randomized, sham-controlled prospective clinical trial. A total of 136 participants will be randomly allocated into the intervention group (verum acupuncture) or the control group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days. Participants in both groups will receive acupuncture sessions twice on the first day of chemotherapy and once consecutively on the following 4 days. Each session takes approximately 30 minutes. The primary outcome measure will be the Common Terminology Criteria for Adverse Events to assess CINV. The secondary outcome measures will be the Eastern Cooperative Oncology Group score, Simplified Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale. Safety will be assessed at each visit. DISCUSSION: The results of this trial will provide clinical evidence for the effect and safety of acupuncture for CINV. TRIAL REGISTRATIONS: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on 28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17 February 2015.

Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase.

Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad­spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo­D­glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real­time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low­molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal­regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.

Identification of regulatory role of DNA methylation in colon cancer gene expression via systematic bioinformatics analysis.

Colon cancer arises from the accumulations of genetic and epigenetic changes. Currently, profiles of DNA methylation and gene expression of colon cancer have not been elucidated clearly. This articles aims to characterize the profile of DNA methylation and gene expression of colon cancer systemically, and acquire candidate genes potentially regulated by altered methylation for this disease.Data were downloaded from The Cancer Genome Atlas database. Differentially methylated CpG sites (DMCs) and differentially methylated regions (DMRs) were calculated via COHCAP. Differentially expressed genes (DEGs) were identified by DESeq2. Weighted gene co-expression network analysis (WGCNA) package in R was applied for WGCNA.Data of 275 solid tumor tissues and 19 adjacent tumor tissues of colon cancer were obtained. A total of 1828 DMCs, including 1390 hypermethylated and 438 hypomethylated CpG sites, were identified between tumor and normal groups. A total of 789 DEGs, containing 435 upregulated genes and 354 downregulated genes were observed. It revealed that 8 DMRs-DEGs and 95 DMCs-DEGs pairs were significantly correlated. Furthermore, genes of yellow and brown modules from WGCNA were significantly correlated with tumor/normal status, and significantly enriched in peroxisome proliferator activated receptor signaling pathway, glutamatergic synapse, and neuroactive ligand-receptor interaction. Genes in the above 2 modules were also significantly enriched in DMCs or DMRs-associated genes. Specifically, ADHFE1, HAND2, and GNAO1 were hypermethylated and downregulated in colon cancer, suggesting that the low expression levels of these genes may be regulated by DNA hypermethylation. In addition, the 3 genes were involved in brown module of WGCNA, indicating their important roles in colon cancer.The investigation of the relationship between DNA methylation and gene expression may help to understand the effect of DNA methylation alteration on genes expression, especially gene co-expression network in the development of colon cancer. Genes such as ADHFE1, HAND2, and GNAO1 may be served as potential candidates for diagnosis and therapy targets in colon cancer.

Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway.

Although Chinese herbal compounds have long been alternatively applied for cancer treatment in China, their treatment effects have not been sufficiently investigated. The Chinese herb Spatholobus suberectus is commonly prescribed to cancer patients. HPLC analysis has shown that the main components of Spatholobus suberectus are flavonoids that can be classified as phytoestrogens, having a structure similar to estrogen. This study was designed to investigate the effects of Spatholobus suberectus column extract (SSCE) on the estrogen receptor-positive (ER+) breast cancer cell line MCF-7 and its possible molecular mechanism. In our study, MTT assay was performed to evaluate cell viability. The results show that SSCE (80, 160, and 320 µg/ml) significantly decreased the viability of MCF-7 cells. SSCE also triggered apoptosis, arrested the cell cycle at the G0/G1 phase, and inhibited cell migration. A dual-luciferase reporter system showed that SSCE suppressed intranuclear p-ER activity; Western blot analysis confirmed the repressed expression of phosphorylated-ER alpha (p-ERα), ERK1/2, p-ERK1/2, AKT, p-AKT, p-mTOR, PI3K, and p-PI3K, indicating that SSCE suppressed the MAPK PI3K/AKT signaling pathway. Collectively, our results suggest that SSCE causes apoptosis, an arrest in the G0/G1 phase, and a decrease in migration in ER+ MCF-7 cells via hypoactivity of the ER and suppression of the MAPK PI3K/AKT pathway.

Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

OBJECTIVE: To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. METHODS: Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor ß1 (TGF-ß1) were analyzed by western blot. RESULTS: Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-ß1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-ß1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-ß1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). CONCLUSION: HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis.

Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy-associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available.

Inhibitory effects of Guben Yiliu Formula II (II) and its blood activation prescriptions on the growth of MCF-7 human breast cancer xenografts in nude mice.

OBJECTIVE: To investigate the inhibitory effects of Guben Yiliu Formula II(II, GFII) and its blood activation prescription (BAP) on the growth of MCF-7 human breast cancer xenografts in nude mice, and explore their mechanisms of action. METHODS: After the establishment of the MCF-7 human breast cancer xenograft model in nude mice, the mice in the GFII and BAP groups were administered with GFII (6.56 g/mL) and BAP (1.65 g/mL) by gavage for 28 days, respectively. The tumor volume and weight were measured twice a week throughout the treatment period. Apoptotic cells were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of microtubule associated protein 1 light chain 3 (LC3) was examined by immunohistochemistry, and Western blotting analysis was performed to detect the expression of anti-apoptotic protein Bcl-2 and LC3, as well as the effects on phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. RESULTS: Compared with the control group, the GFII and BAP groups could significantly inhibit the growth of MCF-7 human breast cancer xenografts in nude mice. The expression of Bcl-2 protein was lower in the GFII and BAP than in the control group, whereas both the percentage of apoptotic cells and LC3-II/LC3-I ratio were higher than in the control group. In addition, significantly reduced expression of phospho-Akt, phosphor-mTOR and mTOR were observed in the blood activation group (P<0.05). CONCLUSIONS: To some extent, the GFII and its BAP can exert their inhibitory effect on the growth of MCF-7 human breast cancer xenografts by inducing the cell apoptosis and autophagy. In addition to the induction of cell apoptosis, we also found that the BAP of GFII could induce cell autophagy by inhibiting of PI3K/Akt/mTOR signaling pathway, and then suppress the breast cancer cell growth.