PAQR3: a novel tumor suppressor gene

PAQR3, also known as RKTG (Raf kinase trapping to Golgi), is a member of the progestin and adipoQ receptor (PAQR) family. The role of PAQR3 as a tumor suppressor has recently been established in different types of human cancer in which PAQR3 exerts its biological function through negative regulation of the oncogenic Raf/MEK/ERK signaling. Multiple studies have found that PAQR3 downregulation frequently occurs in human cancers and is very often associated with tumor progression and shortened patients’ survival. Moreover, restoring the expression of PAQR3 could induce apoptosis and inhibit proliferation and invasiveness of cancer cells. Downregulation of PAQR3 by oncogenic microRNAs has also been reported. In this review, we summarized current knowledge concerning the role of PAQR3 in tumor development. To our knowledge, this is the first review on the role of this novel tumor suppressor.     

Trunk lean gait modification and knee joint load in people with medial knee osteoarthritis: The effect of varying trunk lean angles

Objective

To evaluate whether increased lateral trunk lean toward the symptomatic lower extremity during gait in people with medial knee osteoarthritis (OA) immediately alters symptoms or medial knee load, as measured by the external knee adduction moment (KAM).

Methods

Participants with medial knee OA (n = 22) underwent 3‐dimensional gait analysis to measure KAM peaks (early and late stance) and KAM impulse. Following the analysis of natural gait, participants were trained to lean their trunk toward the symptomatic leg during ipsilateral stance over 3 randomly ordered conditions (6°, 9°, and 12° lean). A projection screen displayed real‐time trunk angles and target levels. Pain/discomfort in the knees, the hip, and the back were measured across conditions. Load‐modifying effects of increasing lean magnitudes were investigated using linear mixed models. Mediating effects of peak lean timing and participant characteristics (pain and malalignment) were evaluated.

Results

Increased trunk lean reduced all KAM measures (P < 0.001), with larger lean angles achieving greater reductions. Efficacy of load reduction improved with later peak lean timing for all measures of the KAM. Participant characteristics did not mediate the effect of trunk lean on the KAM, and symptoms did not change across conditions (P > 0.05).

Conclusion

Increased trunk lean reduced medial knee load in a dose‐response manner. Slightly later achievement of peak trunk lean improved the load‐modifying effect of this gait strategy. No immediate symptomatic changes were identified. Future research should determine if long‐term implementation of this gait strategy is feasible and whether it can modify disease symptoms and OA progression.     

Myeloma during a decade: Clinical experience in a single centre

One hundred and fifty-six patients with multiple myeloma weretreated over a period of 12 years at St. Bartholomew's Hospital.The progress of the disease was affected in 96/156 patients(61%). Response was defined as achieving a plateau of M component.A partial or complete response was seen in 68/120 patients treatedconventionally (56.5%), and in 28/36 patients treated with high-dosetherapy (77.7%). The median survival of the group as a wholewas 20 months, with a 2-year survival of just over 40%. In the36 patients treated with high-dose therapy, median survivalwas 6 years, and in a small group who have had maintenance Interferontherapy, the median has not yet been reached. In a univariateanalysis, age, intensity of therapy, haemoglobin and creatininelevels were significant, but multivariate analysis showed thatonly age and intensity of therapy were independent predictorsfor survival. The outlook for relapsed patients who showed progressionof disease remains poor, but palliation was best achieved bysteroid and Interferon in combination. Patients who achievecomplete responses and are maintained on Interferon appear tobe doing better both in terms of freedom from symptoms and insurvival, and methods to enable an elderly population to toleratethis form of therapy need to be explored. intensive chemotherapy, maintenance and relapse therapy, myeloma, survival     

Radiotherapy in the treatment of Hodgkin's disease.

Eighty-seven untreated patients with localised Hodgkin's disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin's disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.     

The effect of food and concurrent chemotherapy on the bioavailability of oral etoposide.

There is no information on the effect of food or concurrent drug administration on the bioavailability of oral etoposide, despite the fact that treatment is frequently administered over several days and most often in combination with other cytotoxic agents. The influence of these factors has been studied in 11 patients, receiving combination cytotoxic therapy for extensive small cell lung carcinoma. Neither food nor concurrent oral or intravenous chemotherapy had a significant effect on the mean plasma concentrations of etoposide, achieved following oral administration. Wide variation in peak plasma concentrations and in area under the concentration time curve (AUC) occurred both between and within patients. It appears unnecessary for patients receiving etoposide (at 100 mg) to fast prior to drug administration. Furthermore, oral etoposide (at 100 mg and at 400 mg) may be given in combination with other cytotoxic agents without compromising its bioavailability.