Chemotherapeutic Cycle Research Articles

Abstract 2026: MicroRNA-214 is a negative regulator of p53

Abstract The p53 transcription factor mediates multiple cellular functions including the response to genotoxic stress, differentiation, cell cycle and apoptosis. Since p53 inactivation is a critical event in tumor development, the regulation of p53 and its pathway is of prime importance in the understanding of tumorigenesis. While a number of microRNAs have been shown to be regulated by p53, microRNA regulation of p53 is still not well documented. Here we demonstrate that miR-214, a putative oncogenic miRNA, regulates p53 protein but not mRNA level by direct targeting 3′UTR of p53. Ectopic expression of miR-214 represses p53 and enhances the resistance to radiation- or chemotherapeutic agent-induced cell cycle arrest and apoptosis in wild-type but not mutated p53 cells. Introduction of p53 cDNA lacking 3′UTR largely abrogates miR-214-induced cell growth and survival. Depletion of endogenous miR-214 elevates protein level of p53 and induces apoptosis in human cancer cell lines expressing wild-type p53. These findings indicate that miR-214 is an important posttranscriptional regulator of p53 and exerts its oncogenic activity through targeting p53. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2026.

Ewing's sarcoma of the mandible in a young child

Ewing's sarcoma (ES) is a malignancy primarily affecting bone tissue that is commonly diagnosed in adolescents and young adults. Its occurrence in the head and neck region is unusual and generally involves the mandible and maxilla. An extensive review of the literature shows only few cases of the oral ES in patients under the age of 5. This paper reports a rare case of ES of the mandible in a 4-year-old girl, which had been previously misdiagnosed and treated as a dental abscess. In the clinical examination, a hard immobile expansive mass of 5 cm in diameter was observed on the left side of the mandible. Radiographic examination revealed a radiolucent lesion with ill-defined borders and wide vestibular bone plate destruction. Microscopically, the tumor was composed by monotonous small round cells that exhibited immunoreactivity for CD99, vimentin and pancytokeratin. The patient was subjected to multiagent chemotherapy with ifosfamide, carboplatin, etoposide, vincristine, cyclophosfamide and doxorrubycin (VAC/ICE regimen). However, after the first chemotherapeutic cycle, the patient died due to disseminated infection. This case elucidates the importance of professional knowledge of the relevant aspects of malignant lesions such as ES.

Prediction of Progression-Free Survival in Patients With Multiple Myeloma Following Anthracycline-Based Chemotherapy Based on Dynamic FDG-PET

: Dynamic positron emission tomography (PET) studies with F-18-deoxyglucose were performed in patients with multiple myeloma who received anthracycline-based chemotherapy to evaluate the impact of full kinetic analysis and assess its value with regard to progression-free survival (PFS).The evaluation included 19 patients (56 metastatic lesions) with multiple myelomas. All patients received combined anthracycline-based chemotherapy. PFS served as a reference for the PET data. All patients were examined prior to the onset of chemotherapy and on days 23 to 28 after the onset of the first cycle (prior to the second cycle). The following parameters were retrieved from the dynamic PET studies: Standardized Uptake Value (SUV), fractal dimension (FD), 2 compartment model with computation of K1, k2, k3, k4 (unit: 1/min), the fractional blood volume (vB), and the FDG-influx according to Patlak were calculated. : The observed PFS varied from <1 month to 64.1 months with a median PFS of 26 months. Most kinetic parameters demonstrated only small changes, primarily declining after 1 cycle. We compared the kinetic data of each study using a Wilcoxon matched-pairs signed rank test. The results were considered significant for P < 0.05. The test revealed a significant change for the SUV (z = 4.954, P < 0.0000), the FD (z = 5.036, P < 0.0000), the fractional blood volume vB (z = 4.116, P < 0.0000) and influx (z = 2.614, P < 0.0090) when the absolute values of the first and the second study were compared. We dichotomized the patients according to the PFS of 18 months and defined 2 survival groups. The data demonstrate that the correct classification rate (CCR) of group 2 (survival: >18 months) was generally higher (exceeding 94%) than for group 1. The use of the baseline SUV led to a CCR of 82% for the group 2 with the longer survival. The CCR of group 1 with the short survival varied between 55% and 70% depending on the parameter and the study used for prediction. Furthermore, the CCR for both groups based only on the data of the second study was somewhat lower (74%-75%) as compared with the baseline FDG study (75%-82%). Finally, the combined use of the 6 predictor variables, namely SUV, k3, and FD (selected by the Wilcoxon rank sum test) of each study led to the highest CCR of 85% for both groups. This combination was in particular useful for the prediction of group 2 with the longer survival with a CCR of 94%. Best cutoff-values for the differentiation between short and long PFS were SUV of 4.0 and a k3 of 0.07 of the baseline study. : The results demonstrate, that a full kinetic analysis of the FDG studies prior and after 1 chemotherapeutic cycle in patients with multiple myeloma is helpful for the prediction of PFS and may be used to identify those patients who benefit from this chemotherapeutic protocol. A high SUV (>4.0 SUV) as well as a high k3 (>0.07) of the baseline study were bad prognostic parameters and related to a short PFS.

급성골수성백혈병환자의 항암화학요법 주기내의 호중구감소증과 영양상태

본 연구는 급성골수성백혈병의 우선적인 치료방법인 항암화학치료제 투여 후 발생되는 호중구 감소기간을 잘 관리하기 위하여 호중구감소증 정도와 영양상태와의 관련성을 규명한 서술적 조사연구이다. 본 연구는 B시 P대학병원에서 1차 강화항암화학치료까지 받고 회복한 성인환자 54명의 환자의 의무기록지를 열람하여 조사하였다. 연구결과, 항암화학요법 주기내의 호중구감소증이 지속되는 기간은 6일에서 28일(평균 14.78일)이었으며, 호중구감소증이 시작되는 시기는 5일째에서 15일째 사이(평균 9.54일)에 나타났으며, 최저백혈구수의 시기는 평균 18.41일째였으며, 27.8%에서 19일째 가장 적은 백혈구수를 보였다. 항암요법 주기내의 항암화학요법 시작시와 절대호중구수가 가장 낮은 시기의 총단백질량, 체중, 체질량지수와 같은 영양상태 변화는 거의 없었으며, 알부민, 콜레스테롤은 유의하게 감소하였다. 대상자의 일반적인 특성에 따른 호중구감소증은 성별, 나이, 동반질환유무, 체표면적에 따른 차이가 없었다. 호중구감소증과 영양상태간의 상관관계는 없었으나, 급성골수성백혈병 환자의 호중구감소 기간 동안의 영양상태에 대한 정보는 제공해 줄 수 있을 것으로 기대된다. This study aims to investigate chemotherapy-induced neutropenia, nutritional status and both relation of patients with acute myeloid leukemia during 1st consolidation chemotherapy and the therapy-related cytopenic phase in order to determine more effective nutritional support. We review medical records of total 54 cases received first consolidation chemotherapy on P hospital in Busan. The duration of neutropenia(Absolute Neutrophil Count<<TEX>$1000/{\mu}{\ell}$</TEX>) is mean 14.78 days, neutropenia occur on mean 10th(9.54) day of chemotherapy(D10). The nutritional parameters of total protein, body weight, BMI showed no significant interval change during chemotherapeutic cycle except albumin, cholesterol. The neutropenia wasn't dependent on general factor of gender, age, comorbidities, Body Surface Area(BSA). The correlation wasn't revealed between neutropenia and nutritional status. In conclusion, although nutritional status didn't affect neutropenia, this study provides detailed information on the neutropenic response of acute myeloid leukemia patients during induction chemotherapy.

Presence of Herpes Simplex Virus on the Oral Mucosa in Patients Undergoing Chemotherapy

The aim of this study was to confirm the presence of herpes simplex virus type 1 and 2 on the oral mucosa, in patients undergoing chemotherapy, by means of polymerase chain reaction (PCR). The research was carried out on 40 patients receiving chemotherapy as treatment for different malignancies. The status of oral mucosa and viral presence were assessed in all patients at the initial examination (prior to chemotherapy), and at the control examination (two weeks after the initiation of the chemotherapeutic cycle). The presence of HSV-1 was detected in 28 patients (70%) prior to chemotherapy, of whom 7 (25%) manifested oral complications. The control examination showed the presence of HSV-1 in 35 patients (87.5%), of whom 23 (65.7%) presented oral mucosa changes. HSV-2 has not been detected in any of the patients.

Side effects of adjuvant chemotherapy and radiotherapy concurrently after conservative surgery for breast cancer

Observe the side effects of adjuvant chemotherapy and radiotherapy concurrently after breast conservative surgery and investigate it feasible. 40 breast cancer patients of conservative surgery were divided into two groups randomizedly, 20 patients of the study group were given adjuvant chemotherapy and radiotherapy concurrently, 20 patients of the control group were given adjuvant thermotherapy and radiotherapy sequently. Observe the side effects of the patients in the two groups and follow them 6 months. The leukopenia within the third chemotherapeutic cycle and the oral mucitis within the fourth chemotherapeutic cycle in the study group were more severe than those in the control group (P < 0.05). The other side effects within every chemotherapeutic cycles were similar in both groups, including skin reaction in radiotherapeutic area, gastroenteric reaction, alopecia, arthralgia, neurotoxicity and abnormal hepatic function. Following the patients of the two groups in 6 months, there were no significance in hemogram, hepatic and renal function, electrocardiogram and chest x-ray. It is feasible and safe to give the adjuvant chemotherapy and radiotherapy concurrently to the breast cancer patients after conservative surgery.

Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures during chemotherapy in an epileptic patient

To report a pharmacokinetic interaction between valproic acid (VPA) and anticancer agents observed in an epileptic patient. A 34-year old male epileptic patient receiving VPA underwent cisplatin-based chemotherapy for the treatment of a testicular tumour. The first chemotherapeutic cycle decreased the serum VPA concentration and caused severe generalized tonic-clonic seizures. Thus, thereafter, the serum VPA concentration was monitored along with the chemotherapy. In a patient receiving VPA daily, severe seizures were observed 7 weeks after the first chemotherapeutic cycle, at which the serum VPA concentration was found to be reduced by approximately 50% of the initial level (90-100 microg ml(-1)). The following cycles (six cycles over a 7-month period) also caused seizures in association with decreased serum VPA concentrations. In contrast, the serum concentration of phenytoin, which was given daily after the second chemotherapeutic cycle, remained at a therapeutic concentration (10-20 microg ml(-1)). After the completion of chemotherapy, the serum concentration of a tumour marker, hCGbeta, decreased to 1.2 ng ml(-1) from more than 120 ng ml(-1) prior to the chemotherapy in this patient. Careful monitoring of VPA concentrations are necessary during cisplatin-based chemotherapy because anticancer agents can reduce the serum concentration and antiepileptic activity of VPA.

Relationship between plasma concentrations of 5-fluorouracil and 5-fluoro-5,6-dihydrouracil and toxicity of 5-fluorouracil infusions in cancer patients.

This study investigated the relationship among the pharmacokinetics of 5-fluorouracil (5-FU) and 5-fluoro-5,6-dihydrouracil (5-FDHU); the activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells; and treatment-related toxicity in 26 patients with surgically resected colorectal cancer treated with short daily infusions of 5-FU adjuvant chemotherapy, each cycle consisting of 5 consecutive days every 4 weeks. After the first chemotherapeutic cycle, severe stomatitis and diarrhea occurred in 5 patients and were related to the variations in the systemic disposition of the drug rather than to DPD activity. These patients showed a significant decrease in 5-FU clearance, and an increase in the 5-FU/5-FDHU area under the time-concentration curve (AUC) ratio, as compared with patients who experienced mild toxicities, whereas a low DPD activity was observed in only 2 patients. In conclusion, the results of this study demonstrate that the alterations in 5-FU and 5-FDHU pharmacokinetics are related to severe toxicities in patients treated with short intravenous infusion of 5-FU.

Radiological assessment of neoadjuvant chemotherapy in breast cancer

Neoadjuvant chemotherapy has become the standard of treatment for patients with locally advanced breast cancer and is now a potential treatment for patients with earlier stage operable disease. Preoperative chemotherapy allows more patients to be treated with breast-conserving surgery and enables direct in vivo assessment of response, which correlates with outcome. The role of imaging is to evaluate the therapeutic response in term of shrinkage of the tumour in order to safely perform breast-conservation surgery. Neoadjuvant chemotherapy is also a good model to determine which radiological procedure is the most effective to predict histopathological response. Although controversial, several articles reported that physical examination correlates best with pathologic findings in the measurement of the primary tumour. Mammography allows monitoring changes in size and density of the tumour, but cannot identify changes in the inner structure. Ultrasound is the most accurate predictor of size for axillary lymph nodes. Physical examination associated with mammography and ultrasound is a valuable non-invasive combination for assessing tumour dimension. MRI is the best modality for assessment of response in term of tumour size and in the detection of multifocal or multicentric disease. The study of residual tumour vascularity is interesting as the diagnosis is based on the early contrast enhancement. The disappearance of this early contrast enhancement allows correct identification of the response to chemotherapy, even if several studies have reported false negative and false positive cases. Conversely, the detection of a persistent wash out phenomenon in residual tumour permits detection of non-responders. Breast helical CT can be an alternative to breast MRI for the measurement of residual tumour volume and correlation with pathologic findings. Colour Doppler ultrasound and the use of ultrasound contrast agents have given conflicting results because of their operator-dependence. Other functional imaging modalities have been proposed for the assessment of response to neoadjuvant chemotherapy. Mammoscintigraphy using 99mTc sestamibi, shows that a rapid clearance of the tracer can predict the lack of tumour response to chemotherapy, however a slower tracer clearance cannot certify an objective response. Positron emission tomography using 18FDG shows significant difference in tracer uptake between responding and non-responding tumours early in the course of therapy. After the second chemotherapeutic cycle, both techniques are able to distinguish between complete, partial or no response. The disadvantage of the 18 FDG PET is the cost of the technique and the problem of access to the machines. It has also a limited spatial resolution. Combined 18FDG PET and MRI provide useful information because of the high spatial resolution of MR imaging. In conclusion, studying the effect of neoadjuvant chemotherapy will demonstrate the accuracy of these complementary functional imaging techniques.

Vasculitis allergica bei lymphoplasmozytischem Immunozytom

Allergic Vasculitis in a Patient with Lymphoplasmacytic Immunocytoma. Two years after the Initial manifestation of a chronically persisting allergic vasculitis a lymphoplasmacytic immunocytoma was diagnosed in a 50-year-old female patient. Cancer chemotherapy was initiated according to the CHOP-regimen. Complete remission of the lymphoma was already achieved after the second chemotherapeutic cycle, whereas the allergic vasculitis was only gradually declining. After the sixth cycle the therapy was continued with interferon alpha. At that time the dermatosis was also completely healed. Now, twelve months later, there hasn't been any relapse of the vasculitis. The coincidence of a malignant tumor and a leukocytoclastic vasculitis is a rare event with a malignant myeloma being the most frequently detected neoplasm. Other in the literature reported malignant tumors associated with an allergic vasculitis are mentioned.

Changes in Lymphocyte Number during Cancer Chemotherapy and Their Relation to Clinical Response

Since hematologic examination during cancer chemotherapy is generally limited to the evaluation of neutrophil and platelet numbers, at present there are no clear data about the possible prognostic significance of changes in lymphocyte number in relation to the clinical efficacy of chemotherapy itself. To obtain some preliminary data about this issue, we have evaluated changes in lymphocyte number and percentage in a group of 50 advanced non-small cell lung cancer patients treated with three cycles of cisplatin (20 mg/m2/day) plus etoposide (100 mg/m2/day) i.v. for three days every 21 days. The clinical response consisted of partial response (PR) in nine (18%), stable disease (SD) in 18 (36%) and progressive disease (PD) in the remaining 23 (46%) patients. The lymphocyte percentage increased during chemotherapy, without, however, a significant difference with respect to the pretreatment values. In contrast, the mean number of lymphocytes observed after the first chemotherapeutic cycle significantly decreased in patients with PD, whereas it increased in patients with PR or SD, even though the difference did not reach statistical significance. These preliminary data, which have to be confirmed in a large number of patients and in patients treated with other chemotherapeutic schedules for different tumor types, seem to suggest that a chemotherapy-induced decline in lymphocyte number may be associated with a lack of efficacy of chemotherapy itself.

Adjuvant regional arterial port chemotherapy after resection of colorectal liver metastases

Between 1986 and 1995 we performed radical hepatic resections (R0 resections) in 109 patients with hepatic metastases following colorectal carcinoma. In 50 patients a hepatic arterial port device was implanted for adjuvant regional chemotherapy (HAI). Mitomycin C, 5-fluorouracil, and since 1993 folinic acid have been administered during 6 monthly repeated courses. In 9 patients, the treatment had to be withdrawn because of complications. The remaining 59 patients were not treated. In 73% of the patients after port implantation mostly minor complications occurred during chemotherapy. Our results confirmed a markedly increased survival rate during the first 3 postoperative years, followed by a prolongation of median survival time of treated patients compared to untreated patients. Nevertheless, the observed differences of median survival were not statistically different. In contrast, the 5-year survival rates of both groups were not different. The frequency, localization, and resectability of recurrences were not influenced by adjuvant chemotherapy. However, the lengthening of mean survival time in the treated group might reflect a delay in the occurrence of early recurrences. In conclusion, adjuvant hepatic arterial chemotherapy following resection of colorectal hepatic metastases might be able to prolong the time until recurrence, but does not help to avoiding it. Therefore, it did not increase the rate of cure following R0 resections of colorectal hepatic metastases in our series. Taking into account the high rate of local complications of the port systems in our series, angiographic controls are strongly recommended prior to each chemotherapeutic cycle.

In Vitro Effects of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (RhGM-CSF) on Polymorphonuclear Cell (PMN) and Monocyte (MO) Functional Capacities in Ovarian Cancer Patients Versus Human Volunteers

Human polymorphonuclear cells (PMN) and monocytes (MO) from four ovarian cancer patients and seventeen normal donors were in vitro pretreated with different concentrations (25, 50 and 100IU, respectively) of rhGM-CSF. Phagocytosis and killing of PMN and MO as well as PMN polarization were evaluated in cancer patients before treatment (T0) and at the end of each chemotherapeutic cycle (T1, T2, T3 and T4, respectively) in comparison with normal donors. RhGM-CSF did not affect phagocytosis and killing of PMN and MO. On the other hand, this cytokine was per se endowed with the capacity to enhance PMN polarization in both cancer patients (at T2 interval) and normal donors.

F wave studies after intrathecal methotrexate administration.

Electrophysiological examinations were done on 20 patients aged 40-71 years with recently diagnosed high grade non-Hodgkin's lymphomas. General chemotherapy and intrathecal chemotherapy in order to prevent central nervous system (CNS) involvement were begun. On the first day of chemotherapeutic cycle patients received intrathecally methotrexate (ITMTX) and prednisolone. Electrophysiological study was carried out twice in each subject: before ITMTX injection and a day after injection. The study procedure included: a conventional nerve conduction examination (peripheral conduction velocity and compound muscle action potential amplitude), the F wave latency and amplitude measurement and F ratio (F-M-1/2M) calculation for peroneal and tibial nerve bilaterally. Results of the first and the second examinations were statistically compared by t-Student's test. No significant differences between values of estimated parameters were found. The study revealed no recent alterations in proximal, paraspinal motor conduction and motor neuron excitability due to antidromical activation after single ITMTX administration.

Application of Positron Emission Tomography in Colorectal Carcinoma

New diagnostic methods like the positron emission tomography (PET) provide functional information about tumors and metastases. Tumor perfusion can be quantitatively evaluated with the use of radiolabeled tracers. Furthermore, quantitative data on the tumor metabolism are obtained with metabolically active radio-pharmaceuticals. PET studies with 18F-deoxyglucose and other tracers like amino acids can help to achieve and early diagnosis of tumor recurrence. While the sensitivity of PET is high for recurrent colorectal tumors (29/30 true positive), false positive results may be obtained in patients with inflammatory reactions. Therefore, a quantitative evaluation of the data is mandatory, and the results must be interpreted in combination with preexisting clinical data. 18F-labeled fluorouracil (FU) can be used to obtain quantitative data on kinetics and therapeutic effects. The comparison of systemic and regional tracer injection showed that perfusion and FU transport into the tumor cells can be independent parameters. The outcome of chemotherapy can be predicted using 18F-labeled FU and PET prior to the first chemotherapeutic cycle. A correlation of 0.86 was noted for the 18F-FU accumulation and the tumor growth rate during chemotherapy. Studies in primary colorectal tumors treated with regional FU infusion demonstrated a correlation of the FU accumulation with tumor blood flow and metabolism. PET can be used in these patients to select the ones who are most likely to respond to therapy. Since the number of radiolabeled cytostatic drugs is limited at present, the development of new radiolabeled cytostatic agents is the major aim of a combined working group from the EORTC and the EEC Programme on PET.

Effect of cytotoxic drugs on the function of the hypothalamo-pituitary-adrenal axis.

We measured the serum concentration of thyroid-stimulating hormone (TSH), its response to exogenic TSH-releasing hormone (TRH), as well as cortisol plasma levels before and after stimulation with adrenocorticotrophic hormone in 15 patients before, during and after a chemotherapeutic cycle. 3/6 patients receiving only cytotoxic drugs developed a marked suppression of the TSH response to TRH and 1 of these patients showed an impairment of the adrenal function under chemotherapy. This was also observed in 7/9 patients receiving both cytotoxic drugs and corticosteroids; however, the individual pattern of the impairment was quite variable. 5/9 patients in this group developed a suppression of the TSH response to TRH. Impairment of the hypothalamo-pituitary-adrenal axis function under cytotoxic drugs and/or corticosteroids occurs with great variability and the mechanisms involved in its etiology are not yet fully understood.