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Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules merits further exploration. In this study, we combined oncolytic measles virus (MV) with the natural triterpenoid compound ursolic acid (UA) and evaluated their combination effect against HCC cells, including those harboring hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. We found that the combination of MV and UA synergistically induced more cell death in Huh-7 HCC cells through enhanced apoptosis. In addition, increased oxidative stress and loss of mitochondrial potential were observed in the treated cells, indicating dysregulation of the mitochondria-dependent pathway. Similar synergistic cytotoxic effects were also found in HCC cells harboring HBV or HCV genomes. These findings underscore the potential of oncolytic MV and UA combination for further development as a treatment strategy for HCC. [ABSTRACT FROM AUTHOR]

Purpose. Real-world evidence refers to patient data derived from the healthcare process. In this study, we used National Health Insurance Research Database (NHIRD) assessments and clinical studies of Ge Gen Tang (GGT, 葛根湯) in patients with common cold to establish a real-world study model of Traditional Chinese Medicine formulae. GGT is widely prescribed for the treatment of common cold in Taiwan, generally in combination with other medicines. The aim of this study was to determine whether a correlation exists between GGT combined with other medicines and an improvement in cold symptoms. We also established a GGT prescription compatibility system by analyzing Taiwan's NHIRD records for GGT prescription patterns in patients with different types of common cold. Materials and Methods. We extracted and analyzed records from the NHIRD for the period 2000–2015 to determine the most common clinical applications of GGT. GGT and GGT with Chuan Xiung Cha Tiao San were most commonly prescribed for common cold, as per NHIRD recommendations. Records for adults aged 20–65 years who were prescribed GGT for the treatment of common cold (Diagnosis Code ICD-9-460) were included in this study. We assessed the following indicators of the common cold, before and after treatment with GGT: nasal congestion, cough, runny nose, sneezing, sore throat, hoarseness, stiff shoulder, headache, and general physical condition. Results. The cold symptom scores before and after taking the GGT prescriptions significantly differed in the 29 volunteers. The 29 volunteers reported a significantly lower headache severity score after medication than before medication (p < 0.004). Furthermore, patient scores for general physical condition decreased significantly (p < 0.01) after medication. [ABSTRACT FROM AUTHOR]

(1) Background: The microbial phase in the vaginal environment has been found to regulate the physiological activity of host cells. Studies have demonstrated that abnormal microbial growth in the vagina and a significant reduction in the proportion of lactic acid bacteria promote the occurrence of spontaneous preterm birth (sPTB). However, the contributing mechanism remains unknown. (2) Methods: This study uses extracellular vesicles (EVs) secreted by the probiotic Lactobacillus crispatus, commonly found in the vagina, to explore their potential to attenuate placental cells caused by oxidative stress induction. (3) Results: We found that L. crispatus-derived EVs improved Akt phosphorylation and attenuated both cell senescence and death in placental cells caused by oxidative stress induction. In addition, L. crispatus-derived EVs enhanced the resistance to H2O2 induction mediated by increasing mitochondrial fusion. (4) Conclusion: This is the first study to demonstrate that L. crispatus in the vagina can not only regulate the physiological functions of placental cells through the delivery of L. crispatus-EVs but also reduce cell senescence. As cell senescence is related to the occurrence of sPTB, these results indicate that maintaining the population of L. crispatus in the vaginal environment should be an adjuvant treatment strategy to avoid sPTB. [ABSTRACT FROM AUTHOR]

Aim: Evidence has provided an explanation of the correlation between the nervous system and the tumor microenvironment. Neurotransmitters may be involved in different aspects of cancer progression. The glycoalkaloid solanine has been reported to suppress neural signaling pathways and exists in numerous plants, including Solanum nigrum, which have been demonstrated to inhibit cancer cell proliferation. Methods: We evaluated the potentials of solanine on inhibiting acetylcholine-induced cell proliferation and migration in hepatocellular carcinoma cells. Results: The results indicated that solanine markedly attenuated cell proliferation and migration via inhibiting epithelial-mesenchymal transition and matrix metalloproteinases in acetylcholine-treated Hep G2 cells. In addition, exosomes derived from acetylcholine-treated Hep G2 cells were isolated, and solanine showed inhibiting effects of extrahepatic metastasis on blocking cell proliferation in exosome-treated A549 lung carcinoma cells through regulating microRNA-21 expression. Conclusion: Solanine has strong potential for application in integrative cancer therapy. [ABSTRACT FROM AUTHOR]

Objective. Leukemia is a cancer of the blood cells. Leukemic THP-1 and U937 cells were used in this study as monocytic effectors cells for proliferation responses and macrophage-like cells induction in leukemia. Pardaxin is an antimicrobial peptide isolated from the marine fish species. Methods. After treatment for 5 days, pardaxin significantly suppressed cell viability and arrested cell cycle at G0/G1 phase in leukemic cells which were evaluated. Results. Pardaxin also induced cell differentiation and maturation of THP-1 and U937 cells into macrophage-like cells with phagocytotic ability. Moreover, pardaxin elevated the expression of MyD88 but not toll-like receptor (TLR)-2 in both leukemic cells. TLR-2 blocking peptide was used to confirm that pardaxin attenuated phagocytotic ability and superoxide anion production in leukemic cells via activating MyD88 protein. Conclusions. These findings suggested that pardaxin has a therapeutic potential for leukemia. [ABSTRACT FROM AUTHOR]

This study aimed to examine the association of social support, social factors, and maternal complications with caesarean deliveries in native and immigrant women, and to explore the association between acculturation and caesarean deliveries in immigrant women in Taiwan. This prospective panel study was conducted from August 2012 through April 2014 and included 222 native and 147 immigrant pregnant women in Taiwan. Caesarean rates did not differ significantly between native and immigrant women, including the overall caesarean rate (28.8%, 32.0%), medically indicated caesarean (22.5%, 24.5%), and caesarean without medical indications (6.3%, 7.5%). Results of multiple logistic regression models revealed that maternal complications and household activity support were positively associated with caesarean deliveries. Both native and immigrant women with high levels of informational support were less likely to receive caesareans. Immigrant women who were older than 35 years, had a middle level socioeconomic status, and perceived a high level of acceptance of caesarean in Taiwan were more likely to have caesarean deliveries. Informational support was a protective factor for caesarean delivery, whereas household activity support offered by the family was positively associated with caesarean delivery. Perceived acceptance level in mainstream society could affect immigrant women’s use of caesarean delivery. [ABSTRACT FROM PUBLISHER]

Afatinib (Gilotrif™) is widely used to treat patients with mutant activating epidermal growth factor receptor- (EGFR-) dependent lung adenocarcinoma; however, it has various adverse side effects. Here, we report a patient with afatinib-induced paronychia. After Chinese medicine treatment with the well-known anticancer Chinese herbs, Jen-Ren-Hwo-Minq-Saan, and decoction of Ban-Zhi-Lian (Scutellaria barbata) with Bai-Hua-She-She-Cao (Hedyotis diffusa Willd), patient’s condition was significantly improved. This shows that these Chinese medicines can not only be used in cancer treatment but also be used in the afatinib-induced paronychia. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains the fourth leading cause of cancer-related death in the USA with a 5-year survival rate of 5 %. The effects of epidermal growth factor receptor and vascular endothelial growth factor A blockade with chemotherapy on pancreatic tumor growth were examined. Mice bearing human PANC-1 cell xenografts were divided into three groups: T-CR (gemcitabine, cisplatin, and 5-fluorouracil), T-TR (cetuximab, bevacizumab, gemcitabine, cisplatin, and 5-fluorouracil), and vehicle control (T). The therapies were administered via intraperitoneal injections every 4 days for seven cycles from 7 weeks after cancer cell implantation. Mice treated with T-TR had significant reductions in tumor weight as compared to the control group ( p < 0.05). Although mice in the T-CR group experienced a significant reduction in body weight gain, serum albumin, and gastrocnemius muscle mass ( p < 0.05), no such reductions were observed in the T-TR group. Mice treated with T-TR had slightly increased CD11c DC and CD49b NK cell levels in the spleen ( p < 0.05) and significantly lower tumor VEGF expression ( p < 0.05). Tumor carcinoembryonic antigen expression was significantly reduced in both treatment groups ( p < 0.05). Thus, addition of bevacizumab and cetuximab to gemcitabine, cisplatin, and fluorouracil may represent an effective treatment option for pancreatic cancer that warrants further study. [ABSTRACT FROM AUTHOR]

Chemotherapy is a major clinical treatment for managing patients with advanced and recurrent ovarian cancer. However, the clinical performance of chemotherapy is limited, and adverse effects have been observed. Integrating chemotherapy with current chemotherapeutic drugs and novel antitumor ingredients might improve the clinical performance of current chemotherapy for ovarian cancer. The aqueous extract of Solanum nigrum leaves (AE-SN), a key ingredient in many traditional Chinese medicine formulae, has exhibited tumor suppression efficacy in numerous human cancer cells but not in ovarian cancer cells. In this study, tumor suppression efficacy was determined using the ES-2, SKOV-3, and OVCAR-3 human ovarian cancer cell lines. The half-maximal inhibitory concentrations of the AE-SN in ES-2 and SKOV-3 cells were 1.052 and 1.779 mg/mL, respectively. AE-SN treatment increased the accumulation of mammalian microtubule-associated protein 1 light chain 3 A/B, an autophagic cell marker, in all the tested cell lines; however, it activated the cleavage of caspase-3, an apoptotic marker, only in SKOV-3 cells. Furthermore, the AE-SN also promoted tumor suppression efficiency of cisplatin, doxorubicin, and docetaxel in the tested ovarian cancer cells. In addition, AE-SN-enhanced cell death was associated with AE-SN-induced caspase-3 cleavage in SKOV-3 cells. In conclusion, the AE-SN exhibited tumor suppression efficacy and improved the tumor suppression efficiency of cisplatin, doxorubicin, and docetaxel in human ovarian cancer cells. Therefore, the AE-SN is a candidate antitumor ingredient that can be used in developing future integrated chemotherapy for managing ovarian cancer. [ABSTRACT FROM AUTHOR]

Bioceramic is a kind of material which emits nonionizing radiation and luminescence, induced by visible light. Bioceramic also facilitates the breakup of large clusters of water molecules by weakening hydrogen bonds. Hydrogen bond weakening, which allows water molecules to act in diverse ways under different conditions, is one of the key mechanisms underlying the effects of Bioceramic on biophysical and physical-chemical processes. Herein, we used sound to amplify the effect of Bioceramic and further developed an experimental device for use in humans. Thirteen patients who suffered from various chronic and acute illnesses that severely affected their sleep patterns and life quality were enrolled in a trial of Bioceramic resonance (i.e., rhythmic 100-dB sound waves with frequency set at 10 Hz) applied to the skin surface of the anterior chest. According to preliminary data, a “Propagated Sensation along Meridians” (PSM) was experienced in all Bioceramic resonance-treated patients but not in any of the nine control patients. The device was believed to enhance microcirculation through a series of biomolecular and physiological processes and to subject the specific meridian channels of Traditional Chinese Medicine (TCM) to coherent vibration. This noninvasive technique may offer an alternative to needle acupuncture and other traditional medical practices with clinical benefits. [ABSTRACT FROM AUTHOR]

Chemotherapy is the main approach for treating advanced and recurrent hepatocellular carcinoma (HCC), but the clinical performance of chemotherapy is limited by a relatively low response rate, drug resistance, and adverse effects that severely affect the quality of life of patients. The aqueous extract of Solanum nigrum (AE-SN) is a crucial ingredient in some traditional Chinese medicine (TCM) formulas for treating cancer patients and exhibits antitumor effects in human HCC cells. Therefore, this study examined the tumor-suppression efficiency of AE-SN integrated with a standard chemotherapeutic drug, namely, cisplatin or doxorubicin, in human HCC cells, namely, Hep3B and HepJ5. The results suggested that the integrated treatment with AE-SN-potentiated cisplatin and doxorubicin induced cytotoxicity through the cleavage of caspase-7 and accumulation of microtubule-associated protein-1 light chain-3 A/1B II (LC-3 A/B II), which were associated with apoptotic and autophagic cell death, respectively, in both the Hep3B and HepJ5 cells. In conclusion, AE-SN can potentially be used in novel integrated chemotherapy with cisplatin or doxorubicin to treat HCC patients. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the effect of conception with infertility treatment on planned cesarean delivery. The participants were from a panel of primiparous pregnant women in northern Taiwan. The data analysis included 771 women with a singleton pregnancy, of whom 160 had a planned cesarean delivery and 611 who had a vaginal delivery. The study women answered structured questionnaires during the second and third trimesters of pregnancy, and at one-month postpartum. Women who conceived with infertility treatment were more likely to have planned cesarean deliveries than women who conceived without it (44.7% versus 18.1%, p < 0.001; crude odds ratio: 3.66, 95% confidence interval [CI]: 2.24-5.98). After adjustment for maternal age over 35 years, whether they were currently unmarried, selection of time for birth in advance, gestational hypertension, and birthweight < 2500 g, women who conceived with infertility treatment were 2.95 times (95% CI: 1.47-5.92) more likely to have planned cesarean deliveries. The increased risk for planned cesarean deliveries among singleton women who conceived with infertility treatment cannot be explained by older maternal age or higher number of morbidities during pregnancy. Counseling for women who conceive with infertility treatments may be needed to decrease unnecessary cesarean deliveries. [ABSTRACT FROM AUTHOR]

Fermented wheat germ extract (FWGE) is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s) to be 643.76 μg/mL and 246.11 μg/mL after 48 h of FWGE treatment. FWGE treatment also induced programmed cell death by activating the caspase-7 cleavage in both SKOV-3 and ES-2 cells, but only caspase-3 and poly(adenosine diphosphate-ribose) polymerase cleavages were activated in SKOV-3 cells. Moreover, FWGE exhibited combination drug effects with cisplatin and docetaxel in SKOV-3 and ES-2 cells by enhancing the cytotoxicity of both drugs. In conclusion, we found that FWGE not only suppressed cell growth but also induced caspase-3-related and caspase-7-related cell death in human ovarian carcinoma cells. FWGE treatment further enhanced the cytotoxicity of cisplatin and docetaxel, suggesting that FWGE is a potential ingredient in the development of adjuvant chemotherapy with cisplatin or docetaxel for treating ovarian cancer patients. [ABSTRACT FROM AUTHOR]

(1) Background: The microbial phase in the vaginal environment has been found to regulate the physiological activity of host cells. Studies have demonstrated that abnormal microbial growth in the vagina and a significant reduction in the proportion of lactic acid bacteria promote the occurrence of spontaneous preterm birth (sPTB). However, the contributing mechanism remains unknown. (2) Methods: This study uses extracellular vesicles (EVs) secreted by the probiotic Lactobacillus crispatus, commonly found in the vagina, to explore their potential to attenuate placental cells caused by oxidative stress induction. (3) Results: We found that L. crispatus-derived EVs improved Akt phosphorylation and attenuated both cell senescence and death in placental cells caused by oxidative stress induction. In addition, L. crispatus-derived EVs enhanced the resistance to H2O2 induction mediated by increasing mitochondrial fusion. (4) Conclusion: This is the first study to demonstrate that L. crispatus in the vagina can not only regulate the physiological functions of placental cells through the delivery of L. crispatus-EVs but also reduce cell senescence. As cell senescence is related to the occurrence of sPTB, these results indicate that maintaining the population of L. crispatus in the vaginal environment should be an adjuvant treatment strategy to avoid sPTB. [ABSTRACT FROM AUTHOR]

Thrombomodulin (TM) has been shown to regulate many physiological and pathological processes, including inflammation, thrombosis, and tumor progression. TM is also a natural anticoagulant that maintains circulatory homeostasis in endothelial cells. However, little is known regarding the role of TM in the progression and metastasis of cervical cancer. TM-specific RNA interference and a cDNA expression vector were used to manipulate TM expression in cervical cancer cells. Cell growth and cell migration were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, transwell migration assays, and a biosensor system. TM silencing did not affect the growth rate of the cells. However, cell migration was dramatically enhanced after silencing of TM in HeLa cells. The overexpression of TM in cervical cancer cells only slightly influenced their proliferative capacity. After overexpression of TM in HeLa cells, their migratory capability was suppressed. Furthermore, we found that the decreased expression of E-cadherin and increase of zeb-1 and snail expression in TM-silenced cells which may be correlated with the results of knocking-down TM increases the migratory ability in this study. Our results demonstrate that TM may slightly regulate the growth but played the important role in the migratory ability of cervical cancer cells, suggesting that TM could potentially serve as a novel prognostic and therapeutic target in cervical cancer. [ABSTRACT FROM AUTHOR]

Cervical cancer is an important health issue for women worldwide, and the endoplasmic reticulum stress pathway is important for determining the chemotherapeutic response to cancer. However, the role of glucose-regulated protein 94 (GRP94) in taxane therapy for cervical cancer remains unclear. In this study, we generated GRP94 knockdown (GRP94-KD) Hela cells using short hairpin RNAs and found that GRP94-KD cells were resistant to taxane treatment in an MTT assay. Scrambled control cells demonstrated higher levels of apoptosis when treated with taxanes in comparison to GRP94-KD cells, as determined by cell cycle profiling, 4′,6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Caspase 3 and caspase 7 activity was also higher in scrambled control cells treated with taxane in comparison to GRP94-KD cells. Moreover, we found that depletion of GRP94 altered the levels of the apoptosis-related proteins Bcl2 and Bad, leading to sensitivity to taxane. Exposure to taxane also induced the expression of Bad in scrambled cells but not in GRP94-KD cells. In addition, the expression of Bcl2 was increased dramatically in GRP94-KD cells, whereas only a small increase was observed in scrambled cells. Therefore, we conclude that silencing GRP94 may increase resistance to taxane treatment in cervical cancer cells by altering the activation of the apoptosis pathway. In addition, GRP94 may represent a key biomarker for determining the therapeutic efficacy of taxane treatment in cervical cancer patients. [ABSTRACT FROM AUTHOR]

Thrombomodulin (TM), a natural anticoagulation factor, maintains circulation homeostasis in endothelial cells. TM has additional roles in modulating inflammation, thrombosis, and carcinogenesis. However, there is little information on the role of TM in the progression and metastasis of ovarian cancer. RNA silencing and cDNA expression vectors were used to manipulate target gene expression in ovarian cancer cells. Cell growth and migration were evaluated by an MTT assay, a wound-healing migration assay, a transwell migration assay, and a biosensor system. In this study, we found that TM silencing may enhance the growth rate of cells. The migratory ability of ovarian cancer cells was enhanced dramatically after TM silencing. TM overexpression in ovarian cells suppressed the proliferation and migration capability. Furthermore, we found that skov-3 cells treated with TM shRNA expressed high levels of fibronectin and vimentin and that the expression of these markers correlated positively with their migratory ability. Our results demonstrate that TM expression may regulate cell growth and migration in ovarian cancer cells. This finding suggests that TM may be a novel prognostic and therapeutic target for ovarian cancer. [ABSTRACT FROM AUTHOR]

A significant proportion of cesarean deliveries in Taiwan were without medical indications and/or on maternal request. The purpose of this study was to understand the decision-making process of choosing an elective cesarean delivery (ELCD) among primiparas in Taiwan. This qualitative exploratory study was guided by grounded theory. Data were collected through in-depth interviews with 20 primiparous women, 15 of whom chose ELCD. Verbatim transcriptions were analyzed using constant comparative analysis and methods of open, axial, and selective coding. The core category that describes the process of ELCD decision making among primiparas is 'controlling risks of childbirth and ensuring well-being.' The decision process can be divided into three phases: (1) Pre-decision: risk perception, including two subcategories, negative pre-existing ideas about normal spontaneous delivery (NSD) caused worry, and desire for ELCD as the solution; (2) In-decision: risk assessment. Women proactively collected information about NSD and cesarean delivery, and then weighed the personal risk between NSD and ELCD. Risk assessment focused on seven dimensions including safety, health, comfort, efficiency, feminine charms, time and economy; (3) Post-decision: marching onward fearlessly, including two subcategories, belief in ELCD and stress relief, and persuading stakeholders to agree and gaining the required resources for ELCD. At different phases of decision-making, women revealed different concerns, though the sequence of phases was not necessarily unidirectional. Health care providers should be aware of the decision phase and intervene at appropriate times. It is difficult to change a women's decision to have ELCD in the post-decision phase. [ABSTRACT FROM AUTHOR]

Purpose. Although Shi Quan Da Bu Tang (SQDBT) has been used to treat cancer patients clinically, very few studies evaluating the effectiveness of SQDBT using objective indicators have been published. The study objectives were to examine the effectiveness of SQDBT for alleviating hematotoxicity, as indicated by white blood cell (WBC) counts and hemoglobin (Hb) levels, among patients with breast carcinoma receiving chemotherapy. Methods. The authors identified patients with breast carcinoma who received chemotherapy in a teaching hospital in Taipei in 2008 through a chart review process. Only patients with initial WBC counts of <4000/µL were included. The case group was composed of 47 chemotherapy courses treated with SQDBT, whereas the comparison group included 257 courses without SQDBT. The complete blood count test was done before start of a chemotherapy course and 1 week after chemotherapeutic drugs were given. Results. Age, cancer stage, cancer status, use of granulocyte colony-stimulating factor, and chemotherapy drugs were controlled in the model. Patients who took SQDBT had significantly increased WBC counts, especially neutrophils, and Hb after chemotherapy (adjusted β = 1202.51, 95% confidence interval [CI] 440.45-1964.57 for WBC; β = 834.83, 95% CI = 197.35-1472.31 for neutrophils; β = 0.34, 95% CI = 0.05-0.63 for Hb). There were no significant differences in tumor markers CEA and CA153 between patients given SQDBT or not after chemotherapy. Conclusion. SQDBT is effective in alleviating hematotoxicity among patients with breast carcinoma receiving chemotherapy, without affecting the presentation of tumor markers in the short term. More study is needed to determine long-term outcomes such as recurrence and survival. [ABSTRACT FROM PUBLISHER]

This cohort study assessed the structural relationships among social support, acculturation, and postpartum depressive symptoms experienced by marriage-based immigrant mothers in Taiwan. Data were collected at 1 and 6 months postpartum from 203 immigrant mothers married to Taiwanese men in Taipei, Taiwan. The structural equation modeling results showed that social support and postpartum depression were directly and negatively related. Higher social support and lower depression at 1 month postpartum were related to a positive social attitude (i.e., accepting attitude toward mainstream society). Social attitude was a moderator of the relationship between depression at 1 month and social support at 6 months postpartum, where a positive social attitude decreased the negative effect of depression at 1 month on social support at 6 months. Social support in the early postpartum period not only directly decreased postpartum depression, but also indirectly decreased postpartum depression through improving social attitude. [ABSTRACT FROM AUTHOR]

The objectives of researchers in this study were to examine acceptance and adherence to mainstream Taiwanese postpartum cultural practices and their association with postpartum depressive symptoms among Chinese and Vietnamese immigrant mothers married to Taiwanese men. While the postpartum cultural practices in China are similar to mainstream Taiwanese practices, those of Vietnam differ from Taiwanese practices. This cross-sectional survey was conducted in Taiwan from October 2007 through March 2008, and included190 immigrant mothers from China and Vietnam who had delivered a child within the past year. Immigrant mothers from China had higher levels of acceptance and adherence to mainstream Taiwanese postpartum cultural practices and a lower rate of postpartum depressive symptoms than immigrant mothers from Vietnam, but the association between adherence to “doing-the-month” practices and postpartum depressive symptoms did not vary significantly between Chinese and Vietnamese mothers. Adherence to these practices was negatively associated with postpartum depressive symptoms among immigrant mothers (OR = 0.93, 95% CI: 0.90–0.96) after adjustment for social support, duration between moving to Taiwan and delivery, and country of origin. Adherence to mainstream postpartum cultural practices was negatively associated with postpartum depressive symptoms for both Chinese and Vietnamese immigrant women married to Taiwanese men. [ABSTRACT FROM AUTHOR]

Background: Glucose-regulated protein 78 (GRP78) plays an important role in the therapeutic treatment and progression of cancer. However, little is known about the effect of GRP78 expression to curcumin in hepatocellular carcinoma (HCC). Materials and Methods: In this study, we generated GRP78 knockdown cells (GRP78KD) by a short interfering RNA (siRNA) technique. The antiproliferation effects of curcumin were determined by MTT assay, TUNEL assay, and cell cycle determination. Results: We found that GRP78KD cells were more resistant to curcumin treatment compared with the parental cells in MTT assay. The apoptosis cell population was increased in scrambled-siRNA cells treated with curcumin compared with GRP78KD cells in cell cycle distribution and TUNEL assays. Finally, we found that knocking down GRP78 causes resistance to curcumin treatment through the suppression of caspase-3 and caspase-8 expression levels. Conclusions: We conclude that the expression level of GRP78 may contribute to the therapeutic effect of curcumin on HCC cells. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common cancers worldwide. Gut microbiota are highly associated with CRC, and Fusobacterium nucleatum was found to be enriched in CRC lesions and correlated with CRC carcinogenesis and metastases. Paris polyphylla is a well-known herbal medicine that showed anticancer activity. The present study demonstrates that P. polyphylla inhibited the growth of CRC cells. In addition, treating with active compounds pennogenin 3-O-beta-chacotrioside and polyphyllin VI isolated from P. polyphylla inhibited the growth of F. nucleatum. We also found that extracellular vesicles (EVs) released from F. nucleatum could promote mitochondrial fusion and cell invasion in CRC cells, whereas active components from P. polyphylla could dampen such an impact. The data suggest that P. polyphylla and its active ingredients could be further explored as potential candidates for developing complementary chemotherapy for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the advancing treatments, female breast cancer is one of the most common cancers and a leading cause of cancer deaths in women. To help broaden the therapeutic spectrum of breast cancer, we identified the natural compound ursolic acid (UA) as a potentiator that enhances the oncolytic activity of measles virus (MV) against breast cancer cells through the induction of apoptosis. In addition, to increase clinical applicability, we further generated UA nanoparticles that achieved improved solubility. UA nanoparticles similarly synergized with MV in killing breast cancer cells by triggering apoptosis, and this synergistic anticancer effect was also observed in various breast cancer cell types. This study demonstrates for the first time that UA and its nanoparticles enhance MV's oncolytic activity in breast cancer cells, suggesting that such combinations may be worth further exploring as an anticancer strategy against breast cancer. Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women's cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA's potentiation of apoptotic killing by MV. To circumvent UA's poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA's applicability. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), including hepatitis C virus (HCV)-induced HCC, is a deadly disease highly refractory to chemotherapy, thus requiring the continuous identification of novel treatment strategies. Berberine (BBR) has been previously reported to inhibit hepatoma cell growth, but the main type of cell death elicited by BBR, and whether the alkaloid can inhibit hepatoma cells carrying HCV genomes, is unclear. Herein, we show that BBR treatment induced a biphasic cell death irrespective of the presence of HCV subgenomic replicon RNA, first triggering apoptosis that then progressed to necrosis between 24 and 48 h post-treatment. Furthermore, BBR treatment potentiated the HCV replicon-induced reactive oxygen species (ROS) production, inhibition of which with an antioxidant attenuated the cell death that was elicited by BBR in these cells. Moreover, BBR dampened the autophagic response in HCV RNA-positive or negative hepatoma cells, and pharmacological inhibition of autophagy conversely augmented the BBR-induced cell death. Finally, BBR inhibited the growth of Huh-7 cells that were persistently infected with the full-length genome HCV particles, and concomitant pharmacological inhibition of autophagy potentiated the killing of these cells by BBR. Our findings suggest that combining BBR with the inhibition of autophagy could be an attractive treatment strategy against HCC, irrespective of the presence of the HCV genome. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer. [ABSTRACT FROM AUTHOR]

Oncolytic virotherapy represents an emerging development in anticancer therapy. Although it has been tested against a variety of cancers, including breast cancer, the efficacy of oncolytic viral vectors delivered as a monotherapy is limited. Enhancing viral oncolytic therapies through combination treatment with anticancer agents is a feasible strategy. In this study, we considered a chemovirotherapeutic approach for treating breast adenocarcinoma using oncolytic measles virus (MV) and the chemotherapeutic agent camptothecin (CPT). Our results demonstrated that co-treatment of MV with CPT yielded enhanced cytotoxicity against breast cancer cells. Low dosage CPT combined with MV was also found to elicit the same therapeutic effect as high doses of CPT. At the lower dosage used, CPT did not inhibit the early stages of MV entry, nor reduce viral replication. Further studies revealed that co-treatment induced significantly enhanced apoptosis of the breast cancer cells compared to either MV or CPT alone. Overall, our findings demonstrate the potential value of MV plus CPT as a novel chemovirotherapeutic treatment against breast cancer and as a strategy to enhance MV oncolytic activity. [ABSTRACT FROM AUTHOR]

This study compared symptom severity, symptom interference and use of complementary and alternative medicine (CAM) between cancer survivors after curative treatment and individuals who did not have cancer. Factors associated with CAM use among cancer survivors were examined. A cross‐sectional survey was conducted of 146 cancer survivors (77 breast and 69 colorectal cancer survivors who had completed conventional treatment 1–5 years previously and were cancer‐free) from a hospital's cancer registration system (survivor group), and 161 healthy individuals without cancer (comparison group). The two groups were frequency‐matched for sex and age. Findings indicated higher use of CAM in the survivor group (54.1%) than the comparison group (36.6%). There were no significant differences in overall symptom severity and interference between the two groups. Multivariate logistic regression showed that prior use of CAM (OR = 5.14, 95% CI: 2.34–10.69) and higher symptom interference (OR = 1.04, 95% CI: 1.001–1.08) were positively related to CAM use in the survivor group. The survivors did not have higher symptom severity and symptom interference with daily life, but were more likely to use CAM than the comparison group. Medical staff should discuss symptom interference and use of CAM with cancer survivors to guide them in the appropriate use of CAM. [ABSTRACT FROM AUTHOR]