Treatment Of Metastatic Carcinoma Research Articles

Genetic and iatrogenic defects in peripheral tolerance associated with anti-nephrin antibody-associated minimal change disease

Introduction: Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear. Case Presentation: Here, we present two patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3 leading to reduced regulatory T-cells (Tregs). Serum could not be obtained from this patient during the active phase of MCD to directly establish the presence of anti-nephrin antibodies. However, this patient demonstrated IgG dusting over podocyte cell bodies by immunofluorescence microscopy, as well as colocalization of IgG with nephrin in confocal microscopy. The second patient developed MCD in the context of immune checkpoint inhibitor (ICI) treatment for metastatic carcinoma. Anti-nephrin antibodies were detected in this patient during active disease. The patient’s kidney biopsy also showed evidence of binding of anti-nephrin antibodies within the glomeruli. Conclusion: These cases demonstrate that genetic and iatrogenic mechanisms of breakdown in peripheral tolerance can lead to MCD.

Combination Chemotherapy for Metastatic Hepatic Carcinoma and the Relation of Immune Status to the Response

Metastatic carcinoma presents a significant challenge in cancer treatment due to its aggressive nature and propensity for resistance to traditional therapeutic approaches. This systematic research paper delves into the development and evaluation of a novel combination chemotherapy regimen involving the use of 5-fluorouracil, cyclophosphamide & mitomycin C, and PHA skin test in the treatment of metastatic carcinoma, lymphomas, and breast cancer. The study aims to investigate the efficacy and safety profile of this combined chemotherapeutic approach, utilizing scientific methodology and analysis to assess its potential as a promising treatment option for patients with advanced cancer.

In colon cancer cells fascin1 regulates adherens junction remodeling.

Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination. Few studies have examined AJ remodeling in cancer cells consequently, it remains poorly understood and unleveraged in the treatment of metastatic carcinomas. Fascin1 is an actin-bundling protein that is absent from the normal epithelium but its expression in colon cancer is linked to metastasis and increased mortality. Here, we provide the molecular mechanism of AJ remodeling in colon cancer cells and identify for the first time, fascin1's function in AJ remodeling. We show that in colon cancer cells fascin1 remodels junctional actin and actomyosin contractility which makes AJs less stable but more dynamic. By remodeling AJs fascin1 drives mechanoactivation of WNT/β-catenin signaling and generates "collective plasticity" which influences the behavior of cells during cell migration. The impact of mechanical inputs on WNT/β-catenin activation in cancer cells remains poorly understood. Our findings highlight the role of AJ remodeling and mechanosensitive WNT/β-catenin signaling in the growth and dissemination of colorectal carcinomas.

Simplified/same day (s)-GOLF as first-line treatment of metastatic carcinoma of unknown primary (CUP).

e15665Background: CUP represents a therapeutic challenge in oncological practice. Evidence lacks to support particular chemotherapy selection and empirical therapies are commonly extrapolated from ...

Targeted osmotic lysis of metastatic carcinomas by simultaneous blockade of sodium pumps and stimulation of voltage‐gated sodium channels (842.1)

Metastatic carcinomas (MCs) overexpress voltage‐gated sodium channels (VGSCs) by up to 1500‐fold. We reasoned that electrical stimulation of VGSCs with concomitant blockade of Na+, K+‐ATPase (sodium pumps) would produce a rapid increase in intracellular sodium, causing an influx of water. This would cause the MC cells to swell and burst. To test this hypothesis in vitro, we cultured MDA‐MB‐231 cells, which overexpress NaV1.5 VGSCs by 1400‐fold. Treatment with the sodium pump blocker ouabain then electrical stimulation of the cells produced lysis in as little as 16 sec. Ouabain or electric current alone did not lyse the cells. Treatment did not lyse MCF‐10a (normal breast) cells. To test the hypothesis in vivo, we established MDA‐MB‐231 allographs in nude mice. When tumor diameter reached approximately 1 cm, we administered 10 mg/kg ouabain s.c. or saline. 30 and 60 min later, tumors received 60 sec of 10V DC delivered through direct contact stimulation. This single‐treatment produced 70% cell lysis in tumors treated with both ouabain and stimulation. Tumors treated with saline alone and saline plus stimulation averaged 10% lysis. Ouabain alone produced 15% cell death. Treatment did not affect noncancerous tissue. In survival studies, single day treatment attenuated tumor growth by 45%. 3‐Day treatment attenuated growth by 60%. Thus, targeted osmotic lysis can be an effective treatment of MCs that overexpress VGSCs.

CT-guided interstitial brachytherapy for metastatic carcinoma of lymph nodes in mediastinum

Objective To investigate the technique,safety and clinical value of CT-guided percutaneous interstitial brachytherapy for metastatic carcinoma of lymph nodes in mediastinum.Methods Eight patients with metastatic carcinoma of lymph nodes in mediastinum were treated by CT-guided interstitial implant of radioactive seeds in our department.Anterior approach were performed on all cases,125I radioactive seeds were implanted by setting CT Gantry at an oblique angle,three-dimensional reconstruction with SCT and separation the narrow gap between aortic arch and superior vena cava with fiatscalp core.Dose distributions were checked by TPS after operation.The improvement in clinical symptoms and lymph node sizes were documented in order to investigate the therapeutic effects.Results The particle coverage rate was 93.5％ ± 1.5％.According to the CT scans two months later,3 patients ( 37.5％ ) had complete ablation,4 (50％) partial ablation,and 1 ( 12.5％ ) stable disease.Overall response rate (CR + PR) for this group of patients was 87.5％.The symptoms of all patients including shortness of breath (5 patients),cough (4 patients),dysphagia (4 patients) showed varying degree of improvement.No edema of head-and-neck and upper extremity was observed.There was no major vascular,tracheal and esophageal injury.A small amount of pneumothorax was observed in one patient.Conclusions CT-guided percutaneous interstitial brachytherapy,a minimally invasive procedure associated with favorable therapeutic results,is a promising technique for treatment of metastatic carcinoma of lymph nodes with local pressure symptoms which may not respond to conventional therapy. Key words: Brachytherapy; Carcinoma; metastatic lymph node; Interstital irradiation; Implantation

A Pilot Phase II Trial of Valspodar Modulation of Multidrug Resistance to Paclitaxel in the Treatment of Metastatic Carcinoma of the Breast (E1195): A Trial of the Eastern Cooperative Oncology Group

Background: To assess the activity and toxicity of valspodar (PSC-833) in combination with paclitaxel in women with anthracycline refractory, metastatic breast cancer. Patients and Methods: Limited, multi-institutional, Phase II trial of valspodar at 5 mg/kg/dose orally every 6 hours for 12 doses in combination with paclitaxel 70 mg/m2 administered intravenously as a 3-hour infusion beginning 4 hours after the fifth dose of valspodar, every 3 weeks. Eligible patients had bi-dimensionally measurable metastatic carcinoma of the breast, prior anthracycline therapy or a medical contraindication to anthracycline therapy, no more than one prior chemotherapy for recurrent or metastatic breast cancer, and adequate organ function. Treatment was continued until disease progression or unacceptable toxicity. Results: Thirty-four patients are evaluable for response and 37 for toxicity. Two (6 percent) patients achieved a complete response and 5 (15 percent) a partial response for an objective response rate of 21 percent (95 percent confidence interval of 9 to 38 percent). Median duration of response was 9.7 months (95 percent confidence interval 8.0–17.2 months), median time to progression was 3.3 months (95 percent confidence interval 2.0–4.2 months), and median survival was 12 months (95 percent confidence interval 8.1–17.3 months). The toxicity experienced was acceptable. Conclusions: Combination valspodar plus paclitaxel is an active regimen and has acceptable toxicity. The combination is not clearly more active than single agent paclitaxel.

What patients want to know about disease and treatment

8240 Background: Treatment of metastatic carcinomas is accompanied with disturbing facts about disease and treatment, therefore many doctors as well as patients, prefers “not-to-tell if not-asked” and vice versa attitude. Also, communication with patients is complicated because little is known about what patients actually wants to know about disease and treatment. To improve communication with patients, we have conducted a survey with primary aim to determine how well our patients are informed and which information they find to be most useful. Also, age related differences are analyzed. Methods: The self-designed questioner (18 questions) is distributed among 200 hospitalized patients at the medical oncology department. Patients were stratified according to gender, age and education. Results: There were 99 females, 101 males; 31% of patients are elderly (>60 yrs, median 67). Age related differences were most prominent. Elderly patients are most interested about treatment duration (79%), less for side effects (40%), and the rate of treatment failure (30%).Younger patients are almost equally interested for all treatment aspects. 52% elderly patients, think that information about rate of expected response is not useful at all, as compared to 28% of younger; 93% elderly would prefer verbal information rather that written inform consent (only 7%); 72% of younger patients prefers verbal information, 21% would like to get all informing options (verbal, written, internet); 15% of elderly don't know any relevant information about diseases (as compared to 1% of younger patients); 59% of the elderly were not informed about the side effects of the treatment (25 % of younger). None of the elderly patients claimed to be disinterested to get more information about disease and treatment (7,5% of younger). Conclusions: Majority of patients are most interested about treatment duration, side effects of treatment, and rate of therapy failure. Elderly patients were clearly less informed about all aspects of the planed treatment. However, it seems that elderly patients are at least equally interested about disease and treatment and prefer rather verbal communication with the doctors, than written information. No significant financial relationships to disclose.

Preservation of Activities Daily Living (ADL) in a phase-II impact study of oral capecitabine and vinorelbine in the treatment of metastatic carcinomas in patients 70 and older: The GERICO-01 Study by the French FNCLCC Group

8160 Background: In the next 2 decades, 70% of all cancers will occur in elderly patients (pts) above 70 . Methods : In Gerico-01, with pts 70 years or older, the primary endpoint of the study was the autonomy preservation as measured by the ADL in 6 item; 2nd objectives were toxicity (NCI-CTC v2), PK study of V, the serum PSA or CA 15–3 levels variation and the tumor targets evaluation (RECIST); the primary tumors were either metastatic disease from a primary Breast, or a lung or a prostate Ca. The treatment was Q-3 weeks an oral combination chemotherapy (CT) with C day 1–14 at a starting dose of 750 mg/m2 twice a day and oral V, days 1 and 8 at a starting dose of 45 mg/m2/d. After three cycles the dose could be escalated up to 1000 mg/m2 twice a day and 60 mg/m2 respectively. At inclusion, the creatinin clearance must be above 30 ml/min (Cokroft Formula). Dose adaptation was according to the observed toxicity. C+V was discontinued in progressive disease, or the loss of 2 or more ADL criteria, or any grade III-IV toxicities. Results : Between december 2002 and 2003, 65 pts were included in 8 different French centers and 12 are still under treatment. The pts' median age was 75 yrs (70–86); the primary was a breast in 28, a prostate in 31 and a lung Ca in 6 pts. ADL preservation/ improvement was seen in 22 evaluated pts at 6 cycles and decreased in 6 pts. Among breast carcinoma there were 5 partial remission, 1 in prostate and 1 in lung ca, stable disease was seen in 2 breast, 9 prostate, 1 lung; C+V was stopped in 9 progressive disease, 3 cases of toxicity, 1 pt. refusal. Among 15 Severe Adverse Events, 1 hand-foot syndroma, 2 overdosages, 1 occlusion, 1 femoral neck fracture and 1 tachycardia. Conclusion : Although response rate remains limited, this oral C+V regimen is very well tolerated in elderly pts in preserving their ADL and a good quality of life for pts with uncurable disease. No significant financial relationships to disclose.

Preservation of Activities Daily Living (ADL) in a phase-II impact study of oral capecitabine and vinorelbine in the treatment of metastatic carcinomas in patients 70 and older: The GERICO-01 Study by the French FNCLCC Group

8160 Background: In the next 2 decades, 70% of all cancers will occur in elderly patients (pts) above 70 . Methods : In Gerico-01, with pts 70 years or older, the primary endpoint of the study was the autonomy preservation as measured by the ADL in 6 item; 2nd objectives were toxicity (NCI-CTC v2), PK study of V, the serum PSA or CA 15–3 levels variation and the tumor targets evaluation (RECIST); the primary tumors were either metastatic disease from a primary Breast, or a lung or a prostate Ca. The treatment was Q-3 weeks an oral combination chemotherapy (CT) with C day 1–14 at a starting dose of 750 mg/m2 twice a day and oral V, days 1 and 8 at a starting dose of 45 mg/m2/d. After three cycles the dose could be escalated up to 1000 mg/m2 twice a day and 60 mg/m2 respectively. At inclusion, the creatinin clearance must be above 30 ml/min (Cokroft Formula). Dose adaptation was according to the observed toxicity. C+V was discontinued in progressive disease, or the loss of 2 or more ADL criteria, or any grade III-IV toxicities. Results : Between december 2002 and 2003, 65 pts were included in 8 different French centers and 12 are still under treatment. The pts' median age was 75 yrs (70–86); the primary was a breast in 28, a prostate in 31 and a lung Ca in 6 pts. ADL preservation/ improvement was seen in 22 evaluated pts at 6 cycles and decreased in 6 pts. Among breast carcinoma there were 5 partial remission, 1 in prostate and 1 in lung ca, stable disease was seen in 2 breast, 9 prostate, 1 lung; C+V was stopped in 9 progressive disease, 3 cases of toxicity, 1 pt. refusal. Among 15 Severe Adverse Events, 1 hand-foot syndroma, 2 overdosages, 1 occlusion, 1 femoral neck fracture and 1 tachycardia. Conclusion : Although response rate remains limited, this oral C+V regimen is very well tolerated in elderly pts in preserving their ADL and a good quality of life for pts with uncurable disease. No significant financial relationships to disclose.

The mutated androgen receptor and its implications for the treatment of metastatic carcinoma of the prostate.

Androgen deprivation is the most effective therapy for patients with advanced prostatic carcinoma. The lack of androgen stimulation on these cells causes them to become apoptotic. Although therapeutic efficacy of initial androgen deprivation in prostate cancer is high, the emergence of androgen-independent cancer is inevitable. Withdrawal of the antiandrogen flutamide elicits surprising activity in these cancers. In numerous studies the response rates cell line harbors a mutation in codon 877 of the androgen receptor. The mutant receptor loses androgen specificity and is activated by various steroids as well as flutamide. Identical and similar mutations have now been isolated from human prostate cancer tissue. The discovery of the mutated androgen receptor sheds light on the emergence of androgen-independent cancer and should facilitate the development of more efficacious therapies.

CO 2 laser subcapsular orchidectomy in the treatment of prostate cancer.

Hormonal manipulation remains the main method of treatment in metastatic carcinoma of the prostate. Traditional techniques of surgical castration may result in complications due to bleeding within the scrotum. Because of its cutting and hemostatic properties the carbon dioxide laser has been used in performing subcapsular orchidectomy in an attempt to reduce such complications. Postoperative hormonal assays have demonstrated a response identical to orchidectomy, and no treatment complications were encountered in our series. Subcapsular orchidectomy using the carbon dioxide laser may offer an advantage over traditional methods of surgical castration by reducing the frequency of postoperative hematoma.

Megestrol acetate in the treatment of metastatic carcinoma of the prostate.

Although current hormonal therapy of prostate cancer may not appear to have altered survival appreciably, there have been considerable changes that may significantly affect the future management of this disease. A number of new hormonal agents have been introduced that still require definition of their therapeutic efficacy. Megestrol acetate, a hormonal agent with multiple sites of action in androgen metabolism, has recently been investigated in the treatment of patients with metastatic and locally advanced disease, and in those patients whose disease progresses with other hormonal therapies. Megestrol acetate plus mini-dose diethylstilbestrol (DES) is associated with fewer side effects than standard-dose DES and has equivalent therapeutic efficacy in the treatment of patients with metastatic disease. In patients with locally advanced disease that may benefit from hormonal cytoreduction, megestrol acetate is effective and well tolerated. Megestrol acetate has a role in the palliation of patients with progressive disease despite initial hormonal therapy. Considerable controversy surrounds the therapy of carcinoma of the prostate; further studies are required to define optimal hormonal therapy.

Therapeutic options in treatment of advanced carcinoma of the prostate.

Considerable controversy continues to surround the therapy of metastatic carcinoma of the prostate. Until recently orchiectomy and diethylstilbestrol (DES) were the only treatment options available. The development of megestrol acetate is of interest because of its broad spectrum of activity and excellent patient acceptability. Interim results of a study comparing megestrol acetate 120 mg/d plus mini-dose DES 0.1 mg/d with DES 3 mg/d are reported. Megestrol acetate had minimal side effects, with 2% of patients withdrawing from the megestrol acetate arm because of toxicity, compared with 37% from the DES arm. Significant cardiovascular toxicity occurred in 33% of patients taking DES and in 7% taking megestrol acetate. Both therapies achieved permanent suppression of serum testosterone to castrate levels. Time to progression and overall survival were longer with DES treatment, 17 versus 23 months and 24 versus 44 months, respectively, but this was not significant (P = .34 and P = .16, respectively). A review of the literature on the treatment of metastatic carcinoma of the prostate is presented to determine what should be recommended as standard therapy. Total androgen blockade is analyzed critically and results of therapy are compared with other modalities. Based on efficacy, cost, toxicity, and patient acceptability, orchiectomy still should be considered standard therapy and total androgen blockade should be considered experimental.

Monoclonal Antibodies in the Treatment of Metastatic Carcinoma to the Liver

Thirteen patients with metastatic liver carcinoma were treated with hepatic irradiation, leukopheresis and monoclonal antibodies to test the tumoricidal effects of murine 17-1A immunoglobulin G (IgG) Mab. A significant increase in survival for this group of patients was identified.

Hormonal therapy trials in prostatic cancer. An EORTC Genitourinary Group study.

In this paper the authors review the completed and current EORTC Genitourinary Group trials for metastatic carcinoma of the prostate. In terms of time to progression and length of survival, there is no significant difference between any of the effective endocrine treatments that have been studied. The statistical analysis of the different variables used in trials 30,761 and 30,762 determines three risk groups of patients. There is no need for very special laboratory investigations to establish a prognosis. Orchiectomy is the cheapest and safest endocrine treatment in metastatic carcinoma of the prostate.

Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate

Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate

Cyproterone acetate lead-in prevents initial rise of serum testosterone induced by luteinizing hormone-releasing hormone analogs in the treatment of metastatic carcinoma of the prostate.

Luteinizing hormone-releasing hormone (LH-RH) analogs are an effective treatment of metastatic carcinoma of the prostate. However, they induce an initial rise in serum testosterone responsible for 10-30% of diseases flares. The efficacy of the antiandrogen cyproterone acetate (CPA) was tested in 15 patients with metastatic carcinoma of the prostate. 10 patients were given 100 mg CPA t.i.d. from day 1 to 14 in association with the LH-RH analog Buserelin, 500 micrograms t.i.d., from day 7 to 14.5 patients were given CPA and Buserelin at the same doses from day 1 to 7. Serum testosterone determinations were obtained on days 1-7, 8, 11 and 14, at 08.00 h, and on days 8, 11, 1 h after each analog injection in group 1, and on days 1, 4 and 7 at 08.00 h and 1 h after each analog injection in group 2. All the patients were then treated by orchidectomy. Pretreatment with CPA blunted the initial rise of testosterone which never rose above pretreatment levels. Simultaneous treatment had no demonstrable effects on the rise of serum testosterone. It is concluded that pretreatment with CPA allows a safer use of LH-RH analogs in the treatment of metastatic carcinoma of the prostate.

Clinical assessment of solid phase immunoadsorbent assay of human prostatic acid phosphatase

A new solid phase immunoenzyme assay for human prostatic acid phosphatase was tested in clinical practice. Clearly elevated levels of prostatic acid phosphatase (PAP) were found with advancing age and even more so in patients with benign prostatic hyperplasia (BPH). In patients with localized carcinoma of the prostate there was no elevation of levels above those observed in patients with BPH. When lymph node metastases were found at staging lymphadenectomy, the preoperative level of prostatic acid phosphatase was elevated in 7 of 12 cases. Good response to hormone treatment of metastatic carcinoma of the prostate was indicated by decrease of PAP-levels to normal. Rising levels often preceded the clinical manifestation of progression.

256 Steroid receptors and response to medroxyprogesterone treatment in metastatic carcinoma of the breast

256 Steroid receptors and response to medroxyprogesterone treatment in metastatic carcinoma of the breast