"An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis." (MeSH 2013)
Latest Research Publications
Web Resources: Mitomycin (6 links)
This list of publications is regularly updated (Source: PubMed).
Recurrent verrucous carcinoma of the urinary bladder after transurethral resection followed by intravesical mitomycin, and a review of the literature.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Xeroderma pigmentosum with bilateral ocular surface squamous neoplasia and review of the literature.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.
Biochem Pharmacol. 2016; 105:91-100 [PubMed] Related Publications
Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair.
J Natl Cancer Inst. 2016; 108(7) [PubMed] Article available free on PMC after 01/07/2017 Related Publications
METHODS: Patients underwent FA functional screening for the presence (or lack) of tumor FancD2 nuclear foci formation on their archival tumor material, utilizing a newly developed method (Fanconi Anemia triple-stain immunofluorescence [FATSI]), performed in a Clinical Laboratory Improvement Amendments-certified laboratory. FATSI-negative patients were selected for enrollment in a two-arm dose escalation trial of veliparib, or veliparib/mitomycin-C (MMC).
RESULTS: One hundred eighty-five of 643 (28.7%) screened patients were FATSI-negative. Sixty-one received veliparib or veliparib/MMC through 14 dose levels. Moderate/severe toxicities included fatigue (DLT at veliparib 400mg BID), diarrhea, and thrombocytopenia. Recommended doses are 300mg BID veliparib and veliparib 200mg BID for 21 days following 10mg/m(2) MMC every 28 days. Six antitumor responses occurred, five in the combination arm (3 breast, 1 ovarian, 1 endometrial [uterine], and 1 non-small cell lung cancer). Two patients have received 36 and 60 cycles to date. BRCA germline analysis among 51 patients revealed five deleterious mutations while a targeted FA sequencing gene panel showed missense/nonsense mutations in 29 of 49 FATSI-negative tumor specimens.
CONCLUSIONS: FATSI screening showed that a substantial number of patients' tumors have FA functional deficiency, which led to germline alterations in several patients' tumors. Veliparib alone or with MMC was safely administered to these patients and produced clinical benefit in some. However, a better understanding of resistance mechanisms in this setting is needed.
Improving Access to Adjuvant Intravesical Therapy for Non-Muscle Invasive Bladder Cancer in a Community Hospital.
Urol Nurs. 2015 Nov-Dec; 35(6):287-91 [PubMed] Related Publications
Targeting of pegylated liposomal mitomycin-C prodrug to the folate receptor of cancer cells: Intracellular activation and enhanced cytotoxicity.
J Control Release. 2016; 225:87-95 [PubMed] Related Publications
Appendicovesical Fistula Following Transurethral Resection of Bladder Tumor With Mitomycin C.
Urology. 2016; 89:e1-2 [PubMed] Related Publications
Mitomycin C and Capecitabine (MiX Trial) for Therapy of Patients with Metastasized, Breast Cancer Pretreated with Anthracycline.
Anticancer Res. 2016; 36(1):419-25 [PubMed] Related Publications
PATIENTS AND METHODS: From 03/2004 to 06/2007, a total of 39 patients were recruited and received mitomycin C in combination with capecitabine. The primary end-point was to determinate the tumor response according to Response Evaluation Criteria in Solid Tumors and the rate of toxicities (safety). The secondary study objective was the evaluation of the time to progression (i.e. efficacy).
RESULTS: The median time to progression was 9.3 months (95% confidence interval=6.6-12.0 months) and the median survival was 12.8 months (95% confidence interval=6.8-18.8 months). Most treatment-related adverse events were mild to moderate.
CONCLUSION: Mitomycin C and capecitabine is a good taxane-free option in patients with metastatic breast cancer previously treated with anthracycline.
Gemcitabine and mitomycin induced autophagy regulates cancer stem cell pool in urothelial carcinoma cells.
Biochim Biophys Acta. 2016; 1863(2):347-59 [PubMed] Related Publications
The role of hyperthermia as a treatment for non-muscle invasive bladder cancer.
Expert Rev Anticancer Ther. 2016; 16(2):189-98 [PubMed] Related Publications
Phase I study of cetuximab in combination with 5-fluorouracil, mitomycin C and radiotherapy in patients with locally advanced anal cancer.
Eur J Cancer. 2015; 51(18):2740-6 [PubMed] Related Publications
METHODS AND MATERIALS: Patients with locally advanced anal cancer, T2 (≥4 cm)-4N0-3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule.
RESULTS: Thirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46-70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3-4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%.
CONCLUSION: The MTDs were determined as 5FU 800 mg/m(2) on RT days 1-4 and 29-32 and MMC 8 mg/m(2) on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.
Proteasomal inhibition sensitizes cervical cancer cells to mitomycin C-induced bystander effect: the role of tumor microenvironment.
Cell Death Dis. 2015; 6:e1934 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Cytoreduction and hyperthermic intraperitoneal chemotherapy: The learning curve reassessed.
Eur J Surg Oncol. 2016; 42(2):244-50 [PubMed] Related Publications
METHODS: The first consecutive 100 CRS-HIPEC procedures of three institutions were compared to those of the pioneer hospital. The training provided by the pioneer hospital consisted of hands-on training during the first ten procedures; hereafter guidance was available on consult basis. Operation characteristics, morbidity and completeness of cytoreduction were evaluated by case sequence. Locally-estimated-scatter-plot smoothing was used to evaluate the learning curve.
RESULTS: From four institutions 372 cases were included. A macroscopic complete cytoreduction was reached in 66% of the cases in the pioneer hospital and in 86% in the new hospitals (p < 0.001). Complete cytoreduction rates were higher at start off in the new institutions compared with the experienced institution and increased significantly in the first 100 procedures. The new hospitals started with lower morbidity than the experienced hospital, which did not significantly decrease during the study period.
CONCLUSION: New institutions that were trained and mentored by an experienced CRS-HIPEC hospital performed better from the beginning with regard to complete cytoreduction and morbidity rate with than the experienced center. An improvement in complete cytoreduction rate during the first 100 procedures was observed in the new institutions.
Corneal melanosis successfully treated using topical mitomycin-C and alcohol corneal epitheliectomy: a 3-year follow-up case report.
Arq Bras Oftalmol. 2015 Jul-Aug; 78(4):255-6 [PubMed] Related Publications
Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53.
Mol Cancer Res. 2015; 13(12):1533-43 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
IMPLICATIONS: The combination of a chemotherapy agent and proteasome inhibitor at sublethal doses induced synergistic apoptosis, in particular under hypoxia, in vitro and in vivo through coordinated action of Bcl-xL and p53 on Bak activation.
Curcumin Improves the Tumoricidal Effect of Mitomycin C by Suppressing ABCG2 Expression in Stem Cell-Like Breast Cancer Cells.
PLoS One. 2015; 10(8):e0136694 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Predictive Factors for Time to Progression after Hyperthermic Mitomycin C Treatment for High-Risk Non-Muscle Invasive Urothelial Carcinoma of the Bladder: An Observational Cohort Study of 97 Patients.
Urol Int. 2016; 96(1):83-90 [PubMed] Related Publications
PATIENTS AND METHODS: A longitudinal, cohort study of 97 patients with high-risk NMIBC treated with ≥4 HM instillations on a prophylactic schedule was conducted. The primary outcome was time-to-progression survival; secondary outcomes were overall survival, cancer-specific survival, and adverse events. Descriptive statistics, Kaplan-Meier survival analyses, Cox proportional hazards modelling, and univariate and multivariable regression were performed.
RESULTS: The presence of initial complete response (CR; no evidence of disease at first check video-cystoscopy and urine cytology) post-HM treatment was an independent predictor of good response to HM. Female patients and those without carcinoma in situ (CIS) also appeared to respond better to the intervention. The overall bladder preservation rate at a median of 27 months was 81.4%; 17/97 (17.5%) patients died during the course of the study.
CONCLUSIONS: High-risk NMIBC patients can be safely treated with HM and have good oncological outcome. However, those without an initial CR have a poor prognosis and should be counselled towards adopting other treatment methodologies such as cystectomy. Female gender and lack of CIS may be good prognostic indicators for response to HM.
Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.
Biochem Pharmacol. 2015; 97(3):331-40 [PubMed] Related Publications
European Association of Urology Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma: 2015 Update.
Eur Urol. 2015; 68(5):868-79 [PubMed] Related Publications
OBJECTIVE: To provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians.
EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using these keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; instillation; neoadjuvant treatment; recurrence; risk factors; and survival. References were weighted by a panel of experts.
EVIDENCE SYNTHESIS: Due to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing interest in UTUC. The 2009 TNM classification is recommended. Recommendations are given for diagnosis and risk stratification as well as radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Recommendations are also provided for patient follow-up after different therapeutic strategies.
CONCLUSIONS: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours.
PATIENT SUMMARY: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.
Pegylated liposomal mitomycin C prodrug enhances tolerance of mitomycin C: a phase 1 study in advanced solid tumor patients.
Cancer Med. 2015; 4(10):1472-83 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
Combining Mitomycin C and Regional 70 MHz Hyperthermia in Patients with Nonmuscle Invasive Bladder Cancer: A Pilot Study.
J Urol. 2015; 194(5):1202-8 [PubMed] Related Publications
MATERIALS AND METHODS: Between 2009 and 2011, 20 patients with intermediate and high risk nonmuscle invasive bladder cancer were treated with intravesical mitomycin C (40 mg) combined with regional hyperthermia. Treatment consisted of 6 weekly sessions followed by a maintenance period of 1 year with 1 hyperthermia-mitomycin C session every 3 months. Regional hyperthermia was administered using a 70 MHz phased array system with 4 antennas. Toxicity was scored using CTC (Common Toxicity Criteria) 3.0.
RESULTS: The records of 18 of 20 patients could be analyzed. Median followup was 46 months. Of the 18 patients 15 (83%) completed the induction period of 6 treatments. Four patients (22%) discontinued treatment because of physical complaints without exceeding grade 2 toxicity. Toxicity scored according to CTC 3.0 was limited to grade 1 in 43% of cases and grade 2 in 14%. Mean T90 and T50 bladder temperatures were 40.6C and 41.6C, respectively. The 24-month recurrence-free survival rate was 78%.
CONCLUSIONS: Treatment with regional hyperthermia combined with mitomycin C in patients with intermediate and high risk nonmuscle invasive bladder cancer is feasible with low toxicity and excellent bladder temperatures.
Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models.
Circulation. 2015; 132(9):834-47 [PubMed] Related Publications
METHODS AND RESULTS: We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats.
CONCLUSIONS: MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC-induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease.
Mitomycin C Pharmacokinetics as Predictor of Severe Neutropenia in Hyperthermic Intraperitoneal Therapy.
Ann Surg Oncol. 2015; 22 Suppl 3:S873-9 [PubMed] Related Publications
METHODS: A total of 45 patients undergoing CRS-HIPEC for peritoneal carcinomatosis of colorectal origin between 2004 and 2010 were followed. For each patient, MMC was measured in plasma at different times during HIPEC and the area under the MMC concentration-time curve (MMC-AUC) was calculated.
RESULTS: The incidence of neutropenia was 40 %. No demographic, clinical, or surgical factors increased the risk of neutropenia. However, we found that the occurrence of neutropenia and its gravity increased in direct correlation with an increase in MMC plasma concentration 30 min (T30) and 45 min (T45) after the start of HIPEC. The same correlation was observed between the MMC-AUC and the risk of neutropenia.
CONCLUSIONS: Neutropenia is a frequent complication associated with MMC-HIPEC. The results of our study indicate the feasibility and the potential benefit of a protocol including the MMC dosage at T30 after the start of HIPEC. A threshold of 572 µg/L gives a predictive sensitivity of 86 % and a specificity of 80 %. These results must be considered in the management of patients undergoing MMC-HIPEC in order to place high-risk patients under neutropenic monitoring while the other patients can undergo simple hematological monitoring.
BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301).
BMC Cancer. 2015; 15:432 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
METHODS AND DESIGN: The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use.
TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613000513718 ).
VEGF111b, a C-terminal splice variant of VEGF-A and induced by mitomycin C, inhibits ovarian cancer growth.
J Transl Med. 2015; 13:164 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
METHORDS: VEGF111b mRNA was detected in ovarian cancer cell lines SKOV3 and OVCAR3 by RT-PCR. Western blot was used to detect VEGF111b and VEGF165b protein in the CMs and lysates of OVCAR3 cells. MTT and colony formation assay were used to detect the short-term and long-term proliferation inhibition ability of ovarian cancer cells with VEGF111b overexpression. Cell-cycle analysis was performed to further characterize VEGF111b inhibition effects. VEGF111b signaling on ovarian cancer cells were determined by western blot. The expression levels of Ki67, PCNA, CD31 and VEGF in VEGF111b overexpression xenograft model were detected by immunohistochemistry.
RESULTS: Under the effect of mitomycin C, we identify a new member of VEGFxxxb family-VEGF111b in ovarian cancer cell lines. SKOV3 and OVCAR cells were transfected with empty lentivirus, VEGF111b or VEGF165b lentivirus. VEGF111b and VEGF165b overexpression inhibits proliferation of the ovarian cancer cells, but inhibition effect of VEGF111b is slightly less efficient than VEGF165b. Cell cycle analysis was further used to elucidate the mechanism involved in the inhibition effect. Further, we detected the expression of VEGF-R2 in SKOV3 and OVCAR3 cells, and shown that VEGF111b might bind to conventional VEGF-R2 with the results of reducing VEGF-R2 tyrosine phosphorylation and downstream signaling to have anti-tumor effects. In vivo VEGF111b overexpression inhibits ovarian cancer growth in xenograft mice.
CONCLUSION: Our results show that VEGF111b, as a new member of VEGFxxxb family, with similar properties to VEGF165b, plays potent anti-tumor effect in vitro and in vivo that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth. This also opens a new avenue for treating ovarian cancer.
Results of Intravesical Chemo-Hyperthermia in High-risk Non-muscle Invasive Bladder Cancer.
Asian Pac J Cancer Prev. 2015; 16(8):3241-5 [PubMed] Related Publications
MATERIALS AND METHODS: Between November 2011-September 2013, 43 patients with high-risk non-muscle-invasive bladder cancer undergoing adjuvant chemo-hyperthermia in two centers were evaluated retrospectively. Treatment consisted of 6 weekly sessions, followed by 6 sessions. Recurrence and progression rate, recurrence-free interval and side effects were examined. Analyzed factors included age, gender, smoking status, AB0 blood group, body mass index, T stage and grade, concominant CIS assets. The associations between predictors and recurrence were assessed using multivariate Cox proportional hazard analyses.
RESULTS: A total of 40 patients completed induction therapy. Thirteen (32.5%) were diagnosed with tumor recurrence. Median follow-up was 30 months (range 9-39). Median recurrence-free survival was 23 months (range 6-36). The Kaplan-Meier-estimated recurrence-free rates for the entire group at 12 and 24 months were 82% and 61%. There was no statistically significant difference between patient subgroups. Cox hazard analyses showed that an A blood type (OR=6.23, p=0.031) was an independent predictor of recurrence- free. Adverse effects were seen in 53% of patients and these were frequently grades 1 and 2.
CONCLUSIONS: Intravesical therapy with combination of mitomycin-C and chemohyperthermia seems to be appropriate in high-risk patients with non-muscle-invasive bladder cancer who cannot tolerate or have contraindications for standard BCG therapy.
Long-term outcome of patients with frequently recurrent non-muscle-invasive bladder carcinoma treated with one perioperative plus four weekly instillations of mitomycin C followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon-α2b instillations: prospective randomised FinnBladder-4 study.
Eur Urol. 2015; 68(4):611-7 [PubMed] Related Publications
OBJECTIVE: To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC.
DESIGN, SETTING, AND PARTICIPANTS: Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1-2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study.
INTERVENTION: One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses.
RESULTS AND LIMITATIONS: The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98-4.13; p<0.001). There were no significant differences in the probability of progression, disease-free mortality, or overall survival.
CONCLUSIONS: Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence.
PATIENT SUMMARY: We demonstrated in non-muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78-80% to 43-45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guérin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b.
TRIAL REGISTRATION: The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.
Intravenous siRNA Silencing of Survivin Enhances Activity of Mitomycin C in Human Bladder RT4 Xenografts.
J Urol. 2015; 194(1):230-7 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
MATERIALS AND METHODS: We assessed the effectiveness of siRNA therapy using 2 newly developed pegylated cationic liposome carriers, PCat and PPCat. Each has a fusogenic lipid to destabilize the endosomal membrane. PPCat further contains paclitaxel to enhance in vivo delivery and transfection of survivin siRNA. In vitro antitumor activity was evaluated by short-term MTT and long-term clonogenicity cytotoxicity assays. In vivo intravenous therapy was assessed in mice bearing subcutaneous tumors.
RESULTS: Nontarget siRNA showed no antitumor activity in vitro or in vivo. Treatment of cultured cells with mitomycin C at a 50% cytotoxic concentration enhanced survivin mRNA and protein levels. Adding PPCat or PCat containing survivin siRNA reversed survivin induction and enhanced mitomycin C activity (p <0.05). In tumor bearing mice single agent mitomycin C delayed tumor growth and almost tripled the survivin protein level in residual tumors. Adding PPCat-survivin siRNA, which alone resulted in a minor survivin decrease of less than 10%, completely reversed mitomycin C induced survivin and enhanced mitomycin C activity (p <0.05).
CONCLUSIONS: Results indicate that there is effective in vivo survivin silencing and synergism between mitomycin C and PPCat-survivin siRNA. This combination represents a potentially useful chemo-gene therapy for bladder cancer.
Tailoring heated intraperitoneal mitomycin C for peritoneal metastases originating from colorectal carcinoma: a translational approach to improve survival.
Br J Cancer. 2015; 112(5):851-6 [PubMed] Article available free on PMC after 01/07/2017 Related Publications
METHODS: The MMC sensitivity was determined for 12 CRC cell lines and correlated to mRNA expression of 37 genes related to the Fanconi anaemia (FA)-BRCA pathway, ATM-ATR pathway and enzymatic activation of MMC. Functionality of the FA-BRCA pathway in cell lines was assessed using a chromosomal breakage assay and western blot for key protein FANCD2. Bloom syndrome protein (BLM) was further analysed by staining for the corresponding protein with immunohistochemistry (IHC) on both CRC cell lines (n=12) and patient material (n=20).
RESULTS: High sensitivity correlated with a low BLM (P=0.01) and BRCA2 (P=0.02) at mRNA expression level. However, FA-BRCA pathway functionality demonstrated no correlation to MMC sensitivity. In cell lines, weak intensity staining of BLM by IHC correlated to high sensitivity (P=0.04) to MMC. Low BLM protein expression was significantly associated with an improved survival in patients after CRS and HIPEC (P=0.04).
CONCLUSIONS: Low BLM levels are associated with high MMC sensitivity and an improved survival after HIPEC.
Tumor growth and metastasis can be inhibited by maintaining genomic stability in cancer cells.
Front Med. 2015; 9(1):57-62 [PubMed] Related Publications