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Biomedical subjects

S Hammond

Publications and source records attributed to S Hammond.

At least 19 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗
PubMed2004

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗
PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗
PubMed2004

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗
PubMed2004

Inflammatory myofibroblastic tumor following hematopoietic stem cell transplantation: report of two pediatric cases.

Inflammatory myofibroblastic tumors are benign neoplasms histologically composed of lymphocytes, histiocytes, macrophages, foam cells, and plasma cells among a spindle-shaped stroma. Their etiology and potential for metastatic spread is controversial. Numerous predisposing factors have been suggested, including preceding infections, radiotherapy, and local trauma. We present two cases of pseudotumors that developed in children following hematopoietic stem cell transplantation. These are the first cases after hematopoietic transplant reported in the literature. As these neoplasms are difficult to diagnose and are often confused with highly aggressive tumors, our cases demonstrate that a high index of suspicion for such lesions must be maintained when evaluating masses in post transplant patients.

Child↗
PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗
PubMed2001

Homology-driven assembly of a sequence-ready mouse BAC contig map spanning regions related to the 46-Mb gene-rich euchromatic segments of human chromosome 19.

Draft sequence derived from the 46-Mb gene-rich euchromatic portion of human chromosome 19 (HSA19) was utilized to generate a sequence-ready physical map spanning homologous regions of mouse chromosomes. Sequence similarity searches with the human sequence identified more than 1000 individual orthologous mouse genes from which 382 overgo probes were developed for hybridization. Using human gene order and spacing as a model, these probes were used to isolate and assemble bacterial artificial chromosome (BAC) clone contigs spanning homologous mouse regions. Each contig was verified, extended, and joined to neighboring contigs by restriction enzyme fingerprinting analysis. Approximately 3000 mouse BACs were analyzed and assembled into 44 contigs with a combined length of 41.4 Mb. These BAC contigs, covering 90% of HSA19-related mouse DNA, are distributed throughout 15 homology segments derived from different regions of mouse chromosomes 7, 8, 9, 10, and 17. The alignment of the HSA19 map with the ordered mouse BAC contigs revealed a number of structural differences in several overtly conserved homologous regions and more precisely defined the borders of the known regions of HSA19-syntenic homology. Our results demonstrate that given a human draft sequence, BAC contig maps can be constructed quickly for comparative sequencing without the need for preestablished mouse-specific genetic or physical markers and indicate that similar strategies can be applied with equal success to genomes of other vertebrate species.

Animals↗
PubMed2001

Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.

BACKGROUND: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS: METHODS: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided. RESULTS: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. CONCLUSIONS: Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

Adolescent↗
PubMed2001

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗
PubMed2001

Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer.

Dyspnea is a common symptom of lung cancer that can impact patient physical, social, and psychological well-being. Study goals were to evaluate quality of life (QOL) and dyspnea in patients with lung cancer and the relationships between QOL, dyspnea, trait anxiety, and body consciousness. Sociodemographic and cancer-related variables (stage, cell type, performance status) were evaluated. One hundred twenty outpatients with stage I-IV lung cancer participated in the study. Patients completed 5 questionnaires assessing QOL, dyspnea, trait anxiety, body consciousness, and pain. Eighty-seven percent of study participants experienced dyspnea. Patients with high dyspnea scores had lower QOL (P = 0.04). Dyspnea was worse in men than in women (P = 0.02), and there was a trend towards older patients reporting more severe dyspnea than younger patients (P = 0.06). There was no difference in dyspnea based on cancer stage, cell type, or performance status. Pain and anxiety scores were higher in patients with high dyspnea (P = 0.02, P = 0.03). Dyspnea was more severe in patients taking opioid analgesics when compared to non-opioids or no pain medications (P = 0.03). No significant association was found between dyspnea, anxiety, and private body consciousness.

Adult↗
PubMed2001

Clinical trials in a rural population: professional education aspects.

BACKGROUND: While the majority of cancer patients in rural New Hampshire and Vermont are treated in community hospitals, few have entered clinical trials. This report describes a rural hospital consortium as a single Cancer and Leukemia Group B (CALGB) affiliate that used local cancer teams and itinerant oncologists to develop a clinical trials program. METHOD: Grafted onto an existing oncology outreach program, educational programs were developed to help identify patients and recruit them to cooperative group clinical trials. Outcomes included the number of patients accrued to clinical trials, and a comparison of the quality of audited research records with those of affiliated institutions of the CALGB. The consequences of the program were to measure changes in patterns of care of breast, prostate, colorectal, and lung cancers during the study period. These included diagnostic, staging, and treatment changes that occurred over time. RESULTS: 3.3% of incident cases were accrued to clinical trials during the study period, more often for breast and colorectal than for lung and prostate cancers. Reasons that were identified for low accrual were lack of clinical trials for the majority of cases, including the elderly. More than 65% of the patients in the outreach population were older than 65, compared with 50% at the cancer center. Patterns of care did change for breast and prostate cancers, but were similar to national trends.

Adult↗
PubMed1999

Cytologic diagnosis and grading of ductal carcinoma in situ.

BACKGROUND: Fine-needle aspiration cytology plays an important role in the preoperative diagnosis of palpable masses as well as impalpable lesions that can only be sampled by stereotactic or ultrasound techniques. A further refinement of cytologic diagnosis would be the ability to distinguish among the different types of ductal carcinoma in situ (DCIS) also between in situ and invasive malignant disease. METHODS: Sixty-six cases of histologically proven, pure DCIS (39 high grade, 12 cribriform, and 15 low/intermediate grade) with a preoperative cytology report of carcinoma were retrieved from our files. All the cytology (wet-fixed and air-dried smears) was reviewed by G.M., and the histology sections were reviewed by G.T. Seven cytologic features, including cellularity, cell dissociation, nuclear size, cell uniformity, nucleoli, nuclear margins, and chromatin pattern, were assigned scores from 1 to 3. The presence of calcium, necrosis, and foamy macrophages was recorded. Cell clusters were examined for evidence of a cribriform pattern. Fat and stromal fragments were closely checked for infiltration by tumor cells. RESULTS: The cell type was predominantly large and pleomorphic in high grade DCIS, whereas it was mainly small and well differentiated in the cribriform and low grade types. Calcium and necrosis were seen in most high grade lesions and less frequently in the cribriform and low grade ones. Macrophages were more common in high grade and cribriform DCIS than in low/intermediate grade DCIS. Cribriform spaces were noted only in cribriform DCIS. Stromal and fat infiltration by tumor cells was not present in any of the aspirates. Myoepithelial cells were rarely seen. CONCLUSIONS: The presence of pleomorphic carcinoma cells, calcium, necrosis, and macrophages in the aspirate accompanied by "casting" calcification on the mammogram is virtually diagnostic of high grade (comedo) DCIS. Cribriform DCIS shows features of low grade carcinoma with a typical cribriform pattern of punched-out holes in the cell clusters. Low/intermediate grade DCIS has no particular distinguishing features. Cancer (Cancer Cytopathol)

Biopsy, Needle↗
PubMed1999

Possible association of retinoic acid with bone marrow transplant nephropathy.

Bone marrow transplant (BMT) nephropathy is characterized by the acute onset of nephritis more than 100 days after BMT. The renal lesion in BMT nephropathy is similar to radiation nephritis, but BMT nephropathy occurs earlier and with lower radiation doses than radiation nephritis. The combined effects of chemotherapeutic agents and nephrotoxic drugs given before and after BMT appear to sensitize or unmask radiation nephritis. Reporting of drugs that may contribute to BMT nephropathy is critical for the development of optimal treatment regimens. Herein, we report two cases of BMT nephropathy that developed coincident with retinoic acid therapy. Both patients received autologous BMT for neuroblastoma after preparative therapy with total body irradiation/melphalan/carboplatin/etoposide. They were randomized to receive cis-retinoic acid as part of a clinical trial. Both patients developed acute nephritis during their second 2-week course of retinoic acid on post-BMT days 105 and day 139. The nephritis was associated with hypertension, anemia, thrombocytopenia, azotemia, hematuria, and proteinuria. Clinical features, laboratory evaluation, and renal biopsy indicated that these two patients developed radiation-induced BMT nephropathy. The fact that both patients developed nephritis concurrent with retinoic acid therapy raises a concern that retinoic acid may have unmasked radiation injury and triggered BMT nephropathy.

Adrenal Gland Neoplasms↗
PubMed1999

The "stable" ruptured abdominal aortic aneurysm gives a false sense of security.

BACKGROUND: Operative mortality for ruptured abdominal aortic aneurysms (rAAA) has not changed over the past 4 decades. Previous studies have attempted to identify preoperative risk factors that impact upon survival. METHOD: A retrospective review of 25 patients with rAAA treated during a 2-year period was performed. Patients were divided into groups based upon the presence (GpI), absence (GpIIa), or subsequent development of preoperative hypotension (GpIIb). Time intervals from initial presentation to arrival in the operating room (IP-OR), to cross clamp application (IP-XC), and from observed hypotension to cross clamp (HYPO-XC) were recorded. RESULTS: Average time intervals for IP-OR and IP-XC were significantly shorter for GpI compared with GpIIa and GpIIb. No difference in HYPO-XC was noted between GpI and GpIIb. Mortality was 33% for GpI, 25% for GpIIa, and 87.5% for GpIIb. CONCLUSIONS: Normal admission blood pressure led to a decreased sense of urgency, creating avoidable delays and missed opportunities for salvage.

Aged↗
PubMed1999

[Fatigue in healthy and cancer patients. 1. A qualitative study on conceptual analysis].

UNLABELLED: Interest in fatigue-research has grown since the finding that fatigue/tiredness is the most frequently reported symptom of cancer and its treatment. But even though several authors have tried to conceptualise fatigue, its mechanisms are still poorly understood. The aim of this study was twofold: 1) to explore fatigue in cancer patients, inductively, and 2) to compare experiences of fatigue/tiredness of healthy individuals with that of cancer patients to identify cancer-specific fatigue/tiredness and related concepts. PATIENTS AND METHODS: A qualitative research strategy was adopted using a grounded theory approach. The prospective study took place in the Oncology Department of the Kantonsspital St. Gallen (Switzerland) with samples of 20 cancer patients and 20 healthy individuals. Unstructured, tape recorded interviews were conducted to collect data. The transcripts of the interviews were analysed using content analysis and constant comparison. RESULTS: Different themes emerged between the two groups although both fitted a classification system, which categorised fatigue into physical, affective and cognitive expressions of fatigue/tiredness. Physical signs were more frequent than affective and cognitive signs in both groups. In the cancer patients, fatigue involved decreased physical performance, extreme, unusual tiredness, weakness and unusual need for rest, which was distinctly different for healthy persons. Affective and cognitive distress was also more prominent in cancer patients. Interestingly, the concept of malaise was not identified by either sample and not understood as an expression of fatigue by this German speaking population. Linguistic differences in the description of fatigue/tiredness between healthy and ill individuals revealed different perceptions of the phenomenon. A step-like theory, explaining the production of fatigue/tiredness was tentatively put forward involving nociception, perception and expression of tiredness. CONCLUSIONS: The emerging concepts break tiredness/fatigue into expression of physical, affective and cognitive tiredness/fatigue. The experience is different between healthy individuals and cancer patients. Generalisability of data needs precaution but the results of the study identifies and clarifies ideas that might form an important basis for further, controlled studies.

Activities of Daily Living↗