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PubMed1980

Cytotoxic effect in vivo of selected chemotherapeutic agents on synchronized murine fibrosarcoma cells.

The cytotoxic effects in vivo of single doses of either adriamycin (ADM), 1-beta-D-arabinofuranosylcytosine (Ara-C), bleomycin (BLM), cis-diamminedichloroplatinum (II) (cis-DDP), or cyclophosphamide (CY) on murine fibrosarcoma (FSa) cell populations were determined. Tumour cells were separated and synchronized by centrifugal elutriation. Viable tumour cells from selected elutriator fractions were then injected i.v. into whole-body-irradiated mice. Twenty minutes later selected doses of ADM, Ara-C, BLM, cis-DDP or CY were administered to selected groups of these animals. Fourteen days later the mice were killed. Killing of injected tumour cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung cells by each of the chemotherapeutic agents was evidenced by a reduction in the lung colonies per cell injected in treated animals. Under these conditions the response of FSa cells in vivo to the 5 drugs tested differed both qualitatively and quantitatively. Ara-C was S-phase-specific in toxicity. ADM, BLM, and cis-DDP were preferentially toxic to S, G2+M and G1 cells respectively. CY, a drug requiring bioactivation to form alkylating metabolites, was found to be equally toxic to G1 and G2+M enriched populations, but less effective in killing cell populations enriched with early-S cells.

Animals↗
PubMed2003

Malignant stromal tumor of the colon in an infant: diagnostic difficulties and differential diagnosis.

Gastrointestinal stromal tumor is a rare pathology in childhood. It may occur anywhere along the alimentary tract and represents with a wide spectrum of signs and symptoms according to location. An infant with malignant colonic stromal tumor that has presented with a huge abdominal mass and lower gastrointestinal bleeding is reported to discuss the difficulties in diagnosis and differential diagnosis of this unusual tumor.

Chemotherapy, Adjuvant↗
PubMed1970

In vitro malignant transformation by methylcholanthrene of the progeny of single cells derived from C3H mouse prostate.

Cell lines derived from C3H mouse ventral prostate grow to a monolayer, do not pile up, and do not give tumors on inoculation into isologous mice. When treated with carcinogenic hydrocarbons, these cells produce piledup colonies that give rise to fibrosarcomas in mice; these colonies are termed transformed. Individual single cells were treated with 0.5 per cent dimethyl sulfoxide (DMSO), and 2 per cent of them gave rise to clones containing transformed colonies. Under optimal conditions, treatment of individual single cells with 3-methylcholanthrene (MCA) led to the formation of transformed colonies in 100 per cent of the clones. From recloning experiments, it appears probable that all the progeny of the MCA-treated cells were potentially transformed, although the time required for the transformation to be scored was variable. It is concluded that in this system the carcinogen does not select for pre-existing malignant cells.

Animals↗
PubMed1981

Loss of tumor-specific and idiotype-specific immunity with age.

The ultraviolet light-induced fibrosarcoma 1591 undergoes "first-set rejection" when transplanted into normal syngeneic mice. We found, however, that the primary resistance of normal mice decreases with age, beginning at 9--12 mo, equivalent to middle age for mice. Mice lose with age the capacity to mount both idiotypic and anti-idiotypic responses responsible for controlling the growth of tumor. This loss was correlated with quantitative as well as qualitative changes in the response, such as changes in specificity and clonotype. Normal young mice regularly expressed a dominant common anti-1591 "idiotype" as defined by an anti-idiotypic probe. The capability of normal mice to respond with lymphocytes of this dominant common idiotype began to decline at about 8 mo of age. At this time, animals still generated tumor-specific lymphocytes, but these lymphocytes appear to be idiotypically different lymphocyte clones. With further increase in age, animals responded with tumor-reactive lymphocytes that showed a marked cross-reactivity to other tumor target cell lines. Both in vivo and in vitro, the capability of normal mice to mount an immune response that was specific for the 1591 tumor cells decreased between 9 and 14 mo, which was the age individual mice became increasingly susceptible to a challenge with 1591 tumor cells. Thus, our data suggest that clones of tumor-specific T cells provide primary and early protection of young animals against challenge with malignant 1591 cells. However, the dominance of these tumor-specific T cell clones in a primary immune response is lost in middle-age. Because the ability of animals to mount anti-idiotypic immune response also declined in middle-aged animals, it is possible that the observed loss of clonal dominance of tumor-specific clones with increasing age is at least partially related to age-dependent changes in the anti-idiotypic compartment.

Aging↗
PubMed2001

Sarcomatoid differentiation in renal cell carcinoma: a study of 101 cases.

Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.

Adenocarcinoma↗
PubMed1996

Immunotherapy of established murine tumors with large multivalent immunogen and cyclophosphamide.

Plasma membrane vesicles isolated from tumor cells can be incorporated onto 5-microns diameter microspheres and antigen in this form, termed large multivalent immunogen (LMI), augments generation of tumor-specific cytotoxic T lymphocyte (CTL) responses in vivo. Treatment of mice with LMI at the time of challenge with tumor significantly reduced growth of several tumors in their syngeneic hosts. Our report describes the effects of LMI on established progressing tumors, including P815 solid tumor and two fibrosarcomas in a lung-metastasis model. Treatment of mice bearing established tumors (7 to 12 days) with LMI alone did not significantly reduce tumor growth or extend host survival, but highly synergistic effects of combined treatment with cyclophosphamide (Cy) and LMI were found. Cy alone reduced the size of P815 solid tumors, but within a few days, the tumors began to grow progressively, and survival was only marginally extended. However, Cy followed 2 to 3 days later by a single injection of LMI resulted in prolonged reduction of tumor growth and significant extension of survival; in some experiments, tumors became undetectable in the majority of treated mice, and the mice survived indefinitely. Essentially the same results were obtained in experiments examining survival of mice bearing established MCA-203 fibrosarcoma. LMIs were uniquely effective in acting synergistically with Cy; antigen in the form of irradiated tumor cells or plasma membrane in adjuvant were ineffective, and free plasma-membrane antigen (not on microspheres) had only marginal effects. There has been considerable interest in the possibility of using tumor antigen to enhance tumor-specific immune responses, and clinical trials using this approach are showing some promise. The results described here suggest that altering the form of antigen by purifying plasma membranes and incorporating them onto microspheres might significantly improve the efficacy of tumor immunotherapy with antigen.

Animals↗
PubMedDate not supplied

Computed tomography of monkey brain tumors.

Thirty-five Japanese monkeys were inoculated intracerebrally with chick embryo fibroblasts that were producing Schmidt-Ruppin strain of Rous sarcoma virus. Tumors were induced in 54.3% (19/35). Computed tomography detected tumors in 10 symptomatic animals with an average latency of 32.6 (15-43) days. At autopsy, the brains were sectioned into 5 mm slices, coplanar to the CT image. Various CT features of high- and low-density area correlated well with the histopathological findings, such as tumor, hemorrhage, necrosis, and peritumoral edema. Contrast-enhanced CT detected 10 tumors greater than 4 mm in diameter, and there was +/- 2 mm potential error in determining tumor size. Follow-up CT revealed growth of tumors in four animals and stabilization of tumor in two animals. Large brain size, 90-110 g in adult monkeys, and availability of induced tumors offer an excellent brain tumor model for CT studies.

Animals↗
PubMed1979

Recovery from sublethal damage by acutely hypoxic tumour cells in vivo and in vitro.

The ability of acutely hypoxic tumour cells to recover from sublethal damage following irradiation in vivo and in vitro has been measured using a single tumour system. The methods of assay were tumour growth delay, local tumour control and tumour cell survival in vitro following treatment in vivo or in vitro. Tumours in vivo or cells in vitro rendered acutely hypoxic during irradiation were irradiated with either single doses or two doses 24 hours apart. Cells left in situ had a greater capacity for recovery than those treated either in vivo or in vitro and then assayed in vitro. It is suggested that tumours may not show a systematically reduced capacity for recovery relative to normal tissues, unless chronically hypoxic tumour cells have a reduced capacity for recovery and determine the response. However, the results imply that deductions as to the ability of tumour cells to recover from sublethal damage (whether chronically hypoxic or not), which rely on in vitro assays, may underestimate the extent of recovery.

Animals↗
PubMedDate not supplied

In vitro cytotoxicity of the conjugate adriamycin with anti-sarcoma monoclonal antibody 19-24.

Monoclonal antibody (MoAb) 19-24, which recognizes a cell surface sarcoma-associated antigen p102, was linked via a biotin-avidin-biotin bridge to adriamycin (ADR). The molar ratios of ADR: total protein ranged from 2 to 7.5. Significant differences were not observed between the binding ability of the ADR-MoAb conjugate and of the unconjugated MoAb 19-24 to fresh sarcoma tissue membranes. The ADR-MoAb conjugate also retained the ability to compete with MoAb 19-24 for binding to sarcoma-associated antigen p102. In vitro cytotoxicity studies using human fibrosarcoma cells showed that the ADR-MoAb conjugate maintained 40% of the efficacy of free ADR. However, the conjugate was not cytotoxic to p102 antigen negative rat fibrosarcoma SP-24 cells. These data support the suggestion that MoAb-drug conjugates might be helpful in developing highly specific antisarcoma therapeutic agents.

Antibodies, Monoclonal↗
PubMed2005

[Surgical approaches to the skull base neoplasms].

OBJECTIVE: To discuss the best surgical approach to the skull base neoplasms. METHODS: Retrospective analysis the 79 skull base neoplasms cases treated with surgical resection in Qilu hospital of Shandong university from 1992 to 2002. Eleven surgical approaches including midfacial degloving, frontal coronal discission, nasal eversion, maxillary swing, partial maxillary resection, total resection of orbit, mandibular swing, combination of front, temple, preauricular, post aureum, neck, and transoral approaches were used to resect the tumor which involved fossae pterygopalatine, paranasal sinuses, nasopharynx, antero, meso and posterobasilar region, lobi frontalis and lobi temporalis of cerebrum. RESULTS: Seventy-nine skull base neoplasms were totally removed and no one died from the operation. Although 5 cases complicated with cerebrospinal fluid leak and all recovered within 1 week, no serious cranium-cerebrum complication occurred. In 29 patients with benign tumor including 11 cases of meningioma, 3 cases of chondroma, 1 case of hemangio-meningioma, 1 case of cavernous hemangioma, 2 cases of osteodysplasia fibromas, 9 cases of neurofibroma, 1 case of glomus jugular tumor, 1 case of neurilemmoma, 19 have survived over 5 years and the longest one has survived over 8 years. For 50 patients with malignant tumor including 3 cases of well-differentiated squamous cell carcinoma, 17 cases of moderately differentiated squamous cell carcinoma, 11 cases of poorly differentiated squamous cell carcinoma, 1 case of undifferentiated carcinoma, 2 cases of chondrosarcoma, 5 cases of canceration of papilloma, 2 cases of adenocarcinoma, 1 case of esthesioneuroblastoma, 2 cases of malignant fibrohistiocytoma, 1 case of fibrosarcoma, 2 cases of malignant mixed tumour, 3 cases of sarcoma survival rates of 3 and 5 years were 59.2% (29/49), 38.5% (10/26) respectively. CONCLUSION: In order to resect the tumor completely and reduce the complication and malformation as far as possible, different surgical approaches must be designed according to the pathological changes characters and involved area,and the surgeon should select the shortest approach, avoid to damage the important neurovascular structure, and resect the tumor through the natural anatomy space by the shelter incision.

Adult↗