Chrysin-Enhanced Cytotoxicity of 5-Fluorouracil-Based Chemotherapy for Colorectal Cancer in Mice: Investigating its Effects on Cyclooxygenase-2 Expression

Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

Neoadjuvant immunotherapy in microsatellite stability or mismatch repair proficient colorectal cancer / 中华胃肠外科杂志

Immunotherapy has become an important treatment option for microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) colorectal cancer. From late-line to first-line treatment, and even in neoadjuvant setting for early stage colorectal cancer, promising efficacy was observed with immunotherapy. In microsatellite stability (MSS) or mismatch repair proficient (pMMR) colorectal cancer, the researches of neoadjuvant immunotherapy have been conducted constantly. This paper focuses on the recent researches and progress of neoadjuvant immunotherapy for MSS or pMMR colorectal cancer. Neoadjuvant immunotherapy alone led to a good pathological response in a subset of patients. Studies of induction or consolidation immunotherapy before or after neoadjuvant chemoradiotherapy or concurrent immunotherapy during radiotherapy showed higher pathological complete remission (pCR) rates as compared to standard chemoradiotherapy. Studies on sequential dual immunotherapy after radiochemotherapy and targeted therapy combined with neoadjuvant immunotherapy are ongoing. At present, most of these are pilot studies with small sample size. More researches and long-term follow-up are needed to prove the efficacy of neoadjuvant immunotherapy in MSS or pMMR colorectal cancer.

Combination Effect of Tamoxifen and Ascorbic Acid Treatment on Breast Cancer Cells (MCF-7) and Cervical Cancer Cells (HeLa) Kesan Rawatan Kombinasi Tamoksifen dan Asid Askorbik ke atas Sel Kanser Payudara (MCF-7) dan Sel Kanser Serviks / Jurnal Sains Kesihatan Malaysia

@#Breast cancer and cervical cancer are among the leading causes of death among women in the world. Even though chemotherapy is available as cancer treatment, the development of drug resistance in both cancer cells has reduced the efficacy of chemotherapeutic drugs in such treatment. The current study was aimed to evaluate the cell viability of human breast cancer cells, MCF-7, and cervical cancer cells, HeLa upon the combination treatment of ascorbic acid and tamoxifen. The cell viability was measured using the MTT assay, with an incubation period of 72 hours in a humidified CO2 incubator. The concentrations of tamoxifen and ascorbic acid that reduced 50% of the cell population (IC50) were determined from the dose-response curve. The IC50 concentration was used to determine the cell viability in the treated cells. CompuSyn software was used to evaluate the combined effects towards both cells upon treatment and the results were calculated as combination index (CI). The data were analyzed using GraphPad Prism (version 7). Statistical analysis was performed using an independent t-test. The IC50 values of tamoxifen and ascorbic acid on MCF-7 cells were 14.53 µg/ml and 15.8 µg/ml respectively, while the IC50 values of tamoxifen and ascorbic acid on HeLa cells were 11.09 µg/ml and 202.3 µg/ml respectively. The combination of tamoxifen and ascorbic acid exerted a greater growth reduction percentage in both cells compared to tamoxifen alone. The results indicated that ascorbic acid synergizes the cytotoxic effect of tamoxifen at lower concentrations towards MCF-7 cells with a CI less than 1. However, the combination of tamoxifen and ascorbic acid exerted an antagonistic effect in HeLa cells, with a CI more than 1.

Pulsed electromagnetic fields stimulation combined with sclerostin antibody improves bone metabolism and bone microstructure in postmenopausal osteoporosis rabbits / 中国组织工程研究

BACKGROUND: Both pulsed electromagnetic fields (PEMF) stimulation and sclerostin antibody (Scl-Ab) have good effects on the bone metabolism of ovariectomized (OVX) New Zealand rabbits, but research on the combined intervention of PEMF and Scl-Ab in the OVX rabbits is rarely reported. OBJECTIVE: To explore the effect of PEMF combined with Scl-Ab on postmenopausal osteoporosis and to explore the therapeutic value for osteoporosis. METHODS: An animal model of postmenopausal osteoporosis was made in New Zealand white rabbits after ovariectomy. The experimental animals were randomly divided into OVX control group, PEMF group, Scl-Ab group and PEMF+Scl-Ab group, with 10 rats in each group. On the 1st day after surgery, the PEMF group was given PEMF magnetic therapy once a day; the Scl-Ab group was given subcutaneous injection of Scl-Ab twice a week; the PEMF+Scl-Ab group received PEMF magnetic therapy once a day, five times a week, and Scl-Ab subcutaneous injections twice a week; the OVX group was injected subcutaneously with the same dose of normal saline twice a week for 8 weeks. After 8 weeks of treatment, bone metabolism index, bone mineral density, and MicroCT bone microstructure parameters were detected. All animal procedures were approved by the Department of Experimental Animal Science, Fudan University (approval No. 20171263A193). RESULTS AND CONCLUSION: Bone mineral density was significantly decreased in the New Zealand white rabbits after 6 months of OVX, suggesting that the osteoporosis model was successfully established. Compared with the OVX group, the bone mineral density of the L3 vertebral body in the PEMF group, the Scl-Ab group and the PEMF+Scl-Ab group increased significantly (P < 0.05). Compared with the OVX group, serum bone-specific alkaline phosphatase levels were significantly higher, and serum tartrate-resistant acid phosphatase 5b levels were significantly lower in the PEMF group, the Scl-Ab group and the PEMF+Scl-Ab group. The serum tartrate-resistant acid phosphatase 5b level in the PEMF+Scl-Ab group was significantly lower than that in the PEMF group and the Scl-Ab group. The bone metabolism index and bone microstructural parameters (bone volume fraction, trabecular thickness, trabecular number, and trabecular separation) of the PEMF+Scl-Ab group were significantly better than those of the PEMF group and the Scl-Ab group (all P < 0.05). These findings indicate that the combination of Scl-Ab and PEMF can enhance bone mineral density and improve bone metabolism and bone microstructure in postmenopausal osteoporosis New Zealand white rabbits.

Patients experiences on the use of dihydroartemisinin piperaquine as an alternative first line artemisinin-based combination treatment for uncomplicated malaria in Northern Ghana

Background:Three different artemisinin-based combination therapies (ACTs) namely; artesunate-amodiaquine, artemether-lumefantrine and dihydroartemisinin-piperaquine (being the latest to be introduced) are concurrently being used forthe treatment of falciparummalaria in Ghana. This study assessed patients’ experience, perceptions and willingness to use dihydroartemisinin-piperaquine, brand name duo-cotecxin as an alternative first line ACT for the treatment of falciparummalaria in Northern Ghana.Methods:This was a qualitative study using phenomenology approach where sixty in-depth interviews were conducted with two groups; thirty patients who were given duo-cotecxin, one group and thirty interviews with patients who were given other ACTs (artesunate-amodiaquine, artemether-lumefantrine) as another group. The interviews were conducted between August and November, 2015 Purposive sampling technique was used to select study participants. The interviews were transcribed andcoded into themes using QSR NVivo 11 software for thematic content analysis.Results:All patients who used duo-cotecxin reported that the drug was very good in treating uncomplicated malaria compared to other ACTs they had used in the past. Some of the patients who used other ACTs could not complete their doses because of the side effects. However, none of the patients who used duo-cotecxin reported side effects. The findings revealed high acceptance and preference to use duo-cotecxin to treat uncomplicated malaria compared with other ACTs. All the participants were also willing to recommend duo-cotexcin to their relatives and friends to use. Conclusions: Duo-cotecxin as an alternative first line ACT for treatment of uncomplicated malaria is highly accepted, preferred and there was willingness to use it compared with other first line recommended ACTs.

Essential Role of Chinese Medicines in Mesenchymal Stem Cells Transplantation for Treatment of Ischemic Stroke / 中国结合医学杂志

Ischemic stroke accounts for the majority of all strokes and has been primary causes of long-term disability and mortality in worldwide. Mesenchymal stem cell (MSC) therapy suggests significantly improved effects on neurological functional outcome, neurogenesis, angiogenesis, blood-brain barrier permeability, inflammatory injury, neuroprotection and so on, following stroke. However, the occurrence of adverse effects results in restriction of the therapy. Chinese medicine accumulates abundant clinical experiences on stroke for over two thousand years, and some formulae and active ingredients of Chinese medicines have presented obvious efficacies in clinical treatment. Therefore, based on Chinese medicine theory, we provide some ideas of screening agents for combination treatment of Chinese medicines and MSC for ischemic stroke, and summarize the potentials of Chinese medicines in MSC treatment and analyze the feasibilities of Chinese medicines against side effects of MSC therapy. Consequently, we propose Chinese medicines combing with MSC should be a promising approach to clinical stroke treatment in future.

Preparation of multifunctional nanoscaled red blood cells drug delivery system and its photothermal and photodynamic effects / 国际生物医学工程杂志

Objective To prepare a red blood cells based multifunctional nanoscaled drug delivery system,and to study its in vitro photothermal and photodynamic effects.Methods The indocyanine green (ICG)/doxorubicin (DOX) co-loaded nanoscaled red blood cells (DIRAs) were prepared using an extrusion method.The morphology,particle size,encapsulation efficiency,and stability were determined.The heating related change of particle size was studied using a size and potential tester.The in vitro photothermal effect was studied using an infrared imaging device.The uptake of DIRAs to 4T1 cells was studied using a CLSM examination.The in vitro photodynamic effect was studied using a fluorescence probe and CLSM examination.Results DIRAs were successfully prepared with a uniform and homogeneous size which was about (97.0±20.1) nm.The Zeta potential was about-21.6 mV and the encapsulation efficiency of ICG and DOX were 93.5％ and 95.2％,respectively.The DIRAs had excellent stability within 28 days.This nanoscaled drug delivery system had identical photothermal effect compared to free ICG.The cellular uptake of DOX was significantly improved after the laser irradiation and the photodynamic effect was enhanced.Conclusions The prepared DIRAs have regular shape,suitable particle size,high encapsulation efficiency and high photothermal conversion efficiency.DIRAs can improve the cellular uptake of DOX and enhance the photodynamic efficiency.This biomimetic muhifunctional nano-system could facilitate breast cancer treatment by combining PTT7PDT and chemotherapy.

Clinical study of combination treatment with Clofazimine and others for patients with multidrug-resistant tuberculosis / 中国生化药物杂志

Objective To evaluate the clinical efficacy and safety of combination treatment with clofazimine ( Cfz ) and other antituberculosis drugs for patients with multidrug-resistant tuberculosis(MDR-TB).Methods 32 cases of MDR-TB patients were treated with combination regimens that included clofaziminefrom October 2011 to September 2016 in our hospitol,according to the history of drug use and drug susceptibility test results using individualized chemotherapy,the starting dose of clofazimine was 0.1 g/day,oral,some patients with adverse reactions and tolerance adjusted to 0.05 g/day,treatment for the last 12 months for three consecutive sputum mycobacterium tuberculosis culture and sputum smear acid-fast bacilli were cured,observe the clinical efficacy and safety.Results After treatment with the combined regimen,56.2%(18/32) of patients were cured,43.8%(14/32) of patients failed treatment, there was no statistically significant difference in the number of drug-resistant patients before and after CFZ treatment,there was no statistically significant difference between the time of failure and the time of CFZ treatment,after taking CFZ combined with anti-tuberculosis program,the number of drug users was statistically significant of patients cured and failed (P<0.05).The average time of sputum culture inversion was 16w.90.6% (29/32) of patients with adverse reactions,mainly including skin color change,ichthyosis and gastrointestinal tract and other adverse reactions, through dose adjustment and symptomatic treatment to continue treatment.The average duration of treatment with clofazimine was about 13 months.ConclusionClofazimine was welltolerated,combination treatment with Clofazimine and others for patients with MDR-TBhave better efficacy .

Effects of combination treatment with L-carnitine and 5-fluorouracil on proliferation and apoptosis in MGC803 cells / 中国药学杂志

OBJECTIVE: To investigate the effects of combination treatment with L-carnitine and 5-fluorouracil on the proliferation and cell apoptosis of gastric cancer MGC803 cells. METHODS: MGC803 cells were divided into control group, 5-fluorouracil group and the combination of L-carnitine and 5-fluorouracil group (L-carnitine +/→5-fluorouracil group) in vitro. The inhibitory rate of cells was measured by MTT assay. The apoptosis rate and cell cycle of cells were detected by FLOW. Western blot was used to analyzed the expression of Bcl-2, Bax, adenine nucleotide translocator1 (ANT1) and cleaved-PARP. RESULTS: Compared with 5-fluorouracil group, the inhibition rate of MGC803 cells was increased when cells were treated with the combination of L-carnitine and 5-fluorouracil. The apoptosis rate of cells was raised and the cells were blocked at S phase. In addition, the combination group can decrease the expression of Bcl-2 and increase the expression of Bax, ANT1 and cleaved-PARP. At the same time, the apoptosis rate of cells and the cell cycle were different with the different dosage regimen when treated with the combination. Compared with the L-carnitine + 5-fluorouracil group, the apoptosis rate of cells was increased to (24.17 ± 3.12)% from (19.60 ± 1.06)% (P < 0.05). The G0/G1 phase proportion of cells was decreased to (62.62 ± 1.04)% from (72.95 ± 0.91)%, and the S phase proportion of cells was increased to (37.35 ± 1.03)% from (27.05 ± 0.91)% (P < 0.001). CONCLUSION: Treatment with L-carnitine and 5-fluorouracil could enhance the inhibitory effect of 5-fluorouracil on MGC803 cells. The possible mechanism of action is achieved by regulating the expression of Bcl-2 protein family and influencing the cell cycle.

<b>Efficacy of a Combination Treatment for Glossalgia with three Kampo Medicines : Orengedokuto, Bukuryoin, and Kososan Extracts</b> / 日本東洋医学雑誌

A patient with intractable glossalgia was successfully treated with a combination of three Kampo medicines : orengedokuto, bukuryoin, and kososan extracts. Then, 3 more patients with glossalgia were administered similar treatment based on the experience of the first case. The clinical features of these four patients and the efficacy of the combination Kampo treatment are reported herein. <br>A 61-year-old man with a 3-year history of glossalgia had been treated with psychopharmaceuticals for 4 months at another hospital, without any relief from symptoms. Upon referral to this Kampo clinic, the patient was treated with goreisan extract, daisaikoto extract, or other Kampo medicines, but these medicines were not effective. The prescription was then changed to a combination of orengedokuto, nichinto, and kososan extracts, which ameliorated the glossalgia symptoms almost by half. Furthermore, the glossalgia improved completely after the nichinto extract in the Kampo combination was replaced with bukuryoin extract. <br>After successful treatment of the first patient, three other patients were treated with the same Kampo combination. Two patients showed improvement within 2 weeks, but the combination treatment was ineffective in the other patient, whose symptoms finally improved with a zinc supplementation from Polaprezinc. The clinical features of the patients with good outcome were generally characterized by a combination of symptoms such as glossalgia, tendency toward depression, and digestive symptoms. <br>The combination treatment was prescribed as a substitute for seinetsugeutsuto decoction, and it was effective in three of the four patients with glossalgia. These results indicate that the combination treatment could be a candidate medicine to treat glossalgia.

Combination treatment with herbal medicines and Western medicines in atopic dermatitis: Benefits and considerations / 中国结合医学杂志

Herbal medicines (HMs) are often used in combination with Western medicines (WMs) to improve therapeutic efficacies of orthodox medicines. This review discussed the current status of combination treatment with HMs and WMs in clinical practices. The influence of HMs on bioavailability of WMs was also discussed from the pharmacokinetic point of view. In addition, benefits and considerations of combination treatment were discussed using data obtained from clinical trials and randomized controlled trials of HMs treatment in skin diseases.

Trends of Antipsychotic Drugs Use in Schizophrenia Patients from Hebei Province / 中国药房

OBJECTIVE:To provide reference for rational use of antipsychotic drugs in schizophrenia patients. METHODS:The general information and antipsychotic treatment information,which were extracted from the database of prior drug investigation in Mental Health Center of Hebei Province in 2002,2006 and investigation data in 2012 of 5014 schizophrenia patients,were ana-lyzed. RESULTS:Over time,the frequency of the first generation antipsychotic drugs decreased(P0.05). Over time,the proportion of inpatients receiving monotherapy decreased,while that of inpatients receiving combination treatment increased (χ2=18.682,P<0.01). CONCLUSIONS:The second generation antipsychotic drugs have gradually replaced the first generation antipsy-chotic drugs,and have became the leading drugs in the treatment of schizophrenia in Hebei province. The proportion of inpatients receiving combination treatment has increased,which is different from the domestic and foreign prevention and treatment guide-lines.

Clinical efficacy evaluation of mifepristone alone and combined with Gongliuxiao capsule in the treatment of uterine fibroids / 中国生化药物杂志

Objective To investigate and compare the clinical efficacy of mifepristone alone and combined with Gongliuxiao capsule in the treatment of uterine fibroids.Methods 106 patients with uterine fibroids in Harrison International Peace Hospital from December 2012 to December 2013 were selected.The patients were randomly divided into control group and experimental group(n=53).The former were treated with mifepristone alone while the later were treated with the combination of mifepristone and Gongliuxiao capsule.All the patients were given 2 courses of treatment with 12 weeks for a course.The menstrual phase,volume of menstruation,uterus and the volorne of uterine fibroids before and after the treatment,and the clinical efficacy of both groups were evaluated.All the results were recorded and compared. Results The menstrual phase,volume of menstruation,uterus and uterine fibroids of both groups after the treatment were significantly less than those before treatment (P <0.05 ).And the total effective rate of experimental group was 92.45%,which was significantly higher than 73.58% of control group.Both groups had some mild adverse reactions,which didn’t affect the treatment.Conclusion The combination of mifepristone and Gongliuxiao capsule has a great efficacy in the treatment of uterine fibroids.Compared with the use of mifepristone alone,the combination treatment is much more effective.

Comparison of the efficacy of lamivudine combined adefovir dipivoxil and entecavir monotherapy in the treatment of naive patients with chronic hepatitis B：a Meta analysis / 重庆医学

Objective To analyse the efficacy of lamivudine(LAM) combined adefovir dipivoxil(ADV) and entecavir(ETV) in the treatment of naive patients with chronic hepatitis B (CHB) .Methods Cochrane Library ,MEDLINE ,Web of Science ,CNKI (China National Knowledge Infrastructure ) ,WANFANG database and VIP database were searched and the references of eligible studies were screened .All relevant literatures published before March 6th ,2012 were reviewed .Comparison of the efficacy of lami-vudine combined adefovir dipivoxil and entecavir in the treatment of naive patients with chronic hepatitis B was included and Rev Man 5 .1 software was used for Meta analysis .Results Four eligible studies (587 patients in all) were included for the analysis .In the entecavir monotherapy group ,the serum ALT normalization rate was a little higher at the 12 weeks and 24 weeks of the treat-ment compared to the combination group[OR=0 .52 ,95% CI(0 .28 ,0 .97) ,Z=2 .04 ,P=0 .04] ,[OR=0 .45 ,95% CI(0 .22 ,0 .95) , Z=2 .11 ,P=0 .04] ,respectively .But after 36 weeks there was no significance between the two groups .For HBV DNA undetect-able rate ,there were no significant differences between the two groups at the 12 weeks ,24 weeks ,36 weeks ,48 weeks ,18 months , 24 months and 30 months of the treatment (P=0 .22 ,P=0 .30 ,P=0 .86 ,P=0 .31 ,P=0 .93 ,P=0 .84 and P=0 .83 respectively) . At the 48 weeks ,HBeAg negative rate has no significant difference between the two groups [OR=0 .93 ,95% CI(0 .29 ,2 .95) ,Z=0 .13 ,P=0 .90] .Conclusion Both LAM+ADV combination therapy and ETV monotherapy are effective in the treatment of naive patients with CHB ,but further studies are still needed to obtain long term results and safety by high quality ,large scale randomized controlled trials .

Effects and mechanism of prednisone and TACI-Ig combination on auto-antibody production in MRL/lpr mice / 安徽医科大学学报

Objective To investigate the effects and partial mechanism of prednisone and TACI-Ig combination on MRL/Mpslac-lpr ( MRL/lpr) mice. Methods MRL/lpr mice were randomly divided into 6 groups, which includ-ed model group, prednisone (2. 5, 5. 0 mg/kg) group, TACI-Ig (15. 0 mg/kg) group, prednisone and TACI-Ig combination [(2. 5+7. 5) mg/kg, (2. 5+15. 0) mg/kg] group. BALB/c mice were set as normal group. Pred-nisone was given intragastrically everyday and TACI-Ig was given subcutaneously every two days for 13 weeks. In the meantime, the normal and model group were treated with an equal volume of normal saline. The general sign and proteinuria level were observed in the treatment period. The sections of spleen and kidney tissues for pathologi-cal analysis were stained with HE. Serum levels of auto-antibodies and BAFF were detected by ELISA kit. The per-centage of plasma cells and CD138 expression in the spleen were detected by flow cytometry analysis and immuno-histochemistry, respectively. Results The skin damage and the proteinuria level were improved and decreased by prednisone and TACI-Ig combination treatment. The spleen and kidney pathology were also improved including re-ducing germinal center formation and alleviating the glomerular fibrosis, mesangial cell hyperplasia and inflammato-ry cell infiltration, respectively. What was more, the percentage of splenic plasma cells ( CD19 -CD138 +) was re-duced significantly, which maybe resulted in the decrease in ANA. However the high level of anti-dsDNA antibody was not influenced by the combination treatment. The serum level of BAFF was also reduced by the combination treatment. Conclusion Prednisone and TACI-Ig combination treatment has a beneficial effect on murine SLE, which may be associated with the inhibition of plasma cell differentiation and the secretion of auto-antibody.

Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade

Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.

Ultrathin split-thickness skin grafting followed by narrowband UVB therapy for stable vitiligo: An effective and cosmetically satisfying treatment option.

Background: Different surgical techniques in the form of tissue or cellular grafting procedures are used alone or in combination with narrowband UVB (NBUVB) to treat stable vitiligo resistant to medical treatment. Aim: To evaluate the cosmetic results obtained with ultrathin split-thickness skin grafts followed by NBUVB therapy in resistant, stable vitiligo. Methods: Forty patients of stable vitiligo were treated with ultrathin split-thickness grafting and the patients were then put on NBUVB therapy. The results obtained were analyzed by the extent of repigmentation achieved as well as the final cosmetic outcome at the recipient as well as donor sites. Results: The first evidence of repigmentation was seen in the second week after starting NBUVB. On objective assessment, more than 90% repigmentation was seen in 83% of patients and the overall cosmetic results at the recipient site were graded as good to excellent in 90% patients at the end of NBUVB treatment. Perigraft halo of depigmentation was seen in six patients (15%) on the recipient site. Hypertrophic scarring was observed in two patients at the donor site. Conclusions: Ultrathin split-thickness skin grafting, when combined with NBUVB therapy, leads to better cosmetic outcome with faster onset of repigmentation in resistant stable vitiligo.

Scheduled Interval Trans-Catheter Arterial Chemoembolization Followed by Radiation Therapy in Patients with Unresectable Hepatocellular Carcinoma

Combination treatment of trans-catheter arterial chemoembolization (TACE) and conformal radiation therapy (RT) reported promising results in patients with hepatocellular carcinoma (HCC), but, optimal interval was not determined. We hypothesized that a two-week interval between TACE and RT would be optimal. Therefore, we designed this study to evaluate the safety and efficacy of scheduled interval TACE followed by RT. HCC patients who were not eligible for standard therapies were enrolled for scheduled interval TACE followed by RT (START). Patients received TACE on the first day of treatment, and then RT was delivered after 14 days. The entire course of treatment took between four and five weeks. In 81 patients (96.4%), START was completed in the planned treatment period. RT was delayed in the remaining three patients because of decreased liver function or poor performance status after TACE. Of the 81 patients, objective response was observed in 57 patients (70.4%). One unexpected death occurred after START due to hepatic failure. Other toxicities were manageable. The median survival was 14.7 months. There was a significant difference in overall survival according to the response to START (P < 0.001). In conclusion, START is safe and feasible.

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity.

Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.