Paclitaxel activity for the treatment of non-Hodgkin's lymphoma: final report of a phase II trial

In order to determine the activity of paclitaxel in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II clinical trial in which eligible patients received paclitaxel 200 mg/m² intravenously over 3 h. Treatment was repeated every 3 weeks. Patients achieving complete or partial responses after two courses of paclitaxel continued to receive therapy for a maximum of eight courses, otherwise they were removed from the study. Of 96 evaluable patients, 45 (47%) had primary refractory disease, and 51 (53%) had relapsed lymphoma. The median number of prior treatment regimens was two (range one to 10 regimens). 45 patients had low-grade, 44 had intermediate-grade, and seven had mantle cell lymphoma. 24/96 patients responded (10 complete and 14 partial remissions) for an overall response rate of 25% (95% CI 17–35%). Patients with relapsed lymphoma had a higher response rate than those with primary refractory disease (19/51=37% v 5/45 =11%; P  < 0.01), and patients with relapsed intermediate-grade lymphoma had a higher response than those with relapsed low-grade lymphoma (9/18=50% v 10/31 = 32%; P  = 0.22). The treatment was very well tolerated with the most common side-effects being alopecia (100%), peripheral neuropathy (35% of ≥ grade II), and arthralgia/myalgia (25% of ≥ grade II). After the first course of paclitaxel, grade III/IV thrombocytopenia and neutropenia were observed in 21% and 23% of the patients respectively. 23 episodes of neutropenic fever developed after 250 courses of paclitaxel therapy (8%). We conclude that paclitaxel, at this dose and schedule, is an active new drug for the treatment of non-Hodgkin's lymphoma. The activity of paclitaxel combination programmes are currently under investigation.     

Association between mucosal hyperplasia of the appendix and adenocarcinoma of the colon

Mucosal hyperplasia of the appendix is a seemingly benign change of poorly understood significance, at times found in patients with colorectal malignancy. To determine the incidence of this change and its association with colonic adenocarcinoma, we have examined the appendiceal mucosa in 122 ileocolectomy specimens gathered between 1987 and 1990, and in 273 consecutive appendectomies carried out during 1990 at The Methodist Hospital in Houston, Texas. We found that 23 out of 122 ileocolectomies (18.8%) showed mucosal hyerplasia of the appendix and, of these, 17 (77%) were associated with colorectal malignancy, predominantly of the right side. Moreover, 24 of 273 appendectomies (8.8%) exhibited the presence of mucosal hyperplasia and, of these, six (25%) also were associated with adenocarcinoma of the colon. On the basis of this significant rate of association, we feel that a concomitant colorectal carcinoma should be ruled out in patients who exhibit mucosal hyperplasia of the appendix.     

Nuclear/cytoplasmic ratio correlates strongly with survival in non-disseminated neuroendocrine carcinoma of the lung

In order to verify whether quantitative morphological indices of neuroendocrine carcinoma of the lung may help to predict survival, 47 biopsies (from 37 males and 10 females; 16–82 years of age) were studied by light microscopy. Areal fractions of nuclei, cytoplasm, stroma, and blood vessels were determined using a standard point counting method. The counts were made in six non-coincident microscopic fields in each case, and the areal fractions of nuclei, of the entire tumour cell, stroma, blood vessels and the nuclear/cytoplasmic ratio were computed. In a multivariate linear regression analysis, survival in months after biopsy was considered the dependent variable of age and of all morphometric parameters listed above. The significance level was set at 5%. For all patients (disregarding staging) survival was negatively correlated (P< 0.001, multiple r=0.5435) with age and nuclear/cytoplasmic ratio. When only patients with disease confined to the thorax (stages I. II and III) were taken into account, the accuracy of the Function predicting survival increased considerably (P=0.004, multiple r=0.7957). The use of simple stereological methods therefore, proved to be of value in predicting survival in patients with neuroendocrine carcinomas of the lung.     

Estrogen Steroid-Receptor Binding in the Canine Epididymis

The epididymis of the dog has been studied with regard to its ability to bind estrogens. A proteinaceous molecule was demonstrated in the high-speed supernatant friction of disrupted cells that bound E₂β and sedimented in a low salt sucrose density gradient with a coefficient of variation of 7-8S with respect to bovine serum albumin. This binding protein was able to transport E₂β to the nucleus at elevated temperatures, where it is sedimented as a 4S in a 5–20% sucrose density gradient. The specificity of the receptor protein for estrogens was demonstrated using competition analysis. Studies concerning the physical properties of the estrogen binder revealed a protein of molecular weight of 200,000, Stokes' radius of 51 Å and a fractional ratio of 1.32.
Östrogen-Steroid-Rezeptorbindung im Nebenhoden des Hundes

Zusammenfassung

Der Nebenhoden des Hundes wurde im Hinblick auf seine Fähigkeit, Östrogene zu binden, untersucht. Im Überstand hochtourig zentrifugierter zertrümmerter Zellen, die E₂β gebunden hatten, wurde ein proteinartiges Molekül nachgewiesen, das in einem niedrigen Salz-Saccharose-Dichtegradienten mit einem Sedimentationskoeffizienten von 7-8S bezogen auf Rinderserumalbumin sedimentiert wurde. Dieses Bindungsprotein war in der Lage, E₂β bei erhöhten Temperaturen zum Kern zu transportieren, wo es in einem 5–20% Saccharose-Dichtegradienten bei 4S sedimentierte.
Die Spezifität des Rezeptorproteins für Östrogene wurde mittels Kompetitionsanalyse nachgewiesen. Die Untersuchungen bezüglich der physikalischen Eigenschaften ergaben ein Protein mit dem MG 200.000, einem Radius von 51 Å und einem Friktionsverhältnis von 1.32.     

A comparative study of palatal height in a Saudi and Egyptian population

SUMMARY The present study constitutes an attempt to compare normal traits for palatal height and width at different stages of dentition development of two ethnic groups of the Middle East. The observations were obtained from 346 randomly selected normal subjects, 188 Saudis and 158 Egyptians. The stone models were divided into three categories in both groups — primary, mixed and permanent dentitions. Palatal index values were calculated at two levels. Vernier calipers were used to measure the palatal width. Palatal depth was measured by profile Gauge by Vitrex. The results of this study demonstrate no significant difference between ethnic groups at levels 1 and 2 in relation to the palatal height, width and index. For both groups, palatal index increased significantly from the primary to mixed and permanent dentition at level 1.
At level 2, palatal index and height showed decreases in measurement in the mixed dentition compared with the primary and the permanent dentitions.
Subjective assessment of the palatal height correlated with palatal index. The casts were then labelled so that the shallow group had the smallest palatal index followed by the normal and the deep group had the largest palatal index. The results contribute to the information available on the development of palatal shape within two Middle Eastern populations. Knowledge of the normal range in shape can act as a baseline for studies of certain oral developmental abnormalities.     

Oestrogen receptor‐β1 but not oestrogen receptor‐βcx is of prognostic value in apocrine carcinoma of the breast

Apocrine carcinoma of the breast, which frequently expresses oestrogen receptor‐β (ER‐β) in the absence of ER‐α and only infrequently is treated endocrinologically, gives an opportunity to investigate the clinicopathological role of ER‐β in breast cancer independent of ER‐α expression or tamoxifen treatment. Several isotypes of ER‐β, ER‐β1–5 etc., have been identified thus far; however, the clinicopathological importance of each ER‐β isotype in breast cancer is still uncertain. Here we aimed to clarify the clinicopathological importance of ER‐β1 and ER‐βcx (ER‐β2) in apocrine carcinomas, immunohistochemically examining expressions of ER‐β1 and ER‐βcx in 47 apocrine carcinomas. Positivity for ER‐β1 and ER‐βcx was observed in 41 (87%) and 18 (38%) of 47 cases, respectively. ER‐β1 positivity was related to smaller tumor size (P=0.0359), lower histological grade (P=0.0322), and higher disease‐free survival (P<0.0001), whereas ER‐βcx status was related to none of these parameters. ER‐β1 positivity was also associated with favorable clinical outcome in 24 so‐called triple‐negative (ER‐α‐negative/PR‐negative/HER2‐negative) apocrine carcinomas. ER‐β1 itself, independent of ER‐α expression and tamoxifen treatment, seems to have a tumor‐suppressive effect, at least in apocrine carcinomas. Further study of ER‐β1 is desired to optimize breast cancer treatment.     

Role of growth factors in oesophageal mucosal healing: A work in progress

Abstract Reflux of gastroduodenal contents into the oesophagus results in dynamic cycles of injury followed by cell proliferation and repair. These processes are receiving increased attention due to the high incidence of gastro-oesophageal reflux disease and the rising incidence of adenocarcinoma of the oesophagus. Repeated cycles of injury and repair may lead to abnormal differentiation followed by abnormal growth. This article summarizes the research performed by our group in the field of oesophageal injury and repair. We initially developed an in vivo perfused rabbit oesophagus model that served to study the effects of various components of the gastroduodenal juice on several parameters of oesophageal injury. We have shown that pepsin causes severe morphological oesophagitis at an acidic pH but is ineffective at an alkaline pH. We have also demonstrated that trypsin causes severe morphological oesophagitis at an alkaline pH but not at an acidic pH. Bile salts were found to disrupt the oesophageal barrier at both pH levels. We have also studied the effects of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on oesophageal regeneration. We used an ex vivo oesophageal explant model for these experiments. Both EGF and IGF-I cause a dose-dependent increase in oesophageal DNA synthesis, cell proliferation and mucosal growth. These effects are synergistic and can be inhibited by specific tyrphostins. We are currently studying the role of growth factors as therapeutic agents and the role of growth factors in the development of Barrett's oesophagus and adenocarcinoma.