Chemotherapeutic Treatment Of Patients Research Articles

99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent, primary brain tumors

Malignant brain tumors carry a pejorative prognosis and necessitate aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With limited response rate and potential toxicity to chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. To define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy response in recurrent primary brain tumors. In a retrospective analysis, thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT system. A MIBI uptake index (UI) was computed as the ratio of counts in the lesion to those in contralateral region. For all patients, we compared changes over time in UI with MRI and clinical data. The changes in UI agreed well with the clinical and MRI-based assessments in 97% of cases. In 44% of these cases, the scintigraphic response appeared before the MRI response. In instances of treatment failure or rebound, the concordance between scintigraphy and MRI was 52%, and the scintigraphic response appeared before the MRI response in 48% of cases. This study confirms our previous results obtained on a short series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT in prediction of chemotherapy response. Moreover, in cases of tumor progression, we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an average 4 months before MRI changes.

Complete Reversal of ABCG2-Depending Atypical Multidrug Resistance by RNA Interference in Human Carcinoma Cells

In the chemotherapeutic treatment of patients with disseminated neoplasms, multidrug resistance (MDR) is a major obstacle. ABCG2 (BCRP/MXR), a member of the superfamily of adenosine triphosphate-binding cassette (ABC) transporters, was demonstrated to be associated with "atypical" forms of multidrug-resistant phenotypes of cancer cells. To overcome the ABCG2-depending MDR, two specific anti-ABCG2 small interfering RNAs (siRNAs) were designed for transient triggering of the gene-silencing RNA interference (RNAi) pathway in the human gastric carcinoma cell line EPG85-257RNOV, exhibiting an atypical MDR phenotype. Because both siRNAs showed biological activity, for stable inhibition of ABCG2 corresponding short hairpin RNA (shRNA) expression vectors were constructed. By treatment of EPG85-257RNOV cells with these constructs, expression of the targeted ABCG2-encoding mRNA and transport protein was inhibited completely. Furthermore, anti-ABCG2 shRNA-treated cells increased cellular drug accumulation to the same level measured in drug-sensitive parental cells. These effects were accompanied by complete reversal of the drug-resistant phenotype. Thus, the data indicate that siRNA- and shRNA-mediated RNAi-based gene therapy may be applicable in preventing and reversing ABCG2-depending atypical MDR.

Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease.

Chemotherapeutic treatment for patients with symptomatic coronary artery disease to reduce cardiovascular events may be initiated in response to elevated antibody titers against Chlamydia pneumoniae or cytomegalovirus. How antibody titers are associated with the endovascular presence of these microorganisms is still unclear. Antibody titers against C pneumoniae (microimmunofluorescence) and cytomegalovirus (ELISA) in patients undergoing primary (coronary desobliterates, n=80) or repeated CABG (occluded vein grafts, n=45) were correlated with the endovascular presence of the 2 microorganisms. C pneumoniae was detected by means of a nested polymerase chain reaction (PCR) and by culturing. Both conventional PCR and quantitative PCR were applied for detection of cytomegalovirus. C pneumoniae (PCR/culture) was detected in 19/9% (15/80 and 7/80) of coronary desobliterates and in 18/11% (8/45 and 5/45) of occluded vein grafts. There was no statistical evidence that IgG values differed between patients with or without C pneumoniae detection who were undergoing primary CABG. In contrast, repeated-CABG patients with a positive PCR (P=0.0027) or C pneumoniae culture (P=0.0018) had distinctly elevated IgG titers compared with patients in whom C pneumoniae was not detected. Cytomegalovirus could not be detected in the examined specimens. Cytomegalovirus infection does not seem to be associated with advanced coronary artery lesions. C pneumoniae antibody titers are not associated with the endovascular presence of C pneumoniae in patients with coronary artery disease. The observed strong association between elevated IgG titers and the detection of C pneumoniae in occluded vein grafts warrants further investigation.

Analysis of tumour gene expression following chemotherapeutic treatment of patients with bowel cancer

Analysis of tumour gene expression following chemotherapeutic treatment of patients with bowel cancer

Hydroxyurea for Treatment of Unresectable and Recurrent Meningiomas. II. Decrease in the Size of Meningiomas in Patients Treated with Hydroxyurea

In this paper the authors present the first evidence that meningiomas respond to treatment with hydroxyurea. Hydroxyurea was administered as an adjunct chemotherapeutic treatment in patients with recurrent and unresectable meningiomas. Hydroxyurea was used because experimental data demonstrated that it inhibits growth of cultured human meningioma cells and meningioma transplants in nude mice by inducing apoptosis. The authors therefore treated four selected patients with hydroxyurea. All patients had undergone multiple gross resections and all except one received radiotherapy. Three patients with recurrent Grade I meningiomas assessed according to World Health Organization (WHO) guidelines received hydroxyurea because of an increased tumor growth rate, documented by magnetic resonance (MR) imaging, within a 6- or 12-month interval. A fourth patient with a malignant meningioma (WHO Grade III) began a course of treatment with hydroxyurea immediately after his sixth palliative operation without waiting for another relapse to be demonstrated on MR imaging. Because of their location and invasive growth behavior none of the meningiomas could have been removed completely by surgical intervention. All patients received hydroxyurea at a dosage level of 1000 to 1500 mg/day (approximately 20 mg/kg/day). In a man with a large sphenoid wing meningioma invading the right cavernous sinus and the temporal base, the intracranial tumor mass was reduced by 60% during 6 months of treatment. A woman with a large ball-shaped meningioma of the right sphenoid wing invading the cavernous sinus exhibited a 74% decrease of the initial tumor volume in 10 months of treatment with oral hydroxyurea. Serial MR images obtained monthly revealed that the process of size reduction was continuous and proportionate. The shrinkage of the tumor was accompanied by a complete remission of symptomatic trigeminal neuralgia after 2 months and by improved abducent paresis after 5 months. The third patient had a slowly growing meningioma that exhibited a 15% reduction in mass when reassessed after 5 months of hydroxyurea treatment. The fourth patient with the malignant meningioma in the left cerebellopontine angle has had no recurrence for 24 months. Long-term treatment with hydroxyurea may result in full remission of tumors in meningioma patients. The preliminary data indicate that hydroxyurea provides true medical treatment in patients with unresectable and recurrent meningiomas, replacing palliative surgery and radiotherapy in the management of this disease.

Gamma knife radiosurgery as a lesioning technique in movement disorder surgery.

Fifty-five patients underwent radiosurgical placement of lesions either in the thalamus (27 patients) or globus pallidus (28 patients) for treatment of movement disorders. Patients were evaluated pre- and postoperatively by a team of observers skilled in the assessment of gait and movement disorders who were blinded to the procedure performed. They were not associated with the surgical team and concomitantly and blindly also assessed a group of 11 control patients with Parkinson's disease who did not undergo any surgical procedures. All stereotactic lesions were made with the Leksell gamma unit using the 4-mm secondary collimator helmet and a single isocenter with dose maximums from 120 to 160 Gy. Clinical follow-up evaluation indicated that 88% of patients who underwent thalamotomy became tremor free or nearly tremor free. Statistically significant improvements in performance were noted in the independent assessments of Unified Parkinson's Disease Rating Scale (UPDRS) scores in the patients undergoing thalamotomy. Eighty-five and seven-tenths percent of patients undergoing pallidotomy who had exhibited levodopa-induced dyskinesias had total or near-total relief of that symptom. Clinical assessment indicated improvement of bradykinesia and rigidity in 64.3% of patients who underwent pallidotomy. Independent blinded assessments did not reveal statistically significant improvements in Hoehn and Yahr scores or UPDRS scores. On the other hand, 64.7% of patients showed improvements in subscores of the UPDRS, including activities of daily living (58%), total contralateral score (58%), and contralateral motor scores (47%). Ipsilateral total UPDRS and ipsilateral motor scores were both improved in 59% of patients. One (1.8%) of 55 patients experienced a homonymous hemianopsia 9 months after pallidotomy due to an unexpectedly large lesion. No other complications of any kind were seen. Follow-up neuroimaging confirmed correct lesion location in all patients, with a mean maximum deviation from the planned target of 1 mm in the vertical axis. Measurements of lesions at regular interals on postoperative magnetic resonance images demonstrated considerable variability in lesion volumes. The safety and efficacy of functional lesions made with the gamma knife appear to be similar to those made with the assistance of electrophysiological guidance with open functional stereotactic procedures. Functional lesions may be made safely and accurately using gamma knife radiosurgical techniques. The efficacy is equivalent to that reported for open techniques that use radiofrequency lesioning methods with electrophysiological guidance. Complications are very infrequent with the radiosurgical method. The use of functional radiosurgical lesioning to treat movement disorders is particularly attractive in older patients and those with major systemic diseases or coagulopathies; its use in the general movement disorder population seems reasonable as well.

Osmotic blood-brain barrier disruption and chemotherapy in the treatment of high grade malignant glioma: patient series and literature review.

In the past, chemotherapeutic treatment of patients with high grade malignant gliomas following surgery and radiation has not added significantly to the 12-14 month median survival rate. Over four years, 37 patients with high grade malignant gliomas underwent 246 treatment procedures with a combination of methotrexate, cyclophosphamide, and procarbazine given in association with hyperosmolar mannitol-induced transient breakdown of the blood-brain barrier. These patients have demonstrated a median survivorship of 22 months after considering age, Karnofsky Performance Score, and necrosis by the Cox Proportional Hazards model. The study group had a mean age of 43 years, and mean Karnofsky Performance Score of 67%. Sixty-five percent of the procedures had well-documented barrier disruption. Sixteen percent remained in complete remission while 24 patients (65%) had partial or temporary remission. Progression-free intervals after blood-brain barrier disruption/chemotherapy ranged from 1-47 (mean 15) months. Neurotoxicity has been minimal with one peri-procedural mortality and five patients suffering an increase in neurologic deficit after a procedure. The results of this study are consistent with and further extend the reported literature on this method of brain tumor therapy as described in other centers. Chemotherapy in conjunction with osmotic disruption of the blood-brain barrier may provide the pharmacokinetic advantage sufficient to significantly improve survival in patients with high grade malignant glioma.

Preclinical antitumor activity of 5-aza-2′-deoxycytidine agains human head and neck cancer xenografts

The antitumor activity of 5-aza-2'-deoxycytidine (5-aza-dCyd), a nucleoside analog, was established in human head and neck cancer xenografts, transplanted in nude mice. A significant response was noted in 3 of 5 lines, when the drug was injected intraperitoneally at a maximum tolerated dose of 2 mg/kg every four days for three doses. In two most sensitive lines 1 out of 6 tumors regressed completely. The antitumor activity of the drug may depend on the schedule used, as illustrated by the fact that just one of these two lines appeared to be sensitive when treated with low daily doses (0.25 mg/kg). In two lines, 5-aza-dCyd showed equal or better antitumor activity when compared to the conventional drugs known to produce remissions in patients with head and neck cancer (cisplatin, methotrexate, bleomycin, 5-fluorouracil and cyclophosphamide). 5-Aza-dCyd is a drug with potential value in the chemotherapeutic treatment of patients with head and neck cancer [corrected].

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.

Chemotherapy in Gynecologic Cancer

Although progress in the chemotherapeutic treatment of patients with solid tumors has been slow, such treatment may afford some benefit to patients with most types of recurrent or disseminated gynecologic cancer that cannot be helped with either irradiation or surgery.

Rebound phenomenon of phytohemagglutinin skin reactivity in leukemia and malignant lymphoma after chemotherapy.

Serial evaluation of host immunocompetence was made by the phytohemagglutinin (PHA) skin test in 13 patients with leukemia and malignant lymphoma, receiving antineoplastic chemotherapy to induce remission. A rebound phenomenon of skin reactivity to PHA was observed after each period of chemotherapeutic treatment in patients with a good response to therapy, but not in patients with a poor prognosis. It is concluded that sequential evaluation of skin reactivity to PHA, as well as in vitro lymphocyte stimulation, is valuable clinically in assessing the progress of malignancies and the response of patients to therapy.

CHEMOTHERAPY IN GYNECOLOGIC CANCER

Although progress in the chemotherapeutic treatment of patients with solid tumors has been slow, such treatment may afford some benefit to patients with most types of recurrent or disseminated gynecologic cancer that cannot be helped with either irradiation or surgery.