Anticancer Drug Sensitivity Test Research Articles

Patient tissue-derived FGFR4-variant and wild-type colorectal cancer organoid development and anticancer drug sensitivity testing

ObjectivesFGFR4-variant and wild-type colorectal cancer (CRC) organoids were developed to investigate the effects of FGFR4-targeted drugs, including FGFR4-IN and erdafitinib, on CRC and their possible molecular mechanism. MethodsClinical CRC tissues were collected, seven CRC organoids were developed, and whole exome sequencing (WES) was performed. CRC organoids were cultured and organoid drug sensitivity studies were conducted. Finally, an FGFR4-variant (no wild-type) CRC patient-derived orthotopic xenograft mouse model was developed. Western blot measured ERK/AKT/STAT3 pathway-related protein levels. ResultsWES results revealed the presence of FGFR4-variants in 5 of the 7 CRC organoids. The structural organization and integrity of organoids were significantly altered under the influence of targeted drugs (FGFR4-IN-1 and erdafitinib). The effects of FGFR4 targeted drugs were not selective for FGFR4 genotypes. FGFR4-IN-1 and erdafitinib significantly reduced the growth, diameter, and Adenosine Triphosphate (ATP) activity of organoids. Furthermore, chemotherapeutic drugs, including 5-fluorouracil and cisplatin, inhibited FGFR4-variant and wild-type CRC organoid activity. Moreover, the tumor volume of mice was significantly reduced at week 6, and p-ERK1/2, p-AKT, and p-STAT3 levels were down-regulated following FGFR4-IN-1 and erdafitinib treatment. ConclusionsFGFR4-targeted and chemotherapeutic drugs inhibited the activity of FGFR4-variant and wild-type CRC organoids, and targeted drugs were more effective than chemotherapeutic drugs at the same concentration. Additionally, FGFR4 inhibitors hindered tumorigenesis in FGFR4-variant CRC organoids through ERK1/2, AKT, and STAT3 pathways. However, no wild-type control was tested in this experiment, which need further confirmation in the next study.

Singular value thresholding two-stage matrix completion for drug sensitivity discovery

Incomplete data presents significant challenges in drug sensitivity analysis, especially in critical areas like oncology, where precision is paramount. Our study introduces an innovative imputation method designed specifically for low-rank matrices, addressing the crucial challenge of data completion in anticancer drug sensitivity testing. Our method unfolds in two main stages: Initially, the singular value thresholding algorithm is employed for preliminary matrix completion, establishing a solid foundation for subsequent steps. Then, the matrix rows are segmented into distinct blocks based on hierarchical clustering of correlation coefficients, applying singular value thresholding to the largest block, which has been proved to possess the largest entropy. This is followed by a refined data restoration process, where the reconstructed largest block is integrated into the initial matrix completion to achieve the final matrix completion. Compared to other methods, our approach not only improves the accuracy of data restoration but also ensures the integrity and reliability of the imputed values, establishing it as a robust tool for future drug sensitivity analysis.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC)

BackgroundRecently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient‘s groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test.MethodsOn the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides.ResultsThe conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response.ConclusionsTherefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

In Vitro Anticancer Drug Sensitivity Sensing through Single-Cell Raman Spectroscopy

Traditional in vitro anticancer drug sensitivity testing at the population level suffers from lengthy procedures and high false positive rates. To overcome these defects, we built a confocal Raman microscopy sensing system and proposed a single-cell approach via Raman-deuterium isotope probing (Raman-DIP) as a rapid and reliable in vitro drug efficacy evaluation method. Raman-DIP detected the incorporation of deuterium into the cell, which correlated with the metabolic activity of the cell. The human non-small cell lung cancer cell line HCC827 and human breast cancer cell line MCF-7 were tested against eight different anticancer drugs. The metabolic activity of cancer cells could be detected as early as 12 h, independent of cell growth. Incubation of cells in 30% heavy water (D2O) did not show any negative effect on cell viability. Compared with traditional methods, Raman-DIP could accurately determine the drug effect, meanwhile, it could reduce the testing period from 72–144 h to 48 h. Moreover, the heterogeneity of cells responding to anticancer drugs was observed at the single-cell level. This proof-of-concept study demonstrated the potential of Raman-DIP to be a reliable tool for cancer drug discovery and drug susceptibility testing.

Intratumoral gene expression of dihydrofolate reductase and folylpoly-c-glutamate synthetase affects the sensitivity to 5-fluorouracil in non-small cell lung cancer

BackgroundVarious factors related to the sensitivity of non-small cell lung carcinoma (NSCLC) to 5-fluorouracil (5-FU) have been reported, and some of them have been clinically applied. In this single-institutional prospective analysis, the mRNA expression level of five folic acid-associated enzymes was evaluated in surgical specimens of NSCLC. We investigated the correlation between the antitumor effect of 5-FU in NSCLC using an anticancer drug sensitivity test and the gene expression levels of five enzymes.Materials and methodsForty patients who underwent surgery for NSCLC were enrolled, and the antitumor effect was measured using an in vitro anticancer drug sensitivity test (histoculture drug response assay) using freshly resected specimens. In the same sample, the mRNA expression levels of five enzymes involved in the sensitivity to 5-FU were measured in the tumor using real-time PCR. The expression levels and the result of the sensitivity test were compared.ResultsNo correlation was found between dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), or DPD/OPRT expression and the antitumor effects of 5-FU. On the other hand, a correlation was found between thymidylate synthase (TS), folylpoly-c-glutamate synthetase (FPGS), and dihydrofolate reductase (DHFR) expression and 5-FU sensitivity.ConclusionExpression of FPGS and DHFR may be useful for predicting the efficacy of 5-FU-based chemotherapy for NSCLC.

抗がん剤感受性試験（CD-DST）による大腸がんの予後および治療効果予測の有用性

抗がん剤感受性試験（CD-DST）による大腸がんの予後および治療効果予測の有用性

Development of an anti-cancer drug sensitivity test using a urine sample-derived organoid culture for dog bladder cancer

Development of an anti-cancer drug sensitivity test using a urine sample-derived organoid culture for dog bladder cancer

Identification of the optimal cetuximab concentration that is effective against oral squamous cell carcinoma in collagen gel droplet embedded culture drug sensitivity testing.

Anticancer drug sensitivity testing using the collagen gel droplet embedded culture drug sensitivity test (CD-DST) on oral squamous cell carcinoma (OSCC) samples beginning from 2010 has been conducted. The present study investigated the effect of adding cetuximab (Erbitux®), a molecularly targeted drug, on anticancer drug activity against clinical OSCC specimens. A total of 25 specimens were obtained from 25 patients with OSCC between October 2013 and December 2017. The present study conducted anticancer drug sensitivity testing for cisplatin (CDDP), 5-fluorouracil (5-FU), cetuximab, three-drug combination, single agent and multi drug combinations, and cetuximab addition to the aforementioned regimens using CD-DST. In addition, the optimum concentration of each drug was evaluated. The overall evaluation success rate of the CD-DST method for OSCC specimens was 84.0% (21 of 25 cases); sensitivity to anticancer drugs and cetuximab could be evaluated. The in vitro efficacy rate of a cetuximab single agent and CDDP + 5-FU (PF) at a cut-off value of 50% was similar to the known clinical response rate. However, at a cut-off value of 50%, the in vitro efficacy of PF + cetuximab was calculated to be 40%, which was higher than the clinical response rate. The CD-DST method could be used to evaluate cetuximab, a molecularly targeted drug. Furthermore, its additive effect on conventional chemotherapy could be evaluated. The CD-DST method is suitable for evaluating and selecting chemotherapy regimens, including molecularly targeted drugs. Future studies are required to generate and evaluate relevant clinical data.

In vivo drug screening method of radiosensitizers using tumor-bearing chick embryo.

In radiotherapy, tumor hypoxia is the main factor responsible for treatment resistance, and the development of radiosensitizers that can overcome this is imperative. However, many drugs that are effective in vitro and in vivo fail in clinical trials, and thus it is necessary to develop an animal model that can be used for the correct evaluation of pharmacokinetics and activity. Developing chicken eggs are commonly used in various research fields such as anticancer drug sensitivity tests and cardiotoxicity tests. We examined whether the radiosensitizing activity of etanidazole, as a hypoxic cell radiosensitizer, could be evaluated using tumor-bearing chick embryo. Following the transplantation of mouse mammary carcinoma EMT6 cells on day 11, a solid tumor was formed on day 15 and an evaluation of the time-course of the tumor revealed that the tumor weight was the highest on day 18. The maximum dose of etanidazole that did not affect tumor growth and fetal survival was 1.0mg and the maximum X-ray dose was 8Gy. Etanidazole was intravenously administered 10min prior to single dose X-ray irradiation. A significant tumor growth inhibitory effect was confirmed with 1.0mg of etanidazole in combination with 8Gy X-ray. In the case of mouse colon cancer colon26 cells, the combination of 3.0mg of etanidazole and 2Gy X-ray showed 2.79 times higher radiosensitizing activity than that observed for the control group. These results demonstrate that it is possible to evaluate the activity of radiosensitizers using tumor-bearing chick embryo.

Anti-Cancer Drug Sensitivity Assay with Quantitative Heterogeneity Testing Using Single-Cell Raman Spectroscopy.

A novel anti-cancer drug sensitivity testing (DST) approach was developed based on in vitro single-cell Raman spectrum intensity (RSI). Generally, the intensity of Raman spectra (RS) for a single living cell treated with drugs positively relates to the sensitivity of the cells to the drugs. In this study, five cancer cell lines (BGC 823, SGC 7901, MGC 803, AGS, and NCI-N87) were exposed to three cytotoxic compounds or to combinations of these compounds, and then they were evaluated for their responses with RSI. The results of RSI were consistent with conventional DST methods. The parametric correlation coefficient for the RSI and Methylthiazolyl tetrazolium assay (MTT) was 0.8558 ± 0.0850, and the coefficient of determination was calculated as R2 = 0.9529 ± 0.0355 for fitting the dose–response curve. Moreover, RSI data for NCI-N87 cells treated by trastuzumab, everolimus (cytostatic), and these drugs in combination demonstrated that the RSI method was suitable for testing the sensitivity of cytostatic drugs. Furthermore, a heterogeneity coefficient H was introduced for quantitative characterization of the heterogeneity of cancer cells treated by drugs. The largest possible variance between RSs of cancer cells were quantitatively obtained using eigenvalues of principal component analysis (PCA). The ratio of H between resistant cells and sensitive cells was greater than 1.5, which suggested the H-value was effective to describe the heterogeneity of cancer cells. Briefly, the RSI method might be a powerful tool for simple and rapid detection of the sensitivity of tumor cells to anti-cancer drugs and the heterogeneity of their responses to these drugs.

Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of 5-FU based adjuvant chemotherapy in patients with stage II-III colorectal cancer: 10-year follow up results.

e15605Background: Considering the cumulative neurotoxicity induced by oxaliplatin, 5-fluorouracil (5-FU)-based therapy is one of the standard adjuvant chemotherapeutic choices for stage III colorec...

MP65-12 ORGANOID 3D CULTURE SYSTEM FOR BLADDER CANCER MODELING

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2018MP65-12 ORGANOID 3D CULTURE SYSTEM FOR BLADDER CANCER MODELING Victor Romanov, William Berg, Terry Whyard, Wei Lee, Olga Povcher, Daniel Rittenberg, and Wayne Waltzer Victor RomanovVictor Romanov More articles by this author , William BergWilliam Berg More articles by this author , Terry WhyardTerry Whyard More articles by this author , Wei LeeWei Lee More articles by this author , Olga PovcherOlga Povcher More articles by this author , Daniel RittenbergDaniel Rittenberg More articles by this author , and Wayne WaltzerWayne Waltzer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2078AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The absence of in vitro bladder cancer models recapitulating the diversity of urothelial tumors hinders our understanding of the disease pathogenesis and postpones development of the effective therapeutic modalities. Recent achievement in the development of 3D organoid systems enable stem or progenitor cells to form diverse, multicellular structures, that can self-renew, self-organize, and differentiate. Development of 3D organoid culture from bladder urothelium provides an unique model for studying cancer. These structures can be genetically modified to mimic individual steps of bladder cancer tumorigenesis. 3D spheroids derived from bladder tumors can be directly used in preclinical applications METHODS We developed 3D organoid cultures of urothelial cells that derived from experimental animals (mice) and human (ureter and bladder). Optimal conditions for preferential organoid development were determined. In addition 3D spheroids were established from surgical samples of papillary tumors. These structures were analyzed morphologically and biochemically. Tumor derived spheroids were also used for anti-cancer drug sensitivity testing. RESULTS We established procedure for generation organoids derived from single cell from bladder or ureter. These structures were characterized immunocytochemically and was shown that different types of urothelial cells were present. For bladder cancer derived organoid we used different preparative procedure based on the partial digestion of the tissue. In this case spheroids were formed from cellular conglomerates. Using tumor derived spheroids in drug sensitivity assay we have showed that potential drug-Clostridium perfringens toxin is superior as compared to currently exploited chemotherapeutical modalities for intravesical treatment. CONCLUSIONS Organoid 3D urothelial culture can be used for studying tumorigenesis in bladder cancer and for preclinical testing of potential chemotherapeutic agents. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e863 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Victor Romanov More articles by this author William Berg More articles by this author Terry Whyard More articles by this author Wei Lee More articles by this author Olga Povcher More articles by this author Daniel Rittenberg More articles by this author Wayne Waltzer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Collagen gel droplet-embedded culture drug sensitivity testing in hard palate cancer-predicted antitumor efficacy of cetuximab: A case report.

In vitro anticancer drug sensitivity assessments have been performed for various types of cancer, and an association with clinical response has been observed. The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an in vitro anticancer drug sensitivity test that has recently reported to be useful in oral squamous cell carcinoma (OSCC). CD-DST allows for the analysis of a smaller number of cells compared with other anticancer drug sensitivity tests. The present study reported a successful analysis of anticancer drug sensitivity using CD-DST on cervical lymph node tissue dissected following neoadjuvant chemotherapy from a 55-year-old man with advanced hard palate cancer. Tumor resection and bilateral neck dissection were performed following neoadjuvant chemotherapy (docetaxel + cisplatin + 5-fluorouracil; TPF) for hard palate cancer T2N2cM0. Local recurrence and cervical multiple skin metastasis occurred ~8 months after surgery, and the patient received six doses of cetuximab (C-mab) + cisplatin + 5-fluorouracil (C-mab + PF) administration, which is a type of molecular-targeted therapy. Following the use of the CD-DST method, the clinical response was noted as stable disease following execution of TPF and partial response following execution of C-mab + PF. In addition, low sensitivity by TPF and high sensitivity by C-mab + PF were reported. The CD-DST method reflected the clinical response for the patient, and the results of the current study indicate that CD-DST is a useful tool for selecting chemotherapeutic drugs for patients with OSCC.

Collagen gel droplet-embedded culture drug sensitivity testing in squamous cell carcinoma cell lines derived from human oral cancers: Optimal contact concentrations of cisplatin and fluorouracil.

The collagen gel droplet-embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that uses a method of three-dimensional culture of extremely small samples, and it is suited to primary cultures of human cancer cells. It is a useful method for oral squamous cell carcinoma (OSCC), in which the cancer tissues available for testing are limited. However, since the optimal contact concentrations of anticancer drugs have yet to be established in OSCC, CD-DST for detecting drug sensitivities of OSCC is currently performed by applying the optimal contact concentrations for stomach cancer. In the present study, squamous carcinoma cell lines from human oral cancer were used to investigate the optimal contact concentrations of cisplatin (CDDP) and fluorouracil (5-FU) during CD-DST for OSCC. CD-DST was performed in 7 squamous cell carcinoma cell lines derived from human oral cancers (Ca9-22, HSC-3, HSC-4, HO-1-N-1, KON, OSC-19 and SAS) using CDDP (0.15, 0.3, 1.25, 2.5, 5.0 and 10.0 µg/ml) and 5-FU (0.4, 0.9, 1.8, 3.8, 7.5, 15.0 and 30.0 µg/ml), and the optimal contact concentrations were calculated from the clinical response rate of OSCC to single-drug treatment and the in vitro efficacy rate curve. The optimal concentrations were 0.5 µg/ml for CDDP and 0.7 µg/ml for 5-FU. The antitumor efficacy of CDDP at this optimal contact concentration in CD-DST was compared to the antitumor efficacy in the nude mouse method. The T/C values, which were calculated as the ratio of the colony volume of the treatment group and the colony volume of the control group, at the optimal contact concentration of CDDP and of the nude mouse method were almost in agreement (P<0.05) and predicted clinical efficacy, indicating that the calculated optimal contact concentration is valid. Therefore, chemotherapy for OSCC based on anticancer drug sensitivity tests offers patients a greater freedom of choice and is likely to assume a greater importance in the selection of treatment from the perspectives of function preservation and quality of life, as well as representing a treatment option for unresectable, intractable or recurrent cases.

Anticancer Drug Sensitivity Testing, a Historical Review and Future Perspectives

Background: Clinical cancer treatment and therapy have been gradually improved by experimental and clinical advancements worldwide, especially after the advent of different types of individualized cancer therapy (ICT). Objective: Despite the longest history of anticancer drug sensitivity testing (DST) among ICT, its therapeutic applications for clinical cancer trials need to be updated. Methods: DST techniques are widely diversified and improved a great deal, but they have not been matured to cure all cancer patients in clinics. Results: The retrospection and panorama of historic and evolutionary developments of DST including clinical relevance, advantageous, technical cautions, limitations of varied models and methodologies at present stage are addressed. Conclusion: Future directions and novel ideas must be established. Keywords: Anticancer drugs, cancer stem cell, clinical cancer therapy, drug combinations, drug sensitivity test, individualized cancer therapy, neoplasm metastasis.

Abstract 329: Establishment of three-dimensional primary tumor cell culture method and novel drug sensitivity test

Abstract Background Predicting sensitivity to anticancer drug and selecting the most effective drug may help to enhance the therapeutic value, leading to improve patients’ QOL. For these purposes, primary cancer cell from patient specimen is being studied on anticancer drug sensitivity test. In general cell culture method, primary cancer cells are difficult to culture because of fibroblast cells are increasing predominantly than cancer cells. For resolving the problem, collagen-gel-embedding culture method has been developed. However this culture method remain having some problems, for example, complexity of the cell culture preparation from small cancer tissue like a biopsy sample, low efficiency of primary cancer cells and difficulty in multi-drug sensitivity test. Therefore we developed a three dimensional (3D) cancer cell culture kit that could conduct a primary tumor cell culture and an evaluation of the anticancer drug sensitivity in one-step process after dissociated small cancer tissue. For 3D cell culture we have used NanoCulture Plate (NCP) which is scaffold based 3D culture system and easily form spheroids than other culture systems. Spheroids microenvironment are closely resemble to actual tumor biology, and are therefore more relevant for drug sensitivity. In this report, we carried out a sensitivity test in a lung adenocarcinoma specimen harboring EGFR gene exon19 deletion mutation indicating susceptibility to gefitinib to confirm the efficacy of the system. Method Dissociation of cancer tissue and primary cancer cell culture were performed by using 3D cancer cell culture kit and NCP. Partially digested cancer fragments from surgical specimens were seeded and cultured for 3 days. The spheroids were composed of both CK-18 expressing cancer cells and α-SMA expressing fibroblast cells, then spheroids were treated with gefitinib. After 4 days of drug treatment, the susceptibility of the cells to gefitinib was investigated an index of viability by ATP assay. Detection of EGFR mutations was performed by SRL Inc., using real-time PCR that combines scorpion technology and Amplification Refractory Mutation System (ARMS). Result and conclusion We found that primary cells with EGFR exon19 deletion were highly susceptible to gefitinib, whereas the cells with intact EGFR were not. These finding indicated the feasibility of 3D cancer cell culture kit and NanoCulture Plate for primary cell culture and screening of effective anticancer drugs. The cell lines generated through this procedure may help to advance our knowledge of certain forms of lung cancer and may also be useful for developing patient-specific anti-cancer drug screening procedures. To clarify the causal relationship between the mutation type and susceptibility, additional experiment and optimization of this kit are currently underway. Citation Format: Hiroshi Goji, Manami Shimomura, Yasushi Uemura, Tetsuya Nakatsura, M.Mamunur Rahman, Manabu Itoh. Establishment of three-dimensional primary tumor cell culture method and novel drug sensitivity test. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 329. doi:10.1158/1538-7445.AM2015-329

Abstract 1351: Expression of klotho enhances the apoptotic response of cancer cells to anticancer agents

Abstract (Introduction) We have reported that the klotho gene, which is an anti-aging gene known to be a tumor suppressor, is a prognostic factor for lung cancer patients. In this study, we determined whether klotho expression may have a predictive value of the efficacy of anti-cancer agents for cancer treatment. (Methods) We performed co-transfection of klotho and GFP-plasmid into MCF-7c3 cells, which stably express procaspase-3, and treated the cells with various kinds of anti-cancer agents. We observed typical apoptosis morphologically using fluorescent microscopy and evaluated the apoptotic response. (Results) Western blot analysis revealed high klotho expression in the cells transfected with the klotho gene plasmid. There was no evidence of klotho expression in the normal MCF-7c3 cells. The anti-cancer drug sensitivity test showed that docetaxel significantly induced more typical apoptosis in the cells with klotho than in the cells without klotho (41.2% and 18.3%, respectively; p &amp;lt; 0.05). Paclitaxel also significantly induced more typical apoptosis in the cells with klotho than in the cells without klotho (34.9% and 14.9%, respectively; p &amp;lt; 0.05). However, there was no significant difference in the apoptosis rates induced by other anti-cancer drugs, such as cisplatin, carboplatin, pemetrexed, gemicitabine, vinorelbine, etoposide, and gefitinib. (Conclusion) A high expression of the klotho protein can markedly increase the apoptotic response of MCF-7c3 cells to docetaxel and paclitaxel. These results suggest that klotho expression may indicate the predictive value of chemotherapy and play an important role in cancer treatment. Apoptosis induced by taxane-induced stratified expression of klotho proteinRate of apoptosisDocetaxelPaclitaxelA: Klotho(-)/GFP(-)14.8%19.3%A vs B: p&amp;gt;0.05A vs B: p&amp;gt;0.05B: Klotho(-)/GFP(+)18.3%14.9%B vs C: p=0.01B vs C: p=0.03C: Klotho(+)/GFP(+)41.2%35.9% Citation Format: Yujin Kudo, Jitsuo Usuda, Hideyuki Furumoto, Sachio Maehara, Keishi Ohtani, Tatsuya Inoue, Taichiro Ishizumi, Yasufumi Kato, Masatoshi Kakihana, Naohiro Kajiwara, Tatsuo Ohira, Norihiko Ikeda. Expression of klotho enhances the apoptotic response of cancer cells to anticancer agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1351. doi:10.1158/1538-7445.AM2014-1351

Anticancer drug sensitivity test on squamous cell carcinoma cell lines derived from human oral cancers: Optimal contact concentrations of CDDP and 5-FU using the CD-DST

The collagen gel droplet embedded culture drug sensitivity test (CD-DST) is an anticancer drug sensitivity test that uses a method of three-dimensional culture of very small samples, and it is suited to primary culture of human cancer cells. It is a useful method for oral squamous cell carcinoma (OSCC), in which the cancer tissues needed for testing are in limited supply. However, as the optimal contact concentrations of anticancer drugs for OSCC treatment have yet to be established, CD-DST for OSCC is currently carried out by applying the optimal contact concentrations for stomach cancer.

Increased response of oxaliplatin or irinotecan on in vitro chemosensitivity to 5-fluorouracil in patients with colorectal cancer

Purpose: Five-fluorouracil (5-FU) is the basement drug of chemotherapy in patients with colorectal cancer. Recently, 5-FU and oxaliplatin or irinotecan is to be used by merging. This study investigated the chemosensitivity of 5-FU in patients with colorectal cancer, the additional effects of oxaliplatin or irinotecan to chemosensitivity when they are combined, and the effects of clinicopathologic factors to chemosensitivity. Methods: We performed in vitro chemosensitivity test for the fresh tumor tissue of 48 patients of colorectal cancer and evaluated the chemosensitivity to standard drugs (5-FU, 5-FU plus oxaliplatin: FOx, and 5-FU plus irinotecan: FIri) by using Histoculture drug response assay. Results: The average chemosensitiviy of FOx and FIri were significantly higher than that of 5-FU (32.3% and 36.0% vs. 21.8%, P<0.001). The chemosensitivity of FOx in the lymph node (LN) negative group was higher than LN positive group (35.3% vs. 19.3%, P=0.008). The group of under 70-year-old and the group of negative distant metastasis showed the trends of increased sensitivity to FOx (P=0.052, respectively). The chemosensitivity to FIri in the well or moderately differentiated group was significantly higher than the poorly differentiated goup (35.2% vs. 15.0%, P=0.038). Ki-67 positive group showed significantly increased chemosensitivity to FIri (P=0.021). Conclusion: This study demonstrates that combination of oxaliplatin or irinotecan to 5-FU can be more effective than 5-FU on in vitro chemosensitivity assay in colorectal cancer tissues. Oxaliplatin might be effective in LN negative group, and irinotecan might be effective in well differentiated group and Ki-67 positive group. Keywords: Anticancer drug sensitivity tests, Colorectal neoplasm, Fluorouracil, Oxaliplatin, Irinotecan

The usefulness of anticancer drug sensitivity test (HDRA) for the adjuvant chemotherapy and profiling in pancreatic cancer tissue after HDRA

The usefulness of anticancer drug sensitivity test (HDRA) for the adjuvant chemotherapy and profiling in pancreatic cancer tissue after HDRA