פרופסור עפר מרימסקי

מאמרים בתחום סרטן המעי הגס

 

1. Int J Oncol. 1998 Apr;12(4):921-5.

 

Mononuclear cells release low molecular weight factors with anti-cancer activity:

A lower level of production by cells of cancer patients.

 

Cohen-Aloro D(1), Merimsky O, Bar-Yehuda S, Klein B, Kayzer S, Fishman P.

 

Author information:

(1)Laboratory of Clinical and Tumor Immunology, The Felsenstein Medical Research

Center, Tel-Aviv University, Rabin Medical Center, Petach-Tikva, Israel.

 

Following the clinical observations that tumor metastases are extremely rare in

striated muscles we defined recently a low molecular weight factor which is

released by muscle cells (muscle factor, MF) and possesses specific

anti-proliferative activity against tumor cells. we demonstrate that peripheral

blood mononuclear cells constitutively release low molecular weight factor (LMF)

similar to the MF which is capable of inhibiting in vitro the proliferation of

carcinoma, melanoma, leukemia and lymphoma cell lines. The proliferation of

normal cells such as bone marrow or fibroblasts was not inhibited but slightly

stimulated following incubation with the LMF. Biochemical purification of this

factor by several HPLC steps revealed that the inhibitory activity against tumor

cells was concentrated within two definitive peaks. The LMF affects tumor cell

growth by arresting them in the G0/G1 of the cell cycle and its activity is

species and tumor non-specific. In vivo studies in melanoma- bearing mice

revealed that the LMF inhibited melanoma growth when given either

intraperitoneally or orally. Mononuclear cells from cancer patients with

different malignancies (non-Hodgkin lymphoma, malignant melanoma, colon carcinoma

and carcinoma of the rectum) secreted lower level of LMF in comparison to healthy

subjects. The capability of the LMF to inhibit tumor cell growth and promote

normal cell proliferation combined with its bioavailability in vivo may lead to

its potential therapeutic and diagnostic use.

 

PMID: 9499456  [PubMed - indexed for MEDLINE]

 

 

2. Invasion Metastasis. 1997;17(4):169-75.

 

Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional

administration: animal study.

 

Gutman M(1), Sofer D, Lev-Chelouche D, Merimsky O, Klausner JM.

 

Author information:

(1)Department of Surgery B, Tel Aviv Sourasky Medical Center, affiliated to the

Sackler School of Medicine, Tel Aviv University, Israel.

 

Tumor necrosis factor (TNF) is a highly cytotoxic cytokine. However, due to its

severe side effects, the only clinical situation allowing its administration in

humans is isolated limb perfusion (ILP). Early studies have shown that TNF alone

is of limited efficacy even at high doses via ILP, and that a chemotherapeutic

agent needs to be added. The most commonly used drug in this setting is melphalan

which is considered to be synergistic with TNF. However, since melphalan has not

been commonly used in sarcoma, we believed that confirmation of its synergistic

effect with TNF in an experimental sarcoma model could prove valuable for future

drug choice. B16F10 melanoma and CT26 colon carcinoma cells were injected

subcutaneously (s.c.) into mice, while GF fibrosarcoma cells were injected s.c.

into the hindleg of Wistar rats. The animals were then divided into four

treatment groups: TNF alone, melphalan alone, TNF and melphalan, and 0.9% NaCl

controls. Mice were treated with intraperitoneal injections and rats by ILP. TNF

dosage was 20 microgram for mice and 200 microgram for rats. Melphalan was given

at 5-10 mg/kg for both mice and rats. Results showed synergism of TNF and

melphalan in both modes of therapy. In the systemic administration groups (mice

carrying B16F10 and CT26 tumors), tumors increased in size in all but the

combined TNF-melphalan group. In the regional delivery groups (rats carrying GF

sarcoma cells treated via ILP), there was a 16% decrease in tumor volume in rats

treated with TNF alone, a 29% decrease in rats treated with melphalan, and a 75%

decrease in the combined TNF-melphalan group. In conclusion, TNF and melphalan

proved to be highly synergistic in both systemic and regional delivery. This fact

makes melphalan an adequate choice for TNF perfusion in advanced limb

malignancies.

 

PMID: 9778589  [PubMed - indexed for MEDLINE]

 

 

3. Anticancer Res. 1996 Nov-Dec;16(6B):3673-7.

 

Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo.

 

Gutman M(1), Szold A, Ravid A, Lazauskas T, Merimsky O, Klausner JM.

 

Author information:

(1)Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv University,

Israel.

 

Thalidomide was recently suggested to be angiogenesis-inhibitor following the

demonstration of its activity in a rabbit cornea micropocket model. The purpose

of the present study was to test its efficacy in solid tumors in mice. B16-F10

melanoma and CT-26 colon carcinoma cells were injected subcutaneously,

intravenously and intraperitoneally, and mice received daily gavage of 0.3-1.0 mg

thalidomide starting either two or 10 days following tumor cell injection. The

tumors were measured and compared with controls. There was no growth retardation

in CT-26 bearing mice nor in mice with pulmonary or peritoneal metastases of

B16-F10 melanoma. In 3/7 groups of mice with SC B16-F10 tumors, growth

retardation was demonstrated, however the difference was not statistically

significant. All tumors eventually reached maximal size, similar to controls.

Morphological evaluation of the blood vessels oriented towards the tumor revealed

that in both thalidomide and control groups, all mice had developed an intact

network of new blood vessels. In our model for the oral administration of

thalidomide inhibition of tumor growth and angiogenesis did not occur. We

hypothesize that the lack of sustained antiangiogenic response was either due to

immune modulation or to tumor heterogeneity and adaptation.

 

PMID: 9042240  [PubMed - indexed for MEDLINE]

 

 

4. Oncol Rep. 1996 Jul;3(4):747-50.

 

Adjuvant levamisole and fluorouracil in high risk colorectal cancer patients.

 

Merimsky O(1), Inbar M, Gutman M, Chaitchik S.

 

Author information:

(1)TEL AVIV SOURASKY MED CTR,DEPT SURG,IL-64239 TEL AVIV,ISRAEL. TEL AVIV

UNIV,SACKLER FAC MED,IL-69978 TEL AVIV,ISRAEL.

 

Adjuvant chemotherapy in colorectal cancer patients is aimed at decreasing the

relapse rate of the disease and increasing the disease-free and the overall

survival of the patients. In a prospective study we evaluated the efficacy of

5-FU plus levamisole as an aduvant therapy for 153 patients with Dukes' B-2 or C

colon or rectal cancer following a curative-intended surgery. Adjuvant

chemotherapy was started within 4 to 6 weeks following the operation. Combination

of 5-FU 375 mg/m(2)/day was given intravenously over 15-20 min for 5 consecutive

days, every month for 1 year. Levamisole 50 mg t.i.d. was administered orally

during the first 3 days of each course of chemotherapy. Rectal cancer patients

were also irradiated to the tumor bed and pelvic lymphatics. The dose intensities

(DI) of 5-FU and levamisole in our study were 432.6 mg/m(2)/w and 103.8

mg/m(2)/w, respectively. Failure analysis in Dukes' B and C patients showed that

the rectum accounted for 47.5% of the relapses, of which only 3 cases were in the

vicinity of the resected area. Almost half of the failures were observed within

the year of adjuvant treatment. The liver was the most common site for first

relapse (50%). The 3-year disease-free survival of Dukes' B-2 patients group was

84%, compared with 64% in Dukes' C. The main toxic manifestations were diarrhea,

nausea and vomiting, weakness and mucositis. No dose reduction was needed. Our

protocol, using lower DI of levamisole yielded similar results with a lower rate

of toxicity than other common protocols.

 

PMID: 21594447  [PubMed]

 

 

5. Cancer Detect Prev. 1996;20(4):300-7.

 

Detection of colon cancer by monitoring the intracellular fluorescein

fluorescence polarization changes in lymphocytes.

 

Merimsky O(1), Duetsch M, Tirosh R, Wohl I, Weinreb A, Chaitchik S.

 

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Israel.

 

Structuredness of the cytoplasmic matrix (SCM)-responding lymphocytes from

healthy donors can be differentiated from SCM-responding lymphocytes of patients

with malignant disease on the basis of the change in the intracellular

fluorescein fluorescence polarization (IFFP) induced by their exposure to various

antigens. We have found that the overall sensitivity, specificity and positive

and negative predictive values of the test were 92.0, 92.6, 96.3, and 84.7%,

respectively. We demonstrated the capability of the test to distinguish between

healthy people and colorectal cancer patients per stage of the disease. We also

found a significant difference in IFFP values between Dukes' C patients and

patients with metastatic disease, rendering the test potentially helpful in

follow-up.

 

PMID: 8818390  [PubMed - indexed for MEDLINE]

 

 

6. Tumour Biol. 1996;17(2):75-80.

 

Tumor ploidy as a risk factor for disease recurrence and short survival in

surgically treated Dukes' B2 colon cancer patients.

 

Nori D(1), Merimsky O, Saw D, Cortes E, Chen E, Chassin J.

 

Author information:

(1)Department of Radiation Oncology, New York Hospital Medical Center of Queens,

New York, N.Y., USA.

 

The risk factors for colon cancer recurrence following a curative intent surgery

include the tumor location and size, the presence of adhesions, perforation,

bowel obstruction, depth of invasion, histological grade, percentage of S phase

content and cell kinetic profile. The DNA content of tumor cells has recently

been suggested as an additional prognostic factor. In this study we assessed the

tumor ploidy as a prognostic factor for recurrence and survival in colon cancer

patients. The DNA content of colon cancers in 20 Dukes' B2 patients followed up

at our center, who relapsed either locally or systemically, following surgical

treatment was measured by image analysis. The data were pair-matched for age,

sex, tumor site and grade, and the period of follow-up with 20 Dukes' B2 patients

who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients with

recurrence, whereas only in 8 (40%) in the control group. Nonaneuploid DNA

content was found in 12 (60%) patients of the control group, but in only 4 (20%)

patients with a relapse. Aneuploidy was associated with a significantly higher

tumor recurrence rate (p = 0.024) and shorter overall survival (p < 0.002). Our

data point to a possible indication of a systemic adjuvant chemotherapy in Dukes'

B2 colon cancer patients who have aneuploid tumors on image analysis. This should

be further investigated in a prospective controlled randomized study.

 

PMID: 8658016  [PubMed - indexed for MEDLINE]

 

 

7. J Surg Oncol. 1995 Aug;59(4):239-42.

 

Tumor ploidy as a risk factor for disease recurrence and short survival in

surgically-treated Dukes' B2 colon cancer patients.

 

Nori D(1), Merimsky O, Samala E, Saw D, Cortes E, Chen E, Turner JW.

 

Author information:

(1)Department of Radiation Oncology, New York Hospital Medical Center of Queens,

Flushing 11355-5095, USA.

 

The risk factors for colon cancer recurrence following a curative intent surgery

include the presence of metastatic disease, the tumor location and size, number

of positive lymph nodes, the presence of adhesions, perforation, bowel

obstruction, depth of invasion, histological grade, percentage of S-phase

content, and cell kinetic profile. The DNA content of colon cancers in 20 Dukes'

B2 patients in follow-up evaluation at our center, who relapsed, either locally

or systemically following surgical treatment was measured by image analysis. The

data were pair-matched for age, sex, tumor site, and grade with 20 Dukes' B2

patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients

with recurrence, as compared with only in 8 (40%) in the control group.

Aneuploidy was associated with significantly higher tumor recurrence rate (P =

0.024) and shorter overall survival (P < 0.002). Our data may point out a

possible indication for systemic adjuvant chemotherapy in Dukes' B2 colon cancer

patients who have aneuploid tumors on image analysis. This warrants further

investigation in a prospective controlled randomized study.

 

PMID: 7630171  [PubMed - indexed for MEDLINE]

 

 

8. Int J Radiat Oncol Biol Phys. 1994 Nov 15;30(4):831-7.

 

Postoperative high dose-rate intravaginal brachytherapy combined with external

irradiation for early stage endometrial cancer: a long-term follow-up.

 

Nori D(1), Merimsky O, Batata M, Caputo T.

 

Author information:

(1)Department of Radiation Oncology, New York Hospital Medical Center of Queens,

Flushing 11355.

 

PURPOSE: To evaluate the long-term control of disease and cure rate,

complications, second malignancy, and survival of early-stage endometrial cancer

patients treated with surgery, high dose-rate brachytherapy, and external beam

radiation therapy.

METHODS AND MATERIALS: From 1969 through 1979, 300 patients with clinically

staged Stage I-II endometrial cancer underwent total abdominal hysterectomy and

bilateral salpingo-oopherectomy, followed by high dose-rate intravaginal

radiation, 7 Gy x 3 to 0.5 cm from the mucosal surface, using a remote

afterloading technique. External beam radiation therapy, 40 Gy to midplane in 4

weeks, was delivered to high risk patients through AP/PA and lateral fields.

RESULTS: The patients were followed for 5-24 years (median 12). The actuarial

progression-free survival rate was 96.6%. Post-treatment grade 1-2 actuarial

complication rate was 9.5%, including cystitis (4.5%), vaginal stenosis (2.5%),

proctitis (1.5%), vaginal necrosis (0.5%), and partial bowel obstruction (0.5%).

Neither grade 3-4 complications nor additional late complications were observed

in any of our patients. Relapse rate was only 3.7%, of which 45.5% were local,

45.5% were distant, and 9% were mixed. All the patients with relapse were

postmenopausal, age range of 58-77 years, with tumor grade 2-3 in 64%. Second

primary cancer rate was 12.8% (mostly breast and colon). Factors that were

associated with improved prognosis were young age, premenopausal, low grade, no

extrauterine disease, and a histology of adenocarcinoma (adenocarcinoma with

squamous metaplasia).

CONCLUSION: High dose rate intravaginal radiation therapy combined with surgery

and external beam radiation therapy achieved a high cure rate small number of

minor complications. No long-term treatment-related complications were noted in

any of the patients. This treatment combination may be safely applied to patients

with early stage endometrial cancer.

 

PMID: 7960984  [PubMed - indexed for MEDLINE]

 

 

9. Anticancer Drugs. 1991 Oct;2(5):447-51.

 

Treatment of advanced colorectal cancer by 5-fluorouracil-leucovorin combination

with or without allopurinol: a prospective randomized study.

 

Merimsky O(1), Inbar M, Chaitchik S.

 

Author information:

(1)Department of Oncology, Ichilov Hospital, Tel-Aviv Sourasky Medical Center,

Sackler Faculty of Medicine, Tel-Aviv University, Israel.

 

5-Fluorouracil (5-FU) remains the most effective chemotherapeutic agent in the

management of patients with metastatic colorectal cancer. Leucovorin enhances its

efficacy, but also its toxicity. Cited data suggest modulation of 5-FU toxicity

by high dose allopurinol. In a prospective randomized trial we assessed the

ability of allopurinol in a conventional dose to modulate the toxicity of

5-FU-leucovorin combination without compromising its efficacy in 50 patients with

advanced colorectal cancer. Twenty-seven patients were randomized for allopurinol

but had no benefit in terms of response or reduced toxicity over the other 23.

Survival of responders with colon cancer was longer than that of non-responders

(p = 0.013). Although allopurinol failed to reduce 5-FU-leucovorin toxicity, it

did not lower its expected efficacy.

 

PMID: 1804386  [PubMed - indexed for MEDLINE]