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PubMedDate not supplied

Family caregivers of elderly patients with cancer: understanding and minimizing the burden of care.

Family caregivers play an essential role, usually unpaid, in caring for patients with cancer. Most older patients with cancer are cared for by a family member, who may not be prepared for the challenges. The needs of older patients are diverse and may include assistance with medication, transportation for treatment, activities of daily living, and emotional support. The activities that caregivers find most stressful include helping patients with their self-care, managing their treatment and symptoms, and dealing with the suffering of a family member. Families may be affected by other stressors, such as changes in roles and employment and disruptions in schedules (eg, frequent clinic visits). Caregivers respond to these stressors differently; older spouses may be particularly vulnerable because of their own frailty. There can also be negative effects on caregivers' psychological, social, or physical health functioning. Social and economic deficits due to caregiving may include lifestyle disruption, less socializing, and greater out-of-pocket and lost productivity costs. Studies have shown, however, that caring for an older person with cancer also has rewards, such as satisfaction and a greater sense of self-worth. The negative aspects of caregiving can be lessened by psychological support and assistance in problem solving from healthcare professionals. Caregivers should also be provided with options to reduce the stress of frequent clinic visits, such as using long-acting growth factors or telephone triage. Educating caregivers on pertinent aspects of cancer management and the community resources available to them can be done through individual contact with health professionals or through more-formal educational programs.

Aged↗
PubMed2005

[Is early first intercourse a risk factor for cervical cancer?].

Sexual behavior has long been known to be a risk factor for cervical carcinoma. Certain sexual risk factors are related to an increased risk of chronic infection of the cervical transformation zone with high-risk human papilloma viruses (HPVs). Numerous retrospective analyses consider early first intercourse a probable risk factor for later development of cervical carcinoma. Since risk factors are associated, it is unclear whether early first intercourse is an independent risk factor for cervical neoplasia. Few comprehensive retrospective studies are available. It is possible that the cervical transformation zone is particularly vulnerable to infection between menarche and the age of sixteen. During this phase there are a large number of undifferentiated cells at the periphery of the metaplasia, practically at the surface of the cervix. It seems that this area is particularly susceptible to HPV infection. There are also indications that there is no secondary immune response to HPV at the time of early first intercourse, making the immune response to HPV less efficient. Other possible risk factors for cervical cancer include genetic predisposition, nutrition, smoking, Chlamydia or HSV-2 infections, drug abuse, oral contraception, immune suppression and early first pregnancy. Education appears important to encourage responsible sexual behaviour in young people.

Adolescent↗
PubMed2003

Circulation of the spinal cord: an important consideration for thoracic surgeons.

The spinal cord has significant thoracic arterial watershed areas rendering it vulnerable to intraoperative ischemic damage, clearly mandating a need for postoperative neurologic monitoring. Mechanisms of hypoperfusion include aortic cross-clamping, rib retraction, intercostal artery interruption, and costovertebral junction bleeding. We report cases of primary lung cancer resection, resection of pulmonary metastasis adherent to the thoracic aorta, resection of cartilaginous tumor with chest wall invasion, and esophagomyotomy for achalasia-all complicated by postoperative paraplegia. We review spinal cord circulation, describe mechanisms and patterns of neurologic dysfunction of susceptible watershed areas, and outline roles of preoperative spinal angiography and intraoperative evoked potentials.

Adult↗
PubMed2002

AIDS-related tumors: integrating antiviral and anticancer therapy.

The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relative stability in the number of patients developing systemic NHL. AIDS-related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non-AIDS-defining tumors, such as Hodgkin's disease, anal, head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1977

Primary cancer of the liver in Kenyan children.

In 9 years in Kenya, 34 examples of primary liver cancer wer diagnosed in patients in the first two decades of life. This represents 4.7% of all liver cancers during this period. The larger proportion (29) were hepatocellular carcinoma. In the second decade, there was a notable association with macronodular cirrhosis. Analogy with experimental work suggests that cells in mitotic cycle may be more vulnerable to the effect of environmental carcinogens. Five examples of hepatoblastoma were identified at ages from 2 months to 14 years; none showed the features of "mixed" tumours. The ratio of hepatoblastoma to hepatocellular carcinoma was the reverse of that found in other large series of juvenile hepatic tumours. The histopathological features of these tumours are described and problems of their classification are discussed.

Adolescent↗
PubMed2002

Chronic effects of toxic environmental exposures on children's health.

Children have unusual patterns of exposure to environmental chemicals, and they have vulnerabilities that are quite distinct from those of adults. Increasingly, children's exposures to chemicals in the environment are understood to contribute to the causation and exacerbation of certain chronic, disabling diseases in children including asthma, cancer, birth defects, and neurobehavioral dysfunction. The protection of children against environmental toxins is a major challenge to modern society.

Asthma↗
PubMed2005

Fear of death.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH) founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient and support to caregivers and encourages the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. For many, cancer is synonymous with death. Fearing death is a rational response. For too long, medicine has ignored this primeval fear. Increasingly, clinicians recognize and address end-of-life issues, facing patients' and our own emotional vulnerabilities in order to connect and explore problems and fears. Listening and learning from the patient guides us as we acknowledge much of the mystery that still surrounds the dying process. Rarely is there a simple or right answer. An empathetic response to suffering patients is the best support. Support is vital in fostering the adjustment of patients. A silent presence may prove more helpful than well-meant counsel for many patients. Through an examination of eight caregiver narratives of their patients' experiences, the role of the health care provider in the dying process, particularly in regard to challenging fear, is reviewed.

Adolescent↗
PubMed2004

The contribution of factor V Leiden and prothrombin G20210A mutation to the risk of central venous catheter-related thrombosis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the incidence of central venous catheter (CVC)-related thrombosis and the contribution of two common inherited coagulation disorders (factor V Leiden, prothrombin G20210A mutation) to this complication in a large hospital population. DESIGN AND METHODS: In a prospective setting, patients were assessed daily for signs and symptoms suggestive of thrombosis. Routine Doppler-ultrasound was performed weekly in all patients until CVC removal. Doppler-ultrasound examinations were stored on videotape and assessed by two blinded observers. In the case of clinically suspected thrombosis the physicians followed routine diagnostic and therapeutic procedures. The presence of factor V Leiden and prothrombin G20210A mutation and other potential risk factors were assessed in all patients. RESULTS: In 252 consecutive patients the cumulative incidence of-CVC related thrombosis was 30% (clinically manifested thrombosis: 7%). The relative risk of factor V Leiden or prothrombin G20210A mutation for thrombosis was 2.7 (CI95% 1.9 to 3.8). In addition, a personal history of venous thrombosis was associated with CVC-related thrombosis, whereas the severity of thrombosis was affected by the absence of anticoagulants and the presence of cancer. INTERPRETATION AND CONCLUSIONS: Thrombosis is frequently observed after central venous catheterization. Common inherited abnormalities in blood coagulation contribute substantially to CVC-related thrombosis. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in vulnerable patients, a priori determination of common inherited and acquired risk factors may form a basis to guide these treatment decisions.

5' Untranslated Regions↗
PubMed1978

Does ultraviolet-evoked prostaglandin formation protect skin from actinic cancer?

The role of increased prostaglandin activity which results from exposure of human skin to ultraviolet light is uncertain. Evidence from the effects of prostaglandins on epithelial cells in vitro suggests that prostaglandin E reduces proliferative activity in the epidermis, probably through a cyclic-A.M.P.-dependent mechanism, thus reducing the vulnerability of epidermis to the mutagenic effects of ultraviolet exposure.

Cell Division↗
PubMed2004

Cost of cancer clinical trials in elderly patients.

Of all cancers, > 50% currently occur in individuals >or= 65 years of age and this figure is expected to rise to 70% by 2030, due to a progressive expansion of the older population [1]. Clinical trials are needed in order to establish the benefits and risks of antineoplastic treatment in older individuals. It is reasonable to expect that the costs of these trials may be higher than in younger individuals, as older patients are more vulnerable to therapeutic complications and may need more supportive care, and the benefits of treatment may be less because of a reduced life-expectancy and competitive causes of death [2]. This article explores a cost-effective approach to clinical trials in older individuals, after reviewing the basic concepts of economic analysis and unique aspects of geriatric oncology that may affect the cost of treatment. In the process, the cost differences of cancer treatment in younger and older patients will be explored.

Age Factors↗
PubMed2003

Therapeutic approaches to AIDS-related malignancies.

The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relatively stability in the number of patients developing systemic NHL. AIDS related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non AIDS-defining tumors, such as Hodgkin's disease, anal and head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Special report. Drug theft from hospital pharmacies: lessons from the 'Syracuse scam'.

Theft and drug diversion by employees from hospital pharmacies pose increasing security concerns for institutions as evidenced by the indictment in May 1996 by an Onondaga County, Syracuse, NY, grand jury of four men--one an associate hospital pharmacy director--on charges relating to the theft and resale of more than $3 million in prescription drugs from two Syracuse hospitals over an eight-year period. The drugs were used to treat cancer patients. In this report, we'll give you in-depth details of what was stolen and how it was stolen. We'll present some advice from experts on how to prevent your hospital from becoming vulnerable to such large-scale losses. And we'll give you insight into a vast black market that may indicate that what took place at the two Syracuse hospitals may not be an isolated occurrence.

Drug Costs↗
PubMed1998

Patterns of death in world leaders.

This study presents an analysis of the mortality patterns of people who become world leaders. Using information in the public domain, we identified 261 world leaders who died between 1965 and 1996. Of these, 118 died while in office, 44% violently, often by assassination. Of the 143 leaders who died after leaving office, 11% died violently. The violent deaths occurred worldwide but most frequently in the Middle East/South Asia and sub-Saharan Africa regions. The most frequent natural causes of death among world leaders were heart disease, cancer, and stroke. Mortality patterns reveal that the longevity of those leaders who died of natural causes could have been predicted by U.S. life tables. This study suggests that world leaders are neither biologically "tougher" nor more vulnerable to disease than others; however, their odds of dying violently while in office are high.

Aged↗
PubMed2001

Muc4/sialomucin complex in the mammary gland and breast cancer.

MUC4 is a one of the membrane mucins of the mucin gene (MUC) family, characterized by mucin tandem repeat domains and a transmembrane domain which associates it with the cell plasma membrane. Although MUC4 is encoded by a single gene, it is produced by epithelial cells as a heterodimer through a proteolytic cleavage mechanism. This heterodimer is found in both membrane and soluble forms associated with epithelia. Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland. The protective mechanism(s) may be highjacked by some carcinomas, such as those of the breast, to increase tumor progression. Two mechanisms are proposed to contribute to the MUC4 functions. First, MUC4 acts as an anti-adhesive or anti-recognition barrier at epithelial or tumor cell surfaces. Second, MUC4 can bind the receptor tyrosine kinase ErbB2 and alter its cellular signaling. Expression of MUC4 in mammary gland is repressed by posttranscriptional mechanisms involving basement membrane and TGF-beta, which are relieved during pregnancy to permit secretion of MUC4 into milk. These mechanisms are also abrogated in some breast cancers, providing a scenario for promotion of tumor progression. These observations imply important functions for MUC4 in both normal mammary function and in breast cancer.

Animals↗
PubMed2026

Inactivation of CDK12 Enhances Mitochondrial Efficiency to Suppress DNA Damage.

Inactivation of cyclin-dependent kinase 12 (CDK12) characterizes a subset of prostate cancers but it is not understood how cells adapt to declining activity of this major transcription elongation kinase. To probe this response, we developed a cell line resistant to an inhibitor targeting CDK12 and its paralog, CDK13. CDK13 can compensate for the loss of CDK12, which is why we used the dual inhibitor THZ531. Targeted drug screening of the parental and resistant cell lines revealed cross-resistance to other transcriptional kinases but no clear acquired point of vulnerability. Using genome-wide mapping of mRNA-stabilization based on metabolic labelling of RNA, we report selective mRNA stabilization of factors promoting oxidative phosphorylation in the resistant cells. We go on to show that loss of CDK12 activity enhances ATP production both in cell line models and in patient tumours. Finally, we show that dual inhibition of CDK12/13 results in excessive phosphorylation of the DNA damage H2AX in prostate cancer cells but not in our CDK12/13 inhibitor-resistant model system. In brief, we propose that inactivation of CDK12 rewires cellular energy metabolism to suppress DNA damage.

Humans↗
PubMed2026

Targeting super-enhancer-driven SKIL transcription by CDK7 inhibitor THZ1 to suppress gastric cancer progression.

BACKGROUND: Gastric cancer (GC) is a lethal malignancy characterized by high incidence, mortality, and limited treatment options. Transcriptional addiction is a key cancer hallmark that drives tumor pathogenesis, making its inhibition a promising therapeutic strategy for GC. The study aims to investigate the roles and mechanisms of super-enhancer (SE)-driven oncogenic transcriptional addiction in GC progression and to identify novel targetable vulnerabilities. METHODS: We utilized cellular and animal models to assess the effects of THZ1 treatment and CDK7 knockdown on GC progression. RNA sequencing was employed to elucidate the potential molecular mechanism of THZ1 treatment. ChIP-seq was performed to establish SE landscape in GC. Integrative analysis of transcriptomic and SE profiling was used to identify THZ1-targeted oncogenic genes. Rescue experiments were conducted to confirm that THZ1 treatment suppresses GC malignant progression by targeting SE-driven SKIL transcription. RESULTS: GC cells exhibited pronounced sensitivity to THZ1 compared to normal gastric mucosa cells, and the treatment potently suppressed tumor growth and migration in both cellular and animal models. CDK7 was significantly upregulated in GC tissues, and its knockdown inhibited malignant progression in vitro and in vivo, whereas its overexpression accelerated tumor progression. Mechanistically, SE-driven oncogenic transcriptional amplification underlies GC cell susceptibility to THZ1, supported by the identification of novel oncogenic genes such as SKIL. SKIL, a key Hippo pathway regulator, was highly expressed in GC cells, and its elevated expression predicted poor patient prognosis. SKIL silencing attenuated malignant phenotypes, while its overexpression diminished THZ1’s suppression of GC cell proliferation and migration. CONCLUSION: Our findings demonstrate that THZ1 inhibits GC progression by disrupting SE-driven oncogenic transcription, thereby offering CDK7 inhibition as a promising therapeutic intervention for GC.

Stomach Neoplasms↗
PubMedDate not supplied

Characterization of local inflammatory response in an isolated lung perfusion model.

BACKGROUND: Current phase I trials of isolated lung perfusion for treatment of pulmonary metastases have an arbitrarily determined length of perfusion. Our objective was to examine the temporal course of the local and distant inflammatory response as a function of the length of perfusion (ischemia) and subsequent reperfusion in an equivalent animal model. METHODS: Sixty male Fischer 344 rats were randomized into four groups (n = 15). Each group underwent left isolated lung perfusion with buffered Hespan for 10, 30, 60, or 90 minutes. Subsequently, two subgroups of five animals within each group were allowed to reperfuse for 1 or 3 hours, respectively. Non-perfused right lung was used as control. At each time point, lung specimens were assayed for TNF-alpha by ELISA and histologic sections were examined. RESULTS: There was no significant difference between the left and right lung tissue levels of TNF-alpha at the termination of the ischemic period. However, on reperfusion, the left lung TNF-alpha levels increased significantly above the ischemia baseline in all groups, with a greater magnitude of rise in the groups with 60 and 90 minutes of preceding ischemia (12,757 +/- 1985 vs. 3524 +/- 494 pg/g, and 16,914 +/- 1657 vs. 6530 +/- 1104 pg/g, respectively; p < 0.05). There was no significant elevation in tissue levels of TNF-alpha in the right lung. Histologic changes consistent with early pulmonary edema were first detected at 12 hours following onset of reperfusion. CONCLUSIONS: Reperfusion following prolonged pulmonary ischemia during isolated lung perfusion results in a significant elevation of local tissue levels of TNF-alpha and may render the perfused lung vulnerable to the adverse effects of the inflammatory cascade.

Animals↗