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Biomedical subjects

T Onishi

Publications and source records attributed to T Onishi.

At least 73 records · Page 4Linked to original sources
PubMed1999

Papillary renal cell carcinoma: clinicopathological characteristics and evaluation of prognosis in 42 patients.

OBJECTIVE: To determine the clinicopathological characteristics of histologically defined papillary renal cell carcinoma (RCC) in relation to prognosis. PATIENTS AND METHODS: In total, 768 patients with RCC underwent nephrectomy at our university hospital between 1957 and 1995. RCC was classified into clear-cell carcinoma in 689 patients (89.7%, no follow-up in 14), chromophobe cell carcinoma in 36 (4.7%, no follow-up in two) and papillary RCC in 43 (5.6%, no follow-up in one). In the present study, the 42 patients with papillary RCC who underwent nephrectomy and were followed up were those in whom the clinicopathological features of the papillary RCC were assessed. Factors assessed were the presence or absence of foam-cell infiltration, occurrence of bleeding and/or necrosis, presence or absence of a pseudocapsule, mixed occurrence with clear-cell carcinoma, presence or absence of solid variants, cytoplasmic appearance (basophilic vs eosinophilic cells), stage, nuclear grade of malignancy, and angiographic appearance in relation to prognosis. The prognosis was also compared among patients with clear-cell, chromophobe cell and papillary RCC. RESULTS: The prognosis was significantly better in patients with foam-cell infiltration (P=0.03), with a pseudocapsule (P=0.07), with no solid variants (P=0.001) and with basophilic cells (P<0.001). There were also significant differences in survival between patients with low-stage (1+2) and high-stage (3+4) disease (P=0.003), and among grades 1-3 (grade 1 vs 2, P=0.05; grade 1 vs 3, P<0.001, grade 2 vs 3, P=0.006). Furthermore, the prognosis in patients with papillary RCC was worse than in those with chromophobe cell carcinoma (P=0.02), but there was no significant difference in survival between patients with papillary RCC and those with clear-cell carcinoma. CONCLUSION: The clinicopathological features (e.g. the presence or absence of foam cells, of a pseudocapsule and of solid variants, cytoplasmic appearance, and the stage and nuclear grade of malignancy) are important prognostic factors for patients with papillary RCC. Furthermore, the prognosis in patients with papillary RCC is similar to those with clear-cell carcinoma.

Adolescent↗
PubMed1999

An assessment of the immunological environment based on intratumoral cytokine production in renal cell carcinoma.

OBJECTIVE: To assess the immunological relationship between tumour and host, focusing on the production of T-cell helper (Th) subset-derived cytokines in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 35 patients (19 men and 16 women, mean age 56.9 years, range 39-78) with RCC, who had undergone nephrectomy. Using enzyme-linked immunosorbent assays, the levels of Th1-derived cytokines were measured, including interleukin (IL)-2 and interferon (IFN)-gamma, and Th2-derived cytokines, including IL-4, IL-5, IL-6, IL-10 and others. RESULTS: There was no detectable IL-2 or IFN-gamma production (below the detection limit) except in two patients; IL-4 was produced in 18 patients (51%) and of these, 15 (43%) showed a higher level than the mean. IL-5 was produced in 12 patients (34%), all of whom showed a higher level than the mean, and IL-6 was produced in 32 (91%) of whom 10 (29%) showed a higher level than the mean. IL-10 was detected in 28 patients (80%) of whom 14 (40%) showed a higher level than the mean. The production of these cytokines was closely related to the stage and grade of malignancy. Furthermore, there were significant correlations between the levels of production of IL-4 and IL-5 (r2=0.92), IL-4 and IL-10 (r2=0.91), and IL-5 and IL-10 (r2=0.85). CONCLUSION: The intratumoral immunological environment in patients with RCC shows a tendency to produce Th2-related cytokines in accordance with the stage and grade; this suggests a role in humoral but not in cellular immunity.

Adult↗
PubMed1999

Cloning of feline cDNA encoding the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a CD28 homologue which down-modulate T cell responses rather than augment them. To investigate its biological role in feline immune system, we cloned and sequenced full-length feline CTLA-4 (fCTLA-4) cDNA by RT-PCR from pokeweed mitogen stimulated peripheral blood lymphocytes. The fCTLA-4 contains an open reading frame of 669 nucleotides, coding for a polypeptide of 223 amino acids. The predicted fCTLA-4 amino acids sequence shows the homology of 86.6%, 87.0%, and 76.2% with human, bovine, and murine molecules respectively. The hexapeptide motif (MYPPPY) within the extra-cellular domain of CTLA-4 molecule, which is believed to be responsible for interaction with the B7 family members, is completely conserved in all the species.

Abatacept↗
PubMed1999

Duration of antibodies against 24 kd protein of Rhipicephalus sanguineus extract in dogs infested with the adult ticks.

A 24 kd protein from Rhipicephalus sanguineus (Rs24p) which was common to larvae, nymphs, male and female whole body and salivary gland extract of males and female was detected specifically in the serum from dogs after repeated infestation with adult R. sanguineus. The duration of antibodies against Rs24p in dogs infested with adults was examined by Western blotting analysis. Anti-Rs24p antibody was detected in two of 4 dogs during the period of 40 days in the first infestation. In the second infestation, all dogs showed positive reaction against Rs24p, but the duration of the antibodies varied greatly among the animals.

Animals↗
PubMed1999

Expression of recombinant feline serum amyloid A (SAA) protein.

Feline serum amyloid A (SAA) cDNA clone was isolated from a hepatic mRNA of a mixed-breed cat. The feline SAA cDNA clone contains 333 nucleotides and deduced amino acid sequence shows 87.4%, 73.9%, and 65.8% homology with dog, human and mouse SAA respectively. Relative to the human and mouse SAA proteins, an additional peptide of eight amino acids is specified in the feline cDNA clone. Recombinant feline SAA (rfSAA) was expressed at high levels using pGEX bacterial expression system. Cleavage from the fusion moiety, and purification using glutathione-sepharose yielded pure soluble form of rfSAA. Antibodies generated against rfSAA were specific for feline SAA and showed no cross-reactivity with human SAA. Furthermore, antibodies against human SAA did not react with feline SAA. These results indicate that antigenicity of feline SAA is totally different from human SAA.

Amino Acid Sequence↗
PubMed1999

Cloning of a full length cDNA encoding canine Interleukin-4.

Primer designed on the basis of the conserved transcription start point (tsp) region of human and bovine gene transcripts, encoding the Interleukin-4 (IL-4), and subsequently the gene specific primer and an adaptor primer pair, was successfully used, to generate the full-length complementary DNA (cDNA) sequence coding for canine IL-4 (cIL-4), from pokeweed mitogen stimulated canine peripheral blood lymphocytes. The full-length cIL-4 contains an open reading frame of 399 nucleotides (nt), with a 5' ends of 66 base pairs (bp) and 3' ends of 125 bp. The nucleotide sequence contains six possible Asn-X-Thr or Asn-X-Ser linked glycosylation sites. Five sequence motifs of TATT or ATTTA, responsible for the regulation of gene expression, are found in the 3' untranslated region.

Amino Acid Sequence↗
PubMed1999

Localization of Smads, the TGF-beta family intracellular signaling components during endochondral ossification.

Members of the transforming growth factor-beta (TGF-beta) family transduce signals from the cell membrane to the nucleus via specific type I and type II receptors and Smad proteins. Smad1 and Smad5 mediate intracellular signaling of bone morphogenetic protein (BMP), whereas Smad2 and Smad3 transduce TGF-beta signaling. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 inhibit signaling by members of the TGF-beta superfamily. Here, we examined the expression of Smad1 to Smad7 proteins during endochondral ossification of epiphyseal plate of growing rats using immunohistochemical techniques. The expression of Smad proteins was correlated with the expression of TGF-beta1 and its receptors, and BMP-2/4 and BMP receptors. The results show that TGF-beta1 and BMP-2/4 were actively expressed in chondrocytes that are undergoing proliferation and maturation, which overlaps with expression of their corresponding type I and type II receptors. The Smads, however, exhibited a distinct expression pattern, respectively. For example, Smad1 and Smad5 were highly expressed in proliferating chondrocytes and in those chondrocytes that are undergoing maturation. The TGF-beta/activin-restricted Smads were also expressed in a nearly complementary fashion; Smad2 was strongly expressed in proliferating chondrocytes, whereas Smad3 was strongly observed in maturing chondrocytes. Smad4 was broadly expressed in all zones of epiphyseal plate. Inhibitory Smads, Smad6 and Smad7, were strongly expressed in the zone of cartilage that contained mature chondrocytes. Our findings show a colocalization of the pathway-restricted and inhibitory Smads with activating ligands or ligands whose action they antagonize and their receptors in various zones of epiphyseal growth plate, suggesting that TGF-beta superfamily Smad signaling pathways plays a morphogenic role during endochondral bone formation.

Activin Receptors, Type I↗
PubMed1999

[Clinical studies on inverted papilloma of the urinary tract].

BACKGROUND: Inverted papilloma of the urinary tract is believed to be a benign neoplasm based on its histologic morphology and clinical behavior. In recent years, however, several investigators have warned against too optimistic an approach, emphasizing the possibility of malignant cellular transformation within the lesion, or its eventual association with other urothelial tumors such as transitional cell carcinoma or carcinoma in situ. We here report on 35 clinicopathologically diagnosed cases of inverted papilloma, and present the clinical significance attributed to these lesions in view of the current literature. PATIENTS AND METHODS: From 1976 to 1997, 35 cases of inverted papilloma of the urinary tract were treated at our hospital. This report presents the clinical features of these cases, the results of prognosis research, an investigation of the cases in which inverted papilloma and transitional cell carcinoma were found to co-exist, and a discussion of the recurrent cases of inverted papilloma found in previous literature. RESULTS: The patients ranged from 24 to 77 years of age, with a mean of 54 years, and included 4 women and 31 men. The most frequently occurring symptom was grosshematuria, and more than 90% of the 35 cases occurred in the bladder. In 2 of the 35 cases, transitional cell carcinoma coexisted with the inverted papilloma, at a different location in the bladder in one case and within the same neoplasm in the ureter in the other case. Clinical courses after treatment were followed in 29 of the 35 cases, with a follow-up period of from 8 months to 19 years (mean follow-up, 5 years and 4 months). Of these 29 cases, 2 showed recurrence, one at 16 and one at 30 months after the initial resection. Many previous reports show that the association of inverted papilloma and transitional cell carcinoma is stronger in the upper urinary tract and recurrence of inverted papilloma almost always happens with 2 years. CONCLUSION: This study suggests that some cases of urinary inverted papilloma show recurrence or malignant potential. Our results indicate that all cases of urinary inverted papilloma should be treated and followed as cases of low-grade transitional cell carcinomas. Consequently, all cases must be followed for two years or more after the initial operation.

Adult↗
PubMed1998

Decreased circulating levels of vitamin K and 25-hydroxyvitamin D in osteopenic elderly men.

Changes in the circulating factors participating in involutional osteoporosis have been intensively investigated in women, but little is known about this in men. We investigated the possible participation of circulating factors including testosterone, vitamin D metabolites, and vitamins K1 and K2 in osteopenia in elderly men. In a group of 27 ambulatory men aged 74 +/- 10 years (mean +/- SD; range, 60 to 90), the bone mineral density (BMD) of the second to fourth lumbar vertebrae was measured by dual-energy x-ray absorptiometry (DXA) and expressed as a Z score, the age-adjusted BMD value for the Japanese population (mean +/- SD, 0 +/- 1). Although the plasma level of total testosterone significantly decreased with age in the group, it did not significantly correlate with the Z score. However, the plasma levels of 25-hydroxyvitamin D (25-OHD), phylloquinone, menaquinone-7 (MK-7), and albumin were significantly positively correlated with the Z score. Moreover, plasma 25-OHD and both phylloquinone and MK-7 were significantly positively correlated in the subjects. These observations suggest that depressed circulating levels of 25-OHD and vitamin K concomitantly and cooperatively participate in osteopenia in elderly men, which may reflect the etiology of the type II moiety of involutional osteoporosis.

Aged↗
PubMed1998

Distinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in rats.

Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are thought to play an important role in bone morphogenesis. The purpose of this study was to determine the locations of BMP-2/-4, osteogenic protein-1 (OP-1, also termed BMP-7), and BMP type II receptor (BMPR-II) during rat fracture healing by immunostaining, and thereby elucidate the possible roles of the BMPs and BMPR-II in intramembranous ossification and endochondral ossification. In the early stage of fracture repair, the expression of BMP-2/-4 and OP-1 was strongly induced in the thickened periosteum near the fracture ends, and coincided with an enhanced expression of BMPR-II. On day 7 after fracture, staining for BMP-2/-4 and OP-1 immunostaining was increased in various types of chondrocytes, and was strong in fibroblast-like spindle cells and proliferating chondrocytes in endochondral bone. On day 14 after fracture, staining with OP-1 antibody disappeared in proliferating and mature chondrocytes, while BMP-2/-4 staining continued in various types of chondrocytes until the late stage. In the newly formed trabecular bone, BMP-2/-4 and OP-1 were present at various levels. BMPR-II was actively expressed in both intramembranous ossification and endochondral ossification. Additionally, immunostaining for BMP-2/-4 and OP-1 was observed in multinucleated osteoclast-like cells on the newly formed trabecular bone, along with BMPR-II. In reference to our previous study of BMP type I receptors (BMPR-IA and BMPR-IB), BMPR-II was found to be co-localized with BMPR-IA and BMPR-IB. BMP-2/-4 and OP-1 antibodies exhibited distinct and overlapping immunostaining patterns during fracture repair. OP-1 may act predominantly in the initial phase of endochondral ossification, while BMP-2/-4 acts throughout this process. Thus, these findings suggested that BMPs acting through their BMP receptors may play major roles in modulating the sequential events leading to bone formation.

Animals↗
PubMed1998

AMY-1, a novel C-MYC binding protein that stimulates transcription activity of C-MYC.

BACKGROUND: The c-myc proto-oncogene has been suggested to play key roles in cell proliferation, differentiation, transformation and apoptosis. A variety of functions of C-MYC, the product of c-myc, are attributed to protein-protein interactions with various cellular factors including Max, YY1, p107, Bin1 and TBP. Max and YY1 bind to the C-terminal region of C-MYC, while p107, Bin1 and TBP bind to the N-terminal region covering myc boxes. The N-terminal region is involved in all the biological functions of C-MYC, and different proteins are therefore thought to interact with the N-terminal region of C-MYC to display different functions. RESULTS: We cloned two cDNAs which encode a novel C-MYC-binding protein of 11 kDa, designated AMY-1 (Associate of C-MYC). The two cDNAs, AMY-1L and AMY-1S, derived from alternative usage of polyadenylation signals, code for the same protein of 11 kDa. AMY-1 was bound via its C-terminal region to the N-terminal region of C-MYC (amino acids nos 58-148) corresponding to the transactivation domain. AMY-1 was localized in the cytoplasm in cells expressing c-myc at low levels, but in the nucleus in the cells of a high c-myc expression in transiently transfected cells. A similar difference in endogenous AMY-1 localization was observed during the cell cycle: AMY-1 translocated from cytoplasm to nucleus during the S phase when c-myc expression was increased. AMY-1 by itself did not recognize the E-box element, the MYC/Max binding sequence, nor did it transactivate via the element, but stimulated the activation of E-box-regulated transcription by MYC/Max. FISH analyses revealed that the amy-1 gene was located at 1p32.2-1p33 in human genome. CONCLUSIONS: AMY-1 is a 11 kDa protein which binds to the N-terminal region of C-MYC and stimulates the activation of E-box-dependent transcription by C-MYC. AMY-1, which mostly localizes in the cytoplasm, translocates into the nucleus in the S phase of the cell cycle upon an increase of c-myc expression, and may thus control the transcriptional activity of C-MYC.

Amino Acid Sequence↗
PubMed1998

Effects of infestation by Rhipicephalus sanguineus on lymphocyte blastogenic responses to mitogens in dogs.

Mitogen blastogenic responses of lymphocytes from dogs infested with adult Rhipicephalus sanguineus and the effects of salivary gland extracts (SGE) of the tick on the blastogenic responses of lymphocytes from normal dogs were studied. Infestation by R. sanguineus significantly suppressed concanavalin A, phyto-hemagglutinin and pokeweed mitogen responses of lymphocytes from dogs. The inhibition of lymphocyte responses of dogs in the first infestation was greater than that in the second infestation. SGE from R. sanguineus also suppressed all mitogen blastogenic responses of lymphocytes from healthy dogs in vitro. These suppressive effects of SGE on the blastogenic responses of PBL to mitogens were significantly inhibited by trypsin digestion. It is suggested that some proteins in SGE contribute to the suppressive effects of SGE on the blastogenic responses of peripheral blood lymphocytes from dogs.

Animals↗
PubMed1998

[Study on the relationship between tumour necrosis factor gene polymorphism and prognosis in the patients with renal cell carcinoma].

BACKGROUND: Clinical significance of polymorphism of tumour necrosis factor (TNF) genes encoded on the short arm of the 6th chromosome in the patients with renal cell carcinoma (RCC) has not been evaluated well so far. We studied on the TNF genes polymorphism of RCC focusing on the relationship between the genetic polymorphism and the prognosis. METHODS: The subjects were seventy-three patients with RCC treated at our hospitals during the past 20 years. The genomic DNA was examined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) from frozen peripheral blood of these patients. The items examined were the genetic polymorphisms of TNF-alpha (alpha 1, alpha 2) and TNF-beta (beta 1, beta 2), and we tried to study on the prognostic outcome of RCC based upon each zygote of TNF. RESULTS: 1) The proportion of TNF-alpha and TNF-beta polymorphisms: We observed TNF-alpha 1/1 homozygote in 71 patients (97.3%). As to TNF-beta polymorphism, we observed TNF-beta 2/2 homozygote in 33 patients (45.2%), TNF-beta 1/2 heterozygote in 31 (42.5%) and TNF-beta 1/1 homozygote in 9 (12.3%). The proportion of TNF-beta polymorphism was almost the same as that of healthy Japanese. 2) PROGNOSIS: Regarding the 17-year survival, all patients with TNF-beta 1/1 homozygote were alive, and we observed a significantly favourable prognosis in the patients with TNF-beta 1/1 homozygote compared with other zygotes of TNF-beta polymorphism. The reasons for these favourable prognosis were thought that the patients with TNF-beta 1/1 homozygote showed much lower stage and/or grade than those of other zygotes. CONCLUSION: We conclude that the TNF-beta gene polymorphism is a useful marker for understanding the prognosis of RCC and a part of cellular immunity related to the tumour and its host.

Adult↗
PubMed1998

[Study on the relationship between vascular invasion and prognosis in patients with locally confined renal cell carcinoma].

BACKGROUND: There exists controversy concerning the relationship between the vascular invasion and the prognosis in the locally confined renal cell carcinoma (RCC). We have tried to study on the relationship between the vascular invasion and the prognosis in these patients. METHODS: Of the five hundred and forty-eight patients with RCC who did not have lymph node and distant metastasis, the 464 patients without having the micro- and/or macro-vascular invasion (tumour thrombus) were analysed as the control, and the remaining 85 with micro- and/or macro-vascular invasion were subject to this study. RESULTS: There observed a significantly favourable prognosis in the patients with RCC who did not have the vascular invasion (pV0) compared with the patients who had the vascular invasion (pV1a: n = 43, P = 0.00068, pV1b: n = 34, 0 < P < 0.00006, pV2: n = 8, P = 0.012). Furthermore, the patients with pV1a showed a significantly favourable prognosis compared with the patients with pV1b (p = 0.00032), and the patients with pV2 (0 < P < 0.00006), and the patients with pV1b (P = 0.00032), and the patients with pV2 (0 < P < 0.00006), and the patients with pV1b also showed a significantly favourable prognosis compared with the patients with pV2 (0 < P < 0.0006). As to the relationship between the tumour size and vascular invasion (V-stage) the tumour size got larger along with the elevation of the V-stage, and there also observed a significant difference of the tumour size between the patients with pV10 and pV1a (P = 0.00578), with pV0 and pV1b (0 < P < 0.000061) and pV0 and pV2 (P = 0.0002). The same result was obtained in the relationship between the localization of the tumour and prognosis, i.e., the patients with pV2 showed a higher frequency of larger occupation of the tumour within the kidney compared with other V-stage patients. Regarding the recurrence rate, there observed a tendency toward high frequency of recurrence along with the elevation of V-stage. Furthermore, there observed an untoward relationship between the elevation of the V-stage and the periods of recurrence after nephrectomy. In an effort to analyse the disease-free survival, there observed a significant difference among the patients with pV0, pV1a, pV1b and pV2. CONCLUSION: We conclude that the vascular invasion is a very important prognostic factor in the patients with locally confined RCC. Furthermore, along with the elevation of the V-stage, it directly reflects the poorer prognosis.

Carcinoma, Renal Cell↗
PubMed1998

[Study on the clinical characteristics of double cancers associated with renal cell carcinoma].

BACKGROUND: Clinical Features of double cancers associated with renal cell carcinoma (RCC) detected at the clinical course, especially focusing on the comparative analysis between the male and female patients, were unknown. From this background, we tried to search for clinical characteristics of double cancers associated with RCC. PATIENTS: The eight hundred and four patients with RCC have been treated at our University Hospitals and affiliated hospitals, and of them, the 38 patients (male in 25, female in 13) had double cancers during the clinical course, and these patients were objective in our study. RESULTS: 1) When we looked at all patients, there observed gastric cancer most frequently in 14 (36.8%), lung cancer in 3 (7.9%), prostate cancer in 3, bladder cancer in 3, uterine cancer in 3, rectal cancer in 2 (5.3%), thyroid cancer in 2, and pharynx, esophagus, T-cell lymphoma, chronic lymphatic leukaemia (CLL), renal pelvis, sigmoid colon, brain and colon cancers in 1 (2.6%) respectively. 2) As to the male patients, there observed 10 gastric cancers, of them, 2 died of this disease (20%), 3 lung cancers, of them, 2 died of this disease (66.7%), 3 prostate cancers, of them, 2 died of this disease (66.7%), 3 bladder cancers, of them, 1 died of this disease (33.3%), and 1 cancer patient with pharynx died of this disease, esophagus, T-cell lymphoma, CLL, renal pelvis and sigmoid colon died of this disease. Regarding the female patients, there observed 4 gastric cancers, all of them died of this disease, 3 uterine cancers, all of them died of this disease, 2 rectum cancers, all of them died of this disease, 2 thyroid cancers, of them, 1 died of this disease, 1 brain cancer and 1 rectal cancer. Furthermore, as to the timing at the detection of double cancers during the clinical course, the 10 patients (40%) detected double cancers simultaneously in male patients. On the other hand, no patient with double cancers was detected simultaneously in female patients. CONCLUSION: The gastric cancer is most frequently observed as double cancer in both of male and female patients with RCC. But, in the female patients, it shows more frequently died of double cancers associated with RCC compared with those in male. Furthermore, as to the timing at the detection of double cancer is asynchronous in all female patients with RCC.

Adult↗
PubMed1998

[Study on the combined therapy of DNA-methyltransferase inhibitor and interferon-alpha/beta for mouse spontaneously arose renal cell carcinoma, and immunological mechanism induced by the therapy].

BACKGROUND: In order to change the immunological environment of T-helper2 (Th2) predominance, namely humoural immunity, in renal cell carcinoma, we tried to examine the efficacy of combined treatment with DNA-methyltransferase inhibitor (Procainamide) and interferon (IFN)-alpha/beta in basic experiments, and also examined the immunological mechanism induced by this treatment modality. MATERIALS AND METHODS: The monotherapy of Procainamide (10 mg/kg, 20 mg/kg, 30 mg/kg, everyday for 3 weeks, i.p.) and of natural murine IFN-alpha/beta (1 x 10(4) I.U./mouse, 3 times for a week, total 9 times, s.c.), and combined treatment with these 2 drugs for mouse spontaneously arose renal cell carcinoma (RC-2) were undertaken. Furthermore, we examined the expression of cytokine mRNA related to the Th-subset in murine spleen under the tumour burden by the RT-PCR methods. RESULTS: 1) Regarding the anti-tumour efficacy of two kinds of monotherapy (Procainamide and IFN-alpha/beta), no effective result was obtained. On the other hand, the combined treatment with these two drugs induced effective anti-tumour efficacy in the relative mean tumour weight ratio (TRW/CRW), mean tumour weight and the survival rate compared with the control and each monotherapy, especially in the administration of Procainamide dosed at 30 mg/kg. As to the histological degeneration induced by the combined therapy, there still remained the viable tumour cells (grade IIb). 2) In an effort to analyse the immunological changes induced by the administration of Procainamide, there observed the expression of Th1-derived cytokines mRNA such as IFN-gamma, IL-2 and tumour necrosis factor-beta, and except for interleukin (IL)-10, there also observed the disappearance of Th2-derived cytokines mRNA such as IL-4, IL-5 and IL-6 in the murine spleen. CONCLUSION: We draw the conclusion that the treatment with DNA-methyltransferase inhibitor may change the humoural immunological environment into the cellular immunological environment enabling the effective anti-tumour efficacy combined with IFN-alpha/beta in renal cell carcinoma.

Animals↗