Therapy In Cancer Patients Research Articles

The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer

CXCR4, the receptor for stromal cell-derived factor-1(SDF-1), belongs to the chemokine receptor family and has been shown to play an important role in regulating the directional migration of breast cancer cells to sites of metastasis. In the present study, we evaluated the expression of CXCR4 and its association with pathological features and clinical outcome in human breast cancer. Expression of CXCR4 in eight breast cancer cell lines and breast cancer tissues was investigated using conventional PCR. Levels of CXCR4 transcript and protein were examined in human breast cancer tissues (n=120) and corresponding normal tissues (n=32) using real-time quantitative PCR and immunohistochemistry, respectively. The level of CXCR4 expression was analyzed against tumour types, grade, nodal status, recurrence, metastasis, and survival over a median 120 month follow-up period. The expression of CXCR4 was detected in all breast cancer cell lines examined, as well as in breast cancer tissues and breast normal tissues. Breast cancer tissues highly expressed CXCR4 compared with corresponding normal tissues (P=0.029). The level of CXCR4 expression showed a significant difference between node-positive group and node-negative group (19+/-13 vs. 49.7+/-9, respectively, P=0.03). The level of CXCR4 expression was marginal, yet statistically insignificant, higher in tumours from patients with metastatic disease compared with those who remained disease free. No correlation was seen between levels of CXCR4 and the overall survival, although at higher levels of CXCR4 linked to shorter disease free survival (113.0 vs. 136.7 months in patients with low CXCR4, P=0.14, Cox proportional test). The level of CXCR4 expression is significantly correlated with lymph node metastasis. The elevated levels of CXCR4 suggest that the patient has high possibility of lymph node metastasis. CXCR4 may be a useful prognostic indicator and a potential therapeutic target in cancer therapies in patients with breast cancer.

977 Phase I/II trial evaluating blockade of tumour blood supply and tumour cell proliferation with combined bevacizumab and erlotinib HCl as targeted cancer therapy in patients with recurrent non-small cell lung cancer

977 Phase I/II trial evaluating blockade of tumour blood supply and tumour cell proliferation with combined bevacizumab and erlotinib HCl as targeted cancer therapy in patients with recurrent non-small cell lung cancer

Efficacy of UFT plus Tamoxifen for Estrogen-Receptor-Positive Breast Cancer and Tamoxifen plus UFT for???Estrogen-Receptor-Negative Breast Cancer

We conducted a prospective multicentre, collaborative randomised study on postoperative adjuvant therapy in patients with stage II primary breast cancer to evaluate the effect of a combination of tegafur and uracil (UFT) on tamoxifen (TAM) plus mitomycin (MM) in patients with estrogen-receptor-positive [ER(+)] breast cancer and TAM on UFT + MM in patients with estrogen-receptor-negative [ER(-)] breast cancer. MM (13 mg/m(2)) was intravenously administered on the day of surgery for all patients, after which patients with ER(+) were randomised to TAM 20 mg/day (treatment A) or TAM 20 mg/day and UFT 400 mg/day (treatment B). Patients who were ER(-) were randomly allocated UFT 400 mg/day (treatment C) or TAM 20 mg/day and UFT 400 mg/day (treatment D). TAM and UFT were administered orally for 2 years, starting on day 14 after surgery. 5-year disease-free survival (5y DFS), 5-year overall survival (5y OS), and safety. The study commenced in November 1988 and the data cut-off was May 1997 after follow-up of the last patient for 5 years. A total of 765 patients with stage II breast cancer were enrolled. 436 patients with ER(+) [group A: 213, group B: 223] and 317 patients with ER(-) [group C: 162, group D: 155] breast cancer were eligible for this study. The rate of 5y DFS was 83.1% for group A and 90.7% for group B (p = 0.020). There was a significant difference in 5y DFS between the two groups among postmenopausal and positive lymph node metastases patients. The incidence of adverse reactions was 4% for group A and 18% for group B (p < 0.05). The rate of 5y DFS was 77.1% for group C and 85.5% for group D (p = 0.063). The rate of 5y OS was 84.7% for group C and 89.8% for group D (p = 0.216). The incidence of adverse reactions was 18% in group C and 11% in group D (p = 0.06). UFT in combination with TAM + MM showed higher efficacy than TAM + MM as a postoperative combination therapy for breast cancer in patients with ER(+) breast cancer. A trend was observed in favour of the addition of TAM to UFT + MM in postmenopausal and lymph node metastases-negative patients with ER(-) breast cancer.

Integration of Neoadjuvant Chemotherapy and Surgery in the Treatment of Patients with Breast Carcinoma

The use of neoadjuvant chemotherapy has its origins in the management of inoperable locally advanced breast cancer. Several important recent trials have demonstrated that neoadjuvant chemotherapy can increase the resectability rate of primary breast cancer, can allow more patients to successfully undergo breast conservation surgery, and does not confer a survival disadvantage compared with standard, adjuvant chemotherapy. These findings indicate that neoadjuvant chemotherapy is the preferred initial treatment for patients with locally advanced or inflammatory breast carcinoma. Neoadjuvant chemotherapy may also be appropriate in some women with earlier-stage disease. If a patient is predicted to derive little advantage from chemotherapy in the adjuvant setting, it is equally unlikely that an advantage will be seen with neoadjuvant chemotherapy. However, if a woman desires conservative breast surgery and her primary tumor size precludes this approach, neoadjuvant chemotherapy should be offered regardless of clinical disease stage. Careful initial patient assessment and close monitoring of response to neoadjuvant chemotherapy through physical assessment and imaging studies of the primary tumor and nodal metastases are critical in planning breast conservation surgery and have been shown to minimize the risk of local-regional recurrence. The clinical and pathologic response of the primary breast tumor to neoadjuvant chemotherapy appears to be a surrogate marker for the response of occult micrometastases and therefore patient outcome. The most exciting aspect of neoadjuvant chemotherapy in the multidisciplinary management of breast cancer is that neoadjuvant chemotherapy allows for the potential rapid evaluation of promising novel cancer therapies in patients who are predicted to do poorly on the basis of their minimal response to standard cytotoxic regimens. This remains a fertile area for ongoing and future trials of neoadjuvant chemotherapy. By using neoadjuvant chemotherapy, not only can we advance the field of breast cancer research but we may also offer our individual patients an early chance for potentially curative therapy.

Heat-induced p53-dependent signal transduction and its role in hyperthermic cancer therapy

A tumour suppressor gene product, p53, is well known to be activated by genotoxic stress such as radiation and DNA damaging agents. Recently, it has been found that non-genotoxic physiological stresses such as heat, cold and low pH also activate p53, which regulates the expression of downstream genes. p53 was found to contribute to heat sensitivity through Baxmediated apoptosis via activation of caspase-3 in the human cancer cells. This study reviews heat-induced p53-dependent signal transduction and heat sensitivity via a p53-regulated pathway for apoptosis in human cancer cells with identical genetic backgrounds except for p53 status. Furthermore, based on recent reports, it is proposed that p53 status could be a useful indicator in predictive assays for hyperthermic cancer therapy. Hyperthermia treatment based on such predictive assays might improve the outcome and efficiency of cancer therapy in the future. It is further proposed that manipulation of mp53 by glycerol as a chemical chaperone may provide a new cancer therapy for patients with mp53-tumours.

Future prospects for reconstructive surgery in breast cancer.

Reconstructive surgery has become an integral part of primary breast cancer therapy in patients requiring total mastectomy. State-of-the-art reconstructions with autogenous tissue are transverse rectus abdominis (TRAM) flap procedures. Superior aesthetic results in terms of both appearance and consistency, seem to outweigh the disadvantages of impaired abdominal wall competence and donor site scars. The "free," microvascular TRAM flap may be the way to minimize abdominal wall weakness, since only a little portion of the rectus abdominis muscle must be sacrificed. Despite all discussions, breast reconstruction using silicone (gel) implants is a safe and reliable method and will be in the future. However, not every patient may be the right candidate for silicone reconstruction. Advantages of using silicone implants include (relatively) simple technique, short operation time, and no donor site morbidity. In patients suffering from breast-conserving therapy failures, plastic surgery has to address skin and parenchymal loss in an irradiated environment. Oncoplastic surgery, such as volume shrinking or volume replacement techniques, are useful for immediate reconstruction in breast-conserving therapy.

Risk of secondary myeloid leukemia and myelodysplastic syndrome following standard-dose chemotherapy or high-dose chemotherapy with stem cell support in patients with potentially curable malignancies.

Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome (s-MDS) probably represent the worst possible long-term complications of cancer therapy in patients originally cured of their primary malignancy. The frequency and type of s-AML and s-MDS are reviewed for patients treated with standard and/or high-dose chemotherapy for Hodgkin's disease, non-Hodgkin's lymphoma (NHL), and breast or testicular cancer. Patients treated for Hodgkin's disease, have a 20- to 40-fold increased risk of developing s-AML, this risk increasing with the number of mechlorethamine-containing cycles given as well as following splenectomy and in patients more than 40-50 years of age. Generally, patients with NHL, breast or testicular cancer experience a lower, 2- to 15-fold, risk of developing s-AML. Epipodophyllotoxins appear to be the most important factor for s-AML in patients treated for testicular cancer. Doses of 2g/m2 or more are associated with an increased risk of s-AML and, with these high doses, a cumulative incidence of 2% 3% at 5 years is observed. Adjuvant cyclophosphomide, methobrexate, 5-Fu therapy in breast cancer patients does not appear to increase risk significantly as compared to the general population. The extent of the leukemogenic potential of anthracyclines remains to be defined. NHL patients receiving mechlorethamine, prednimustine or long-term maintenance therapy are also at an increased risk of s-AML. A considerably increased risk of developing AML, with a cumulative incidence of approximately 9% at 5 years, has been observed following allogenic bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PBSCT) in patients with NHL. It is likely that the increased risk of s-AML/s-MDS following high-dose chemotherapy with ABMT or PBSCT is related to prior treatment rather than to high-dose chemotherapy itself. However, this issue remains to be conclusively addressed. s-AML or s-MDS rarely develops after allogenic bone marrow transplantation. s-AML and s-MDS increasingly represent a problem in modern cancer therapy because of better treatment strategies, which result in improved cure rates. Patients who receive chemotherapy must be informed about the potential risk of developing s-AML or s-MDS. Future studies should include a follow-up long enough to record the occurrence of all s-AML/s-MDS and all potential influencing factors reliably. These data would enable risk factors to be defined and risk/benefit analyses to be carried out, allowing the correct assessment of current and future therapy strategies.

Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma.

Recently, major advances have been made in the identification of antigens from human melanoma which are recognized by T cells. In spite of this, little is known about the optimal ways to use these antigens to treat patients with cancer. Progress in this area is likely to require accurate preclinical animal models, but the availability of such models has lagged behind developments in human tumor immunology. Whereas many of the identified human melanoma antigens are normal tissue differentiation proteins, analogous murine tumor antigens have not yet been identified. In this paper we identify a normal tissue differentiation antigen, tyrosinase-related protein 2 (TRP-2), expressed by the murine B16 melanoma which was found by screening a cDNA library from B16 with tumor-reactive cytotoxic T lymphocytes (CTL). A peptide conforming to the predicted MHC class I H2-Kb binding motif, TRP-2181-188, was identified as the major reactive epitope within TRP-2 recognized by these anti-B16 CTLs. By site-directed mutagenesis, it was shown that alteration of this epitope eliminated recognition of TRP-2. It was further demonstrated that a CTL line raised from splenocytes by repeated stimulation in vitro with this peptide could recognize B16 tumor and was therapeutic against 3-d-old established pulmonary metastases. The use of TRP-2 in a preclinical model of tumor immunotherapy may be helpful in suggesting optimal vaccination strategies for cancer therapy in patients.

Future prospects for reconstructive surgery in breast cancer

Reconstructive surgery has become an integral part of primary breast cancer therapy in patients requiring total mastectomy. State-of-the-art reconstructions with autogenous tissue are transverse rectus abdominis (TRAM) flap procedures. Superior aesthetic results in terms of both appearance and consistency, seem to outweigh the disadvantages of impaired abdominal wall competence and donor site scars. The “free,” microvascular TRAM flap may be the way to minimize abdominal wall weakness, since only a little portion of the rectus abdominis muscle must be sacrificed. Despite all discussions, breast reconstruction using silicone (gel) implants is a safe and reliable method and will be in the future. However, not every patient may be the right candidate for silicone reconstruction. Advantages of using silicone implants include (relatively) simple technique, short operation time, and no donor site morbidity. In patients suffering from breast-conserving therapy failures, plastic surgery has to address skin and parenchymal loss in an irradiated environment. Oncoplastic surgery, such as volume shrinking or volume replacement techniques, are useful for immediate reconstruction in breast-conserving therapy. © 1996 Wiley-Liss, Inc.

Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer.

The distribution of iodine-131 (131I) labelled antibody to carcinoembryonic antigen (CEA) has been studied in 16 patients with colorectal cancer. Levels of tumour and normal tissue radioactivity were measured by serial gamma-camera imaging and counting of blood and urine. Maximum concentrations were found in tumour 8 h after administration and varied up to 9-fold in different patients. Higher levels were found on average in tumour than in any other tissue. Liver, lung and blood were the other tissues in which antibody was concentrated relative to the rest of the body. Antibody cleared from all these tissues over 1 week. Second antibody directed against the antitumour (first) antibody was given 24 h after first antibody in order to accelerate clearance from the blood. This increased the tumour to blood ratio but had little effect on other tissues. Cumulative radiation dose to tumour and normal tissue was estimated. In patients with the most efficient localisation the tumour to body ratio was 20:1 and tumour to blood ratio 5:1. This may be sufficient for effective therapy of cancer in patients selected for efficient antibody localisation. The data may be used to estimate the effect of different therapeutic strategies. For instance, in the time after second antibody administration the average tumour to blood ratio of radiation dose was 11:1, suggesting that two phase systems in which the therapeutic modality is given after a good tumour to normal tissue ratio is obtained may be effective for the majority of patients.

Utility of Differential Leukocyte Counts in Cancer Management

In 1,811 adult patients receiving diverse treatments for cancers other than leukemia, the absolute neutrophil count closely paralleled the total leukocyte (WBC) count. All of the 1,260 patients with WBC counts higher than 5,000/cu mm had more than 1,500 neutrophils per cubic millimeter. Routine differential leukocyte counts are rarely useful in managing the cancer therapy for patients with a WBC count greater than 5,000/cu mm, and only add to the cost of their care.

Postoperative cancer therapy for patients with carcinoma of the thoracic esophagus: an attempt of aggressive chemotherapy combined with proper nutritional support for patients with distant node metastasis.

The prognosis of patients with advanced thoracic esophageal carcinoma is still poor. In general, patients having distant lymph-node metastasis do not survive for more than 3 years. Therefore, a new therapeutic regimen employing aggressive chemotherapy for these patients has been attempted. In this regimen, three kinds of anticancer drugs Pepleomycin, and twice as much as Adriamycin and Mitomycin of the conventional level for a short period of time are used. Eleven cases were treated with this chemotherapy under active enteral and parenteral nutritional support of 45 to 50 kcal/kg daily. Two patients over 70 years of age died of pneumonitis. Four patients with recurrence of cancer in the lungs, liver and cervical nodes died after 10, 12, 13 and 14 months following surgery, respectively. Five patients have been alive for more than 2 years. These results indicate that this therapy is more effective than other conventional therapies. It has been shown that aggressive chemotherapy combined with proper nutritional support is effective for patients with node metastasis.

CLINICAL APPRAISAL OF COMBINED VITAMIN B6 IN ANTICANCER THERAPY FOR CANCER PATIENTS

gate the methods of diminishing the side effects of antitumor drugs. Vitamin B6, pyridoxal-phosphate that participates to both amino acid metabolism and heme synthesis was administered th the patients with cancer who have been injected antitumor agents, for the purpose of alleviating the side effects of the agents. The molecular structure of pyridoxal-phosphate is shown below . CHO 110,4\,CH2-0-P-OH OH 1-18C/N/ (pyridoxal -5'-phosphate) MATERIALS AND METHODS Animal Experiment Male, Donryu rats*', weigh*1 The animals were supplied from Central Laboratories far Experimental Animals in Tokyo. ing 130 to 150 g were used. The animals were fed the normal pellet*2 or vitamin B6 free diet*3, with water ad libitum. The animals were inoculated subcutaneously with ascitic fluid of AH 130 (one of the ascitic hepatoma) , which was obtained from rats seventh day after inoculation and containing approximately 107 cells. The animals were divided into seven groups of 10 rats each (Tabulation 1). The normal pellet was given the first to the fifth group. The first group served as the control. The Tabulation 1 1 st group control 2 nd group AH 130 was inoculated subcutaneously 3 rd group AH 130 was inoculated subcutaneously Mitomycin C given the 4th group AH 130 was inoculated subpellet cutaneously + Vitamin B6 5 th group AH 130 was inoculated subcutaneously Mitomycin C Vitamin B6 6 th group AH 130 was inoculated subcutaneously given 7 th group AH 130 was inoculatedVitamin B 6 free subcutaneously + di et D esoxypyridoxine