Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells.

BACKGROUND: Shc is the adaptor protein that exists in three isoforms, P46, P52 and P66, and acts as a bridge between activated cell surface receptors and downstream signalling molecules which act in extracellular signal-regulated cell events such as cell cycle progression. In our previous studies, Shc was shown to be a substrate of the tyrosine kinase c-Src in vitro and in vivo. RESULTS: Using green fluorescent protein-fusion Shc (GFP-Shc), we have shown that following epidermal growth factor (EGF) stimulation of A431 cells, all Shc isoforms were rapidly recruited from the cytoplasm to the plasma membrane (within 5 min) and then redistributed to the cytoplasmic vesicle structures (in the next 10-20 min). Indirect immunofluorescent study demonstrated that all Shc isoforms co-localize with EGF receptor (EGFR) and activated c-Src in both plasma membranes and cytoplasmic vesicle structures. Our previous study has shown that EGF induces the indirect association of EGFR and c-Src and activation of c-Src in A431 cells. An immunoprecipitation study demonstrated that the EGFR-Src association and c-Src activation are augmented in cells expressing GFP-Shc P52 or P66, but not P46. In addition, P52 and P66, but not P46, are in association with EGFR-Src complex. We also found that EGFR and Shc can be dissociated from c-Src by the addition of a synthetic peptide that corresponds to the autophosphorylation site of c-Src. Interestingly, the peptide-induced dissociation of the complex was not affected by the tyrosine phosphorylation state of the peptide. CONCLUSION: These results demonstrated a dynamic subcellular movement of Shc in response to EGF, and suggested a hitherto unknown scheme whereby Shc can work not only as a substrate of c-Src but also as a mediator of the EGF-induced activation of c-Src in an isoform-specific manner.

[A trial of digitization and digital analysis of analog clinical images of bladder cancer].

Owing to the recent developments in computed radiography and the picture archiving and communication system, all clinical images of bladder cancer can now be digitized, and recording, archiving, transportation and analysis of these images is becoming popular. We analyzed various kinds of analog images of bladder cancer after they were digitized via a simple image analyzer. The image analyzers we utilized were very useful for us to understand and become familiar with digitization of analog images of bladder cancer as well as digital analysis.

[Renal cancer with bone metastasis as initial symptom].

With a progress of image diagnosis method asymptomatic renal cancers have much chance to be disclosed, but renal carcinoma of which symptoms were caused by metastatic lesion are discovered as an initial symptom has not been decreased. In this paper we reported additional 4 patients who visited our hospital with an initial symptom of metastatic bone pain and were diagnosed that the primary lesion was the kidneys. We further conducted a follow-up study on 4 patients reported previously and discussed on renal cancer with bone metastasis as the initial symptom. Case 1 was a 51-year-old man with lumbar metastasis, case 2 was a 34-year-old woman with vertebral metastasis, case 3 was a 77-year-old man with femur metastasis and case 4 was a 65-year-old woman with femur metastasis. In three of the 4 patients except for case 1, extirpations of the primary lesions were performed. Case 3 and 4 received internal fixation for metastatic lesion in bone. In occasionally four cases, the prognosis was relatively favorable even in advanced renal carcinoma with bone metastasis, so surgical procedures should be made positively for relief of pain in metastatic lesion, maintenance of function and prevention of bone fracture.

[A case of renal cancer complicated with acute hypercalcemia and acute pancreatitis].

A 55-year-old man who had liver metastasis after undergoing surgery for renal cancer was hospitalized immediately on May 4, 1987 with complaints of general malaise, epigastric pain, nausea and vomiting. Because of abnormally high levels of blood calcium 15.6 mg/dl and serum amylase 2,069 IU/l, the case was diagnosed as hypercalcemic crisis and acute pancreatitis. Following recovery from the critical stage with administration of elcatonin and FOY, therapy for cancer initiated. We report the clinical course of this patient and discuss about hypercalcemia and acute pancreatitis as cases of oncologic emergency.

[A study on six cases of renal cell carcinoma detected by renal ultrasound during health screening].

From April 1986 to March 1988, 7,800 subjects (3,887 men and 3,913 women, age from 24 to 80 years, with a mean age of 48.7 years) underwent renal ultrasound during a screening by our Health Service. Of these subjects 29 were suspected to have solid masses in the kidneys. Further examination with computerized tomography (CT) was employed. Four angiomyolipomas and 16 malformations of the kidneys were diagnosed clinically at that time. Among 9 subjects who underwent complete urological evaluation including excretory urography (IVP), CT and renal angiography 6 malignant renal tumors were disclosed. Six patients were treated by radical nephrectomy. In this report we studied the 6 patients whose tumors were pathologically diagnosed as renal cell carcinoma (RCC). The six patients were 48 to 60 years old with a mean age of 55.8 years. There were 4 men and 2 women. There are no signs or symptoms referable to RCC. In 1 patients microscopic hematuria was detected via a laboratory study. Erythrocyte sedimentation rate (ESR) was slightly evaluated in 4 patients. In the 6 patients, the renal tumors were diagnosable by CT and all tumors had positive findings for malignant neoplasms angiographically. An IVP, without nephrotomography, did not reveal a small tumor growing in the upper pole of the right kidney of 1 patient. Surgical specimens were 180-475 g in weight. Tumors, were found in the right kidneys (2) and in the left kidneys (4), were well circumscribed. The size of the tumors measured from 3 to 7 cm in the longest axis. Pathological diagnosis was made as renal cell carcinoma 3 with G1, pT2a, 2 with G2, pT2a and 1 with G2, pT2b.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case report of renal cancer detected unexpectedly by X-ray CT during observations in the clinical course of cervical carcinoma].

The case is a 55-year old woman whose mother died of gastric cancer. In 1984 she underwent radiotherapy for cervical squamous cell carcinoma stage IIIb and had since been under the periodical observations. In 1987 she happened to undergo abdominal X-ray CT scans, and with an image of tumor mass revealed in the right kidney, she was admitted to our hospital. A clinical diagnosis of the right renal cancer was made, and radical nephrectomy was performed. Histological diagnosis was renal cell cancer pT2N0M0. This is the 7th reported case among the cases of double cancer of the cervix and the kidney in Japan. Multiple primary malignancies consist of these two cancers, and the renal carcinoma as an incidental finding with image procedure were discussed.

[A trial of digitization and digital analysis from analogue clinical images of the renal cancer].

The advancement in image diagnostic methods has been great in recent years and image diagnosis has become indispensable for the diagnosis of renal and other cancers. However, the clinical images are fixed and recorded on film as analog images for storage and the expansion of storage space, the poor efficiency in arrangement and control and the inconvenience of transfer have become big problems. Digitization of the clinical images offers the advantages of solving these problems and of allowing a variety of image analyses to be made easily. The tendency is for the digitization of all images for medical use in the near future. We applied a handy image analysis system (Shonic GA) using a personal computer as the mainframe and tried to digitize the analog images of a pyelogram, DSA, ultrasonogram, and X-ray CT of renal carcinoma for digital analysis. The results were displayed. This system is handy and easy to operate and thus is useful for the purposes of understanding and gaining experience in digitization and digital analyses of images for medical use.

Cyclosporine G and D in experimental autoimmune uveoretinitis in the rat.

Two analogs of cyclosporine A (CsA), cyclosporine G (CsG) and cyclosporine D (CsD), were compared to CsA with regards to their effects on experimental autoimmune uveoretinitis (EAU) as well as their adverse effects on renal functions. When administered daily on days 0-14 after immunization with S-antigen, CsA was the most effective of all in inhibiting EAU followed by CsG: 20-30 mg/kg/day of CsG appeared to have the same effect as 5 mg/kg/day of CsA. The effect of CsD was the least. When administered from day 7 after immunization, CsA and CsG were also effective in inhibiting the development of EAU. As for the adverse side effects, CsA was the most nephrotoxic: the toxic changes were morphologically found with doses of CsA at 10 mg/kg/day or higher. CsG and CsD were not nephrotoxic even at 30 mg/kg/day. The effects of CsG on immune responses were very similar to those of CsA. Both agents exhibited selective inhibition on the cell-mediated immune responses to S-antigen, while having no effect on antibody production.

[Two cases of renal cancer detected by ultrasonic scan during mass screening and subsequent MRI].

Reported herein are the cases of two woman, aged 47 and 69, respectively, who were each found to have a right renal carcinoma, both carcinomas discovered incidentally by an abdominal ultrasonic scan during a mass screening, with no other signs or symptoms of renal cancer being indicated. Following clinical diagnostic verification, using X-ray CT, and an MRI, radical nephrectomies were performed. In each instance, the pathohistological diagnosis was renal cell carcinoma, pT2N0M0V0. The clinical imagings, including the MRI, are presented, and the diagnostic techniques used in this imaging and the screening modality in cases of asymptomatic renal cancer are discussed.