Choice Of Chemotherapeutic Agents Research Articles

Blastocystis hominis and the evaluation of efficacy of metronidazole and trimethoprim/sulfamethoxazole

Blastocystis hominis is commonly found in the intestinal tract of humans. Although the pathogenicity of this unicellular parasite is controversial, anti-protozoan agents are usually administered to infected individuals. At present, the first choice of chemotherapeutic agent is Metronidazole as described in the literature. In this study, we evaluated the effects of metronidazole and Trimethoprim/Sulfamethoxazole (TMP/SMX) on persons infected with B.hominis. A total of 104 subjects infected with B. hominis were admitted to the laboratory from 2002 to 2003. All individuals were non-immunocompromised and subjects were monitored for 1 year after treatment. All stool samples were microscopically examined after staining with iodine and by culturing in an egg slant medium. Of the 104 infected individuals (52+/-16 years of age, M:F=60:44) with B. hominis infection, 28 were discharging large numbers of parasites before treatment. Of 28 severely infected individuals, 12 were treated with metronidazole/250-750 mg at a regimen of 3 x/day/10 days and 4 of the 12 were eradicated. Nine individuals were treated with TMP/SMX/1 tab at a regimen of 3 x/day/10 days and 2 of the 9 were eradicated. For severe B. hominis infections, it appears that metronidazole and TMP/SMX are effective in some individuals, but not all.

Protein levels of p21, p27, cyclin E and Bax predict sensitivity to cisplatin and paclitaxel in head and neck squamous cell carcinomas

Regression of tumor mass by chemotherapy is caused by growth suppression and/or apoptosis of tumor cells. Therefore, expression levels of cell cycle molecules and apoptosis should be predictive markers for the efficacy of a drug. In the present study, the relationship between expression of molecules in the cell cycle and apoptosis and chemosensitivity was investigated in head and neck squamous cell carcinoma cell lines. Expression of p53, p21, p27, cyclin D1, cyclin E, and Bax in 17 such cell lines were analyzed by Western blot analysis. The concentrations of four chemotherapeutic agents (cisplatin, 5-FU, vincristine, and paclitaxel) resulting in 50% cell growth inhibition were calculated as IC50 values for each cell line. Cell cycle analysis was performed using a FACScan flow cytometer. Cells with strong expression of p21, p27, or Bax showed significantly higher sensitivity to cisplatin, and cells with strong expression of Bax or weak expression of cyclin E showed significantly higher sensitivity to paclitaxel. Cisplatin most effectively killed cells expressing both p21 and p27 or either at G1 phase. Though the assessments of p21, p27, Bax, and cyclin E expression in tumor tissues have been reported to be useful as prognostic factors in head and neck squamous cell carcinoma, these correlations might not only describe the malignant biological behavior of the tumor, but also the response to chemotherapy. Furthermore, p21/p27 expression might be a useful guide for the choice of chemotherapeutic agents.

Management of recurrent ovarian cancer: evidence-based decisions.

In this era of advanced medical technology, recurrent ovarian cancer continues to be a therapeutic dilemma. Most of these patients will succumb to their disease process. For this reason, it is of paramount importance for all clinicians to recognize that the primary goal of salvage therapy is to maximize disease-free survival and quality of life. With this goal in mind, they can offer patients a variety of different modalities to control disease, including second-look surgery, secondary or interval cytoreduction, second-line chemotherapy, hormonal therapy, and immunotherapy. The role of second-look surgery has yet to be delineated, but the modality can be helpful in evaluating disease status and guiding further therapy in patients receiving first-line platinum-based chemotherapy or in research protocols. Interval cytoreductive surgery has been shown to confer a survival advantage in a small subset of patients with localized resectable disease proven to be platinum sensitive. The choice of chemotherapeutic agents and the prognosis depend directly on whether the patient is a platinum-sensitive responder. Many agents are approved for the treatment of recurrent ovarian cancer, and the treatment of each patient should be individualized depending on the cumulative toxicities and performance status. Extensive ongoing research trials are underway to elucidate the best salvage therapy.

Sinus histiocytosis (Destombes-Rosai-Dorfman disease) revealed by paraplegia

Sinus histiocytosis with massive cervical lymphadenopathy (Rosai-Dorfman disease) is a non-neoplastic lymphoproliferative disorder. Extranodal involvement, especially of the nervous system, is unusual. We report a case revealed by neurological symptoms. A 10-year-old girl presented with paraparesis due to a dural extramedullary mass on magnetic resonance imaging. Massive cervical lymphadenopathy appeared secondarily. Radiological investigations showed mediastinal, paranasal sinus and lower eyelid involvement. The diagnosis of Rosai-Dorfman disease was established histologically and by immunohistochemical studies of nodal lesions by the demonstration of characteristic sinus histiocytosis with sheets of S-100 protein and CD-68 positive large histiocytes displaying lymphocyte phagocytosis. A dramatic response occurred with complete resolution of all clinical findings after treatment with corticosteroids and etoposide, although neurological lesions were unchanged on magnetic resonance imaging. Despite its rarity, this case underlines the unknown pathogenesis of this disease (immune dysfunction?) and the difficulties of treatment (choice of chemotherapeutic agents, duration).

Study on the relationship between the Bcl-2/Bax ratio and the growth types of leukemic cells and drug resistance in acute myelogenous leukemia.

The ratio of Bcl-2 to Bax (Bcl-2/Bax) in 40 patients with acute myelogenous leukemia (AML) were determined. At the same time, the CFU-L of AML patients and drug resistance were detected by cell culture and MTT assay. The results showed that Bcl-2/Bax in AML was significantly higher than that in normal control (P < 0.001). Bcl-2/Bax ratio in colony growth group was higher than that in no-growth group (P < 0.05). Between drug resistance group and drug sensitivity group there was a significant difference in Bcl-2/Bax ratio (P < 0.05). There were more cases of drug resistance in high ratio group (H) than in low ratio group (L) (P < 0.05). Meanwhile, Complete Remission(CR) rate in group H was obviously lower than that in group L (P < 0.05) and patients in group H tended to have poor response. The above results indicated that the alteration of Bcl-2 and Bax is an important mechanism in the pathogenesis, progress and the development of drug resistance in AML. The determination of Bcl-2/Bax ratio has far-reaching implication in the treatment, choice of chemotherapeutic agents, and prediction of prognosis.

Proceedings of the British Institute of Radiology The combination of chemotherapy and radiotherapy in clinical practice, 10 May 1990

The problem of understanding the response of tumours and normal tissues to combinations of chemotherapy and radiotherapy are complex. The ways in which chemotherapy added to radiotherapy may lead to an improved therapeutic index can be considered under three headings. Spatial co-operation: the use of drugs and radiation to hit disease in different anatomical sites (primary, metastatic). Independent cell kill: if the chemotherapy does not compromise the delivery of a full course of radiotherapy then any cell kill from the drugs should carry a benefit. Enhancement of tumour response: greater than expected tumour cell kill from the combination. The first two mechanisms do not imply interaction between the effects of drugs and radiation. Gains observed in the clinic are probably attributable to one or other of these processes. Synergism between drugs and radiation in the clinical setting is elusive. The optimum therapy probably consists of the best available radiotherapy combined with the best chemotherapy, reducing as far as possible interactions between them in critical normal tissues. Such detrimental interactions can be minimized by choice of chemotherapeutic agents and by maintaining as large a time interval as possible between chemotherapy and radiotherapy.

Management of Cancer During Pregnancy

Although cancer during pregnancy is infrequent, its management is difficult for patients, their families, and their physicians. When termination of the pregnancy is unacceptable, decisions regarding the use of irradiation and chemotherapy are complicated by the well-known high risks of abortion and fetal malformation. This risk is concentrated in the first trimester and varies with the choice of chemotherapeutic agents or combinations of agents. There is only minimal evidence of increased risk of malformation or abortion in the second or third trimester. Recent progress in cancer therapy has made cure a reasonable goal, and for some malignant neoplasms, cure is still possible even when initial therapy is modified or delayed. When cure is a reasonable goal, curative therapy should not be compromised by modification or delay. When treatment for cure or significant palliation is not possible, however, the goal should shift to protection of the fetus from damage by the injudicious use of teratogenic cancer therapy. This report will review the available data that may assist in these difficult decisions.

Treatment of advanced, unresectable, cervical carcinoma already subjected to complete irradiation therapy

Thirty-seven patients with unresectable, previously irradiated, epidermoid carcinoma of the cervix were treated with one of three chemotherapy protocols: (i) moderate dose methotrexate, (ii) high dose methotrexate, and (iii) adriamycin. The choice of chemotherapeutic agent was based on renal and hepatic function. Antineoplastic effect was followed by physical and pelvic examinations, X rays, and scans. Review of the data of patients treated over a period of 3 years demonstrated a clinical response in all three categories. Of interest is the fact that moderate dose methotrexate was the most effective protocol and was well tolerated.