The influence of cytoreductive surgery on the response to chemotherapy of a rat renal cancer

Summary The potential ability of cytoreductive surgery to increase the effectiveness of chemotherapy (vindesine) was tested utilizing male Wistar Lewis rats transplanted simulataneously with intraperitoneal and flank implants of a spontaneously arising renal adenocarcinoma. Cytoreduction was accomplished in some animals by removing the flank tumor 5–7 weeks following implantation; all animals received vindesine (IP injection of 0.5 mg/kg on two successive weeks). While vindesine reduced tumor growth, in no case did the addition of cytoreductive surgery enhance the effect of chemotherapy. The addition of cytoreductive surgery to marginally effective chemotherapy was found to be ineffective or even detrimental.Abbreviations VDR vindesine - IP intraperitoneal     

A comparison of the cell lines used in meningioma research

BACKGROUND: Immortal cell lines and cell lines derived from operative specimens transplanted into animal models are used in meningioma research. We address 2 criticisms of the mouse xenograft flank tumor model: Why are tumor induction rates derived from operative specimens low and inconsistent? Are flank tumors meningiomas? METHODS: Meningioma cell cultures were processed for Giemsa-band karyotyping and flow cytometry. Mouse flank tumors induced subcutaneously were analyzed microscopically, immunohistochemically, and ultrastructurally. Giemsa-band studies identified meningiomas with simple karyotype (相似文献   

Permanent flank bulge is a consequence of flank incision for radical nephrectomy in one half of patients

The objective of the study was to determine the incidence and predictors of post operative pain and flank bulging in patients undergoing nephrectomy for a renal tumor through a flank or thoracoabdominal incision. Only one previous retrospective study (1974) has directly addressed this issue in urologic patients. This reported a 3% incidence of flank bulging. This was at variance with our own experience. To determine the incidence of pain and post-operative flank bulge after flank or thoraco-abdominal incision, a cross sectional survey among in 70 patients, who had a nephrectomy for a renal tumor between 1996 and 2000, was assessed by telephone interview. Four surgeons contributed patients to the study. Thirty-four of seventy (49%) patients complained of a flank bulge persisting more than 1 yr after surgery. Durable flank pain was experienced by 24%. This was severe in 3% of patients. Median pain magnitude was 5/10. There was no difference in bulge incidence between surgeons (P = 0.49). Flank bulging occurred more frequently in left sided nephrectomy (P = 0.054) than right. Other parameters including gender, age, and tumor size had no correlation with the rate of either complication. In all patients who described a flank bulge, the deformity was durable; there were no cases of spontaneous resolution. Patients described a significant impact on QOL, particularly in those under 60 yrs. The overall rate of postoperative flank bulging is considerably higher than has been previously reported. This deformity affects quality of life. The observation that almost 50% of patients experience a flank bulge following a flank incision supports the shift towards laparoscopic nephrectomy, and should be incorporated into decision making regarding the optimal surgical approach. This may be particularly relevant in the choice between open partial nephrectomy and laparoscopic radical nephrectomy in a patient with a normal contralateral kidney.     

In vivo antiproliferative effects of gamma-interferon and tumor necrosis factor alpha in a rat renal cell carcinoma model system

We have investigated the antiproliferative activities of recombinant rat-gamma-interferon and recombinant human tumor necrosis factor alpha in a rat renal cell carcinoma model system. The tumor was transplanted subcutaneously, the drugs were administered peritumorally. Gamma-interferon treatment starting two days after tumor implantation resulted in a dose-dependent growth inhibiting effect. Tumor necrosis factor alpha was only effective at the highest concentration. Different combinations of the drugs have additive or synergistic antiproliferative effects. The combination of both highest doses completely inhibited tumor growth without any obvious toxic effects on the rats. Rechallenge of the cured rats with a tumor piece in the contralateral flank did not result in a tumor specific immune response. Shortening of the treatment period to two weeks resulted in an increased lag-period, but finally all tumors started to grow. Furthermore, the anti-tumor effect was dependent on tumor volume at start of therapy. Monotherapy could not inhibit tumor growth of an established tumor. The combination with both highest doses, however, inhibited tumor growth even when treatment was started at a tumor volume of two to five cm3. Treatment with gamma-interferon and tumor necrosis factor is most effective at low tumor burden. These studies suggest that clinical application of these drugs is most effective in an adjuvant setting.     

转单链鼠白介素12基因前列腺癌RM-1细胞的致瘤性观察

目的：探讨前列腺癌的免疫基因治疗。方法：将mIL-12基因体外转染鼠前列腺癌RM－1细胞，接种C57BL／6小鼠，观察其致瘤性。结果：转基因RM－1细胞大部分丧失致瘤性；一侧接种转AdmIL-12的RM－1细胞，引起对侧接种野生型RM－1细胞成瘤延迟、肿瘤生长减缓。结论：IL－12可诱发抗肿瘤免疫反应。     

Estramustine potentiates the effects of irradiation on the dunning (R3327) rat prostatic adenocarcinoma

The present study was designed to determine if estramustine phosphate (EMP) could potentiate the effects of irradiation on the Dunning (R3327) prostatic adenocarcinoma in rats. Two groups of male Copenhagen × Fisher F1 rats carrying bilateral tumors in the flank were used. Irradiation was given with a linear accelerator 6 MV, in a dose of 6 Gy/day for 4 days to the tumor on one side while the tumor on the other side served as control. EMP (360 μg/24 hours) was administered with osmotic pumps to one group of rats for 2 weeks, starting 1 week before irradiation. Tumor growth was calculated by measuring tumor volume, and tumor blood flow was measured 8 weeks after treatment. Irradiation alone effectively delayed tumor growth and EMP enhanced these effects. Tumor blood flow was stimulated by EMP treatment irrespective of radiotherapy. Volume density of tumor epithelium was effectively decreased by irradiation but no significant effects could be seen after EMP. In conclusion, the present study shows that EMP potentiates irradiation on rat prostatic adenocarcinoma, and further evaluation of this therapeutic approach in the clinical treatment of prostatic carcinoma is thus justified. © 1994 Wiley-Liss, Inc.     

Second-look laparotomy for Wilms' tumor: indications and results in 19 patients

Nineteen of 74 children with Wilms' tumor underwent second-look laparotomy. Transperitoneal operation was done in five cases referred after flank operation elsewhere. Four had a change in stage from I to II or III, while one considered "inoperable" was resected (4/5 survived). Reoperation was done in two late referrals after operations with tumor spill. One had recurrent flank disease; the other had a flank mass with unrecognized diaphragmatic and intracaval extension (1/2 survived). Three children with giant tumors initially considered unresectable were successfully resected after cytoreduction with chemotherapy (3/3 survived). Two of three patients with bilateral Wilms' tumor survived reoperative procedures (partial or total nephrectomy). Five children with late intraabdominal recurrence (3 liver: 2 flank) eventually died despite reoperation and adjunctive therapy. All five had unfavorable histology. One child with en bloc hepatic resection had successful reoperation for suprahepatic vena caval obstruction due to regeneration of liver, but subsequently died. Ten of the 19 patients survived (52.6%) following reoperation and adjunctive therapy. Second-look laparotomy is quite useful in patients inadequately staged with flank operations, in cases of bilateral Wilms' tumor, and in children with initially unresectable tumors following cytoreduction. Patients with extensive tumor spill at a previous procedure may benefit from early reoperation. Late recurrence of tumor (especially with unfavorable histology) and/or liver metastases carried an ominous prognosis.     

A case of leiomyosarcoma of the kidney

Leiomyosarcoma of the left kidney seen in a 58-year-old man is reported. On April 10, 1982, he complained of left flank pain. He visited our hospital and left solitary renal cyst was suspected. He had been treated as an outpatient, but left flank pain became exacervated. On May 18, he was admitted to our hospital. On June 7, radical nephrectomy was done under the diagnosis of left renal cell carcinoma. At operation, the tumor invased directory to the psoas muscle and abdominal wall, and could not be completely resected. Pathological diagnosis was renal cell carcinoma with sarcomatoid change. On July 1, he was discharged from the hospital. In December, left flank distention appeared and back pain became exacervated. On February 8, 1983, he was readmitted to our hospital. Low density area was found in left psoas muscle by CT scanning and recurrence of renal cell carcinoma was suspected. alpha-Interferon therapy had been done, but tumor increased remarkably and caused ileus. He died on June 14, 1983. The autopsy revealed a child head-sized cystic tumor in the upper retroperitoneal space, a 5 X 5 X 5 cm metastasis of the left lobe of the liver, a 3 X 3 X 4 cm tumor to the left upper lobe with cavity formation and direct invasion into the spleen, diaphragma and gastric serosa. These metastatic lesions were leiomyosarcoma. Retrospectively, the primary tumor of kidney revealed primary leiomyosarcoma of kidney.     

In vivo gene transfer of pigment epithelium-derived factor inhibits tumor growth in syngeneic murine models of thoracic malignancies

OBJECTIVE: Pigment epithelium-derived factor is known to be an inhibitor of angiogenesis. We hypothesized that in vivo gene transfer of pigment epithelium-derived factor may inhibit tumor angiogenesis and growth in syngeneic models of thoracic malignancies. METHODS: An adenovirus vector encoding the human pigment epithelium-derived factor cDNA (AdPEDF) was used to transduce human lung cancer cells in vitro. Transgene expression was assessed using Western analysis. Three different murine flank tumors (2 lung, 1 colon) were then established in syngeneic mice and treated intratumorally with phosphate-buffered saline, AdPEDF, or an empty vector (AdNull). Endpoints measured included transgene expression, tumor size, and animal survival, as well as microvessel density within the tumor. Additionally, a murine pulmonary metastasis model was established by intravenous injection of a syngeneic colon adenocarcinoma cell line expressing a marker gene (beta-galactosidase). One day later, treatment (phosphate-buffered saline, AdNull, or AdPEDF) was administered intrapleurally. Tumor burden (gross and histologic inspection, lung weight, and beta-galactosidase expression) was then evaluated 13 days after vector dosing, and survival was recorded. RESULTS: AdPEDF-derived expression of pigment epithelium-derived factor was demonstrated in vitro and in vivo. In syngeneic murine lung cancer flank tumors, intratumoral administration of AdPEDF significantly inhibited tumor growth (P <.01), prolonged mouse survival (P <.01), and decreased microvessel density (P <.01) compared with control groups. In the pulmonary metastasis model, AdPEDF-treated mice exhibited significantly reduced lung lesions, lung weight (P <.0005), beta-galactosidase expression (P <.05), and animal survival was prolonged (P <.05). CONCLUSION: Gene transfer of pigment epithelium-derived factor suppresses tumor vascularization and growth, while prolonging survival in syngeneic murine models of thoracic malignancies.     

Leiomyoma of the kidney. Differential diagnostic aspects of renal cell carcinoma with increasing clinical relevance

Renal leiomyoma is a rare benign tumor which has its origin in smooth muscle cells of different structures of the kidney. The clinical incidence of renal leiomyoma is much lower than the frequency described in large autopsy studies. Renal leiomyomas are mainly located in the renal capsula and pelvis or next to those structures. Clinical symptoms are nonspecific (e.g., flank pain or flank tumor) or completely absent, making most of the leiomyomas an incidental finding during routine diagnostics. A differential diagnosis between renal leiomyoma and renal cell carcinoma on the basis of medical imaging is extremely difficult. Therefore, laparotomy and nephrectomy are performed in most cases of suspected renal cell carcinoma. The definitive diagnosis of a leiomyoma is only possible after histological examination of the tumor. Due to the rising number of diagnoses resulting from improved medical imaging, renal leiomyomas are gaining more importance in the differential diagnosis of renal cell carcinoma, especially with respect to kidney-sparing surgery.     

Small intestinal submucosa does not promote PAIII tumor growth in Lobund-Wistar rats

BACKGROUND: Site-specific remodeling and angiogenesis are two observations associated with the use of small intestinal submucosa (SIS) as a tissue repair graft. Its angiogenic capacity has raised questions concerning its effect on tumor growth and metastasis in clinical tumor resection cases. The effect of SIS on the ability of neoplastic (prostate adenocarcinoma) cells to establish, grow, and metastasize was examined in Lobund-Wistar (L-W) rats. MATERIALS AND METHODS: In one study, SIS, expanded polytetrafluoroethylene (ePTFE), or human cadaveric dermis was placed in a subcutaneous pocket on the flank of L-W rats and immediately inoculated with PA-III cell suspension. Tumors were allowed to establish and metastasize for 5 weeks prior to sacrifice. Rate of tumor growth, tumor weight, and frequency of lung metastases were assessed. In a second study, SIS was placed in a resected tumor bed and tumors were allowed to recur. Rate of tumor growth, tumor weight, and frequency of lung metastases were assessed after 3 weeks. RESULTS: ePTFE hastened the rate of formation of palpable tumors compared to controls and other materials; cadaveric dermis and SIS did not. No differences between materials were noted in final tumor weight nor in the frequency of metastasis to the lungs. Following surgical tumor resection, residual tumor cells led to recurrence of same-site tumors in all animals, but in the defects augmented with SIS, the tumors were significantly smaller than those which regrew in the resected, unaugmented group. CONCLUSIONS: This study demonstrates that SIS does not enhance tumor establishment, growth, or metastasis in de novo tumors. Furthermore, SIS appears to reduce the rate of tumor growth, but not metastasis, when applied in direct contact with a residual tumor bed in a rat model of prostate-related tumors.     

Biologic Determinants of Tumor Growth in Healing Wounds

The morphologic characteristics of a scar may render it an "immunologically privileged site" providing fertile ground for tumor occurrence and growth. We sought to extend this concept and to determine the effect of different stages of wound healing on tumor occurrence. Syngeneic strain-2 guinea pigs and a methylcholanthrene-induced liposarcoma (MCA-2) were used. Incisional flank wounds were created at appropriate intervals such that at the time of tumor inoculation each group of animals had a sequentially aged wound which was a) acute, b) three weeks old, c) nine weeks old, d) 11 weeks old, e) created one week after tumor injection, or f) no wound. Wounds which were three, nine, or 11 weeks old consistently caused a significant increase in tumor growth rate following inoculation of a single cell tumor suspension (<.001). The delayed wounds, or those created following after tumor injection, and the acute wounds did not promote increased tumor growth. This study demonstrates that the ability of a wound to amplify or retard tumor growth may vary with its age. As a postulate we suggest that the relative paucity of lymphatic regeneration within scar tissue may render it an "immunologically privileged site" such that early recognition and destruction of tumor cells within the scar may be delayed long enough for the tumor to grow to a "critical size." Subsequent to this regardless of the host's immunocompetence the tumor can no longer be destroyed by an immune mechanism. The general lack of progressive growth of tumor cells placed in acute wounds suggests that they were not protected from immunocompetent cells and were destroyed by the ongoing inflammatory response to injury. Therefore, different biologic characteristics of a surgical scar are important in potentiating or retarding tumor growth. Variations in such factors may account for the local recurrence of cancer in operative wounds.     

Preoperative insulin reverses cachexia and decreases mortality in tumor-bearing rats

As a model of surgical stress in the cancer-bearing animal, we resected large flank sarcomas from cachectic rats under ether anesthesia and closed wounds primarily. The metabolic cost of tumor resection was measured using a long-term continuous indirect calorimeter. In the immediate postresection period energy balance decreased and host energy expenditure increased significantly (P less than 0.005). In animals with similar tumor weights, mortality following resection was determined by the degree of cachectic depletion. We then considered whether improvement of preoperative host nutritional status with insulin treatment might improve a subsequent surgical outcome. Insulin, when administered exogenously to cachectic tumor-bearing rats, has been shown to stimulate food intake and preserve host weight and does not stimulate tumor growth. When individual rats bearing a cachexia-producing flank sarcoma demonstrated a decline in food intake to less than 75% of predicted (approximately 25 days after tumor implantation), they were randomized to receive either daily injections of NPH insulin (2 units/100 g/day) for 5 days or no treatment for 5 days. Animals then underwent tumor resection and 14-day survival was measured. All resections were performed in an unbiased manner without the surgeon's knowledge of each rat's treatment status. In an experiment using 59 rats, insulin-treated rats had a threefold higher 5-day preoperative food intake and did not lose weight in the preoperative period, while untreated rats lost 17 g (P less than 0.001). Mortality in the insulin-treated group was 10% versus 28% in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of growth hormone on tumor and host in an animal model

Background: The relative effects of growth hormone on tumor versus host growth and protein metabolism are not known. This study examines the influence of recombinant rat growth hormone (r-rGH) on host and tumor growth, host body composition, and protein synthesis of tumor and host in tumor-bearing rats. Methods: After left flank implantation of methylcholanthrene-induced sarcoma, 28 Fischer rats with palpable tumor were treated with s.c. saline or 1 mg/kg/day r-rGH for 11 days. At death, fractional protein synthetic rates (FSRs) of tumor, liver, and gastrocnemius muscle were determined. In a separate experiment, 27 tumor-bearing rats received saline or 1 mg/kg/day r-rGH for 2 weeks. Tumor and host growth and host body composition were analyzed. Results: Animals treated with r-rGH had significantly higher liver FSR than did controls (233 ± 27%/day vs. 110 ± 4%/day, respectively). No significant differences were associated with growth hormone administration with respect to tumor growth, host composition, or FSR of tumor or muscle. Conclusions: Growth hormone stimulates liver protein synthesis, without changing tumor growth, protein synthesis, or host composition in this rat sarcoma model. Further investigation of growth hormone as an anticachectic agent is warranted. The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Multicystic nephroma in an elderly man. Case report

Multicystic nephroma is a relatively rare tumor of the kidney presenting unclear histological origin. Abdominal mass is a common onset sign in children while abdominal flank pain or abdominal discomfort, hematuria and recurrent urinary tract infections usually affect adults. Preoperative diagnosis is impossible especially in the adult variant of the tumor where clear cells carcinoma with cystic degeneration must always be suspected. We herein report a case of a 77 year old man complaining of flank abdominal pain and recurrent episodes of urinary tract infection due to a right-sided multicystic nephroma successfully treated with nephrectomy.     

Therapeutic activity of 3,3'-diindolylmethane on prostate cancer in an in vivo model

BACKGROUND: Prostate cancer (PC) is the second leading cancer-related death in men in Western countries. Hence, efficient anti-carcinogenic and therapeutic compounds against PC are badly needed. We have previously shown that 3,3'-diindolylmethane (DIM) has a suppressive effect on the growth of human breast and PC cell lines. The objective of this study was examination of the potential therapeutic effects of DIM in an in vivo model. METHODS: TRAMP-C2, a mouse PC cell line, was injected into the flank of male C57BL/6 mice. When tumors appeared, mice were injected intraperitoneally with either corn oil (vehicle) or DIM (2.5, 5, or 10 mg per kg body weight) 3-times a week, for 3 weeks, and tumor volumes were measured bi-weekly with calibermeters. Later, the tumors were removed, their final weights and volumes were measured, and tumor sections were tested for histological studies. RESULTS: DIM had a significant inhibitory effect, caused by diminished tumor growth. Histological examination of tumors from treated groups revealed apoptosis and decreased cell proliferation, compared with the controls. DIM didn't affect body weights or kidney and liver functioning. CONCLUSIONS: The inhibitory action of DIM on tumor growth was demonstrated in vivo. Hence, this compound at the concentrations tested may offer an effective and non toxic therapeutic means against tumor growth in rodents, and may serve as a potential natural anti-carconigenic compound in humans.     

Spontaneously ruptured multilocular cystic nephroma

Multilocular cystic nephroma is a relatively rare benign tumor of the kidney. An adult case of spontaneously ruptured multilocular cystic nephroma was reported. A 33-year-old woman who presented with a right flank colic attack. The preoperative diagnosis was spontaneously ruptured renal tumor. A right nephrectomy was performed. A multilocular cystic lesion, 10 cm in diameter, was found in the removed specimen, which had a hematoma inside and direct tumor extension into the renal pelvis. On microscopic examination, the surface of loculi was covered by a layer of hobnail epithelium, and septa were composed of fibrous tissue with dilated vessels, lacking in normal renal components. There were no signs of malignancy. The lesion extending into the renal pelvis showed the same microscopic findings. The final diagnosis was multilocular cystic nephroma. Two respects, spontaneous rupture and tumor extension into the renal pelvis, were unique to the present case. There has been no report of spontaneously ruptured mutilocular cystic nephroma. The tumor extension into the renal pelvis, however, has been found in several reports. This growth pattern might be one of the characteristics of this benign renal tumor.     

The effects of streptozocin-induced diabetes and weight-matched pair feeding on tumor growth and survival in fischer rats

Sixty-one 150- to 180-g Fischer rats were assigned to one of four experimental groups: nondiabetic, tumor bearer (ND-TB, n = 15); diabetic, non-tumor bearer (D-NTB, n = 19); diabetic, tumor bearer (D-TB, n = 16); or nondiabetic, weight-matched control, tumor bearer (WM-TB, n = 11). The WM group was housed in metabolic cages and fed H₂O ad libitum and rat chow to achieve appropriate carcass weight (comparable to D-NTB). Diabetes was induced with a single dose of streptozocin (STZ) 40 mg/kg body wt iv, 10 days prior to tumor inoculation. Viable methylcholanthrene-induced sarcoma cells (1 × 10⁶) were injected into the right flank on Day 0. Body weight and tumor volume were assessed every 3 days. On the day of death, the animal and excised tumor were weighed. Dividing the growth curves versus time into two phases based on tumor volumes 0–20 and 20–60 cm³ defined a significant early growth (0–20 cm³) delay of 5 days in the D-TB and WM groups vs the ND-TB group. The growth rate from 20–60 was not different in any group. Tumor growth retardation seen in STZ-induced diabetic animals can be mimicked and exceeded in a pair-fed, weight-matched control group. Diabetic and starved animals have smaller tumors and live longer than ad lib fed, nondiabetic animals. The delay in tumor growth is a reflection of the retardation in the early (0–20 cm³) growth rate.     

The effects of perfluorochemicals on tumor growth and chemotherapy response

Hypoxia, leading to cells in resting or slow replication phases may be a cause of chemotherapy and radiation therapy resistance in some tumors. Perfluorochemicals (PFC) may potentiate response to these therapies by increasing oxygen delivery to the tumor, forcing cells into more therapy-responsive replicating phases. To assess the effects of PFC on tumor growth and chemotherapy response, 91 ACI rats bearing 1 cc flank Morris hepatoma tumors were divided into groups: Group I, control; Group II, Adriamycin (ADR) 10 mg/kg intraperitoneally (IP); Group III, Cytoxan (CTX) 100 mg/kg IP; Group IV, PFC 20 mL/kg IV; Group V, ADR and PFC; Group VI, CTX and PFC. Animals were kept in 0.5 FiO2 for 24 hours after treatment, and mortality and tumor volumes determined 2 weeks later. Tumor DNA turnover was measured using opposing pathways assay of 14C-thymidine uptake and degradation. In a separate group, tumor tissue pO2 was measured polarographically with an oxygen microelectrode before and after injection of PFC (20 mL/kg). The survival was significantly reduced in group IV (4%) compared with group I, control (73%). Both ADR and CTX slowed the growth of the tumor, while PFC alone significantly accelerated tumor growth. The tumor response to ADR was potentiated by the addition of PFC. These results were confirmed by DNA synthesis evaluation. The mean pO2 level prior to injection was 6.6 +/- 1.96 mmHg compared with 18.92 +/- 1.00 mmHg after PFC injection (P less than or equal to .01).(ABSTRACT TRUNCATED AT 250 WORDS)