Cancer cell resistance mechanisms: a mini review

Cancer is a leading cause of death worldwide accounting to 13 % of all deaths. One of the main causes behind the failure of treatment is the development of various therapy resistance mechanisms by the cancer cells leading to the recurrence of the disease. This review sheds a light on some of the mechanisms developed by cancer cells to resist therapy as well as some of the structures involved such as the ABC members' involvement in chemotherapy resistance and MET and survivin overexpression leading to radiotherapy resistance. Understanding those mechanisms will enable scientists to overcome resistance and possibly improve treatment and disease prognosis (AU)

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Cancer cell resistance mechanisms: a mini review.

Cancer is a leading cause of death worldwide accounting to 13 % of all deaths. One of the main causes behind the failure of treatment is the development of various therapy resistance mechanisms by the cancer cells leading to the recurrence of the disease. This review sheds a light on some of the mechanisms developed by cancer cells to resist therapy as well as some of the structures involved such as the ABC members' involvement in chemotherapy resistance and MET and survivin overexpression leading to radiotherapy resistance. Understanding those mechanisms will enable scientists to overcome resistance and possibly improve treatment and disease prognosis.

[Primary Sjögren's syndrome and neuromyelitis optica]. / Syndrome de Goujerot-Sjögren primitif et neuromyélite optique de Devic.

Neuromyelitis optica (NMO) is characterized by the association of optic neuritis and myelitis without any other neurological signs. In 30 % of the cases, NMO is associated with a systemic disorders. We report two cases of NMO associated with primary Sjögren's syndrome that was diagnosed during an acute flare of NMO. The relationship between NMO and Sjögren's syndrome has not been clearly identified. This association likely reflects the coexistence of two autoimmune disorders. The prognosis of NMO appears to be more severe in patients having coexisting Sjögren's syndrome, which renders useful to search for this association in patients with neuromyelitis optica.

[Celiac disease and ischemic stroke]. / Maladie coeliaque et accidents vasculaires cérébraux ischémiques.

INTRODUCTION: Neurological manifestations of celiac disease are various. An association with ischemic stroke is not common and has not been well documented. We report two cases. OBSERVATIONS: The first patient had experienced several transient ischemic strokes in the past 2 years and then had an acute ischemic stroke involving the territory of the right posterior cerebral artery. Investigations revealed celiac disease with no other recognizable etiology. The clinical course was marked by persistent visual aftereffects, but no new vascular event. The second patient had been followed since 1998 for celiac disease confirmed by pathology and serology tests. She was on a gluten-free diet. The patient had an ischemic stroke involving the territory of the left middle cerebral artery. Apart from a positive serology for celiac disease and iron deficiency anemia, the etiological work-up was negative. DISCUSSION: The mechanisms of vascular involvement in celiac disease are controversial. The most widely incriminated factor is autoimmune central nervous system vasculitis, in which tissue transglutaminase, the main auto-antigen contributing to maintaining the integrity of endothelium tissue, plays a major role. Other mechanisms are still debated, mainly vitamin deficiency. CONCLUSION: Being a potentially treatable cause of ischemic stroke, celiac disease must be considered as a potential etiology of stroke of unknown cause, particularly in young patients, and even without gastrointestinal manifestations.

[Neurological manifestations of chronic inflammatory bowel disease]. / Manifestations neurologiques des maladies inflammatoires chroniques de l'intestin.

INTRODUCTION: Several extra-intestinal manifestations of inflammatory bowel disease have been reported, although reports of neurologic disorders are rare. CASE REPORTS: We report two cases of peripheral and central neurological manifestations of inflammatory bowel disease. The first case is a 33-year-old woman who developed acute inflammatory demyelinating motor polyneuropathy in association with Crohn's disease. Her symptoms improved with immunomodulatory therapies. Our second case is a 46-year-old woman, previously diagnosed with ulcerative colitis that subsequently developed ischemic stroke concomitantly to severe exacerbation of digestive symptoms. Her radial and humeral pulses were unequal bilaterally. Associated Takayashu's arteritis was suspected. The cardiovascular and immunological assessments were negative. Complementary investigations were foreseen but the patient died early of acute abundant rectal bleeding. CONCLUSION: This paper focuses essentially on the probable manifestations of inflammatory bowel disease in the nervous system, particularly peripheral neuropathies and stroke. We discuss different pathophysiologic mechanisms incriminated, notably thromboembolism and immunological abnormalities.

[Cauda equina syndrome revealing neuroblastoma]. / Syndrome de la queue de cheval révélant un neuroblastome.

INTRODUCTION: Neuroblastoma is the most common solid tumor of childhood. Neurological involvement is rare resulting from cord or nerve compression. CASE REPORT: A 7-year-old child was hospitalized for cauda equina syndrome. MRI showed retroperitoneal lesion with dumbbell intradural spreading. Blood and urinary catecholamine level were elevated confirming the diagnosis of neuroblastoma. She was treated with chemotherapy alone with partial neurological recovery. DISCUSSION AND CONCLUSION: Cauda equina compression revealing neuroblastoma is exceptional especially at an early phase in the youngest patients. Treatment is based on surgical resection and/or chemotherapy and/or radiation therapy. Long-term prognosis is sometimes poor with neurological sequels.

[POEMS syndrome with plasmocytoma lytic bone lesion]. / POEMS syndrome avec plasmocytome ostéolytique.

INTRODUCTION: Crow-Fukase or Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes syndrome (POEMS) is a rare multisystemic affection with incompletely elucidated etiopathogenesis. CASE REPORT: We report a case of POEMS syndrome in a 48-year-old adult revealed four months before admission by areflexic flask tetraparesis prevalent on the lower limbs in connection with demyelinating and axonal CIDP "like" sensoriomotor neuropathy of the four limbs electroneuromyographically. The patient presented elevated protein level in the CSF with monoclonal standard IgG gammapathy associated with a narrow band lambda, suggesting POEMS syndrome. Further explorations revealed skin lesions with glomeruloid angiomas, edematous vasomotor disorders as well as erythrocyanose, hypogonadism, papillar edema and a lytic bone lesion of the left scapula. Radiotherapy was associated with corticosteroids and plasma exchanges. Outcome was good with resolution of the symptoms and stabilization of the neuropathy. DISCUSSION: POEMS syndrome is rare; the diagnosis is based on necessary criteria, the presence of a demyelinating and axonal polyneuropathy associated with an IgA or IgG monoclonal gammapathy, the light chain being almost entirely lambda, associated to other characteristic elements, in particular glomeruloid angiomas, endocrinopathy, sclerosing plasmocytoma which must be carefully required. Treatment is based on surgical cure or radiotherapy for bone lesion and non specific treatments such as corticosteroid therapy, plasma exchanges and IVIG.

[Acute disseminated encephalomyelitis associated with hepatitis A virus infection]. / Encéphalomyélite aiguë disséminée associée à une infection au virus de l'hépatite virale A chez l'adulte.

INTRODUCTION: Hepatitis virus A (HVA) infection is usually a benign infection, but it can lead to severe manifestations and neurological symptoms. CASE REPORT: We report the case of a 44-year-old man who was admitted for pyramidal tetraparesis, loss of proprioceptive sensitivity and cranial nerve involvement. He had developed concomitally jaundice and fatigue. Brain MRI and cerebrospinal fluid examination were normal. Blood tests revealed elevated serum transaminase and anti-hepatitis A virus (IgM and IgG) levels. Acute disseminated encephalomyelitis (ADEM) was diagnosed and the patient was treated with high dose intravenous then oral corticosteroid therapy. The clinical condition continued to deteriorate and the patient died at eight months. DISCUSSION: ADEM is exceptionally associated with HVA infection or after vaccination for hepatitis A. Other neurological complications, including either peripheral or central nervous system, are reported. The clinical presentation and the outcome of our patient are atypical.

[Manic-depressive psychosis as prevalent manifestation of multiple sclerosis]. / La psychose maniacodépressive comme manifestation prévalente d'une sclérose en plaques.

INTRODUCTION: Manic-depressive psychosis (MDP) and multiple sclerosis (MS) coexistence is unusual but well-proven. OBSERVATIONS: We report two cases observed in two women aged 30 and 31, who were followed up for neurological episodes associated with concomitant or deferred manic or depressive fits. Brain magnetic resonance imaging revealed multiple zones of high intensity signals in the white matter. Biological balance was normal. The diagnosis of multiple sclerosis (MS) was established. Given to treat acute episodes, high-dose corticosteroids enabled regression of the psychological fits. Similarly, long-term treatment in one patient enabled significant regression of fits, which became less frequent and less severe. DISCUSSION/CONCLUSION: The MDP-MS association may be due to local MS-related brain damage or to common genetic susceptibility. The positive effect of corticosteroids against psychological fits is another finding favouring an organic cause of these disorders.

[Sturge--Weber-Klippel--Trenaunay syndrome (case report)]. / Syndrome de Sturge-Weber--Klippel-Trenaunay (une observation).

INTRODUCTION: Sturge-Weber syndrome is characterized by capillary malformations in the face, associated with leptomeningeal and choroidal venous malformations. Klippel-Trenaunay syndrome consists of the triad: capillary malformation of one leg, ipsilateral hypertrophy and varicose veins. OBSERVATION: We report the case of a 23-year-old male patient who presented a complex congenital neurocutaneous syndrome with vascular malformations involving the brain, face and limbs and associated with epilepsia and leptomeningeal calcifications. The patient fulfilled the diagnostic criteria of both vascular phacomatosis syndromes. DISCUSSION AND CONCLUSION: Similar descriptions of dual or overlapping syndromes have been published. Many show that there is no clear distinction between Klippel-Trenaunay syndrome and Sturge-Weber syndrome. There is a clinical and biological overlap. The complexity of the disease phenotypes shows that a classification based on an eponymous category does not enable resolution of the nosological problems. Some authors suggest that these vascular malformations are best described in anatomical/histological or functional terms. We report a new observation that illustrates these difficulties.

Pregnancy following infertility: a concern?

This study is to assess whether a waiting time to pregnancy (WTP) >1 year elevates the risk of adverse pregnancy outcomes in essentially healthy women with a single normal fetus at a gestational age of >20 weeks. Comparisons were made between those who conceived spontaneously with those who conceived after treatment for infertility. A retrospective analysis of 1,020 pregnancies occurring after a delay (WTP) of >1 year was undertaken over a 6-year period. Of these pregnancies, 24 resulted from advanced reproductive techniques and were excluded, as were four first trimester abortions, leaving 992 women. Of these 992, study group A (treated) consisted of 553 (56%) women, of whom 312 (56%) were primigravidae (A1). The pregnancy outcomes were compared with those of the remaining 439 (46%) women who conceived spontaneously, group B (control, untreated). Of these women, 234 (53%) were primigravidae (B1). Results suggested that primigravidae in the study group showed an increased risk of pre-term births and this risk was statistically significant between the gestations of 34 and 37 weeks. This risk remained elevated after adjustment for covariates. Pregnancies of women in group A1 were appreciably shorter than those of primigravidae who got pregnant without treatment (36.1 +/- 0.8 weeks vs 39.2 +/- 2.1 weeks); had lower birth weights (2684 +/- 481 g vs 3481 +/- 703 g) and were more likely to be admitted to the neonatal intensive care unit. Primigravidae among the treated group showed a statistically significant risk of caesarean births.

[Parry-Romberg syndrome with dysphonia]. / Syndrome de Parry-Romberg avec dysphonie.

INTRODUCTION: Parry-Romberg syndrome is a clinical entity consisting of progressive hemifacial atrophy appearing at a young age. This syndrome has features of linear scleroderma 'en coup de sabre'. The aetiology of this affection is poorly understood. A number of neurologic disorders associations have been reported particularly seizures. CASE REPORT: We report case of Parry Romberg syndrome in 29 years old men associated with dysphonia. Neurological examination and Brain CT scan were normal. DISCUSSION AND CONCLUSION: Different mechanisms have been discussed, immunological disorders, sympathic dysfunction or infectious origin. Management consists on reconstructive surgery, symptomatic treatment, with psychological issues.

Adverse outcome of pregnancy following air travel: a myth or a concern?

OBJECTIVE: To assess whether air travel elevates the risk of adverse pregnancy outcomes in essentially healthy women with single non-anomalous fetuses at a gestational age greater than 20 weeks. METHODS: A retrospective analysis of air travel during the current pregnancy and pregnancy outcome was undertaken in 992 women admitted for delivery over a 12-month period. The study group of 546 (55%) women, of whom 57% were primigravidae, travelled at least once during pregnancy, and were compared with a control group of 447 women (45%), of whom 54% were primigravidae, who did not travel by air. RESULTS: The primigravidae in the study group showed an increased risk of preterm birth, and this risk was statistically significant between the gestations of 34 and 37 weeks (adjusted odds ratio 1.5, 95% confidence intervals 1.2, 1.8); this risk remained elevated after adjustment for covariates. These women's pregnancies were appreciably shorter than those of primigravidae who did not fly (36.1 +/- 0.8 vs. 39.2 +/- 2.1 weeks) and their babies had lower birthweights (2684 +/- 481 vs. 3481 +/- 703 g). and were more likely to be admitted to the neonatal intensive care unit. This group of air travellers is unusual for the uncommonly long and frequent duration of air travel, which is not routinely undertaken in most parts of the world. There were no thromboembolic events complicating any pregnancies. CONCLUSIONS: Primigravid women who travel by air appear to be at higher risk for preterm birth. Multicentre large studies are required to confirm or repute these findings.

Maternal mortality: a twenty-year survey at the King Faisal University Hospital, Al-Khobar, Eastern Saudi Arabia.

This was an institutional study of all maternal deaths that occurred among 56422 total births at the King Faisal University Hospital, Al-Khobar, Saudi Arabia, between 1983 and 2002. The underlying cause of each maternal death and potentially avoidable factors were analysed. There were 16 maternal deaths in the hospital during the study period, giving a maternal mortality rate of 28.4/100,000 births. The leading cause of death was haemorrhage in seven (43.75%) patients, followed by pulmonary embolism in four (25%) and general anaesthesia in two (12.5%) mothers. The risk factors noted were maternal age 35 years and parity 5 coupled with iron deficiency anaemia. The main avoidable factors were failure of the patients to seek timely medical care and to follow medical advice. More than half the number of direct obstetrical causes of death was thought to be preventable. A rapidly changing attitude of women towards childbirth is occurring through progressively increasing female education and community health programmes in the region. Further reduction of maternal mortality rates in the community is envisaged through greater patient acceptance of medical advice, family spacing and proficient obstetric services.

Ocular penetration of oral clarithromycin in humans.

Clarithromycin has a wide spectrum of activity against many gram-positive and gram-negative organisms, intracellular pathogens, and opportunistic pathogens. To examine the penetration of clarithromycin in the ocular tissues, 21 patients who underwent elective cataract surgery (Group I) received a single 500-mg dose of clarithromycin orally either 4, 8, 10, 12, or 22 hours before cataract surgery, and 21 patients who underwent elective retina/vitreous surgery (Group II) received 500 mg every 12 hours orally for 3 days before the surgery with the last dose given either 3, 6, 8, 11, or 24 hours before the surgery. Serum from all patients was assayed for clarithromycin prior to drug administration and at the time ocular specimen was taken. Aqueous, iris, and vitreous samples were also assayed for clarithromycin concentration. The concentrations of clarithromycin in the aqueous fluid 4, 8, 10, 12, and 22 hours after administration were: (mean +/- SD) 0.13+/-0.05, 0.137+/-0.11, 0.074+/-0.03, 0.06+/-0.02, and 0.074+/-0.04 microg/ml, respectively. Concentration of clarithromycin in vitreous 3, 6, 8, 11, and 24 hours after administration were: (mean +/- SD) 0.11+/-0.02, 0.257+/-0.13, 0.27+/-0.21, 0.307+/-0.26 and 0.108+/-0.07 microg/ml, respectively. The mean concentration of clarithromycin in the iris was 6.2 microg/g. In conclusion, this data suggest that clarithromycin widely penetrates and adequately concentrates in the aqueous humor, vitreous humor, and iris tissue after oral administration and therefore is effective in the management of many infectious ocular conditions.

Cancer in the Eastern Region of Saudi Arabia: A population-based study (1987-1988).

This study presents the findings of the first population-based tumor registry in the Eastern region (ER). Data on all cancer sites, in 1987 and 1988, were captured from all health facilities in the ER. A regional population census was obtained from regional health authorities. Cancer deaths were obtained from death registries. Age-specific rate, crude incidence rate (CIR), age-standardized incidence rate (ASR) and relative age-standardized incidence rate (%ASR) were compared with available population-based data from 137 tumor registries. 1559 primary cancer cases were captured. The CIR and ASR/100,000/year for cancer among Saudi males were respectively 59.8 and 125.7. The corresponding rates among Saudi females were 43.6 and 95.5. These rates rank very low on the international scale. Cancer sites with the highest %ASR among Saudi males were lung, lymphomas, leukemias, urinary bladder and tumors of uncertain primary. For Saudi females, these sites were breast, leukemias, tumors of brain and nervous system, thyroid and tumors of uncertain primary. Lung cancer was the leading cause of death from cancer among Saudi males. The first regional population-based cancer registry in Saudi Arabia was established in 1987. The overall cancer ASR in the ER is low. The leading cancer sites with the highest %ASR are lung in Saudi males and breast in Saudi females.

Six years' experience with continuous ambulatory peritoneal dialysis and chronic hemodialysis in Saudi children.

Eighty children with End Stage Disease (ESRD) were treated in our unit over a six year period. Forty-eight were treated with CAPD (mean age = 5.8 years) and thirty-two with HD (mean age = 8.2 years). The average duration of treatment was 14.8 months in the CAPD group and 14.2 months in the HD group. There were 22 failures of peritoneal catheter in the CAPD group out of 70 catheters compared to 19 failures of vascular access devices out of 45 in the HD group. Peritoneal catheter failure was due to resistance or recurrent peritonitis in 10 (45.4%) and obstruction in nine (41%), whereas vascular access devices failure was due to thrombosis in six (31.5%) and infection in five (26.3%). Fifteen (31.3%) of the CAPD patients died and eight (16.7%) transferred to HD, whereas five (15.6%) HD patients died and four (12.5%) transferred to CAPD. The three year actuarial rates for CAPD were 81% at one year, 55% at two years and 42% at three years, while for HD was 94%, 85% and 64%, respectively. In this unique experience at the Kingdom so far, we found that a fully integrated service of dialysis including both CAPD and HD are essential. Such a system allows the optimal mode of treatments to be chosen for a child at any time and allows the child to move freely from one treatment to another when needed.

Correlation between Barr bodies and neutrophil drumsticks.

There is a marked difference between the frequencies of neutrophil nuclear drumsticks and mucosal cell Barr bodies in any given woman despite the fact that both represent an inactivated X chromosome. We present results of a prospective study carried out on 100 normal Saudi females to assess the statistical correlation between these two variables. We conclude that each is independent of the other. The lack of statistical correlation perhaps relates to maturational and nuclear configuration factors.

Evaluation of an intensive care unit in a teaching hospital in Saudi Arabia.

Intensive Care Units (ICU) in general hospitals have become a standard requirement in tertiary care centres. However, the appropriateness of their use is not widely known. We have used the Therapeutic Intervention Scoring System (TISS) to evaluate a multidisciplinary ICU in a teaching hospital in Saudi Arabia. The average occupancy rate was 79%, the nurse: patient ratio was 1:1.4, duration of stay 4.1 +/- 3.5 days, and mortality was 1.4%. The distribution of severity of illness was as follows: Classes I & II, 82%, and Classes III & IV, 18%. The average TISS points were: daily per patient 15.1 +/- 2.7 (range 11.5-21.7), total per day 125.6 +/- 38.2 (range 35-211), and patient points per nurse was 21.1. We conclude that, although less than 20% of patients required unique ICU services, the use of our ICU was appropriate to the current medical and manpower training needs of the community it was designed to serve, but the basis of nurses' complaints of overwork remains to be determined.