Can Kampo medicine prolong the life of metastatic colorectal cancer (MCRC) patients with chemotherapy?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15120-e15120
Author(s):  
K. Sasaki ◽  
K. Oono ◽  
K. Harada ◽  
T. Someya ◽  
Y. Takada ◽  
...  

e15120 Background: Many in vivo and in vitro studies have shown that Kampo medicine has various biological and immunological activities, including anti-cancer effect. However, we have little data on efficacy of survival period on MCRC patients (pts) with chemotherapy and Kampo therapy. The aim of this study was to evaluate the survival benefit on MCRC pts treated with Kampo medicine and chemotherapy. Methods: From 2002 to 2007, we treated 66 patients with MCRC. These patients were treated with chemotherapy (CPT-11 + S-1) and/or Kampo medicine (Jyuzen-Taiho-To, TJ-48) on out-patient basis. TJ-48 was given orally at a dose of 7.5g, three times daily. We randomly divided the MCRC pts following two treatment groups; chemotherapy plus Kampo medicine (Group A, n=33) and chemotherapy only (Group B, n=33). Results: Pts and tumor characteristics were much the same between the two groups at baseline. Pts treated with Kampo medicine in combination with chemotherapy (Group A) had a median survival of 20.5 months compared with 15 months for Group B (p=0.12). One and 2 years survival rates were 72% and 13%. No toxic death was reported. The overall 1, 2 and 3 years survival rate were 69, 24 and 12% respectively in Group A, 57, 0 and 0% in Group B. Adverse events did not increase in Group A. TJ-48 is low cost medicine ($1.8 / day). All patients were treated on an out-patient clinic. Conclusions: These results confirmed that the Kampo medicine is helpful and capable of prolonging the survival periods in pts with MCRC. No significant financial relationships to disclose.

2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.


TECHNOLOGY ◽  
2016 ◽  
Vol 04 (01) ◽  
pp. 60-69 ◽  
Author(s):  
Charles C. Sharkey ◽  
Jiahe Li ◽  
Sweta Roy ◽  
Qianhui Wu ◽  
Michael R. King

This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.


1976 ◽  
Vol 85 (6_suppl) ◽  
pp. 2-32 ◽  
Author(s):  
Thomas R. Van De Water

An experiment was designed to answer the question as to whether or not the neural elements of the statoacoustic ganglion complex have a trophic effect upon the histodifferentiation of the sensory structures of the embryonic mouse inner ear anlage as it develops in vitro. The embryonic inner ear anlage with associated otic mesenchyme and statoacoustic ganglion complex was excised from 11, 12, and 13-day CBA/C57 mouse embryos. The inner ear explants of each gestational age group were further divided into two groups: the first group “A” (with) statoacoustic ganglion was explanted to the organ culture system without further surgical intervention; the second group “B” (without) statoacoustic ganglion underwent further surgical manipulation during which their statoacoustic ganglion complexes were dissected away prior to explantation to in vitro. The explanted embryonic inner ears were allowed to develop in organ culture until the equivalent of gestation day 21 in vivo was reached for each group; then all cultures were fixed and histologically processed and stained by a nerve fiber stain, in combination with a stain for glucoprotein membranes. Each specimen was code labeled and scored for histodifferentiation of sensory structures. Light microscopic observations confirmed that in group “A” cultures, statoacoustic ganglion neurons and their nerve fibers were present in association with the developed sensory structures; neither ganglion cell neurons nor their nerve fibers were found to be present in the sensory structures that developed in the group “B” organ culture specimens. Quantification revealed no consistent trend of greater occurrence of any sensory structure in the groups of explants analyzed. The presence of such a trend would have signified the probable existence of a trophic effect of the statoacoustic ganglion neural elements upon development of inner ear sensory structures in the group “A” explants of the 11, 12, and 13-day embryo inner ear organ culture specimens when compared to the aganglionic group “B” cultures. Microscopic comparison of the sensory structures and their sensory hair cells that developed in the organ cultures revealed no differences in the quality of the histodifferentiation of either group “A” or group “B” explants. A base to apex pattern of histodifferentiation of the organ of Corti sensory structures, which has been described to occur in vivo, was noted to occur in the in vitro developed cochlear ducts of all of the explanted inner ears without respect to whether neural elements were present (“A”) or absent (“B”) during development. It was concluded from the quantification of histodifferentiation data and the above observation on the pattern of differentiation of Corti's organ that no trophic effect of neural elements of the statoacoustic ganglion complex influencing the histodifferentiation of sensory structures of 11, 12, and 13-gestation day mouse embryo inner ear explants as they differentiate in vitro could be demonstrated.


Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1383-1388 ◽  
Author(s):  
LL Lenny ◽  
R Hurst ◽  
J Goldstein ◽  
LJ Benjamin ◽  
RL Jones

Abstract Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha- galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.


2019 ◽  
Vol 31 (1) ◽  
pp. 198
Author(s):  
F. Kotarski ◽  
B. Zimmer ◽  
C. Wrenzycki

The sex ratio of newborn calves and embryos produced in vivo is ~1:1. However, numerous studies on bovine in vitro-produced embryos suggest that the sex ratio may differ from 1:1 and that the rate of development may be influenced by the sex of the embryo under certain culture conditions. The duration of sperm-oocyte interaction and sperm pre-incubation also affect the sex ratio of bovine embryos produced in vitro. It is well documented that in vitro male embryos reach the more advanced stages earlier than do their female counterparts. Selection of developmentally more advanced embryos in anticipation that they have a greater developmental capacity may be one of the underlying causes of the disproportionate number of males among offspring born after transfer of in vitro-produced embryos. The aim of the present study is to test whether a pre-incubation of sperm before IVF might improve the developmental rates and also influence the sex ratio of the resulting embryos. Bovine cumulus-oocyte complexes were recovered from abattoir-derived ovaries by the slicing method. After 24h of maturation, fertilization was realised using a standard protocol. Prior to IVF, sperm cells from 2 different bulls were treated as follows: sperm within group A were pre-incubated in IVF medium for one hour. This step was omitted for sperm in group B (control). After 19h of co-culture of COC and sperm, presumptive zygotes were cultured in SOFaa for a period of 7 days. Cleavage and developmental rates were recorded at Day 3 and 7 (Day 0=IVF). Day 7 blastocysts from all groups were sexed using bovine and Y chromosome-specific primers. Data were analysed by ANOVA. As shown in Table 1, sperm pre-incubation did not affect the cleavage and developmental rates for the individual bull (P>0.05). On average, at Day 7 of development a higher number of blastocysts was determined when embryos had been produced from pre-incubated sperm (P ≤ 0.05). This held true for both bulls. The shift in favour of male embryos was detectable in all groups of embryos, with a drastic one for bull 1 after sperm pre-incubation. In conclusion, sperm pre-incubation accelerated embryo development and possibly enhanced the proportion of male embryos, which was already shifted toward males. Table 1.Developmental rates, developmental kinetics and sex ratio of embryos after sperm pre-incubation before IVF (mean±standard deviation)


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 547
Author(s):  
Mariangela Garofalo ◽  
Laura Bertinato ◽  
Monika Staniszewska ◽  
Magdalena Wieczorek ◽  
Stefano Salmaso ◽  
...  

Malignant melanoma, an aggressive form of skin cancer, has a low five-year survival rate in patients with advanced disease. Immunotherapy represents a promising approach to improve survival rates among patients at advanced stage. Herein, the aim of the study was to design and produce, by using engineering tools, a novel oncolytic adenovirus AdV-D24- inducible co-stimulator ligand (ICOSL)-CD40L expressing potent co-stimulatory molecules enhancing clinical efficacy through the modulation of anti-cancer immune responses. Firstly, we demonstrated the vector’s identity and genetic stability by restriction enzyme assay and sequencing, then, by performing in vitro and in vivo pre-clinical studies we explored the anti-cancer efficacy of the virus alone or in combination with anti PD-1 inhibitor in human melanoma cell lines, i.e., MUG Mel-1 and MUG Mel-2, and in immunocompetent C57BL/6 melanoma B16V mouse model. We showed that both monotherapy and combination approaches exhibit enhanced anti-cancer ability and immunogenic cell death in in vitro settings. Furthermore, AdV-D24-ICOSL-CD40L combined with anti PD-1 revealed a fall in tumor volume and 100% survival in in vivo context, thus suggesting enhanced efficacy and survival via complementary anti-cancer properties of those agents in melanoma therapy. Collectively, the novel oncolytic vector AdV-D24-ICOSL-CD40L alone or in combination with anticancer drugs, such as check point inhibitors, may open novel therapeutic perspectives for the treatment of melanoma.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eva Blank ◽  
Jasmin Grischke ◽  
Andreas Winkel ◽  
Joerg Eberhard ◽  
Nadine Kommerein ◽  
...  

Abstract Background Peri-implant mucositis and peri-implantitis are highly prevalent biofilm-associated diseases affecting the tissues surrounding dental implants. As antibiotic treatment is ineffective to fully cure biofilm mediated infections, antimicrobial modifications of implants to reduce or prevent bacterial colonization are called for. Preclinical in vivo evaluation of the functionality of new or modified implant materials concerning bacterial colonization and peri-implant health is needed to allow progress in this research field. For this purpose reliable animal models are needed. Methods Custom made endosseous dental implants were installed in female Sprague Dawley rats following a newly established three-step implantation procedure. After healing of the bone and soft tissue, the animals were assigned to two groups. Group A received a continuous antibiotic treatment for 7 weeks, while group B was repeatedly orally inoculated with human-derived strains of Streptococcus oralis, Fusobacterium nucleatum and Porphyromonas gingivalis for six weeks, followed by 1 week without inoculation. At the end of the experiment, implantation sites were clinically assessed and biofilm colonization was quantified via confocal laser scanning microscopy. Biofilm samples were tested for presence of the administered bacteria via PCR analysis. Results The inner part of the custom made implant screw could be identified as a site of reliable biofilm formation in vivo. S. oralis and F. nucleatum were detectable only in the biofilm samples from group B animals. P. gingivalis was not detectable in samples from either group. Quantification of the biofilm volume on the implant material revealed no statistically significant differences between the treatment groups. Clinical inspection of implants in group B animals showed signs of mild to moderate peri-implant mucositis (4 out of 6) whereas the mucosa of group A animals appeared healthy (8/8). The difference in the mucosa health status between the treatment groups was statistically significant (p = 0.015). Conclusions We developed a new rodent model for the preclinical evaluation of dental implant materials with a special focus on the early biofilm colonization including human-derived oral bacteria. Reliable biofilm quantification on the implant surface and the symptoms of peri-implant mucositis of the bacterially inoculated animals will serve as a readout for experimental evaluation of biofilm-reducing modifications of implant materials.


Blood ◽  
1957 ◽  
Vol 12 (10) ◽  
pp. 883-906 ◽  
Author(s):  
WOLF W. ZUELZER ◽  
FLOSSIE COHEN ◽  
ABNER R. ROBINSON ◽  
KATHRYN BEATTIE

Abstract A "study in depth" is reported concerning the case of hemolytic disease of a group B infant born to a group O mother, whose group A twin was apparently unaffected. It was shown that the hemolytic disease of the affected infant was due to a specific anti-B antibody. The study included parallel examinations of the antibodies in the sera of the three individuals. The specificity of the B-anti-B reaction was demonstrated in vitro and in vivo. The powerful anti-B antibody of the mother had no effect on the group A twin, in whose serum anti-B was present in large amounts. In vitro, studied by the usual technics of cross absorption the maternal and the fetal anti-A and anti-B serum antibodies behaved as if strictly specific. By applying successive absorption, elution and neutralization techniques, however, it was possible to demonstrate additional cross-reacting antibodies in the maternal serum which could be separated from one another and from the specific anti-A and anti-B antibodies. From the erythrocytes of the normal group A twin such cross-reacting antibody could be eluted. The cross-reacting anti-B antibody, isolated in pure form in eluates, could be shown to be loosely attached to group A erythrocytes without producing visible agglutination reactions while after elution from A cells it did visibly agglutinate group B cells. It could be eluted from A cells, absorbed by fresh A cells and reeluted while retaining its anti-B effect. It was neutralized by group B saliva only. A separate anti-A antibody with similar properties was eluted from B cells and specifically neutralized by group A saliva. A partial affinity of these antibodies for heterologous erythrocytes but not for specific soluble substances was thus demonstrated. These findings support neither the linkage hypothesis of cross reactions between anti-A and anti-B nor the C-anti-C hypothesis of hemolytic disease. They are in keeping with the view that group O sera contain variable complexes of anti-A and anti-B antibodies, composed of multiple fractions with different partial specificities. It is suggested that the occurrence or non-occurrence of cross-reacting antibodies found in sera of group O mothers whose infants develop hemolytic disease is best explained on this basis. It is further stressed that the demonstration of an antibody in mother or child in ABO hemolytic disease does not necessarily indicate its pathologic significance.


2020 ◽  
Author(s):  
Shuai Li ◽  
Huifang Zhao ◽  
Xiaobo Han ◽  
Lang He ◽  
Omar Mukama ◽  
...  

Abstract BackgroundNeural stem cells(NSCs)therapy remains one of the most potential approaches for neurological disorders treatment. The discovery of human induced pluripotent stem cells (hiPSCs) and the establishment of hiPSC-derived human neural stem cells (hiNSCs) have revolutionized our technique to cell therapy. Meanwhile, it is often required that NSCs are stored and transported long distances for research or treatment. Although high survival rates could be maintained, conventional methods of cell transport (dry ice or liquid nitrogen) are inconvenient and expensive. Therefore,the establishment of a safe, affordable, and frequent obtained hiPSCs and hiNSCs, with characteristics that match fetal hNSCs and a simple, low-cost way to store and transport, are incredibly urgent. MethodsWe reprogrammed human urinary cells to iPSCs using a virus-free technique and differentiated the iPSCs toward iNSCs/neurospheres and neurons, under Good Manufacturing Practice (GMP)-compatible conditions. The pluripotency of iPSCs and iNSCs was characterized by a series of classical methods (surface markers, karyotype analysis and in vitro and in vivo differentiation capabilities, etc).ResultsHere, our results showed that we successfully generated hiNSCs/neurospheres from more available, non-invasive, and more acceptable urinary cells by a virus-free technique and their differentiation into neural networks. Moreover,hiNSCs survived longer as neurospheres at ambient temperature than those cultured in a monolayer. Approximately 7 days, the neural viability remained at > 80%, while hiNSCs cultured in a monolayer died almost immediately. Neurospheres exposed to ambient temperature that were placed under standard culture conditions (37 ℃, 5% CO2) recovered their typical morphology, and retained their ability to proliferate and differentiate. ConclusionsIn this study, we provided a simple method for the storage of NSCs as neurospheres at ambient temperature as an alternative to more costly and inconvenient traditional methods of cryopreservation. This will enable hiNSCs to be transported over long distances at ambient temperature and facilitate the therapeutic application of NSCs as neurospheres without any further treatment.


2006 ◽  
Vol 91 (8) ◽  
pp. 3181-3188 ◽  
Author(s):  
Guneet Makkar ◽  
Ernest H. Y. Ng ◽  
William S. B. Yeung ◽  
P. C. Ho

Abstract Context: Impaired implantation in assisted reproduction cycles with high serum estradiol (E2) concentrations may be related to abnormal endometrial functions. Objective: The in vivo expression of T helper type 2 (Th2) cytokines in the periimplantation endometrium of infertile patients was compared between natural and stimulated cycles. Interventions and Main Outcome Measures: Uterine flushings and endometrial biopsies were collected 7 d after the LH surge in natural cycles or after human chorionic gonadotropin injection in stimulated cycles. Th2 cytokines were determined by immunolocalization and by ELISA. Natural cycles were in group A, whereas stimulated cycles with peak serum E2 of no more than 20,000 pmol/liter (moderate responders) and more than 20,000 pmol/liter (excessive responders) were classified as group B and group C, respectively. Results: Higher E2 had a negative effect on IL-11 and IL-6 expression in the endometrium and IL-11 concentration in the uterine flushing. In endometrial biopsies, a significantly lower immunostaining of stromal IL-11 (P < 0.001) and glandular IL-6 (P < 0.05) was detected in group C compared with that of groups A and B. IL-11 concentration by ELISA was significantly lower in group C (P < 0.05). Endometrial leukemia inhibitory factor and IL-4 expression was similar in the three groups. In uterine flushings, a significantly higher percentage of women in group C had undetectable IL-11 and a lower IL-11 concentration (P < 0.01) compared with group A, whereas no difference in IL-6 concentration was noted in the three groups. Conclusion: Reduced expression of IL-11 and IL-6 in periimplantation endometrium may account for lower implantation in excessive responders.


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