Percentage Of Cell Inhibition Research Articles

BIOCOMPATIBLE AND ANTIMICROBIAL CELLULOSE ACETATE NANOFIBER MEMBRANE FROM BANANA (MUSA ACUMINATA X BALBISIANA) PSEUDOSTEM FIBERS FOR WOUND HEALING AND TISSUE ENGINEERING

Electrospun nanofiber membranes play a vital role in the biomedical field, especially for wound healing and tissue engineering applications. This study explored the development of biocompatible and antibacterial cellulose acetate electrospun nanofiber membranes prepared from banana pseudostem fibers. Cellulose rich dissolving pulp from alkali treated banana pseudostem fibers was subjected to esterification reaction to produce cellulose acetate. The synthesized cellulose acetate and chlorhexidine (CHX), an antimicrobial agent, were dissolved in 2:1 acetone:N,N-dimethylacetamide solvent and subsequently electrospun into a nanofiber membrane. FT-IR spectroscopy of the nanofiber confirmed the presence of cellulose acetate and the successful incorporation of CHX into the nanofibers. SEM imaging showed that the fiber diameter of the nanofiber membrane ranged from 200 nm to 300 nm. The MTT cytotoxicity assay and antimicrobial assay of nanofibers revealed that the nanofiber membrane with chlorhexidine concentration of 1.0 w/v was the optimum formulation as it achieved potent antimicrobial activity (zone of inhibition (ZOI): Escherichia coli – 18.38 mm and Staphylococcus aureus – 22.51 mm), while exhibiting low cytotoxicity to human intestinal epithelial cell line, HIEC-6 (percent cell inhibition: 13.07% and IC50: >100 μg/mL). The results indicated successful preparation of biocompatible and antimicrobial nanofiber membranes from banana pseudostem fiber with potential application in wound healing and tissue engineering.

Antiproliferative effect of methanolic extract of Allophylus cobbe in C127I cell lines

Scientific world is in search of newer and effective therapies against cancer and nature form a good source of drugs. The present study was undertaken to assess the antiproliferative potential of methanolic extract of A. cobbe in C127I cell lines. The leaves of A. cobbe were shade dried and was extracted using methanol and qualitative phytochemical analysis was performed. The extract was assessed for its cytotoxicity by MTT dye reduction assay in C127 I cells maintained using DMEM and 10 per cent foetal bovine serum at concentrations of 320, 160, 80, 40, 20, 20 and 5 µg/mL and the percent cell inhibition and IC50 were calculated. Acridine Orange/Ethidium bromide staining was used to detect the possible mechanism of cytotoxicity. From the results of MTT assay, it could be seen that there was a dose dependent inhibition of cell proliferation of C127I which was maximum at a concentration of 320 µg/mL. The IC50 value of the methanolic extracts was found to be 64.63 µg/mL respectively. The effect was comparable to doxorubicin. The extract and positive control treated cells showed orange to red fluorescence when stained with Acrdine Orange/ Ethidium bromide compared to greenish fluorescence in the control cells indicating apoptosis in the treated cells. The study concluded that methanolic extract of A. cobbe induced cytotoxicity by apoptosis of cancer cells.

Apoptosis Event in Hela Cells Treated with Cisplatin, Gallic Acid and Combination of Both

Adverse effect of conventional chemotherapeutic agent using single anticancer drugs had led to application of combination therapy in cancer treatments. Combination of polyphenolic compounds and anticancer agent was studied and shown promising outcomes in vitro. In cancer treatment, mode of cell death through apoptosis is one of the targeted approaches in many preclinical drug development studies and has been identified as a key mechanism of chemotherapy-induced cell death. 
 
 Hence, this study was conducted to evaluate the apoptosis event of HeLa cells treated with gallic acid (GA) combined with cisplatin (CIS). HeLa cells were treated for 24,48 and 72 hours with CIS and GA at IC50 (Table 1) concentrations, and the combination of CIS and GA (CIS– GA) was chosen based on a previous study (66.73 percent cell inhibition [1]. To compare the anticancer effects of cisplatin and gallic acid individually and in-combination on apoptosis in HeLa cells, flow cytometry assay was carried out. 
 According to the findings, during every incubation period, the CIS-GA combination treatment group consistently showed the highest level of antiproliferative activity in HeLa cells, followed by the CIS and GA treatment group. CIS and GA combined treatment response was time-dependent, with an increase in apoptotic cells as incubation time increase (Figure 1). At 72 hours, the combination of CIS and GA treatment showed a significant improvement (74.6%), and improvements were also shown after 24 and 48 hours (56 percent and 60.2 percent).
 Taken together, these findings suggest that combination therapy enhances the cell death magnitude in HeLa cells. Additionally, these findings have positive implications for the use of a combination therapy approach in cancer treatment.

In Vitro Cytotoxicity Test of Red Okra (Abelmoschus esculentus) Fruit Ethanolic Extract on HeLa Cells

Background: Cancer is one of the leading causes of death in pets. Among various therapeutic methods, chemotherapy is still the main choice to treat advanced and metastatic cancers. However, because of its non-target-specific mode of action, chemotherapy often causes severe side effects in patients. Purposes: This study aimed to analyze the cytotoxic effect of red okra fruit extract (Abelmoschus esculentus) on HeLa cells with a comparison of several incubation periods of therapy. Methods: Red okra fruit was extracted by the maceration method using 96% ethanol. Then its cytotoxic potency was tested in vitro on HeLa cells based on the MTT tetrazolium reduction assay. Results: The results of the MTT test showed a decrease in the viability of HeLa cells along with an increase in the concentration of red okra extract (400, 800, dan 1,600 ppm), where the highest percentage of cell inhibition was obtained at a concentration of 1,600 ppm for each group of 24, 48, and 72 hours of therapy. The lowest IC50 value was obtained by the 48-hour therapy group, which was 631.78 ppm, indicating the optimal duration of therapy of red okra against HeLa cells. Conclusion: The ethanolic extract of red okra (Abelmoschus esculentus) has an anticancer effect by inhibiting the growth and proliferation of HeLa cells. Thus, red okra fruit has potential benefits in the management of animals diagnosed with cancer.

Screening of Anticancer and Immunomodulatory Properties of Recombinant pQE-HAS113 Clone Derived from Streptococcus Equi

Objective: Streptococcus equi has been identified to contain the hyaluronan synthase gene (HAS), which could have a role in the cell proliferation activity. The objective of this research was to determine anticancer properties of HAS113 recombinant clone. Methodology: The intracellular and extracellular portions of the expressed gene products of pQE-HAS113 were harvested and evaluate for anticancer properties against prostate cancer cell (PC3) and breast cancer cell (MCF-7). To evaluate anti-proliferative properties of pQE-HAS113, two assays were carried out: MTT assay, which was used for assessing percent cell inhibition and apoptosis assay, through the AO/EB stain of living, apoptotic, as well as necrotic cells. For evaluation of the immunomodulatory properties of pQE-HAS113 on RAW264.7 in terms of IL-6, IFN-γ & IL-8 expression, flow cytometry examination was done. The harvested intracellular and extracellular portions of pQE-HAS113 were tested. Results: The results indicated that the percentage proliferation of both the prostate cancer and breast cancer cells were 2.1% and 7.2% respectively against the intracellular portions of pQE-HAS113. While in case of the extracellular portions of pQE-HAS113 the proliferation rate of both the prostate cancer and breast cancer cells were 6.5% and 6.7% respectively. The PQE-HAS113 intracellular clone gene has shown proinflammatory activity by stimulating the expression of IL-6, INF-γ, & IL-8 in the RAW264.7 macrophage cells. Conclusion: Thus, the results from the present study indicated that the expressed product of recombinant clone of HAS 113, pQE-HAS113 has potential to be used as anti-proliferative and apoptosis inducing substance for prostate and breast cancer. Keywords: Streptococcus equi; breast cancer; cell proliferation; apoptosis ass

<i>In Vitro</i> Antioxidant and Anticancer Potency of <i>Tabernaemontana divaricata</i> (L.) Flowers

A study was performed to identify an antioxidant and anticancer property of the flower of <em>Tabernaemontana divaricata</em> (L.). <em>In vitro</em> antioxidant activity was identified through the execution of various free radical scavenging assays like DPPH (1,1-diphenyl-2-picrylhydrazyl) radical, superoxide anion radical, nitric oxide radicals, hydrogen peroxide radicals in ethanolic flower extract of<em> T. divaricata</em> (L.). As a result of these scavenging methods, DPPH radicals were repressed at the percentage of 38.9% in 1000 ?g/ml. Likewise in the same concentration of extract, repression of superoxide anion radicals, nitric oxide radicals, and hydrogen peroxide radicals occurred at 49.3%, 56.4% and, 31.2% respectively. <em>In vitro</em> antiproliferative activity of the ethanolic flower extract was evaluated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay to find the percentage of cell inhibition as well cell viability of HepG2 (Hepatocellular carcinoma), HeLa (Cervical adenocarcinoma) and A549 (Lung adenocarcinoma) cancer cell lines. Growth of all these cell lines was inhibited at 89.7%, 91.2% and 90.4% in 500 ?g/ml. MTT assay exhibited IC<sub>50</sub> value at 15.6 ?g/ml of extract concentration. The effect of plant extract concentration was identified through decreasing the percent of viable cancer cells when compared to control cells. The results showed that dose dependent cytotoxic activity of <em>T. divaricata</em> (L.) against all cancer cell lines. The present work concluded that flower of <em>T. divaricata</em> (L.) can act on various cancer cells under <em>in vitro</em> condition via neutralizing effect of free radicals.

Anticancer evaluation of Moringa oleifera leaf extracts against lung cancer cell lines

Moringa oleifera is a promising anticancer plants especially its leaf extracts having anticancer activities. In our study, we evaluate the anticancer activity of Moringa oleifera leaf extracts against A549 cell lines. The present investigate states that the percentage of cell inhibition of methanolic extract was found to be high against the A549 Cancer cell lines.

Electrochemical, spectroscopic and theoretical monitoring of anthracyclines' interactions with DNA and ascorbic acid by adopting two routes: Cancer cell line studies.

Pharmacodynamic interactions of three anthracycline antibiotics namely doxorubicin (DXH), epirubicin (EpiDXH) and daunorubicin (DNR) with DNA in the absence and presence of ascorbic acid (AA) as natural additive were monitored under physiological conditions (pH = 7.4, 4.7 and T = 309.5K). Route–1 (Anthracycline–AA–DNA) and Route–2 (Anthracycline–DNA–AA) were adopted to see the interactional behavior by cyclic voltammetry (CV) and UV-visible spectroscopy. In comparison to Route–2; voltammetric and spectral responses as well as binding constant (Kb) and Gibb’s free energy change (ΔG) values revealed strongest and more favorable interaction of anthracycline–AA complex with DNA via Route–1. Kb, s (binding site sizes) and ΔG evaluated from experimental (CV, UV-Vis) and theoretical (molecular docking) findings showed enhanced binding strength of tertiary complexes as compared to binary drug–DNA complexes. The results were found comparatively better at pH 7.4. Consistency was observed in binding parameters evaluated from experimental and theoretical techniques. Diffusion coefficients (Do) and heterogeneous electron transfer rate constant (ks,h) confirmed the formation of complexes via slow diffusion kinetics. Percent cell inhibition (%Cinh) of anthracyclines for non-small cell cancer cell lines (NSCCLs) H-1299 and H-157 were evaluated higher in the presence of AA which further complimented experimental and theoretical results.

CYTOTOXICITY OF METABOLITES PRODUCED BY ENDOPHYTIC FUNGUS CLADOSPORIUM SP. ISOLATED FROM MARINE MACROALGAE ON IN­VITRO MCF­7, HELA, AND DU-145 CELL LINES

Objective: To investigate the in vitro cytotoxicity effect of the crude ethyl acetate extract of Cladosporium sp. on MCF-7, HeLa, and DU-145 cell lines.Methods: In vitro cytotoxicity was evaluated by tetrazolium reduction assay. The percentage of cell inhibition was analyzed using probit analysis to obtain 50% inhibitory concentration (IC50). Morphological alteration of the cell lines after exposure with extract was observed under an inverted microscope.Results: The ethyl acetate extract of the metabolite performed an anticancer activity for cancer cell line MCF-7, HeLa, and DU-145 with IC50 respectively 8.46 μg/ml; 9.87 μg/ml; and 98.03 μg/ml. The extract shows greater the anticancer activity and has strong antiproliferative on MCF-7 and HeLa cell line than DU-145. Confirmation morphological were observed under the inverted microscope showed a morphological change in cancer cells when incubated with the extract.Conclusion: From the performed assay, the crude extract of Cladosporium sp. exhibit cytotoxic activity against MCF-7, HeLA, and DU-145.

Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells

The co-contamination of cereals, grains, crops, and animal feeds by mycotoxins is a universal problem. Humans and animals are exposed to several mycotoxins simultaneously as evidenced by extensive studies on this topic. Yet, most studies have addressed the effects of mycotoxins individually. Aflatoxin B1 and ochratoxin A can induce immunotoxicity. However, it remains unclear whether a combination of these mycotoxins aggravates immunotoxicity and the potential mechanism underlying this effect. In this study, we used the cell line 3D4/21, swine alveolus macrophages and innate immune cell. The results showed that the percentage of cell inhibition, annexin V/PI-positive rates, and the expression of pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) significantly increased and the release of lactate dehydrogenase and phagocytotic index were significantly decreased at different concentrations of aflatoxin B1 and ochratoxin A combination when compared with control. The combination of aflatoxin B1 and ochratoxin A significantly decreased the production of GSH and increased reactive oxygen species level. However, N-acetylcysteine suppressed the oxidative stress and alleviated the immunotoxicity induced by the combination. The combination of aflatoxin B1 and ochratoxin A markedly enhanced the degradation of IκBa, the phosphorylation of nuclear factor kappa B (p65), and the translocation of activated nuclear factor kappa B (NF-κB) into the nuclei as demonstrated by western blotting and confocal laser scanning microscopy. These effects could be reversed by BAY 11-7082, a specific inhibitor of NF-κB. Taken together, a combination of aflatoxin B1 and ochratoxin A could aggravate immunotoxicity by activating the NF-κB signaling pathway.

ANTICANCER & CYTOTOXIC POTENTIAL OF AQUEOUS EXTRACT OF TRITICUM AESTIVUM ON HELA CELL LINE

The objective of the study was to analyze the anticancer property of the leaves of Triticum aestivum on HeLa cells. The Indian medicinal plant Triticum aestivum that is used in traditional medicine for cancer and non cancerous diseases was collected. The crude aqueous extract was prepared by using standard protocols. The antiproliferative effect of the aqueous extract was evaluated in vitro by employing MTT assay. The potency of each plant extract concentration was calculated in terms of percent cell inhibition of VERO and HeLa cells. The extract showed dose dependent anticancer activity on the cancer cell line i.e HeLa cell line while the extract did not show any cell toxic potential to the normal cell line i.e. Vero cell line. . The MTT assay showed an anti proliferative activity (IC 50 ) for the HeLa cell line at 133.6 μg/ml of crude extract. Keywords: Triticum aestivum , HeLa cells, VERO Cell line, MTT assay, cytotoxic, aqueous extract

Ethanol Extracts of Selected Cyathea Species Decreased Cell Viability and Inhibited Growth in MCF 7 Cell Line Cultures

Cancer is the cause of more than 6 million deaths worldwide every year. For centuries, medicinal plants have been used in the treatment of cancer. Chemotherapy, radiotherapy, surgery and acupuncture point stimulation are also used to treat cancer. The present study was intended to reveal the cytotoxic and anticancer potential of selected Cyathea species and to highlight their importance in the pharmaceutical industry for the development of cost-effective drugs. Cytotoxic studies using brine shrimp lethality bioassays and MCF 7 cell line cultures were carried out. Compared to petroleum ether, chloroform and acetone extracts, the ethanol extracts of selected Cyathea species were found to be more effective against brine shrimps. The ethanol extracts were further subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assays. A decrease in cell viability and an increase in growth inhibition were observed for the MCF 7 cell line. The maximum percentage of cell inhibition was observed in Cyathea crinit, followed by Cyathea nilgirensis and Cyathea gigantea. The results of the present study suggest that Cyathea species are an effective source of cytotoxic compounds.

Evaluation of cytotoxicity of aqueous extract of Graviola leaves on squamous cell carcinoma cell-25 cell lines by 3-(4,5-dimethylthiazol-2-Yl) -2,5-diphenyltetrazolium bromide assay and determination of percentage of cell inhibition at G2M phase of cell cycle by flow cytometry: An in vitro study.

Introduction:Malignancies constitute a wide variety of disorders having high mortality and morbidity rates. Current protocols for management include surgical intervention, chemotherapy, and radiation which possess numerous adverse effects. Many phytochemicals are available with anticancer properties similar to anticancer drugs. Major benefit of these compounds is apparent lack of toxicity to normal tissues. Graviola (botanical name: Annona Muricata) contain bioactive compound “annonaceous acetogenins” known for anticancer activity on cancer cell lines.Aims:To determine cytotoxicity of Graviola and percentage cell inhibition at G2M phase of cell cycle.Settings and Design:The cytotoxicity of aqueous extract of Graviola leaves on squamous cell carcinoma (SCC-25) cell lines at various concentrations evaluated using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The percentage of SCC-25 cell inhibition at G2M phase of cell cycle determined using flow cytometry.Methods:Graviola Leaves, American Type Culture Collection SCC-25 cell lines were procured from Skanda Laboratories, Bengaluru. The cytotoxicity of aqueous extract of Graviola on SCC-25 cells at various concentrations evaluated using MTT assay. The percentage of SCC-25 cell inhibition at G2M phase of cell cycle determined using flow cytometry.Statistical Analysis:Statistical analysis was done using one-way ANOVA.Results:MTT assay showed statistically significant (P < 0.001) dose-dependent inhibition of SCC-25 cell lines by Graviola with IC50 value of 12.42 μg/ml. Flow cytometry revealed that Graviola at 25 and 50 g/ml arrested 53.39% and 52.09% cells in G2M phase of cell cycle respectively, which was statistically significant.Conclusion:Graviola showed significant cytotoxic activity and percentage of cell inhibition at G2M phase cell cycle against SCC-25 cell lines.

Sulfone derivatives reduce growth, adhesion and aspartic protease SAP2 gene expression.

Fungal virulence factors represent a strategy for the design of new compounds with effective activities against Candida spp. Dichloromethyl-4-chloro-3-nitrophenylsulfone (named Compound 1) and chlorodibromomethyl-4-hydrazino-3-nitrophenylsulfone (Compound 2) versus Candida albicans virulence factors (SAP2 expression and adhesion to Caco-2 cell line) were investigated. Candida albicans SC5314 and its mutants: Δsap9, Δsap10, Δsap9/10 were used. MICs of the Compounds (concentrated at 0.0313-16 µg/ml) were determined using M27-A3. Percentage of cell inhibition was assessed spectrophotometrically (OD405) after 48 h at 35 °C. The SAP2 expression was analyzed with the use of RT-PCR; relative quantification was normalized against ACT1 in cells grown in YEPD and on Caco-2. Adherence assay of C. albicans to Caco-2 was performed in a 24-well-plate. Compound 1 showed higher activity (% = 100 at 4 µg/ml) than Compound 2 (MIC90 = 16 µg/ml). Dichloromethyl at the para position of the phenyl ring exerted anti-Candidal potential. Under Compound 1, SAP2 was down-regulated in all the strains (P ≤ 0.05). Conversely, SAP2 was over-expressed in Δsap9-10 (untreated cells) compared with the wild-type. The Compounds significantly affected adherence to epithelium (P ≤ 0.05). The tested sulfones interfered with the adhesion of C. albicans cells to the epithelial tissues without affecting their viability after 90-min of incubation. The Compounds' mode of action was attributed to the reduced adhesiveness and the lower SAP2 expression. Saps9-10 play a role in C. albicans adhesion and they can be involved in the sulfone resistance mechanisms.

Application of response surface method to evaluate the cytotoxic potency of Ulva fasciata Delile, a marine macro alga

Bioprospecting of marine natural products has recently produced a substantial number of drug candidates. Ulva fasciata Delile, belonging to the family Ulvaceae, is a green marine macro alga that grows profusely on the coastal seashore of South India. In the present study, we investigated the in vitro cytotoxic potential of a methanolic extract of U.fasciata Delile (MEUF) using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay against human colon carcinoma (HT-29), human hepatocyte carcinoma (Hep-G2), and human breast carcinoma (MCF-7) cell lines. Response surface methodology (RSM) was applied using central-composite experimental design (CCD) to obtain optimum combined effect of concentration and cancer cells with highest cytotoxicity. The effect of concentration, cancer cell lines as independent variables on absorbance (OD), percent cell survival and percent cell inhibition as dependent variables was investigated. Maximum cytotoxic activity of MEUF was established for Hep-G2 with lowest OD or percent cell survival; highest percent cell inhibition with significant difference (p>0.05) was compared to HT-29 and MCF-7.

Prospective evaluation of an in vitro radiation resistance assay in locally advanced cancer of the uterine cervix: A Southwest Oncology Group Study

Objectives To investigate the feasibility of performing a fresh-tissue, in vitro radiation resistance assay (IVRRA) in a cooperative group setting and to assess the association of IVRRA results with clinical outcomes. Methods Women with Stages IIB–IVA carcinoma of the uterine cervix without obvious para-aortic lymphadenopathy on imaging were eligible. Primary tumor biopsies were shipped to a central testing facility where agar-based cell suspensions were exposed to 300 cGy of RT ± cisplatin and cultured for 5 days. 3H-thymidine incorporation was used to determine percent cell inhibition (PCI) of test specimen compared to that of the untreated control. Tumors were considered to exhibit extreme radiation resistance (ERR), intermediate radiation resistance (IRR) or low radiation resistance (LRR) based on a standard data set from 39 previously studied specimens. Standardized doses of external beam radiation and intracavitary brachytherapy, when feasible, in addition to platinum-based chemotherapy were mandated. Progression-free survival (PFS) was the primary endpoint. Clinical response and overall survival (OS) were secondary endpoints. Clinical investigators were blinded to assay data and vice versa. Results Thirty-six patients were enrolled, but analysis was limited to 17 patients whose specimens were adequate for IVRRA. The median follow-up time among patients still alive at last contact was 40 months (range: 0–56 months). There was no association between IVRRA and response. In the Cox model, IRR/ERR tumors showed worse PFS [HR = 11.2 (95% CI 1.3–96, p = 0.03)] and worse OS [HR = 11.7 (95% CI 1.4–99.6, p = 0.03)] compared to LRR tumors when IVRRA was performed with RT alone, but there were no associations between IVRRA and PFS or OS when cisplatin was added to the IVRRA. Conclusions IVRRA (RT alone) results correlated with PFS and OS in this prospective trial, but follow-up trials are indicated to address feasibility and to confirm results in an expanded cohort. If confirmed, IVRRA could potentially direct molecular identification of novel targeted therapeutic approaches which might counteract radiation resistance.

Biomarker and in vitro chemoresistance profiles of undifferentiated ovarian cancers

2532 Background: To determine the biomarker expression and drug resistance patterns of undifferentiated ovarian cancers. Methods: Biomarker expression was determined by immunohistochemistry. In vitro drug resistance profiles were analyzed by assays exposing tumors to suprapharmacologic doses of chemotherapy. Results: Of 177 ovarian cancer specimens, 63 were classified as undifferentiated tumors and 114 well-differentiated cancers were used for comparison. Of the undifferentiated tumors, 46.7% were primary cancers and the remainder were recurrent cancers. Most of the well-differentiated tumors were obtained from primary (82%) vs. recurrent disease specimens. The average DNA index and S-phase fraction were significantly higher in the undifferentiated vs. well-differentiated tumors (1.42 vs. 1.23, p=0.025 for DNA index; 1.69 vs. 3.06, p&lt;0.0001 for S phase fraction). In addition, the percent of tumors with p53 mutations was also higher in the undifferentiated compared to the well-differentiated tumors (47.8% vs. 17.8%; p=0.005). The mean percent cell inhibition was significantly lower in the undifferentiated tumors compared to well-differentiated cancers after exposure to etoposide (54%±21 vs. 80%±18; p=0.0002), doxorubicin (59%±28 vs. 80.0%±21; p=0.07), and topotecan (61.7%±20 vs. 71%±21; p=0.015). Compared to well-differentiated tumors, undifferentiated tumors tended to be more resistant to etoposide (40% vs. 11%), doxorubicin (22% vs. 9%), and topotecan (19% vs. 16%). However, the drug resistance patterns after exposure to taxanes (paclitaxel and taxotere) and platinums (carboplatin and cisplatin) were similar. Conclusions: Undifferentiated tumors of the ovary have a significantly different biomarker expression and drug resistance profiles compared to well-differentiated tumors. Given that undifferentiated cancers provide a treatment challenge for the clinician, this data can provide additional prognostic and therapeutic information, and warrants further investigation. No significant financial relationships to disclose.

Inhibitory effect of schisandrin B on gastric cancer cells in vitro

To investigate the inhibitory effect and possible mechanism of action of schisandrin B in SC-B on gastric cancer cells in vitro. SC-B consisted of schisandrin B, aloe-emodin, and Astragalus polysaccharides. Exponentially growing human gastric cancer SGC-7901 cells were divided into six treatment groups: (1) control group (RPMI 1640 medium); (2) negative control group (2% DMSO); (3) positive control group (50 mg/L 5-Fluorouracil, 5-FU); (4) low-dose group (LSC, final concentration of schisandrin B, 25 mg/L); (5) moderate-dose group (MSC, final concentration of schisandrin B, 50 mg/L); (6) high-dose group (HSC, final concentration of schisandrin B, 100 mg/L). Follow-up was done at 12-48 h. An MTT (Methylthiazolyldiphenyl-tetrazolium bromide) assay was used to examine the inhibitory effect of SC-B on gastric cancer cells. The mitosis index was assessed using an inverted microscope. Flow cytometry was used to visualize the cell cycle. An RT-PCR (Reverse transcription-Polymerase chain reaction) -based assay was used to detect mRNA expression for cyclin D1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The MTT assay showed that the number of living cells in the LSC, MSC and HSC groups was significantly smaller than that in the DMSO-treated group (P < 0.05) at 12-48 h. The inhibitory rate (IR) of the LSC group was 41.15% +/- 3.86%, 59.24% +/- 5.34% and 69.93% +/- 7.81% at 12, 24 and 48 h, respectively. The IR of the MSC group was 42.82% +/- 4.94%, 62.68% +/- 7.58% and 71.79% +/- 8.12% at 12, 24 and 48 h, respectively. The IR of the HSC group was 37.50% +/- 3.21%, 40.34% +/- 2.98% and 61.99% +/- 4.88% at 12, 24 and 48 h, respectively. These results suggested that a moderate dosage had the most obvious inhibitory efficacy at 48 h. Compared to the DMSO group, the mitosis index of the LSC, MSC, HSC groups was greatly decreased (P < 0.05) at all time points. Any dose of SC-B suppressed mitosis within 12-48 h. Compared to the DMSO group, the percentage of cells in the G0/G1 phase of the MSC group was greatly increased, and that of the S + G2M phase was greatly decreased, while the percentage of cell inhibition (PCI) in the MSC group was greatly increased (P < 0.05). This suggested that SC-B could exclusively arrest cells in the G0/G1 phase. Cyclin D1 mRNA expression was lower in the MSC group than that in the DMSO group (P < 0.05). SC-B can inhibit the proliferation and aberrant mitosis of human gastric cancer SCG-7901 cells in vitro. This inhibitory effect may be due to the down-regulation of cyclin D1 mRNA expression, which causes cell cycle arrest of gastric cancer cells.

Extreme drug resistance in primary brain tumors: in vitro analysis of 64 resection specimens.

Understanding chemoresistance profiles of brain tumors may aid in more educated selection of chemotherapeutic regimens for clinical trials and patient treatment. Although the literature contains many reports of the application of drug resistance assays, little is known about extreme drug resistance (EDR) in primary brain tumors. We undertook this study to determine chemoresistance profiles for brain tumors. From September 1991 to February 1998, we collected 64 brain tumor specimens from patients admitted to the Johns Hopkins Hospital. Tumors were classified according to the revised World Health Organization system. Brain tumor specimens were tested against 13 different chemotherapeutic agents using an extreme drug resistance assay. Results were reported as percent cell inhibition (PCI) (compared to control cultures). A drug resistance profile (extreme, intermediate, or low) was determined based on statistical comparison to a historical database of tumor specimens tested against the same panel of chemotherapeutic agents. Brain tumor specimens were classified histologically as Grade IV astrocytoma (glioblastoma multiforme, n = 35), Grade II/III astrocytoma (n = 11), oligodendroglioma (n = 6), meningioma (n = 9), hemangiopericytoma (n = 2), and ependymoma (n = 1). A large percentage of glioblastomas displayed extreme drug resistance to paclitaxel (69%, n = 35), SN38 (75%, n = 28), and vincristine (38%, n = 29). The majority of Grade II/III astrocytomas displayed extreme drug resistance to carboplatin (67%, n = 6), cisplatin (60%, n = 10), and paclitaxel (60%, n = 10). In a similar fashion, oligodendrogliomas displayed extreme drug resistance to vincristine (60%, n = 5) and paclitaxel (50% n = 6). Most meningiomas displayed extreme drug resistance to vincristine (75%, n = 8), dacarbazine (63%, n = 8), and 4-HC (50%, n = 8). Through the continued analysis of brain tumor specimens and compilation of data from multiple institutions, chemoresistance profiles could assist in the development of rationale clinical trials and treatment regimens for patients with brain tumors.

Microcytotoxicity and Serum Blocking Factors in Malignant Melanoma and Halo Nevus

Microcytotoxicity assays of patients with malignant melanoma and halo nevi were performed. No good correlation could be found between percent cell inhibition and histopathological level of melanoma or the clinical staging. The percent cell inhibition was usually an index of response to vaccinia virus immunotherapy. Actively regressing halo nevi showed high levels of percent cell inhibition, whereas inactive halo nevi had low levels of percent cell inhibition and blocking factor. Immunologic reactivity to melanoma cells may be a common feature of melanoma and halo nevus.