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J L Chin

Publications and source records attributed to J L Chin.

At least 55 records · Page 3Linked to original sources
PubMed1993

Metallothionein in testicular germ cell tumors and drug resistance. Clinical correlation.

BACKGROUND: Metallothioneins (MT) are endogenous metalloproteins involved in the homeostasis of essential metals and detoxification of toxic metals. Some recent experimental studies suggested tumor resistance to cisdiamminedichloroplatin may be associated with overexpression of MT in the tumor. METHODS: The presence of MT in 33 primary testicular germ cell tumor specimens was assessed immunohistochemically using a rabbit polyclonal rat liver MT antibody that cross-reacted with human MT. The data were correlated with the patients' clinical course. RESULTS: Seminomas stained weakly or not at all for MT, regardless of the clinical stage. Most nonseminomas stained heavily for MT. The more advanced staged nonseminomas tended to stain more heavily for MT. CONCLUSIONS: In view of the considerable experimental evidence as well as some inferential clinical data involving MT in cis-diamminedichloroplatin resistance, there appears to be a role for MT in cis-diamminedichloroplatin resistance in germ cell tumors. Further studies to elucidate the role of MT in germ cell tumor chemoresistance are warranted.

Cisplatin↗
PubMed1993

Modulation of both cisplatin nephrotoxicity and drug resistance in murine bladder tumor by controlling metallothionein synthesis.

The role of metallothionein (MT) in cisplatin (cis-DDP) resistance and renal toxicity was investigated in C3H mice inoculated with mouse bladder tumor (MBT-2). C3H mice were inoculated s.c. with 1 x 10(6) MBT-2 cells/mouse on day 0. Mice were given injections of proparglyglycine (PPG) (500 mumol/kg s.c.) once a day for 3 days from day 7 to day 9 and with ZnSO4 (200 mumol/kg s.c.) once a day for 2 days from day 8 to day 9. cis-DDP (50 mumol/kg i.p.) was administered 10 days after MBT-2 cell inoculation. Since MT contents in the tumor and kidneys were significantly increased by administration of ZnSO4, both the antitumor activity of cis-DDP and its renal toxicity were reduced. However, coadministration of PPG reduced MT induction in tumor without affecting the level of renal MT. As a result, PPG could clearly overcome the MT-mediated cis-DDP resistance of tumors without compromising the protective effect exerted by renal MT on nephrotoxicity of the drug. It was suggested, therefore, that PPG may be a promising adjunct in cancer chemotherapy to overcome the drug resistance of tumors caused by the elevated level of MT.

Alkynes↗
PubMed1993

Intrarenal bacillus Calmette-Guerin therapy for upper urinary tract carcinoma in situ.

Of 17 renal units from 11 patients treated with intrarenal bacillus Calmette-Guerin (BCG) for positive selective upper tract urine cytology 16 had negative radiographic studies and 1 had a papillary renal pelvic lesion. The standard diagnostic maneuvers were used to rule out other sources of positive cytology from the lower tracts. Six patients had bilateral involvement, 3 had prior contralateral nephroureterectomy and 2 had unilateral positive cytology but were poor surgical risks. The BCG solution was administered weekly by retrograde ureteral catheterization and instillation during 1 hour. One patient had fever during the initial treatment and received antituberculous therapy. Other side effects included transient hematuria in 3 patients and irritative urinary symptoms in most patients. Of 11 patients (12 renal units) 8 had normalization of the urinary cytology with a median followup of 36 months. One patient had unilateral conversion of the cytology result but the contralateral papillary tumor persisted, requiring nephroureterectomy. The remaining 2 patients had persistently positive cytology results and the disease progressed. Longer followup and further experience with intrarenal BCG are required before the exact role of this treatment modality in upper tract urothelial malignancies, including carcinoma in situ, can be determined.

Aged↗
PubMed1992

Loin pain-hematuria syndrome: role for renal autotransplantation.

The loin pain-hematuria syndrome is a poorly understood constellation of symptoms consisting of persistent hematuria and intractable loin pain with negative comprehensive urological evaluation. The patients are severely debilitated by the pain and are usually dependent on narcotics. Various medical and surgical treatments have been tried unsuccessfully, ultimately leading to nephrectomy in many instances. The symptoms may subsequently occur contralaterally. Renal autotransplantation as a form of nephron-sparing denervation therapy for relief of pain was performed on 12 kidneys in 10 patients (2 bilaterally). Excluding 3 patients with followup of less than 1 year (all 3 are pain-free), 8 of the 9 autotransplantations have resulted in dramatic relief of pain, curtailment of narcotic use and return of the patient to normal daily function. Median followup was 43 months (range 15 to 53 months). The remaining patient had pain in the graft area necessitating transplant nephrectomy 4 months later. For patients severely affected by pain and narcotic dependence with this syndrome, renal autotransplantation may provide a nephron-sparing surgical solution.

Adult↗
PubMed1991

Concomitant treatment of MBT-2 bladder tumour by tumour necrosis factor alpha and interferon alpha in conjunction with delayed type hypersensitivity immunotherapy.

In our previous study [9], we reported the anti-tumour effect of TNF on mouse bladder tumour (MBT-2) both in vivo and in vitro. Inoculation of a single dose of TNF alone caused significant but transient tumour growth inhibition. Subsequent repeated doses of TNF did not sustain or augment the anti-tumour effect. The current experiments were undertaken to assess the anti-tumour activity of (i)-concomitant treatment of TNF-A and IFN-A against MBT-2 bladder tumour and (ii)-concomitant TNF + IFN-A treatment in conjunction with T-DTH (delayed-type hypersensitivity) immunotherapy. Systemic administration of multiple doses of TNF + IFN-A in vivo caused initial partial tumour regression followed by tumour growth inhibition up to 14 days following treatment. This combined treatment showed an enhanced anti-tumour effect compared to TNF-A treatment alone. Immunotherapy of MBT-2 tumour-bearing mice with T-DTH "immune" effector cells alone did not cause significant tumour growth inhibition. In contrast, concomitant administration of both T-DTH effector cells and TNF + IFN-A in MBT-2 tumour-bearing mice resulted in significant tumour growth inhibition for up to 16 days. The immune effector cells conferring immunotherapy were isolated from the spleens of tumour-immunized, "DTH-primed" animals and were characterized as Lyt 1+2- helper/DTH T cells (CD4+ phenotype). These cells mediate both DTH response to MBT-2 tumour antigens as well as anti-MBT-2 tumour protection. In vitro treatment of the "immune" cells with TNF-A resulted predominantly in the proliferation of Lyt 1+ T cells versus Lyt 2+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Characterization of MBT-2 tumour cell "variant" resistant to tumour necrosis factor.

Previously we reported sensitivity of MBT-2 murine bladder tumour to tumour necrosis factor (TNF) in vivo and in vitro [8]. We showed that with prolonged exposure of cultured MBT-2 tumour cells to TNF, a resistant MBT-2 "variant" tumour cell population emerged in vitro. This concurred with the finding of transient in vivo cytotoxic effect of TNF against MBT-2 tumour. Herein, we delineate phenotypic changes in MBT-2 cells associated with TNF resistance. Parent MBT-2 (MBT-2P) and the TNF-resistant "variant" MBT-2R cells were compared in terms of in vitro sensitivity to TNF, DNA profile, karyotype and in vitro growth kinetics. We conclude that acquisition of resistance to TNF may be due to cell cycle derangement and differences in in vitro growth characteristics. DNA indices and karyotype of "variant" MBT-2R cells were not altered, indicating the anti-tumour action of TNF is not-mutagenic.

Animals↗
PubMed1991

Immunohistochemical localization of metallothionein in transitional cell carcinoma of the bladder.

Metallothionein is a metal binding protein thiol found in high concentrations in the liver and kidney. Recent evidence has linked overexpression of cellular metallothionein with tumor cell resistance to chemotherapeutic drugs, such as alkylating agents and cis-diamminedichloroplatinum (II) (cisplatin). We studied the metallothionein content of 9 human transitional cell carcinomas of the bladder with immunohistochemical methods. All tumors stained positive for metallothionein and the staining was localized almost exclusively to the cytoplasm. Uroepithelium displaying dysplastic changes or carcinoma in situ demonstrated the greatest intensity of staining, while staining in the invasive portions of the tumor was weak and variable. These findings were of interest, since combination chemotherapy of invasive transitional cell carcinoma of the bladder often is ineffective against carcinoma in situ. Normal uroepithelium stained strongly in all 3 patients who experienced disease progression and death, and in only 1 of the 5 who are currently without evidence of disease.

Aged↗
PubMed1990

Ex-vivo microvascular reconstruction before renal allograft and autograft transplantation.

Microvascular reconstruction was performed ex vivo on 50 kidneys that had vascular anomalies or had sustained vascular injury during procurement before allograft transplantation or autotransplantation. The authors review the various surgical techniques used to facilitate the in-situ vascular anastomoses during transplantation and to salvage otherwise an unusable allograft. The complications associated with the microvascular repair were negligible. The authors conclude from the results of their study that ex-vivo microvascular reconstruction is a valuable adjunct to renal transplantation.

Anastomosis, Surgical↗
PubMed1989

Microvascular reconstructive "bench" surgery for donor kidneys before transplantation: techniques and results.

Forty kidneys (10 from live donors) with either multiple renal arteries or damaged vasculature were reconstructed accurately ex vivo with microsurgical techniques before transplantation. The end product in all cases was a kidney requiring a single arterial and venous in situ anastomosis. The warm ischemia time was minimized by this adjunctive "bench" microsurgery. There was no surgical complication relating to the vascular reconstruction. The potential technical and hemodynamic benefits of this surgical approach to kidneys with multiple vessels are discussed. In addition, some kidneys with damaged vasculature can be salvaged for transplantation with microvascular reconstruction.

Anastomosis, Surgical↗
PubMed1988

Vena caval extension of right renal vein for cadaveric renal transplants.

A short right renal vein can create technical problems during cadaveric renal transplants. A method is described of right renal vein extension. The technique incorporates the proximal vena cava into the right renal vein, using the cephalad vena caval opening as the new renal vein ostium. The potential advantages of this method are discussed.

Cadaver↗
PubMed1988

Anti-tumor effect of tumor necrosis factor and its induction of tumor variant of MBT-2 transitional cell carcinoma of the bladder.

The effect of tumor necrosis factor (TNF), a potential anti-tumor agent, was assessed both in vivo and in vitro against MBT-2 transitional cell carcinoma of the bladder in C3H/HeHa mice. Systemic administration of either single or multiple doses of TNF into tumor bearing animals resulted in partial tumor regression and had a consistent but transient anti-tumor effect. Compared to control, untreated tumor bearing animals, TNF-treated tumor bearing mice had significantly smaller tumor volumes and slower tumor growth rates over the period of 12 days following TNF inoculation. No significant difference in tumor volumes and tumor growth rates between controls and TNF-inoculated mice was observed from day 12 to day 21 after TNF treatment. Assessment of TNF cytotoxicity against in vitro MBT-2 cell line using 3[H]-thymidine proliferation assay showed significant sensitivity of MBT-2 cells to treatment with TNF. A "Variant" MBT-2 cell line was derived by sequential culturing of the original MBT-2 cells in the presence of progressively higher concentrations of TNF in culture medium. Although the significant growth suppression on the MBT-2 tumor appears to be transient, further studies are warranted which may elucidate the immunologic and biologic behavior of TNF and this transplantable animal tumor.

Animals↗
PubMed1987

Zoladex (ICI 118,630): clinical trial of new luteinizing hormone-releasing hormone analog in metastatic prostatic carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.

Adenocarcinoma↗