In this phase I clinical trial cancer patients suffering from solid tumors or lymphomas, recurring after and/or refractory against standard treatment are treated intravenously (iv) with increasing doses of tTF-NGR(tTF= truncated tissue factor; NGR=Asn-Gly-Arg). The objectives of this trial are to evaluate the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of intravenously (iv) infused daily applications of tTF-NGR for 5 days every 3 weeks in patients with cancer, who had obtained all standard treatment known for their disease entity prior to entry on study. Further objectives are to determine the perfusion and vascular volume fraction of measurable tumor lesions versus normal reference tissue before and after tTF-NGR application by MRI as a biological surrogate parameter for biological activity of the investigational medicinal product (IMP), tTF-NGR, and to obtain pharmacokinetic data.

Start Date01 Mar 2017

Sponsor / Collaborator

Universitätsklinikum Münster

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100 Clinical Results associated with tTF-NGR(University of Münster)

100 Translational Medicine associated with tTF-NGR(University of Münster)

100 Patents (Medical) associated with tTF-NGR(University of Münster)

212

Literatures (Medical) associated with tTF-NGR(University of Münster)

02 Nov 2023·Human Reproduction

Impact of low- or moderate-risk gonadotoxic chemotherapy prior to testicular tissue freezing on spermatogonia quantity in human (pre)pubertal testicular tissue

Article

Author: Mirallié, Sophie ; Rondanino, Christine ; Daudin, Myriam ; Feraille, Aurélie ; Rives, Nathalie ; Brugnon, Florence ; Barbotin, Anne-Laure ; Giscard d'Estaing, Sandrine ; Dumont, Ludovic ; Liard, Agnès ; Bubenheim, Michael ; Ancelle, Amélie ; Roux, Christophe ; Schneider, Pascale

AbstractSTUDY QUESTIONWhat is the impact of low- or moderate-risk gonadotoxic chemotherapy received prior to testicular tissue freezing (TTF), and of the cancer itself, on spermatogonia quantity in testicular tissue from (pre)pubertal boys?SUMMARY ANSWERVincristine, when associated with alkylating agents, has an additional adverse effect on spermatogonia quantity, while carboplatin has no individual contribution to spermatogonia quantity, in testicular tissue of (pre)pubertal boys, when compared to patients who have received non-alkylating chemotherapy.WHAT IS KNOWN ALREADYThe improved survival rates after cancer treatment necessitate the inclusion of fertility preservation procedures as part of the comprehensive care for patients, taking into consideration their age. Sperm cryopreservation is an established procedure in post-pubertal males while the TTF proposed for (pre)pubertal boys remains experimental. Several studies exploring testicular tissue of (pre)pubertal boys after TTF have examined the tubular fertility index (TFI, percentage of seminiferous tubule cross-sections containing spermatogonia) and the number of spermatogonia per seminiferous tubule cross-section (S/T). All studies have demonstrated that TFI and S/T always decrease after the introduction of chemotherapeutic agents, especially those which carry high gonadotoxic risks such as alkylating agents.STUDY DESIGN, SIZE, DURATIONTesticular tissue samples from 79 (pre)pubertal boys diagnosed with cancer (from 6 months to 16 years of age) were cryopreserved between May 2009 and June 2014. Their medical diagnoses and previous chemotherapy exposures were recorded. We examined histological sections of (pre)pubertal testicular tissue to elucidate whether the chemotherapy or the primary diagnosis affects mainly TFI and S/T.PARTICIPANTS/MATERIALS, SETTING, METHODS(Pre)pubertal boys with cancer diagnosis who had been offered TTF prior to conditioning treatment for hematopoietic stem cell transplantation were included in the study. All the patients had previously received chemotherapy with low- or moderate-risk for future fertility. We have selected patients for whom the information on the chemotherapy received was complete. The quantity of spermatogonia and quality of testicular tissue were assessed by both morphological and immunohistochemical analyses.MAIN RESULTS AND THE ROLE OF CHANCEA significant reduction in the number of spermatogonia was observed in boys treated with alkylating agents. The mean S/T values in boys exposed to alkylating agents were significantly lower compared to boys exposed to non-alkylating agents (P = 0.018). In contrast, no difference was observed for patients treated with carboplatin as the sole administered alkylating agent compared to the group of patients exposed to non-alkylating agents. We observed an increase of S/T with age in the group of patients who did not receive any alkylating agent and a decrease of S/T with age when patients received alkylating agents included in the cyclophosphamide equivalent dose (CED) formula (r = 0.6166, P = 0.0434; r = −0.3759, P = 0.0036, respectively). The TFI and S/T decreased further in the group of patients who received vincristine in combination with alkylating agents (decrease of 22.4%, P = 0.0049 and P < 0.0001, respectively), but in this group the CED was also increased significantly (P < 0.0001). Multivariate analysis, after CED adjustment, showed the persistence of a decrease in TFI correlated with vincristine administration (P = 0.02).LIMITATIONS, REASONS FOR CAUTIONThis is a descriptive study of testicular tissues obtained from (pre)pubertal boys who were at risk of infertility. The study population is quite heterogeneous, with a small number of patients in each sub-group. Our results are based on comparisons between patients receiving alkylating agents compared to patients receiving non-alkylating agents rather than chemotherapy-naive patients. The French national guidelines for fertility preservation in cancer patients recommend TTF before highly gonadotoxic treatment. Therefore, all the patients had received low- or moderate-risk gonadotoxic chemotherapy before TTF. Access to testicular tissue samples from chemotherapy-naive patients with comparable histological types of cancer was not possible. The functionality of spermatogonia and somatic cells could not be tested by transplantation or in vitro maturation due to limited sample sizes.WIDER IMPLICATIONS OF THE FINDINGSThis study summarizes the spermatogonial quantity of (pre)pubertal boys prior to TTF. We confirmed a negative correlation between the cumulative exposure to alkylating agents and spermatogonial quantity. In addition, the synergistic use of vincristine in combination with alkylating agents showed a cumulative deleterious effect on the TFI. For patients for whom fertility preservation is indicated, TTF should be proposed for chemotherapy with a predicted CED above 4000 mg/m2. However, the data obtained from vincristine and carboplatin use should be confirmed in a subsequent study including more patients.STUDY FUNDING/COMPETING INTEREST(S)This study had financial support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. The sponsors played no role in the study. The authors declare no conflicts of interest.TRIAL REGISTRATION NUMBERN/A.

01 Nov 2023·Journal of Hospital Infection

Bacterial contamination of water used as thermal transfer fluid in fluid-warming devices

Article

Author: Indra, A ; Schnetzinger, M ; Kimberger, O ; Heger, F

INTRODUCTIONRecent reports implicated heater-cooler units (HCUs), which are used for warming infusions, blood or in extracorporeal membrane oxygenation devices, as a possible origin of healthcare-associated infections (HAIs) with potentially pathogenic bacteria, such as non-tuberculous mycobacteria [1]. This represents a source of contamination in a usually sterile setting.AIMTo analyse water from infusion heating devices (IHDs) for bacterial contamination, and to determine if IHDs are a potential source in the transmission of HAIs.METHODSThermal transfer fluid (TTF; 300-500 mL) was collected from the reservoirs of 22 independent IHDs and processed on different selective and non-selective media for colony count and identification of bacteria. Strains of Mycobacterium spp. were analysed by whole-genome sequencing.RESULTSBacterial growth was observed in all 22 TTF samples after cultivation at 22 °C and 36 °C. Pseudomonas aeruginosa was the most frequent pathogen identified, present in 13.64% (3/22) of samples at >100 colony-forming units/100 mL. Colonization with Mycobacterium chimaera, Ralstonia pickettii and Ralstonia mannitolilytica was detectable in 9.09% (2/22) of samples. Primary sequencing of the detected M. chimaera suggests a close relationship with a M. chimaera strain detected in an outbreak in Switzerland which led to the death of two patients.DISCUSSIONContamination of TTF represents a germ reservoir in a sensitive setting. Handling errors of IHDs may lead to the distribution of opportunistic or facultative bacterial pathogens, increasing the risk of transmission of nosocomial infections.

27 Sep 2023·Molecules (Basel, Switzerland)

A Rapid and Quantitative Method for Determining Seed Viability Using 2,3,5-Triphenyl Tetrazolium Chloride (TTC): With the Example of Wheat Seed.

Article

Author: Wang, Shuonan ; Zhou, Feng ; Qiu, Nianwei ; Zhong, Sunyaxin ; Wu, Mengmeng ; Sun, Jing ; Mao, Xinyue

Current colorimetric methods for quantitative determination of seed viability (SV) with 2,3,5-triphenyl tetrazolium chloride (TTC) have been plagued by issues of being cumbersome and time-consuming during the experimental process, slow in extraction and staining, and exhibiting inconsistent results. In this work, we introduced a new approach that combines TTC-staining with high-temperature extraction using dimethyl sulfoxide (DMSO). The optimization of the germination stage, TTC-staining method, and 1,3,5-triphenylformazan (TTF) extraction method were meticulously carried out as follows: When the majority of wheat seeds had grown the radicle, and the length of radicles was approximately equal to the seed length (24 h-germination), 2 g germinating seeds were placed into a beaker (20 mL) containing 5 mL 10 g·L^-1 TTC solution. The seeds were stained with TTC in the dark at 25 °C for 1 h. Following the staining, 1 mL 1 mol·L^-1 H₂SO₄ was added to stop the reaction for 5 min. The H₂SO₄ solution was then removed, and the seeds were gently rinsed with deionized water. Subsequently, the TTF produced in the seeds was extracted directly with 5 mL DMSO solution at 55 °C for 1 h. The absorbance of the extract was measured at 483 nm, and the index of SV was calculated according to a predetermined TTC calibration curve and expressed by mg TTC·g^-1 (seed)·h^-1. The new method has been demonstrated to be rapid, stable, and highly sensitive, as evidenced by the accurate measurement of seed viability with different aging degrees.

100 Deals associated with tTF-NGR(University of Münster)

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoma	Phase 1	-	University of Münster	-
Neoplasms	Preclinical	DE	University of Münster	01 Mar 2008

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02902237 (CTgov)	Phase 1	Malignant Solid Neoplasm \| Lymphoma	24	tTF-NGR	(eqspmtlqct) = rhzeeyezdn kphqgabkrq (udsohzagem, uncyaszgtc - owdwngepan) View more	-	08 Dec 2020
NCT02902237 (ESMO2020)	Phase 1	Neoplasms	17	tTF-NGR	uuraekkgno(escuxomffs) = Isolated Troponin T hs elevation occurred as DLT and was interpreted as sensitive early sign for myocardial cell hypoxia, valuable for prevention of clinically relevant side effects. yzuxbrslob (qaciqxazot ) View more	-	17 Sep 2020
NCT02902237 (Pubmed \| Cancers (Basel)) Manual	Phase 1	Neoplasms	17	tTF-NGR	(gidvxxwonw) = solated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae ucfsyzscpa (nuuihrlcee ) View more	Positive	07 Jun 2020

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