Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials.

Obtaining a complete response (CR) is the most powerful predictor of survival in extensive-stage small cell lung cancer (SCLC). Improvements in long-term survival in extensive-stage SCLC can be made if the proportion of complete responders to induction therapy can be increased. We performed a phase II trial of the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP regimen) in extensive-stage SCLC. The primary endpoint for this trial is the proportion of patients (pts) obtaining a CR rather than overall response. The null hypothesis for this trial consists of the absence of a CR rate >20%. Paclitaxel was given at doses of 135 (3 pts) or 170 mg/m(2) i.v. over 3 h on day 1. Cisplatin 60 mg/m(2) was given on day 1. On days 1-3 etoposide 80 mg/m(2) per day i.v. was given. G-CSF was used from days 5 to 14 of each cycle. Cycles were repeated q21 days. A two-stage design was used for patient accrual, based on the occurrence of complete responses. Initially, 16 patients were to be accrued. If more than three complete responses were to occur, a further 20 patients would be accrued to the study (Simon's optimal two stage design). Sixteen patients were enrolled. Two patients had a CR (13%) and nine patients had a partial response (56%) for an overall response rate of 69%. The trial was suspended due to the low CR rate. Review of the literature for paclitaxel based front-line treatment combined with EP therapy, in extensive stage SCLC, consistently shows a CR rate <20% but high overall response rate is maintained (thus most responses are partial). As virtually all long-term survivors in extensive-disease SCLC have had a CR to induction therapy and CR remains the strongest predictor of survival for this disease, this may suggest that paclitaxel added to standard EP may improve progression-free survival (and possibly median survival) but is unlikely to significantly improve long-term survival. Initial randomized phase III data confirm the absence of impact on survival for this triple-drug regimen compared to EP therapy alone. Furthermore, other regimens comparing favorably to the EP regimen have all shown consistent CR rates >20% in the phase II setting. In conclusion, consideration should be given to the use of CR rate as a phase II endpoint to determine if a particular regimen should be compared to the standard in a phase III setting for extensive-stage SCLC. A two-stage phase II design based on a minimum required completed responses for further patient accrual is recommended.

Phase II and pharmacokinetic/pharmacodynamic trial of sequential topoisomerase I and II inhibition with topotecan and etoposide in advanced non-small-cell lung cancer.

PURPOSE: In vitro and in vivo preclinical models have demonstrated synergistic activity when topoisomerase I and II inhibitors are administered sequentially. Topoisomerase I inhibitors increase topoisomerase II levels and increase cell kill induced by topoisomerase II poisons. We evaluated this hypothesis in a cohort of patients with advanced non-small-cell lung cancer (NSCLC). METHODS: A group of 19 patients with advanced NSCLC (70% adenocarcinoma) received topotecan at a dose of 0.85 mg/m2 per day as a continuous 72-h infusion from days 1 to 3. Etoposide was administered orally at a dose of 100 mg twice daily for 3 days on days 7-9 (schedule and dose derived from prior phase I trials). Total and lactone topotecan concentrations were measured at the end of the 72-h infusion. Blood samples were obtained immediately after each 72-h topotecan infusion in order to measure the mutational frequency at the hypoxanthine phosphoribosyl transferase (HPRT) locus in peripheral lymphocytes. RESULTS: A total of 55 cycles were administered. Toxicity was mainly hematologic with grade 4 neutropenia occurring in 7% of courses. Only one partial response and two stable diseases were observed. The 1-year survival rate was 33%. There was a statistically significant difference between steady-state lactone concentrations between cycle 1 and cycle 2 with decreasing concentrations with cycle 2 (P = 0.02). This was explained by a statistically significant increase in the clearance of topotecan lactone during cycle 2 (P = 0.03). Total but not lactone concentrations correlated with nadir WBC, ANC and platelet levels. Steady-state plasma lactone levels correlated with the mutational frequency at the HPRT locus (P = 0.06). In the one patient with a partial response a sixfold increase in HPRT mutational frequency was observed, which was not seen in patients with progressive disease. CONCLUSION: The combination of topotecan and etoposide in this schedule of administration has minimal activity in adenocarcinoma of the lung. This lack of activity may be due to the delay in administration of etoposide after the topotecan as studies have shown that the compensatory increase in topoisomerase II levels after treatment with topoisomerase I inhibitors is shortlived (<24 h). The HPRT mutational frequency results suggest that the lack of clinical response may be associated with failure to achieve sufficient cytotoxic dose as indicated by a lack of increase in mutational frequency in those patients with progressive disease. HPRT mutational frequency may correlate with plasma steady-state topotecan lactone levels. Future studies should be directed toward earlier administration of topoisomerase II inhibitors after topoisomerase I inhibition.

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.

Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients.

BACKGROUND: Standard endosonographic (EUS) staging criteria are unreliable for staging esophageal carcinoma after neoadjuvant therapy; however, measurement of tumor size reduction can identify patients who have achieved a pathologic response. In the current study the authors prospectively compared survival between patients classified as responders and those classified as nonresponders by EUS. METHODS: The maximal transverse cross-sectional area of the tumor was measured before and after neoadjuvant therapy in patients who were candidates for multimodality treatment. Response was defined as a > or = 50% reduction in tumor area. RESULTS: A total of 59 patients at 2 centers were followed for a median of 19 months. EUS assessed response in 34 patients (58%). Overall, responders had a median survival of 17.6 months compared with 14.5 months for nonresponders (P < 0.005). Survival was significantly longer in responders compared with nonresponders in the patient subgroup who underwent surgical resection (19.7 months vs. 14.6 months; P < 0. 005), the patient subgroup with adenocarcinoma (21.4 months vs. 10.8 months; P < 0.005), and the patient subgroup initially classified as having T3N1 disease (17.6 months vs. 14.1 months; P < 0.05). Survival was not found to differ significantly between responders and nonresponders in the subgroup of patients with squamous cell carcinoma. EUS response was the only clinical variable that was associated with survival time in a multivariate analysis (relative hazard = 0.27; P < 0.005). CONCLUSIONS: Patients with esophageal carcinoma who respond to neoadjuvant treatment as identified by EUS measurement of reduction in tumor size have a significantly better prognosis than nonresponders.

Multi-institutional phase I/II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma.

PURPOSE: To determine the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP) and thoracic radiotherapy. PATIENTS AND METHODS: Thirty-one patients were enrolled onto this study. During the phase I section of this study, the dose of paclitaxel was escalated in groups of three or more patients. Cycles were repeated every 21 days. For cycles 1 and 2, paclitaxel was administered according to the dose-escalation schema at doses of 100, 135, or 170 mg/m(2) intravenously over 3 hours on day 1. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles 1 and 2, concurrent with radiation) was determined, that dose was used in all subsequent patients entered onto the phase II section of this study. For cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m(2) in all patients. On day 2, cisplatin 60 mg/m(2) was administered for all cycles. On days 1, 2, and 3, etoposide 60 mg/m(2)/d (cycles 1 and 2) or 80 mg/m(2)/d (cycles 3 and 4) was administered. Chest radiation was given at 9 Gy/wk in five fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-stimulating factors were used during cycles 3 and 4 only. RESULTS: Twenty-eight patients were assessable. The MTD of paclitaxel was 135 mg/m(2), with the dose-limiting toxicity being grade 4 neutropenia. Cycles 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles 3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fever occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall response rate was 96% (complete responses, 39%; partial responses, 57%). After a median follow-up period of 23 months (range, 9 to 40 months), the median survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 months) CONCLUSION: The MTD of paclitaxel with radiation and EP treatment is 135 mg/m(2) given over 3 hours. In this schedule of administration, a high response rate and acceptable toxicity can be anticipated.

Evaluation of interleukin-6 in bronchoalveolar lavage fluid and serum of patients with lung cancer.

Increased levels of serum interleukin 6 (IL-6) are found in patients with lung cancer, and it has been shown that this is part of a systemic inflammatory response syndrome. This study was designed to measure IL-6 levels in bronchoalveolar lavage (BAL) fluid of patients with lung cancer and to describe the relationship of BAL fluid IL-6 to the known systemic increase in IL-6. Increased levels of BAL fluid IL-6 can be found in patients with lung cancer as compared with patients with chronic obstructive pulmonary disease who have acute infection (P = .007). In patients with cancer, no correlation between BAL fluid IL-6 and serum IL-6 was found (P = .8). BAL fluid IL-6 did not correlate with the number of lymphocytes or macrophages found in this fluid. BAL fluid IL-6 does not correlate with tumor size. Although serum IL-6 was higher in patients with extensive stage small cell lung cancer as compared with levels in patients with limited stage disease (P = .06), their corresponding BAL fluid levels were not different (P = .9). Serum IL-6 correlated with other acute phase reactants. This study thus demonstrates the feasibility of utilizing BAL fluid analysis for local cytokine/tumor marker production in lung carcinoma. It also shows that a local increase in IL-6 in the BAL fluid is independent of the systemic inflammatory response syndrome, whereas the serum increase in IL-6 is part of this syndrome.

Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data.

Although the association between malignancy and thromboembolic disease is well established, the relative risk of developing initial and recurrent deep vein thrombosis (DVT) or pulmonary embolism (PE) among patients with malignancy versus those without malignancy has not been clearly defined. The Medicare Provider Analysis and Review Record (MEDPAR) database was used for this analysis. Patients hospitalized during 1988-1990 with DVT/PE alone, DVT/PE and malignancy, malignancy alone, or 1 of several nonmalignant diseases (other than DVT/PE) were studied. The association of malignancy and nonmalignant disease with an initial episode of DVT/PE, recurrent DVT/PE, and mortality were analyzed. The percentage of patients with DVT/PE at the initial hospitalization was higher for those with malignancy compared with those with nonmalignant disease (0.6% versus 0.57%, p = 0.001). The probability of readmission within 183 days of initial hospitalization with recurrent thromboembolic disease was 0.22 for patients with prior DVT/PE and malignancy compared with 0.065 for patients with prior DVT/PE and no malignancy (p = 0.001). Among those patients with DVT/PE and malignant disease, the probability of death within 183 days of initial hospitalization was 0.94 versus 0.29 among those with DVT/PE and no malignancy (p = 0.001). The relative risk of DVT/PE among patients with specific types of malignancy is described. This study demonstrates that patients with concurrent DVT/PE and malignancy have a more than threefold higher risk of recurrent thromboembolic disease and death (from and cause) than patients with DVT/PE without malignancy. An alternative management strategy may be indicated for such patients.

Endoscopic ultrasound in restaging of esophageal cancer after neoadjuvant chemoradiation.

BACKGROUND: Endoscopic ultrasound (EUS) is established as the most accurate method currently available for determining the depth of primary cancer invasion (T stage). Standard EUS criteria may not be accurate in assessing depth of cancer invasion and nodal status after patients have received chemotherapy or radiotherapy. METHODS: We conducted a prospective study to determine whether EUS estimation of tumor size could be used to assess response to preoperative chemoradiation. Using EUS, TNM stage was assessed in 31 patients (22 men, 9 women; mean age 62 years) with cancer of esophagus or cardia (19 adenocarcinoma, 12 squamous cell cancer) before initiation of combined radiation and 5-fluorouracil/cisplatin (and/or carboplatinum) chemotherapy. The cross-sectional area of the tumor in the transverse plane at the location where the tumor had maximal thickness was calculated to estimate tumor size. EUS staging and measurement of maximal cross-sectional area were repeated at completion of chemoradiation just before surgery. Response to preoperative chemoradiation was defined as 50% reduction in maximal cross-sectional area. Surgical staging was compared between responders and nonresponders. RESULTS: Eight patients who did not undergo surgery were excluded from analysis. EUST stage in the remaining 23 patients before therapy was as follows: 3 T2, 16 T3, and 4 T4. After chemoradiation, EUS T staging was changed in 6 patients (3 T4 downstaged to T3, 2 T3 downstaged to T2, and 1 T3 downstaged to T1). At surgical pathological examination, 3 patients had no residual tumor in the esophagus (T0), 5 had T1, 3 had T2, 10 had T3, and 2 had T4 tumors. EUS T staging accuracy after adjuvant therapy was only 43%. Maximal cross-sectional area decreased from a mean of 5.5 +/- 2.4 to 1.6 +/- 0.9 cm2 in responders, whereas maximal cross-sectional area went from 7.0 +/- 3.0 to 5.4 +/- 2.2 cm2 in nonresponders (p = 0.009). Ten of thirteen patients with at least a 50% reduction in maximal cross-sectional area (responders) had T0, T1, or T2 tumors at surgery, whereas 9 of 10 nonresponders had T3 or T4 tumors at surgery (p = 0.001). CONCLUSIONS: (1) Standard EUS staging criteria are not accurate after neoadjuvant chemoradiation, (2) reduction in maximal cross-sectional area of tumor appears to be a more useful measure for assessing response of esophageal cancer to preoperative chemoradiation, and (3) responders have an increased likelihood of downstaging at surgery than nonresponders.

A brief intensive cisplatin-based outpatient chemotherapy regimen with filgrastim and megestrol acetate support for advanced non-small cell lung cancer: results of a phase II trial.

To evaluate the efficacy and toxicity of a brief, intensive cisplatin-based outpatient chemotherapy regimen with filgrastim and megestrol acetate support for patients with stage IIIB and IV non-small cell lung cancer (NSCLC) and a favorable performance status. Thirty patients with no prior chemotherapy were enrolled in this phase II protocol. Patients received cisplatin 50 mg/m2, ifosfamide 2 g/m2, mesna, and a 7-day course of oral etoposide beginning on days 1, 15, 29, 43. and 57 for a total treatment duration of 10 weeks. Filgrastim was administered for 7 days after each course of oral etoposide. Megestrol acetate 250 mg PO was administered throughout the duration of chemotherapy. Thirty patients were evaluable for toxicity and 27 for response. Among those evaluable for response, partial remission occurred in 11 (41%) patients, and median survival was 10.5 months. Nadir neutrophil count of < 500/mm3 occurred in 19 (63%) patients. Weight loss occurred in only nine patients (median 3.4 kg, range 1.6-7.3). There was no difference between pre- and post-treatment weights (P=0.35). Two patients developed pulmonary embolism. Grade 3 or 4 non-hematologic toxicity occurred infrequently. This regimen appears to be similar in efficacy to the most active regimens reported by other investigators. Innovative features of the regimen include the brief treatment duration, the use of serial 7-day courses of filgrastim to facilitate weekly chemotherapy treatments, and the use of megestrol acetate to minimize constitutional symptoms. However the use of megestrol acetate in this setting may be associated with an increased risk of thromboembolic complications. This may provide a model for other palliative regimens specifically designed for patients with a favorable performance status and advanced NSCLC.

Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer.

PURPOSE: This randomized phase II study evaluated the efficacy and toxicity of etoposide phosphate when used in combination with cisplatin in the treatment of small-cell lung cancer. PATIENTS AND METHODS: Patients with previously untreated small-cell lung cancer were randomized to receive cisplatin in combination with either etoposide or etoposide phosphate. Molar-equivalent doses of etoposide and etoposide phosphate were used. Response rate, time to progression, survival, and toxicity were compared. RESULTS: Major response rates with etoposide phosphate and etoposide were 61% (95% confidence interval, 55% to 67%) and 58% (95% confidence interval, 52% to 64%), respectively (P = .85). No significant differences in median time to progression or survival were observed in patients who received etoposide phosphate versus etoposide. Grade 3 and 4 leukopenia occurred in 63% of patients who received etoposide phosphate compared with 77% who received etoposide (P = .16). CONCLUSION: The combination of etoposide phosphate and cisplatin is effective in the treatment of small-cell lung cancer, and can be administered with acceptable toxicity. Although this study was not designed to be a formal comparative trial, the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar-equivalent etoposide doses. Because of its greater ease of administration, etoposide phosphate is preferable to etoposide for routine clinical use.

Chemotherapy in colorectal carcinoma.

The use of chemotherapy in patients with colorectal carcinoma has changed considerably in recent years. New drugs, drug combinations, and innovative methods of administration are now available for the palliative treatment of patients with metastatic disease. Based on the results of recent clinical trials, adjuvant chemotherapy appears to prolong survival for certain patients who have undergone surgical resection of colorectal cancer. This review article includes a summary of pertinent medical literature and ongoing clinical trials, and provides treatment recommendations.

Pulmonary venous infarction.

Pulmonary venous infarction, although rare, can develop in patients with the various pathologic conditions outlined. The triad of cough, dyspnea, and hemoptysis should raise clinical suspicion. The venous phase of pulmonary arteriography is the best way to document pulmonary venous obstruction, although MR imaging may also prove useful in the future. Treatment of patients with pulmonary venous infarction should be determined on the basis of the obstructing pathologic findings. Antibiotic therapy is important, as evidenced by the early experimental experience with this condition. It may be the only treatment available to patients with idiopathic fibrosing mediastinitis. Pulmonary resection, however, can be accomplished when a localized obstructing lesion is identified.

Pulmonary venous infarction secondary to squamous cell carcinoma.

This type of pulmonary venous infarction has not been previously reported, namely: pulmonary vein obstruction from squamous cell carcinoma. Furthermore, this case is unique in that the characteristic pathologic vascular changes observed with pulmonary venous infarction were contrasted with a noninfarcted upper lobe that was removed from the same patient one year later.

[Prognostic significance of nucleolar markers in chronic lymphocytic leukemia]. / Prognosticheskaia znachimost' nukleoliarnykh markerov pri khronicheskom limfoleikoze.

The morphological criteria have been identified permitting the prognosis of the course character of chronic lymphoid leukemia (CLL). Slow progressing of CLL is attended by the accumulation in the peripheral blood of lymphocytes in the transient stage G0----G1 with ring-like nucleoli surrounded by the perinuclear area. In rapid progressing of the disease, lymphoid cells in stages G1 and S with homogenous nucleoli containing the nucleolar lipid component, are observed in the blood of CLL patients.

Management of non-resectable liver metastases from colorectal cancer.

Among patients who develop recurrent cancer following resection of the colorectal primary, 60-80% develop liver metastases. For such patients, liver resection is the only treatment that offers the potential for cure. Patients with four or fewer liver metastases and no apparent extrahepatic disease should be considered for resection. Patients with non-resectable liver metastases who are asymptomatic may prefer to receive no treatment until such time as symptoms occur. Those with symptomatic or rapidly progressive disease may be offered a variety of treatment approaches: Systemic chemotherapy (20% response rate); hepatic artery infusion; portal vein infusion; intraperitoneal chemotherapy; hepatic resection plus regional chemotherapy; hepatic artery ligation; hepatic artery ligation plus portal vein chemotherapy, and others. The advantages and disadvantages of each are discussed.

[The nucleolar apparatus of the lymphoid cells in AKR mice at different stages of leukemogenesis]. / Nukleoliarnyi apparat limfoidnykh kletok myshei linii AKR na razlichnykh étapakh leikozogeneza.

Morphological features of nuclear apparatus in mice leukemic cells of the peripheral blood, lymph nodes, thymus, bone marrow and spleen were studied. These cells were taken from 12-months-old AKR mice. Enlarged percentage of cells with nucleolar lipid component in thymus characterizes preleukemic state for 6-months-old AKR line mice.

[The spatial reorganization of the perinucleolar area of hematopoietic cells in human leukemias]. / Prostranstvennaia reorganizatsiia perinukleoliarnoi zony gemopoéticheskikh kletok pri leikozakh u cheloveka.

The structure of perinucleolar zone in nuclei of peripheral blood hemopoietic cells has been studied. The cells of human patient with chronic lympholeukemia, chronic myeloleukemia, various forms of acute leucosis have been investigated. The phenomenon of radial strings and border structures has been found in these cells. The features have been revealed by visualization of ribonucleoproteides and lipoproteins. The same process takes place in human lymphocytes after 6-24 h of 3-phosphoglyceric aldehyde stimulation in vitro. A comparative study of morphologic peculiarities of hemopoietic cell nucleolar apparatus depending on cell cycle phase has been performed. The action of cytostatics upon the structure of nucleus perinucleolar zone has been investigated.

Motor neuron disease and paraproteinemia.

We studied two patients with motor neuron disease and paraproteinemia. One had amyotrophic lateral sclerosis (ALS) and IgG lambda monoclonal gammopathy. The second had slowly progressive muscular atrophy and an IgM kappa paraprotein, followed by a biclonal gammopathy when an IgA kappa paraprotein appeared. Treatment with immunosuppressive agents and plasmapheresis lowered the serum concentration of the paraproteins. The ALS syndrome progressed despite therapy. The other patient improved, was stable for several years, but then deteriorated despite continued therapy.

An autoanalyzer test for the quantitation of platelet-associated IgG.

A new quantitative antiglobulin consumption (QAC) test for the measurement of platelet-associated IgG is described. In this test washed platelets are incubated with anti-IgG at a final dilution of 1:2 million. The unneutralized fraction of anti-IgG remaining in solution is then measured with an Autoanalyzer and soluble IgG is used for calibration. The dose-response curves depicting the percent neutralization of anti-IgG by platelets and by soluble IgG were compared in detail and found to be nearly identical, indicating that platelet-associated IgG can be accurately quantitated by this method. The mean IgG values were 2,287 molecules/platelet for normal adults and 38,112 molecules/platelet for ITP patients. The Autoanalyzer QAC test is a sensitive and reproducible assay for the quantitation of platelet-associated IgG.

[Demonstration and characteristics of the perinucleolar zone of the nucleus--a new morphological criterion of the nucleolar test system]. / Vyiavlenie i kharakteristika perinukleoliarnoi zony iadra--novogo morfologicheskogo kriteriia nukleoliarnoi test-sistemy.

A dynamic structure of interphase nucleus--perinucleolar zone has been detected and studied in cell systems on high-level transcription and proliferation activity by means of light and fluorescent microscopy methods. A new light-microscopic level classification of nucleoli taking into account the structure of this zone is introduced. The percentage of nucleoli type distribution may be used as criterion of tissue synthesis activity. An introduction of a new morphological criterion in classical Smetana nucleolar test is under discussion.