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Biomedical subjects

M Sorensen

Publications and source records attributed to M Sorensen.

At least 19 recordsLinked to original sources
PubMed2001

Postoperative and late survival outcomes after major amputation: findings from the Department of Veterans Affairs National Surgical Quality Improvement Program.

BACKGROUND: A surgical risk model is used to analyze postoperative mortality and late survival for older veterans who underwent above- or below-knee amputations in 119 Veterans Affairs (VA) hospitals from 1991 to 1995. METHODS: Preoperative medical conditions and laboratory values abstracted by the VA National Surgical Quality Improvement Program were linked to subsequent hospitalization and survival through 1999. Logistic regression and proportional hazards models were used to develop risk indexes for postoperative mortality and long-term survival. RESULTS: Thirty-day postoperative mortality was 6.3% for 1909 below-knee and 13.3% for 2152 above-knee amputees. Mortality varied greatly between the lowest-highest risk index quartiles (0.8%-18.4% for below-knee amputation and 2.3%-31.1% for above-knee amputation). Surviving patients had 10,827 subsequent VA hospitalizations during a median 32-month follow-up. Survival probabilities for below- and above-knee amputees were 77% and 59% at 1 year, 57% and 39% at 3 years, and 28% and 20% at 7.5 years. The lowest quartile of survival risk had a 61% five-year survival compared with 14% for the highest-risk quartile. CONCLUSION: A generic surgical risk model can be of use in stratifying prognosis after major amputation. The heavy burden of hospital use by these patients suggests the need for better disease management for this high-risk, high-cost patient population.

Adult↗
PubMed2001

Postoperative and amputation-free survival outcomes after femorodistal bypass grafting surgery: findings from the Department of Veterans Affairs National Surgical Quality Improvement Program.

PURPOSE: A noncardiac surgery risk model was used as a means of analyzing variations in postoperative mortality and amputation-free survival for older veterans undergoing femorodistal bypass grafting surgery. METHODS: A prospective cohort study was undertaken in 105 Veterans Affairs (VA) hospitals at the time of index operation from 1991 to 1995. Each patient was linked to subsequent hospitalizations, major amputation surgery, and survival through 1999. Logistic regression and proportional hazards models were used as a means of developing risk indices on the basis of risk factors from the VA National Surgical Quality Improvement Program. A total of 4288 male veterans 40 years or older underwent artificial, vein, or in situ bypass grafting surgery at the femoral to tibial level. The main outcome measures were 30-day postoperative mortality and amputation-free survival. RESULTS: Approximately half of all patients had undergone an earlier revascularization or amputation at any level for vascular disease. The 30-day postoperative mortality rate was 2.1% and varied greatly between mortality risk index quartiles (0.6%-5.2%). In a median 44.3 months of follow-up, surviving patients had 17,694 subsequent VA hospitalizations, 1147 patients (26.7%) underwent subsequent major amputation, and 1913 patients (44.6%) died. The overall survival probability was 88% at 1 year and 63% at 5 years; 1- and 5-year (any sided) limb salvage rates were 87% and 74%, respectively, for patients who underwent a femoropopliteal bypass grafting procedure, compared with 77% and 63%, respectively, for patients who underwent a tibial bypass grafting procedure. When amputation and death were combined as end points, amputation-free survival probability rates at 1, 3, and 7.5 years were 74%, 56%, and 29%, respectively. Patients with the best 20% survival risk scores had observed mean survival probability rates 30% higher than patients in the poorest 20% of survival risk. CONCLUSION: Risk indices derived from the preoperative workup may be of use to clinicians in assessing and communicating risk and prognosis. Risk-adjustment of outcomes is critical for evaluating future disease management initiatives for patients with advanced peripheral arterial disease.

Aged↗
PubMed2001

[Polymorphic markers for the angiotensinogen and angiotensin-converting enzyme in Yakuts. Lack of association with blood pressure level].

Allele frequency distributions of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the M235T polymorphism of the angiotensinogen gene was studied in a random sample of the indigenous population of the Sakha Republic. The allelic variants of these genes did not showed an association with blood pressure in Yakuts.

Angiotensinogen↗
PubMed2000

A dose escalating study of topotecan preceding cisplatin in previously untreated patients with small-cell lung cancer.

BACKGROUND: The aim was to define the MTD of topotecan (TPT) given before cisplatin in patients with previously untreated SCLC. PATIENTS AND METHODS: Alternating cycles A and B to a total of 6 cycles were given. Cycle A: TPT days 1-5 and cisplatin (50 mg/m2) day 5. Cycle B consisted of teniposide, carboplatin, vincristine, and cisplatin. TPT was escalated at doses 0.75, 1.0, 1.25, and 1.5 mg/m2. DLT was defined for the first cycle as grade 4 neutropenia with fever or when lasting > 7 days, or grade 4 thrombocytopenia. RESULTS: Fifteen patients with limited disease and six patients with extensive disease were included. No episodes of DLT were recorded in the first cycles A and consequently 1.5 mg/m2 was defined as MTD. At 1.5 mg/m2 (11 patients, 30 cycles), four and three episodes of grade 4 thrombocytopenia and neutropenia lasting more than seven days occurred in subsequent cycles A. Thrombocytopenia and anaemia were cumulative as more cycles were administrated. Non-hematological toxicity was mild. The response rate was 86% (95% confidence interval (95% CI): 64%-97%) with 33% (95% CI: 15%-57%) achieving CR. CONCLUSIONS: 1.5 mg/m2 TPT can be delivered safely with 50 mg/m2 cisplatin on day 5 in patients with previously untreated SCLC.

Adolescent↗
PubMed1999

Effect of cellular ATP depletion on topoisomerase II poisons. Abrogation Of cleavable-complex formation by etoposide but not by amsacrine.

Topoisomerase (topo) II poisons have been categorized into ATP-independent and -dependent drugs based on in vitro studies. We investigated drug-induced topoII-DNA complexes in intact cells almost completely depleted of ATP. Virtually no DNA single-strand breaks (SSBs), as measured by alkaline elution, were detected in energy-depleted cells treated with the topoII poisons etoposide, teniposide, daunorubicin, doxorubicin, mitoxantrone, or clerocidin. This inhibition was reversible; subsequent incubation with glucose restored the level of DNA SSBs. The effect of ATP depletion was specific for topoII, because topoI-mediated cleavable complexes induced by camptothecin were unaffected by ATP depletion. Furthermore, etoposide-induced DNA-protein complexes and DNA double-strand breaks, as measured by filter elution techniques, and topoIIalpha and -beta trapping, as measured by a band depletion assay, were completely inhibited by energy depletion. Differences in drug transport could not explain the effect of ATP depletion. The topoII poison amsacrine (m-AMSA) was unique with respect to ATP dependence. In ATP-depleted cells, m-AMSA-induced DNA SSBs, DNA double-strand breaks, DNA-protein complexes, topoIIalpha and -beta trapping were only modestly reduced. The accumulation of m-AMSA was reduced in ATP-depleted cells, which indicates that drug transport could contribute to the modest decrease in m-AMSA-induced cleavable complexes. In conclusion, drug-induced topoII-DNA complexes were completely antagonized in ATP-depleted cells, except in the case of m-AMSA. One possible interpretation is that m-AMSA mainly produces prestrand passage DNA lesions, whereas the other topoII poisons tested exclusively stabilize poststrand passage DNA lesions in intact cells.

Adenosine Triphosphate↗
PubMed1998

Immunohistochemical detection of DNA topoisomerase IIalpha, P-glycoprotein and multidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) differ significantly in their clinical response to topoisomerase IIalpha (topo-IIalpha)-directed drugs, such as etoposide and teniposide, as NSCLC is virtually insensitive to single-agent therapy, while SCLC responds in two-thirds of cases. Preclinical studies have indicated that resistance to topo-IIalpha drugs depends on topo-IIalpha content and/or activity, the altered-topo-II multidrug resistance phenotype (at-MDR) and/or one of two different drug efflux pumps, P-glycoprotein (P-gp) and the multidrug resistance protein (MRP). Immunohistochemical analysis on paraffin-embedded tissue from 27 cases of untreated NSCLC and 29 cases of untreated SCLC (of which additional tumour biopsies after treatment with topo-IIalpha-directed drugs were available in ten cases) yielded the following results: NSCLC had significantly less topo-IIalpha than SCLC (P < 0.0001), as only 5 out of 27 NSCLC cases had > 5% positive cells compared with 28 out of 29 SCLC, and 0 out of 27 NSCLC had > 25% positive cells compared with 26 out of 29 SCLC. P-gp was detected in > 5% of cells in only 3 out of 27 NSCLC and in 6 out of 29 SCLC, and MRP in 5 out of 27 of NSCLC and 9 out of 29 SCLC. After treatment of patients with SCLC with either etoposide or teniposide, which are topo-IIalpha-directed drugs, there was an increase in MRP (P < 0.1) and P-gp (P < 0.05) positivity, while topo-IIalpha decreased (P < 0.05). In conclusion, the major difference between untreated NSCLC and SCLC was in topo-IIalpha content. In the small series of ten patients treated for SCLC, all three MDR phenotypes appeared to increase.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Low-level resistance to camptothecin in a human small-cell lung cancer cell line without reduction in DNA topoisomerase I or drug-induced cleavable complex formation.

To study the evolution of camptothecin (CPT) resistance, we have established two small-cell lung cancer cell lines with low (3.2-fold, NYH/CAM15) and high (18-fold, NYH/CAM50) resistance to CPT by stepwise drug exposure. NYH/CAM50 cells had reduced topoisomerase I (topo I) content and activity, and consequently CPT-induced DNA single strand breaks (SSBs) were reduced, as measured by alkaline elution. In contrast, NYH/CAM15 cells had identical topo I content and activity as compared with wild-type (wt) cells. CPT-mediated SSBs and the rate of their reversal after drug removal were also equal in wt and NYH/CAM15 cells, as were doubling time, the fraction of cells in S-phase and DNA synthesis rate in response to CPT. As the conversion of DNA SSBs to DNA double strand breaks (DSBs) is thought to represent a critical event leading to cell death, we measured DNA DSBs by neutral elution. In contrast to DNA SSBs, CPT induced fewer DNA DSBs in NYH/CAM15 than in wt cells. DNA flow cytometry showed that, in CPT-treated cells, the G1 phase was emptied as cells accumulated in late S- and G2M phase. A Spearman rank correlation showed that depletion of G1 and accumulation in late S and G2M correlated to CPT sensitivity in these three cell lines. In conclusion, acquired resistance to CPT can occur without a reduction in either topo I enzyme or CPT-induced cleavable complex formation, while a decrease in the level of CPT-induced DNA DSBs may be of major importance in the early stages of CPT resistance.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Current therapy of small cell lung cancer.

This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated with initial versus delayed radiotherapy. No survival differences in the larger study of the two studies were detected, which compared alternating with sequential delivery of radiotherapy (n = 335). The optimal way to deliver radiotherapy still must be defined. Two small, randomized studies on dose intensity with the use of growth factor support in patients with extensive disease reached conflicting results. Two randomized trials including patients with poor prognosis were discontinued prematurely, owing to interim analyses reporting a significant disadvantage in survival associated with oral single-agent etoposide compared with intravenous multiagent treatment. Thus, oral etoposide has a very limited role as single-agent treatment in the palliative setting. Convincing data have emerged regarding the camptothecins. Randomized studies of both the camptothecins and the taxanes in combination with established drugs are awaited with interest. Unfortunately, too many studies still lack sufficient statistical power, and large randomized studies are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

pH-dependent regulation of camptothecin-induced cytotoxicity and cleavable complex formation by the antimalarial agent chloroquine.

Two classes of drugs interact with DNA topoisomerase (topo) I, namely topoI poisons such as the camptothecins, which create DNA single-strand breaks and the catalytic inhibitors, which do not. Here, we demonstrate that the antimalarial agent chloroquine is a catalytic inhibitor of eukaryote topoI, as the drug inhibited topoI-mediated DNA relaxation. Chloroquine is known to be a topoII catalytic inhibitor and as such is able to inhibit the activity of a topoII poison, i.e. etoposide. We now show that chloroquine also inhibits the topol poison camptothecin as camptothecin-stimulated nicking of plasmid DNA was inhibited by chloroquine. These observations also apply to endogenous topoI in whole cells. Accordingly, camptothecin-induced single-strand breaks as well as cytotoxicity were antagonised by chloroquine. Further, in a band depletion assay in whole cells, chloroquine prevented camptothecin-mediated topoI trapping, indicating that chloroquine inhibits topoI by interfering with the DNA binding step of the enzyme. In contrast to camptothecin, chloroquine is a weak base and therefore does not enter the cell if the extracellular fluid is acidic, as is the case in most solid tumors. This leads to the possibility of directing cytotoxicity to solid tumors with low extracellular pH by combining a neutral anticancer agent, i.e. camptothecin with a weak base antagonist, i.e. chloroquine. To test the feasibility of this principle, we investigated the drug combination at varying extracellular pH. We found that the antagonising effect of chloroquine on camptothecin-mediated trapping of topoI and DNA single-strand break formation was abolished at acidic extracellular pH. In a clonogenic assay, camptothecin in combination with chloroquine selectively killed cells at low pH (6.2), while camptothecin cytotoxicity was antagonised by chloroquine at normal pH (7.2). In conclusion, we show that the topoI catalytic inhibitor chloroquine inhibits camptothecin and that chloroquine can target the cytotoxic effect of camptothecin to tumor cells in acidic environments.

Antimalarials↗
PubMed1997

The effect of beta-turn structure on the permeation of peptides across monolayers of bovine brain microvessel endothelial cells.

PURPOSE: To investigate the effects of the beta-turn structure of a peptide on its permeation via the paracellular and transcellular routes across cultured bovine brain microvessel endothelial cell (BBMEC) monolayers, an in vitro model of the blood-brain barrier (BBB). METHODS: The effective permeability coefficients (Peff) of the model peptides were determined across BBMEC monolayers. The dimensions of the aqueous pores in the tight junctions (TJs) of the BBMEC monolayers were determined using a series of hydrophilic permeants. This value and the molecular radius of each peptide were used to calculate the theoretical paracellular (PP*) and transcellular (PT*) permeability coefficients for each peptide. RESULTS: A comparison of the theoretical PP* values with the observed Peff values was made for a series of model peptides. For the most hydrophobic peptides (Ac-PheProXaaIle-NH2 and Ac-PheProXaaIleVal-NH2; Xaa = Gly, Ile), it was concluded that the Gly-containing peptide of each pair more readily permeates BBMEC monolayers via the transcellular pathway than the Ile-containing analog. In addition, the Gly-containing peptides, which exhibit more beta-turn structure, were shown to be more lipophilic than the Ile-containing peptides as estimated by the log of their 1-octanol:HBSS partition coefficients (log Po/w). However, the three hydrophilic peptide pairs (Ac-TyrProXaaAspVal-NH2, Ac-TyrProXaaAsnVal-NH2, and Ac-TyrProXaaIleVal-NH2; Xaa = Gly, Ile) were found to permeate BBMEC monolayers predominantly via the paracellular pathway. No differences were observed in the Peff values of the hydrophilic peptides having higher beta-turn structures as compared to the peptides lacking these structural features. In addition, the Ile-containing peptides exhibited significantly higher log Po/w values than the Gly-containing hydrophilic peptides. CONCLUSIONS: Hydrophobic peptides that exhibit significant beta-turn structure in solution are more lipophilic as measured by log Po/w, and more readily permeate BBMEC monolayers via the transcellular route than hydrophobic peptides that lack this type of solution structure. Similar secondary structural features in hydrophilic peptides do not appear to sufficiently alter the physicochemical properties of the peptides so as to alter their paracellular flux through BBMEC monolayers.

Animals↗
PubMed1997

In vitro cross-resistance and collateral sensitivity in seven resistant small-cell lung cancer cell lines: preclinical identification of suitable drug partners to taxotere, taxol, topotecan and gemcitabin.

The acquisition of drug-resistant tumour cells is the main problem in the medical treatment of a range of malignant diseases. In recent years, three new classes of anti-cancer agents, each with a novel mechanism of action, have been brought forward to clinical trials. These are the topoisomerase I (topo I) poisons topotecan and irinotecan, which are both camptothecin derivatives, the taxane tubulin stabilizers taxol and taxotere and, finally, the antimetabolite gemcitabin, which is active in solid tumours. The process of optimizing their use in a combination with established agents is very complex, with numerous possible drug and schedule regimens. We describe here how a broad panel of drug-resistant small-cell lung cancer (SCLC) cell lines can be used as a model of tumour heterogeneity to aid in the selection of non-cross-resistant regimens. We have selected low-fold (3-10x) drug-resistant sublines from a classic (NCI-H69) and a variant (OC-NYH) SCLC cell line. The resistant cell lines include two sublines with different phenotypes towards alkylating agents (H69/BCNU and NYH/CIS), two sublines with different phenotypes against topo I poisons (NYH/CAM and NYH/TPT) and three multidrug resistant (MDR) sublines (H69/DAU, NYH/VM, and H69/VP) with combinations of mdr1 and MRP overexpression as well as topoisomerase II (topo II) down-regulation or mutation. Sensitivity to 20 established and new agents was measured in a standardized clonogenic assay. Resistance was highly drug specific. Thus, none of the cell lines was resistant to all drugs. In fact, all resistant cell lines exhibited patterns of collateral sensitivity to various different classes of drugs. The most intriguing pattern was collateral sensitivity to gemcitabin in two cell lines and to ara-C in five drug-resistant cell lines, i.e. in all lines except the lines resistant to topo I poisons. Next, all sensitivity patterns in the nine cell lines were compared by correlation analysis. A high correlation coefficient (CC) for a given pair of compounds indicates a similar pattern in response in the set of cell lines. Such data corroborate the view that there is cross-resistance among the drugs. A numerically low coefficient indicates that the two drugs are acting in different ways, suggesting a lack of cross-resistance between the drugs, and a negative correlation coefficient implies that two drugs exhibit collateral sensitivity. The most negative CCs (%) to the new drug leads were: taxotere-carmustine (BCNU) (-75), taxol-cisplatin (-58), ara-C-taxol (-25), gemcitabin-doxorubicin (-32), camptotecin-VM26 (-41) and topotecan-VP16 (-17). The most negative correlations to the clinically important agent VP-16 were: cisplatin (-70); BCNU (-68); camptothecin (-38); bleomycin (-33), gemcitabin (-32); ara-C (-21); topotecan (-17); melphalan (-3); and to the other main drug in SCLC treatment cisplatin were: doxorubicin (-70); VP-16 (-70); VM-26 (-69); mAMSA (-64); taxotere (-58); taxol (-58). Taxol and taxotere were highly correlated (cross-resistant) to VP-16 (0.76 and 0.81 respectively) and inversely correlated to cisplatin (both -0.58). Similarly, camptothecin and topotecan were correlated to cisplatin but inversely correlated to VP-16 and other topo II poisons. From the sensitivity data, we conclude that collateral sensitivity and lack of cross-resistance favours a cisplatin-taxane or topo I-topo II poison combination, whereas patterns of cross-resistance suggest that epipodophyllotoxin-taxane or topo I poison-cisplatin combinations may be disadvantageous.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Maintenance of exercise behavior for individuals at risk for cardiovascular disease.

The purpose of the study was to examine psychological factors associated with maintenance of exercise behavior in a population of middle-aged individuals with elevated risk factors for cardiovascular disease. 191 males and 17 females took part in a one-year diet and/or exercise intervention during 1990-1991. Four years later questionnaires were sent out to the 200 former participants who were still available for contact. 67.9% of those who answered (n = 140) were categorized as exercisers, and 30.7% were categorized as nonexercisers. The majority of the exercisers had exercised at least one and a half years. A chi-squared analysis showed that whether the individuals were exercising or not at present was independent of whether they had exercised or not during the intervention study. Discriminant analyses were used to determine how well physical self-perceptions at different times would categorize exercisers and nonexercisers. Current physical self-perceptions categorized the Active Exercisers (86.9%) and the Nonexercisers (63.3%) the best (in total 79.1% correct classifications). Neither change in physical self-perceptions during the intervention not change in physical self-perceptions from the end of the intervention until four years later, classified the exercise behavior as well. Three social cognitive models, The Self-perception model, The Health Belief model, and The Self-efficacy model, were investigated as discriminators between Active Exercisers and Nonexercisers. Active Exercisers were classified better than Nonexercisers, and current physical self-perceptions showed the highest percentage of total correct classifications. The proposed models were also analyzed as predictors of the variance in self-rated Motivation for Exercise. Outcome Expectations, Compliance Self-efficacy, Perceived Fitness, and Exercise Mastery explained 45% of the variance in self-rated Motivation for Exercise.

Attitude to Health↗
PubMed1996

Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients.

PURPOSE: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). PATIENTS AND MATERIALS: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 microg/m2/h without granulocyte colony-stimulating factor (G-CSF) and 47 to 74 microg/m2/h with G-CSF. RESULTS: Without G-CSF, two of eight patients who received 47 microg/m2/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 microg/m2/h (with a platelet count < 25,000/microL in one). With G-CSF, zero of seven patients treated with 47 microg/m2/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/microL in five) entered at 59 microg/m2/h. Among 39 patients entered at > or = 25 microg/m2/h 9-AC with or without G-CSF, fatigue, diarrhea, and nausea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicities of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia ( r = .85). CONCLUSION: The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 microg/m2/h without G-CSF or 47 microg/m2/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance.

Adult↗
PubMed1995

With a different voice: integrating the psychosocial perspective into routine oncology care.

We have established a psychosocial support system that is highly integrated with physician activities and that is tailored to the special needs of our patient population. The core of this system is the close interaction between the physician and the patient counselor, who is a clinical social worker and psychotherapist. Viewed as a permanent member of the breast cancer team, the patient counselor provides psychosocial care in the oncology clinic using normal clinic events as vehicles for interaction. Thus, time spent waiting in the clinic and follow-up phone calls can be converted to sessions for psychological counselling. This approach has been effective in our patient population, where social biases and financial constraints limit the use of out-of-clinic psychiatric services.

Breast Neoplasms↗
PubMed1995

Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecan.

Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel mechanism of action. Topotecan (TPT), a hydrophilic derivative of camptothecin, is currently undergoing phase II clinical trials in small-cell lung cancer (SCLC). Human SCLC OC-NYH cells were made more than 6-fold resistant to topotecan by stepwise drug exposure and resistance was stable for 70 passages without drug. NYH/TPT cells had half the topoisomerase I level and activity of wild-type cells. However, no difference in camptothecin or topotecan inhibition of topoisomerase I-mediated DNA relaxation was found, indicating that the enzyme itself was unchanged in the resistant cell. In NYH/TPT cells, topoisomerase II alpha and beta levels were increased approximately 2-fold. Accordingly, the topoisomerase II-directed drug etoposide (VP-16) induced an increased number of DNA single-strand breaks in NYH/TPT cells. However, sensitivity to different topoisomerase II-targeting agents in NYH/TPT cells varied from increased to decreased, indicating a role for as yet unidentified factors acting on the pathway to cell death after topoisomerase II-induced DNA damage has occurred. Of 20 anti-cancer agents tested, only hydroxyurea showed marked collateral hypersensitivity in NYH/TPT cells.

Antigens, Neoplasm↗