DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

Spontaneous dissecting aneurysms of coronary arteries in a cardiac allograft

Dissecting aneurysms of coronary arteries are a rare finding and have never been reported in a cardiac allograft. We found two spontaneous dissecting aneurysms on the middle third of both the left anterior descending and the right coronary arteries in a female cardiac transplantation recipient. She died 43 days after cardiac transplantation after developing human cytomegalovirus pneumonia and pancreatitis. Dissecting coronary aneurysms, microfoci of subendocardial coagulative necrosis, and area of subepicardial dystrophic calcifications were discovered at necropsy examination.     

Concomitant radiotherapy with mitomycin C and bleomycin compared with radiotherapy alone in inoperable head and neck cancer: final report

Purpose: To compare the efficacy of concomitant irradiation with mitomycin C and bleomycin in patients with inoperable head and neck carcinoma with radiotherapy alone.

Methods and materials: Between March 1991 and December 1993, 64 patients with inoperable head and neck carcinoma (41 with oropharyngeal site) were randomized to radiotherapy alone (group A) or radiotherapy combined with simultaneous application of mitomycin C and bleomycin (group B). In both groups patients were irradiated five times weekly with 2 Gy to a total dose of 66–70 Gy. The planned concomitant treatment in group B was: bleomycin 5 units twice a week IM, total dose 70 units, mitomycin C 15 mg/m² IV after delivery of 10 Gy, and 10 mg/m² IV on the last day of radiotherapy. To enhance the effect of these two drugs, patients received also nicotinamide, chlorpromazine, and dicoumarol.

Because significantly better results were achieved in arm B for patients with inoperable oropharyngeal carcinoma, the study was closed and such patients were after December 1993 routinely treated with the combined therapy (as in arm B). Until October 1996, we treated and followed up 48 such consecutive patients.

Results: Median follow-up of our study patients is 42 months. Complete remission (CR) rate in group A was 31% and in group B 59% (p = 0.04); disease-free survival (DFS) in group A was 8% and in group B 37% (P = 0.01); and overall survival (OS) was 7% in group A and 26% in group B (p = 0.08). CR rate for patients with oropharyngeal carcinoma was 29% in group A (N = 21) and 75% in group B (N = 20) (p = 0.007); DFS in group A was 10% and in group B 48% (p = 0.001); and the OS was 10% in group A and 38% in group B (p = 0.019). In patients with inoperable oropharyngeal carcinoma treated after December 1993, complete remission was achieved in 32/48 (67%, 95% CI: 52%–80%). DFS at the median follow-up of 14 months was 60% (95% CI 43–77%) and OS 58% (95% CI 42–74%).

Conclusion: From the results of our study it seems that the concomitant treatment significantly improves CR rate, DFS, and OS in patients with inoperable oropharyngeal carcinoma in comparison with radiotherapy alone.     

Metabolic pathway analyses identify proline biosynthesis pathway as a promoter of liver tumorigenesis

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miR-122 Inhibits Hepatocarcinoma Cell Progression by Targeting LMNB2

In the present study, we investigated the role of miR-122 in hepatocarcinoma progression and explored the mechanism. In hepatocarcinoma tissues and cells, we used qRT-PCR to validate the miR-122 expression level. Next, we used colony formation by crystal violet staining assay to compare cell proliferation ability, and we used scratch test or Transwell assay to compare cell migration or invasion ability. We then conducted bioinformatics or luciferase reporter gene assay to prove the regulation effect of miR-122 on lamin B2 (LMNB2), and the biological function of LMNB2 was analyzed. We used nude mouse tumorigenicity assay to test the inhibition effect of miR-122 ASO therapy against hepatocarcinoma. miR-122 was reduced in hepatocarcinoma tissues compared to the paracarcinoma tissues, which was relatively low or high in hepatocarcinoma cell line SMMC7721 or Hep3B, and overexpressed miR-122 inhibited proliferation, migration, and invasion in hepatocarcinoma cells. Additionally, some reports showed that LMNB2 was regulated by miR-122, which inhibited the expression of LMNB2. Moreover, LMNB2 functioned to promote cell proliferation, migration, and invasion. We could achieve the inhibition of hepatocarcinoma using miR-122 therapy through decreasing LMNB2 expression in vivo. Our data indicated that miR-122 could inhibit hepatocellular carcinoma cell progression by targeting LMNB2 and as a therapeutic target for hepatocarcinoma treatment.     

Interferon gamma regulates HLA-D expression on solid tumors in vivo

In vivo administration of recombinant human interferon-γ, rIFN-γ, to nude mice bearing human tumor xenografts resulted in a strong induction of HLA-DR expression on the tumor cells in 2 of 3 lines tested. The induction was dose-dependent and declined rapidly after cessation of therapy. IFN-γ also switched on DQ and DP products when the xenograft cells were treated in vitro. The in vivo alteration of tumor surface properties by rIFN-γ may have therapeutic implications.     

Brachytherapy for T1-T2 floor-of-the-mouth cancers: the Gustave-Roussy Institute experience

: In a retrospective analysis, we evaluated the Gustave-Roussy Institute’s experience of locoregional control, survival, and complications of low-dose rate brachytherapy for carcinoma of the floor of the mouth.

: Between 1970 and 1985, 160 patients with previously untreated carcinoma of the floor of the mouth received interstitial brachytherapy as definitive treatment. Of the 160 patients, 79 (49%) had T1 and 81 (51%) had T2 lesions, and 127 (79%) had N0 and 33 (21%) had N1; 84% of tumors arose from the anterior floor of the mouth. Brachytherapy was performed with ¹⁹²Ir wires, according to the Paris system rules, followed by neck dissection (T2 or N1) or follow-up (T1N0).

: With a follow-up period of 9–19 years, the observed survival rates were 89% at 2 years and 76% at 5 years, and the local control rates were 93% in T1 and 88% in T2 tumors. A low rate of distant metastases was noticed (5%); 31% of patients developed a second primary cancer. Severe mucosal necrosis was observed in <10% of patients. Any grade of bone necrosis was seen in 18% of cases (only 2.5% had G3 necrosis). This complication occurred more frequently in patients with poor dental status and in those treated without dental protection during implantation (p <0.001).

: Radical brachytherapy offers excellent local control (89%) and an acceptable rate of complications (<10% severe necrosis) that may be significantly decreased with dental care and the use of protective devices. The high incidence of second malignancies remains a major concern in these patients.     

Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery

To identify important prognostic factors predictive of survival and tumor control in patients with metastatic melanoma to the brain who underwent gamma knife radiosurgery.

A total of 122 consecutive patients with 332 intracranial melanoma metastases underwent gamma knife radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain irradiation (WBI). The median tumor volume was 0.8 cm³ (range: 0.02–30.20 cm³), and the median prescribed dose was 20 Gy (range: 14–24 Gy). Median follow-up was 6.8 months. Univariate and multivariate analyses of survival and freedom from progression were performed using the following parameters: status of systemic disease, intracranial tumor volume, number of lesions, tumor location, Karnofsky performance status, gender, age, and WBI.

Overall median survival was 7.0 months from time of radiosurgery and 9.1 months from the onset of brain metastasis. In multivariate analysis, improved survival was noted in patients with total intracranial tumor volume <3 cm³ (p = 0.003) and inactive systemic disease (p = 0.0065), whereas other parameters studied were of lesser importance (tumor location, p = 0.056, and Karnofsky performance status, p = 0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom from subsequent brain metastasis depended on intracranial tumor volume (p = 0.0018) and status of systemic disease (p = 0.034).

Conclusions: Stereotactic radiosurgery is an effective treatment modality for patients with intracranial metastatic melanoma. Tumor volume and status of systemic disease are good independent predictors of survival and freedom from tumor progression.