Desmoplasia: a response or a niche?

Summary: Desmoplasia-the presence of a rich stroma around a tumor-has long been associated with a poor clinical outcome in patients with cancer. It is considered to be a response to the presence of invasive tumor cells. There is now evidence that desmoplasia is the result of coordinated changes in several stromal cells under the control of a single gene product, CD36, whose repression leads to a decrease in fat accumulation and an increase in matrix deposition. The presence of these changes in tumor-free human breast tissue strongly suggests that desmoplasia may precede and not always follow the presence of malignant cells. This concept has an important clinical implication for women at high risk of developing breast carcinoma, considering that the presence of desmoplasia in normal breast tissue detected in the form of mammographic density is one of the strongest risk factors. Cancer Discov; 2(9); 772-4. ?2012 AACR.     

Clinical Research of a Modified Midfacial Degloving in a Maxillectomy （with a Report of a Typical Case）

OBJECTIVE To investigate the feasibility of employing a modified midfacial degloving in maxillectomy. METHODS Eight patients with carcinoma of the maxillary sinus underwent a modified midfacial degloving operation.The tumors were classified according to the 2002 AJCC system.The TNM staging of the cases was as follows:1 T4aN0M0,2 T3N0M0 and 5 T2N0M0.Of the 8 cases,1 patient underwent extended maxillectomy;exenteration of the orbit;tumorectomy of the sphenomaxillary and infratemporal fossae.Two patients received a total maxillectomy,and 5 a partial resection of the maxilla. Postoperative pathological report:4 well-di?erentiated squamous carcinoma,2 moderately-differentiated squamous carcinoma,1 mucoepidermoid carcinoma and 1 adenoid cystic carcinoma. RESULTS A modified midfacial degloving operation can sufficiently expose a field of operation,resect the tumor within a safe margin,and leave no facial cicatricles.One patient died of intracranial metastasis 8 months a er operation.We observed no recurrences or metastasis in other patients during the period of follow-up. CONCLUSION The major advantages of employing the modified midfacial degloving in maxillectomy is that a facial incision can be avoided.It has an advantage of minimal invasive surgery.     

Pharmacogenomics: a reality or still a promise?

Although notable progress has been made in the treatment of non-small-cell lung cancer (NSCLC) in recent years, this disease is still associated with a poor prognosis for most patients. Modern techniques have facilitated the identification of specific genetic factors that may play a role in disease progression and patient response to therapy, prompting research efforts to identify the clinical predictors of outcome for NSCLC. Recent evidence suggests that the application of a pharmacogenomic approach has the potential to greatly improve survival in certain subpopulations of patients with NSCLC, which could profoundly influence the decision-making process used in evolving treatment strategies for this malignancy.     

Scopulariopsis brevicaulis: a keratinophilic or a keratinolytic fungus?

The morphologic expression of human hair and nail invasion in vitro by Scopulariopsis brevicaulis isolates was studied by light microscopy on whole material and on semi-thin sections, and also by scanning and transmission electron microscopy. Only three isolates of the nine that were examined were keratinolytic, capable of both attacking keratinic substrates and demolishing their keratin. The process showed all the characteristic of enzymatic digestion and was in agreement with the biochemical and morphogenetic scheme proposed for other keratinolytic fungi during their invasion of human hair in vitro. All the active isolates were capable of developing structures related to surface erosion and radial penetration contemporaneously. However the extent and rate of keratinolysis were rather low when compared with the efficiency of other keratinolytic fungi. This finding suggests that S. brevicaulis is of secondary importance in the mineralization of keratinic substrates in natural environments. From the medical standpoint the mere demonstration of keratinolytic activity means that it may be regarded as a real cause of primary infection.     

TNF: a tumor-suppressing factor or a tumor-promoting factor?

TNF-α is a major inflammatory cytokine named for its ability to induce rapid hemorrhagic necrosis of experimental cancers. During efforts to harness this antitumor activity in cancer treatments in the 1980s, a paradoxical tumor-promoting role of TNF became apparent. The cellular and molecular complexity of mammalian tumor microenvironments makes these opposing effects difficult to study. The fruit fly Drosophila melanogaster provides a simpler model system for studying complex cellular and genetic interactions that lead to tumor formation and progression. The paper from Marcos Vidal's group shows that both the tumor-suppressing and tumor-promoting roles of TNF are conserved in Drosophila, and that oncogenic Ras is the switch. The links between inflammation and cancer are now more fully understood, but it is still not clear whether TNF has potential as a target or a therapeutic in malignant disease, or both. Research in an invertebrate organism may provide important insights.     

TNF-α is a novel target of miR-19a

Many studies have demonstrated the overexpression and amplification of the miR-17-92 cluster in malignant human cancers, including B-cell lymphomas and lung cancers. The purpose of this study was to investigate for the first time, the expression of the miR-17-92 cluster in esophageal squamous cell carcinoma (ESCC). The miR-17-92 cluster was found to be overexpressed in 21 out of 28 (75%) esophageal cancer samples. It was also found that overexpression of the miR-17-92 cluster could promote cellular growth in vivo and in vitro. Furthermore, inhibition of miR-19a by antisense oligonucleotides (ONs) induced apoptosis, while antisense ONs against miR-17-5p, miR-18a, miR-20a and miR-92-1 did not exhibit such an effect. In addition, it was found that antagomir-19a treatment could impair tumor growth in vivo. Using Human Apoptosis RT2 Profiler PCR Array 384HT, we found that tumor necrosis factor-α (TNF-α) was up-regulated 12-fold in cells transfected with miR-19a antisense ONs compared to the cells treated with the control scramble ONs. MiR-19a was predicted to target the 3' untranslated region of TNF-α mRNA, and this was confirmed by luciferase reporter assay. Taken together, we conclude that the miR-17-92 cluster is overexpressed in ESCC and that TNF-α is a novel target of miR-19a.     

Adding Mendelian randomization to a meta-analysis—a burgeoning opportunity

Current literature is teeming with tens of thousands of meta-analyses, but only a small fraction made seminal contributions to enriching our understanding of the mechanisms of carcinogenesis, possibly due to chance, bias, confounding, or reverse causality. The incorporation of Mendelian randomization (MR) with a meta-analysis has revolutionized traditional practice and is emerging as a viable technique to strengthen causal unconfounded inferences from observational data. We therefore highlight the importance of integrated MR meta-analysis in cancer epidemiology and provide an overview of three existing instrumental selection strategies in medical literature.     

Pregnancy-associated breast cancer: a case— control study in a young population with a high-fertility rate

Pregnancy-associated breast cancer (PABC) is not a rare event. The association frequently imposes a management challenge. We intended to review the clinical features, therapy, and outcome of patients with PABC seen at a single institution over a five-year period and to compare those with that seen in a matched control group. Data of all patients with PABC diagnosed during pregnancy were retrospectively reviewed (Group I). For each patient in Group I, three matched controls with breast cancer without pregnancy were identified (matched for age, stage, and year of diagnosis, Group II). 72 patients in Group I and 216 in Group II were identified. Their median age was similar (34 vs 35 y, respectively). The median number of prior pragnancies for patients in Groups I and II was 5. Patients had shorter duration of symptoms prior to diagnosis as compared with their controls (5.6 vs 9.4 months,P<0.0001). 3%, 31%, 40%, and 26% of patients had Stage I to IV, respectively. A pattern that was similar to that seen in our breast cancer population. Pregnancy was terminated in 34 patients (47%), while 38 (53%) had normal spontaneous vaginal delivery. 47 patients in Group I had surgery; 37 (52%) had modified radical mastectomy and 10 (14%) had conservative surgery. In 37 patients surgery was performed after termination of pregnancy and 10 had surgery performed during pregnancy. The median number of positive lymph nodes in Group I was 4 as compared with 2 for patients in Group II. No patients in Group I had systemic chemotherapy during first trimester, while only 4 (6%) and 3 (4%) received adjuvant or neoadjuvant during second and third trimester, respectively. No congenital malformation in the newborns was diagnosed. None of the patients in Group I received radiotherapy during pregnancy.     

Calvarial Metastasis of a Renal Cell Carcinoma, Mimicking a Primary Alveolar Soft Part Sarcoma, in a Young Girl—a Rare Case Report

Renal cell carcinoma (RCC) is characterized by an unpredictable clinical behavior. It has a tendency for early metastasis, which, at times is the initial presentation and therein poses a diagnostic challenge. We present a rare case of a disseminated RCC in a 15-year-old girl, who primarily presented with an occipital soft tissue mass. Computed tomography (CT) of the head revealed a soft tissue mass in the scalp, eroding the occipital bone and extending intracranially. Biopsy examination showed overlapping features of an alveolar soft part sarcoma (ASPS) and a RCC. Immunohistochemistry (IHC) showed diffuse positivity for CD10 and focal positivity for vimentin. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. The patient was recommended a clinical ‘work-up’ to rule out a possible primary in the kidneys. Her CT scan abdomen unraveled a large, lobulated, heterogeneous cystic mass, involving the middle and upper pole of the left kidney. Diagnosis of a metastatic RCC was ascertained. The present case represents a rare manifestation of a RCC metastasizing at an unusual location i.e. calvarium in the youngest patient known, so far and masquerading a primary ASPS. It also highlights the value of clinico-patho-radiological correlation, including CD10 as a useful IHC marker in diagnosing a RCC in young patients, especially when histopathological features overlap with ASPS.     

Is a cancer diagnosis a trigger for health behaviour change? Findings from a prospective,population-based study

Background:

A healthy lifestyle following a cancer diagnosis may improve long-term outcomes. No studies have examined health behaviour change among UK cancer survivors, or tracked behaviours over time in survivors and controls. We assessed smoking, alcohol and physical activity at three times (0–2 years before a cancer diagnosis, 0–2 years post-diagnosis and 2–4 years post-diagnosis) and at matched times in a comparison group.

Methods:

Data were from waves 1–5 of the English Longitudinal Study of Ageing; a cohort of older adults in England. Behavioural measures were taken at each wave. Generalised estimating equations were used to examine differences by group and time, and group-by-time interactions.

Results:

Of the 5146 adults included in the analyses, 433 (8.4%) were diagnosed with cancer. Those with a cancer diagnosis were less likely to be physically active (P<0.01) and more likely to be sedentary (P<0.001). There were no group differences in alcohol or smoking. Smoking, alcohol and activity reduced over time in the whole group. Group-by-time interactions were not significant for smoking (P=0.17), alcohol (P=0.20), activity (P=0.17) or sedentary behaviour (P=0.86), although there were trends towards a transient improvement from pre-diagnosis to immediately post-diagnosis.

Conclusion:

We found little evidence that a cancer diagnosis motivates health-protective changes. Given the importance of healthy lifestyles, strategies for effective support for behaviour change in cancer survivors need to be identified.     

Why Life Oscillates – from a Topographical Towards a Functional Chronobiology

Chronobiology has identified a multitude of rhythms within our body as well as within each living cell. Some of these rhythms, such as the circadian and circannual, interact with our environment, while others run on their own, but are often coupled to the circadian or to other body rhythms. Recent evidence shows that these rhythms might be more important for our health than expected: Disturbance of the circadian rhythms by jet lag or shift work not only evokes autonomic disturbances but also increases the incidence of cancer, as shown in this issue of Cancer Causes and Control. The occurrence of rhythms in the organism obviously bears several advantages: (1) It increases organismic stability by calibrating the system’s characteristics: Regulation curves in time and space are crucial for controlling physiological long-term stability. To determine its properties continuously the system varies its parameters slightly over several time scales at different frequencies—akin to what our body does, e.g. in heart-rate variability. (2) Tuning and synchronization of rhythms saves energy: It was Huygens who observed that clocks on a wall tend to synchronize their beats. It turned out later that synchronisation is a very common phenomenon observed in bodies’ rhythms and can be found, for example, when we relax or sleep. At such times energy consumption is minimal, our body working most efficiently. (3) Temporal compartmentalization allows polar events to occur in the same space unit: there are polarities in the universe of our body, which cannot happen simultaneously. Systole and diastole, inspiration and expiration, work and relaxation, wakefulness and sleep, reductive and oxidative states cannot be performed efficiently at the same time and place. Temporal compartmentalization is probably the most efficient way to mediate between these polarities. Chronobiology and chronomedicine are opening a new and very exciting understanding of our bodies’ regulation. The biological time and its oscillations gain more attention and importance as these interrelations are understood.