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The balance between matrix metalloproteinases and their inhibitors is a critical factor which affects tumor invasion and metastasis. We have established a rat bladder carcinoma cell line, LMC19, which is tumorigenic, invasive and metastatic to the retroperitoneal lymph nodes and to the lungs in nude mice. LMC19 cells secrete pro-gelatinases A and B as well as tissue inhibitors of matrix metalloproteinase (TIMP1 and TIMP2). We conducted the present study to determine whether or not over-expression of TIMP1 and TIMP2 can affect the metastatic potential of LMC19 cells. We transfected the cells with an expression vector containing TIMP1 or TIMP2 cDNA, isolated several clones over-expressing TIMP1 or TIMP2 and assessed their invasive and metastatic potential by inoculation at an orthotopic site (urinary bladder) in nude mice. Our results show that the transfectants over-expressing TIMP1 and TIMP2 marginally affect primary tumor growth, local invasion or metastasis to the retroperitoneal lymph nodes but significantly inhibit extravascular growth of pulmonary tumor emboli. Our results suggest that the net activity of matrix metalloproteinases of tumor cells may be a critical factor that controls extravasation at this distant metastatic site.

We established 5 rat bladder cell lines (MYU3L, MYU4, MYU6s, MYKU1L and MYP3). EGF stimulated DNA synthesis of all the cells in monolayer culture, regardless of the number of EGF receptors. In soft agar, only MYU3L formed colonies, and EGF enhanced their growth. However, EGF did not induce the other cells to grow in soft agar. In contrast, TGF-beta 1 inhibited the growth of the cells, but a tumorigenic cell and the cells which were established from large in vivo tumors were more resistant than the others to TGF-beta 1. We tested the effect of growth factors on the invasive potential of MYP3 cells (non-tumorigenic), MYU3L cells (tumorigenic/highly invasive but not metastatic) from newly established cell lines, and another metastatic cell line, LMC19. MYP3 expressed only a trace amount of 92-kDa gelatinase (MMP-9), whereas MYU3L expressed interstitial collagenase (MMP-1) and MMP-9, and LMC19 expressed 72-kDa gelatinase (MMP-2) and MMP-9. The release of MMP-2 in LMC19 was stimulated by TGF-beta 1, but EGF had no effect on the release of any MMPs in either type of cells. These observations suggest that EGF acted as a mitogen on all the cells tested, but did not enhance the malignant phenotype. Further, the loss of responsiveness to the suppressive effect of TGF-beta 1 may be an important step toward a malignant phenotype. Some of malignant tumors may utilize TGF-beta 1 for enhancing their invasive and metastatic potential.

Numerous studies have reported a correlation between the production of gelatinases A and B by cancer cells and invasive and metastatic potential. It has been suggested that the expression of gelatinase A (72-kDa type IV collagenase) is associated more closely with the metastatic phenotype of malignant cells in vitro and in vivo than that of gelatinase B (92-kDa type IV collagenase). We have established a rat bladder carcinoma cell line, MYU3L, which is tumorigenic and locally invasive but is not metastatic to the distal organs in nude mice. The MYU3L cell line secretes pro-gelatinase B but not any detectable level of pro-gelatinase A. We undertook the present study to determine whether over-expression of gelatinase A can affect the metastatic potential of MYU3L cells. We transfected MYU3L cells with an expression vector containing human pro-gelatinase A cDNA under the transcriptional control of the SR alpha promoter. Two stable transfectants over-expressing gelatinase A activity were isolated. We assessed the biological behavior of the transfectants by an orthotopic site (urinary bladder) inoculation and an i.v. injection in nude mice. Our results demonstrate that the induced expression of human gelatinase A enzyme markedly accelerates the metastatic phenotype of the rat bladder carcinoma cell line MYU3L. Our results suggest that gelatinase A produced by tumor cells plays a major role in the metastatic process.

IntroductionEarlier reports of laparoscopic adrenalectomy (LA) for adrenal myelolipoma are limited.Presentation of caseBetween June 2000 and September 2012, we performed right adrenal resections using LA and open adrenalectomy (OA) in patients with myelolipoma (n = 3 and n = 3, respectively). Then, we evaluated patients' background characteristics and short- and long-term outcomes for both groups. The median maximum diameters of tumors were 3.5 (3.0–4.4) cm and 7.1 (7.0–9.5) cm for the LA and OA groups, respectively. The median durations of the operation were 152 (117–188) min and 218 (153–230) min, and the median blood loss volumes were 50 (20–160) mL and 290 (62–1237) mL in the LA and OA groups, respectively. The median postoperative lengths of hospital stay were 4 (4–4) days and 11 (11–13) days for the LA and OA groups, respectively. Conversion from LA to an open approach during surgery was not necessary in any of the cases. Additionally, perioperative morbidity and mortality were not observed.DiscussionThe limitation of this study is its methodological design; it is a case series and not a matched-control study, which would be difficult to conduct owing to the rare nature of adrenal myelolipoma. However, we esteem that LA will become widespread in the future because it is feasible, cosmetic, and less invasive.ConclusionLA was a safe, feasible, and effective approach to adrenal myelolipoma, assisted by advancement in preoperative imaging diagnostic techniques.

A woman was operated on for pulmonary metastasis four years after a radical resection of the rectum, and four years thereafter a solitary metastasis to the left adrenal was found. An elevated serum carcinoembryonic antigen (CEA) level indicated the lesion. Adrenalectomy was performed and the patient has been well with no further evidence of disease.

We describe 2 cases of prostatic carcinoma with pulmonary metastasis. In the first case there was no lymph node or bone metastasis, and in the second case there was only one bony metastatic lesion. Presentation, etiology and management are discussed.

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