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M M Lieber

Publications and source records attributed to M M Lieber.

At least 199 records · Page 11Linked to original sources
PubMed1984

Soft agar colony formation assay for in vitro chemotherapy sensitivity testing of human renal cell carcinoma: Mayo Clinic experience.

Two hundred six different samples of human renal carcinoma were tested for in vitro chemotherapy sensitivity using a soft agar colony formation assay similar to that originally described by Salmon and colleagues. Eighty of 159 (50 per cent) evaluable tumor tests showed colony formation in vitro and gave clinical drug sensitivity information. Two-thirds of tumors were resistant to all drugs tested, despite a median number of drugs tested per tumor of 14.5. Five tumors (6 per cent) were remarkably sensitive to numerous anticancer drugs in vitro. The most active drugs found in vitro were teniposide, actinomycin D, bleomycin, hydroxyurea, mitoguanazone dihydrochloride, mitomycin C and L-alanosine. Fourteen other drugs tested showed low in vitro cytotoxicity.

Adenocarcinoma↗
PubMed1984

Improved optical detection of colony enlargement and drug cytotoxicity in primary soft agar cultures of human solid tumour cells.

The presence of cellular aggregates in cell suspensions derived from human solid tumours often complicates subsequent evaluation of colony formation in primary soft agar cultures (Agrez et al., 1982b). In the present study, performance of a conventional colony formation assay was observed to lack sufficient sensitivity to identify growth and active chemotherapeutic agents in the majority of specimen cultures. Modification of conventional methodologies to include filtration of cell suspensions, use of "proliferation control" and "cytotoxicity control" cultures as well as vital staining were found to be essential for the valid assessment of primary soft agar cultures in our laboratory. In addition, application of drugs to culture surface in place of culture incorporation appeared to facilitate culture performance and drug sensitivity testing.

Antineoplastic Agents↗
PubMed1984

Activation and inactivation of cancer chemotherapeutic agents by rat hepatocytes cocultured with human tumor cell lines.

While colony formation assays provide sensitive indices of tumor cell proliferation and growth inhibition imposed by many chemotherapeutic agents, drugs which require metabolic activation lack activity in such assays. In the present study, we have utilized freshly isolated rat hepatocytes for the activation of drugs which are metabolized by hepatic microsomal as well as extra-microsomal enzymes. Hepatocytes in fluid medium are placed over soft-agarose matrix containing tumor-derived cells (e.g., A204, A549) within 35-mm culture dishes; drug and/or drug vehicle is added directly to the hepatocyte layer, and cultures are incubated for 24 hr prior to removal of the hepatocyte layer. Tumor cell colony formation is assessed following 7 to 10 days of incubation. Cyclophosphamide was used as a prototype agent to assess utility of the coculture methodology. In vivo treatment of rats with phenobarbital prior to hepatocyte isolation enhances cyclophosphamide toxicity in vitro, whereas pretreatment with carbon tetrachloride markedly reduced subsequent in vitro cyclophosphamide cytotoxicity. Hepatocyte:tumor cell cocultures provide an efficient means to detect metabolic activation and inactivation of several selected cancer chemotherapeutic agents as well. In the presence of hepatocytes, the 50% growth-inhibitory concentrations for cyclophosphamide, indicine N-oxide, and procarbazine are markedly decreased, whereas the 50% growth-inhibitory concentrations for [2,5-bis(1-aziridinyl)-3,6-diazo-1,4-cyclohexadiene-1,4-diyl]bis(c arbamic acid)diethyl ester, 1,3-bis-chloro(2-chloroethyl)-1-nitrosourea, dacarbazine, 5-fluorouracil, ftorafur, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, and vincristine are significantly increased. By contrast, the 50% growth-inhibitory concentrations for actinomycin D, mitomycin C, 6-mercaptopurine, and other agents are unaffected by hepatocyte presence. Cryopreserved hepatocytes exhibit detectable levels of drug activation, although inadequate for routine use. Results suggest that hepatocyte:tumor cell cocultures may be well-suited for assessing the degree to which hepatic metabolism may activate or inactivate new anticancer drugs.

Animals↗
PubMed1983

Soft agar colony formation assay for in vitro testing of sensitivity to chemotherapy of gynecologic malignancies.

In vitro growth of tumor cells may provide a way of testing the effectiveness of chemotherapeutic agents in the treatment of cancer. In 1980 and 1981, operations for gynecologic malignancy were performed on 610 Mayo Clinic patients, and malignant tissue and fluids were obtained from 204 cancers that involved the vulva, uterus, fallopian tubes, and ovaries. These yielded 76 clonogenic stem-cell preparations; and various chemotherapeutic agents were tested against these 76 tumors on soft agar. Considered in this study were the overall process of culturing the samples of tumors and, especially, the data from the preparations that showed sufficient growth of tumor cells for testing. Our guiding concerns were the usefulness of this method to gynecologists and the possible benefits to patients.

Agar↗
PubMed1983

In vitro chemotherapy sensitivity testing of primary human colorectal carcinomas.

The cells obtained from 138 tumor samples taken from 135 patients with colorectal malignancies were cultured in vitro in a soft agar colony formation assay similar to that of Salmon and colleagues [1]. Significant colony formation occurred for 63 (51%) of evaluable tumor cultures, 53 of which were also tested against chemotherapeutic agents in vitro. The median number of drugs tested per tumor was 15. Using 70% inhibition of colony formation as the criterion for significant drug-induced cytotoxicity, only 3/53 (6%) of the tumors were noted to be sensitive to any drug. When colony counts generated by initially plated small tumor cell aggregates were taken into account, 8/40 (20%) of the tumors were noted to be sensitive in vitro to one or more agents. Because of the low rate of drug sensitivity found with this in vitro assay, its current role in the prospective assignment of chemotherapeutic treatment for patients with colorectal carcinoma is somewhat limited.

Antineoplastic Agents↗
PubMed1983

In vitro chemotherapy sensitivity patterns of human colon carcinoma continuous cell lines.

The cells obtained from four established human colon carcinoma cell lines were cultured in soft agar in the presence of eight chemotherapeutic agents that have been used clinically in patients with metastatic colorectal carcinoma. 5-Fluorouracil, mitomycin C, adriamycin, and cis-platinum were highly cytotoxic in vitro at the concentrations employed. These findings were in marked contrast to in vitro chemotherapy sensitivity patterns previously reported by us for a large series of primary human colorectal carcinomas cultured in soft agar. The possible reasons behind these differences are discussed.

Adenocarcinoma↗
PubMed1983

Hematoporphyrin derivative: quantitative uptake in dimethylhydrazine-induced murine colorectal carcinoma.

The selective affinity of hematoporphyrin derivative (HpD) for dimethyl-hydrazine-induced colorectal malignancies in mice was evaluated both visually and by a quantitative microfluorescent photometric technique. A significant correlation was found between higher concentrations of HpD in colon biopsies determined by microfluorescence spectroscopy and the presence of carcinoma cells in these biopsies as identified by histologic examination. Visual inspection of the gross fluorescence of tumor-bearing colons in this experimental model, however, was not helpful in differentiating malignant from nonmalignant tissue. The implications of this study regarding the clinical application of HpD tumor fluorescence for the detection of colorectal carcinoma are discussed.

Animals↗
PubMed1983

Proliferative potential of cells from normal human colon epithelium, adenomas, and carcinomas of the large bowel.

The proliferative potential of nonmalignant and malignant cells obtained from the human large bowel was assessed with a soft agar culture colony-forming technique and by flow cytometry to analyze cell cycle kinetics. No colony formation occurred with samples of normal human adult colon mucosa. The absence of colony formation in all but 1 of 24 evaluable colorectal adenomas suggested that malignancy of tissue in vivo is generally necessary for colony formation to occur in soft agar cultures. A high proliferative index (S + G2/M), as assessed by flow cytometry, was significantly associated with higher soft agar culture counts in a series of 25 colorectal carcinomas.

Adenoma↗
PubMed1983

Sarcomatoid renal carcinoma.

Sarcomatoid renal carcinoma made up 1 per cent of renal parenchymal tumors resected from 1967 to 1980. The majority of patients with this aggressive type of renal carcinoma were symptomatic and had a palpable renal mass at the time of diagnosis. Only 2 of 13 patients had tumor confined within the renal capsule at the time of operation. One of these patients survived and 12 of 13 died rapidly of metastatic renal carcinoma, with a median survival of 6.3 months from the time of diagnosis. This distinctive histologic variant of renal carcinoma has a highly malignant biological behavior and, as effective adjuvant treatment for renal carcinoma becomes available, should be one of the tumor types treated vigorously.

Adenocarcinoma↗
PubMed1983

Villous adenocarcinoma of the male urethra.

We report on 2 men with multifocal papillary adenocarcinoma arising in the bulbous urethra proximal to a urethral stricture. Histologically, the tumors appeared similar to villous adenocarcinomas of the colon and rectum. Both patients were treated with segmental urethrectomy. Villous adenocarcinoma of the male urethra is a distinctive clinicopathologic entity. Although uncommon it should be added to squamous cell carcinoma and transitional cell carcinoma on the list of tumor types causing cancer of the male urethra.

Adenocarcinoma↗
PubMed1983

Well differentiated (grade 1) clear cell renal carcinoma.

We reviewed the experience at this clinic from 1950 to 1980 with cases of grade 1 clear cell renal carcinoma. We wanted to determine whether patients with well differentiated clear cell renal tumors had the favorable clinical course that has been demonstrated for those with well differentiated oncocytic renal tumors. Of the 46 patients identified with pure grade 1 clear cell renal carcinoma two-thirds were discovered incidentally during diagnostic tests for unrelated complaints. These tumors generally were small, with 67 per cent being 6 cm. in diameter or smaller. Of all tumors 83 per cent were pathologic stage 1 (confined within the renal capsule). However, 10 patients have died of metastatic renal carcinoma and 3 are alive with disease. Actuarial survival curves show a significantly poorer prognosis for patients with grade 1 clear cell renal tumors compared to patients with grade 1 oncocytic renal tumors or to an age and sex-matched control group. We conclude that whereas well differentiated oncocytic renal tumors behave like benign renal tumors, well differentiated clear cell renal tumors can behave like aggressively malignant renal carcinomas and should be treated as such.

Adenocarcinoma↗
PubMed1982

Improved detection of drug cytotoxicity in the soft agar colony formation assay through use of a metabolizable tetrazolium salt.

Use of a metabolizable tetrazolium salt was observed to facilitate assessments of tumor cell drug sensitivity in the soft-agar colony formation assay. Enzyme-mediated staining permits discrimination between viable and non-viable groups of cells so that drug-induced cytotoxicity is clearly identifiable by visual inspection as well as by computerized image analysis. The technique appears to be especially useful in the evaluation of primary tumor cell cultures which often contain substantial numbers of non-viable cellular aggregates.

Antineoplastic Agents↗
PubMed1982

Human colorectal carcinoma: patterns of sensitivity to chemotherapeutic agents in the human tumor stem cell assay.

The human tumor stem cell assay (HTSCA) was applied to 103 primary and metastatic colorectal carcinomas. Thirty-four carcinomas could not be evaluated for colony formation (clonogenicity) because of microbial contamination. Of the remaining 69 carcinomas, 18 (26%) demonstrated clonal growth in vitro. Colony formation did not correlate with the clinicopathologic stage of the tumor, the histological grade of the tumor, the method used to disperse the solid tumors into single cells (mechanical or enzymatic), or cell viability (exclusion of trypan-blue) prior to plating. The in vitro chemotherapy sensitivity data of the 18 tumors which formed colonies indicated that most tumors were generally resistant to chemotherapeutic drugs and that a few tumors were sensitive to multiple agents. Use of the human tumor stem cell assay may facilitate an individualized approach to clinical chemotherapy of colorectal carcinoma for certain patients.

Adenocarcinoma↗
PubMed1982

Cell aggregates in the soft agar "human tumour stem-cell assay".

We evaluated colony formation in soft agar by cells obtained after mechanical and/or enzymatic disaggregation of 455 malignant human tumours. Counting and assessment of cell colonies in the agar plates were done by inverted microscopy, computerized image analysis, and inspection of serial photomicrographs of the agar plates. Our results indicate that standard methods of tumour disaggregation did not usually produce single-cell suspensions and that aggregates of tumour cells varying greatly in size were placed in the agar. Most groupings of cells identified as colonies 1-3 weeks after plating arose from enlargement of preexisting aggregates of cells.

Agar↗