Publications by authors named "Alexey Belyaev"

16 Publications

  • Page 1 of 1

History and current status of cancer registration in Russia.

Cancer Epidemiol 2021 08 2;73:101963. Epub 2021 Jun 2.

Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France.

Background: Russia, then part of the Union of Soviet Socialist Republics (the USSR), introduced compulsory cancer registration in 1953, but a clear overall contemporary description of the cancer surveillance system in Russia is not available.

Methods: We summarized historical landmarks and the development of the standards of classification and coding of neoplasms in Russia and described current population-based cancer registries' (PBCR) procedures and practices.

Results: Cancer registration is organized according to the administrative division of the Russian Federation. More than 600,000 cases are registered annually. All medical facilities, without exception, are required to notify the PBCR about newly diagnosed cases, and each regional PBCR is responsible for registering all cancers diagnosed in citizens residing in the region. The data collection can be described as passive and exhaustive. Hematological malignancies, brain, and CNS tumors are often not referred to cancer hospitals in some regions, explaining the problems in registering these cancers.

Conclusion: Russia's cancer registration system is population-based, and practices seem to be generally internationally comparable. However, coding practices and national guidelines are still outdated and not up to the most recent international recommendations. Further analyses are needed to assess the comparability, validity, completeness, and timeliness of Russia's PBCRs data.
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http://dx.doi.org/10.1016/j.canep.2021.101963DOI Listing
August 2021

TiLoop Bra Assisted Breast Reconstruction - Our Experience.

Chirurgia (Bucur) 2021 Mar-Apr;116(2 Suppl):84-90

Additional covering of the lower pole with allomaterial or its synthetic analogues during immediate breast reconstruction is being perfomed at the N.N. Petrov National Medical Research Oncology Center, Ministry of Healthcare of Russian Federation for last 7 years. Initially, epidermal flap was the only option for lower pole coverage, later ADM was used as part of clinical approbation. Average complication rate ranges from 20-35% due to blood circulatory (supply) disorders. Since 2018, a titanized mesh (TiLoop Bra) been used as a additional coverage of the lower pole. From July 2018 to April 2019, 103 breast reconstructions were performed using TiLoop-BRA mesh. All operations were performed due to malignant tumors of breast, of which in 94 operations were performed for unilateral breast carcinoma, 9 for bilateral breast carcinoma.74 patients received neoadjuvant therapy, 31 received adjuvant therapy, 17 patients required radiation therapy. Overall complications rates significally decreased. Complete loss of breast implant and mesh endoprosthesis 5.88%, Capsular contracture 17.65 %, Only mesh removal due to painful syndrome 5.88%,* Red breast * syndrome (by analogy with ADM) 5.88%.
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http://dx.doi.org/10.21614/chirurgia.116.2 Suppl.S84DOI Listing
May 2021

Frequency and molecular characteristics of PALB2-associated cancers in Russian patients.

Int J Cancer 2021 01 6;148(1):203-210. Epub 2020 Oct 6.

N.N. Petrov Institute of Oncology, St. Petersburg, Russia.

PALB2 is а high-penetrance gene for hereditary breast cancer (BC). Our study aimed to investigate the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young-onset and/or familial and/or bilateral BC cases but none in 96 ovarian cancer (OC) or 172 pancreatic cancer patients. Subsequently, seven recurrent PALB2 pathogenic alleles were selected from this and previous Slavic studies and tested in an extended patient series. PALB2 pathogenic variants were detected in 5/585 (0.9%) "high-risk" BC, 10/1508 (0.7%) consecutive BC and 5/1802 (0.3%) OC cases. Haplotyping suggested that subjects with Slavic alleles c.509-510delGA (n = 10) and c.172-175delTTGT (n = 4) as well as carriers of Finnish c.1592delT mutation (n = 4) originated from a single founder each, while PALB2 p.R414X allele (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was revealed in 5/10 chemonaive BCs and in 0/2 BC samples obtained after neoadjuvant therapy. Multigene sequencing identified somatic PALB2 inactivating point mutation in one out of two tumors without PALB2 LOH but in none of four BCs with PALB2 LOH. Genomic instability, as determined by NGS, was observed in four out of five tumors with biallelic PALB2 inactivation but not in the BC sample with the preserved wild-type PALB2 allele. PALB2 germ-line mutations contribute to a small fraction of cancer cases in Russia. The majority although not all PALB2-driven BCs have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors.
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http://dx.doi.org/10.1002/ijc.33317DOI Listing
January 2021

Frequency and spectrum of founder and non-founder BRCA1 and BRCA2 mutations in a large series of Russian breast cancer and ovarian cancer patients.

Breast Cancer Res Treat 2020 Nov 9;184(1):229-235. Epub 2020 Aug 9.

Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint-Petersburg, Russia.

Background: The spectrum of BRCA1 and BRCA2 mutations in Slavic countries is characterized by a high prevalence of founder alleles.

Methods: We analyzed a large data set of Russian breast cancer (BC) and ovarian cancer (OC) patients, who were subjected to founder mutation tests or full-length BRCA1 and BRCA2 analysis.

Results: The most commonly applied test, which included four founder mutations (BRCA1: 5382insC, 4153delA, 185delAG; BRCA2: 6174delT), identified BRCA1 or BRCA2 heterozygosity in 399/8533 (4.7%) consecutive BC patients, 230/2317 (9.9%) OC patients, and 30/118 (25.4%) women with a combination of BC and OC. The addition of another four recurrent BRCA1 mutations to the test (BRCA1 C61G, 2080delA, 3819del5, 3875del4) resulted in evident increase in the number of identified mutation carriers (BC: 16/993 (1.6%); OC: 34/1289 (2.6%); BC + OC: 2/39 (5.1%)). Full-length sequencing of the entire BRCA1 and BRCA2 coding region was applied to 785 women, very most of whom demonstrated clinical signs of BRCA-driven disease, but turned out negative for all described above founder alleles. This analysis revealed additional BRCA1 or BRCA2 mutation carriers in 54/282 (19.1%) BC, 50/472 (10.6%) OC, and 13/31 (42%) BC + OC patients. The analysis of frequencies of founder and "rare" BRCA1 and BRCA2 pathogenic alleles across various clinical subgroups (BC vs. OC vs. BC + OC; family history positive vs. negative; young vs. late-onset; none vs. single vs. multiple clinical indicators of BRCA1- or BRCA2-associated disease) revealed that comprehensive BRCA1 and BRCA2 analysis increased more than twice the number of identified mutation carriers in all categories of the examined women.

Conclusion: Full-length BRCA1 and BRCA2 sequencing is strongly advised to Slavic subjects, who have medical indications for BRCA1 and BRCA2 testing but are negative for recurrent BRCA1 and BRCA2 mutations.
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http://dx.doi.org/10.1007/s10549-020-05827-8DOI Listing
November 2020

Melatonin Administered before or after a Cytotoxic Drug Increases Mammary Cancer Stabilization Rates in HER2/Neu Mice.

Chemotherapy 2020 7;65(1-2):42-50. Epub 2020 Aug 7.

Department of Carcinogenesis and Oncogerontology, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health, St. Petersburg, Russian Federation.

Introduction: The effects of chemotherapy are known to depend on the time of administration. Circadian rhythms are disturbed in tumors and in tumor bearers. Agents involved in controlling the circadian rhythms (chronobiotics) potentially can modify the outcomes of chemotherapeutics administered at different times of the day. Pineal hormone melatonin (MT) is a prototypic chronobiotic.

Objective: The aim of the study was to investigate if MT can affect efficacy or toxicity of chemotherapy drugs administered at the extreme time points of the working day of hospital personnel.

Methods: Cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and adriamycin and docetaxel (AT) cytotoxic drug combinations were administered on day 0 at 11:00 a.m. or at 5:00 p.m. (UTC+03:00) to 6-month-old female HER2/neu transgenic FVB/N mice bearing mammary adenocarcinomas. Some mice were additionally provided with MT in drinking water (20 mg/L) at night 1 week before or 3 weeks after treatment or during both periods. Tumor node sizes, body weight, and blood cell counts were determined right before treatment and on days 2, 7, 14, and 21.

Results: Significant decrease in the mean tumor node volume was found by days 14 and 21 upon all CAF and AT treatment schedules, except in animals treated with AT at 5:00 p.m. without supplementation with MT. In the latter case, mean tumor node volume on day 21 was the same as in the control. Supplementation of AT administered at 5:00 p.m. with MT improved the tumor response. CAF and AT regimens supplemented with MT also augmented the number of tumor nodes that did not increase by more than 20% by day 21 as compared to CAF or AT alone, respectively. This effect was significant in groups treated with AT at 5:00 p.m. and consistent upon other schedules. On day 7, leukopenia and anemia were registered in groups treated with CAF regimen; however, blood cell counts normalized by day 14. Both CAF and AT were associated with drop in the body weight registered on day 7. Supplementation with MT did not affect changes of the body weight and blood counts.

Conclusions: MT supplementation to cytotoxic drugs can improve antitumor response, especially if it is blunted because of an inappropriate time of administration.
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http://dx.doi.org/10.1159/000509238DOI Listing
May 2021

Mitomycin C plus cisplatin for systemic treatment of recurrent BRCA1-associated ovarian cancer.

Invest New Drugs 2020 12 26;38(6):1872-1878. Epub 2020 Jun 26.

N.N. Petrov National Medical Research Center of Oncology, Leningradskaya, 68, Pesochny-2, 197758, St.-Petersburg, Russia.

Background Previous studies on neoadjuvant therapy for BRCA1-driven ovarian cancer (OC) demonstrated higher efficacy of mitomycin C plus cisplatin combination as compared to standard drug schemes. These data call for evaluation of the utility of this regimen for the treatment of recurrent BRCA1-associated OC. Methods The study included 12 BRCA1 germ-line mutation carriers, whose disease relapsed after one (n = 4) or two (n = 8) lines of chemotherapy. The patients received cisplatin 100 mg/m and mitomycin C 10 mg/m, given every four weeks, for 6 (n = 10), 8 (n = 1) or 5 (n = 1) cycles. Retrospective data on conventional treatment of OC relapses in BRCA1 heterozygotes (n = 47) served as a control. Results Grade 3-4 toxicities were observed in 4/12 (33%) cases. There were 6 complete responses (CR), 4 partial responses (PR) and 2 instances of stable disease (SD). Comparison of patients receiving mitomycin C plus cisplatin (n = 4) or conventional therapy (n = 44) at first relapse demonstrated marginal improvement of the progression-free survival (PFS) (16.6 months vs. 10.2 months, P = .067). Use of mitomycin C plus cisplatin (n = 8) for the treatment of second relapse resulted in significant prolongation of PFS as compared to standard regimens (n = 31) (14.8 months vs. 4.8 months, P = .002). Conclusions Mitomycin C plus cisplatin shows promising activity in recurrent BRCA1-driven ovarian cancer.
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http://dx.doi.org/10.1007/s10637-020-00965-8DOI Listing
December 2020

Comparative analysis of expression of mutant and wild-type alleles is essential for reliable PCR-based detection of MET exon 14 skipping.

Biochimie 2019 Oct 28;165:267-274. Epub 2019 Aug 28.

N.N. Petrov Institute of Oncology, St.-Petersburg, Pesochny, Leningradskaya 68, 197758, Russia; St.-Petersburg Pediatric Medical University, St.-Petersburg, Litovskaya 2, 194100, Russia; I.I. Mechnikov North-Western Medical University, St.-Petersburg, Kirochnaya street 41, 191015, Russia; St.-Petersburg State University, St.-Petersburg, Universitetskaya Naberezhnaya 7/9, 199034, Russia.

MET exon 14 skipping (exon 14Δ) mutations are associated with tumor sensitivity to a number of tyrosine kinase inhibitors, however clinical testing for MET gene status remains complicated. We developed a simple allele-specific PCR cDNA-based test, which allowed for the identification of MET exon 14Δ allele in 35 (2.5%) out of 1415 EGFR mutation-negative lung carcinomas (LCs). MET exon 14Δ was significantly associated with elderly age and non-smoking status of the patients. A total of 34 (97%) out of 35 tumors carrying MET exon 14Δ showed preferential expression of the mutated allele; this imbalance was attributed to the down-regulation of the expression of the wild-type gene copy. Sanger sequencing confirmed the presence of genomic exon 14 splice site mutations in 24/35 (68.6%) cases, which showed MET exon 14 skipping by PCR. In addition to LCs described above, some carcinomas demonstrated low-abundance MET exon 14Δ-specific signal. Low-level expression of MET exon 14Δ allele may potentially compromise the results of allele-specific PCR-based tests, therefore comparison of the level of expression of mutated and normal alleles is essential for the reliability of MET gene testing.
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http://dx.doi.org/10.1016/j.biochi.2019.08.014DOI Listing
October 2019

Productivity losses associated with premature mortality due to cancer in Russia: A population-wide study covering 2001-2030.

Scand J Public Health 2019 Jul;47(5):482-491

6 Section of Cancer Surveillance, International Agency for Research on Cancer, France.

Productivity losses related to premature cancer mortality have been assessed for most developed countries but results for Russia are limited to cross-sectional reports. The aim of this study was to quantify productivity costs due to cancer mortality in Russia between 2001 and 2015 and project this to 2030. : Cancer mortality data (2001-2015) were acquired from the State Cancer Registry, whereas population data, labour force participation rates and annual earnings were retrieved from the Federal State Statistics Service. Cancer mortality was projected to 2030 and the human capital approach was applied to estimate productivity losses. : The total annual losses increased from US6.5b in 2001-2005 to US$8.1b in 2011-2015, corresponding to 0.24% of the annual gross domestic product. The value is expected to remain high in 2030 (US$7.5b, 0.14% of gross domestic product). Productivity losses per cancer death are predicted to grow faster in women (from US$18,622 to US$22,386) than in men (from US$25,064 to US$28,459). Total losses were found to be highest for breast cancer in women (US$0.6b, 20% of overall losses in women) and lung cancer in men (US$1.2b, 24%). The absolute predicted change of annual losses between 2011-2015 and 2026-2030 was greatest for cervix uteri (+US$214m) in women and for lip, oral and pharyngeal cancers in men (+US$182m).
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http://dx.doi.org/10.1177/1403494819845565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651608PMC
July 2019

Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer.

Int J Gynecol Cancer 2018 10;28(8):1498-1506

N.N. Petrov Institute of Oncology.

Objectives: Cisplatin and mitomycin C exert high activity towards BRCA1-deficient cells. This study aimed to evaluate the efficacy of a combination of these drugs in hereditary BRCA1-associated ovarian cancer (OC).

Methods: Twelve OC patients, who could not be treated by primary debulking surgery owing to extensive tumor spread, were given neoadjuvant cisplatin (100 mg/m) and mitomycin C (10 mg/m) every 4 weeks for 3 (n = 9), 2 (n = 2), or 4 (n = 1) cycles.

Results: The decrease of tumor burden and complete surgical cytoreduction were achieved in all patients. Pathologic complete response, defined as the absence of tumor cells in surgically removed tissues, was observed in 2 (17%) of 12 cases. Retrospective analysis of 62 OC in BRCA1 mutation carriers subjected to conventional neoadjuvant chemotherapy schemes revealed 36 objective tumor responses (58%) and 37 instances (60%) of complete cytoreductive surgery; however, none of these patients demonstrated pathologic complete response.

Conclusions: The combination of cisplatin plus mitomycin C showed promising results in BRCA1-driven OC and therefore deserves further clinical evaluation.
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http://dx.doi.org/10.1097/IGC.0000000000001352DOI Listing
October 2018

Breast and cervical cancer incidence and mortality trends in Russia 1980-2013.

Cancer Epidemiol 2018 08 26;55:73-80. Epub 2018 May 26.

University of Tampere, Faculty of Social Sciences, Epidemiology Group, Arvo, Arvo Ylpön katu 34, 33520 Tampere, Finland. Electronic address:

Background: Breast and cervical cancer are among the leading causes of preventable cancer deaths in women in Russia. The aim of this study is to analyze changes in breast and cervical cancer incidence and mortality trends using data from the Russian State Cancer Registry.

Methods: The age-standardized rates of cervical cancer incidence (1993-2013) and mortality (1980-2013) were analyzed using piecewise linear regression. Age-period-cohort models were used to estimate the temporal effects and provide future predictions.

Results: Breast and cervical cancer incidence rates uniformly increased over two decades from 33.0 to 47.0 per 100,000 and from 10.6 to 14.2 per 100,000, respectively. Breast cancer mortality rates however declined from 17.6 to 15.7 in 2013, while cervical cancer mortality increased steadily from 5.6 to 6.7. Breakpoints in the risk occurred in cohorts born 1937-1953, indicating a recent generational decrease in breast cancer mortality, but a concomitant increase in cervical cancer. Cervical cancer has already surpassed breast cancer in terms of years of life lost (YLL) (23.4 per death vs 18.5 in 2009-2013), while future projections suggest that the annual YLL could reach 1.2 million for cervical cancer and (decline to) 1.8 million for breast cancer by the year 2030.

Conclusion: The temporal patterns of breast cancer incidence and mortality in Russia are in line with other countries in Europe, although cervical cancer rates and the risk of occurrence in recent generations is rapidly increasing; these trends underscore the need to place immediate priority in national cervical vaccination and screening programs.
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http://dx.doi.org/10.1016/j.canep.2018.05.008DOI Listing
August 2018

Results and prospects of development of new polyphenolic drugs for cancer patients.

Oncotarget 2017 Nov 7;8(59):100951-100956. Epub 2017 Nov 7.

N.N. Petrov National Medical Research Center of Oncology, Saint-Petersburg, Russia.

The conference "Results and prospects of development of new polyphenolic drugs for cancer patients" took place at the N.N. Petrov National Medical Research Center of Oncology (PNMRCO) on May 31, 2017, and gathered researchers involved in development and evaluation of medicinal products based on the novel lignin-derived soluble polyphenolic polymer BP-Cx-1. BP-Cx-1 is the platform for a portfolio of innovative pharmacological products such as BP-C1, BP-C2 and BP-C3.
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http://dx.doi.org/10.18632/oncotarget.22307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725075PMC
November 2017

Comparative efficacy evaluation of catheter intraperitoneal chemotherapy, normothermic and hyperthermic chemoperfusion in a rat model of ascitic ovarian cancer.

Int J Hyperthermia 2018 08 18;34(5):545-550. Epub 2017 Sep 18.

a Scientific Laboratory of Cancer Chemoprevention and Oncopharmacology , N.N. Petrov Research Institute of Oncology , St. Petersburg , Russia.

Objectives: The choice of an optimal administration route for intraperitoneal (IP) chemotherapy and a suitable chemotherapeutic regime in the treatment of ovarian cancer remains a controversy. We investigated survival outcomes according to catheter intraperitoneal chemotherapy (CIPC), normothermic and hyperthermic chemoperfusion (NIPEC and HIPEC) with cytostatic drugs dioxadet and cisplatin in rats with transplantable ascitic ovarian cancer.

Methods: Ascitic liquid containing 1 × 10 tumour cells was inoculated to female Wistar rats and 48 hours after rats received dioxadet and cisplatin at the maximum tolerated doses. Dioxadet at doses 1.5, 30 and 15 mg/kg and cisplatin at doses 4, 40 and 20 mg/kg body weight were administered for CIPC, NIPEC and HIPEC, respectively. Rats in the control groups received physiological saline and CIPC with physiological saline was regarded as the untreated control. The antitumor activity of the drugs was evaluated as an increase in average life expectancy (ALE). Analysis of the data was based primarily on Bayesian statistics and included Kaplan-Meier method, log-rank test and hazard ratio (HR) estimation.

Results: Compared to the untreated control CIPC, NIPEC and HIPEC with dioxadet significantly increased ALE by 13, 15 and 17 days, whereas with cisplatin by 10, 24 and 5 days, respectively.

Conclusions: Dioxadet and cisplatin show similar efficacy in the CIPC route. Compared with CIPC IP chemotherapy by chemoperfusions is more effective for both the drugs. Dioxadet in HIPEC showed highest survival benefit whereas largest effect during NIPEC is achieved with cisplatin.
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http://dx.doi.org/10.1080/02656736.2017.1375161DOI Listing
August 2018

Detection of BRCA1 gross rearrangements by droplet digital PCR.

Breast Cancer Res Treat 2017 Oct 27;165(3):765-770. Epub 2017 Jun 27.

N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.

Purpose: Large genomic rearrangements (LGRs) constitute a significant share of pathogenic BRCA1 mutations. Multiplex ligation-dependent probe amplification (MLPA) is a leading method for LGR detection; however, it is entirely based on the use of commercial kits, includes relatively time-consuming hybridization step, and is not convenient for large-scale screening of recurrent LGRs.

Materials And Methods: We developed and validated the droplet digital PCR (ddPCR) assay, which covers the entire coding region of BRCA1 gene and is capable to precisely quantitate the copy number for each exon.

Results: 141 breast cancer (BC) patients, who demonstrated evident clinical features of hereditary BC but turned out to be negative for founder BRCA1/2 mutations, were subjected to the LGR analysis. Four patients with LGR were identified, with three cases of exon 8 deletion and one women carrying the deletion of exons 5-7. Excellent concordance with MLPA test was observed. Exon 8 copy number was tested in additional 720 BC and 184 ovarian cancer (OC) high-risk patients, and another four cases with the deletion were revealed; MLPA re-analysis demonstrated that exon 8 loss was a part of a larger genetic alteration in two cases, while the remaining two patients had isolated defect of exon 8. Long-range PCR and next generation sequencing of DNA samples carrying exon 8 deletion revealed two types of recurrent LGRs.

Conclusion: Droplet digital PCR is a reliable tool for the detection of large genomic rearrangements.
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http://dx.doi.org/10.1007/s10549-017-4357-7DOI Listing
October 2017

Both heat and new chemotherapeutic drug dioxadet in hyperthermic intraperitoneal chemoperfusion improved survival in rat ovarian cancer model.

J Surg Oncol 2016 Mar 29;113(4):438-42. Epub 2015 Dec 29.

Department of Cancer Chemoprevention and Oncopharmacology in N.N. Petrov Research Institute of Oncology of the Russian Ministry of Health, 68, Leningradskaya Street, Pesochny, Saint-Petersburg, Russia.

Background And Objectives: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the time of Cytoreductive Surgery (CRS) is an actively researched treatment in patients with advanced ovarian cancer. Relative contribution of heat and chemotherapeutic agents during HIPEC as well as efficacy of a new agent dioxadet for regional chemotherapy in a rat model of ovarian cancer was studied.

Methods: Sixty rats were divided into three groups: no treatment control group (n = 19), hyperthermia without chemotherapy (HIPEP) (n = 14), HIPEC + cisplatin (n = 14), HIPEC + dioxadet (n = 13). The intra-abdominal tumor was not resected. End points were: median survival (primary), cause of death (secondary).

Results: The median survival of the animals in the control group, HIPEP group, HIPEC + cisplatin, HIPEC + dioxadet were 9 (CI; 8-23), 22.5 (CI; 12-43), 25.5 (CI; 13-62), 49 (Cl; 28-70) days, respectively. The P-values control versus HIPEP, HIPEC + cisplatin versus HIPEC + dioxadet were 0.006, 0.002, and 0.001, respectively.

Conclusion: During HIPEC both the heat and the cytotoxic drug had antitumor effects in a rat ovarian cancer model. Dioxadet showed potential as a drug for regional chemotherapy. J. Surg. Oncol. 2016;113:438-442. © 2015 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jso.24140DOI Listing
March 2016

Experimental study of antitumour activity and effects on leukocyte count of intraperitoneal administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet in a rat model of ovarian cancer.

J Chemother 2016 Jun;28(3):203-9

a N. N. Petrov Research Institute of Oncology of the Russian Ministry of Health , Saint-Petersburg , Russia.

Survival of rats with advanced ovarian cancer after intraperitoneal (i.p.) administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet and effects of these treatment modalities on leukocyte count were evaluated in two independent series of experiments. Hyperthermic intraperitoneal chemoperfusion with dioxadet (15 mg/kg) provided median survival of rats of 49 days (95% CI 28-70), i.p. administration of dioxadet (1.5 mg/kg) of 28 days (95% CI 16-36; P = 0.020). Single i.p. injection of dioxadet caused a significant decrease in total number of leukocytes (17-52%), granulocytes (18-75%), lymphocytes (18-62%) and monocytes (12-46%) in the peripheral blood of tumour-bearing rats compared to untreated animals. After HIPEC with dioxadet, the total number of leukocytes, granulocytes, lymphocytes and monocytes in peripheral blood of rats remained significantly higher than the corresponding values in the group with dioxadet.
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http://dx.doi.org/10.1179/1973947815Y.0000000040DOI Listing
June 2016

Note: tip enhanced Raman spectroscopy with objective scanner on opaque samples.

Rev Sci Instrum 2012 Jun;83(6):066102

Laboratory of Ferroelectric Nanoelectronics, INRS-EMT, 1650 Boul. Lionel-Boulet, Varennes J3X1S2 Québec, Canada.

We report on 14 nm lateral resolution in tip-enhanced Raman spectroscopy mapping of carbon nanotubes with an experimental setup that has been designed for the analysis of opaque samples in confocal side-access through a novel piezo-driven objective scanner. The objective scanner allows for fast and stable laser-to-tip alignment and for the adjustment of the focus position with sub-wavelength precision to optimize the excitation of surface plasmons. It also offers the additional benefit of imaging the near-field generated Raman scattering at the gap between tip and sample as direct control of the tip enhancement.
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http://dx.doi.org/10.1063/1.4725528DOI Listing
June 2012
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